Neuropathic Pain

Amanda Macone, MD; James A. D. Otis, MD, FAAN, DABPM


Semin Neurol. 2018;38(6):644-653. 

In This Article


Despite all of the treatments previously mentioned, many patients have refractory chronic neuropathic pain, for which cannabis may play a role. To date, there have been five randomized control trials assessing the effectiveness of marijuana use for mixed etiologies of neuropathic pain[59–61] and on HIV-related neuropathy.[62,63] Of the studies assessing the effectiveness of marijuana in the management of mixed neuropathic pain, two studies found that marijuana was more effective than placebo at transiently improving pain levels when used up to three times a day.[59,60] One placebo-controlled, randomized, crossover study had mixed results.[61] Patients in this study were randomized to inhale low- (1% tetrahydrocannabinol [THC]), medium- (4%), or high-dose (7%) marijuana or placebo cannabis during one study session, and then crossed over to an alternative dose every 2 weeks. Results revealed that changes in spontaneous pain from baseline were only statistically significant for the high-dose group (7% THC) at 30, 45, and 60 minutes post-dose. Also, when they adjusted for the minimum pain score achieved compared with baseline pain score over the course of the study, there was no statistical significance between placebo and any of the THC doses. There was statistical significance in the somnolence and euphoria patients experienced with both the 4 and 7% THC doses compared with placebo for 30 to 120 minutes.[61] The RCTs assessing the effectiveness of cannabis in the management of HIV neuropathy have both shown positive results compared with placebo.[62,63] In a prospective randomized placebo-controlled trial of 50 patients, cannabis cigarettes were found to significantly reduce pain after the first cigarette compared with placebo (72 vs. 15%), and also to reduce daily pain (34 vs. 17%). The main common side effects of cannabis are dry mouth and a "high."[62]

Cannabis use, especially in inhaled forms, does raise safety concerns. A 1-year prospective cohort study was conducted to assess safety issues among individuals with chronic noncancer pain using quality-controlled herbal cannabis, containing 12.5% THC.[64] The results suggested that when other conventional treatments have failed, quality-controlled herbal cannabis at an average dose of 2.5 g/day in non-naive cannabis users may be safe as part of a carefully monitored pain management program. Ultimately, the study showed that while mild to moderate adverse effects were increased in the cannabis-using group compared with placebo, there was no statistically significant increase in severe adverse effects in the cannabis-using group compared with the placebo group. Mild to moderate adverse effects observed in the cannabis-using group included somnolence, amnesia, cough, nausea, dizziness, euphoric mood, hyperhidrosis, and paranoia. Secondary outcomes measuring pulmonary function tests and neurocognitive performance did not show any statistically significant difference between cannabis users and placebo group. Secondary efficacy outcomes showed greater reduction in pain among cannabis users than among controls and greater improvement of physical function in cannabis users than in controls. The study did have several limitations, including modest sample size (215 participants), high dropout rate (30%), short follow-up time (1 year), a study population composed primarily of experienced cannabis users, and potential observational bias. More research is still needed to understand which cannabinoids are most useful for the management of neuropathic pain.

The American Society of Addiction Medicine recommends its members and other physician organizations and their members reject responsibility for providing access to cannabis and cannabis-based products until such time that these materials receive marketing approval from the Food and Drug Administration.[65,66]