NATMED24M • Natural Medicines Offer

Table of Contents

NATMED24M • Natural Medicines Offer

How to Receive Credit

NetCE 3 Hour Course #98010 • Cannabinoid Overview

98010 • Cannabinoid Overview

1. INTRODUCTION

2. GLOSSARY

3. THE AGRICULTURE IMPROVEMENT ACT OF 2018

4. CANNABINOIDS

5. REVIEWING THE EVIDENCE: EFFICACY AND SAFETY

6. GENERAL SAFETY CONSIDERATIONS

7. CONSIDERATIONS FOR NON-ENGLISH-PROFICIENT PATIENTS

8. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

NetCE 2 Hour Course #98020 • Commonly Abused Supplements

98020 • Commonly Abused Supplements

1. INTRODUCTION

2. ABUSE POTENTIAL RELATED TO WEIGHT LOSS AND/OR ATHLETIC PERFORMANCE

3. LAXATIVES

4. ABUSE POTENTIAL RELATED TO RECREATIONAL USE

5. ABUSE POTENTIAL RELATED TO OPIOID-LIKE EFFECTS

6. CONSIDERATIONS FOR NON-ENGLISH-PROFICIENT PATIENTS

7. CONCLUSION

Works Cited

NetCE 4 Hour Course #98030 • Getting to the Point: Acupuncture and Acupoint Therapies

98030 • Getting to the Point: Acupuncture and Acupoint Therapies

1. HISTORY: A BRIEF GLIMPSE

2. ACUPUNCTURE

3. MOXIBUSTION

4. ACUPRESSURE

5. TRANSCUTANEOUS ELECTRICAL ACUSTIMULATION (TEAS)

6. CONSIDERATIONS AND COMPARISONS

7. CONSIDERATIONS FOR NON-ENGLISH-PROFICIENT PATIENTS

8. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

NetCE 3 Hour Course #98080 • Top-Selling Herbal Supplements

98080 • Top-Selling Herbal Supplements

1. INTRODUCTION

2. APPLE CIDER VINEGAR (ACV)

3. ASHWAGANDHA

4. ECHINACEA

5. ELDERBERRY

6. TURMERIC

7. SPECIAL CONSIDERATIONS

8. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

NATMED24M • Natural Medicines Offer

Chelsey McIntyre, PharmD

www.netce.com

Copyright © 2025 NetCE, All rights reserved.

NATMED24M • Natural Medicines Offer

Expiration Date: 06/30/2025

How to Receive Credit

To complete this Special Offer for continuing education credit please go to http://www.netce.com/specials in your browser.

For assistance with receiving continuing education credit, please contact us at help@netce.com.

98010 • Cannabinoid Overview

Chelsey McIntyre, PharmD

www.netce.com

Copyright © 2022 NetCE, All rights reserved.

Because of recent legal changes at both the federal and state levels related to medical and/or recreational use, access to and interest in cannabinoids has been increasing. Patients may be asking about various cannabinoids, including safety and potential uses. Healthcare professionals should be well informed about these substances so that they can provide evidence-based recommendations and appropriate safety warnings.

Table of Contents

98010 • Cannabinoid Overview

Course Overview

Audience

Accreditations & Approvals

Designations of Credit

Individual State Nursing Approvals

Individual State Behavioral Health Approvals

Special Approvals

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planners

Division Planners Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

Implicit Bias in Health Care

1. INTRODUCTION

2. GLOSSARY

3. THE AGRICULTURE IMPROVEMENT ACT OF 2018

4. CANNABINOIDS

5. REVIEWING THE EVIDENCE: EFFICACY AND SAFETY

TETRAHYDROCANNABINOL (THC)

CANNABIDIOL (CBD)

CANNABIDIVARIN (CBDV)

TETRAHYDROCANNABIVARIN (THCV)

CANNABINOL (CBN)

CANNABIGEROL (CBG)

CANNABICHROMENE (CBC)

6. GENERAL SAFETY CONSIDERATIONS

DELTA-8 TETRAHYDROCANNABINOL (DELTA-8 THC)

CLASS-WIDE SERIOUS ADVERSE EFFECTS OF CANNABINOIDS

CONTAMINATION CONCERNS

DRUG TESTING CONCERNS

SAFETY IN CHILDREN

7. CONSIDERATIONS FOR NON-ENGLISH-PROFICIENT PATIENTS

8. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

98010 • Cannabinoid Overview

Education Category. Alternative Medicine

Release Date. 11/01/2022

Expiration Date. 10/31/2025

Course Overview

Because of recent legal changes at both the federal and state levels related to medical and/or recreational use, access to and interest in cannabinoids has been increasing. Patients may be asking about various cannabinoids, including safety and potential uses. Healthcare professionals should be well informed about these substances so that they can provide evidence-based recommendations and appropriate safety warnings.

Audience

This course is designed for healthcare professionals whose patients are taking or are interested in taking cannabinoid products.

Accreditations & Approvals

In support of improving patient care, TRC Healthcare/NetCE is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. NetCE has been approved by NBCC as an Approved Continuing Education Provider, ACEP No. 6361. Programs that do not qualify for NBCC credit are clearly identified. NetCE is solely responsible for all aspects of the programs. As a Jointly Accredited Organization, NetCE is approved to offer social work continuing education by the Association of Social Work Boards (ASWB) Approved Continuing Education (ACE) program. Organizations, not individual courses, are approved under this program. Regulatory boards are the final authority on courses accepted for continuing education credit. Continuing Education (CE) credits for psychologists are provided through the co-sponsorship of the American Psychological Association (APA) Office of Continuing Education in Psychology (CEP). The APA CEP Office maintains responsibility for the content of the programs. NetCE is accredited by the International Accreditors for Continuing Education and Training (IACET). NetCE complies with the ANSI/IACET Standard, which is recognized internationally as a standard of excellence in instructional practices. As a result of this accreditation, NetCE is authorized to issue the IACET CEU.

Designations of Credit

This activity was planned by and for the healthcare team, and learners will receive 3 Interprofessional Continuing Education (IPCE) credit(s) for learning and change. NetCE designates this enduring material for a maximum of 3 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. NetCE designates this continuing education activity for 3 ANCC contact hour(s). NetCE designates this continuing education activity for 3 pharmacotherapeutic/pharmacology contact hour(s). NetCE designates this continuing education activity for 3 pharmacology hour(s) for physician assistants. NetCE designates this continuing education activity for 3.6 hours for Alabama nurses. NetCE designates this continuing education activity for 1 NBCC clock hour(s). Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 3 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Completion of this course constitutes permission to share the completion data with ACCME. Social workers participating in this intermediate to advanced course will receive 3 Clinical continuing education clock hours. Successful completion of this CME activity, which includes participation in the evaluation component, enables the learner to earn credit toward the CME and/or Self-Assessment requirements of the American Board of Surgery's Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit. Through an agreement between the Accreditation Council for Continuing Medical Education and the Royal College of Physicians and Surgeons of Canada, medical practitioners participating in the Royal College MOC Program may record completion of accredited activities registered under the ACCME's "CME in Support of MOC" program in Section 3 of the Royal College's MOC Program. NetCE is authorized by IACET to offer 0.3 CEU(s) for this program. NetCE designates this continuing education activity for 3 credit(s). AACN Synergy CERP Category A.

Individual State Nursing Approvals

In addition to states that accept ANCC, NetCE is approved as a provider of continuing education in nursing by: Alabama, Provider #ABNP0353 (valid through July 29, 2025); Arkansas, Provider #50-2405; California, BRN Provider #CEP9784; California, LVN Provider #V10662; California, PT Provider #V10842; District of Columbia, Provider #50-2405; Florida, Provider #50-2405; Georgia, Provider #50-2405; Kentucky, Provider #7-0054 through 12/31/2025; South Carolina, Provider #50-2405; West Virginia RN and APRN, Provider #50-2405.

Individual State Behavioral Health Approvals

In addition to states that accept ASWB, NetCE is approved as a provider of continuing education by the following state boards: Alabama State Board of Social Work Examiners, Provider #0515; Florida Board of Clinical Social Work, Marriage and Family Therapy and Mental Health Counseling, CE Broker Provider #50-2405; Illinois Division of Professional Regulation for Social Workers, License #159.001094; Illinois Division of Professional Regulation for Licensed Professional and Clinical Counselors, License #197.000185; Illinois Division of Professional Regulation for Marriage and Family Therapists, License #168.000190;

Special Approvals

This activity is designed to comply with the requirements of California Assembly Bill 1195, Cultural and Linguistic Competency.

Course Objective

The purpose of this course is to provide healthcare professionals in all practice settings the knowledge necessary to increase their understanding of the various cannabinoids.

Learning Objectives

Upon completion of this course, you should be able to:

1. Explain the difference between hemp and cannabis.

2. Outline the action and effects of delta-9-tetrahydrocannabinol (THC).

3. Review the evidence for the use of cannabidiol for various conditions.

4. Discuss the potential safety concerns of various cannabinoids.

Faculty

Chelsey McIntyre, PharmD, is a clinical pharmacist who specializes in drug information, literature analysis, and medical writing. She earned her Bachelor of Science degree in Genetics from the University of California, Davis. She then went on to complete her PharmD at Creighton University, followed by a clinical residency at the Children’s Hospital of Philadelphia (CHOP). Dr. McIntyre held the position of Drug Information and Policy Development Pharmacist at CHOP until her move to Washington state in 2017, after which she spent the next six years as a clinical editor for Natural Medicines, a clinical reference database focused on natural products and alternative therapies. She continues to create rigorous professional analysis and patient education materials for various publications while also practicing as a hospital pharmacist. Her professional interests include provider and patient education, as well as the application of evidence-based research to patient care.

Faculty Disclosure

Contributing faculty, Chelsey McIntyre, PharmD, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planners

John M. Leonard, MD

Sharon Cannon, RN, EdD, ANEF

Alice Yick Flanagan, PhD, MSW

James Trent, PhD

Division Planners Disclosure

The division planners have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

The Director of Development and Academic Affairs has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

Implicit Bias in Health Care

The role of implicit biases on healthcare outcomes has become a concern, as there is some evidence that implicit biases contribute to health disparities, professionals' attitudes toward and interactions with patients, quality of care, diagnoses, and treatment decisions. This may produce differences in help-seeking, diagnoses, and ultimately treatments and interventions. Implicit biases may also unwittingly produce professional behaviors, attitudes, and interactions that reduce patients' trust and comfort with their provider, leading to earlier termination of visits and/or reduced adherence and follow-up. Disadvantaged groups are marginalized in the healthcare system and vulnerable on multiple levels; health professionals' implicit biases can further exacerbate these existing disadvantages.

Interventions or strategies designed to reduce implicit bias may be categorized as change-based or control-based. Change-based interventions focus on reducing or changing cognitive associations underlying implicit biases. These interventions might include challenging stereotypes. Conversely, control-based interventions involve reducing the effects of the implicit bias on the individual's behaviors. These strategies include increasing awareness of biased thoughts and responses. The two types of interventions are not mutually exclusive and may be used synergistically.

1. INTRODUCTION

Cannabis refers to Cannabis sativa, Cannabis indica, and hybrids of these two plant species. Cannabis is a flowering annual plant that is grown worldwide and is commonly referred to as either cannabis or hemp. Cannabis contains more than 100 cannabinoids, which are concentrated in the flowers and leaves [1].

Marijuana, the colloquial term for cannabis, has generally referred to Cannabis containing high quantities of the main psychoactive cannabinoid delta-9-tetrahydrocannabinol (THC).

Hemp, on the other hand, has historically referred to Cannabis harvested for its fibrous stalks for use in industrial applications, which include fiber, cosmetics, and clothing. Hemp is also harvested for its seeds, which are used to make hemp seed oil. Hemp seed oil contains no to only low levels of cannabinoids, including THC and cannabidiol (CBD). Hemp oil, on the other hand, is obtained from the flower and/or leaves of the plant and contains THC and higher amounts of CBD [2].

2. GLOSSARY

Cannabis: An informal term used to refer to products classified as marijuana.

Cannabis: A term referring to all forms of the plant, which includes the species Cannabis sativa and Cannabis indica, as well as hybrids of these two species. This term can refer to both marijuana and hemp.

Cannabinoids: The pharmacologically active chemicals unique to Cannabis. These chemicals are primarily found in the flowers and leaves; the stalk and seed of the plant contain only negligible quantities.

3. THE AGRICULTURE IMPROVEMENT ACT OF 2018

In 2018, the Agriculture Improvement Act, also known as the Farm Bill, completely changed the landscape for the sale of cannabinoid products in the United States. This new bill defines hemp as Cannabis sativa and any part of that plant, including the seeds thereof and all derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers, whether growing or not, with a THC concentration of not more than 0.3% on a dry weight basis. According to the Farm Bill, cannabis (or what we commonly refer to as marijuana) is considered Cannabis sativa containing more than 0.3% THC. The Farm Bill made hemp and its constituents, including CBD, exempt from the Controlled Substances Act and legal for sale [1,2].

The U.S. Domestic Hemp Production Program was a direct result of the Farm Bill. This program makes it legal to grow hemp in all 50 states and provides details about licensing hemp producers, testing THC levels, disposing plants exceeding maximum THC levels, and ensuring compliance. The Farm Bill paved the way for the legal sale of various cannabinoids and hemp-based products without Drug Enforcement Agency (DEA) oversight, which led to a surge in consumer interest and product availability that has only continued to increase [1,2].

4. CANNABINOIDS

Cannabis contains various constituents, including hydrocarbons, amino acids, sugars, fatty acids, and terpenes. Terpenes are the aromatic compounds responsible for its distinctive smell, but they are not unique to Cannabis; terpenes are found in many other plants, including citrus [1].

The pharmacologically active constituents unique to Cannabis are the cannabinoids. Although THC and CBD often steal the spotlight, Cannabis actually contains more than 100 different cannabinoids. The relative abundance of these naturally occurring cannabinoids varies [1].

Some cannabinoids have psychoactive properties. THC is considered to be the primary psychoactive cannabinoid. A number of other cannabinoids are not considered psychoactive but have piqued the interest of researchers as well as the public for a variety of other pharmacologic effects.

The following cannabinoids are the most well-studied to date and will be discussed in more detail during the course [1]:

- THC

- CBD

- Cannabidivarin (CBDV)

- Tetrahydrocannabivarin (THCV)

- Cannabinol (CBN)

- Cannabigerol (CBG)

- Cannabichromene (CBC)

While the focus of this course will be on these plant cannabinoids, or phytocannabinoids, synthetic THC that is chemically identical to naturally occurring THC is also available. Some products approved by the U.S. Food and Drug Administration (FDA), such as dronabinol and nabilone, contain synthetic forms of THC and are regulated as prescription medications. These are not subject to the regulations for products derived from Cannabis. Similarly, K2/Spice, the general name for the class of compounds known as synthetic cannabinoids, will not be discussed in this course.

5. REVIEWING THE EVIDENCE: EFFICACY AND SAFETY

TETRAHYDROCANNABINOL (THC)

THC, or the delta-9 THC isomer more specifically, is the most prominently occurring THC isomer and the most familiar psychoactive cannabinoid found in Cannabis. Recreational use of cannabis can be attributed to THC. While pure THC does exist, it is typically studied in the form of a cannabis extract standardized to THC content, or it is used in conjunction with other cannabinoids (often CBD).

Selective breeding and the use of genetic modification has altered the Cannabis plant in important ways over the past few decades. For example, cannabis preparations confiscated in the United States have contained increasingly higher concentrations of THC over time. From 1995 to 2014, the average THC content increased from 4% to approximately 12%. And in one decade, from 2008 to 2017, the average THC concentration increased from 9% to 17%. This can significantly increase the "dose" of THC, leading to more substantial impairment and a higher likelihood of associated adverse effects [1].

THC is known to exert most of its pharmacologic activity through the endocannabinoid system. This system is comprised of endocannabinoids, endogenous neurotransmitters that bind to cannabinoid (CB) receptors. CB1 receptors are found in the central nervous system; CB2 receptors are found on immune cells, including leukocytes, and to a lesser extent in the brain [1].

Laboratory and animal research shows that THC exhibits psychoactive, analgesic, and antispasticity effects that are modulated through CB1 agonism. THC seems to be a partial CB1 receptor agonist with limited CB2 agonist activity, but it has also demonstrated anti-inflammatory and immunosuppressive effects via CB2 agonism. The well-known antiemetic effects of THC seem to be achieved through agonism of both CB1 and CB2. Unfortunately, because most human research on the use of THC involves the use of whole cannabis, it is not always easy to determine which clinical effects are attributable to THC alone [1].

Efficacy

While cannabis is often used recreationally, either inhaled or ingested, it is frequently touted for a variety of conditions, such as amyotrophic lateral sclerosis, dementia, HIV/AIDS-related wasting, Crohn disease, epilepsy, glaucoma, chronic pain, and chemotherapy-induced nausea and vomiting. However, there is not good evidence indicating that cannabis is beneficial for use in these conditions. There is some evidence for the use of THC-containing products in patients with multiple sclerosis and in those with neuropathic pain.

Multiple Sclerosis

While it is unclear if smoking cannabis improves multiple sclerosis-related symptoms, a prescription product available in Canada and most of Europe, as well as other products containing the combination of THC and CBD, seem to reduce spasticity in patients with multiple sclerosis. Nabiximols, a prescription oromucosal spray containing whole-plant cannabis extract (Sativex), is available in most of Europe and Canada but is not yet approved in the United States. Each actuation of this cannabis extract spray is standardized to deliver THC 2.7 mg and CBD 2.5 mg [1].

A meta-analysis of the available research shows that using a prescription oromucosal spray containing cannabis extract for at least two weeks modestly reduces subjective spasticity, but not bladder dysfunction, when compared with placebo. Effects might last more than 11 months, but discontinuation of use may cause rebound symptoms. Much of the research on the prescription product was funded by the manufacturer.

Evidence Based Practice Recommendation

The American Academy of Neurology asserts that clinicians might offer oral cannabis extract to patients with multiple sclerosis to reduce patient-reported symptoms of spasticity and pain (excluding central neuropathic pain).

https://www.aan.com/Guidelines/home/GuidelineDetail/641

Last Accessed: October 25, 2022

Level of Evidence: A (Established as effective for the given condition in the specified population.)

The American Academy of Neurology states that a prescription cannabis extract does not improve objective measures of spasticity, reduce the number of urinary incontinence episodes, or reduce multiple sclerosis-related tremors [1].

A meta-analysis of the available research in patients with multiple sclerosis shows that taking oral cannabis extracts containing THC 25–30 mg and CBD 8–18 mg (e.g., Cannador, Society of Clinical Research) daily for up to 15 weeks modestly reduces subjective spasticity, neuropathic pain, and bladder dysfunction, but not objective spasticity measures, when compared with placebo [1].

Despite generally positive research on multiple sclerosis-related symptoms with prescription or other standardized products, research on the use of any other cannabis products is limited. Keep in mind that nonprescription cannabis products can contain a wide range of THC or CBD, in very different ratios, which would be expected to significantly alter any effects, clinical or adverse.

Neuropathic Pain

Evidence Based Practice Recommendation

The National Institute for Health and Care Excellence recommends against starting Cannabis sativa extract to treat neuropathic pain in non-specialist settings, unless advised by a specialist to do so.

https://www.nice.org.uk/guidance/cg173

Last Accessed: October 25, 2022

Level of Evidence: Expert Opinion/Consensus Statement

Inhaled cannabis seems to temporarily improve neuropathic pain, but it is unclear what the optimal dose might be. A meta-analysis of small studies in patients with chronic neuropathic pain secondary to a variety of causes shows that inhaling cannabis containing THC 1.6–96 mg daily for up to two weeks reduces pain intensity. To achieve a pain reduction of at least 30%, six patients would need to be treated [1].

A small individual clinical study in patients with spinal cord injury shows that inhaling cannabis containing THC 2.9% or 6.7% reduces neuropathic pain, with a number needed to treat of three to achieve a pain reduction of at least 30% during an eight-hour period [1].

Safety

Most commonly, dizziness, dry mouth, fatigue, headache, increased appetite, nausea, paranoid and dissociative thinking, and sedation are associated with cannabis when consumed via any usual route. When inhaled, cannabis use has commonly been associated with upper respiratory tract symptoms, such as cough and wheeze. Intoxicating doses of cannabis can impair memory, motor coordination, reaction time, and visual perceptions for as long as eight hours [1].

Serious adverse effects have also been reported with ingestion or inhalation of cannabis, usually with large doses or with extended use. Respiratory effects specifically are associated with smoking or vaping cannabis and can include coughing, wheezing, inflammation of the upper respiratory tract, and e-cigarette, or vaping, product-use associated lung injury (EVALI). Potential neurologic effects include anxiety, psychosis, cognitive impairment, mood disturbances, cannabinoid hyperemesis syndrome (CHS), withdrawal syndrome, and seizures. Atrial fibrillation, ventricular arrhythmia, and myocardial infarction are possible cardiovascular effects [1].

Abuse Potential

Cannabis can be habit-forming. Meta-analyses show that as many as 47% of regular cannabis users develop some form of dependence and up to 9% of all users develop cannabis use disorder. For context, substance use disorders occur in approximately 20% to 30% of all tobacco users, 15% of those who try cocaine, and 25% of those who try heroin. However, it is not always clear if those presenting with cannabis use disorder are truly addicted or simply demonstrating high levels of dependence with heavy use. Additionally, it is unclear how the increasing concentration of THC in cannabis affects this dependence rate [1].

Drug Interactions

In vitro research and some case reports show that using cannabis can increase the risk of bleeding when administered with drugs, herbs, and supplements that increase the risk of bleeding. Patients receiving warfarin, other anticoagulants, or antiplatelet agents should be monitored more closely for bleeding, especially when cannabis use is not on a regular or consistent basis.

Cannabis can also affect certain cytochrome P450 (CYP450) enzymes. Based on pharmacology and some in vitro research, cannabis might inhibit or induce CYP450 enzymes, including CYP 2C9, 2E1, and 3A4, potentially increasing or decreasing the levels and corresponding effects of substrates of these enzymes. Based on pharmacology, certain CYP450 inhibitors and inducers might increase or decrease the levels and corresponding effects of cannabis, but these concerns are theoretical at this time [1]. Theoretically, using cannabis with drugs, herbs, and supplements that have sedative properties may cause additive therapeutic and adverse effects.

Even though many of these interactions have not been substantiated in humans, they could be useful to keep in mind, especially for patients taking narrow therapeutic index drugs or patients who are regular users of cannabis. Gather information from patients about cannabis use and add this to their medical history or patient profile. Consider the impact of cannabis use when patients start or stop a medication or complain of any new side effects.

Special Populations

Pregnancy and Lactation

Cannabis crosses the placenta, and use during pregnancy has been associated with numerous negative maternal and fetal outcomes in observational studies. THC is excreted into the breast milk for at least six weeks following cessation of use and can cause delayed motor development in the infant [1]. Patients should be informed of these risks and discouraged from using cannabis while pregnant or breastfeeding.

Patients with Diabetes

In patients with type 1 diabetes, cannabis use has been associated with worsened glycemic control, increased glycated hemoglobin (HbA1c), and an increased risk for diabetic ketoacidosis. In patients with type 2 diabetes, cannabis use has been associated with an increased risk for diabetic nephropathy, myocardial infarction, and peripheral arterial occlusion. Until more is known, tell patients with diabetes to be cautious using cannabis [1].

CANNABIDIOL (CBD)

CBD is a nonpsychoactive constituent of Cannabis and may constitute up to 40% of cannabis extracts. Since hemp is not subject to regulation by the DEA, hemp is the main source of most of the available CBD products on the market [3].

Unlike THC, extensive laboratory research has confirmed that CBD does not act on CB receptors. Instead, CBD seems to interact or interfere with a number of endocannabinoid and non-endocannabinoid signaling systems. For instance, CBD can inhibit the cellular uptake and degradation of anandamide, an endocannabinoid. Anandamide is a highly potent, endogenous agonist of CB1 and CB2. By altering the function of this molecule, CBD can indirectly affect the function of the endocannabinoid system.

