Four randomized-controlled trials examined the effects of cannabinoids for pain in SCI; one study found that cannabinoids significantly reduced pain, two studies found no significant difference in pain reduction between cannabinoids and placebo and in the fourth study the RCT analysis of the primary outcome measure was not possible due to the high drop-out rate, the open-label part showed a significant reduction in pain.
Wilsey et al. (2016) found cannabis vapor significantly reduced pain post-SCI compared to placebo vapor. Rintala et al. (2010) examined the effect of dronabinol versus an active control (diphenhydramine) on neuropathic pain post-SCI in a small pilot RCT (n=5). They had two dropouts during the first phase of the study: one participant dropped out while on dronabinol due to side effects and the other participant on dronabinol did not want to stop medication for wash-out phase. The study found no significant difference in pain intensity between the two treatments in the 5 participants who completed the full trial. In addition to the small size of the RCT, limitations include the use of convenience sampling and use of two different baseline measures: the end of week 1 for phase 1 versus the end of wash-out for phase 2.
Hagenbach et al. (2007)conducted a study primarily examining the effectiveness of THC in improving spasticity and secondarily, in improving spastic pain in people with SCI. In the first phase of the study, 22 participants received 10mg of oral THC which was then dose titrated until maximum tolerance or treatment dose was reached for 6 weeks. The main analysis of the RCT part of the study was not possible due to the high dropout rate. In the open-label phase they found a significant reduction in pain of people with SCI post treatment (p=0.047). There was no significant reduction of pain compared to placebo on day 8 and 43 when comparing the intervention group of open-label part of the study to the placebo group in the RCT part of the study. Four patients noted pain relief (18%), but five (23%) reported pain augmentation and four dropped out: pain was one of the major reasons for the high dropout rate. We assign it a lower level of evidence (i.e., level 2) than would be expected of an RCT (i.e., PEDro≥6 RCT).
Andresen et al. (2016) did an RCT on the effects of the endocannabinoid palmitoylethanolamide (PEA), marketed in ultramicronized form as Normast. They administered it or a placebo twice a day with 12 hours between dosages for 12 weeks. Using a numeric rating scale from 0 to 10, they found no significant difference in neuropathic pain intensity between the two groups (p=0.46).
There is level 1b evidence (Wilsey et al. 2016) that natural cannabis vapour improves neuropathic pain post- SCI.
There is level 1b evidence (Andresen et al. 2016) that ultramicronized Palmitoylethanolamide (PEA/Normast) does not significantly improve chronic neuropathic pain post-SCI.
There is level 2 evidence (from one randomized-controlled crossover pilot trial: Rintala et al. 2010) that synthetic dronabinol may not be effective in reducing neuropathic pain intensity post SCI.
There is conflicting level 2 evidence (from one randomized controlled trial: Hagenbach et al. 2007) for the use of synthetic delta-9-tetra hydrocannabinol in reducing spastic pain in SCI individuals.