nabilone and Neuralgia

Cannabinoids have a long record of recreational and medical use and become increasingly approved for pain therapy. This development is based on preclinical and human experimental research summarized in this review. Cannabinoid CB. Cannabinoids consistently produced antinociceptive effects in preclinical models, whereas they heterogeneously influenced the perception of experimentally induced pain in humans and did not provide robust clinical analgesia, which jeopardizes the translation of preclinical research on cannabinoid-mediated antinociception into the human setting.

Topics: Analgesia; Analgesics; Animals; Cancer Pain; Cannabidiol; Cannabinoid Receptor Agonists; Cannabinoids; Dronabinol; Humans; Mice; Mice, Knockout; Neuralgia; Nociception; Pain Management; Receptor, Cannabinoid, CB1; Retrospective Studies

This review is one of a series on drugs used to treat chronic neuropathic pain. Estimates of the population prevalence of chronic pain with neuropathic components range between 6% and 10%. Current pharmacological treatment options for neuropathic pain afford substantial benefit for only a few people, often with adverse effects that outweigh the benefits. There is a need to explore other treatment options, with different mechanisms of action for treatment of conditions with chronic neuropathic pain. Cannabis has been used for millennia to reduce pain. Herbal cannabis is currently strongly promoted by some patients and their advocates to treat any type of chronic pain.. To assess the efficacy, tolerability, and safety of cannabis-based medicines (herbal, plant-derived, synthetic) compared to placebo or conventional drugs for conditions with chronic neuropathic pain in adults.. In November 2017 we searched CENTRAL, MEDLINE, Embase, and two trials registries for published and ongoing trials, and examined the reference lists of reviewed articles.. We selected randomised, double-blind controlled trials of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment of conditions with chronic neuropathic pain in adults, with a treatment duration of at least two weeks and at least 10 participants per treatment arm.. Three review authors independently extracted data of study characteristics and outcomes of efficacy, tolerability and safety, examined issues of study quality, and assessed risk of bias. We resolved discrepancies by discussion. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 30% and 50% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardised mean differences for pain intensity, sleep problems, health-related quality of life (HRQoL), and psychological distress. For tolerability, we calculated number needed to treat for an additional harmful outcome (NNTH) for withdrawal due to adverse events and specific adverse events, nervous system disorders and psychiatric disorders. For safety, we calculated NNTH for serious adverse events. Meta-analysis was undertaken using a random-effects model. We assessed the quality of evidence using GRADE and created a 'Summary of findings' table.. We included 16 studies with 1750 participants. The studies were 2 to 26 weeks long and compared an oromucosal spray with a plant-derived combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) (10 studies), a synthetic cannabinoid mimicking THC (nabilone) (two studies), inhaled herbal cannabis (two studies) and plant-derived THC (dronabinol) (two studies) against placebo (15 studies) and an analgesic (dihydrocodeine) (one study). We used the Cochrane 'Risk of bias' tool to assess study quality. We defined studies with zero to two unclear or high risks of bias judgements to be high-quality studies, with three to five unclear or high risks of bias to be moderate-quality studies, and with six to eight unclear or high risks of bias to be low-quality studies. Study quality was low in two studies, moderate in 12 studies and high in two studies. Nine studies were at high risk of bias for study size. We rated the quality of the evidence according to GRADE as very low to moderate.Primary outcomesCannabis-based medicines may increase the number of people achieving 50% or greater pain relief compared with placebo (21% versus 17%; risk difference (RD) 0.05 (95% confidence interval (CI) 0.00 to 0.09); NNTB 20 (95% CI 11 to 100); 1001 participants, eight studies, low-quality evidence). We rated the evidence for improvement in Patient Global Impression of Change (PGIC) with cannabis to be of very low quality (26% versus 21%;RD 0.09 (95% CI 0.01 to 0.17); NNTB 11 (95% CI 6 to 100); 1092 participants, six studies). More participants withdrew from the studies due to adverse events with cannabis-based medicines (10% of participants) than with placebo (5% of participants) (RD 0.04 (95% CI 0.02 to 0.07); NNTH 25 (95% CI 16 to 50); 1848 participants, 13 studies, moderate-quality evidence). We did not have enough evidence to determine if cannabis-based medicines increase the frequency of serious adverse events compared with placebo (RD 0.01 (95% CI -0.01 to 0.03); 1876 participants, 13 studies, low-quality evidence).Secondary outcomesCannabis-based medicines probably increase the number of people achieving pain relief of 30% or greater compared with placebo (39% versus 33%; RD 0.09 (95% CI 0.03 to 0.15); NNTB 11 (95% CI 7 to 33); 1586 participants, 10 studies, moderate quality evidence). Cannabis-based medicines may increase nervous system adverse events compared with placebo (61% versus 29%; RD 0.38 (95% CI 0.18 to 0.58); NNTH 3 (95% CI 2 to 6); 1304 participants, nine. The potential benefits of cannabis-based medicine (herbal cannabis, plant-derived or synthetic THC, THC/CBD oromucosal spray) in chronic neuropathic pain might be outweighed by their potential harms. The quality of evidence for pain relief outcomes reflects the exclusion of participants with a history of substance abuse and other significant comorbidities from the studies, together with their small sample sizes.