CBD also seems to act on other receptors. CBD has demonstrated activity on transient receptor vanilloid type 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1). TRPV1 and TRPA1 are ion channels expressed almost exclusively by sensory neurons that play an important role in various sensations, including pain, cold, itch, and other protective responses. CBD can also enhance the activity of 5-HT1A (serotonin) receptors and has demonstrated affinity for various other pharmacologically important receptors throughout the body, such as peroxisome proliferator-activated receptors (PPAR) [3].

Legal Implications

In May 2019, FDA approved of a specific, oil-based prescription formulation of CBD (Epidiolex). While the passage of the 2018 Farm Bill exempted hemp and its constituents, including CBD, from the Controlled Substances Act and made them legal for sale, FDA approval of a prescription CBD product further complicated things [3].

Because CBD is the active ingredient in a prescription product, it has been said that legally it cannot be included in foods and dietary supplements. However, this sentiment has been disputed and enforcement has been lacking. Dietary supplements and foods containing CBD are abundant in the marketplace [3].

Efficacy

CBD is frequently touted for mental health, pain management, sleep, substance use disorder, and gastrointestinal disorders, but the majority of the evidence for CBD use is for treatment-resistant epilepsy. Research for other purported indications is inconclusive [3].

Because of how readily available CBD products have become, you may be getting a lot of questions from patients about the touted uses of these products. We will first discuss the use of CBD with the most evidence, and then we will briefly review the evidence available for some other conditions of interest.

Treatment-Resistant Epilepsy

A prescription CBD solution approved by the FDA is labeled for the adjunctive treatment of Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. Prescription CBD is an oil-based oral solution standardized to contain CBD extract 100 mg/mL in sesame oil. The extract is highly purified from a plant source. Originally classified by the DEA as a Schedule V controlled substance, it was descheduled in April 2020 [3].

In children with Dravet syndrome and children and adults with Lennox-Gastaut syndrome or tuberous sclerosis complex, adjunctive treatment with this prescription formulation reduces seizure frequency from baseline by 39% to 49%, compared with only 13% to 27% in those receiving placebo. Nearly half of patients experience at least a 50% reduction in seizure frequency from baseline. Results of open-label extension studies demonstrate similar efficacy for sustained periods of up to three years [3].

While this prescription formulation has also been evaluated for use in other forms of epilepsy (e.g., Sturge-Weber syndrome, febrile infection-related epilepsy syndrome [FIRES], epileptic encephalopathy of genetic origin), the available research is limited, and it is not labeled for these uses. It is unclear if other CBD products are beneficial for use in seizure disorders [3].

Mental Health

Research on the use of CBD for mental health benefits is inconclusive. In healthy patients, several small, low-quality studies show that oral CBD 15 mg or 150 mg modestly improves emotional exhaustion, depression or anxiety symptoms, and the ability to cope with stress, when compared with standard care or placebo, but it is not clear if CBD is beneficial in patients diagnosed with anxiety or depression [3].

In patients with social anxiety disorder, oral CBD 300–600 mg daily or as a single dose reduces overall anxiety and anxiety associated with public speaking. However, for some patients, anxiety was only reduced before or after and not necessarily during the speaking event. CBD does not seem to reduce speaking anxiety in patients at higher risk for psychiatric complications. Differences due to study size, baseline anxiety, and the use of nonstandardized products may explain some of the variability in outcomes observed [3].

In patients with post-traumatic stress disorder, a small study shows that taking high-purity oral CBD 300 mg attenuates cognitive impairment associated with the recall of traumatic events when compared with placebo. However, it does not improve anxiety, alertness, or discomfort. Patients in the CBD group had more psychiatric comorbidities at baseline [3].

Pain

Although CBD products, both oral and topical, are regularly touted for pain relief, they do not seem to reduce acute pain and effects on chronic pain are even less clear. Even though CBD salves and balms are really popular for muscle and joint pain relief, there does not seem to be evidence supporting topical absorption of CBD.

In healthy volunteers with experimentally induced pain, several small clinical studies show that single oral doses of CBD 200–800 mg do not seem to reduce acute pain when compared with placebo. In patients with acute low back pain presenting to the emergency department, oral CBD 400 mg, in addition to the standard treatment of acetaminophen 1,000 mg with ibuprofen 400 mg, does not reduce pain or the need for rescue analgesia with oxycodone over two hours when compared with placebo [3].

A small observational cohort study shows that taking oral CBD for eight weeks is associated with reductions in pain and opioid use and improvements in sleep quality. However, due to the observational nature of the study, it is unclear if this is a direct result of CBD use [3].

Sleep

Although CBD has demonstrated sedative effects in animal research, it has not been evaluated for insomnia or other sleep disorders in clinical studies [3].

Substance Use Disorders

In patients with various substance use disorders, CBD may play a role in reducing cravings and substance use, but it is unclear if these marginal benefits actually translate into relapse prevention. Unfortunately, most studies in this area are generally small and low quality. Interestingly, CBD has been evaluated for use in patients with cannabis use disorder.

In patients with cannabis use disorder of moderate severity, a small clinical study shows that taking synthetic CBD oil 400 mg or 800 mg in two divided doses daily for four weeks seems to reduce overall cannabis consumption, based on urine metabolite levels, when compared with placebo. The 400-mg dose, but not the 800-mg dose, seems to increase self-reported abstinence from cannabis by about 0.5 days per week when compared with placebo [3].

Safety

Oral CBD has been used with apparent safety at doses of 200–1,200 mg daily in the short term, for up to four to 13 weeks. CBD seems to be well tolerated when taken by mouth. Prescription CBD is reported to cause somnolence in up to 30% of patients and diarrhea in up to 24% of patients, but keep in mind that doses for treatment-resistant epilepsy exceed those used in most nonprescription CBD products. Doses of prescription CBD exceeding 15–20 mg/kg daily and/or taken in combination with other anticonvulsants (e.g., clobazam, valproic acid) are more likely to cause certain adverse effects like somnolence, diarrhea, elevation of liver transaminases, and weight loss/gain. Decreased appetite, drowsiness, dry mouth, fatigue, and vomiting have also been commonly reported. Pharmacogenetic variation has been shown to affect susceptibility to CBD-associated adverse effects including diarrhea, sedation, and elevation of liver transaminases [3].

Abuse Potential

There has been some concern that CBD can be used as a substance of abuse, but overall, these concerns seem unfounded. Single 750-mg doses of CBD were rated no differently than placebo for "drug-liking", likelihood of repeat use, or occurrence of positive effects (e.g., feeling "high" or "stoned") among healthy recreational polydrug abusers in a clinical study. Higher single doses of 1,500 mg or 4,500 mg were rated with a higher likelihood for repeat use and the presence of "positive effects", but these ratings were still lower than those for dronabinol, a synthetic version of THC, and alprazolam [3].

Unlike THC, limited research suggests that CBD does not cause driving impairment. A small study has found that inhaling vaporized cannabis containing CBD 13.75 mg does not increase lane weaving when compared with placebo. Lane weaving observed in those inhaling this product was equivalent to having a blood alcohol concentration (BAC) of 0.02%, which is below the lower limit of clinically relevant impairment that is considered to occur with a BAC of 0.05%. Keep in mind that the study only tested a single dose of CBD, which may not be indicative of real-world use [3].

Abrupt discontinuation following short-term CBD use does not seem to be associated with withdrawal symptoms in healthy volunteers [3].

Drug Interactions

CBD can affect certain CYP450 enzymes. Some clinical research has suggested that CBD might inhibit CYP2C9, 2C19, and 3A4, potentially increasing the levels and corresponding effects of substrates of these enzymes. This represents the potential for a large number of drug interactions. Based on in vitro and animal research, CBD also might inhibit CYP 1A1, 1A2, 1B1, 2A6, 2B6, and 2C8 enzymes, but these concerns are theoretical at this time. Patients receiving substrates of these enzymes, especially narrow therapeutic index drugs metabolized by CYP2C9, 2C19, or 3A4, should be monitored for potential interactions. Based on theoretical pharmacology, certain CYP450 enzyme inhibitors and inducers might increase or decrease the levels and corresponding effects of CBD [3].

Clinical studies have demonstrated modest to substantial increases in the concentrations of some drugs when CBD, including prescription CBD, is used concomitantly. These drugs include brivaracetam, caffeine, citalopram, clobazam, eslicarbazepine, everolimus, rufinamide, sirolimus, stiripentol, tacrolimus, topiramate, and zonisamide. Theoretically, using CBD with drugs, herbs, and supplements that have sedative properties may cause additive therapeutic and adverse effects [3].

Gather information from patients about CBD use and add this to their medical history or patient profile. Consider the impact of CBD use when patients start or stop a medication or complain of any new side effects.

Special Populations

Children

While a specific prescription CBD oral solution product has been used safely in children as young as 1 year of age, the safety of other forms of CBD have not been evaluated in children [3].

Pregnancy and Lactation

Due to concerns related to contamination with THC, heavy metals, pesticides, and more, CBD may not be safe for use while pregnant or breastfeeding. Frequent contamination of CBD can be dangerous to the fetus. Similarly, animal research has demonstrated that high levels of CBD can adversely affect the reproductive system of male offspring. The FDA strongly advises against its use during pregnancy [3].

CANNABIDIVARIN (CBDV)

Cannabidivarin is a nonpsychoactive cannabinoid with structural similarity to CBD. The concentration of cannabidivarin is greater in Cannabis indica than in Cannabis sativa. While cannabidivarin is structurally similar to CBD, it is the biosynthetic precursor to tetrahydrocannabivarin, which results from the isomerization of cannabidivarin under acidic conditions. Based on the available laboratory and animal research, it seems to act through many of the same receptor pathways as CBD [4].

Efficacy

Although there is interest in using cannabidivarin for various neurologic or neuromuscular and gastrointestinal disorders, research is mostly limited to in vitro and animal studies. While the FDA and the European Medicines Agency have granted cannabidivarin an orphan designation for use in the treatment of Fragile X syndrome and Rett syndrome, there is not enough reliable information about the clinical effects of cannabidivarin for these uses [4].

Epilepsy

A large, high-quality clinical study in patients with inadequately controlled focal seizures failed to show that adjunctive therapy with cannabidivarin reduces seizure frequency when compared with placebo, prompting the industry sponsor to abandon research for this indication [4].

Neuropathic Pain

There is limited evidence on the use of cannabidivarin in patients with HIV-associated neuropathic pain. A small clinical study in patients with HIV-associated neuropathic pain failed to show that cannabidivarin reduces pain or medication use when compared with placebo [4].

Safety

Cannabidivarin seems to be safe for short-term use in adults. Doses of up to 800 mg twice daily for up to eight weeks have been evaluated in clinical research, but there is no data for use of higher doses of longer durations. Diarrhea, dizziness, and nausea are commonly reported with use, and higher doses have been associated with abdominal pain, headache, rash, and somnolence [4].

TETRAHYDROCANNABIVARIN (THCV)

Tetrahydrocannabivarin is a nonpsychoactive analogue of THC that is naturally occurring in Cannabis sativa. Tetrahydrocannabivarin may also be derived from cannabidivarin. As with THC, tetrahydrocannabivarin acts on the endocannabinoid system, with a higher affinity for CB2. Laboratory and animal research shows that it exhibits some anti-inflammatory, antiemetic, and antitumor effects via CB1 and CB2 agonism. Additionally, research in healthy adults has shown that tetrahydrocannabivarin might affect overall food intake through CB1 agonism in the brain [5].

Efficacy

This cannabinoid has not been extensively studied in humans, but there is increasing interest in its use as an anti-inflammatory, anticonvulsant, analgesic, antipsychotic, and appetite suppressant. Available research for these conditions is limited to in vitro and animal studies [5].

Safety

While tetrahydrocannabivarin has been used with apparent safety in clinical research for up to 13 weeks, a thorough evaluation of safety outcomes has not been conducted [5].

CANNABINOL (CBN)

Cannabinol, a metabolite of THC, is present in Cannabis in trace amounts. Some research suggests that it might be mildly psychoactive, while other research shows no psychoactive activity. Regardless, it appears to bind to CB2 receptors and demonstrates weak affinity for CB1 receptors [6].

Efficacy

Although there is interest in using cannabinol as an analgesic, appetite stimulant, immunomodulator, and sleep aid, it has not been evaluated in clinical studies [6].

Safety

Cannabinol has not been thoroughly evaluated for safety [6].

Drug Interactions

In in vitro studies, certain CYP 450 enzyme inhibitors increased the levels and effects of cannabinol. In other in vitro research, cannabinol inhibited certain CYP450 enzymes, potentially increasing the levels and effects of substrates of these enzymes. Even though these interactions have not been substantiated in humans, they could be useful to keep in mind, especially for those taking narrow therapeutic index drugs or those who are regular users of cannabinol [6].

CANNABIGEROL (CBG)

Cannabigerol, a CBD-like nonpsychoactive cannabinoid, is naturally occurring in Cannabis sativa and is abundant in industrial hemp. Cannabigerol also utilizes some of the same receptor pathways as CBD [7].

Efficacy

Although there is interest in using cannabigerol for conditions such as cachexia, dyslipidemia, Huntington disease, and inflammatory bowel disease, available research is limited to in vitro and animal studies. Some research shows that the anti-inflammatory effects of cannabigerol might be greater when used in combination with CBD, but cannabigerol also seems to reverse the antiemetic effects of CBD when used concomitantly [7].

Safety

Cannabigerol has not been thoroughly evaluated for safety [7].

CANNABICHROMENE (CBC)

Cannabichromene, a nonpsychoactive cannabinoid, is one of the most abundant cannabinoids found in Cannabis. Cannabichromene does not strongly affect CB1 receptors, but it does have activity at CB2 receptors [8].

Efficacy

Although there is interest in using cannabichromene for its anti-inflammatory, analgesic, and anticonvulsant effects, available research is limited to in vitro and animal studies. Some research shows that the analgesic effects of cannabichromene might be greater when used in combination with other cannabinoids (e.g., cannabinol) [8].

Safety

A thorough evaluation of safety outcomes with cannabichromene has not been conducted [8].

Drug Interactions

Preliminary clinical research suggests that cannabichromene might have sedative and hypnotic effects. Be aware that using cannabichromene with drugs, herbs, and supplements that have sedative properties may cause additive therapeutic and adverse effects [8].

6. GENERAL SAFETY CONSIDERATIONS

DELTA-8 TETRAHYDROCANNABINOL (DELTA-8 THC)

Delta-8 THC, an isomer of delta-9 THC (THC), is another psychoactive cannabinoid found in Cannabis that has serious safety issues. Delta-8 THC is estimated to be 50% to 75% as psychoactive as delta-9 THC [9].

The concentration of naturally occurring delta-8 THC in cannabis and hemp is low, and therefore most delta-8 THC is synthetically manufactured from CBD. Delta-8 THC may be synthetically derived from delta-9 THC and CBD [9].

Neither the safety nor efficacy of delta-8 THC has been evaluated in clinical studies.

Legal Implications

Because delta-8 THC is not acknowledged in the 2018 Farm Bill, its U.S. federal regulatory status is unclear. It is banned or restricted in some states, while remaining legal in others. The combination of its unclear regulatory status and its psychoactive effects have led to rapid increases in delta-8 THC availability and interest [9].

Safety

A thorough evaluation of safety outcomes with delta-8 THC has not been conducted. In the first seven months of 2021 alone, hospitalization occurred in 18% of 661 reported exposures to delta-8 THC. In the eight-month period ending in July 2021, 14 of 22 cases reported to the FDA presented to the hospital for adverse effects related to delta-8 THC-containing products [9].

According to data compiled from sources including the FDA, the Centers for Disease Control and Prevention (CDC), and the American Association of Poison Control Centers, some of the most common adverse effects associated with delta-8 THC include difficulty thinking and speaking, a dreamlike state, euphoria, feeling "high," and vision and time distortion. Serious safety signals also have been observed, including Brugada ECG pattern and cannabinoid hyperemesis syndrome, frequently leading to emergency room visits and hospitalization [9].

CLASS-WIDE SERIOUS ADVERSE EFFECTS OF CANNABINOIDS

Cannabinoid Hyperemesis Syndrome (CHS)

Excessive and prolonged cannabis use (e.g., two to three times daily over two years) can lead to a condition called cannabinoid hyperemesis syndrome (CHS). It is characterized by cyclic attacks of nausea and vomiting that are not alleviated by conventional antiemetics. Anecdotally, patients commonly report temporary relief of their symptoms with bathing in extremely hot water, and this is often what clues providers in to this diagnosis. CHS has occurred with smoking and/or oral use and has even been linked to severe complications resulting in death in several cases [10].

There are also case reports of CHS with delta-8 THC and K2/Spice. Non-THC cannabinoids (e.g., CBD, cannabigerol) also may play a role [10].

The cornerstone of long-term treatment for CHS is complete discontinuation of cannabis use, but benzodiazepines and capsaicin also may play a role in short-term symptom management [10].

E-cigarette, or Vaping, Product-Use Associated Lung Injury (EVALI)

E-cigarette, or vaping, product-use associated lung injury (EVALI) has occurred among adults and children using e-cigarette, or vaping, products. The majority of patients experiencing EVALI reported using THC-containing products in the three months prior to the development of symptoms. It is not clear if EVALI is the direct result of THC or another component of the formulation, like vitamin E acetate. The FDA has warned the public to stop using all THC-containing vaping products because of this risk [1].

CONTAMINATION CONCERNS

Contamination concerns are rampant with cannabis products, increasing the risk of serious adverse effects with their use. Cannabis sativa is a phytoremediator. Phytoremediators are plants that readily absorb contaminants from the soil. For this reason, cannabis products are at high risk for contamination from pesticides, heavy metals, bacteria, and fungus.

Most commercially available delta-8 THC is synthetically manufactured from CBD. For this reason, delta-8 THC products may contain heavy metals and other contaminants that may have been added or accidentally created during the synthesis of delta-8 THC. The process of synthesis may also increase the risk for variability in delta-8 THC content [1,9].

Product Quality and Cross Contamination with Other Cannabinoids

Product quality is lacking and cross contamination of cannabis products with other cannabinoids is abundant. Commercially available CBD products, especially those intended for vaping, have been frequently shown to be contaminated with THC or synthetic cannabinoids.

An analysis of seven commercially available CBD e-liquid formulations found that two products were contaminated with an undeclared synthetic cannabimimetic (5F-ADB) and another two contained undeclared THC. Off-the-shelf evaluations of commercially available oral CBD products have consistently demonstrated issues with product standardization and labeling.

In an analysis of 84 commercially available CBD products in the United States, only 31% of products were accurately labeled and 21% of products contained unlabeled THC. Other assessments of 14 products commercially available in Europe and 25 products available in the United States found that up to 90% of the products were inaccurately labeled and that up to 86% of products contained detectable quantities of THC [11,12].

CBD is also available in an e-liquid formulation for use in e-cigarettes intended for vaping. Interestingly, when CBD is exposed to temperatures typically occurring in e-cigarettes, it can be converted to delta-8 THC, cannabinol, cannabichromene, and other cannabinoids. Commercially available CBD, especially those intended for vaping, may be contaminated with synthetic cannabinoids, increasing the risk of serious associated adverse effects [11,12].

The increasing prevalence of delta-8 THC is also causing contamination concerns, as both the contaminant and the frequently contaminated. Some products labeled as hemp containing CBD might contain undeclared delta-8 THC. Delta-8 THC products might also contain other cannabinoids given that they are synthesized from other cannabinoids [9].

DRUG TESTING CONCERNS

In general, THC can be detected in blood tests for up to three days, saliva tests for up to four days, urine tests for anywhere from three to 21 days, and hair tests for up to 90 days after cannabis use [13,14].

Frequent contamination issues may be the root cause for many false positive results. For example, patients who use CBD might return a positive test due to the presence of trace amounts of THC. Use of other cannabinoids might also be responsible for false positive results on certain immunoassays testing for THC in the urine. Clinical research shows that high dose cannabinol use resulting in cannabinol urine concentrations about five times greater than the minimum THC concentration produce a positive THC signal on a specific immunoassay [13,14].

Make sure patients are adequately informed of the risks and unknowns related to drug testing with cannabinoids and cannabinoid-containing products.

SAFETY IN CHILDREN

Cannabis

There has been a recent uptick in accidental ingestion of cannabis-containing edibles in children ages 12 years and younger. Legalization of recreational cannabis and the availability of these more appealing food forms, like gummies, are likely to blame. Accidental ingestion of cannabis-containing edibles in children has been associated with ataxia, coma, hypotonia, hypothermia, lethargy, nystagmus, respiratory depression, seizures, and tremors [1].

Delta-8 THC

With the rise in popularity of delta-8 THC, delta-8 THC-containing gummies and other products resembling candy or cookies have been mistakenly consumed by children, often resulting in hospital admission. In the first seven months of 2021 alone, the American Association of Poison Control Centers statistics indicate that 39% of the 661 reported exposures to delta-8 THC occurred in children younger than 18 years old, with some requiring ICU admission. In two cases, children presented with deep sedation, hypotension, and a slowed heart rate following accidental ingestion of gummies containing delta-8 THC. In another case, a 2-year-old child presented with sedation and acute encephalopathy following accidental ingestion of gummies containing an estimated delta-8 THC dose of 15 mg/kg [9].

CBD

While prescription CBD (Epidiolex) has been safely used in children, there is not enough reliable information about the safety of other forms of CBD in children. In a poison control center report of 1,581 CBD exposures in children and adults, 5.7% of cases involved tachycardia. Most exposures were oral, single-substance exposures, but it is not clear what doses of CBD precipitated these reports [3].

7. CONSIDERATIONS FOR NON-ENGLISH-PROFICIENT PATIENTS

For patients who are not proficient in English, it is important that information regarding the benefits and risks associated with the use of medical marijuana and other cannabinoids be provided in their native language, if possible. When there is an obvious disconnect in the communication process between the practitioner and patient due to the patient's lack of proficiency in the English language, an interpreter is required. Interpreters can be a valuable resource to help bridge the communication and cultural gap between patients and practitioners. Interpreters are more than passive agents who translate and transmit information back and forth from party to party. When they are enlisted and treated as part of the interdisciplinary clinical team, they serve as cultural brokers who ultimately enhance the clinical encounter. In any case in which information regarding treatment options and medication/treatment measures are being provided, the use of an interpreter should be considered. Print materials are also available in many languages, and these should be offered whenever necessary.

8. CONCLUSION

Use of cannabis and cannabinoid-containing products continues to increase as regulations generally allow for increased access. In addition to recreational use, these products have consistently been touted for their health benefits, but the reality is that there is not a lot of evidence for their use, especially outside of prescription or other standardized products. Further, these products are not without serious safety concerns, including adverse effects, drug interactions, contamination, and product quality concerns. When patients ask questions or offer information about their potential or current usage of these products, it is imperative that clinicians provide evidence-based recommendations and appropriate safety warnings to help patients make informed decisions.

Works Cited

1. TRC Healthcare Natural Medicines Database. Cannabis. Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=947. Last accessed October 19, 2022.

2. TRC Healthcare Natural Medicines Database. Hemp. Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1605. Last accessed October 19, 2022.

3. TRC Healthcare Natural Medicines Database. Cannabidiol (CBD). Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1439. Last accessed October 19, 2022.

4. TRC Healthcare Natural Medicines Database. Cannabidivarin (CBDV). Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1601. Last accessed October 19, 2022.

5. TRC Healthcare Natural Medicines Database. Tetrahydrocannabivarin (THCV). Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1600. Last accessed October 19, 2022.

6. TRC Healthcare Natural Medicines Database. Cannabinol (CBN). Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1611. Last accessed October 19, 2022.

7. TRC Healthcare Natural Medicines Database. Cannabigerol (CBG). Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1602. Last accessed October 19, 2022.

8. TRC Healthcare Natural Medicines Database. Cannabichromene (CBC). Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1609. Last accessed October 19, 2022.

9. TRC Healthcare Natural Medicines Database. Delta-8-Tetrahydrocannabinol (Delta-8-THC). Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1653. Last accessed October 19, 2022.

