gw-1000 and Pain

Patients with multiple sclerosis (MS) may suffer from spasticity and pain during their disease course. Baclofen, dantrolene, diazepam and gabapentin have been used as first-line options to treat these conditions, with modest results. Medical use of marijuana smoking has bypassed traditional clinical trials and has been legalized as a therapeutic option for MS-related spasticity and pain in some countries. Cannabis-derived drugs have been tested and approved for medical use.. With the development of nabiximols by the pharmaceutical industry, more countries have made it possible for patients with MS to have legal access to cannabis-related therapies. The evidence-based data on nabiximols and MS-related spasticity, pain, and urinary symptoms is consistent. There are over 7,500 patients reported in 33 studies (12 from the United Kingdom and 11 from Italy).. Nabiximols is safe and effective for patients with MS whose spasticity could not be treated with the first-line oral drugs. At present, legislation, bureaucracy and costs involved in prescribing this drug limit the experience of neurologists from many countries. There is no scientific evidence that smoking marijuana can be beneficial to patients with MS.

Topics: Cannabidiol; Cannabinoid Receptor Modulators; Dronabinol; Drug Combinations; Humans; Medical Marijuana; Multiple Sclerosis; Muscle Spasticity; Pain; Urologic Diseases

Cannabis has been employed medicinally throughout history, but its recent legal prohibition, biochemical complexity and variability, quality control issues, previous dearth of appropriately powered randomised controlled trials, and lack of pertinent education have conspired to leave clinicians in the dark as to how to advise patients pursuing such treatment. With the advent of pharmaceutical cannabis-based medicines (Sativex/nabiximols and Epidiolex), and liberalisation of access in certain nations, this ignorance of cannabis pharmacology and therapeutics has become untenable. In this article, the authors endeavour to present concise data on cannabis pharmacology related to tetrahydrocannabinol (THC), cannabidiol (CBD) et al., methods of administration (smoking, vaporisation, oral), and dosing recommendations. Adverse events of cannabis medicine pertain primarily to THC, whose total daily dose-equivalent should generally be limited to 30mg/day or less, preferably in conjunction with CBD, to avoid psychoactive sequelae and development of tolerance. CBD, in contrast to THC, is less potent, and may require much higher doses for its adjunctive benefits on pain, inflammation, and attenuation of THC-associated anxiety and tachycardia. Dose initiation should commence at modest levels, and titration of any cannabis preparation should be undertaken slowly over a period of as much as two weeks. Suggestions are offered on cannabis-drug interactions, patient monitoring, and standards of care, while special cases for cannabis therapeutics are addressed: epilepsy, cancer palliation and primary treatment, chronic pain, use in the elderly, Parkinson disease, paediatrics, with concomitant opioids, and in relation to driving and hazardous activities.

Topics: Cannabidiol; Cannabis; Dose-Response Relationship, Drug; Dronabinol; Drug Administration Schedule; Drug Combinations; Humans; Inflammation; Medical Marijuana; Pain

Pharmaceutical cannabinoids such as nabiximols, nabilone and dronabinol, and plant-based cannabinoids have been investigated for their therapeutic potential in treating multiple sclerosis (MS) symptoms. This review of reviews aimed to synthesise findings from high quality systematic reviews that examined the safety and effectiveness of cannabinoids in multiple sclerosis. We examined the outcomes of disability and disability progression, pain, spasticity, bladder function, tremor/ataxia, quality of life and adverse effects.. We identified 11 eligible systematic reviews providing data from 32 studies, including 10 moderate to high quality RCTs. Five reviews concluded that there was sufficient evidence that cannabinoids may be effective for symptoms of pain and/or spasticity in MS. Few reviews reported conclusions for other symptoms. Recent high quality reviews find cannabinoids may have modest effects in MS for pain or spasticity. Future research should include studies with non-cannabinoid comparators; this is an important gap in the evidence.

Topics: Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Drug Combinations; Humans; Multiple Sclerosis; Pain; Quality of Life; Randomized Controlled Trials as Topic; Systematic Reviews as Topic

Answer questions and earn CME/CNE Marijuana has been used for centuries, and interest in its medicinal properties has been increasing in recent years. Investigations into these medicinal properties has led to the development of cannabinoid pharmaceuticals such as dronabinol, nabilone, and nabiximols. Dronabinol is best studied in the treatment of nausea secondary to cancer chemotherapy and anorexia associated with weight loss in patients with acquired immune deficiency syndrome, and is approved by the US Food and Drug Administration for those indications. Nabilone has been best studied for the treatment of nausea secondary to cancer chemotherapy. There are also limited studies of these drugs for other conditions. Nabiximols is only available in the United States through clinical trials, but is used in Canada and the United Kingdom for the treatment of spasticity secondary to multiple sclerosis and pain. Studies of marijuana have concentrated on nausea, appetite, and pain. This article will review the literature regarding the medical use of marijuana and these cannabinoid pharmaceuticals (with emphasis on indications relevant to oncology), as well as available information regarding adverse effects of marijuana use.

