THE AGRICULTURE IMPROVEMENT ACT OF 2018
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].
GENERAL SAFETY CONSIDERATIONS
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.
GENERAL SAFETY CONSIDERATIONS
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].
