The Farm Bill paved the way for the legal sale of various cannabinoids and hemp-based products without DEA oversight, which led to a surge in consumer interest and product availability that has only continued to increase.

While it is unclear if smoking cannabis improves MS-related symptoms, certain oral products combining THC and CBD, such as nabiximols, seem to reduce spasticity in patients with MS. Nabiximols, a prescription oromucosal spray containing cannabis extract (Sativex) is available in most of Europe and Canada but is not yet approved in the United States. Each actuation is standardized to deliver THC 2.7 mg and CBD 2.5 mg. Meta-analyses show that nabiximols modestly reduces subjective spasticity but not bladder dysfunction or neuropathic pain [14,15]. Effects endure over 11 months, but discontinuation of use may cause rebound symptoms [16,17]. Another meta-analysis shows that taking oral cannabis extracts with THC 25–30 mg and CBD 8-18 mg daily for up to 15 weeks modestly reduces subjective spasticity, neuropathic pain, and bladder dysfunction, but not objective spasticity measures [14].

Cannabis crosses the placenta, and its use during pregnancy has been associated with numerous negative maternal and fetal outcomes in observational studies [22]. THC is excreted into the breast milk for at least six weeks after cessation and can cause delayed motor development in infants [29]. Patients should be informed of these risks and discouraged from using cannabis while pregnant or breastfeeding.

The regulatory landscape of CBD is evolving. In May 2019, the FDA approved a specific, oil-based prescription formulation of CBD (Epidiolex) for treating seizures associated with Lennox-Gastaut and Dravet syndromes and tuberous sclerosis complex [30]. The 2018 Farm Bill legalized hemp and its constituents, including CBD, by removing them from the Controlled Substances Act. However, the FDA's approval of a prescription CBD product has added complexity to its legal status [5].

Research on the use of CBD for mental health benefits is inconclusive. For example, research in patients with treatment-resistant anxiety shows that taking CBD up to 800 mg daily for 12 weeks reduces anxiety severity by 43% and modestly improves depression symptoms from baseline. However, benefits were not maintained at a six-month follow-up [39]. Current evidence is insufficient to recommend CBD for management of mental health conditions.

CBDV is a nonpsychoactive cannabinoid that is structurally similar to CBD, and therefore acts through many of the same receptor pathways, exhibiting activity at CB2 but minimally at CB1 [49,68].

Although there is interest in using CBN for its analgesic, anti-inflammatory, and immunologic effects, it has not been evaluated in clinical studies. Due to its mild psychoactive effects, CBN has been studied for its potential benefits in treating insomnia, but the evidence available is inconclusive. For example, a clinical trial involving adults with self-reported poor sleep quality found that taking 20 mg of CBN 90 minutes before bed for a week did not improve sleep quality compared to a placebo [41]. More research is needed to determine the efficacy of CBN for insomnia.

According to data compiled from sources including the FDA, CDC, and the American Association of Poison Control Centers, common adverse effects include difficulty thinking and speaking, dreamlike state, euphoria, feeling "high," and vision and time distortion. More serious symptoms include vomiting, lethargy, hallucinations, lack of muscle coordination, altered heart rate, low blood pressure, difficulty breathing, and coma. Concerning safety signals include Brugada EKG pattern and CHS, frequently necessitating emergency care [76].

Excessive and prolonged cannabis use (e.g., two to three times daily over two years) can trigger a condition called cannabinoid hyperemesis syndrome (CHS). This condition is characterized by cyclic episodes of severe nausea and vomiting resistant to conventional antiemetics. Patients commonly report temporary symptom relief with bathing in extremely hot water, and this is often a clue that points providers to a possible diagnosis. CHS has been documented with both inhaled and oral use and has been linked to severe complications, including several fatalities. 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.

Accidental ingestion of cannabis-containing edibles among children 12 years and younger has increased significantly. This trend correlates with recreational cannabis legalization and the proliferation of appealing food formulations like gummies. The effects of such accidental ingestion can include ataxia, coma, hypotonia, hypothermia, lethargy, nystagmus, respiratory depression, seizures, and tremors [80].