Efficacy of two cannabis-based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial

Avulsion of nerve rootlets from the spinal cord following traction injuries to the brachial plexus frequently produces a highly characteristic pain syndrome. Constant spontaneous crushing and burning pain is felt in the distal part of the anaesthetic limb, frequently accompanied by shooting pain. It is not uncommon for the pain to persist for many years. The consistency of description between subjects coupled with the anatomical precision of the diagnosis provides a remarkable human model of central neuropathic pain. Opioids, anticonvulsants and tricyclic antidepressants are all used in the empirical management of this condition. They are partially effective at best and there is only anecdotal evidence to support their use. Many of our patients have given us spontaneous reports of the efficacy of 'street' cannabis. This has led us to test two cannabis-based whole plant medicinal extracts administered via oromucosal spray to patients with this condition.

Methods
Forty-eight patients were enrolled. They all had at least one brachial plexus root avulsion for at least 18 months. They also had pain of at least 4 out of an 11-point box scale at the time of enrolment. The study was a randomised double-blind crossover trial consisting of three 2-week periods following a run-in period of 7-24 days. Patients continued on all previous stable medications including analgesics. During each 2-week period, subjects received in random order either placebo, delta-9-tetrahydrocannabinol (THC) 25 mg.ml-1 or delta-9-tetrahydrocannabinol 25 mg.ml-1 with cannabidiol (THC:CBD) 25 mg.ml-1, given as patient-activated oromucosal 100-micro-litre sprays. Eleven-point box scales for pain and sleep, short form McGill, visual analogue scale, general health questionnaire-12, sleep disturbance and pain disability index were all recorded.

Results

Table 1 shows a summary of the results at week two of each of the study periods.

Table 1 Pain (11-point box scale, visual analogue scale and short form McGill), sleep quality (11-point box scale), general health questionnaire-12 (GHQ-12) and number of sprays per day of delta-9-tetrahydrocannabinol without (THC) or with (THC:CBD) cannabidiol.

Baseline Placebo THC* THC:CBD*
Pain (box scale) 6.7 6.7 6.1 (p < 0.005) 6.1 (p < 0.002)
Visual analogue scale 60.9 52.9 43.6 (p<0.04) 45.1 (p<0.09)
McGill total intensity 17.3 15.5 13.4 (p<0.04) 13.8 (p<0.14)
Sleep quality 4.8 5.2 6.0 (p<0.001) 5.9 (p<0.01)
GHQ-12 13.4 13.5 12.3 (p<0.18) 10.9 (p<0.02)
Sprays per day n/a 9.2 7.3 6.9
*p-values are shown compared to week two of the placebo period.

Discussion
Both the THC and THC:CBD extracts decreased pain and improved sleep. The effects were moderate although mostly statistically significant. Patients had not maximally titrated their doses at the end of the 2-week study periods. In addition, they remained on their pre-existing analgesic therapy throughout the study. A longer study period and use of cannabis-based medicinal extracts as the sole analgesic may well show a bigger analgesic effect. However, given the refractory nature of the pain in this patient group, this study shows that cannabis-based medicinal extracts represent a significant advance in treatment.

 http://www.cannabis-med.org/studies/ww_en_db_study_show.php?s_id=83