Topics: Analgesics, Non-Narcotic; Antiemetics; Canada; Cannabidiol; Clinical Trials as Topic; Dronabinol; Drug Combinations; Evidence-Based Medicine; Humans; Medical Marijuana; Multiple Sclerosis; Neoplasms; Pain; Treatment Outcome; United Kingdom; United States

Biological activity of cannabinoids is caused by binding to two cannabinoid receptors CB1 and CB2. Psychoactive is not only tetrahydrocannabinol (THC) but also: cannabidiol, cannabigerol or cannabichromen. Formerly, the usefulness of hemp was assessed in the relation to temporary appeasement of the symptoms of some ailments as nausea or vomiting. Present discoveries indicates that cannabis-based drugs has shown ability to alleviate of autoimmunological disorders such as: Multiple sclerosis (MS), Rheumatoid arthritis (RA) or inflammatory bowel disease. Another studies indicates that cannabinoids play role in treatment of neurological disorders like Alzheimer disease or Amyotrophic lateral sclerosis (ALS) or even can reduce spreading of tumor cells. Cannabinoids stand out high safety profile considering acute toxicity, it is low possibility of deadly overdosing and side-effects are comprise in range of tolerated side-effects of other medications. In some countries marinol and nabilone are used as anti vomiting and nausea drug. First cannabis-based drug containg naturally occurring cannabinoids is Sativex. Sativex is delivered in an mucosal spray for patients suffering from spasticity in MS, pain relevant with cancer and neuropathic pain of various origin. Despite the relatively low acute toxicity of cannabinoids they should be avoid in patients with psychotic disorders, pregnant or breastfeeding woman. Cannabinoids prolong a time of reaction and decrease power of concentration that's why driving any vehicles is forbidden. Cannabis side-effects varies and depend from several factors like administrated dose, rout of administration and present state of mind. After sudden break from long-lasting use, withdrawal symptoms can appear, although they entirely disappear after a week or two.

Topics: Arthritis, Rheumatoid; Cannabidiol; Cannabinoids; Cannabis; Contraindications; Dronabinol; Drug Combinations; Humans; Inflammatory Bowel Diseases; Multiple Sclerosis; Muscle Spasticity; Nausea; Nervous System Diseases; Pain; Plant Extracts; Vomiting

Over the last two decades, experimental and clinical data suggest a therapeutic benefit of cannabis-based medicines for a variety of multiple sclerosis (MS) symptoms. Clinical trials, both with synthetic or plant-derived cannabinoids, have demonstrated clinical efficacy of cannabinoids for the treatment of spasticity, neuropathic pain and bladder dysfunction. Nabiximols, a 1:1 mix of delta-9-tetrahydrocanabinol and cannabidiol extract from cloned chemovars, was licensed in the UK in 2010 and has also been approved in other European countries and Canada. The European Federation of Neurological Societies recommends that cannabis should be used only as a second or third line treatment in central neuropathic pain.. After a brief discussion of the endocannabinoid system, this review focuses on the use of cannabis to improve MS symptoms. More specifically, the authors have analyzed clinical studies on cannabis-based medicine extract (CBME), in particular nabiximols, in spasticity, as well as pain, and bladder dysfunction in MS. The authors have considered the large randomized controlled trials examining the psychological effects associated with cannabinoids use as well as long-term follow-up studies.. Despite a number of trials with very promising results, there are still concerns related to relative paucity of data on long-term safety. Also, the long-term efficacy information in terms of the control of symptoms of a disease in which the natural history is progression is sparse. Therefore, further studies are required to improve the current knowledge of nabiximols.

Topics: Analgesics; Animals; Cannabidiol; Dronabinol; Drug Combinations; Humans; Multiple Sclerosis; Muscle Spasticity; Pain; Treatment Outcome; Urologic Diseases

Topics: Cannabidiol; Carbazoles; Delayed-Action Preparations; Dronabinol; Drug Combinations; Humans; Nurse Practitioners; Pain; Plant Extracts; Serotonin Receptor Agonists; Tryptamines

Cannabis sativa L. has been utilized for treatment of pain and sleep disorders since ancient times. This review examines modern studies on effects of Delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on sleep. It goes on to report new information on the effects on sleep in the context of medical treatment of neuropathic pain and symptoms of multiple sclerosis, employing standardized oromucosal cannabis-based medicines containing primarily THC, CBD, or a 1 : 1 combination of the two (Sativex). Sleep-laboratory results indicate a mild activating effect of CBD, and slight residual sedation with THC-predominant extracts. Experience to date with Sativex in numerous Phase I-III studies in 2000 subjects with 1000 patient years of exposure demonstrate marked improvement in subjective sleep parameters in patients with a wide variety of pain conditions including multiple sclerosis, peripheral neuropathic pain, intractable cancer pain, and rheumatoid arthritis, with an acceptable adverse event profile. No tolerance to the benefit of Sativex on pain or sleep, nor need for dosage increases have been noted in safety extension studies of up to four years, wherein 40-50% of subjects attained good or very good sleep quality, a key source of disability in chronic pain syndromes that may contribute to patients' quality of life.

