Analgesic effects of THC in patients with chronic neuropathic pain (CANNA study): study protocol for a randomized, double-blind, placebo-controlled 2-way crossover trial

Abstract Background Cannabis has been used for pain relief for millennia with known side-effects. Despite renewed scientific and medical interest in cannabinoid-based medicines, clinical research has shown only modest analgesic effects in patients with chronic neuropathic pain (CNP). Large meta-analyses have not found convincing evidence of significant analgesic effects, which is possibly related to its efficacy only in a subset of CNP patients, as often observed with analgesic drugs. In the current trial, we will treat patients diagnosed with CNP with 2% THC oil and extensively phenotype them before the start of treatment based on symptomatology, rather than aetiology, to predict treatment effects. We hypothesize that distinct pain phenotypes will exhibit different analgesic effects and aim to identify pain phenotypes associated with a substantial response to 2% THC oil. Methods This randomized, double-blind, placebo controlled 2-way crossover trial is designed to assess the analgesic effects of 2% THC oil in patients with CNP in general, and in defined phenotypical subgroups (primary objectives). Study participants will be phenotyped at baseline using quantitative sensory testing (QST), neurophysiological measurements and various questionnaires on mood, pain and emotion. The study is comprised of a baseline week for baseline measurements and two treatment periods of 5 weeks, where participants will be treated with either 2% THC oil or placebo in a randomized order. Participants will be instructed to titrate the study medication based on both analgesic effect and tolerability to a maximum of 0,75 mL three times a day. During the study period they will rate their pain and sleep quality daily. Discussion The aim of the study is to investigate the analgesic effects of 2% THC oil in patients with CNP and identify subgroups with high analgesic responder rates based on different pain phenotypes based on QST (primary outcomes). Secondary outcomes include the evaluation of the non-analgesic benefits and the safety and tolerability. This study is designed to provide reliable evidence on the analgesic potency of 2% THC oil for the treatment of neuropathic pain. Trial registration Prospectively registered at the International Clinical Trials Registry Platform under identifier CTIS2022-502343-35-00 . Registered 31 October 2022.