Review of: Da Vita et al, JAMA Psychiatry 2018;75(11):1118-1127

Study Type: Meta-analysis of placebo-controlled trials

In the midst of the opioid epidemic, researchers are looking for new ways to treat chronic pain. Interestingly, states that have legalized medical marijuana have fewer opioid prescriptions but no clear reduction in mortality over time (Shover CL et al, Proc Natl Acad Sci U S A. 2019;116(26):12624-12626). Opioid users who smoke marijuana are less likely to drop out of maintenance treatment programs, while benzodiazepine use predicts worse outcomes in this population (Powell et al, J Health Econ 2018:58:29-42; Socías ME et al, Addiction 2018;113:2250-2258). Could marijuana have direct benefits in the treatment of pain?

To address this question, researchers analyzed 18 placebo-controlled trials of cannabinoids as a treatment for mechanically-induced pain in otherwise healthy subjects. A total of 442 participants were included. Mean age was 27 with equal numbers of men and women. Two-thirds of the studies involved synthetic tetrahydrocannabinol (THC), the cannabinoid responsible for the “high” in marijuana, or schedule-III analogues of THC, such as dronabinol and nabilone. The other third used plant-based cannabis. The majority (89%) used a cross-over design where subjects received both cannabinoids and placebo with a washout period between the doses.

Compared to placebo, cannabinoid administration was associated with a small increase in pain threshold and a small-to-medium increase in pain tolerance. However, it did not change overall pain intensity. Cannabinoids made people better able to withstand a greater pain burden, but only to a certain point. They also made the experience of pain less unpleasant (small-to-medium effect size), and this effect was strongest with plant-based cannabis. Unpleasantness is important because it may influence the progression from chronic pain to depression. No significant association was found between cannabinoid administration and hypersensitivity to pain. Gender did not significantly impact any of the outcomes.

The biggest limitation to the study is the lack of blinding as most subjects could probably guess whether or not they were “high.” Furthermore, it is unclear how well mechanically induced pain approximates real, chronic pain. Lastly, cannabidiol (CBD) was not included in the study. CBD is often praised by enthusiasts for its properties and was recently approved in a prescription form for intractable seizures (Epidiolex; see TCPR Jan 2019). Unlike THC, CBD produces no “high” and may have added antipsychotic effects.

TCPR’S TAKE
Despite the widespread use of THC for a variety of ailments, little data exist to support its many claimed benefits. Additionally, the risks, including psychosis, are too large to recommend it to patients as an alternative analgesic.