gw-1000 and Neuralgia

Pooled analysis of nabiximols and placebo in randomized controlled studies (RCTs) of chronic neuropathic pain.. Systematic review and meta-analysis.. A systematic literature search was conducted to identify double-blind placebo-controlled RCTs of nabiximols for chronic neuropathic pain. The clinical endpoint of interest was change from baseline in mean pain score on 11-point numerical rating scales. Mean difference (MD) and standardized mean difference (SMD, Hedges' g) were calculated using fixed effect (FE) and random effects (RE) models. Strength of evidence was assessed using the Cochrane Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. Risk of bias was assessed using the revised Cochrane risk-of-bias tool (RoB 2).. Nine RCTs with 1289 participants were included. Quality of evidence (GRADE) was moderate. One study had a high risk of bias (RoB 2) and five had some concerns. For the pooled endpoint of change from baseline in mean pain score, nabiximols was superior to placebo, with a MD of -0.40 (95% confidence interval [CI]: -.59 to -.21; FE, P < .0001) or -0.44 (95% CI: -.70 to -.19; RE, P = .0006). A SMD of -0.21 (95% CI: -.32 to -.10; FE) or -0.26 (95% CI: -.42 to -.10; RE) indicated an incremental benefit over background analgesia. Results in favor of nabiximols were maintained in sensitivity analyses.. Nabiximols was superior to placebo for reduction of chronic neuropathic pain, with a small effect size. Larger RCTs designed to assess the effect of nabiximols in neuropathic pain are required to reach more definitive conclusions.

Topics: Cannabidiol; Chronic Pain; Dronabinol; Drug Combinations; Humans; Neuralgia; Randomized Controlled Trials as Topic

The management of chronic pain is a complex challenge worldwide. Cannabis-based medicines (CBMs) have proven to be efficient in reducing chronic pain, although the topic remains highly controversial in this field.. This study's aim is to conduct a conclusive review and meta-analysis, which incorporates all randomized controlled trials (RCTs) in order to update clinicians' and researchers' knowledge regarding the efficacy and adverse events (AEs) of CBMs for chronic and postoperative pain treatment.. A systematic review and meta-analysis.. An electronic search was conducted using Medline/Pubmed and Google Scholar with the use of Medical Subject Heading (MeSH) terms on all literature published up to July 2015. A follow-up manual search was conducted and included a complete cross-check of the relevant studies. The included studies were RCTs which compared the analgesic effects of CBMs to placebo. Hedges's g scores were calculated for each of the studies. A study quality assessment was performed utilizing the Jadad scale. A meta-analysis was performed utilizing random-effects models and heterogeneity between studies was statistically computed using I² statistic and tau² test.. The results of 43 RCTs (a total of 2,437 patients) were included in this review, of which 24 RCTs (a total of 1,334 patients) were eligible for meta-analysis. This analysis showed limited evidence showing more pain reduction in chronic pain -0.61 (-0.78 to -0.43, P < 0.0001), especially by inhalation -0.93 (-1.51 to -0.35, P = 0.001) compared to placebo. Moreover, even though this review consisted of some RCTs that showed a clinically significant improvement with a decrease of pain scores of 2 points or more, 30% or 50% or more, the majority of the studies did not show an effect. Consequently, although the primary analysis showed that the results were favorable to CBMs over placebo, the clinical significance of these findings is uncertain. The most prominent AEs were related to the central nervous and the gastrointestinal (GI) systems.. Publication limitation could have been present due to the inclusion of English-only published studies. Additionally, the included studies were extremely heterogeneous. Only 7 studies reported on the patients' history of prior consumption of CBMs. Furthermore, since cannabinoids are surrounded by considerable controversy in the media and society, cannabinoids have marked effects, so that inadequate blinding of the placebo could constitute an important source of limitation in these types of studies.. The current systematic review suggests that CBMs might be effective for chronic pain treatment, based on limited evidence, primarily for neuropathic pain (NP) patients. Additionally, GI AEs occurred more frequently when CBMs were administered via oral/oromucosal routes than by inhalation.Key words: Cannabis, CBMs, chronic pain, postoperative pain, review, meta-analysis.

