gw-1000 and Substance-Withdrawal-Syndrome

Cannabis is a common recreational drug that is generally considered to have low addictive potential. However, an increasing number of cannabis users are seeking treatment for dependence on the drug. There is interest in using agonist (substitution) pharmacotherapies to treat cannabis dependence and here we outline a novel approach involving a buccal spray (nabiximols) that contains tetrahydrocannabinol (THC) and cannabidiol (CBD). We review recent research with nabiximols and highlight findings relevant to clinical practice.

Topics: Cannabidiol; Dronabinol; Drug Combinations; Humans; Marijuana Abuse; Substance Withdrawal Syndrome

The current lack of pharmacological treatments for cannabis use disorder (CUD) warrants novel approaches and further investigation of promising pharmacotherapy. We previously showed that nabiximols (27 mg/ml Δ9-tetrahydrocannabinol (THC)/ 25 mg/ml cannabidiol (CBD), Sativex®) can decrease cannabis withdrawal symptoms. Here, we assessed in a pilot study the tolerability and safety of self-titrated nabiximols vs. placebo among 40 treatment-seeking cannabis-dependent participants.. Subjects participated in a double blind randomized clinical trial, with as-needed nabiximols up to 113.4 mg THC/105 mg CBD or placebo daily for 12 weeks, concurrently with Motivational Enhancement Therapy and Cognitive Behavioral Therapy (MET/CBT). Primary outcome measures were tolerability and abstinence, secondary outcome measures were days and amount of cannabis use, withdrawal, and craving scores. Participants received up to CDN$ 855 in compensation for their time.. Medication was well tolerated and no serious adverse events (SAEs) were observed. Rates of adverse events did not differ between treatment arms (F1,39 = 0.205, NS). There was no significant change in abstinence rates at trial end. Participants were not able to differentiate between subjective effects associated with nabiximols or placebo treatments (F1,40 = 0.585, NS). Cannabis use was reduced in the nabiximols (70.5%) and placebo groups (42.6%). Nabiximols reduced cannabis craving but no significant differences between the nabiximols and placebo groups were observed on withdrawal scores.. Nabiximols in combination with MET/CBT was well tolerated and allowed for reduction of cannabis use. Future clinical trials should explore the potential of high doses of nabiximols for cannabis dependence.

Topics: Adult; Cannabidiol; Cognitive Behavioral Therapy; Craving; Double-Blind Method; Dronabinol; Drug Combinations; Female; Humans; Male; Marijuana Abuse; Middle Aged; Motivation; Pilot Projects; Placebos; Substance Withdrawal Syndrome; Young Adult

The cannabis extract nabiximols (Sativex®) effectively supresses withdrawal symptoms and cravings in treatment resistant cannabis dependent individuals, who have high relapse rates following conventional withdrawal treatments. This study examines the efficacy, safety and cost-effectiveness of longer-term nabiximols treatment for outpatient cannabis dependent patients who have not responded to previous conventional treatment approaches.. A phase III multi-site outpatient, randomised, double-blinded, placebo controlled parallel design, comparing a 12-week course of nabiximols to placebo, with follow up at 24 weeks after enrolment. Four specialist drug and alcohol outpatient clinics in New South Wales, Australia. One hundred forty-two treatment seeking cannabis dependent adults, with no significant medical, psychiatric or other substance use disorders. Nabiximols is an oromucosal spray prescribed on a flexible dose regimen to a maximum daily dose of 32 sprays; 8 sprays (total 21.6 mg tetrahydrocannabinol (THC) and 20 mg cannabidiol (CBD)) four times a day, or matching placebo, dispensed weekly. All participants will receive six-sessions of individual cognitive behavioural therapy (CBT) and weekly clinical reviews. Primary endpoints are use of non-prescribed cannabis (self-reported cannabis use days, urine toxicology), safety measures (adverse events and abuse liability), and cost effectiveness (incremental cost effectiveness in achieving additional Quality Adjusted Life Years). Secondary outcomes include, improvement in physical and mental health parameters, substance use other than cannabis, cognitive functioning and patient satisfaction measures.. This is the first outpatient community-based randomised controlled study of nabiximols as an agonist replacement medication for treating cannabis dependence, targeting individuals who have not previously responded to conventional treatment approaches. The study and treatment design is modelled upon an earlier study with this population and more generally on other agonist replacement treatments (e.g. nicotine, opioids).. Australian and New Zealand Clinical Trial Registry: ACTRN12616000103460 (Registered 1st February 2016).

Topics: Adult; Australia; Cannabidiol; Cannabinoids; Cognition; Cognitive Behavioral Therapy; Combined Modality Therapy; Craving; Double-Blind Method; Dronabinol; Drug Combinations; Female; Humans; Male; Marijuana Abuse; New South Wales; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Treatment Outcome