Topics: Cannabidiol; Cannabis; Clinical Trials as Topic; Dronabinol; Drug Combinations; Humans; Pain; Phytotherapy; Plant Extracts; Plant Preparations; Sleep; Sleep Wake Disorders

Sativex is one of the first cannabis-based medicines to undergo conventional clinical development and to be approved as a prescription medicine. It is an oromucosal spray that allows flexible, individualised dosing. Patients self titrate their overall dose and pattern of dosing according to their response to and tolerance of the medicine. This usually results in the administration of approximately 8-12 sprays/day. Each spray delivers tetrahydrocannabinol 2.7 mg and cannabidiol 2.5 mg, giving an approximate average dose of tetrahydrocannabinol 22-32 mg/day and cannabidiol 20-30 mg/day. Development has concentrated on the treatment of symptoms of multiple sclerosis, notably spasticity and neuropathic pain, as well as the treatment of neuropathic pain of other aetiologies. Positive results in placebo-controlled trials of the use of Sativex as an add-on therapy in these indications demonstrate that Sativex is efficacious and well tolerated in the treatment of these symptoms. Sativex has been approved for use in neuropathic pain due to multiple sclerosis in Canada. If ongoing studies replicate the results already observed, further approvals for the treatment of spasticity in multiple sclerosis and for neuropathic pain are likely.

Topics: Analgesics; Cannabidiol; Cannabinoids; Dronabinol; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Humans; Multiple Sclerosis; Muscle Spasticity; Pain; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic; Self Administration; Sleep Wake Disorders

Bayer AG has recently announced that it acquired exclusive rights for the marketing of GW Pharmaceuticals' new medicine Sativex in Europe and in other regions. Sativex is a sublingual spray on Cannabis extract basis, and is equipped with an electronic tool to facilitate accurate dosing and to prevent misuses. It is standardized for the THC and CBD. The new analgesic is proposed for the treatment of muscle spasticity and pains accompanying multiple sclerosis and as an efficient analgetic for neurogenic pain not responding well to opioids and to other therapies available. The entirely new mechanism of action through the recently discovered cannabinoid receptor system may offer a real therapeutic potential to the drug. Although the Government of Netherlands has authorized the sale of pharmaceutical grade Cannabis herb by pharmacies in the Netherlands, the availability on the pharmaceutical market of the registered preparation may render requests for the authorization of the smoking of Cannabis herb (marihuana) by individuals suffering of multiple sclerosis, neurogenic pain, AIDS wasting syndrome unnecessary. Nevertheless, the "old chameleon" plant Cannabis appears to gradually regain its previous status in mainstream therapy and pharmacy. As long as the plant Cannabis and its products continue to be classified as narcotic drugs, medical use of the new preparation will need close supervision.

Topics: Analgesics; Arachidonic Acids; Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Drug Combinations; Drugs, Investigational; Endocannabinoids; Europe; Humans; Multiple Sclerosis; Pain; Plant Extracts; Polyunsaturated Alkamides

Mood, sleep and pain problems are common comorbidities among treatment-seeking cannabis-dependent patients. There is limited evidence suggesting treatment for cannabis dependence is associated with their improvement. This study explored the impact of cannabis dependence treatment on these comorbidities.. This is a secondary analysis from a 12-week double-blind placebo-controlled trial testing the efficacy of a cannabis agonist (nabiximols) against placebo in reducing illicit cannabis use in 128 cannabis-dependent participants. Outcome measurements including DASS-21 (Depression, Anxiety, and Stress subscales); Insomnia Severity Index (ISI); and Brief Pain Inventory (BPI), were performed at weeks 0, 4, 8, 12 and 24. Each was analysed as continuous outcomes and as binary cases based on validated clinical cut-offs.. Among those whose DASS and ISI scores were in the moderate to severe range at baseline, after controlling for cannabis use, there was a gradual decrease in severity of symptoms over the course of the trial. BPI decreased significantly until week 12 and then rose again in the post-treatment period during weeks 12-24. Neither pharmacotherapy type (nabiximols vs placebo) nor number of counselling sessions contributed significant explanatory power to any of the models and were excluded from the final analyses for both continuous and categorical outcomes.. Participants in this trial who qualified as cases at baseline had elevated comorbidity symptoms. There was no evidence that nabiximols treatment is a barrier to achieving reductions in the comorbid symptoms examined. Cannabis dependence treatment reduced illicit cannabis use and improved comorbidity symptoms, even when complete abstinence was not achieved.