Topics: Cannabidiol; Cannabis; Chronic Pain; Dronabinol; Drug Combinations; Humans; Medical Marijuana; Neuralgia; Pain Management; Pain, Postoperative; Randomized Controlled Trials as Topic; Treatment Outcome

We identified 16 randomized placebo-controlled trials investigating cannabinoids as symptomatic treatment in multiple sclerosis (MS). There is evidence that nabiximols oromucosal spray may reduce subjective symptoms of spasticity and that dronabinol is effective against neuropathic pain in patients with MS. The existing treatment system in Denmark is in conformity with the existing data and there is not sufficient evidence to modify it.

Topics: Cannabidiol; Cannabinoids; Dronabinol; Drug Combinations; Evidence-Based Medicine; Humans; Multiple Sclerosis; Muscle Spasticity; Neuralgia; Treatment Outcome

Refractory spasticity, central neuropathic pain and bladder dysfunction are common clinical problems in patients with multiple sclerosis (MS). None of the currently available oral medications has proven to be reliably effective and can be limited by toxicity. Cannabinoids have shown therapeutic effects on those MS-associated symptoms. Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) Sativex (nabiximols) is an oromucosal spray formulation that contains THC and CBD in an approximate 1:1 ratio and is described as an endocannabinoid system modulator. The efficacy of THC/CBD on MS-associated spasticity, pain and bladder dysfunction has been studied in clinical trials as well as in clinical practice studies. Adverse effects are usually mild or moderate and the low rate of drug discontinuation provides good evidence of long-term tolerability. This article focuses on the pharmacological properties, clinical efficacy and tolerability of THC/CBD in MS patients.

Topics: Cannabidiol; Dronabinol; Drug Combinations; Humans; Multiple Sclerosis; Muscle Spasticity; Neuralgia; Plant Extracts

Pain associated with multiple sclerosis (MS) is frequent, and frequently not alleviated by currently available drugs. Nabiximols is a combination of two plant cannabinoids administered via an oromucosal pump spray and approved in Canada for the treatment of intractable central neuropathic pain due to MS and intractable cancer pain. Nabiximols exerts its analgesic effects through its interaction with the endocannabinoid system to modulate pain transmission via pain networks.. This review examines the characteristics of nabiximols, its pharmacokinetic properties and data on efficacy and tolerability in MS-related neuropathic pain. The authors, furthermore, provide information on the pharmacology and clinical data of nabiximols as neuropathic analgesic in MS.. Nabiximols is an appropriate therapy for pain patients who tend to be particularly resistant to pharmacological interventions. Its action depends on not only the local constellation of the endocannabinoid system signalling, but also the particular functional status of pain pathways and on the specific mechanism of neuropathic pain. It is therefore justifiable that further studies are initiated which aim to define the best responder profile and which explore the full potential of nabiximols in MS-related pain.

Topics: Analgesics; Canada; Cannabidiol; Cannabinoids; Clinical Trials as Topic; Dronabinol; Drug Combinations; Drug Evaluation, Preclinical; Humans; Multiple Sclerosis; Neuralgia; Plant Preparations; Randomized Controlled Trials as Topic

Although not new, the use of cannabis-based drugs for treating chronic pain patients is becoming a hot topic for pain physicians and other specialists due to the constant flow of medical information regarding this pharmacological therapy. Its indication is becoming more clearly targeted towards pain syndromes arising from nerve damage. The number of cases reported, clinical trials and reviews published on this subject exponentially increase year by year. A possible explanation for this may be the fact that neuropathic pain is a highly disabling symptom and, consequently, there is a demand from patients and health professionals for a definitive remedy to treat this pain.. Parallel to the number of articles on the effectiveness, recent articles describing the tolerability of cannabis-based drugs along with a more accurate characterisation of its side-effect profile and/or lack of effectiveness have been published, and they are placing a cautious stop for a more precise prescription of these medications.. This article reviews the current knowledge on the use of Sativex for treating neuropathic pains of different origin, and analyses the balance between the advantages and drawbacks of this therapy.