10. Galli JA, Sawaya RA, Friedenberg FK. Cannabinoid hyperemesis syndrome. Curr Drug Abuse Rev. 2011;4(4):241-249.

11. ElSohly MA, Mehmedic Z, Foster S, Gon C, Chandra S, Church JC. Changes in cannabis potency over the last 2 decades (1995–2014): analysis of current data in the United States. Biol Psychiatry. 2016;79:613-619.

12. Chandra S, Radwan MM, Majumdar CG, Church JC, Freeman TP, ElSohly MA. New trends in cannabis potency in USA and Europe during the last decade (2008–2017). Eur Arch Psychiatry Clin Neurosci. 2019;269:5-15.

13. Verstraete AG. Detection times of drugs of abuse in blood, urine, and oral fluid. Ther Drug Monit. 2004;26:200-205.

14. Taylor M, Lees R, Henderson G, Lingford-Hughes A, et al. Comparison of cannabinoids in hair with self-reported cannabis consumption in heavy, light and non-cannabis users. Drug Alcohol Rev. 2017;36:220-226.

Evidence-Based Practice Recommendations Citations

1. Yadav V, Bever C, Bowen J, et al. Summary of evidence-based guideline: complementary and alternative medicine in multiple sclerosis: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014;82(12):1083-1092. Available at https://www.aan.com/Guidelines/home/GuidelineDetail/641. Last accessed October 25, 2022.

2. National Institute for Health and Care Excellence. Neuropathic Pain: Pharmacological Management. The Pharmacological Management of Neuropathic Pain in Adults in Non-Specialist Settings. London: National Institute for Health and Care Excellence; 2020. Available at https://www.nice.org.uk/guidance/cg173. Last accessed October 25, 2022.

98020 • Commonly Abused Supplements

Chelsey McIntyre, PharmD

www.netce.com

Copyright © 2022 NetCE, All rights reserved.

Dietary supplement use is increasingly common. In addition to their use for the management of medical conditions, dietary supplements are often misused or abused for recreation, body image concerns, athletic performance, and mood enhancement. Healthcare professionals should be well informed about these commonly abused supplements so that they can understand what they are and how they work and provide adequate safety warnings.

Table of Contents

98020 • Commonly Abused Supplements

Course Overview

Audience

Accreditations & Approvals

Designations of Credit

Individual State Nursing Approvals

Individual State Behavioral Health Approvals

Special Approvals

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planners

Division Planners Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

Implicit Bias in Health Care

1. INTRODUCTION

2. ABUSE POTENTIAL RELATED TO WEIGHT LOSS AND/OR ATHLETIC PERFORMANCE

1,3-DIMETHYLAMYLAMINE (1,3-DMAA)

BITTER ORANGE AND OCTOPAMINE

CAFFEINE

EPHEDRA

STIMULANT INTERACTION CONCERNS

3. LAXATIVES

SENNA

CASTOR OIL

SAFETY

4. ABUSE POTENTIAL RELATED TO RECREATIONAL USE

GHB

5. ABUSE POTENTIAL RELATED TO OPIOID-LIKE EFFECTS

KRATOM

6. CONSIDERATIONS FOR NON-ENGLISH-PROFICIENT PATIENTS

7. CONCLUSION

Works Cited

98020 • Commonly Abused Supplements

Education Category. Alternative Medicine

Release Date. 11/01/2022

Expiration Date. 10/31/2025

Course Overview

Dietary supplement use is increasingly common. In addition to their use for the management of medical conditions, dietary supplements are often misused or abused for recreation, body image concerns, athletic performance, and mood enhancement. Healthcare professionals should be well informed about these commonly abused supplements so that they can understand what they are and how they work and provide adequate safety warnings.

Audience

This course is designed for healthcare professionals whose patients are taking or are interested in taking dietary supplements.

Accreditations & Approvals

In support of improving patient care, TRC Healthcare/NetCE is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. NetCE has been approved by NBCC as an Approved Continuing Education Provider, ACEP No. 6361. Programs that do not qualify for NBCC credit are clearly identified. NetCE is solely responsible for all aspects of the programs. As a Jointly Accredited Organization, NetCE is approved to offer social work continuing education by the Association of Social Work Boards (ASWB) Approved Continuing Education (ACE) program. Organizations, not individual courses, are approved under this program. Regulatory boards are the final authority on courses accepted for continuing education credit. Continuing Education (CE) credits for psychologists are provided through the co-sponsorship of the American Psychological Association (APA) Office of Continuing Education in Psychology (CEP). The APA CEP Office maintains responsibility for the content of the programs. NetCE is accredited by the International Accreditors for Continuing Education and Training (IACET). NetCE complies with the ANSI/IACET Standard, which is recognized internationally as a standard of excellence in instructional practices. As a result of this accreditation, NetCE is authorized to issue the IACET CEU.

Designations of Credit

This activity was planned by and for the healthcare team, and learners will receive 2 Interprofessional Continuing Education (IPCE) credit(s) for learning and change. NetCE designates this enduring material for a maximum of 2 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. NetCE designates this continuing education activity for 2 ANCC contact hour(s). NetCE designates this continuing education activity for 2.4 hours for Alabama nurses. NetCE designates this continuing education activity for 0.5 NBCC clock hour(s). Social workers participating in this intermediate to advanced course will receive 2 Clinical continuing education clock hours. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 2 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Completion of this course constitutes permission to share the completion data with ACCME. Successful completion of this CME activity, which includes participation in the evaluation component, enables the learner to earn credit toward the CME and/or Self-Assessment requirements of the American Board of Surgery's Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit. Successful completion of this CME activity, which includes participation in the activity with individual assessments of the participant and feedback to the participant, enables the participant to earn 2 MOC points in the American Board of Pediatrics' (ABP) Maintenance of Certification (MOC) program. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABP MOC credit. Through an agreement between the Accreditation Council for Continuing Medical Education and the Royal College of Physicians and Surgeons of Canada, medical practitioners participating in the Royal College MOC Program may record completion of accredited activities registered under the ACCME's "CME in Support of MOC" program in Section 3 of the Royal College's MOC Program. NetCE is authorized by IACET to offer 0.2 CEU(s) for this program. AACN Synergy CERP Category A. NetCE designates this continuing education activity for 2 credit(s).

Individual State Nursing Approvals

In addition to states that accept ANCC, NetCE is approved as a provider of continuing education in nursing by: Alabama, Provider #ABNP0353 (valid through July 29, 2025); Arkansas, Provider #50-2405; California, BRN Provider #CEP9784; California, LVN Provider #V10662; California, PT Provider #V10842; District of Columbia, Provider #50-2405; Florida, Provider #50-2405; Georgia, Provider #50-2405; Kentucky, Provider #7-0054 through 12/31/2025; South Carolina, Provider #50-2405; West Virginia RN and APRN, Provider #50-2405.

Individual State Behavioral Health Approvals

In addition to states that accept ASWB, NetCE is approved as a provider of continuing education by the following state boards: Alabama State Board of Social Work Examiners, Provider #0515; Florida Board of Clinical Social Work, Marriage and Family Therapy and Mental Health Counseling, CE Broker Provider #50-2405; Illinois Division of Professional Regulation for Social Workers, License #159.001094; Illinois Division of Professional Regulation for Licensed Professional and Clinical Counselors, License #197.000185; Illinois Division of Professional Regulation for Marriage and Family Therapists, License #168.000190;

Special Approvals

This activity is designed to comply with the requirements of California Assembly Bill 1195, Cultural and Linguistic Competency.

Course Objective

The purpose of this course is to provide healthcare professionals in all practice settings the knowledge necessary to increase their understanding of the commonly abused supplements and their adverse effects.

Learning Objectives

Upon completion of this course, you should be able to:

1. Outline supplements with abuse potential related to weight loss and/or athletic performance.

2. Describe how dietary supplements with laxative effects might be abused.

3. Discuss the potential to misuse specific supplements for recreational or opioid-like experiences.

Faculty

Chelsey McIntyre, PharmD, is a clinical pharmacist who specializes in drug information, literature analysis, and medical writing. She earned her Bachelor of Science degree in Genetics from the University of California, Davis. She then went on to complete her PharmD at Creighton University, followed by a clinical residency at the Children’s Hospital of Philadelphia (CHOP). Dr. McIntyre held the position of Drug Information and Policy Development Pharmacist at CHOP until her move to Washington state in 2017, after which she spent the next six years as a clinical editor for Natural Medicines, a clinical reference database focused on natural products and alternative therapies. She continues to create rigorous professional analysis and patient education materials for various publications while also practicing as a hospital pharmacist. Her professional interests include provider and patient education, as well as the application of evidence-based research to patient care.

Faculty Disclosure

Contributing faculty, Chelsey McIntyre, PharmD, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planners

John M. Leonard, MD

Jane C. Norman, RN, MSN, CNE, PhD

Alice Yick Flanagan, PhD, MSW

James Trent, PhD

Division Planners Disclosure

The division planners have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

The Director of Development and Academic Affairs has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

Implicit Bias in Health Care

The role of implicit biases on healthcare outcomes has become a concern, as there is some evidence that implicit biases contribute to health disparities, professionals' attitudes toward and interactions with patients, quality of care, diagnoses, and treatment decisions. This may produce differences in help-seeking, diagnoses, and ultimately treatments and interventions. Implicit biases may also unwittingly produce professional behaviors, attitudes, and interactions that reduce patients' trust and comfort with their provider, leading to earlier termination of visits and/or reduced adherence and follow-up. Disadvantaged groups are marginalized in the healthcare system and vulnerable on multiple levels; health professionals' implicit biases can further exacerbate these existing disadvantages.

Interventions or strategies designed to reduce implicit bias may be categorized as change-based or control-based. Change-based interventions focus on reducing or changing cognitive associations underlying implicit biases. These interventions might include challenging stereotypes. Conversely, control-based interventions involve reducing the effects of the implicit bias on the individual's behaviors. These strategies include increasing awareness of biased thoughts and responses. The two types of interventions are not mutually exclusive and may be used synergistically.

1. INTRODUCTION

Use of dietary supplements continues to increase. In addition to their use for the management of medical conditions, dietary supplements are often misused or abused for recreation, body image concerns, athletic performance, and mood enhancement. Poison control center data indicate that abuse and misuse of dietary supplements occurs across the life span, with reports in adolescents to those older than 60 years of age [1].

Abuse refers to the use of a substance to gain a psychotropic effect. Misuse refers to the use of a substance for reasons other than a psychotropic effect. While abuse and misuse of dietary supplements is similar in many ways to other forms of substance abuse, there are a few things that set it apart from that of prescription medications, alcohol, tobacco, and illicit drugs. Many consumers perceive products that are natural to be synonymous with safety, which is certainly not the case. Additionally, availability of supplements reduces barriers to their access and legality concerns [1].

The focus of this course will be on the following commonly abused supplements, how they work, and their associated safety concerns:

- Stimulants (1,3-dimethylamylamine [1,3-DMAA], bitter orange, caffeine, ephedra, octopamine)

- Laxatives (castor oil, senna)

- Gamma hydroxybutyrate (GHB)

- Kratom

Note that these select supplements are commonly abused in North America. Supplements commonly abused in other parts of the world are beyond the scope of this course.

2. ABUSE POTENTIAL RELATED TO WEIGHT LOSS AND/OR ATHLETIC PERFORMANCE

Stimulants are a class of substances that speed up the body's systems, and for this reason, they are commonly referred to as "uppers." There are numerous U.S. Food and Drug Administration (FDA)-approved stimulants that are safely used under medical supervision for accepted medical uses (e.g., nasal decongestants, treatment of attention deficit hyperactivity disorder [ADHD]). Stimulant supplements are commonly touted for their energy-boosting beneficial effects on athletic performance and for promoting weight loss.

1,3-DIMETHYLAMYLAMINE (1,3-DMAA)

1,3-DMAA, also called methylhexaneamine, is a synthetic stimulant, meaning that it is prepared in a lab. It was originally developed as an ingredient for relieving nasal congestion because of its stimulant and vasoconstrictive activity. It has more recently been marketed in dietary supplements for athletic performance and weight loss [2].

Quality Concerns

Formulations of 1,3-DMAA often list rose geranium oil, geranium oil, or geranium stems as an ingredient on the label. While some manufacturers claim that 1,3-DMAA is a natural compound found in geranium oil, this claim has not been confirmed by laboratory analysis. In 2011, Health Canada determined that there is no credible evidence that 1,3-DMAA is derived from the geranium plant. As a result, there is concern that formulations purportedly containing "rose geranium oil," "geranium oil," and "geranium stems" may actually be adding the synthetic drug to their supplements [2].

Regulatory Concerns

In 2011, Health Canada determined that 1,3-DMAA should be considered a drug and is not allowed to be included in dietary supplements [2]. In 2013, the FDA declared products containing 1,3-DMAA to be illegal and to have potential health risks. 1,3-DMAA has been included on the prohibited lists of the World Anti-Doping Agency (WADA) and the U.S. Department of Defense (DoD) for more than 10 years [2].

Safety

Although 1,3-DMAA has been associated with cardiovascular adverse effects, these concerns have rarely been reported in patients taking 1,3-DMAA alone. Most of the severe adverse effects related to 1,3-DMAA are associated with its use in combination products [2].

Palpitations and tachycardia are the most common adverse effects reported with 1,3-DMAA-containing products. Angina, atrial fibrillation, chest pressure, hypertension, hypotension, and myocardial infarction have also occurred. In case reports of healthy young adults taking 1,3-DMAA-containing combination products prior to exercise, cardiac arrest causing death has occurred [2].

BITTER ORANGE AND OCTOPAMINE

Bitter orange is a small, flowering, fruit-bearing tree whose flowers, leaves, and fruits (including peel) have stimulant effects. Bitter orange has numerous active constituents and pharmacologic effects which vary by plant part and preparation method [3].

The fruit and the peel of bitter orange contain the adrenergic agonists synephrine and octopamine, which are frequently cited on labels as active ingredients. Synephrine and octopamine are chemically similar and occur naturally in the body in small amounts. Structurally, synephrine is similar to epinephrine and octopamine is similar to norepinephrine [3,4].

Quality Concerns

Many marketed bitter orange products contain greater amounts of synephrine and other natural and synthetic amines than is stated on the label, increasing the risk for serious stimulant-related adverse effects. In a laboratory analysis of marketed bitter orange products, only 22% of the products tested had synephrine content within 20% of the amount stated on labels. The analysis also confirmed the presence of the synthetic amines methylsynephrine and isopropyloctopamine, neither of which are permitted in dietary supplements [3].

Similarly, the amount of octopamine found in products marketed for athletic performance is much greater than the quantity found naturally occurring in some plants (e.g., bitter orange). Natural levels of octopamine in bitter orange are less than 0.03%. A review of 32 products showed that octopamine was present in two products at levels as high as 11% and 12.9%, suggesting that manufacturers are adding synthetic octopamine to supplement products. In an analysis of bitter orange extract, octopamine was identified in all three products tested, although it only appeared on the label of two products. One analyzed product contained only 2.8% of the quantity of octopamine stated on the label [4].

Regulatory Concerns

Since the FDA banned ephedra in 2004, bitter orange has been frequently used in products labeled as "ephedra-free." Synephrine, a constituent of bitter orange, is considered a banned substance by the National Collegiate Athletic Association (NCAA). Similarly, octopamine has been included on the WADA prohibited list [3,4].

Safety

Most of the severe adverse effects related to bitter orange are associated with its use in combination products. Hypertension and tachycardia are the most common adverse effects reported with bitter orange-containing products, particularly in combination with caffeine and/or other stimulant ingredients. Other adverse effects reported with the use of bitter orange- or synephrine-containing multi-ingredient products, with or without other stimulants, include blackout, cardiac arrest, collapse, ischemic stroke, myocardial infarction, QT prolongation, tachyarrhythmia, tachycardia, variant angina, ventricular fibrillation, and death [3].

A clinical evaluation of safety outcomes has not been conducted for octopamine, but given its chemical similarity to synephrine, adverse effects similar to those seen with other stimulants can be expected [4].

CAFFEINE

Caffeine might be one of the best-known stimulants. It is a naturally occurring, bitter-tasting methylxanthine compound found in the leaves, seeds, or fruits of more than 60 plants, including coffee (Coffea arabica) beans, cacao (Theobroma cacao) beans, kola (Cola acuminata) nuts, guarana (Paullinia cupana) berries, and tea (Camellia sinensis) leaves. It is structurally related to theophylline, theobromine, and uric acid and is a nonselective adenosine antagonist [5].

Caffeine is present in a wide variety of beverages [5]:

- One cup of brewed coffee provides 95–200 mg of caffeine.

- An 8-ounce serving of black tea provides 25–110 mg of caffeine.

- An 8-ounce serving of green tea provides 30–50 mg of caffeine.

- A 12-ounce soft drink (e.g. cola) provides 20–80 mg of caffeine.

- A serving of sports or energy drink typically provides 48–300 mg of caffeine.

Caffeine is also available alone or in combination with other ingredients in some prescription and over-the-counter products that are approved for specific medical uses (e.g., to help restore mental alertness and wakefulness when experiencing fatigue or drowsiness). Caffeine tablets contain up to about 200 mg of caffeine [5].

Keep in mind that only the amount of added caffeine must be stated on product labels, and the amount of caffeine from caffeine-containing natural ingredients (e.g., coffee, green tea) is not required to be provided, making it difficult to determine the total amount of caffeine in a given product.

Caffeine has been demonstrated to improve athletic performance. It decreases perceived levels of exertion, enabling athletes to feel less tired and increase their performance. It can also improve anaerobic exercise performance. Within limits, the NCAA allows caffeine consumption. During competition, however, urine concentrations must not exceed 15 mcg/mL. Consumption of 600–800 mg of caffeine would need to be consumed two to three hours prior to performance in most people in order to achieve this urine concentration [5].

Safety

A review by Health Canada and a subsequent large meta-analysis conducted in the United States show that caffeine doses up to 400 mg daily are not associated with significant adverse cardiovascular, bone, behavioral, or reproductive effects in healthy adults. Similarly, the U.S. Dietary Guidelines Advisory Committee states that there is strong and consistent evidence that consumption of caffeine 400 mg daily is not associated with increased risk of major chronic diseases, such as cardiovascular disease or cancer, in healthy adults [5].

Caffeine is generally well tolerated, with regular use and in moderate doses. Common side effects include cause anxiety, diarrhea, diuresis, headache, insomnia, muscular tremors, nausea, and restlessness. But caffeine can become unsafe when used long-term and/or in high doses [5].

Acute use of high doses, typically those exceeding 400 mg daily, have been associated with significant adverse effects, such as tachyarrhythmia and sleep disturbances. Some people may experience serious toxicity even at lower doses, owing to caffeine's effects being impacted by smoking status, age, and prior caffeine use [5].

Some caffeine products for supplement use are highly concentrated or pure formulations. These are most concerning because they have a high risk for being mistakenly used in excessive and potentially dangerous doses. Powdered pure caffeine can contain as much as 3.2 grams of caffeine in a single teaspoon and concentrated liquid caffeine can contain about 2 grams of caffeine in as little as one-half cup [5].

With large amounts of caffeine (more than 10 mg per kg daily), there have been reports of aortic dissection, atrial fibrillation, cardiac arrest, celiac artery trunk dissection, chest pain, coronary artery vasospasm, extrasystoles, hemorrhagic stroke, ischemic stroke, tachycardia, transient ischemic attack, and ventricular tachycardia [5].

The acute oral dose of caffeine resulting in death in adults is estimated to be 10–14 grams (150–200 mg per kg), although fatality has occurred at lower doses. Deaths typically have been attributed to ventricular fibrillation [5]. At least two deaths have been linked to the use of highly concentrated and pure formulations. In 2018, the FDA announced that highly concentrated and pure formulations of caffeine are unlawful when sold directly to consumers in bulk quantities [5].

There have been numerous case reports of seizures with excessive caffeine intake and also when combining caffeine with other stimulants. Life-threatening events are also more common after taking caffeine-containing energy or weight loss products when compared with non-caffeine containing products. Deaths have occurred following consumption of caffeine alone or in combination with other stimulants or alcohol [5].

EPHEDRA

Ephedra, sometimes called ma huang, is a stimulant herb usually taken from the stem and branches of Ephedra sinica. It contains the principal alkaloid constituents ephedrine, pseudoephedrine, and sometimes small amounts of phenylpropanolamine. It has a long history of use in traditional Chinese medicine. It has traditionally been used for allergy symptoms, arthritis, asthma, bone pain, bronchitis, edema, headache, nephritis, and symptoms of the common cold and influenza. It has also been marketed as "herbal ecstasy," for use as a recreational drug [6].

While most Ephedra species contain ephedrine alkaloids, Mormon tea (Ephedra nevadensis or Ephedra viridis) is a plant in the Ephedra genus that is devoid of ephedrine and other alkaloids. Some other plants also contain ephedrine alkaloids, including Sida cordifolia and Pinellia ternate [6].

Regulatory Concerns

Because of the potential for serious safety concerns associated with its use, ephedra, Sida cordifolia, Pinellia ternata, or other ephedrine-containing herbs have been banned in the United States since 2004. Despite this ban, ephedra products can still be obtained on the Internet, often in combination products containing caffeine and/or other stimulants (e.g., synephrine, phenylethylamine [PEA], and yohimbine) [6].

Like other stimulants, ephedra is sometimes touted for its performance-enhancing effects, but these effects have not been substantiated in clinical studies. Ephedra appears on the prohibited list of many large sports and other organizations, including the NCAA [6].

Quality Concerns

There is considerable inter- and intra-product variability in labeled ephedra content. This increases concerns about ephedra toxicity.

There is also significant variability in the amounts of constituents found in ephedra supplements. In one study, ephedra supplements were found to contain 1.08–13.54 mg of ephedrine and 0.52–9.46 mg of pseudoephedrine per recommended dose. In other studies, 1 gram of a dry extract of ephedra was found to contain 58.9 mg of total ephedrine alkaloids, comprised of 0.44 mg of norephedrine, 1.09 mg of methylephedrine, 1.01 mg of norpseudoephedrine, 11.21 mg of pseudoephedrine, and 45.15 mg of ephedrine [6].

Norpseudoephedrine, a Schedule IV controlled substance, has been found to be a contaminant in some ephedra products [6].

Safety

Prior to its removal from the U.S. market, ephedra accounted for less than 1% of herbal product sales but was responsible for 64% of herbal adverse reaction reports to poison control centers. In a review of 926 cases of potential ephedra-related adverse effects reported to the FDA, 37 patients had serious or fatal adverse reactions [6].

Ephedra can cause severe life-threatening or disabling adverse effects in some people. It has been linked to significant cardiovascular effects, including cardiac arrhythmias, cardiac arrest, cardiomyopathy, heart failure, and myocardial infarction, as well as seizure, stroke, psychosis, and sudden death. There is some evidence that taking more than 32 mg daily might increase the risk of hemorrhagic stroke, including subarachnoid hemorrhage and intracerebral hemorrhage, by more than threefold [6].

While prolonged use and high doses might increase the risk of serious adverse effects, serious adverse effects have also been reported at low doses (e.g., 20–60 mg of ephedra alkaloids) in the short-term. It is impossible to determine who might be at the greatest risk from ephedra's adverse effects, but people with existing cardiovascular disease and those using combinations of stimulants might be at increased risk [6].

In addition to serious cardiovascular effects, cases of hepatotoxicity (e.g., acute hepatitis, liver failure) from ephedra-containing supplements have been reported after an average of three months of ephedra ingestion. Some cases of hepatotoxicity have resolved with discontinuation of ephedra, but others have required liver transplantation. Immune reactions and contamination have been proposed as potential causes of hepatotoxicity, but the majority of evidence suggests that ephedra-related hepatotoxicity is idiosyncratic in nature [6].

STIMULANT INTERACTION CONCERNS

Interactions with Lab Tests

Some stimulants might cause false-positive test results on urine amphetamine and/or methamphetamine drug screens. This should be considered when interpreting urine drug screen results in patients who deny amphetamine and/or methamphetamine use [5,6].

Interactions with Drugs and Supplements

Stimulants can have a fair amount of drug interactions. The most notable drug interaction concern is for the combination of a stimulant with other drugs or supplements that are stimulants or have stimulant properties. This combination can increase the risk of adverse effects, particularly cardiovascular adverse effects [2,3,4,5,6].