Topics: Analgesics; Cannabidiol; Cannabinoid Receptor Agonists; Cannabis; Comorbidity; Double-Blind Method; Dronabinol; Drug Combinations; Hallucinogens; Humans; Marijuana Abuse; Medical Marijuana; Pain; Sleep; Treatment Outcome

There is increasing interest and evidence for the use of cannabinoid medications in the treatment of cannabis use disorder, but little examination of the correlates of successful treatment. This paper is a secondary analysis of a randomised placebo-controlled trial of nabiximols for the treatment of cannabis use disorder (CUD), aiming to identify which client and treatment characteristics impact treatment engagement and outcomes.. Bayesian multiple regression models were used to examine the impact of age, gender, duration of regular cannabis use, daily quantity of cannabis, cannabis use problems, self-efficacy for quitting, sleep, mental health, pain measures, and treatment group upon treatment engagement (retention, medication dose, and counselling participation) and treatment outcomes (achieving end-of-study abstinence, and a 50% or greater reduction in cannabis use days) among the 128 clients participating in the 12-week trial.. Among the treatment factors, greater counselling attendance was associated with greater odds of abstinence and ≥ 50% reduction in cannabis use; nabiximols with greater odds of ≥ 50% reduction and attending counselling, and reduced hazard of treatment dropout; and higher dose with lower odds of ≥ 50% reduction. Among the client factors, longer duration of regular use was associated with higher odds of abstinence and 50% reduction, and lower hazard of treatment dropout; greater quantity of cannabis use with reduced hazard of dropout, greater odds of attending counselling, and higher average dose; greater pain at baseline with greater odds of ≥ 50% reduction and higher average dose; and more severe sleep issues with lower odds of ≥ 50% reduction. Males had lower odds of attending counselling.. These findings suggest that counselling combined with agonist pharmacotherapy may provide the optimal treatment for cannabis use disorder. Younger clients, male clients, and clients with sleep issues could benefit from extra support from treatment services to improve engagement and outcomes.. Australian New Zealand Clinical Trials Registry (ACTRN12616000103460) https://www.anzctr.org.au.

Topics: Australia; Bayes Theorem; Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Drug Combinations; Humans; Male; Marijuana Abuse; Pain; Substance-Related Disorders

To investigate the action of cannabinoids on spasticity and pain in secondary progressive multiple sclerosis, by means of neurophysiological indexes.. We assessed 15 patients with progressive MS (11 females) using clinical scales for spasticity and pain, as well as neurophysiological variables (H/M ratio, cutaneous silent period or CSP). Testing occurred before (T0) and during (T1) a standard treatment with an oral spray containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Neurophysiological measures at T0 were compared with those of 14 healthy controls of similar age and sex (HC). We then compared the patient results at the two time points (T1 vs T0).. At T0, neurophysiological variables did not differ significantly between patients and controls. At T1, spasticity and pain scores improved, as detected by the Modified Ashworth Scale or MAS (P = .001), 9-Hole Peg Test or 9HPT (P = .018), numeric rating scale for spasticity or NRS (P = .001), and visual analogue scale for pain or VAS (P = .005). At the same time, the CSP was significantly prolonged (P = .001).. The THC-CBD spray improved spasticity and pain in secondary progressive MS patients. The spray prolonged CSP duration, which appears a promising tool for assessing and monitoring the analgesic effects of THC-CBD in MS.

Topics: Administration, Oral; Adult; Cannabidiol; Dronabinol; Drug Combinations; Female; Humans; Male; Middle Aged; Multiple Sclerosis, Chronic Progressive; Muscle Spasticity; Muscle, Skeletal; Pain; Pilot Projects; Treatment Outcome

To assess the efficacy of Sativex, a cannabis-based medicinal extract, as adjuvant treatment in painful diabetic peripheral neuropathy (DPN).. In this randomized controlled trial, 30 subjects with painful DPN received daily Sativex or placebo. The primary outcome measure was change in mean daily pain scores, and secondary outcome measures included quality-of-life assessments.. There was significant improvement in pain scores in both groups, but mean change between groups was not significant. There were no significant differences in secondary outcome measures. Patients with depression had significantly greater baseline pain scores that improved regardless of intervention.. This first-ever trial assessing the efficacy of cannabis has shown it to be no more efficacious than placebo in painful DPN. Depression was a major confounder and may have important implications for future trials on painful DPN.

