A multicentre, open-label, follow-on study to assess the long-term maintenance of effect, tolerance and safety of THC/CBD oromucosal spray in the management of neuropathic pain

Abstract

Peripheral neuropathic pain (PNP) poses a significant clinical challenge. The long-term efficacy of delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray was investigated in this 38-week open-label extension study. In total, 380 patients with PNP associated with diabetes or allodynia entered this study from two parent randomised, controlled trials. Patients received THC/CBD spray for a further 38 weeks in addition to their current analgesic therapy. Neuropathic pain severity was the primary efficacy measure using a pain 0-10 numerical rating scale (NRS). Additional efficacy, safety and tolerability outcomes were also investigated. In total, 234 patients completed the study (62 %). The pain NRS showed a decrease in score over time in patients from a mean of 6.9 points (baseline in the parent studies) to a mean of 4.2 points (end of open-label follow-up). The proportion of patients who reported at least a clinically relevant 30 % improvement in pain continued to increase with time (up to 9 months); at least half of all patients reported a 30 % improvement at all time points. Improvements were observed for all secondary efficacy outcomes, including sleep quality 0-10 NRS scores, neuropathic pain scale scores, subject global impression of change and EQ-5D questionnaire scores. THC/CBD spray was well tolerated for the study duration and patients did not seek to increase their dose with time, with no new safety concerns arising from long-term use. In this previously difficult to manage patient population, THC/CBD spray was beneficial for the majority of patients with PNP associated with diabetes or allodynia.

<p>A Review of Scientific Evidence for THC:CBD Oromucosal Spray (Nabiximols) in the Management of Chronic Pain</p>

“…Randomized clinical trials of THC:CBD oromucosal spray (nabiximols) for the treatment of chronic neuropathic pain conditions are summarized in Table 2. [87][88][89][90][92][93][94][95][96][97][98] THC:CBD oromucosal spray (nabiximols) has shown mainly positive results in studies of patients with MSassociated neuropathic pain ( Table 2). [87][88][89][90] A placebo-controlled RCT of patients with central neuropathic pain due to MS reported a near 2-fold higher mean change from baseline on the 0-10 pain NRS (-2.7 vs -1.4; p = 0.005) during 4 weeks' treatment with THC:CBD oromucosal spray (nabiximols) or placebo as adjunctive analgesia.…”

“…91 The results of studies of THC:CBD spray (nabiximols) in patients with neuropathic pain of origins other than MS are mixed ( Table 2). [92][93][94][95][96][97][98] A RCT registered at ClinicalTrials.gov which compared THC:CBD spray (nabiximols) and placebo for relief of intractable neuropathic pain associated with spinal cord injury found no difference between treatments for change from baseline in pain 0-10 NRS scores (-0.74 vs -0.69; p = 0.71) after 3 weeks' treatment (ClinicalTrials.gov identifier NCT01606202). 92 In a study of central neuropathic pain due to brachial plexus avulsion, the difference in the mean pain severity score during the last 7 days of treatment with THC:CBD oromucosal spray (nabiximols) was statistically significant (p = 0.005) compared with placebo, although failed to satisfy the a priori assumed level for clinical significance.…”

Integrative neuromuscular medicine: Neuropathy and neuropathic pain: Consider the alternatives

“…RCTs involving cannabinoids and cannabis have demonstrated effective analgesia in various patient populations with chronic neuropathic pain refractory to other treatments [155][156][157][158][159][160][161] (see Table S1 online). Due to changes in the legalization of cannabis and the growing use of medical cannabis for chronic pain syndromes, it is important to consider cannabinoid medicine as part of an integrative medicine approach.…”

Dronabinol Is a Safe Long-Term Treatment Option for Neuropathic Pain Patients

“…Clinical trials investigating various indications showed long-term effects of cannabis-based medicine. These studies lasting from 38 weeks to 3.5 years showed no major safety concerns and a generally good tolerability [9-16]. Nevertheless, the medical use of cannabis is controversially discussed.…”