3. LAXATIVES

While laxatives themselves are not addicting, they are commonly misused for weight-loss effects. With the exception of senna, over-the-counter laxatives, which are not exempt from misuse, will not be covered in this course.

SENNA

Senna is the fruit (pod) or leaf of the plant Senna alexandrina. Senna contains sennosides, which are high molecular weight dianthrone glycosides [7].

Because sennosides are prodrugs, they are not absorbed in the gastrointestinal (GI) tract and are instead activated by enzymes in the colon. The cathartic properties of the senna leaf are greater than the fruit. Effects usually occur within 6 to 10 hours after oral administration [7].

Senna is an FDA-approved nonprescription stimulant laxative found in many commercially available products that are approved for the short-term treatment of constipation in adults and children 2 years of age or older. These products contain the active ingredient sennosides [7].

Senna is also available in dietary supplements containing variable amounts of the leaf. Senna leaf is sometimes added to weight loss products or "cleansing" teas, but these uses are unproven and may be unsafe [7].

CASTOR OIL

Castor oil is the oil that comes from castor beans (seeds). Unlike the beans, castor oil does not contain the deadly poison ricin [8].

Castor oil is a stimulant laxative that has been used as a laxative in multiple systems of medicine (e.g., Unani, Ayurvedic) in India since 2000 B.C.E. It is hydrolyzed in the duodenum by pancreatic lipase to release ricinoleic acid [8].

While the exact mechanism of ricinoleic acid is unknown, laxative effects appear to result from a combination of fluid secretion and increased peristalsis. The onset of action is usually within two, but sometimes up to six, hours [8].

Castor oil is sometimes flavored (e.g., with cinnamon, peppermint, or other flavorings) to mask its overall slightly bitter and nauseating taste [8].

SAFETY

Stimulant laxatives can cause abdominal pain and discomfort, bloating, cramping, diarrhea, faintness, flatulence, fecal urgency, and nausea. Use of laxatives at high doses and for long periods might be unsafe. Abuse of laxatives can cause fluid and electrolyte, particularly potassium, losses. Theoretically, this can increase the risk for arrhythmias. There is also a risk of malabsorption as a result of intestinal hypermotility [7,8].

Cases of "cathartic colon" have been described in the literature following chronic use of both senna and castor oil. Cathartic colon refers to radiographically diagnosed anatomic changes to the colon, such as benign narrowing, colonic dilation, and loss of colonic folds. The clinical relevance of such changes is unclear [7,8].

Chronic use of senna can also cause pseudomelanosis coli (pigmented spots along the intestinal mucosa), but this condition is harmless, reverses with cessation, and has not been shown to be associated with an increased risk of developing colorectal adenoma or carcinoma [7].

Long-term use of laxatives is thought to result in habituation and/or tolerance. Habituation refers to a reduced or even absent laxative response, and tolerance refers to the need for increased doses in order to maintain the desired laxative response. Both habituation and tolerance could theoretically be induced by damage to the colon or by an adaptive mechanism counteracting the laxative's effect on motility and/or secretion [9].

Uncontrolled observational studies in humans and conflicting data from prospective animal studies have raised concerns that chronic stimulant laxative use can actually cause nerve or muscle damage to the colon, but these concerns have been largely disproven by higher quality studies [9]. While tolerance may occur in patients with severely slow colonic transit in whom other types of laxatives are ineffective, development of tolerance seems to be uncommon in the majority of users.

Be sure to ask patients about dietary supplement usage while obtaining their medication history. And be on the lookout for purchasing practices that might suggest inappropriate use.

4. ABUSE POTENTIAL RELATED TO RECREATIONAL USE

Like prescription drugs, many supplements are abused on the party scene and for varying other recreational reasons. Among these is gamma-hydroxybutyrate (GHB) for its euphoric, amnestic, and calming effects.

GHB

GHB is a short-chain fatty acid made from gamma aminobutyric acid (GABA). GHB is naturally occurring in the brains of mammals in very small amounts. The highest concentrations in the brain are found in the basal ganglia. GHB is also found in other tissues, including the kidneys, liver, heart, skeletal muscle, and brown fat [10].

GHB is an agonist at GABA-B receptors and is also converted to GABA. The central nervous system (CNS) depressant effects of GHB, especially those observed at higher doses, can be attributed to direct agonist activity at GABA-B receptors. GHB has also been reported to raise dynorphin levels through its effects on the endogenous opioid system. Stimulation of GHB receptors also results in a reduction in dopamine release in the basal ganglia and influences dopamine release in the substantia nigra [10].

GHB abuse became popular among teens and young adults at dance clubs and raves in the 1990s, but use persists today. GHB is used as a party drug, for its euphoric and calming effects and for sexual arousal, and in cases of drug-facilitated sexual assault. It is usually sold as a clear, colorless liquid or as a white powder that can be dissolved in liquid [10].

In the United States, GHB is federally classified as a Schedule I controlled substance, making production, sale, and possession outside of medical use illegal. The major source of GHB is through clandestine synthesis by local operators [10].

An FDA-approved prescription form of the sodium salt of GHB, known as sodium oxybate (Xyrem), is labeled for the treatment of cataplexy or excessive daytime sleepiness in patients 7 years of age or older with narcolepsy. Sodium oxybate is a Schedule III controlled substance and seems to be safe when used appropriately under medical supervision [10].

Several chemically related analogs of GHB, including gamma butyrolactone (GBL) and 1,4-butanediol (BD), are rapidly converted to GHB in the body and have similar effects to the parent compound. Popularity of these analogs increased with the regulatory restriction of GHB as a Schedule I controlled substance. These analogs are legally available as industrial solvents, but are also sold illicitly as supplements for bodybuilding, weight loss, reversal of baldness, drug addiction, and other uses. GBL and BD are abused for the same reasons as GHB. Routine toxicologic screens do not detect the presence of these analogs, so abuse can be difficult to identify [16].

Safety

When used orally without medical supervision (i.e., not as a prescription medicine), GHB is not safe for any use. Serious side effects include ataxia, cardiac arrest, coma, respiratory depression, tonic-clonic seizure, variable heart rate, and death. The analogs GBL and BD have also been associated with a large number of reports of such serious adverse reactions [10,16].

Evidence Based Practice Recommendation

The UK Department of Health asserts that persons providing services to patients who use GHB should advise these individuals to be aware of the added risks of mixing GHB with other sedative drugs.

https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/673978/clinical_guidelines_2017.pdf

Last Accessed: October 27, 2022

Level of Evidence: Consensus Statement/Expert Opinion

Concomitant use of GHB and its analogs with alcohol and some other co-ingestants can increase the risk of CNS and respiratory depression, as well as other severe adverse effects. Alcohol may also inhibit the clearance of GHB [10].

GHB is commonly used in cases of drug-facilitated sexual assault. Patients can help avoid becoming a victim by never taking a drink from a stranger and never leaving a drink unattended. If poisoning is suspected, call poison control at 1-800-222-1222 [10]. There is no antidote for GHB toxicity, and treatment is limited to supportive care. In patients with severe GHB intoxication, maintaining airway patency with intubation, if necessary, is the most important intervention. Because GHB can cause a rapid loss of consciousness, gastric lavage and induction of emesis are contraindicated. Symptomatic bradycardia can be managed with atropine, and seizures respond effectively to benzodiazepines [11,12]. Withdrawal symptoms are best managed with anxiolytics [13].

Regular GHB use can also cause dependence requiring inpatient detoxification. Withdrawal from GHB can cause agitation, anxiety, diaphoresis, delirium with auditory and visual hallucinations, hypertension, insomnia, panic, psychoses, rhabdomyolysis, tachycardia, terror, and tremor [10].

5. ABUSE POTENTIAL RELATED TO OPIOID-LIKE EFFECTS

KRATOM

Similar to an opioid, kratom is mainly used for its opioid-like effects. Kratom, Mitragyna speciosa, is a tropical tree that is native to Southeast Asia. The leaves are the part of the plant that garnered has interest, either when chewed as whole leaves, consumed as beverages prepared from the leaves (e.g., tea, juice), powdered and packaged into gel caps, or as an extract. The leaves have also been crushed and then smoked, but kratom is mostly abused through oral ingestion [14].

Kratom contains a long list of constituents, including corynantheidine, isopaynantheine, mitraciliatine, paynantheine, speciociliatine, speciogynine, and 9-hydroxycorynantheidine, but the alkaloids mitragynine and 7-hydroxymitraginine are thought to be its main active constituents. Twenty kratom leaves are estimated to contain about 18 mg of mitragynine [14].

Kratom contains the mu-opioid receptor agonist 7-hydroxymitragynine. 7-Hydroxymitragynine is estimated to be approximately 10 times as potent as morphine [14].

Kratom also contains a number of mu-opioid receptor partial agonists, including mitragynine. Mitragynine is estimated to be about 25% as potent as morphine, but it is present in much larger quantities than 7-hydroxymitragynine. Mitragynine makes up about 60% of kratom's alkaloid content and 7-hydroxymytragynine makes up 2% [14].

Kratom has both stimulant- and opioid-like properties, and its effects when taken by mouth are dose-dependent. Higher doses of kratom (e.g., 5–15 grams) are said to produce analgesic opioid-like effects, while lower doses (e.g., 1–5 grams) have stimulating effects [14].

Kratom has been used for its psychoactive properties and opium-like effects. It has been used for centuries in Thailand and Malaysia in socioreligious ceremonies, as an aid to combat fatigue in laborers, as an opioid substitute, and for other medical purposes. Several recent surveys have identified self-treatment of acute or chronic pain as the primary use for kratom. However, there is not enough information to support the use of kratom for any condition, and the risks certainly do not outweigh any potential benefits given its safety profile [14].

In the past, kratom use has not been widespread in the United States, but poison control center data show that interest seems to be growing. Between 2014 and 2019, U.S. poison control centers saw a rapid increase in kratom exposures [1].

In 2016, the Drug Enforcement Administration (DEA) attempted to ban kratom by making its mitragynine and 7-hydroxymitragynine constituents Schedule I substances in the United States under the Controlled Substances Act (CSA). This attempt to schedule these constituents was met with intense backlash from the public, industry, and some members of Congress [14]. While the DEA cited concerns of increases in the incidence of kratom-related seizures and calls to poison control centers related to kratom, the DEA ultimately withdrew its intent to schedule based on this strong opposition.

While the kratom tree and its leaves are illegal or restricted in some countries and states, it is not illegal in the United States. It is readily available for in-person purchase in many states, in addition to Internet sales. The manufacturing, sale, or possession of kratom products are not currently regulated by the FDA or DEA, but the DEA has listed kratom as a drug and chemical of concern [15].

Kratom has been reported to be contaminated with various substances, including heavy metals and phenethylamine (PEA), an amphetamine-like substance. In 2018, the Centers for Disease Control and Prevention (CDC) reported a Salmonella outbreak sickening at least 134 people in more than 35 states that was found to be linked to kratom products [14].

Some kratom products have been suspected to be adulterated with respect to the active constituents. In a laboratory analysis, samples of some commercially available kratom products were found to contain 4.5-fold higher concentrations of 7-hydroxymitragynine than are usually present in kratom leaves [14].

Safety

The FDA has warned consumers on multiple occasions that kratom is unsafe. Kratom has been linked to serious adverse effects, including respiratory depression, aggression, hallucinations, delusions, vomiting, seizures, liver damage, severe withdrawal, and death. Short-term use, especially in combination with other substances, has been associated with cases of intrahepatic cholestasis, rhabdomyolysis, seizure, encephalopathy syndrome, and death. Long-term use has been associated with tolerance and withdrawal symptoms, including aggression, anxiety, muscle aches and spasms, nausea and vomiting, shakiness and tremors, and QT interval prolongation [14].

Interactions with Drugs

Kratom seems to inhibit many enzymes commonly involved in the metabolism of drugs, potentially increasing their levels and effects. It also might have overlapping effects with drugs that have similar mechanisms [14].

Interactions with Conditions

In patients with alcohol use disorder or other psychiatric disorders, epidemiologic research suggests an increased risk of suicide with kratom use. In patients with existing cardiac conditions, kratom use can increase the risk of tachycardia [14].

In animal studies, kratom seems to cross the placenta. In humans, there have been multiple reports of neonatal abstinence syndrome (NAS) in infants born to patients using kratom during pregnancy [14].

Do not assume that potentially harmful use of supplements only occurs in young people. With kratom use on the rise among all demographics, increased use of kratom among older adults is particularly concerning as data have shown severe effects in this population [14].

6. CONSIDERATIONS FOR NON-ENGLISH-PROFICIENT PATIENTS

For patients who are not proficient in English, it is important that information regarding the benefits and risks associated with the use of dietary supplements be provided in their native language, if possible. When there is an obvious disconnect in the communication process between the practitioner and patient due to the patient's lack of proficiency in the English language, an interpreter is required. Interpreters can be a valuable resource to help bridge the communication and cultural gap between patients and practitioners. Interpreters are more than passive agents who translate and transmit information back and forth from party to party. When they are enlisted and treated as part of the interdisciplinary clinical team, they serve as cultural brokers who ultimately enhance the clinical encounter.

7. CONCLUSION

Dietary supplement use continues to increase. In 2020, U.S. supplement sales surpassed $10 billion for the first time ever [17]. Unfortunately, with increased use also comes increased abuse and misuse. Recreation, body image concerns, athletic performance, and mood enhancement continue to drive inappropriate use. Knowing the common culprits, how they work, and their potential adverse effects can enhance patient education and the detection of potential supplement abuse.

Works Cited

1. Biggs JM, Morgan JA, Lardieri AB, Kishk OA, Klein-Schwartz W. Abuse and misuse of selected dietary supplements among adolescents: a look at poison center data. J Pediatr Pharmacol Ther. 2017;22(6):385-393.

2. TRC Healthcare Natural Medicines Database. 1,3-DMAA. Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1258. Last accessed October 22, 2022.

3. TRC Healthcare Natural Medicines Database. Bitter Orange. Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=976. Last accessed October 22, 2022.

4. TRC Healthcare Natural Medicines Database. Octopamine. Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1590. Last accessed October 22, 2022.

5. TRC Healthcare Natural Medicines Database. Caffeine. Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=979. Last accessed October 22, 2022.

6. TRC Healthcare Natural Medicines Database. Ephedra. Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=847. Last accessed October 22, 2022.

7. TRC Healthcare Natural Medicines Database. Senna. Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=652. Last accessed October 22, 2022.

8. TRC Healthcare Natural Medicines Database. Castor Bean. Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=897. Last accessed October 22, 2022.

9. Müller-Lissner SA, Kamm MA, Scarpignato C, Wald A. Myths and misconceptions about chronic constipation. Am J Gastroenterol. 2005;100(1):232-242.

10. TRC Healthcare Natural Medicines Database. Gamma-hydroxybutyrate (GHB). Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=950. Last accessed October 22, 2022.

11. Smith KM, Larive LL, Romanelli F. Club drugs: methylenedioxymethamphetamine, flunitrazepam, ketamine hydrochloride, and gamma-hydroxybutyrate. Am J Health-Syst Pharm. 2002;59(11):1067-1076.

12. Benzer TI. Gamma-Hydroxybutyrate Toxicity. Available at https://emedicine.medscape.com/article/820531-overview. Last accessed October 22, 2022.

13. Greene JP, Ahrendt D, Stafford EM. Adolescent abuse of other drugs. Adolesc Med Clin. 2006;17(2):283-318.

14. TRC Healthcare Natural Medicines Database. Kratom. Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1513. Last accessed October 22, 2022.

15. Drug Enforcement Administration. Drugs of Abuse: A DEA Resource Guide. Washington, DC: U.S. Department of Justice; 2020.

16. TRC Healthcare Natural Medicines Database. Gamma Butyrolactone (GBL). Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=820. Last accessed October 22, 2022.

17. Smith T, Majid, F, Eckl V, Reynolds CM. Herbal supplements sales in US increase by record-breaking 17.3% in 2020: sales of immune health, stress relief, and heart health supplements grow during COVID-19 pandemic. HerbalGram. 2021;(131):52-65.

98030 • Getting to the Point: Acupuncture and Acupoint Therapies

Chelsey McIntyre, PharmD

www.netce.com

Copyright © 2022 NetCE, All rights reserved.

Acupoint therapies have existed for thousands of years and are commonly practiced around the world. Patients may seek clarification regarding the various acupoint techniques used today, including information on safety and effectiveness. Healthcare professionals should be well informed about these practices so that they can provide evidence-based recommendations on the use of these treatments.

Table of Contents

98030 • Getting to the Point: Acupuncture and Acupoint Therapies

Course Overview

Audience

Accreditations & Approvals

Designations of Credit

Individual State Nursing Approvals

Individual State Behavioral Health Approvals

Special Approvals

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planners

Division Planners Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

Implicit Bias in Health Care

1. HISTORY: A BRIEF GLIMPSE

ACUPUNCTURE

MOXIBUSTION

ACUPRESSURE

TRANSCUTANEOUS ELECTRICAL ACUSTIMULATION (TEAS)

A NOTE ON THE EVIDENCE

2. ACUPUNCTURE

STYLES OF ACUPUNCTURE

REVIEWING THE EVIDENCE

SAFETY

3. MOXIBUSTION

MOXIBUSTION TECHNIQUES

REVIEWING THE EVIDENCE

SAFETY

4. ACUPRESSURE

REVIEWING THE EVIDENCE

SAFETY

5. TRANSCUTANEOUS ELECTRICAL ACUSTIMULATION (TEAS)

REVIEWING THE EVIDENCE

SAFETY

6. CONSIDERATIONS AND COMPARISONS

REPRODUCTIVE EFFECTS

INTERACTIONS WITH CONDITIONS

COMPARING THE EVIDENCE

7. CONSIDERATIONS FOR NON-ENGLISH-PROFICIENT PATIENTS

8. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

98030 • Getting to the Point: Acupuncture and Acupoint Therapies

Education Category. Alternative Medicine

Release Date. 11/01/2022

Expiration Date. 10/31/2025

Course Overview

Acupoint therapies have existed for thousands of years and are commonly practiced around the world. Patients may seek clarification regarding the various acupoint techniques used today, including information on safety and effectiveness. Healthcare professionals should be well informed about these practices so that they can provide evidence-based recommendations on the use of these treatments.

Audience

This course is designed for healthcare professionals whose patients are using or are interested in using acupoint and/or acupressure therapies.

Accreditations & Approvals

In support of improving patient care, TRC Healthcare/NetCE is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. NetCE has been approved by NBCC as an Approved Continuing Education Provider, ACEP No. 6361. Programs that do not qualify for NBCC credit are clearly identified. NetCE is solely responsible for all aspects of the programs. As a Jointly Accredited Organization, NetCE is approved to offer social work continuing education by the Association of Social Work Boards (ASWB) Approved Continuing Education (ACE) program. Organizations, not individual courses, are approved under this program. Regulatory boards are the final authority on courses accepted for continuing education credit. Continuing Education (CE) credits for psychologists are provided through the co-sponsorship of the American Psychological Association (APA) Office of Continuing Education in Psychology (CEP). The APA CEP Office maintains responsibility for the content of the programs. NetCE is accredited by the International Accreditors for Continuing Education and Training (IACET). NetCE complies with the ANSI/IACET Standard, which is recognized internationally as a standard of excellence in instructional practices. As a result of this accreditation, NetCE is authorized to issue the IACET CEU.

Designations of Credit

This activity was planned by and for the healthcare team, and learners will receive 4 Interprofessional Continuing Education (IPCE) credit(s) for learning and change. NetCE designates this enduring material for a maximum of 4 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. NetCE designates this continuing education activity for 4 ANCC contact hour(s). NetCE designates this continuing education activity for 4.8 hours for Alabama nurses. NetCE designates this continuing education activity for 1 NBCC clock hour(s). Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 4 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Completion of this course constitutes permission to share the completion data with ACCME. Social workers participating in this intermediate to advanced course will receive 4 Clinical continuing education clock hours. Successful completion of this CME activity, which includes participation in the evaluation component, enables the learner to earn credit toward the CME and/or Self-Assessment requirements of the American Board of Surgery's Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit. This activity has been approved for the American Board of Anesthesiology’s® (ABA) requirements for Part II: Lifelong Learning and Self-Assessment of the American Board of Anesthesiology’s (ABA) redesigned Maintenance of Certification in Anesthesiology Program® (MOCA®), known as MOCA 2.0®. Please consult the ABA website, www.theABA.org, for a list of all MOCA 2.0 requirements. Maintenance of Certification in Anesthesiology Program® and MOCA® are registered certification marks of the American Board of Anesthesiology®. MOCA 2.0® is a trademark of the American Board of Anesthesiology®. Successful completion of this CME activity, which includes participation in the activity with individual assessments of the participant and feedback to the participant, enables the participant to earn 4 MOC points in the American Board of Pediatrics' (ABP) Maintenance of Certification (MOC) program. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABP MOC credit. Through an agreement between the Accreditation Council for Continuing Medical Education and the Royal College of Physicians and Surgeons of Canada, medical practitioners participating in the Royal College MOC Program may record completion of accredited activities registered under the ACCME's "CME in Support of MOC" program in Section 3 of the Royal College's MOC Program. NetCE designates this continuing education activity for 4 credit(s). NetCE is authorized by IACET to offer 0.4 CEU(s) for this program. AACN Synergy CERP Category A.

Individual State Nursing Approvals

In addition to states that accept ANCC, NetCE is approved as a provider of continuing education in nursing by: Alabama, Provider #ABNP0353 (valid through July 29, 2025); Arkansas, Provider #50-2405; California, BRN Provider #CEP9784; California, LVN Provider #V10662; California, PT Provider #V10842; District of Columbia, Provider #50-2405; Florida, Provider #50-2405; Georgia, Provider #50-2405; Kentucky, Provider #7-0054 through 12/31/2025; South Carolina, Provider #50-2405; West Virginia RN and APRN, Provider #50-2405.

Individual State Behavioral Health Approvals

In addition to states that accept ASWB, NetCE is approved as a provider of continuing education by the following state boards: Alabama State Board of Social Work Examiners, Provider #0515; Florida Board of Clinical Social Work, Marriage and Family Therapy and Mental Health Counseling, CE Broker Provider #50-2405; Illinois Division of Professional Regulation for Social Workers, License #159.001094; Illinois Division of Professional Regulation for Licensed Professional and Clinical Counselors, License #197.000185; Illinois Division of Professional Regulation for Marriage and Family Therapists, License #168.000190;

Special Approvals

This activity is designed to comply with the requirements of California Assembly Bill 1195, Cultural and Linguistic Competency.

Course Objective

The purpose of this course is to provide healthcare professionals in all practice settings the knowledge necessary to increase their understanding of acupoint and acupressure therapies.

Learning Objectives

Upon completion of this course, you should be able to:

1. Describe the principles from traditional Chinese medicine (TCM) that guide the practice of acupuncture and some related acupoint therapies.

2. Outline the various techniques of and available evidence regarding acupuncture.

3. Discuss the approaches to and evidence of moxibustion.

4. Review available research and techniques of acupressure.

5. Identify uses and safety concerns of trans- cutaneous electrical acustimulation (TEAS).

6. Compare and contrast the various acupoint techniques in terms of clinical uses and safety.

Faculty

Chelsey McIntyre, PharmD, is a clinical pharmacist who specializes in drug information, literature analysis, and medical writing. She earned her Bachelor of Science degree in Genetics from the University of California, Davis. She then went on to complete her PharmD at Creighton University, followed by a clinical residency at the Children’s Hospital of Philadelphia (CHOP). Dr. McIntyre held the position of Drug Information and Policy Development Pharmacist at CHOP until her move to Washington state in 2017, after which she spent the next six years as a clinical editor for Natural Medicines, a clinical reference database focused on natural products and alternative therapies. She continues to create rigorous professional analysis and patient education materials for various publications while also practicing as a hospital pharmacist. Her professional interests include provider and patient education, as well as the application of evidence-based research to patient care.

