Summaries of the 6 studies in this review that examined the use of medical marijuana for CNCP
| STUDY | CLINICAL CONDITION | STUDY DURATION AND PROTOCOL | PRIMARY OUTCOME MEASURE | STUDY SAMPLE | CONTROL | INTERVENTION | OUTCOME | COMMENTS |
|---|---|---|---|---|---|---|---|---|
| Abrams et al,15 2007 | HIV peripheral neuropathy | Study duration was 3 wk Adults with documented HIV and associated sensory neuropathy in 21-d trial with randomization to control group or intervention group for 5 d | Daily diary of pain ratings on a VAS (0–100 mm) | There were 55 participants enrolled: 28 randomized to control group, with 25 completing the study; 27 randomized to intervention group, with 25 completing the study | Cigarettes containing 0% delta-9-THC that appeared identical to the cannabis cigarettes | Cigarettes containing 3.56% delta-9-THC and weighing an average of 0.9 g; smoked 3 times per d | A total of 13 of 25 participants in intervention group had > 30% reduction in pain from baseline to end of treatment compared with 6 of 25 participants in control group; median reduction of NP was 34% in the intervention group compared with 17% in the control group | Smoking the first cigarette reduced chronic pain ratings (AUC) by 72% (intervention) versus 15% (control) compared with chronic pain ratings after smoking the last cigarette of 51% (intervention) versus 5% (control) |
| Corey-Bloom et al,11 2012 | MS | Study duration was 17 d Adults with MS and spasticity smoked 1 cigarette per d for 3 d | Pain intensity measured by VAS (secondary outcome) | There were 37 participants randomized, with 30 completing the study | Cigarettes containing 0% delta-9-THC that appeared identical to the cannabis cigarettes | Cigarettes containing 4% delta-9-THC and weighing an average of 0.8 g; smoked once daily | Smoking cannabis reduced pain scores on the VAS by 5.28 points (95% CI 2.48 to 10.01) more than the control group | There were 17 participants who correctly guessed treatment phase for all 6 visits, with 83% having previous exposure to cannabis. Participants had very low levels of pain to start |
| Ellis et al,13 2009 | HIV peripheral neuropathy | Study duration was 7 wk HIV-infected adults with NP refractory to 2 other analgesics in 5-phase study: 1-wk wash-in phase; randomization to 5-d smoking phase; 2-wk washout phase; 5-d crossover phase; and final 2-wk washout phase | Pain intensity measured by DDS and VAS, a 10-cm line (secondary outcome) | There were 34 participants randomized, with 28 completing the study | Cigarettes that had all cannabinoids removed and that were identical in appearance to active cigarettes | Cigarettes with 1%–8% delta-9-THC potency titrated to tolerance on d 1, followed by 4 d of smoking target dose, with each d composed of 4 sessions separated by 90–120 min | Median difference in pain reduction was 3.3 DDS points (effect size = 0.6; P = .016); proportion with ≥ 30% pain reduction was greater in the active cannabis wk than the placebo cannabis wk (0.46 [95% CI 0.28 to 0.65] vs 0.18 [95% CI 0.03 to 0.32]. The median (range) change in VAS pain scores were −17 (−58 to 52) for cannabis compared with −4 (−56 to 28) for placebo | Patients correctly guessed when they consumed delta-9-THC; however, subanalysis revealed no difference in final outcome. No breakdown of AEs experienced. There were 2 patients who exited the trial owing to psychosis and intractable cough from cannabis. The UKU and DAIDS side effect frequency was greater in the intervention group and there was a trend toward moderate to severe AEs. Greater increase in heart rate among cannabis group (13 of 28 patients) than placebo group (1 of 28 patients) |
| Ware et al,12 2010 | Posttraumatic neuropathy | Study duration was 8 wk Adults ≥ 18 y with posttraumatic or postsurgical pain for at least 3 mo randomized to a sequence of 4 treatment periods, each 14-d period beginning with 5 d on the study drug followed by a 9-d washout period | 11-Point numeric rating scale (secondary measures included sleep, mood, and quality of life) | There were 23 participants randomized, with 21 completing the study | Cannabis containing 0% delta-9-THC prepared by ethanolic extraction | Over 3, 14-d periods, 25-mg doses of various delta-9-THC potencies (2.5%, 6.0%, 9.4%) were delivered through a pipe 3 times per d for the first 5 d of each cycle, followed by a 9-d washout period | Mean (SD) daily pain intensity was lower among intervention group (5.4 [1.6]) than control group (6.1 [1.7]); difference of 0.7 (95% CI 0.02 to 1.4) | Overall, use of cannabis associated with improvements in pain, sleep, and anxiety. Frequency of AEs increased with potency and was greatest for psychiatric disorders (12 events vs 1). Fixed dose and limited quantity (25 mg) might have limited potential AEs |
| Wilsey et al,9 2013 | NP | Study duration was 3, 6-h experimental sessions; there were 3- to 14-d intervals between sessions Adults with type 1 CRPS, spinal cord injury, peripheral neuropathy, or nerve injury | Measured with VAS (0–100 mm) and the NP scale | There were 39 participants randomized and who completed at least 1 session (no dropouts from AEs or experimental intervention) | Placebo cannabis made from whole plant with cannabinoid extraction | Participants were randomized to 1 of 3, 6-h sessions. Cued puff (vaporized) procedure of 0%, 1.29% (low dose), or 3.53% (medium dose) delta-9-THC, with cumulative 8-12 puffs per session | A 30% reduction in pain intensity: 10 of 38 (26%) placebo patients; 21 of 37 (57%) low-dose patients; 22 of 36 (61%) medium-dose patients. For placebo vs low dose, NNT was 3.2 (P = .0069); for placebo vs medium dose, NNT was 2.9 (P = .0023) | Both 1.29% and 3.53% delta-9-THC potencies produced equal antinociception with minimal effect on cognitive testing. Greatest dose effects were noted in learning and memory, with effect sizes in small or medium range |
| Wilsey et al,14 2008 | NP | Study duration was 3, 6-h experimental sessions; there were 3- to 14-d intervals between sessions Adults with type 1 CRPS, spinal cord injury, peripheral neuropathy, or nerve injury | Measured with VAS (0–100 mm) and the NP scale | There were 38 participants randomized, with 32 completing all sessions | Cigarettes made from whole cannabis with cannabinoid extraction | Participants were randomized to 1 of 3, 6-h sessions. Cued puff procedure of 0%, 3.5%, or 7% delta-9-THC | A 0.0035 reduction in VAS pain intensity per min was noted from both 3.5% and 7% cannabis, with cumulative 9 puffs per session | Ceiling effect noted with cumulative dosing, as 3.5% and 7% potencies produced equal antinociception; secondary outcomes improved, including pain unpleasantness (mean difference = −0.21 [95% CI −0.33 to −0.09]; P < .01) and global impression of change (mean difference = 0.12 [95% CI 0.064 to 0.18]; P < .01) |
AE—adverse event, AUC—area under curve, CRPS—complex regional pain syndrome, DAIDS—Division of AIDS, DDS—descriptor differential scale, delta-9-THC—delta-9-tetrahydrocannabinol, MS—multiple sclerosis, NNT—number needed to treat, NP—neuropathic pain, UKU—Udvalg for Kliniske Undersøgelser, VAS—visual analogue scale.