Cannabis-based products associated with chronic pain improvement, review finds

The strongest available evidence is for synthetic and extracted products with high and comparable THC-to-CBD ratios, both of which resulted in improvements in pain severity, according to a systematic review of 18 placebo-controlled trials and seven cohort studies.

Cannabis-based products are associated with reduced pain severity in patients with chronic pain but also carry an increased risk for dizziness and sedation, a recent study found.

Researchers conducted a systematic review of 18 randomized placebo-controlled trials (n=1,740) and seven cohort studies (n=13,095) of one-month duration or more that assessed cannabinoids for chronic pain. They characterized cannabinoids by tetrahydrocannabinol (THC)-to-cannabidiol (CBD) ratio (high, comparable, or low) and source (synthetic, extract or purified, or whole plant). Primary outcomes were measures of pain, physical or general functioning, and adverse events. Adverse events of interest included serious adverse events, adverse events leading to study withdrawal, nausea, dizziness, sedation, psychosis, development of cannabis use disorder, and cognitive deficits. Results were published June 7 by Annals of Internal Medicine. A video summary of the review is also freely available.

The duration of the included studies was one to six months, with most lasting four to eight weeks. Most enrolled patients had neuropathic pain (56%), were middle-aged, were White, and had mean baseline pain scores of 5 to 6 on a scale of 0 to 10. Oral, synthetic products with high THC-to-CBD ratios (>98% THC) were associated with moderate improvement in pain severity in six trials of 390 participants (mean difference, −1.15; 95% CI, −1.99 to −0.54). These products were associated with moderate increase in risk for sedation in two trials of dronabinol and one trial of nabilone totaling 335 participants. They were also associated with large increased risk for study withdrawal due to adverse events and dizziness compared with placebo; however, the rate of serious adverse events did not significantly differ between groups. Sublingual, extracted products with a comparable THC-to-CBD ratio were associated with small improvement in pain severity in seven trials of 702 participants (mean difference, −0.54; 95% CI, −0.95 to −0.19) and overall function on a scale of 0 to 10 in six trials of 616 participants (mean difference, −0.42; 95% CI, −0.73 to −0.16). Compared to placebo, these products were associated with large increased risk for dizziness and sedation and a moderately increased risk for nausea in six trials of 866 participants.

Limitations in the evidence base may affect applicability of the findings, as there were unstandardized and inconsistent reporting about specific cannabis products and a lack of adequate studies of varying products to allow analysis of formulation, route of administration, and dosing, the study authors noted. In all cases other than the two FDA-approved drug products (dronabinol and nabilone), it is unclear whether the products studied are available in the U.S., they said.

In addition, few of the included trials used formulations available in the medical cannabis market, such as CBD-dominant products and smoked or vaporized products, an accompanying editorial noted. “These limitations are well documented in the cannabinoid and chronic pain literature and are due in part to ‘War on Drugs' policies that have overwhelmingly favored studying cannabis-related harms over therapeutic effects,” the editorialists wrote.

Given the slow pace of clinical trials, they said it is likely that the findings of this review will be the best available evidence for some time. “While we await better evidence, we believe that clinicians should meet patients with chronic pain ‘where they are,’” the editorialists wrote. “Conventional analgesic medications are effective only in a subset of persons, so it is no wonder that many patients are drawn to widely available cannabis products. Clinicians can compassionately witness, record, and offer guidance to help patients with chronic pain use cannabis wisely.”