Faculty Disclosure

Contributing faculty, Chelsey McIntyre, PharmD, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planners

John M. Leonard, MD

Jane C. Norman, RN, MSN, CNE, PhD

Alice Yick Flanagan, PhD, MSW

James Trent, PhD

Division Planners Disclosure

The division planners have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

The Director of Development and Academic Affairs has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

Implicit Bias in Health Care

The role of implicit biases on healthcare outcomes has become a concern, as there is some evidence that implicit biases contribute to health disparities, professionals' attitudes toward and interactions with patients, quality of care, diagnoses, and treatment decisions. This may produce differences in help-seeking, diagnoses, and ultimately treatments and interventions. Implicit biases may also unwittingly produce professional behaviors, attitudes, and interactions that reduce patients' trust and comfort with their provider, leading to earlier termination of visits and/or reduced adherence and follow-up. Disadvantaged groups are marginalized in the healthcare system and vulnerable on multiple levels; health professionals' implicit biases can further exacerbate these existing disadvantages.

Interventions or strategies designed to reduce implicit bias may be categorized as change-based or control-based. Change-based interventions focus on reducing or changing cognitive associations underlying implicit biases. These interventions might include challenging stereotypes. Conversely, control-based interventions involve reducing the effects of the implicit bias on the individual's behaviors. These strategies include increasing awareness of biased thoughts and responses. The two types of interventions are not mutually exclusive and may be used synergistically.

1. HISTORY: A BRIEF GLIMPSE

Traditional Chinese medicine (TCM) began more than 2,000 years ago. At that time there was no scientific concept of disease or pharmacology in terms that can be related to our modern understanding of medicine. Therefore, the principles of TCM were formed based on Taoism, a philosophical and religious system of beliefs, attitudes, and practices that focuses on harmony and nature, rather than science [1].

TCM is widely practiced in Asian countries, including China, Taiwan, and Singapore. TCM has also experienced a surge in popularity in Western countries, where it is sometimes used for promoting wellness, preventing illness, and treating chronic conditions. This ancient system of medicine encompasses a range of practices including acupoint therapies, meditation, martial arts, herbal medicine, feng shui, and massage [1].

These modalities and treatment techniques share a theoretical framework defined by the yin and yang relationship. In China, yin and yang are two forces that control the universe. Virtually all medical problems are considered to be due to imbalances in one of these forces. Chinese therapeutics intends to correct imbalances of these forces to cure disease [1].

Yin is the feminine side of nature and includes tranquility, darkness, cold, wetness, and depth. Yang is masculine and represents light, heat, activity, dryness, and height. Yin and yang are not the same as good and bad. Instead, they are considered complementary forces [1].

In TCM, it is thought that disease is caused by an imbalanced or blocked flow of energy, or qi. Additionally, there are 12 meridians that form a continuous pathway throughout the body; qi circulates through the body on these meridians (Figure 1).

Figure 1: BODY MERIDIANS

Source: [1]

According to TCM, acupoints are specifically chosen sites of manipulation located along meridians thought to stimulate or balance specific organs, emotions, or sensory feelings. One example is the P6 acupoint, which is found on the inner forearm, two inches above the wrist joint between the two prominent tendons (Figure 2). This point is frequently used in TCM modalities for the prevention and relief of nausea and vomiting in multiple settings (e.g., chemotherapy-induced, postoperative, motion-related) [1].

Figure 2: P6 ACUPOINT

Source: [1]

There are more than 350 recognized acupoints on the human body, and each acupoint is associated with a list of conditions for which it may be used. Some practitioners may also choose to use certain acupoints for nontraditional indications [2,3].

In this practice, people are diagnosed through evaluation of the tongue and the radial pulse, and by a series of signs and symptoms unique to TCM. Although these diagnostic methods have a long history of traditional use, the findings and diagnoses achieved from these techniques do not directly correlate to Western medicine. Their use as accurate indicators of medical conditions or disease has not been validated in clinical research [1].

Pulse diagnosis and tongue diagnosis are techniques used in many traditional systems of medicine. In pulse diagnosis, practitioners assess a person's pulse for rate, strength, length, and width. The wrist is most commonly used for pulse diagnosis, and the practitioner palpates at three different pressures (superficial, middle, and deep). With tongue diagnosis, practitioners assess the tongue for color, elasticity, veining, and various other qualities. In some cases, a digital device may be used to aid in tongue diagnosis [1].

TCM modalities of acupuncture, moxibustion, acupressure, and transcutaneous electrical acustimulation (TEAS) are thought to stimulate energy flow, unblock energy, and rebalance energy, which results in healing.

ACUPUNCTURE

The practice of acupuncture originated in China more than 2,000 years ago as the primary treatment modality of TCM and involves the insertion of fine needles into specific points on the body along meridians. This acupoint therapy remains one of the most common components of TCM. So common, in fact, that many healthcare plans will cover this treatment. As of 2018, there were more than 35,000 actively licensed acupuncturists and more than 60 accredited acupuncture and oriental medicine schools in the United States, suggesting interest continues to grow [2].

MOXIBUSTION

Another practice of TCM, moxibustion, involves burning an herb, usually mugwort (Artemisia vulgaris), above the skin or on the acupoints to introduce heat into an acupoint for therapeutic effects. Moxibustion may be performed by burning a cone, stick, or loose herb a short distance away from the skin. Additionally, the burning herb may be placed on the head of an acupuncture needle to increase the temperature gradient of the needle. Theoretically, moxibustion opens the 12 meridians and removes cold, dampness, and stagnation, which improves consciousness and prevents the collapse of qi, particularly the yang qi [4].

ACUPRESSURE

Acupressure is another common treatment modality of TCM. Acupressure is similar to acupuncture; however, it involves the use of applied pressure in place of needles. Pressure is applied using hands, thumbs, fingers, or devices to specific places, or acupoints, on the body [3].

TRANSCUTANEOUS ELECTRICAL ACUSTIMULATION (TEAS)

Lastly, acustimulation, another acupoint modality, involves stimulating specific acupoints on the body along meridians. TEAS involves applying a low-intensity electrical current to specific acupoints without puncturing the skin. While this modality is based on principles of TCM, it also incorporates aspects of modern practices by utilizing recently developed medical devices [5].

Although acupuncture, acupressure, and acustimulation are similar and may be used together in a single therapy session, they are individual and specific modalities and should not be confused with one another.

Additionally, TEAS differs from another therapeutic practice, transcutaneous electrical nerve stimulation (TENS), which does not utilize acupoints. It also differs from electroacupuncture, in which an electrical current is passed through embedded acupuncture needles [5].

A NOTE ON THE EVIDENCE

Although a large number of clinical trials show some evidence for the use of acupoint therapies for certain conditions, their ability to show superiority to placebo controls has been contradictory and inconclusive, suggesting that benefits may be due, at least in part, to a placebo effect. This potential effect may also be due to the environment in which these therapies are conducted and the preconceived notions related to acupoint therapies.

The quality of available evidence is also important to note. Most research is limited by a lack of appropriate blinding or sham controls, unclear methodological quality (e.g., heterogeneity, publication bias), overall small sample sizes, and prior expectations of outcomes. Another limiting factor is geographical location. Most available research has been conducted in China; therefore, it is unclear if outcomes are generalizable to other regions or populations.

Sham acupoint procedures were developed to be used as a control intervention in clinical trials, similar to placebo pills used in pharmacological studies. Sham acupuncture treatments include inserting needles into non-acupoints, using a device that masks the presence or absence of a needle (such as the Park Sham Device), or poking acupoints with a toothpick rather than inserting a needle. Essentially, sham acupuncture is placebo acupuncture—it mimics the experience of acupuncture without implementing the methods thought to be responsible for its effects.

In order to mitigate some of the quality concerns commonly observed in acupoint research, investigators have developed a variety of sham acupoint procedures intended to be used as a control intervention in clinical trials. It is important to note that there are several different sham devices available, and the quality of sham design may vary between studies. Additionally, there are controversies surrounding the validity of this technique.

2. ACUPUNCTURE

Acupuncture is a modality in which needles are inserted into more than 350 key points along meridians in the body. These points are referred to as acupoints, and stimulating acupoints through a needle is thought to stimulate the body to correct energy flow and balance [2].

Prior to treatment, traditional acupuncturists conduct a comprehensive medical history and examination similar to TCM practitioners. They may examine the tongue, the face, and the quality of the pulses. Both traditional and Western acupuncturists may palpate to identify points at which pressure causes tenderness or pain. Traditional acupuncturists may also add other modalities from TCM into the acupuncture therapy session [2].

Most states in the United Stated regulate the practice of acupuncture, for which different degrees and certifications are available. The National Certification Commission for Acupuncture and Oriental Medicine (NCCAOM) works with most states to validate the competency of acupuncture practitioners prior to licensure [2].

STYLES OF ACUPUNCTURE

Traditional "Manual" Acupuncture

In this practice, needles are inserted into acupoints. An acupuncture session may involve the insertion of up to 20 very fine needles which are kept in place for different durations, usually about 10 to 30 minutes. The needles can be inserted to a depth of 5–40 mm and can be stimulated by winding by hand [2].

Electroacupuncture

In this practice, acupuncture needles are stimulated by a weak electrical current.

Laser Acupuncture

In this practice, lasers are used to stimulate acupoints. A typical schedule of acupuncture administration is 6 to 12 sessions over three months [2].

Thread Embedding Acupuncture

In this practice, medical threads, such as catgut or polydioxanone (PDO) sutures, are inserted into subcutaneous tissue or muscle at specific points, thus providing long-term chemical stimulation in addition to the mechanical stimulation provided by traditional acupuncture. Typically, PDO threads take approximately four weeks to reach 50% tensile strength and six months to be completely absorbed [2].

REVIEWING THE EVIDENCE

Although there has been extensive research conducted on acupuncture, most data are inconclusive. Additionally, just as some research suggests evidence of benefit for certain indications, research for other indications suggests a lack of benefit.

Cancer-Related Conditions

Cancer-Related Fatigue

Low-quality studies suggest that acupuncture may modestly improve symptoms in patients with cancer-related fatigue. Guidelines from multiple oncology associations include acupuncture and electroacupuncture as a potential treatment option for reducing post-cancer fatigue [2].

Clinical research, mainly preliminary in design and low quality, shows that receiving acupuncture for a total of 6 to 10 sessions over two to ten weeks improves feelings of cancer-related mental and physical fatigue when compared with sham acupuncture or usual care alone [2].

The National Comprehensive Cancer Network (NCCN) guidelines for cancer-related fatigue list acupuncture as a potential nonpharmacologic treatment option for patients who have completed cancer treatment. Additionally, the American Society of Clinical Oncology (ASCO) and the Society for Integrative Oncology recommend acupuncture for patients who have finished cancer treatment and for cancer survivors [2].

Cancer-Related Pain

Evidence Based Practice Recommendation

The Society for Integrative Oncology and the American Society of Clinical Oncology assert that acupuncture should be offered to patients experiencing aromatase inhibitor-related joint pain in breast cancer.

https://ascopubs.org/doi/full/10.1200/JCO.22.01357

Last Accessed: October 27, 2022

Strength of Recommendation/Level of Evidence: Intermediate/Moderate

Low-quality studies suggest that acupuncture may modestly improve symptoms in patients with cancer-related pain. Meta-analyses and preliminary clinical research, mainly low quality, show that acupuncture has a small-to-moderate effect on malignancy-related and surgery-induced pain in patients with cancer when compared with baseline or a control group. Furthermore, when used in combination with analgesics, a meta-analysis of three studies shows that electroacupuncture decreases analgesic use by a small amount [2].

The NCCN guidelines for adult cancer pain highlight acupuncture and electroacupuncture as a potential integrative treatment for vulnerable populations, such as frail or elderly individuals who may not be able to tolerate pharmacological treatments [2].

Chemotherapy-Induced Nausea and Vomiting (CINV)

When used with antiemetics, some research shows that electroacupuncture, with or without manual acupuncture, modestly reduces nausea and vomiting associated with chemotherapy. Manual acupuncture alone also seems to be comparable to some antiemetics.

A clinical study in patients with advanced cancer shows that a combination of manual acupuncture and electroacupuncture with ondansetron during five days of chemotherapy reduces the severity of nausea and vomiting over a total period of 21 days when compared with sham acupuncture. However, it does not increase the number of patients that experience no nausea or vomiting [2].

Another clinical study shows that manual acupuncture is comparable to giving ondansetron 8 mg intravenously for preventing acute nausea and vomiting in the first 24 hours after chemotherapy with paclitaxel and carboplatin [2].

Clinical practice guidelines from the Society for Integrative Oncology (SIO) recommend that acupuncture or acupressure be considered as an adjunct to antiemetic medications for chemotherapy-induced nausea and vomiting (CINV) management [2].

Pain-Related Conditions

Some experts theorize that acupuncture may result in the release of the endogenous opioids known as enkephalins and endorphins, which naturally reduce pain. However, because some research shows acupuncture to be no more effective than sham acupuncture, it is unclear if the effectiveness is due to physiologic stimulation [2].

Back Pain

Clinical research shows that acupuncture reduces pain when compared with either sham acupuncture or no treatment in patients with either chronic or acute low back pain. For chronic low back pain, most clinical research suggests that after three months, acupuncture is no more effective than sham acupuncture, although it does seem to be beneficial when compared with no treatment. Finally, there is some evidence that the analgesic effects of acupuncture may be delayed, with greatest benefit seen months after treatment discontinuation [2].

The analgesic effect of acupuncture seems to be influenced by several factors [2]:

- Number of acupuncture sessions

- A greater number of patients achieve relief of low back pain after 10 treatments compared to only five treatments.

- Depth of needle insertion

- Deep acupuncture appears to be more effective than superficial acupuncture.

- Different acupuncture styles

Motion style acupuncture is a method combining acupuncture with Doin, a manual therapy used in Korean rehabilitation medicine. Research suggests that this treatment improves acute back pain to a greater degree than either traditional acupuncture or electroacupuncture [2].

Despite the uncertain and short-term benefits, guidelines published by the American College of Physicians recommend the use of nonpharmacologic therapy, such as acupuncture, prior to using pharmacologic therapy in patients with chronic low back pain [2].

Neurogenic Conditions

Fibromyalgia

Most preliminary clinical research and meta-analyses of clinical research show that acupuncture improves pain and stiffness and quality of life when compared with no treatment, standard therapy, or sham acupuncture, although older research shows that acupuncture is no different than sham acupuncture for reducing pain [2].

This discrepancy in results might be due to the type of sham acupuncture used and the integrity of blinding procedures. Acupuncture is more effective at relieving pain when compared with the sham acupuncture method that involves placing a needle in the acupoint with a bandage, without piercing the skin. This benefit is not observed when skin is pierced in both sham and real acupuncture groups [2].

HIV/AIDS-Related Peripheral Neuropathy

Research shows that acupuncture does not improve HIV/AIDS-related peripheral neuropathy. For instance, clinical research shows that acupuncture may not be effective for reducing peripheral neuropathy associated with HIV when compared with sham acupuncture at control sites [2].

Osteoarthritis

Meta-analyses of preliminary clinical research show that electrical, laser, and manual acupuncture modestly reduce pain and modestly improve function in patients with hip or knee osteoarthritis when compared with no treatment or sham treatment, or when used as an adjunct to standard treatment. Most individual preliminary clinical trials show sustained reductions in pain for up to 12 weeks [2].

However, available research is generally of low quality and is challenged by an array of conflicting evidence. A meta-analysis of two higher quality studies and some preliminary clinical research did not find a difference between acupuncture and sham acupuncture for improving pain in hip or knee osteoarthritis. Acupuncture is conditionally recommended by The American College of Rheumatology (ACR) for any form of osteoarthritis [2].

It is important to mention that there are a number of pain-related conditions with insufficient evidence to support the use of acupuncture. These conditions include myofascial pain syndrome, shoulder pain, sciatica, pregnancy-related pain, and others. More evidence is needed to rate acupuncture for these uses [2].

Gastrointestinal-Related Conditions

Constipation

A meta-analysis of preliminary clinical research, as well as individual clinical trials, in patients with functional constipation show that receiving manual acupuncture or electroacupuncture for 2 to 10 weeks modestly increases bowel movements and improves stool formation and symptoms when compared with sham acupuncture. However, acupuncture was no more effective than various conventional medications [2].

Dyspepsia

Meta-analyses of preliminary clinical research show that manual and electroacupuncture are more effective than sham acupuncture for improving symptoms of dyspepsia and quality of life. Some individual clinical studies have shown that acupuncture combined with Western medicine (including prokinetic agents, acid suppressants, and antidepressants) improves symptoms more than Western medicine alone [2].

There are also a variety of gastrointestinal-related conditions for which there is very limited evidence to support the use of acupuncture. These conditions include gastroparesis, ulcerative colitis, irritable bowel syndrome, and postoperative ileus [2].

Postoperative Nausea and Vomiting (PONV)

Meta-analyses suggest that acupoint stimulation with acupuncture, acupressure, and electrical stimulation can reduce PONV by up to 50% and may be as effective as conventional antiemetics. Furthermore, other analyses show that acupuncture of the P6 acupoint is effective in reducing incidence of nausea, vomiting, and need for rescue antiemetics postoperatively when compared with no treatment. The effects of acupuncture on acute and delayed vomiting and nausea appear to vary [2].

A meta-analysis of six small clinical trials suggest that acupuncture reduces postoperative vomiting in children when compared with control acupuncture surgery. Additionally, one small study shows that receiving acupuncture on the P6 acupuncture point is as effective as sham acupuncture and dexamethasone [2].

Thus far, the evidence on the use of acupuncture for PONV is promising, and patients may consider it as an adjunctive treatment option. However, there is currently very limited evidence on use for pregnancy-induced and radiation-induced nausea and vomiting.

Other Conditions

Asthma

Most research shows that acupuncture does not improve symptoms of asthma. While some preliminary clinical research suggests that acupuncture or laser acupuncture and probiotics may marginally improve asthma symptoms and pulmonary function, most clinical research supports that acupuncture has no effect on asthma or asthma parameters such as forced expiratory volume in one second and forced vital capacity [2].

Depression

When used with conventional antidepressants, most research shows that acupuncture modestly reduces symptoms of depression. However, it is unclear if acupuncture alone is more effective than conventional antidepressants.

Clinical evidence shows that using manual or electroacupuncture as an adjunct to antidepressants such as selective serotonin reuptake inhibitors modestly reduces depression severity when compared with antidepressants alone [2].

There is also some evidence that acupuncture may be more likely to alleviate symptoms of perimenopausal depression, post-stroke depression, or cancer-related depression when compared with antidepressants or hormone replacement therapy. However, because most of the available research has been conducted in China, it is unclear if these findings are generalizable to other geographic locations [2].

Insomnia

Clinical research shows that manual acupuncture modestly improves sleep quality and might reduce the need for medication when used as an adjunct to sleep hygiene instruction or conventional treatment, sham acupuncture, or a waitlist control group (i.e., a group that serves as an untreated comparator, but eventually goes on to receive treatment at a later date) [2].

Electroacupuncture does not seem to improve sleep efficiency, sleep onset, or insomnia severity when compared with conventional treatment or sham electroacupuncture [2].

Smoking Cessation

Clinical research shows that although acupuncture might have short-term benefits, it does not improve rates of long-term smoking cessation when compared with sham acupuncture [2].

SAFETY

Acupuncture, when used appropriately and performed with sterile needles, is generally well-tolerated and has been safely used in numerous clinical trials for up to 24 months. Some clinical research shows that acupuncture has been used in children without reports of significant adverse effects [2].

Most commonly, acupuncture is associated with dermatologic adverse effects, such as bruising, swelling, and pain. Acupuncture in the eyes can cause trauma to the eyes such as perforation and traumatic cataract. There have been case reports of epidural and subdural hematomas from improper acupuncture, resulting in paresthesia, hemiparesis, quadriparesis, and sensory deficit. There have been case reports of pneumocranium, pneumothorax, hemothorax, acute respiratory and circulatory failure, and death due to inappropriate acupuncture practices. Acupuncture needles that are not removed after treatment might embolize and cause damage to internal organs [2].

3. MOXIBUSTION

Moxibustion is another acupoint modality that is commonly utilized in TCM. Moxibustion involves burning moxa, a dried herbal preparation made of the aged, powdered mugwort herb, at prescribed acupoints on the body. These points are determined based on the patient's symptoms and diagnosis [4].

Moxa is considered to have a warming yang nature that is thought to prevent patients from experiencing a collapse of yang qi energy. There are various techniques used in moxibustion.

MOXIBUSTION TECHNIQUES

Indirect Moxibustion (Interposed Moxibustion)

The ignited moxa cone does not contact the skin directly. Instead, it is separated from the skin by ingredients such as ginseng, salt, garlic, ginger, or aconite cake. In clinical research, indirect moxibustion has improved levels of cellular mediators involved in pain [4].

Direct Moxibustion

The ignited moxa cone is used directly to warm the skin surface at the acupuncture point. Direct moxibustion can be scarring, which involves burning moxa directly on the skin, or "warming," which involves burning moxa above the skin [4].

Thunder-Fire Moxibustion

Moxa-cigars held by a moxibustion box are ignited over the treatment site. The fire head is held about an inch away from the skin and burned for about 30 minutes. To maintain the heat and reduce smoke in the air, the moxibustion treatment is covered with a thick towel [4].

Warm Needle Moxibustion/Acupuncture

This is an integration of acupuncture and moxibustion. A one-inch moxa stick is put on the handle of an acupuncture needle that has been inserted in the body, and the moxa stick is ignited. This method is purported to warm the meridians and promote the flow of qi and blood [4].

Electric Moxibustion

Electric moxibustion has been developed because there are safety concerns with traditional moxibustion, such as excessive heat or potentially toxic chemical components. Electric moxibustion has adjustable and constant heat stimulation that is applied either directly or indirectly to skin and has been shown to increase blood flow in healthy participants [4].

Jade Moxibustion

Involves wearing heated knee pads containing a jade stone for 20 minutes three times weekly for four weeks [4].

REVIEWING THE EVIDENCE

Pain-Related Conditions

Back Pain

Most low-quality clinical research suggests that moxibustion, when used alone or in conjunction with other treatments, may modestly reduce back pain.

A meta-analysis of small, low quality clinical studies in people with chronic low back pain shows that moxibustion reduces pain when compared with acupuncture, massage, or taking ibuprofen 300 mg daily or celecoxib 200 mg daily. Furthermore, adding moxibustion to other treatments such as massage, acupuncture, core stability training, or the medicines celecoxib or meloxicam, further reduces back pain when compared with the active treatment alone [4].

Osteoarthritis

Meta-analyses of small clinical studies in patients with knee osteoarthritis show that moxibustion modestly reduces pain and improves function when compared with sham moxibustion or usual care. A subgroup analysis suggests that moxibustion improves osteoarthritis pain when compared with taking diclofenac, but not when compared with taking celecoxib. However, this finding is limited due to the high heterogeneity of the available research, as well as a high risk for publication bias [4].

Research has also evaluated other types of moxibustion for the treatment of knee osteoarthritis. One clinical trial shows that receiving jade moxibustion improves pain to a greater degree when compared with receiving traditional moxibustion. Another clinical study shows that receiving moxibustion in 12 sessions over six weeks via a specific electrical device (Cettum) improves pain similarly to traditional indirect moxibustion and to a greater extent than usual care [4].

Gastrointestinal-Related Conditions

In human research, moxibustion has been shown to reduce levels of certain inflammatory markers. Other preliminary data suggest that moxibustion may help to protect the gastric mucosa. Due to its perceived anti-inflammatory effects, there is interest in using this therapy for gastrointestinal-related conditions.

Moxibustion has been investigated in patients with diarrhea-predominant irritable bowel syndrome (IBS-D), constipation-predominant IBS (IBS-C), and inflammatory bowel diseases. Currently, there is not enough scientific evidence to support the use of moxibustion for Crohn disease and ulcerative colitis. Additionally, there is very limited evidence on use for constipation and gastritis.

IBS-D

Moxibustion with or without acupuncture appears to be more effective than sham moxibustion, sham acupuncture, or various pharmaceutical agents for improving abdominal pain, discomfort, gas, bloating, and stool consistency. There were also overall improvements in stool form and symptom severity [4].