Topics: Adult; Aged; Cannabidiol; Depression; Diabetic Neuropathies; Double-Blind Method; Dronabinol; Drug Combinations; Female; Humans; Male; Middle Aged; Pain; Pain Measurement; Placebos; Plant Extracts; Quality of Life; Treatment Outcome

The endocannabinoid system (ECS) is involved in the pathophysiology of multiple sclerosis (MS), and relief from pain and spasticity has been reported in MS patients self-medicating with marijuana. A cannabis-based medication containing Delta(9)-tetrahydrocannabinol and cannabidiol (Sativex) has been approved in some countries for the treatment of MS-associated pain. The effects of this pharmaceutical preparation on other clinically relevant aspects of MS pathophysiology, however, are still unclear. In 20 MS patients, we measured the effects of Sativex on clinically measured spasticity and on neurophysiological and laboratory parameters that correlate with spasticity severity or with the modulation of the ECS. Sativex failed to affect spasticity and stretch reflex excitability. This compound also failed to affect the synthesis and the degradation of the endocannabinoid anandamide, as well as the expression of both CB1 and CB2 cannabinoid receptors in various subpopulations of peripheral lymphocytes.

Topics: Adult; Arachidonic Acids; Cannabidiol; Cannabinoids; Dronabinol; Drug Combinations; Endocannabinoids; Female; Humans; Lymphocytes; Male; Middle Aged; Multiple Sclerosis; Muscle Spasticity; Pain; Plant Extracts; Polyunsaturated Alkamides; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Reflex, Stretch; Treatment Outcome; Young Adult

Central neuropathic pain (CNP), pain initiated or caused by a primary lesion or dysfunction of the central nervous system, occurs in ~28% of patients with multiple sclerosis (MS). Delta(9)-Tetrahydrocannabinol/cannabidiol (THC/CBD), an endocannabinoid system modulator, has demonstrated efficacy for up to 4 weeks in randomized controlled trials in the treatment of CNP in patients with MS.. The purpose of this extension was to establish long-term tolerability and effectiveness profiles for THC/CBD (Sativex (R), GW Pharmaceuticals plc, Salisbury, United Kingdom) oromucosal spray in CNP associated with MS.. This uncontrolled, open-label trial was an indefinite-duration extension of a previously reported 5-week randomized study in patients with MS and CNP. In the initial trial, patients were randomized to placebo or THC/CBD. Patients were only required to maintain their existing analgesia in the randomized study. In the open-label trial they could vary their other analgesia as required. All patients (placebo and THC/CBD) who completed the randomized trial commenced the open-label follow-up on THC/CBD (27 mg/mL: 25 mg/mL). Patients titrated their dosage, maintaining their existing analgesia. The primary end point of the trial was the number, frequency, and type of adverse events (AEs) reported by patients. Secondary end points included changes from baseline in 11-point numerical rating scale (NRS-11) neuropathic pain score, hematology and clinical chemistry test results, vital signs, trial drug usage, and intoxication visual analogue scale scores.. Sixty-six patients were enrolled in the randomized trial; 64 (97%) completed the randomized trial and 63 (95%) entered the open-label extension (race, white, 100%; sex, male, 14 [22%]; mean [SD] age, 49 [8.4] years [range, 27-71 years[). The mean (SD) duration of open-label treatment was 463 (378) days (median, 638 days; range, 3-917 days), with 34 (54%) patients completing >1 year of treatment with THC/CBD and 28 (44%) patients completing the open-label trial with a mean (SD) duration of treatment of 839 (42) days (median, 845 days; range, 701-917 days). Mean NRS-11 pain scores in the final week of the randomized trial were 3.8 in the treatment group and 5.0 in the placebo group. In the 28 (44%) patients who completed the 2-year follow up, the mean (SD) NRS-11 pain score in the final week of treatment was 2.9 (2.0) (range, 0-8.0). Fifty-eight (92%) patients experienced > or =1 treatment-related AE. These AEs were rated by the investigator as mild in 47 (75%) patients, moderate in 49 (78%), and severe in 32 (51%). The most commonly reported AEs were dizziness (27%), nausea (18 %), and feeling intoxicated (11%). Two treatment-related serious AEs (ventricular bigeminy and circulatory collapse) were judged to be treatment-related. Both serious AEs occurred in the same patient and resolved completely following a period of discontinuation. Eleven (17%) patients experienced oral discomfort, 4 persistently. Regular oral examinations revealed that 7 (11%) patients developed white buccal mucosal patches and 2 (3%) developed red buccal mucosal patches; all cases were deemed mild and resolved. Seventeen (25%) patients withdrew due to AEs. The mean number of sprays and patients experiencing intoxication remained stable throughout the follow-up trial.. THC/CBD was effective, with no evidence of tolerance, in these select patients with CNP and MS who completed approximately 2 years of treatment (n = 28). Ninety-two percent of patients experienced an AE, the most common of which were dizziness and nausea. The majority of AEs were deemed to be of mild to moderate severity by the investigators.

