Wednesday, 20 Nov 2019

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Medical Use of Cannabis in 2019

JAMA has published an overview of cannabis and its medical uses. Although nearly  10% of cannabis users in the United States report using it for medicinal purposes, there is insufficient evidence to support the use of medical cannabis for most conditions for which its use is advocated or advised.  Nevertheless, there is an increase in favoring the public availability of cannabis, largely for the management of more than 50 medical conditions. 

Currently, 33 states and the District of Columbia have policies allowing the use of cannabis or cannabinoids for the management of specific medical conditions. Nevertheless, the DEA still classifies cannabis as illegal, complicating its medical use and research into its effectiveness as a treatment for medical conditions.  (Editors note: an un-named past FDA official once told me that marijuana [cannabis] would never be FDA approved because of the lack of good evidence, good trials and current unbelievable claims.) 

It is not likely that additional cannabinoids will be approved by the FDA in the near future. Public interest in cannabis and cannabinoids as pharmacotherapy continues to increase, as does the number of medical conditions for which patients are utilizing cannabis and CBD, despite insufficient evidence to support this trend.

Indications for Therapeutic Use Approved by the US Food and Drug Administration

Cannabis has numerous cannabinoids, the most notable being tetrahydrocannabinol (THC), which accounts for its psychoactive effects. Few cannabinoids have high-quality evidence to support their use and are approved for medicinal use by the US Food and Drug Administration (FDA).

Dronabinol and nabilone are cannabinoids approved by the FDA for chemotherapy-induced nausea and vomiting in 1985, with dronabinol gaining an additional indication for appetite stimulation in conditions that cause weight loss, such as AIDS, in 1992. A third cannabinoid, cannabidiol (CBD), was approved by the FDA for 2 forms of pediatric epilepsy, Dravet syndrome and Lennox-Gastaut syndrome, based on positive randomized clinical trials (RCTs). 

Other Medical Indications

Cannabinoids are often cited as being effective for managing chronic pain. The National Academies of Science, Engineering, and Medicine examined this issue and found that there was substantial evidence that cannabis or cannabinoids effectively managed chronic pain, based on their expert committee’s assessment that the literature on this topic had many supportive findings from good-quality studies with no credible opposing findings.

The panel relied on a single meta-analysis of 28 studies, few of which were from the United States, that assessed a variety of diseases and compounds. The primary limitation was that the confidence intervals associated with these findings were large, suggesting unreliability in the meta-analysis results.

A recent meta-analysis of 91 publications found cannabinoids to reduce pain 30% more than placebo (odds ratio, 1.46 [95% CI, 1.16-1.84]), but had a number needed to treat for chronic pain of 24 (95% CI, 15-61) and a number needed to harm of 6 (95% CI, 5-8).

Most supportive studies are for neuropathic pain, with few high-quality studies examining other types of pain. Thus, there is inconclusive evidence that cannabinoids effectively manage chronic pain, and large numbers of patients must receive treatment with cannabinoids for a few to benefit, and that harm is more frequent than most believe.

There is strong evidence to support relief of symptoms of muscle spasticity resulting from multiple sclerosis from cannabinoids as reported by patients, but the association is much weaker when outcomes are measured by physicians 

Other Studies

Cannabis is purported to benefit many other medical conditions, including Parkinson disease, posttraumatic stress disorder, and Tourette syndrome, largely based on cannabinoid effects on spasticity, anxiety, and density of cannabinoid receptors in areas implicated in development of tics, such as the basal ganglia and cerebellum. The strength of the evidence supporting the use of cannabinoids for these diseases is weak, as these studies have been small, often uncontrolled, or crossover studies.

Adverse Effects Are Better Defined Than Clinical Benefits

Acute cannabis use is associated with impaired learning, memory, attention, and motor coordination, judgment decisions and cognitive effects.

Chronic cannabis use is associated with an increased risk of psychiatric illness and addiction. There is a significant associationbetween cannabis use and the development of psychotic disorders, such as schizophrenia, particularly among heavy users.

The chronic cannabis use disorder (CUD) leads to impairment in work, school, and relationships in up to 1/3 of adult users.

Cannabis use is associated with adverse perinatal outcomes as well; a 2019 study showed the crude rate of preterm birth was 12.0% among cannabis users and 6.1% among nonusers. 

Inadequate Evidence to Support Use in Medical Conditions

The quality of the evidence supporting the use of cannabinoids is suboptimal. Studies assessing pain and spasticity are difficult to conduct. Most cannabis RCTs have been short term and small scale and may overestimate treatment effects.

There is a large need for well-designed, large, multisite RCTs of cannabis or cannabinoids to resolve claims of efficacy for conditions for which there are claims of efficacy not supported by high-quality evidence, such as pain and spasticity.

Physicians may be appropriate in their reluctance to recommend medical cannabis for their patients because of the limited scientific evidence supporting and because cannabis remains illegal in federal law.

The author has no conflicts of interest to disclose related to this subject

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