Clinical research in patients with IBS-D shows that moxibustion three times weekly for six weeks produces adequate relief in about 77% to 82% of patients, compared with 37% to 42% of those given sham or placebo moxibustion. These data also suggest that beneficial effects lasted for up to an additional 18 weeks after treatment completion in up to 76% of patients [4].

Thus far, the evidence on the use of moxibustion for IBS-D is promising, and patients may consider it as an adjunctive treatment option.

IBS-C

The available research in patients with IBS-C is limited to a small clinical study showing no benefit with the use of warming moxibustion six times weekly for four weeks when compared with baseline or electroacupuncture [4]. As such, available research suggests that moxibustion may not be effective in patients with IBS-C.

Crohn Disease

Moxibustion administration has only been evaluated in combination with acupuncture; its effect when used alone is unclear. Clinical research in patients with Crohn disease shows that combining herb-partitioned moxibustion with acupuncture three times weekly for 12 weeks induces remission in 74% of patients, compared with only 36% of patients given sham moxibustion and superficial acupuncture [4].

Ulcerative Colitis

A meta-analysis of low-quality clinical research shows that moxibustion with or without acupuncture improves response rate by 24% when compared to control treatment. However, these results are limited by the small number, size, and low quality of the included studies [4].

Other Conditions

Cancer

Moxibustion administration does not seem to be beneficial for cancer treatment. A meta-analysis of five clinical studies shows that moxibustion does not improve treatment response in patients with various cancer types when compared with standard care. There is limited evidence on use of moxibustion for CINV and cancer-related fatigue [4].

Dysmenorrhea

Low-to-moderate quality clinical research in patients with dysmenorrhea shows that moxibustion with or without acupuncture reduces pain, usually when compared with no treatment or usual care. Additional clinical research shows that moxibustion reduces pain intensity similarly to ibuprofen 300 mg twice daily for three days, starting the day before menstruation and repeated for three cycles. Furthermore, at three months after treatment discontinuation, pain intensity remains 13% lower in the patients that received moxibustion [4].

Insomnia

It is unclear if moxibustion is beneficial for insomnia. Although some research has been conducted on the use moxibustion for insomnia, there is not enough reliable evidence to confirm a benefit for these indications [4].

SAFETY

Moxibustion is likely safe when administered appropriately by a qualified practitioner and has been used in clinical research without reports of serious adverse events.

Most commonly, moxibustion is associated with blisters, burns, dizziness, fainting, fatigue, gastrointestinal upset, headache, hypersomnia, itching, pain, rash, redness, and respiratory discomfort. Serious cases of adverse effects caused by moxibustion are generally related to inappropriate administration, such as not removing the moxa from the skin at the appropriate time or accidentally dropping ash onto the skin [4].

4. ACUPRESSURE

Acupressure involves applying pressure using hands, thumbs, fingers, or devices to acupoints. Acupressure can be self-administered or applied by a trained practitioner. Passive acupressure devices are also available that apply pressure continuously at a specific location. For example, wrist bands can apply pressure to the P6 acupoint, which is utilized for the treatment or prevention of nausea and vomiting. Most acupressure points are located near nervous tissue or structures. Duration and frequency of acupressure treatment is individualized to the patient and the condition being treated [3].

REVIEWING THE EVIDENCE

Although there is a large body of research evaluating acupressure for various purposes, most evidence is low quality and inconclusive.

Pain-Related Conditions

Most acupressure points are located near nervous tissue or structures. Researchers suggest that applying pressure at these points may block transmission of pain signals through certain neural gates [3].

Back Pain

Acupressure, administered either alone or as an adjuvant treatment, seems to reduce chronic low back pain. Clinical research in patients with lower back pain shows that acupressure, administered alone or with acupuncture, or acupressure massage with aromatic essential oil in combination with usual care, reduces pain and disability and improves walking ability when compared with physical therapy, usual care, or acupuncture alone [3].

Preliminary clinical research shows that using an acupressure backrest during sedentary work for one month reduces pain and disability by at least 30% when compared with no intervention. Other preliminary clinical research shows that using auricular acupressure for three minutes three times daily for five days each week for four weeks reduces pain by about 40% when compared with performing the same procedure on incorrect acupoints [3].

Auricular acupressure involves the taping of magnetic beads or plant seeds to the ear. In TCM, it is thought to relieve tension and improve circulation [3].

Osteoarthritis

Most research shows that manual acupressure does not improve pain or function in patients with knee osteoarthritis. Additionally, it is unclear if auricular acupressure is beneficial for osteoarthritis.

Clinical research in patients with osteoarthritis of the knee shows that self-administered acupressure alone for up to 16 weeks does not reduce knee pain intensity when compared with receiving sham acupressure, education on knee health, exercise, or no intervention [3].

A small clinical study shows that auricular acupressure four times daily for four weeks is associated with reductions in pain, stiffness, and function on days 3 and 7, but not days 14, 21, or 28, when compared with sham acupressure [3].

It is important to mention that there are a number of other pain-related conditions with insufficient evidence to support the use of acupressure. These conditions include neck and shoulder pain, postoperative pain, and neuropathic pain [3].

Cancer-Related Conditions

Cancer-Related Fatigue

Evidence Based Practice Recommendation

According to the Society for Integrative Oncology and the American Society of Clinical Oncology, reflexology or acupressure may be offered to patients experiencing pain during systemic therapy for cancer treatment.

https://ascopubs.org/doi/full/10.1200/JCO.22.01357

Last Accessed: October 27, 2022

Strength of Recommendation/Level of Evidence: Intermediate/Moderate

Acupressure seems to improve fatigue in patients with cancer. A meta-analysis of mostly small clinical studies in patients with cancer-related fatigue shows that various forms of acupressure, either self-administered or administered by a professional, reduces fatigue by a large amount when compared with usual care, sham acupressure, or acupuncture [3].

Thus far, the evidence on the use of acupressure for cancer-related fatigue is promising, and patients may consider acupressure as an adjunctive treatment option. However, there is very limited evidence on use for breast cancer, cancer-related pain, and chemotherapy-related fatigue [3].

Chemotherapy-Induced Nausea and Vomiting (CINV)

It is unclear if acupressure is beneficial in patients with CINV. Data are conflicting.

Some research, but not all, suggests that acupressure modestly reduces chemotherapy-induced acute and delayed nausea, but not acute or delayed vomiting. Research using acupressure wristbands for CINV is also mixed; some research shows that using a specific passive acupressure wristband product (Sea-Band) reduces nausea and vomiting when compared with usual care alone, but it does not appear to be more effective than sham acupressure [3].

The reasons for these mixed findings may be related to the type of cancer, the chemotherapy regimen used, or the severity of CINV. Larger, higher quality studies are needed to determine which patients, if any, may benefit the most from treatment.

Other Conditions

Dysmenorrhea

Acupressure seems to reduce pain in adults and adolescents with primary dysmenorrhea. Preliminary clinical research in adolescents with primary dysmenorrhea shows that beginning acupressure shortly after menstruation onset reduces the severity of dysmenorrhea for up to two hours after treatment and improves pain and anxiety. Self-administration of acupressure also seems to help reduce pain in dysmenorrhea [3].

Insomnia

Some small clinical studies suggest that manual and auricular acupressure improves sleep in patients with insomnia or sleep disturbances due to various underlying conditions.

Improvement in sleep was reported in small clinical studies, particularly in patients with hypertension or cancer, individuals who receive routine hemodialysis, and patients who are hospitalized or residing in long term care. Larger, higher quality studies are needed to determine which patients are more likely to benefit from treatment [3].

Motion Sickness

It is unclear if acupressure is beneficial in patients with motion sickness. Some clinical research shows that acupressure does not reduce motion sickness in elderly patients, females, or male college students. However, other research in experimentally induced motion sickness shows that acupressure at the P6 point reduces nausea when compared with baseline but has mixed findings when compared with sham acupressure [3].

There are a number of other conditions with insufficient evidence to support the use of acupressure. Some examples include, but are not limited to, PONV, smoking cessation, and irritable bowel syndrome (IBS) [3].

SAFETY

Acupressure in adults and children appears well tolerated when applied appropriately and has been safely used in numerous clinical trials. Most commonly, acupressure is associated with bruising, dizziness, headache, inflammation, and skin irritation [3].

5. TRANSCUTANEOUS ELECTRICAL ACUSTIMULATION (TEAS)

TEAS involves applying low-intensity electrical current to specific acupoints without puncturing the skin. TEAS can be given using electric units with a transcutaneous electrical nerve stimulation (TENS) unit or a Han's acupoint nerve stimulator (HANS) dual-channel unit. The electrodes are attached to specific acupoints on the body to which a small electric current is administered. Common currents include 2–100 Hz in constant or pulsed mode [5].

A specific acustimulation device (ReliefBand) has been used with apparent safety in clinical research with no reports of adverse effects. This device is commercially available and cleared by the U.S. Food and Drug Administration (FDA) for certain types of nausea, retching, and vomiting [5]. Note that FDA clearance and FDA approval are not interchangeable terms. "FDA cleared" typically refers to medical devices, which differs from the rigorous testing required for "FDA approval," which is generally applied to pharmaceutical drugs.

Common acupoints used for acustimulation are the P6 Neiguan point on the wrist, which is used for nausea and vomiting, and the ST36 Zusanli point below the knee, which is used for gastrointestinal discomfort, stress, and fatigue. These and other acupoints have been stimulated alone or in combination in clinical research [5].

Sessions normally last for 30 to 60 minutes and are conducted two to seven days per week for 2 to 12 weeks, or as multiple sessions daily. Occasionally, acustimulation is used in surgical patients, and may be administered prior to, during, and/or daily for up to three days after surgery [5].

REVIEWING THE EVIDENCE

Chemotherapy-Induced Nausea and Vomiting (CINV)

Acustimulation does not seem to be beneficial for CINV. Several clinical trials including patients with breast and liver cancer receiving highly emetogenic chemotherapy such as cisplatin or doxorubicin shows that acustimulation, administered by wearing a specific acustimulation device (ReliefBand) or given via electrodes does not improve CINV when compared with not wearing the device, wearing the device incorrectly, wearing acupressure bands, or sham acustimulation [5].

Additionally, there is insufficient evidence to support the use of TEAS in patients with fatigue or constipation related to chemotherapy [5].

Postoperative Complications

Postoperative Cognitive Dysfunction

Acustimulation seems to be beneficial for preventing postoperative cognitive dysfunction. A meta-analysis of generally good quality clinical research shows that acustimulation, alone or in combination with other therapies, reduces the incidence of postoperative cognitive dysfunction in the first week after surgery by approximately 60% when compared with control groups given sham intervention, no intervention, or other treatments. Although there were also improvements seven days after surgery, these benefits were not observed on day five [5].

Additional preliminary clinical research in elderly patients undergoing laparoscopic cancer surgery shows that acustimulation from 30 minutes before anesthesia induction to the end of surgery modestly reduces the cumulative duration of cognitive decline on postoperative days two and three when compared with no acustimulation. However, there was no effect on the incidence of cognitive decline [5].

Postoperative Ileus

Acustimulation seems to be beneficial for preventing postoperative ileus. A meta-analysis and individual clinical research show that acustimulation modestly improves the time to first flatus or first defecation, the number of spontaneous bowel movements, symptoms such as appetite, belching, and abdominal distension, and the overall incidence of postoperative ileus or gastrointestinal dysfunction when compared with sham acustimulation or routine treatment alone [5].

Acustimulation has been given during or after the operation until postoperative day three for cesarean section, gastric surgery, and colorectal surgery [5].

Postoperative Nausea and Vomiting (PONV)

Acustimulation seems to be effective for preventing PONV; however, it is unclear whether acustimulation is effective for treating PONV or whether it is more effective than antiemetics alone for preventing PONV.

Most clinical research from meta-analyses and individual trials shows that acustimulation reduces the risk of PONV by up to 46% for at least 2 hours, and in some cases for up to 48 hours, after surgery. In addition, a meta-analysis of four studies shows that acustimulation at the P6 acupoint reduces the need for antiemetic rescue [5].

Many studies used acustimulation of the P6 point starting before anesthesia and continuing for up to 72 hours after surgery using a specific acustimulation band (ReliefBand) or HANS electrodes. This device has shown benefit for PONV after gynecological laparoscopy, laparoscopic cholecystectomy, and plastic surgery and appears to be most effective for preventing PONV when used perioperatively and postoperatively as opposed to only preoperative use [5].

Other clinical research in children 4 to 12 years of age undergoing tonsillectomy shows that acustimulation of 20 Hz for five minutes before the induction of anesthesia and five minutes after surgery is as effective as ondansetron 0.15 mg/kg and more effective than no treatment for reducing the incidence of postoperative retching and vomiting on the day of surgery and the day after discharge, but not immediately after surgery or on postoperative day one [5].

Postoperative Pain

Acustimulation seems to be effective for reducing postoperative pain for certain surgeries. Clinical research shows that acustimulation modestly reduces postoperative pain and/or the need for postoperative analgesics when compared with sham acustimulation or routine treatment alone. Types of surgery have included caesarian section, inguinal hernia repair, thoracoscopic surgery, spinal cord surgery, total hip arthroplasty, radical mastectomy, ureteroscopic lithotripsy, gastrectomy, and others. In some cases, acustimulation is initiated prior to, and possibly during, surgery, as well as intermittently after surgery. In others it has only been used postoperatively for up to three days [5].

However, not all research agrees. When used in combination with the antiemetics dexamethasone and tropisetron in female patients undergoing laparoscopic sleeve gastrectomy, acustimulation does not reduce postoperative pain over 48 hours or the need for opioid medication [5].

There is very limited evidence on use for acustimulation in patients with acute or chronic pain. Additionally, it is unclear if acustimulation is beneficial in patients with neck pain or if it improves pain during labor [5].

SAFETY

TEAS is generally well tolerated when used appropriately, short-term. Acustimulation via other methods has also been used with apparent safety in clinical research for up to 12 weeks [5].

6. CONSIDERATIONS AND COMPARISONS

REPRODUCTIVE EFFECTS

Fertility

Until more is known about the safety of acupuncture, moxibustion, acupressure, or TEAS during in vitro fertilization (IVF), recommend against the use of these modalities [2,3,4,5].

Pregnancy and Lactation

Acupuncture

Some clinical research shows that acupuncture has been used during pregnancy and labor without reports of significant adverse effects when used appropriately at most acupoints and performed with sterile needles. There is insufficient reliable information available about the use of electroacupuncture or laser acupuncture during pregnancy; avoid using. There is some concern that acupuncture at the SP6 acupoint on the inner ankle can increase the risk of early contractions and miscarriage [2].

Acupressure

This therapy has been safely used during pregnancy in clinical trials without significant adverse effects [3].

Transcutaneous Electrical Acustimulation (TEAS)

There is currently insufficient reliable information available; however, there is no reason to expect safety concerns when used appropriately [5].

Moxibustion

While this therapy has been used with apparent safety during pregnancy in most clinical studies, some clinical evidence suggests that moxibustion may be associated with premature birth, premature membrane rupture, increased rate of contractions, abdominal pain due to contractions, placental bleeding, reduced or increased fetal movement, and reduced fetal heart rate [4].

There is insufficient reliable information available about the use of moxibustion during lactation; however, it is unlikely that maternal use of moxibustion would pose a significant safety risk to breastfeeding infants [4].

INTERACTIONS WITH CONDITIONS

Asthma

Theoretically, moxibustion may exacerbate asthma symptoms. Clinical reports of respiratory discomfort and asthma exacerbation due to the smoke associated with moxibustion suggest that moxibustion may not be safe for use in patients with asthma. However, some research has suggested a possible beneficial effect of moxibustion in patients with asthma. Until more is known, use with caution [4].

Other Considerations

Although there are no absolute contraindications, it is imperative that acupoint practitioners are fully informed on a patient's health history to ensure safety during treatment. Examples of conditions to watch out for include altered mental status, hemophilia, and needle phobia. Patients should inform their acupoint practitioners regarding any implanted devices, such as pacemakers. Additionally, dermatologic conditions such as cellulitis, burns, or ulcerations should be evaluated prior to treatment [2,3,4,5].

COMPARING THE EVIDENCE

Because these acupoint modalities share similar characteristics and may be used together in a therapy session, patients may have questions regarding specific therapies and their efficacy for specific indications.

Back Pain

Although multiple acupoint therapies have been evaluated for back pain, the study structures and comparators used in this research has varied widely.

Acupuncture

Most research shows that acupuncture seems to reduce back pain more than no treatment. However, it is unclear if acupuncture is more effective than sham acupuncture. Receiving more than five treatments with deep acupuncture seems to offer the most long-term benefit [2].

Moxibustion

Low-quality clinical research shows that moxibustion reduces back pain when compared with acupuncture, massage, or taking ibuprofen or celecoxib. Furthermore, adding moxibustion to other treatments such as massage, acupuncture, core stability training, or the medicines celecoxib or meloxicam, further reduces back pain when compared with the active treatment alone [4].

Acupressure

Clinical research in patients with lower back pain shows that acupressure, used alone or with acupuncture, or acupressure massage with aromatic essential oil in combination with usual care reduces pain and disability and improves walking ability when compared with physical therapy, usual care, or acupuncture alone [3].

Acupuncture, acupressure, and moxibustion have a growing body of evidence suggesting at least modest benefit for back pain. TEAS has not yet been adequately evaluated for this purpose [2,3,4,5].

Insomnia

Although multiple acupoint therapies have been evaluated for insomnia, research has varied widely. Take note of the differences in study structures and patient populations.

Acupuncture and acupressure have a growing body of evidence suggesting at least modest benefit for insomnia. There is currently insufficient evidence to rate the effectiveness of moxibustion for this condition; larger, higher quality studies are needed. TEAS has not yet been adequately evaluated for this purpose.

Acupuncture

Clinical research shows that manual acupuncture modestly improves sleep quality and might reduce the need for medication when used as an adjunct to sleep hygiene instruction or conventional treatment, sham acupuncture, or waitlist control [2].

Acupressure

Most small clinical studies suggest that manual and auricular acupressure modestly improves sleep in patients with insomnia or sleep disturbances due to various underlying conditions including patients with hypertension or cancer, those who are hospitalized or residing in long term care, or those receiving hemodialysis [3].

Moxibustion

Although some research has been conducted on the use of moxibustion for insomnia, there is not enough reliable evidence to confirm a benefit for these indications [4].

Osteoarthritis

Although multiple acupoint therapies have been evaluated for osteoarthritis, the affected joints, as well as the comparators used in clinical studies, have varied widely.

Acupuncture has a growing body of evidence suggesting at least modest benefit for patients with knee or hip osteoarthritis. Some research suggests moxibustion is beneficial for knee osteoarthritis, but it is unclear how it compares to the use of other therapies.

Most research shows that manual acupressure does not improve pain or function in patients with knee osteoarthritis. TEAS has not yet been adequately evaluated for this purpose.

Acupuncture

Meta-analyses of preliminary clinical research show that electrical, laser, and manual acupuncture modestly reduce pain and modestly improves function in patients with hip or knee osteoarthritis when compared with no treatment and sham treatment and when used as an adjunct to standard treatment. Furthermore, most individual preliminary clinical trials show that acupuncture is more effective than control treatments, such as advice or sham acupuncture, for reducing pain in knee and hip osteoarthritis for up to 12 weeks. Acupuncture is conditionally recommended by the ACR for any form of osteoarthritis [2].

Moxibustion

Meta-analyses of small clinical studies in patients with knee osteoarthritis show that moxibustion modestly reduces pain and improves function when compared with sham moxibustion or usual care. A subgroup analysis suggests that moxibustion improves osteoarthritis pain when compared with taking diclofenac, but not when compared with taking celecoxib; however, these findings are uncertain [4].

Acupressure

Most research in patients with osteoarthritis of the knee shows that self-administered acupressure alone for up to 16 weeks does not reduce knee pain intensity when compared with receiving sham acupressure, education on knee health, exercise, or no intervention [3].

Postoperative Nausea and Vomiting (PONV)

Although multiple acupoint therapies have been evaluated for PONV, the study structures and comparators used in this research has varied widely. Acupuncture and TEAS have a growing body of evidence suggesting at least modest benefit at preventing PONV. Currently, there is insufficient evidence to support the use of acupressure in this setting. Moxibustion has not yet been adequately evaluated for this purpose.

Acupuncture

Meta-analyses suggest that acupoint stimulation with acupuncture, acupressure, and electrical stimulation can reduce postoperative nausea and vomiting by up to 50% and may be as effective as conventional antiemetics. Furthermore, other analyses show that acupuncture of the P6 acupoint is effective in reducing incidence of nausea, vomiting, and need for rescue antiemetics postoperatively when compared with no treatment [2].

TEAS

Acustimulation seems to be effective for preventing PONV; however, it is unclear whether acustimulation is effective for treating PONV or whether it is more effective than antiemetics alone for preventing PONV [5].

7. CONSIDERATIONS FOR NON-ENGLISH-PROFICIENT PATIENTS

For patients who are not proficient in English, it is important that information regarding the benefits and risks associated with acupoint therapies be provided in their native language, if possible. When there is an obvious disconnect in the communication process between the practitioner and patient due to the patient's lack of proficiency in the English language, an interpreter is required. Interpreters can be a valuable resource to help bridge the communication and cultural gap between patients and practitioners. Interpreters are more than passive agents who translate and transmit information back and forth from party to party. When they are enlisted and treated as part of the interdisciplinary clinical team, they serve as cultural brokers who ultimately enhance the clinical encounter.

8. CONCLUSION

The popular practice of acupuncture has existed for centuries, with records dating back thousands of years. Acupuncture and related acupoint modalities are widely used on a global scale and continue to grow in popularity as patients seek alternative treatments for various acute and chronic medical conditions. Similarities between these modalities may make it difficult to decipher the effectiveness of individual treatments for certain conditions.

Additionally, quality of evidence remains a concern. The evidence supporting the use of acupoint therapies remains limited to low-quality research. Larger, higher quality studies are needed to determine which patients, if any, are most likely to benefit, and how these treatments compare to the use of other therapies.

Further, no treatment is without safety concerns, including adverse effects, condition interactions, and special considerations. It is imperative that clinicians provide accurate information regarding various acupoint therapies and evidence-based recommendations to help patients make informed decisions about their health.

Works Cited

1. TRC Healthcare Natural Medicines Database. Traditional Chinese Medicine (TCM). Available at https://naturalmedicines.therapeuticresearch.com/databases/health-wellness/professional.aspx?productid=1202. Last accessed October 24, 2022.

2. TRC Healthcare Natural Medicines Database. Acupuncture. Available at https://naturalmedicines.therapeuticresearch.com/databases/health-wellness/professional.aspx?productid=1219. Last accessed October 24, 2022.

3. TRC Healthcare Natural Medicines Database. Acupressure. Available at https://naturalmedicines.therapeuticresearch.com/databases/health-wellness/professional.aspx?productid=1240. Last accessed October 24, 2022.

4. TRC Healthcare Natural Medicines Database. Moxibustion. Available at https://naturalmedicines.therapeuticresearch.com/databases/health-wellness/professional.aspx?productid=1446. Last accessed October 24, 2022.

5. TRC Healthcare Natural Medicines Database. Transcutaneous Electrical Acustimulation. Available at https://naturalmedicines.therapeuticresearch.com/databases/health-wellness/professional.aspx?productid=1289. Last accessed October 24, 2022.

Evidence-Based Practice Recommendations Citations

1. Mao JJ, Ismaila N, Bao T, et al. Integrative medicine for pain management in oncology: Society for Integrative Oncology-ASCO guideline. J Clin Oncol. 2022; [Epub ahead of print]. Available at https://ascopubs.org/doi/full/10.1200/JCO.22.01357. Last accessed October 27, 2022.

98080 • Top-Selling Herbal Supplements

Chelsey McIntyre, PharmD

www.netce.com

Copyright © 2022 NetCE, All rights reserved.

Dietary supplement use is increasingly common, with nearly 60% of survey respondents reporting use of a dietary supplement in the previous month, according to recent data. Groundbreaking surges in sales have been fueled by the COVID-19 pandemic. Patients may be asking about popular herbal supplements, including safety and potential uses. Healthcare professionals should be well informed about these top-selling herbal supplements so that they can provide evidence-based recommendations and appropriate safety warnings.