Topics: Analgesics; Cannabidiol; Chronic Disease; Clinical Trials as Topic; Dronabinol; Drug Combinations; Humans; Neuralgia; Pain Measurement; Plant Extracts

The aim of our study was to better investigate the role of Sativex(®) in improving pain in multiple sclerosis (MS) patients by means of either clinical or neurophysiological assessment.. Pain is a common symptom of MS, affecting up to 70% of patients. Pain treatment is often unsatisfactory, although emerging drugs (including cannabinoids) are giving encouraging results. Clinical pain assessment in MS is very difficult, and more objective tools are necessary to better quantify this symptom and its potential response to the treatments.. We enrolled 20 MS patients (10 with and 10 without neuropathic pain), who underwent a specific clinical (such as visual analog scale) and neurophysiological assessment (by means of laser-evoked potentials and transcranial magnetic stimulation), before and after 4 weeks of Sativex administration.. One month of drug administration in MS patients with neuropathic pain successfully reduced pain rating and improved quality of life. Interestingly, such effects were paralleled by an increase of fronto-central γ-band oscillation and of pain-motor integration strength.. Our data suggest that Sativex may be effective in improving MS-related neuropathic pain, maybe through its action on specific cortical pathways.

Topics: Adult; Brain; Cannabidiol; Dronabinol; Drug Combinations; Female; Humans; Laser-Evoked Potentials; Male; Middle Aged; Multiple Sclerosis; Neuralgia; Pain Management; Pain Measurement; Plant Extracts; Transcranial Magnetic Stimulation

Neuropathic pain caused by chemotherapy limits dosing and duration of potentially life-saving anti-cancer treatment and impairs quality of life. Chemotherapeutic neuropathy responds poorly to conventional treatments, and there is an urgent medical need for new treatments. Recent preclinical studies demonstrate that cannabinoid agonists suppress established chemotherapy-evoked neuropathy.. This was a pilot trial to begin to investigate a currently available cannabinoid agent, nabiximols (oral mucosal spray containing cannabinoids), in the treatment of chemotherapy-induced neuropathic pain.. A randomized, placebo-controlled crossover pilot study was done in 16 patients with established chemotherapy-induced neuropathic pain. A 0-10 point numeric rating scale for pain intensity (NRS-PI) was used as the primary outcome measure.. When examining the whole group, there was no statistically significant difference between the treatment and the placebo groups on the NRS-PI. A responder analysis demonstrated that there were five participants who reported a two-point or greater reduction in pain that trended toward statistical significance and the number needed to treat was five.. Chemotherapy-induced neuropathic pain is particularly resistant to currently available treatments. This pilot trial found a number needed to treat of five and an average decrease of 2.6 on an 11-point NRS-PI in five "responders" (as compared with a decrease of 0.6 with placebo) and supports that it is worthwhile to study nabiximols in a full randomized, placebo-controlled trial of chemotherapy-induced neuropathic pain.

Topics: Analgesics; Antineoplastic Agents; Cannabidiol; Cross-Over Studies; Double-Blind Method; Dronabinol; Drug Combinations; Female; Humans; Male; Middle Aged; Neuralgia; Oral Sprays; Pain Measurement; Pilot Projects; Treatment Outcome

Cannabinoids are known to have analgesic properties. We evaluated the effect of oro-mucosal sativex, (THC: CBD), an endocannabinoid system modulator, on pain and allodynia, in 125 patients with neuropathic pain of peripheral origin in a five-week, randomised, double-blind, placebo-controlled, parallel design trial. Patients remained on their existing stable analgesia. A self-titrating regimen was used to optimise drug administration. Sixty-three patients were randomised to receive sativex and 62 placebo. The mean reduction in pain intensity scores (primary outcome measure) was greater in patients receiving sativex than placebo (mean adjusted scores -1.48 points vs. -0.52 points on a 0-10 Numerical Rating Scale (p=0.004; 95% CI: -1.59, -0.32). Improvements in Neuropathic Pain Scale composite score (p=0.007), sleep NRS (p=0.001), dynamic allodynia (p=0.042), punctate allodynia (p=0.021), Pain Disability Index (p=0.003) and Patient's Global Impression of Change (p<0.001) were similarly greater on sativex vs. placebo. Sedative and gastrointestinal side effects were reported more commonly by patients on active medication. Of all participants, 18% on sativex and 3% on placebo withdrew during the study. An open-label extension study showed that the initial pain relief was maintained without dose escalation or toxicity for 52 weeks.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Analgesics; Cannabidiol; Double-Blind Method; Dronabinol; Drug Combinations; Female; Humans; Hyperesthesia; Male; Middle Aged; Neuralgia; Pain Measurement; Peripheral Nervous System Diseases; Plant Extracts; Psychomotor Performance; Time Factors; Treatment Outcome