Topics: Adult; Analgesics, Non-Narcotic; Analgesics, Opioid; Cannabidiol; Chronic Pain; Codeine; Dronabinol; Humans; Medical Marijuana; Neuralgia; Numbers Needed To Treat; Randomized Controlled Trials as Topic

Neuropathic pain (NPP) is a chronic syndrome suffered by patients with multiple sclerosis (MS), for which there is no cure. Underlying cellular mechanisms involved in its pathogenesis are multifaceted, presenting significant challenges in its management.. A randomized, double-blind, placebo-controlled study involving 15 relapsing-remitting MS patients with MS-induced NPP was conducted to evaluate nabilone combined with gabapentin (GBP). Eligible patients stabilized on GBP (≥1,800 mg/day) with inadequate pain relief were recruited. Nabilone or placebo was titrated over 4 weeks (0.5 mg/week increase) followed by 5-week maintenance of 1 mg oral nabilone (placebo) twice daily. Primary outcomes included two daily patient-reported measures using a 100-mm visual analog scale (VAS), pain intensity (VASpain), and impact of pain on daily activities (VASimpact). Hierarchical regression modeling was conducted on each outcome to determine if within-person pain trajectory differed across study groups, during 63-day follow-up.. After adjustment for key patient-level covariates (e.g., age, sex, Expanded Disability Status Scale, duration of MS, baseline pain), a significant group × time(2) interaction term was reported for both the VASpain (P < 0.01) and VASimpact score (P < 0.01), demonstrating the adjusted rate of decrease for both outcomes was statistically greater in nabilone vs placebo study group. No significant difference in attrition rates was noted between treatments. Nabilone was well tolerated, with dizziness/drowsiness most frequently reported.. Nabilone as an adjunctive to GBP is an effective, well-tolerated combination for MS-induced NPP. The results of this study identify a novel therapeutic combination for use in this population of patients predisposed to tolerability issues that may otherwise prevent effective pain management.

Topics: Adult; Amines; Analgesics; Cyclohexanecarboxylic Acids; Double-Blind Method; Dronabinol; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Multiple Sclerosis, Relapsing-Remitting; Neuralgia; Pain Measurement

Cannabinoids are emerging as potential options for neuropathic pain treatment. This study evaluated an oral cannabinoid, nabilone, in the treatment of refractory human diabetic peripheral neuropathic pain (DPN). We performed a single-center, randomized, double-blind, placebo-controlled, flexible-dose study with an enriched enrollment randomized withdrawal design. DPN subjects with a pain score ≥ 4 (0-10 scale) continued regular pain medications and were administered single-blinded adjuvant nabilone for 4 weeks. Subjects achieving ≥ 30% pain relief (26/37) were then randomized and treated with either flexible-dose nabilone 1-4 mg/day (n=13) or placebo (n=13) in a further 5-week double-blind treatment period, with 30% (11/37) of subjects deemed run-in-phase nabilone nonresponders. For nabilone run-in-phase responders, there was an improvement in the change in mean end-point neuropathic pain vs placebo (mean treatment reduction of 1.27; 95% confidence interval 2.29-0.25, P=0.02), with an average nabilone dose at end point of 2.9 ± 1.1mg/day, and improvements from baseline for the anxiety subscale of the Hospital Anxiety and Depression Scale, the Medical Outcomes Study sleep scale problems index, and the European Quality of Life-5-Domains index score (each P<0.05). Nabilone run-in-phase responders reported greater global end-point improvement with nabilone than with placebo (100% vs 31%; P<0.05). Medication-related confusion led to discontinuation in 2/37 subjects during single-blind nabilone treatment. Potential unmasking occurred in 62% of both groups. Flexible-dose nabilone 1-4 mg/day was effective in relieving DPN symptoms, improving disturbed sleep, quality of life, and overall patient status. Nabilone was well tolerated and successful as adjuvant in patients with DPN.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics; Chemotherapy, Adjuvant; Diabetic Neuropathies; Dose-Response Relationship, Drug; Double-Blind Method; Dronabinol; Female; Humans; Male; Middle Aged; Neuralgia; Placebo Effect; Treatment Outcome; Young Adult