Topics: Administration, Oral; Administration, Sublingual; Adult; Aerosols; Analgesics, Opioid; Cannabidiol; Central Nervous System Diseases; Dronabinol; Drug Combinations; Female; Humans; Male; Middle Aged; Mouth Mucosa; Multiple Sclerosis; Pain; Plant Extracts

To assess the efficacy of a cannabis-based medicine (CBM) in the treatment of pain due to rheumatoid arthritis (RA).. We compared a CBM (Sativex) with placebo in a randomized, double-blind, parallel group study in 58 patients over 5 weeks of treatment. The CBM was administered by oromucosal spray in the evening and assessments were made the following morning. Efficacy outcomes assessed were pain on movement, pain at rest, morning stiffness and sleep quality measured by a numerical rating scale, the Short-Form McGill Pain Questionnaire (SF-MPQ) and the DAS28 measure of disease activity.. Seventy-five patients were screened and 58 met the eligibility criteria. Thirty-one were randomized to the CBM and 27 to placebo. Mean (S.D.) daily dose achieved in the final treatment week was 5.4 (0.84) actuations for the CBM and 5.3 (1.18) for placebo. In comparison with placebo, the CBM produced statistically significant improvements in pain on movement, pain at rest, quality of sleep, DAS28 and the SF-MPQ pain at present component. There was no effect on morning stiffness but baseline scores were low. The large majority of adverse effects were mild or moderate, and there were no adverse effect-related withdrawals or serious adverse effects in the active treatment group.. In the first ever controlled trial of a CBM in RA, a significant analgesic effect was observed and disease activity was significantly suppressed following Sativex treatment. Whilst the differences are small and variable across the population, they represent benefits of clinical relevance and show the need for more detailed investigation in this indication.

Topics: Administration, Oral; Analgesics; Arthritis, Rheumatoid; Cannabidiol; Double-Blind Method; Dronabinol; Drug Combinations; Female; Humans; Male; Middle Aged; Pain; Pain Measurement; Plant Extracts; Treatment Outcome

The objective was to investigate the effectiveness of cannabis-based medicines for treatment of chronic pain associated with brachial plexus root avulsion. This condition is an excellent human model of central neuropathic pain as it represents an unusually homogenous group in terms of anatomical location of injury, pain descriptions and patient demographics. Forty-eight patients with at least one avulsed root and baseline pain score of four or more on an 11-point ordinate scale participated in a randomised, double-blind, placebo-controlled, three period crossover study. All patients had intractable symptoms regardless of current analgesic therapy. Patients entered a baseline period of 2 weeks, followed by three, 2-week treatment periods during each of which they received one of three oromucosal spray preparations. These were placebo and two whole plant extracts of Cannabis sativa L.: GW-1000-02 (Sativex), containing Delta(9)tetrahydrocannabinol (THC):cannabidiol (CBD) in an approximate 1:1 ratio and GW-2000-02, containing primarily THC. The primary outcome measure was the mean pain severity score during the last 7 days of treatment. Secondary outcome measures included pain related quality of life assessments. The primary outcome measure failed to fall by the two points defined in our hypothesis. However, both this measure and measures of sleep showed statistically significant improvements. The study medications were generally well tolerated with the majority of adverse events, including intoxication type reactions, being mild to moderate in severity and resolving spontaneously. Studies of longer duration in neuropathic pain are required to confirm a clinically relevant, improvement in the treatment of this condition.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Brachial Plexus Neuropathies; Cannabidiol; Cross-Over Studies; Double-Blind Method; Dronabinol; Drug Combinations; Female; Humans; Male; Middle Aged; Pain; Pain Measurement; Plant Extracts; Retrospective Studies; Sleep; Time Factors; Treatment Outcome

Randomized controlled trials and observational studies of nabiximols oromucosal spray in patients with multiple sclerosis (MS) spasticity have shown improvement in a range of associated symptoms (pain, spasms, fatigue, bladder dysfunction, and sleep disturbances). This study evaluated the effectiveness and tolerability of add-on nabiximols in the routine management of patients with MS spasticity in Austria, with a focus on spasticity-associated symptoms.. This was an open, prospective, multicenter, observational, non-interventional study of patients with MS spasticity receiving add-on treatment with nabiximols oromucosal spray. Main endpoints were patient-reported changes from baseline in the frequency (counts) or severity (mean Numerical Rating Scale [NRS] scores) of spasticity-associated symptoms, and patient-reported changes from baseline in impairment of daily activities due to spasticity, after 1 and 3 months of nabiximols treatment. No analyses were conducted for statistical significance.. There were 55 patients in the effectiveness population, and 62 in the safety population. Patients reported clinically relevant reductions from baseline to month 3 in the average number of spasms/day (-68.2%) and number of urinary incontinence episodes (-69.3%) in the week prior to the clinic visit, and reductions in mean 0-10 NRS scores for sleep impairment (-47.2%), fatigue (-26.4%), pain (40.4%), and spasticity severity (39.0%). There was no change from baseline in daily activity impairment due to spasticity. The majority of patients were at least partly satisfied with add-on nabiximols for spasticity-associated symptoms. There were 31 adverse events (27 treatment related) reported in 19 patients, with no new safety signals.. Add-on nabiximols improved the severity of MS spasticity and a range of spasticity-associated symptoms during real-world use in Austria. Nabiximols is an option for patients with MS spasticity who fail first-line oral antispasticity treatment.