Table of Contents

98080 • Top-Selling Herbal Supplements

Course Overview

Audience

Accreditations & Approvals

Designations of Credit

Individual State Nursing Approvals

Individual State Behavioral Health Approvals

Special Approvals

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planners

Division Planners Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

Implicit Bias in Health Care

1. INTRODUCTION

2. APPLE CIDER VINEGAR (ACV)

PRODUCTION METHODS

REVIEWING THE EVIDENCE

SAFETY

3. ASHWAGANDHA

REVIEWING THE EVIDENCE

SAFETY

4. ECHINACEA

REVIEWING THE EVIDENCE

SAFETY

5. ELDERBERRY

REVIEWING THE EVIDENCE

SAFETY

6. TURMERIC

FORMULATIONS

REVIEWING THE EVIDENCE

SAFETY

7. SPECIAL CONSIDERATIONS

COVID-19

REPRODUCTIVE EFFECTS

AUTOIMMUNE DISEASES

HEPATOTOXICITY

HYPOGLYCEMIC AGENTS

PATIENT COUNSELING CONSIDERATIONS

PRODUCT QUALITY

8. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

98080 • Top-Selling Herbal Supplements

Education Category. Alternative Medicine

Release Date. 11/01/2022

Expiration Date. 10/31/2025

Course Overview

Dietary supplement use is increasingly common, with nearly 60% of survey respondents reporting use of a dietary supplement in the previous month, according to recent data. Groundbreaking surges in sales have been fueled by the COVID-19 pandemic. Patients may be asking about popular herbal supplements, including safety and potential uses. Healthcare professionals should be well informed about these top-selling herbal supplements so that they can provide evidence-based recommendations and appropriate safety warnings.

Audience

This course is designed for healthcare professionals whose patients are taking or are interested in taking herbal supplements.

Accreditations & Approvals

In support of improving patient care, TRC Healthcare/NetCE is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. NetCE has been approved by NBCC as an Approved Continuing Education Provider, ACEP No. 6361. Programs that do not qualify for NBCC credit are clearly identified. NetCE is solely responsible for all aspects of the programs. As a Jointly Accredited Organization, NetCE is approved to offer social work continuing education by the Association of Social Work Boards (ASWB) Approved Continuing Education (ACE) program. Organizations, not individual courses, are approved under this program. Regulatory boards are the final authority on courses accepted for continuing education credit. Continuing Education (CE) credits for psychologists are provided through the co-sponsorship of the American Psychological Association (APA) Office of Continuing Education in Psychology (CEP). The APA CEP Office maintains responsibility for the content of the programs. NetCE is accredited by the International Accreditors for Continuing Education and Training (IACET). NetCE complies with the ANSI/IACET Standard, which is recognized internationally as a standard of excellence in instructional practices. As a result of this accreditation, NetCE is authorized to issue the IACET CEU.

Designations of Credit

This activity was planned by and for the healthcare team, and learners will receive 3 Interprofessional Continuing Education (IPCE) credit(s) for learning and change. NetCE designates this enduring material for a maximum of 3 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. NetCE designates this continuing education activity for 3 ANCC contact hour(s). NetCE designates this continuing education activity for 3.6 hours for Alabama nurses. NetCE designates this continuing education activity for 1 NBCC clock hour(s). Social workers participating in this intermediate to advanced course will receive 3 Clinical continuing education clock hours. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 3 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Completion of this course constitutes permission to share the completion data with ACCME. Successful completion of this CME activity, which includes participation in the evaluation component, enables the learner to earn credit toward the CME and/or Self-Assessment requirements of the American Board of Surgery's Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit. Successful completion of this CME activity, which includes participation in the activity with individual assessments of the participant and feedback to the participant, enables the participant to earn 3 MOC points in the American Board of Pediatrics' (ABP) Maintenance of Certification (MOC) program. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABP MOC credit. Through an agreement between the Accreditation Council for Continuing Medical Education and the Royal College of Physicians and Surgeons of Canada, medical practitioners participating in the Royal College MOC Program may record completion of accredited activities registered under the ACCME's "CME in Support of MOC" program in Section 3 of the Royal College's MOC Program. AACN Synergy CERP Category A. NetCE is authorized by IACET to offer 0.3 CEU(s) for this program. NetCE designates this continuing education activity for 3 credit(s).

Individual State Nursing Approvals

In addition to states that accept ANCC, NetCE is approved as a provider of continuing education in nursing by: Alabama, Provider #ABNP0353 (valid through July 29, 2025); Arkansas, Provider #50-2405; California, BRN Provider #CEP9784; California, LVN Provider #V10662; California, PT Provider #V10842; District of Columbia, Provider #50-2405; Florida, Provider #50-2405; Georgia, Provider #50-2405; Kentucky, Provider #7-0054 through 12/31/2025; South Carolina, Provider #50-2405; West Virginia RN and APRN, Provider #50-2405.

Individual State Behavioral Health Approvals

In addition to states that accept ASWB, NetCE is approved as a provider of continuing education by the following state boards: Alabama State Board of Social Work Examiners, Provider #0515; Florida Board of Clinical Social Work, Marriage and Family Therapy and Mental Health Counseling, CE Broker Provider #50-2405; Illinois Division of Professional Regulation for Social Workers, License #159.001094; Illinois Division of Professional Regulation for Licensed Professional and Clinical Counselors, License #197.000185; Illinois Division of Professional Regulation for Marriage and Family Therapists, License #168.000190;

Special Approvals

This activity is designed to comply with the requirements of California Assembly Bill 1195, Cultural and Linguistic Competency.

Course Objective

The purpose of this course is to provide healthcare professionals in all practice settings the knowledge necessary to increase their understanding of the most popular herbal supplements and to better counsel patients regarding their use.

Learning Objectives

Upon completion of this course, you should be able to:

1. Describe characteristics of both the supplement market and some top-selling herbal supplements.

2. Discuss the evidence for and safety considerations regarding the use of elderberry, apple cider vinegar (ACV), echinacea, and ashwagandha for common indications.

3. Outline evidence for and common adverse effects of turmeric.

4. Review special considerations related to the use of elderberry, turmeric, ACV, echinacea, and ashwagandha.

Faculty

Chelsey McIntyre, PharmD, is a clinical pharmacist who specializes in drug information, literature analysis, and medical writing. She earned her Bachelor of Science degree in Genetics from the University of California, Davis. She then went on to complete her PharmD at Creighton University, followed by a clinical residency at the Children’s Hospital of Philadelphia (CHOP). Dr. McIntyre held the position of Drug Information and Policy Development Pharmacist at CHOP until her move to Washington state in 2017, after which she spent the next six years as a clinical editor for Natural Medicines, a clinical reference database focused on natural products and alternative therapies. She continues to create rigorous professional analysis and patient education materials for various publications while also practicing as a hospital pharmacist. Her professional interests include provider and patient education, as well as the application of evidence-based research to patient care.

Faculty Disclosure

Contributing faculty, Chelsey McIntyre, PharmD, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planners

John V. Jurica, MD, MPH

Margo A. Halm, RN, PhD, NEA-BC, FAAN

Alice Yick Flanagan, PhD, MSW

James Trent, PhD

Division Planners Disclosure

The division planners have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

The Director of Development and Academic Affairs has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

Implicit Bias in Health Care

The role of implicit biases on healthcare outcomes has become a concern, as there is some evidence that implicit biases contribute to health disparities, professionals' attitudes toward and interactions with patients, quality of care, diagnoses, and treatment decisions. This may produce differences in help-seeking, diagnoses, and ultimately treatments and interventions. Implicit biases may also unwittingly produce professional behaviors, attitudes, and interactions that reduce patients' trust and comfort with their provider, leading to earlier termination of visits and/or reduced adherence and follow-up. Disadvantaged groups are marginalized in the healthcare system and vulnerable on multiple levels; health professionals' implicit biases can further exacerbate these existing disadvantages.

Interventions or strategies designed to reduce implicit bias may be categorized as change-based or control-based. Change-based interventions focus on reducing or changing cognitive associations underlying implicit biases. These interventions might include challenging stereotypes. Conversely, control-based interventions involve reducing the effects of the implicit bias on the individual's behaviors. These strategies include increasing awareness of biased thoughts and responses. The two types of interventions are not mutually exclusive and may be used synergistically.

1. INTRODUCTION

Dietary supplements are products other than tobacco that are intended to supplement the diet through means of ingestion. Examples of common types of dietary supplements include vitamins, minerals, herbals, and amino acids. Dietary supplement use is increasingly common. In 2017–2018, nearly 60% of adults 20 years of age or older in the United States reported using a dietary supplement in the previous month. Women tend to use more supplements than men, and overall dietary supplement use increases with age. Women 60 years of age or older are among the greatest users of dietary supplements. Herbal supplements, often referred to as botanicals, are among the most common dietary supplements used by those 20 to 59 years of age (Figure 1) [1].

Figure 1: MOST COMMON TYPES OF DIETARY SUPPLEMENTS USED BY ADULTS 20 YEARS OF AGE AND OLDER, BY AGE: UNITED STATES, 2017–2018

Source: Reprinted from Mishra S, Stierman B, Gahche JJ, Potischman N. Dietary Supplement Use Among Adults: United States, 2017–2018. NCHS Data Brief. 2021;399:1-8.

In 2020, U.S. supplement sales soared, surpassing $10 billion for the first time ever. U.S. retail sales of herbal supplements totaled $11.3 billion, representing a 17.3% increase from the previous year. This surge was particularly fueled by the sales of supplements touted for immune health, stress relief, and heart health, likely related to the COVID-19 pandemic sweeping the globe [2].

The focus of this course will be on the following top-selling herbal supplements, the research behind their uses, and practical safety concerns: apple cider vinegar (ACV), ashwagandha, echinacea, elderberry, and turmeric.

2. APPLE CIDER VINEGAR (ACV)

ACV is the fermented juice from crushed apples. It contains pectin, vitamins, minerals, and significant quantities of either acetic or citric acid. ACV is chemically different from vinegars derived from other sources [3].

ACV is most commonly used in cooking, especially for salad dressing, but has also been promoted for weight loss, regulation of blood sugar, blood pressure, digestive health, cholesterol reduction, immune support, skin care, and many other uses. In mainstream retail outlets, consumers spent more than $79 million on ACV supplements in 2020, representing an increase of 134% from the previous year [3].

In addition to its traditional liquid form, ACV is also now available in solid dosage forms, including tablets and gummies. The bioactive properties of ACV are influenced by multiple factors, including the raw materials, production method, and geographical conditions [3].

PRODUCTION METHODS

ACV is produced by several methods, including the slower artisanal method and the commercial/industrial method. The artisanal method uses apples and naturally occurring yeast microflora to ferment apple sugars in the absence of oxygen. Wood barrels introduce oxygen, which allows naturally occurring acetic bacteria to convert alcohol into acetic acid. The commercial method adds yeast to apple juice for alcohol production, followed by the incorporation of oxygen via a high-speed motor, which allows acetic bacteria to transform alcohol into acetic acid [3].

The constituents of ACV occur in different concentrations depending on the method. An analysis of ACV products suggests that the artisanal method produces a higher pH and higher concentrations of mineral elements, vitamin C, total phenolic content, and total flavonoid content. In vitro research suggests that ACV produced via the artisanal method has greater antioxidant activity and may have greater inhibitory activity against alpha-glucoside and alpha-amylase enzymes than ACV produced via the commercial method [3].

The process of producing ACV results in the formation of the "mother." The mother is composed of bacteria and yeast. ACV products that are cloudy in appearance and are described as raw or unfiltered typically contain the mother. These products are often labeled as organic or may include a statement about the presence of the mother. Raw or unfiltered ACV products are often preferred for culinary use because they tend to have a more intense apple flavor [3].

People sometimes incorrectly perceive raw or unfiltered ACV products to be spoiled because of their cloudy appearance, and for this reason, they might have a preference for an ACV product that is not cloudy. ACV products that are clear in appearance and are described as filtered or pasteurized typically do not contain the mother [3]. While the health benefits of ACV are often attributed to products containing the mother, this does not seem to be backed by research.

In the United States, there is no regulatory standard for identifying vinegar products. Liquid ACV for food is standardized based on acidity content, usually ranging from 4% to 8%. A laboratory analysis of commercially available ACV tablets shows wide variation in terms of content and acidity. Amounts of acetic acid range from about 1% to nearly 11% and amounts of citric acid range from 0% to nearly 19%. Buyers should be beware that amounts of constituents provided on product labels were not always consistent with laboratory findings [3].

REVIEWING THE EVIDENCE

Type 2 Diabetes

In animal models of diabetes, ACV significantly reduces glycated hemoglobin (HbA1c). ACV is thought to lower blood glucose by delaying the gastric emptying rate and/or preventing carbohydrate breakdown. Findings in humans are not as robust [3].

A small clinical study in patients with type 2 diabetes and dyslipidemia shows that taking ACV 10 mL twice daily in water for eight weeks reduces fasting blood glucose levels, but not insulin levels or insulin sensitivity, when compared with control. A very small clinical study in patients with varying degrees of insulin sensitivity shows that taking ACV 20 grams daily with a meal increases postprandial insulin sensitivity and reduces changes in insulin levels after a meal in patients with insulin resistance, but not in patients with type 2 diabetes [3].

A meta-analysis of lower-quality clinical studies in a diverse population, including patients with overweight or obesity and patients with type 2 diabetes, shows that taking ACV 15–770 mL daily for 30 to 90 days reduces fasting blood glucose levels by about 8 mg/dL and HbA1c by 0.5% when compared with water, another beverage, or no beverage control. However, these beneficial effects on glycemic indices are not observed in subgroup analyses of patients with type 2 diabetes [3].

Evidence Based Practice Recommendation

A meta-analysis published in 2021 found a significant favorable effect of apple cider vinegar consumption on fasting plasma glucose and blood lipid levels.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243436

Last Accessed: October 26, 2022

Level of Evidence: Meta-Analysis

Overall, most clinical studies suggest that oral ACV is not beneficial for improving glucose control in patients with type 2 diabetes, but results may be limited by lack of blinding in many studies, likely because the potent taste of ACV is difficult to mask. It is also unclear if the formulation of ACV alters its effects. A small crossover study in healthy adults found a modestly greater reduction in postprandial glucose with the use of liquid ACV (providing 1.25 grams of acetic acid) when compared with whole or crushed ACV tablets (providing 1.5 grams of ACV) [3].

Tell patients to rely on standard, proven therapies for the treatment of diabetes. ACV does not have enough evidence to support consistent benefits on blood glucose control.

Impaired Glucose Tolerance (Prediabetes)

There has been interest in using oral ACV for prediabetes, but there is not enough reliable information about the clinical effects of ACV for this indication [3].

Weight Loss

While ACV is often promoted for weight loss, the research is limited to just a few small studies. ACV seems to have different effects in healthy adults and in patients with overweight or obesity.

A very small clinical study in healthy adults shows that taking ACV 30 mL daily for four days has no effect on energy expenditure, at rest or during exercise. ACV also did not alter the use of carbohydrates or fats as energy sources [3].

A small clinical study in patients with overweight or obesity shows that, compared with a calorie-restricted diet alone, taking ACV 15 mL twice daily in combination with a calorie-restricted diet for 12 weeks [3]:

- Controls appetite

- Reduces body weight by 4 kg, compared with 2 kg

- Reduces body mass index (BMI) by 2 kg/m^2, compared with 1 kg/m^2

- Reduces hip girth by 6 cm, compared with 3 cm

For patients who are overweight or obese and are interested in trying ACV for its weight loss effects, a trial seems reasonable, but tell them to keep in mind that a small study showing beneficial effects had patients taking ACV in combination with a calorie-restricted diet.

SAFETY

Orally, ACV is well tolerated in the amounts found in foods. It also seems to be well tolerated when used for medical purposes for up to 12 weeks. But the use of larger amounts or for longer durations may be unsafe [3].

Because ACV is so acidic, drinking it straight can cause erosion of tooth enamel and might also exacerbate acid reflux. It is recommended that ACV be diluted in water prior to ingestion or at least followed up with ingestion of a sufficient amount of water if taken undiluted [3].

While topical use of ACV has been suggested for acne, wound disinfection, eczema, dandruff, shingles, insect bites, and sunburns, topical application may actually be unsafe. Mild skin irritation is common, and multiple cases of chemical burns have been reported [3].

3. ASHWAGANDHA

Ashwagandha is a small evergreen shrub found in dry areas of India, the Middle East, and Africa. The roots and berries are the parts that are used as medicine.

Ashwagandha is a well-known adaptogen. Adaptogens are substances that are theorized to help the body resist physiological and psychological stress. In Ayurvedic medicine, ashwagandha is known as a rasayana, or rejuvenator, and is used as a "nourishing agent for fatigue and deficiency of prana (the life vital energy)" [4].

Ashwagandha is the herbal supplement that experienced the greatest sales growth in the mainstream channel in 2020, with sales increasing by 185% from the previous year to a total of $32 million. Sales have quadrupled since 2018 [2].

Ashwagandha contains several active constituents, including alkaloids, steroidal lactones, and saponins. Ashwagandha is often standardized to the content of withanolides, a steroidal lactone, with concentrations ranging from 1.5% to 35%. However, it is unclear which constituents correlate to its clinical effects. Pharmacologic studies have found that ashwagandha has anti-inflammatory, neuroprotective, sleep-inducing, and anxiolytic properties [4].

REVIEWING THE EVIDENCE

Sleep

Ashwagandha seems to be beneficial for improving sleep in those with insomnia and in those experiencing nonrestorative sleep.

A small meta-analysis of clinical studies in a mixed population of healthy adults and patients with insomnia shows that, when compared with placebo, taking ashwagandha root extract or root and leaf extract daily for 6 to 12 weeks improves sleep quality, latency, and efficiency; total sleep time; and wake time after sleep onset. These effects were especially apparent in patients with insomnia and with doses of at least 600 mg daily for at least eight weeks, but the validity of these findings may be limited by the heterogeneity of the included studies [4].

A clinical study in patients with nonrestorative sleep shows that taking ashwagandha extract 125 mg daily for six weeks increases sleep quality by 72%, compared with only 29% in those taking placebo. Small-to-moderate improvements in total sleep time, sleep latency, and number of times awake also occurred [4].

Stress

Some researchers think that ashwagandha has a so-called "anti-stressor" effect. Some preliminary research suggests that ashwagandha suppresses stress-induced increases of dopamine receptors in the corpus striatum of the brain. It might also reduce stress-induced increases in plasma corticosterone, blood urea nitrogen (BUN), and blood lactic acid. In clinical studies, oral ashwagandha seems to help reduce stress and might even reduce stress-related weight gain.

Clinical research in patients with chronic stress and in healthy patients with moderate to high levels of stress shows that taking ashwagandha root extracts 250–600 mg daily reduces perceived stress levels by 30% to 44% and decreases cortisol levels by 22% to 30% when compared with baseline, with results remaining significant when compared with placebo [4].

Another small clinical study in patients with chronic stress shows that taking ashwagandha root extract 500 mg twice daily might also prevent stress-related weight gain when compared with placebo [4].

If patients are looking to try this top-selling botanical, tell them that the best evidence for its use seems to be for sleep and stress. Be sure patients are also practicing good sleep hygiene and using healthy ways to cope with stress.

Anxiety

In vitro studies suggest that ashwagandha has anxiolytic effects, possibly through mimicking the actions of gamma-aminobutyric acid (GABA). In animal studies, ashwagandha enhanced serotonergic transmission by modulating postsynaptic serotonin (5-HT) receptors [4]. However, the effects of ashwagandha on different types of anxiety in humans are less clear.

A small clinical study in Canadian post office employees with moderate-to-severe anxiety shows that taking ashwagandha root 300 mg twice daily for 12 weeks in combination with standard psychotherapy interventions reduces anxiety scores when compared with standard psychotherapy and placebo. Another small clinical study in young, healthy adults with perceived stress shows that taking ashwagandha root and leaf extract 225 mg or 400 mg daily for 30 days improves self-reported anxiety, stress, and depression scores similarly to placebo [4].

Generalized Anxiety Disorder (GAD)

A small clinical study in patients with generalized anxiety disorder (GAD) taking a selective serotonin reuptake inhibitor (SSRI) shows that taking ashwagandha root extract 1 gram daily for six weeks reduces anxiety symptoms by 48%, compared with a reduction of only 27% with placebo [4].

Another small clinical study in patients 16 years or older with GAD shows that taking ashwagandha root powder granules 4 grams three times daily for 60 days produces mild or moderate improvement in anxiety in 98% of patients, compared with 81% of those taking placebo. The lack of statistical comparison to placebo and the substantial placebo effect limits the validity of these findings [4].

Obsessive-Compulsive Disorder (OCD)

A small clinical study in patients with obsessive-compulsive disorder (OCD) shows that taking ashwagandha root extract at a target dose of 120 mg daily for six weeks along with an SSRI reduces OCD symptom severity scores when compared with taking an SSRI alone. However, scores were already significantly lower at baseline in the group receiving an SSRI alone [4].

For diagnosed anxiety, GAD, and OCD, there is no substitute for standard therapy, including medications and psychotherapy. Tell patients that it is probably better to save their healthcare dollars for more proven therapies [4].

SAFETY

Orally, ashwagandha seems to be well tolerated. Doses of up to 1,250 mg daily for up to six months have been used with apparent safety. The safety of ashwagandha when used long-term remains unclear [4].

The most common adverse effects are gastrointestinal (GI) related, including diarrhea, GI upset, nausea, and vomiting. GI adverse effects are reported most often with large doses [4].

While topical use of ashwagandha has been suggested for some conditions, including back pain and wound healing, there is not enough information available to know if topical application is safe. So far, no adverse effects have been reported [4].

Interaction with Other Drugs, Herbs, and Supplements with Sedative Properties

Ashwagandha seems to have sedative effects, so taking it in combination with substances that have sedative effects (e.g., benzodiazepines, other herbs and supplements with sedative properties) might increase the therapeutic and adverse effects of ashwagandha. Use caution in patients taking these combinations. [4]

Interactions with Conditions

Thyroid Disorders

Ashwagandha has been shown to stimulate thyroid hormone synthesis and/or secretion, increasing serum triiodothyronine (T3) and thyroxine (T4) concentrations and reducing serum thyroid stimulating hormone (TSH) levels [4]. This might exacerbate hyperthyroidism. Recommend that patients with hyperthyroidism or those being treated with thyroid hormones use ashwagandha with caution.

Interactions with Lab Tests

Digoxin Serum Assay

Ashwagandha might falsely increase digoxin levels on some serum assays. Withaferin A, a constituent of ashwagandha, has a similar chemical structure to digoxin and is responsible for this potential lab interaction. Immunoassays most likely to be affected include those using fluorescence polarization or microparticle enzymes [4].

4. ECHINACEA

Echinacea refers to the species of perennial plant closely related to sunflowers, daisies, and ragweed. The above-ground parts and the roots of three such species (Echinacea angustifolia, E. purpurea, and E. pallida) have been used as medicines. These plants range in height from 1–5 feet and have purple or pinkish-red flower petals [5].

Although these three species of echinacea are often used interchangeably, very little research has been done to compare them. While some products have been standardized to specific constituents (e.g., alkamides), the active constituents of echinacea have not been identified, so standardization may not be clinically relevant in predicting effectiveness [5].

In mainstream retail outlets, consumers spent an estimated $57 million on echinacea supplements in 2020, representing an increase of 37% from the previous year [2].

REVIEWING THE EVIDENCE

Common Cold

Adults

Echinacea is probably most well known for its role in preventing the common cold, though effects are generally modest. Its use for the treatment of the common cold is not as well established. The fact that these studies have evaluated the use of tinctures, extracts, and teas also makes it difficult to compare doses or even recommend the best dose for a patient to take.

Three meta-analyses have shown that taking various forms of echinacea reduces the risk of developing a cold by 10% to 58%. Another large clinical study shows that daily usage of echinacea with a dosage increase at the first sign of a cold results in 59% fewer cold episodes and 26% fewer days with cold symptoms when compared with placebo. Some clinical studies have demonstrated nonsignificant effects of echinacea on preventing colds, but these were generally smaller studies and more likely to be underpowered [5]. Small, flawed studies have shown that taking echinacea prior to intentional infection with a cold virus and continuing to take it after infection does not reduce the incidence of colds in adults [5].