To compare the effectiveness, safety, and tolerability of add-on nabiximols (NBX) oromucosal spray vs typical oral long-acting opioid (LAO) analgesics in patients with severe (± chronic) peripheral neuropathic back pain poorly responsive to other treatments.. Retrospective analysis of anonymized, propensity score-matched data from the German Pain e-Registry of adult outpatients who initiated NBX or LAO between March 2017 and March 2020.. Data were analyzed from propensity score-matched patients treated with NBX (n = 655) or LAO (n = 655): mean age ≈51 years; 57% female; mean pain duration ≈2.6 years; chronic pain 61%; severe dysfunctional pain 93%. At 6 months, NBX was noninferior to LAO for overall symptom relief, based on the least-squares mean difference between cohorts in change from baseline in patient-reported, pain-related aggregated nine-item scale scores (-27.84%; 95% confidence interval [CI] -29.71 to -25.96; P < 0.001) and individual pain-related scale scores. Subsequent prespecified superiority analysis of the primary endpoint showed that NBX was superior to LAO: all secondary endpoints measuring symptoms of pain and physical function improved significantly with NBX and LAO, with between-group differences favoring NBX (all P < 0.001). Fewer patients treated with NBX than LAO experienced treatment-related adverse events (25.5% vs 76.0%; P < 0.001) or discontinued treatment because of treatment-related adverse events (7.9% vs 29.3%; P < 0.001).. Within study limitations (e.g., observational design, all potential biases), add-on NBX was superior to and better tolerated than add-on treatment with typical oral LAO analgesics in patients with neuropathic back pain inadequately controlled by recommended/established systemic therapies.

Topics: Adult; Analgesics; Analgesics, Opioid; Back Pain; Cannabidiol; Dronabinol; Drug Combinations; Female; Humans; Male; Middle Aged; Neuralgia; Registries; Retrospective Studies

To identify the areas of daily function most affected by the introduction of Sativex, a cannabis-based medicine, and the impact on caregivers and people with multiple sclerosis (MS).. Cannabinoid medicines have recently become available on prescription in several parts of the world, principally for the treatment of spasticity in people with MS. Their efficacy and safety have been demonstrated in the setting of randomised controlled clinical trials. Results of such studies may not always reflect the wider effectiveness that a medicine shows when used in clinical practice.. A short questionnaire survey consisting mostly of multiple-choice questions, along with some free-text questions aimed at the patient and primary caregiver (ie, partner, mother, nurse or outside carer). The questionnaire was developed in consultation with a patient representative organisation, field tested, ethics approval gained, then distributed to prescribers in the United Kingdom, with the request that they in turn forward it to any patients who had received repeat prescriptions for Sativex within the previous 16 weeks. Patients were seen in both a primary care (general practice) and a secondary care (hospital) setting. There was no control group in this study. Most patients had MS, and the primary reasons for using Sativex were spasticity and pain.. The response rate was 57%, with 124 questionnaires returned. The majority of respondents and their caregivers reported improvements across a range of daily functional activities, alongside a reduction in the use of concomitant anti-spasticity medication and in the use of other healthcare resources.

Topics: Activities of Daily Living; Adult; Aged; Aged, 80 and over; Cannabidiol; Caregivers; Dronabinol; Drug Combinations; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Muscle Spasticity; Neuralgia; Off-Label Use; Phytotherapy; Plant Extracts; Practice Patterns, Physicians'; Sleep; Surveys and Questionnaires; United Kingdom

Topics: Analgesics; Analgesics, Opioid; Antineoplastic Agents; Cannabidiol; Cannabinoids; Clinical Trials as Topic; Dronabinol; Drug Combinations; Drugs, Investigational; Humans; Neoplasms; Neuralgia; Pain; Palliative Care; Plant Extracts

Topics: Canada; Cannabidiol; Cannabis; Dronabinol; Drug Approval; Drug Combinations; Humans; Multiple Sclerosis; Neuralgia; Phytotherapy; Plant Extracts