Topics: Austria; Humans; Multiple Sclerosis; Muscle Spasticity; Pain; Prospective Studies; Spasm

Nabiximols is a therapeutic option for patients with multiple sclerosis (MS) spasticity whose symptoms are poorly controlled by conventional oral first-line medications. This study aimed to assess the relationship between changes in spasticity severity (measured on the 0-10 numeric rating scale [NRS]) and the presence of associated symptoms in patients treated with nabiximols, and to investigate the presence of the newly described 'spasticity-plus syndrome'.. We analyzed real-world data from the Italian Medicines Agency e-Registry on 1138 patients with MS spasticity who began treatment with nabiximols. Evaluation time points were baseline, 4 weeks, and 3, 6, 12 and 18 months after treatment start.. Common symptoms associated with MS spasticity in this cohort were pain (38.4% at baseline), sleep disturbances (32.7%), and spasms/cramps (28.5%). Pain was frequently clustered with sleep disturbances (57.2% of pain cases) and spasms/cramps (43.9%). Approximately one-third of patients with data at all evaluation time points maintained treatment at 18 months. Nabiximols reduced the baseline mean spasticity 0-10 NRS score by 24.6% at Week 4, and by 33.9% at 18 months in treatment continuers. Nabiximols resolved a range of MS spasticity-associated symptoms at Week 4, and after 18 months in treatment continuers.. This real-world analysis supports the concept of a spasticity-plus syndrome and suggests that nabiximols can favorably impact a range of spasticity-associated symptoms.

Topics: Cannabidiol; Central Nervous System Diseases; Dronabinol; Drug Combinations; Humans; Multiple Sclerosis; Muscle Cramp; Muscle Spasticity; Pain; Spasm; Treatment Outcome

The German government intends to reduce the barriers for the medical use of cannabis products. A discussion on the indications and contraindications of the medical use of cannabis and on the changes of the regulatory framework has already begun in Germany. It is useful to draw from the experiences of other countries with a more liberal medical use of cannabis.. The Israeli and Canadian experience is outlined by physicians who have been charged with expertise on the medical use of cannabis by their jurisdiction.. In Israel, only the plant-based cannabinoid nabiximol (mixture of tetrahydrocannabinol/cannabidiol) can be prescribed for spasticity/chronic pain in multiple sclerosis and for cancer pain. The costs of nabiximole are reimbursed by some, but not by all health maintenance organizations. The medical use of marijuana is permitted; however, it is strictly regulated by the government. Selected companies are allowed to produce marijuana for medical use, and only certain physicians are licensed to prescribe marijuana as a therapeutic drug for specific indications such as chronic neuropathic, and cancer pain, inflammatory bowel diseases, or posttraumatic stress disorder if conventional treatments have failed. The costs of marijuana are not reimbursed by health insurance companies. In Canada, synthetic cannabinoids and the plant-based (nabiximol) are licensed for neuropathic and cancer pain, HIV-related anorexia and chemotherapy-associate nausea. The costs of these synthetic cannabinoids are covered by health insurance companies. The medical use of marijuana as a treatment option is allowed for individual patients suffering from any medical condition when authorized by a medical practitioner or nurse. Licensed producers are the only source for patients to newly access medical cannabis, although those with previous permission to grow may continue cultivation at the present time. The costs of marijuana are not reimbursed by health insurance companies. There are multiple contraindications for the medical use of cannabis products in both countries.. The use of standardized, synthetic, and plant-based cannabis products should be allowed in Germany for defined medical conditions when high-level evidence of efficacy and safety exists. The costs should be reimbursed by the health insurance companies. Contraindications for the medical use of cannabis should be defined. Growing marijuana by patients for their medical use should not be allowed.

Topics: Canada; Cannabidiol; Cross-Cultural Comparison; Dronabinol; Drug and Narcotic Control; Drug Combinations; Germany; Humans; Insurance Coverage; Israel; Medical Marijuana; National Health Programs; Pain

The therapeutic use of cannabis has generated a lot of interest in the past years, leading to a better understanding of its mechanisms of action. Countries like the United States and Canada have modified their laws in order to make cannabinoid use legal in the medical context. It's also the case in France now, where a recent decree was issued, authorizing the prescription of medication containing "therapeutic cannabis" (decree no. 2013-473, June 5, 2013). Cannabinoids such as dronabinol, Sativex and nabilone have been tested for the treatment of acute and chronic pain. These agents are most promising to relieve chronic pain associated with cancer, with human immunodeficiency virus infection and with multiple sclerosis. However, longer-term studies are required to determine potential long-term adverse effects and risks of misuse and addiction.