In terms of lessening symptom severity or cold duration, small clinical studies have yielded some promising results, but higher-quality research shows that echinacea does not reduce symptom severity or cold duration when compared with placebo [5]. Adults might prevent some colds by taking echinacea on a situational basis (e.g., prior to traveling, during cold season), but taking it once they are already sick does not seem to help much.

Children

Studies of echinacea in children are less convincing. A clinical study in healthy children 4 to 12 years of age shows that taking echinacea 400 mg three times daily for four months reduces the occurrence of cold symptoms, respiratory complications (e.g., pneumonia, otitis media), and antibiotic prescriptions by 30%, 52%, and 62%, respectively. It also reduces the average duration of symptoms during respiratory illness by 1.4 days when compared with vitamin C 50 mg three times daily [5]. Other clinical research has found no benefit. Studies comparing echinacea to placebo in children are lacking. There is not enough evidence to recommend its use in children.

Influenza

Some research shows that echinacea may exhibit antiviral activity against influenza virus. A large clinical study in adults and children at least 12 years of age with early influenza symptoms shows that taking a hot echinacea extract-based drink also containing elderberry five times daily for three days, followed by three times daily for seven days, improves recovery and respiratory complications similarly to oseltamivir. Because there was no placebo group, it is unclear if both treatments were beneficial or if the outcomes were in line with the usual self-limiting nature of influenza. It is also not clear if these effects were due to echinacea, elderberry, or the combination [5].

There is not enough clear evidence to recommend taking an echinacea-elderberry combination for influenza. While echinacea has also been studied for a broad range of other uses, the evidence for its use in many other conditions is currently limited or conflicting.

SAFETY

Orally, echinacea is well tolerated. Doses of up to 16 grams daily for 35 days have been used in adults, but doses vary widely depending upon the specific commercial product used [5]. The most common adverse effects are rashes and adverse GI effects, including abdominal pain, constipation, diarrhea, heartburn, nausea, vomiting, and upset stomach.

Echinacea has also been used topically, including as a cream, mouthwash, and throat spray, for a variety of conditions, including burns, cold sores, psoriasis, and warts. Topical use of echinacea seems to be safe on a short-term basis [5].

Allergic Reactions

Echinacea species are members of the Asteraceae family. Those with a genetic tendency toward allergic conditions (atopy), such as eczema, and those who are sensitive to other members of this family, which include ragweed, chrysanthemums, marigolds, and daisies, seem to be at higher risk for allergic reactions to echinacea [5]. Allergic reactions, including urticaria, runny nose, dyspnea, bronchospasm, acute asthma, angioedema, and anaphylaxis, have been reported with various echinacea preparations.

In a clinical study in 407 children 2 to 11 years of age, about 7% of children experienced a rash after taking echinacea. These rashes may have been caused by an allergic reaction, and there is some concern that such reactions could be severe in some children. However, another study in children 4 to 12 years of age showed that a specific E. purpurea product did not cause allergic or urticarial reactions more frequently than vitamin C [5]. Because of the risk of allergic reaction, the Medicines and Healthcare Products Regulatory Agency in the United Kingdom (UK) recommends against the use of oral echinacea in children younger than 12 years of age [5].

Interactions with Drugs, Herbs, and Supplements

Substrates of Cytochrome P450 (CYP) 1A2 and 3A4

Echinacea might inhibit CYP1A2, increasing the levels of drugs metabolized by this enzyme. Echinacea might increase or decrease levels of drugs metabolized by CYP3A4 through inhibition of intestinal CYP3A4 and induction of hepatic CYP3A4, respectively, though there is some variability depending on the substrate. For patients taking narrow therapeutic index drugs metabolized by these enzymes, use echinacea with caution [5].

5. ELDERBERRY

The deciduous European or black elder tree (Sambuca nigra) is the source of elderberry, a dark purple berry. This same tree is also the source of elderflowers. Both the berries and the flowers have been used in foods and beverages, but the berry is much more commonly used for medicinal purposes [6].

People often use elderberry to support immune health, and it has a long history of use in folk medicine for the treatment of colds and flu. Interestingly, Google searches for elderberry peaked in late March 2020, shortly after the COVID-19 outbreak was declared a global pandemic by the World Health Organization (WHO). In mainstream retail outlets, consumers spent an estimated $275 million on elderberry in 2020, representing an increase of 150% from the previous year [2].

Elderberry products come in a variety of oral dosage formulations, including capsules, syrups, and lozenges, as well as topical dosage forms, including a mouthwash and a periodontal patch.

REVIEWING THE EVIDENCE

Respiratory Illness

Influenza

In vitro, elderberry extract inhibits replication of several strains of influenza A and B. The most convincing evidence for elderberry is for the treatment of influenza in otherwise healthy adults [6].

Small clinical studies in otherwise healthy adults with influenza show that taking elderberry fruit extract within 24 to 48 hours of symptom onset improves symptoms, often within 48 hours, when compared with placebo or other control.

A small clinical study in adults and children 5 years of age or older with influenza, including those with high-risk conditions such as asthma, chronic lung disease, and heart disease, shows that taking elderberry fruit extract does not reduce the duration of symptoms when compared with placebo. The negative findings could be due to the age and baseline health status of the enrolled patients, as well as the use of symptom resolution, rather than symptom improvement, as the primary outcome [6].

As discussed, elderberry has also been studied in combination with echinacea for treating influenza symptoms, but it is unclear whether the combination is better than either ingredient alone. For otherwise healthy patients looking to try elderberry for treating influenza, recommend taking it soon after the onset of symptoms for the greatest benefit [6].

Common Cold

Elderberry has been evaluated for the treatment of influenza, but for the common cold, it has only been evaluated for prevention. Research for the prevention of the common cold is less convincing than that for the treatment of influenza [6].

A large clinical study in healthy adults traveling overseas shows that taking elderberry extract prophylactically, beginning eight days prior to air travel and continuing for four to five days after arrival to the destination, does not reduce the number of colds or impact quality of life, when compared with placebo. But the duration and severity of existing colds was reduced by two days and 58%, respectively [6].

Tell patients that taking elderberry regularly does not seem to actually prevent colds. If they still want to try it, it might make the colds they do catch shorter and a bit less severe.

SAFETY

Orally, elderberry extracts prepared from the ripe fruit seem to be well tolerated. Fruit extracts have most often been used in doses of up to 1,200 mg daily for two weeks or up to 500 mg daily for up to six months [6].

When adverse effects do occur, they are likely due to the ingestion of raw (i.e., uncooked) and unripe green berries. These, along with the seeds, leaves, and other plant parts, contain cyanogenic glycosides that can lead to adverse GI effects (e.g., nausea, vomiting, severe diarrhea), weakness, dizziness, numbness, and stupor. In some patients who are allergic to grass pollen, elder tree pollen might cause an allergic reaction characterized by rhinitis and dyspnea [6].

6. TURMERIC

Turmeric is a spice that is commonly used in cooking. It is also used in traditional Chinese and Indian medicine. Turmeric is derived from the rhizome or root of the turmeric plant (Curcuma longa), which is a perennial herb and a member of the Zingiberaceae (ginger) family. Curcumin, a curcuminoid and the primary active constituent of turmeric, is what gives turmeric its distinctive yellow color [7].

Studies typically evaluate the use of turmeric supplements, not just ground turmeric as a spice. Supplements are often extracts and are usually standardized to curcuminoid (generally curcumin) content [7].

Although turmeric sales only increased by 3% from 2019 to 2020, turmeric sales consistently top the charts with mainstream retail outlet sales totaling close to $100 million in 2020. In addition to its status as a top-selling herbal supplement, turmeric is also incredibly well studied, especially for its anti-inflammatory benefits [2].

FORMULATIONS

The oral bioavailability of curcumin is very low. Curcumin absorption appears to increase when taken [7]:

- With food

- With piperine (the active ingredient in black or white pepper)

- In a capsule

- In a liposomal formulation

- In a nanoparticle formulation

- In a phospholipid complex

- As part of a novel turmeric matrix system

- As a water-dispersible turmeric extract

Some methods of boosting curcumin absorption can be significant, resulting in a five- to seven-fold increase in absorption. Because absorption may be very specific to certain formulations, this aspect should always be considered when reviewing the evidence on the effectiveness and safety of various turmeric products [7].

REVIEWING THE EVIDENCE

Osteoarthritis

Turmeric extracts have been well studied for the treatment of knee osteoarthritis.

Oral Turmeric Compared with Placebo

Meta-analyses of low- to moderate-quality studies in patients with knee osteoarthritis show that taking turmeric extracts reduces pain and improves physical function when compared with placebo, but effects were less pronounced in those with increasing age or BMI. The validity of these findings is limited by the heterogeneity of the included studies [7].

While many small- to moderate-sized individual clinical studies show that specific products containing curcumin or turmeric extracts reduce pain and analgesic use and improve functionality when compared with placebo, not all research agrees [7].

Oral Turmeric Compared with Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

A small meta-analysis in patients with knee osteoarthritis shows that taking turmeric extracts reduces pain better than an NSAID. Individual clinical studies have yielded more conflicting results. While several clinical studies show that taking turmeric extract 500 mg three to four times daily for four to six weeks reduces knee pain similarly to ibuprofen 400 mg two to three times daily, another study shows that taking turmeric extract 500 mg twice daily as an adjuvant to diclofenac 25 mg daily does not improve knee pain or function any better than diclofenac alone [7].

Oral Turmeric in Combination with Other Ingredients

Combination products that include turmeric with a number of different ingredients have also demonstrated improved pain and functionality in patients with osteoarthritis. Other ingredients that have commonly been used in conjunction with turmeric include chondroitin sulfate, glucosamine, Boswellia serrata, ginger, and devil's claw [7].

Topical Turmeric

Evidence Based Practice Recommendation

According to the American Academy of Dermatology and the National Psoriasis Foundation, further studies are required to better assess the role of curcumin in psoriasis.

https://www.jaad.org/article/S0190-9622(20)32288-X/fulltext

Last Accessed: October 26, 2022

Level of Evidence: Expert Opinion/Consensus Statement

Topical administration of turmeric has also been evaluated for knee osteoarthritis. A small clinical study in patients with knee osteoarthritis shows that twice daily topical application of curcumin 5% in a petrolatum-based ointment for 6 weeks only seems to reduce pain by about 11% when compared with placebo [7]. A trial of turmeric might be reasonable for patients experiencing joint pain attributable to osteoarthritis who are either trying to avoid or are not candidates for NSAID therapy.

Rheumatoid Arthritis

Because of turmeric's well known anti-inflammatory properties, it has also been studied for rheumatoid arthritis (RA). In vitro evidence suggests some benefits specific to RA pathogenesis, but its effects on RA in clinical research are modest, at best.

One small study in patients with RA shows that taking 500 mg of a specific curcumin supplement twice daily for eight weeks improves some RA symptoms when compared with diclofenac 50 mg twice daily. Several other small studies show that taking curcumin 250 mg twice daily for three months or 400 mg three times daily for two weeks improves pain, morning stiffness, walking time, and joint swelling when compared with baseline. It is unclear if these effects were meaningful given the lack of statistical comparison to the control groups [7].

Nonalcoholic Fatty Liver Disease (NAFLD)

The global prevalence of nonalcoholic fatty liver disease (NAFLD) is estimated to be around 25%, so the search for potential treatments is on the rise. Clinical research in adults with NAFLD shows that taking curcumin daily reduces NAFLD severity in 30% to 79% of patients, compared with only 5% to 28% with placebo. It also attenuated additional fat deposition in the liver to only 0% to 5%, compared with 18% to 26% in those taking placebo [7]. Metabolic parameters (e.g., liver enzyme levels, BMI, blood glucose levels, HbA1c, lipid levels) also seem to be improved. Variability in some of the specific end points of individual studies might be due to differences in the formulations studied or the duration of treatment.

Emphasize that weight loss is the cornerstone of treatment for NAFLD, but if patients are asking about supplements, a trial of turmeric might provide some small, but encouraging, additional improvements [7].

Like echinacea, turmeric is of interest and has been studied for a variety of other uses, but the research for many of these other conditions is currently limited or conflicting.

SAFETY

Orally, turmeric seems to be safe and well tolerated. Doses of turmeric up to 3 grams daily have been used with apparent safety for up to three months. Doses of curcumin up to 8 grams daily have been safely used for up to two months [7].

Most commonly, turmeric is associated with adverse GI effects, including constipation, dyspepsia, diarrhea, distension, gastroesophageal reflux, nausea, and vomiting. Topically, turmeric also seems to be safe, though turmeric or some of its constituents can cause allergic contact dermatitis and curcumin can cause contact urticaria and pruritus [7].

Contamination is a concern with turmeric. An analysis of randomly selected turmeric products in the United States found that turmeric root products contain 2.5-fold higher concentrations of lead than turmeric-derived curcuminoid extracts. For this reason, choosing a turmeric product with a third-party quality certification is important [7].

Interactions with Drugs, Herbs, and Supplements

Anticoagulant/Antiplatelet Drugs, Herbs, and Supplements

In vitro, curcumin has demonstrated antiplatelet effects. A clinical study in healthy individuals shows taking curcumin alone or in combination with aspirin does not increase antiplatelet effects or bleeding, but it is possible that the dose of turmeric used in this study was too low to see an effect [7].

Increases in the international normalized ratio (INR) have also been observed in cases of patients taking turmeric in combination with warfarin. Use turmeric with caution in patients taking anticoagulant or antiplatelet drugs, herbs, and supplements [7].

Chemotherapy Drugs

Turmeric may interact with chemotherapy drugs that generate free radicals, including alkylating agents, antitumor antibiotics, and topoisomerase I inhibitors. Lower doses of curcumin might have antioxidant effects, while higher doses might have pro-oxidant effects, resulting in inhibition or augmentation of, respectively, the cytotoxic effects of these drugs. More evidence is needed to determine what effect, if any, turmeric might have [7].

P-glycoprotein Substrates

In vitro and animal research shows that curcuminoids and other turmeric constituents can inhibit P-glycoprotein expression and activity, increasing the absorption of P-glycoprotein substrates. For patients taking narrow therapeutic index drugs that are substrates of P-glycoprotein, use turmeric cautiously [7].

Substrates of Cytochrome P450 (CYP) 1A1, 1A2, and 3A4

In vitro and animal research shows that turmeric and/or curcumin might inhibit CYP1A1, 1A2, and 3A4, increasing the levels of drugs metabolized by these enzymes, though some research disagrees. There is also some in vitro evidence that curcumin may induce CYP1A1. For patients taking narrow therapeutic index drugs metabolized by these enzymes, use turmeric cautiously [7].

Sulfasalazine

Curcumin can increase levels of sulfasalazine by more than three times, increasing both the effects and adverse effects of sulfasalazine. Dosage of sulfasalazine may require adjustment [7].

Tamoxifen

A small clinical study in patients with breast cancer taking tamoxifen shows that adding curcumin plus piperine reduces exposure to tamoxifen and its active metabolite when compared with taking tamoxifen alone. This effect was especially apparent among patients who are extensive metabolizers of CYP2D6 substrates. This interaction can potentially result in reduced clinical effects of tamoxifen. Use turmeric with caution in patients taking tamoxifen [7].

Interactions with Conditions

Hormone-Sensitive Cancers and Conditions

Turmeric might have mild estrogenic effects, but research is conflicting. Use turmeric with caution in patients with hormone-sensitive cancers and conditions [7].

Bleeding Disorders

Because turmeric has been reported to have antiplatelet effects, it might increase the risk of bleeding and bruising in patients with bleeding disorders. Use turmeric with caution in patients with bleeding disorders [7].

Bile Duct Obstruction and Gallstones

Because turmeric can cause gallbladder contractions, use turmeric with caution in patients with gallstones and gallbladder disease [7].

7. SPECIAL CONSIDERATIONS

COVID-19

Throughout the pandemic, there have been seemingly countless claims related to the use of supplements for the prevention and/or treatment of COVID-19. In fact, all five of the supplements covered in this course have at some point been touted for the prevention and/or treatment of COVID-19. Despite these claims, there is no good evidence to support using any of these supplements for the prevention or treatment of COVID-19. Instead, recommend that patients make healthy lifestyle choices and choose proven methods for prevention (e.g., vaccination) [2].

REPRODUCTIVE EFFECTS

Fertility

In vitro and animal research suggests that curcumin can reduce fertility, sperm motility and density, and production of testosterone in adult Leydig cells. It can also cause degenerative changes in seminiferous tubules. Advise patients trying to conceive to use turmeric with caution [7].

Pregnancy

When elderberry and ACV are used in typical amounts found in foods, use during pregnancy is likely safe. There is not enough information available to know if use of medicinal amounts of these botanicals is safe in pregnant patients [3,6].

When turmeric is used in typical amounts found in foods, use during pregnancy is likely safe. When used in medicinal amounts, turmeric might stimulate the uterus and increase menstrual flow. Recommend that patients avoid turmeric supplements during pregnancy [7].

Ashwagandha has abortifacient effects and is unsafe for use during pregnancy. Recommend that patients avoid ashwagandha during pregnancy [4].

AUTOIMMUNE DISEASES

Elderberry, echinacea, and ashwagandha can stimulate immune function. Theoretically, these supplements might exacerbate autoimmune disease by stimulating disease activity. For the same reason, these supplements might have drug interactions with immunosuppressant drugs. Recommend that patients with autoimmune diseases (e.g., multiple sclerosis, systemic lupus erythematosus, RA, pemphigus vulgaris) and those taking immunosuppressants use these supplements with caution or avoid their use altogether [4,5,6].

HEPATOTOXICITY

There have been reports of liver injury with the use of some of these popular supplements. Although some herbal supplements are more prone to contamination than others, it is unclear whether reports of hepatotoxicity are the result of contamination, the actual substance itself, or some other mechanism.

Turmeric

There have been at least 60 reports of liver damage, including noninfectious hepatitis, cholestasis, and hepatocellular liver injury, associated with taking turmeric supplements for as little as two weeks to up to eight months. In at least 10 such cases, high dose curcumin and highly bioavailable formulations (e.g., phytosomal curcumin, piperine-containing formulations) were used, but for many cases, formulation, dosing, and duration of use were not reported. In many cases, turmeric was used concomitantly with other supplements, which may have contributed to the risk of liver damage. Most cases of liver damage resolved upon discontinuation of the turmeric supplement. Caution patients that taking turmeric, especially high-dose curcumin and highly bioavailable formulations, in combination with other drugs, herbs, and supplements that might cause liver damage can increase the risk of liver damage [7].

Echinacea

Cases of hepatitis have been reported rarely with echinacea use. In cases in which details were available, liver function tests normalized within one to three months following discontinuation of echinacea [5].

Ashwagandha

Several cases of liver injury have been reported with the use of typical doses, with symptoms including jaundice, nausea, abdominal pain, lethargy, and pruritus. Symptoms began within 2 to 12 weeks of taking ashwagandha and liver enzymes normalized within 1 to 5 months after discontinuation of ashwagandha. None of the cases progressed to liver failure [4].

HYPOGLYCEMIC AGENTS

Turmeric, ACV, and ashwagandha might decrease blood glucose levels in patients with diabetes, increasing the risk of hypoglycemia. Recommend that patients with diabetes carefully monitor blood glucose when taking these supplements, especially when they are taken in combination with antidiabetic drugs and/or other herbs and supplements with hypoglycemic potential [3,4,7].

PATIENT COUNSELING CONSIDERATIONS

The importance of asking patients about dietary supplement usage while obtaining their medication history cannot be understated. This is the perfect opportunity to have a nonjudgmental conversation with patients and to help identify potential safety concerns.

For patients who are not proficient in English, it is important that information regarding the benefits and risks associated with the use of dietary supplements be provided in their native language, if possible. When there is an obvious disconnect in the communication process between the practitioner and patient due to the patient's lack of proficiency in the English language, an interpreter is required. Interpreters can be a valuable resource to help bridge the communication and cultural gap between patients and practitioners. Interpreters are more than passive agents who translate and transmit information back and forth from party to party. When they are enlisted and treated as part of the interdisciplinary clinical team, they serve as cultural brokers who ultimately enhance the clinical encounter.

This is also a great opportunity to remind patients that dietary supplement oversight differs from that of prescription and over-the-counter (OTC) products regulated by the U.S. Food and Drug Administration (FDA). The studies supporting the safe and effective use of supplements tend to be smaller, fewer, flawed, and less rigorous than those supporting prescription and OTC medications.

Because there is no guarantee that these products contain what is listed on the bottle and in the stated amounts, emphasize the importance of choosing a product likely to be of higher quality, such as those with third-party verification.

PRODUCT QUALITY

Verifying the quality of herbal products is difficult. The tests required and the accuracy of the resulting analyses are very different from those used for vitamins and minerals. To ensure the selection of a high-quality product, look for third-party quality certification.

U.S. Pharmacopeia (USP)

In addition to inspecting manufacturing facilities for cGMP compliance at least two times in a three-year period, USP will also conduct random off-the-shelf analyses of verified products to ensure that the contents of the product match those listed on the label. This random testing holds manufacturers to a high standard.

The USP verification stamp can be found on a product's label. USP is typically considered the gold standard for dietary supplement quality verification, though their purview is limited.

National Sanitation Foundation (NSF)

Like USP, NSF is also a strong source of dietary supplement quality verification. However, general NSF certification does not necessarily imply the same quality standards as those seen with USP verification. In order for a manufacturer to list NSF certification on their website, they must pass an NSF inspection of cGMP compliance every six months. NSF does not conduct off-the-shelf analyses of products unless the manufacturer is enrolled in the "Contents Tested and Certified" or "Certified for Sport" programs. Under these programs, manufacturers are subject to random off-the-shelf testing and can place an NSF seal of approval on the product label. That seal of approval will typically state "NSF: Contents Certified" or "NSF: Certified SPORT." Unfortunately, options for NSF-certified herbal products are typically limited as well.

8. CONCLUSION

Dietary supplement use is increasingly common. Sales of herbal supplements seem to be largely driven by pandemic-related health concerns, but sales figures alone do not reflect the effectiveness of a supplement for a given condition, so it is important to examine the research surrounding these blockbuster supplements. Further, no supplement is without safety concerns, such as adverse effects, interactions (e.g., disease, drug, other supplements), and product quality concerns (e.g., contamination). It is imperative that clinicians provide evidence-based recommendations and appropriate safety warnings to help patients make informed decisions about their health.

Works Cited

1. Mishra S, Stierman B, Gahche JJ, Potischman N. Dietary supplement use among adults: United States, 2017–2018. NCHS Data Brief. 2021;(399):1-8.

2. Smith T, Majid, F, Eckl V, Reynolds CM. Herbal supplements sales in US increase by record-breaking 17.3% in 2020: sales of immune health, stress relief, and heart health supplements grow during COVID-19 pandemic. HerbalGram. 2021;(131):52-65.

3. TRC Healthcare Natural Medicines Database. Apple Cider Vinegar. Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=816. Last accessed October 19, 2022.

4. TRC Healthcare Natural Medicines Database. Ashwagandha. Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=953. Last accessed October 19, 2022.

5. TRC Healthcare Natural Medicines Database. Echinacea. Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=981. Last accessed October 19, 2022.

6. TRC Healthcare Natural Medicines Database. Elderberry. Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=434. Last accessed October 19, 2022.

7. TRC Healthcare Natural Medicines Database. Turmeric. Available at https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=662. Last accessed October 19, 2022.

Evidence-Based Practice Recommendations Citations

1. Hadi A, Pourmasoumi M, Najafgholizadeh A, Clark CCT, Esmaillzadeh A. The effect of apple cider vinegar on lipid profiles and glycemic parameters: a systematic review and meta-analysis of randomized clinical trials. BMC Complement Med Ther. 2021;21(1):179. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243436. Last accessed October 26, 2022.

2. Elmets CA, Korman NJ, Prater EF, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures. J Am Acad Dermatol. 2021;84(2):432-470. Available at https://www.jaad.org/article/S0190-9622(20)32288-X/fulltext. Last accessed October 26, 2022.