Topics: Antiemetics; Cannabidiol; Dronabinol; Drug Combinations; Fibromyalgia; Humans; Multiple Sclerosis; Muscle Spasticity; Pain; Plant Extracts

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: Cannabidiol; Cannabis; Dronabinol; Drug Approval; Drug Combinations; Germany; Humans; Multiple Sclerosis; Muscle Spasticity; Pain; Palliative Care; Phytotherapy; Plant Extracts; Psychoses, Substance-Induced

Multiple sclerosis (MS) is a chronic neurological disease that affects 240 per 100 000 Canadians. Of these patients, 10-80% (average 70%) experience pain. Sativex is a cannabis-based drug recently approved for neuropathic pain.. In this study, we determine individuals' preferences between two treatment options as well as the willingness to pay (WTP) for Sativex, expressed as the amount they would pay in insurance premiums to have access to that treatment.. The WTP instrument comprised a decision board as a visual aid, and a questionnaire. A decision board helps clinicians standardize the presentation of treatment information. In this study, the decision board described two treatment options: a three-drug combination (gabapentin, amytriptyline, acetaminophen [paracetamol] {i.e. pills}) and the three-drug combination plus Sativex (i.e. 'pills and oral spray'). Information on efficacy and adverse effects was taken from trial data; wording was guided by a panel of neurologists and tested for clarity on lay people. The instrument was administered to 500 participants from Canada's general population using the bidding game approach. Descriptive statistics were calculated.. Mean (SD) age of participants was 39 (13) years, with a female : male distribution of 56 : 44. The decision board was presented in both English (85%) and French (15%). Of 500 interviewees, 253 (50.6%) chose the 'pills and oral spray'. Mean monthly WTP for the insurance premium for those who chose the 'pills and oral spray' was Can dollars 8 (SD +/- 15, median 4, range 0-200).. Assuming that 51% of the general population are willing to pay additional premiums as reported in this study, the premiums collected would cover the cost of Sativex for all Canadian MS patients experiencing pain, with a surplus.

Topics: Administration, Oral; Administration, Sublingual; Adult; Aerosols; Aged; Aged, 80 and over; Analgesics, Opioid; Attitude to Health; Cannabidiol; Cost-Benefit Analysis; Decision Making; Dronabinol; Drug Combinations; Fees and Charges; Female; Humans; Insurance, Health; Interviews as Topic; Male; Middle Aged; Multiple Sclerosis; Pain; Patient Satisfaction; Plant Extracts; Surveys and Questionnaires

Topics: Analgesics, Opioid; Cannabidiol; Cannabinoids; Carbazoles; Chronic Disease; Dronabinol; Drug Combinations; Humans; Ibuprofen; Oxycodone; Oxymorphone; Pain; Plant Extracts; Serotonin Receptor Agonists; Tryptamines

An oromucosal spray has been developed from the major components of marijuana (cannabis), including tetrahydrocannabinol (THC) and cannabidiol (CBD), in alcohol with a peppermint flavouring, designed to be administered as a spray under the tongue or on the buccal mucosa to relieve pain in multiple sclerosis. Although the available evidence indicates its efficacy in this respect, some patients develop oral burning sensation, stinging or white lesions, probably burns.. To investigate the oral side-effects of oromucosal cannabis spray in multiple sclerosis (MS) patients.. A small open observational study.. A series of nine patients with MS who had been using a marijuana oromucosal spray for at least four weeks, were asked to attend for oral examination. Patients were asked whether they had ever experienced symptoms (dryness; bad taste; stinging) associated with use of the spray. A standard oral examination was carried out using a dental light, and the presence of any mucosal lesions recorded. Where mucosal lesions were present, patients were advised to discontinue the spray and re-attend after four weeks for re-examination. For ethical reasons, biopsies were not undertaken at the first visit.. Of nine patients invited to participate, eight attended. All admitted to a stinging sensation on using the oromucosal cannabis spray, and four had visible oral mucosal white lesions in the floor of the mouth.. Although the white lesions observed were almost certainly burns, resolving or improving on discontinuation of use of the medication, the high alcohol concentration of the oromucosal cannabis spray raises concern in relation to chronic oral use.

Topics: Administration, Oral; Adult; Aerosols; Aged; Burns, Chemical; Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Drug Combinations; Female; Humans; Male; Middle Aged; Mouth Mucosa; Multiple Sclerosis; Pain; Phytotherapy; Plant Extracts

Topics: Analgesics; Arthritis, Rheumatoid; Cannabidiol; Cannabis; Dronabinol; Drug Combinations; Humans; Pain; Plant Extracts; Treatment Outcome