There is currently no pharmacological treatment approved for cannabis dependence. In this proof of concept study, we assessed the feasibility/effects of fixed and self-titrated dosages of Sativex (1:1, Δ(9)-tetrahydrocannabinol (THC)/cannabidiol (CBD)) on craving and withdrawal from cannabis among nine community-recruited cannabis-dependent subjects.. Participants underwent an 8-week double-blind placebo-controlled trial (an ABACADAE design), with four smoke as usual conditions (SAU) (A) separated by four cannabis abstinence conditions (B-E), with administration of either self-titrated/fixed doses of placebo or Sativex (up to 108 mg THC/100 mg CBD). The order of medication administration during abstinence conditions was randomized and counterbalanced. Withdrawal symptoms and craving were assessed using the Cannabis Withdrawal Scale (CWS), Marijuana Withdrawal Checklist (MWC) and Marijuana Craving Questionnaire (MCQ). Medication use was assessed during the study by means of self-reports, vial weight control, toxicology and metabolite analysis. Cannabis use was assessed by means of self-reports.. High fixed doses of Sativex were well tolerated and significantly reduced cannabis withdrawal during abstinence, but not craving, as compared to placebo. Self-titrated doses were lower and showed limited efficacy as compared to high fixed doses. Participants reported a significantly lower "high" following Sativex or placebo as compared to SAU conditions. Cannabis/medication use along the study, as per self-reports, suggests compliance with the study conditions.. The results found in this proof of concept study warrant further systematic exploration of Sativex as a treatment option for cannabis withdrawal and dependence.

Topics: Adult; Cannabidiol; Cannabis; Craving; Double-Blind Method; Dronabinol; Drug Combinations; Female; Humans; Male; Marijuana Abuse; Marijuana Smoking; Middle Aged; Plant Extracts; Substance Withdrawal Syndrome; Substance-Related Disorders; Treatment Outcome; Young Adult

There are no medications approved for treating cannabis dependence or withdrawal. The cannabis extract nabiximols (Sativex), developed as a multiple sclerosis treatment, offers a potential agonist medication for cannabis withdrawal.. To evaluate the safety and efficacy of nabiximols in treating cannabis withdrawal.. A 2-site, double-blind randomized clinical inpatient trial with a 28-day follow-up was conducted in New South Wales, Australia. Participants included 51 DSM-IV-TR cannabis-dependent treatment seekers.. A 6-day regimen of nabiximols (maximum daily dose, 86.4 mg of Δ9-tetrahydrocannabinol and 80 mg of cannabidiol) or placebo with standardized psychosocial interventions during a 9-day admission.. Severity of cannabis withdrawal and cravings (Cannabis Withdrawal Scale), retention in withdrawal treatment, and adverse events. Secondary outcomes include postwithdrawal cannabis use, health outcomes, and psychosocial outcomes.. Nabiximols treatment significantly reduced the overall severity of cannabis withdrawal relative to placebo (F8,377.97 = 2.39; P = .01), including effects on withdrawal-related irritability, depression, and cannabis cravings. Nabiximols had a more limited, but still positive, therapeutic benefit on sleep disturbance, anxiety, appetite loss, physical symptoms, and restlessness. Nabiximols patients remained in treatment longer during medication use (unadjusted hazard ratio, 3.66 [95% CI, 1.18-11.37]; P = .02), with 2.84 the number needed to treat to achieve successful retention in treatment. Participants could not reliably differentiate between nabiximols and placebo treatment (χ21 = 0.79; P = .67), and those receiving nabiximols did not report greater intoxication (F1,6 = 0.22; P = .97). The number (F1,50 = 0.3; P = .59) and severity (F1,50 = 2.69; P = .10) of adverse events did not differ significantly between groups. Both groups showed reduced cannabis use at follow-up, with no advantage of nabiximols over placebo for self-reported cannabis use (F1,48 = 0.29; P = .75), cannabis-related problems (F1,49 = 2.33; P = .14), or cannabis dependence (F1,50 < 0.01; P = .89).. In a treatment-seeking cohort, nabiximols attenuated cannabis withdrawal symptoms and improved patient retention in treatment. However, placebo was as effective as nabiximols in promoting long-term reductions in cannabis use following medication cessation. The data support further evaluation of nabiximols for management of cannabis dependence and withdrawal in treatment-seeking populations.. anzctr.org.au Identifier: ACTRN12611000398909.

Topics: Adult; Australia; Cannabidiol; Cannabinoid Receptor Agonists; Combined Modality Therapy; Double-Blind Method; Dronabinol; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Marijuana Abuse; Middle Aged; Placebo Effect; Placebos; Psychotherapy; Severity of Illness Index; Substance Withdrawal Syndrome; Treatment Outcome

Open-label studies are not ideal for providing robust evidence for long-term maintenance of efficacy of medicines, especially where medicines provide symptom relief and where long-term use of a placebo may be problematic and not ethical.. To evaluate the maintenance of efficacy of Sativex in subjects who have gained long-term symptomatic relief of spasticity in multiple sclerosis (MS), and to assess the impact of sudden medicine withdrawal.. An enriched enrolment randomized withdrawal study design was used. Eligible subjects with ongoing benefit from Sativex for at least 12 weeks entered this 5-week placebo-controlled, parallel-group, randomized withdrawal study. Each subjects' previous effective and tolerated dose was continued.. A total of 18 subjects per group were enrolled. Demographics showed a mean duration of MS of 16.4 years, spasticity 12.7 years, mean duration of Sativex use of 3.6 years (median 3.4 years) and a mean daily dose of 8.25 sprays. Primary outcome of time to treatment failure was significantly in favour of Sativex (p = 0.013). Secondary endpoints showed significant changes in the Carer and Subject's Global Impression of Change scales in favour of Sativex.. Maintenance of Sativex efficacy in long-term symptomatic improvement of spasticity to a group of subjects with MS has been confirmed using this study design.

Topics: Aged; Cannabidiol; Cannabinoids; Dronabinol; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Muscle Spasticity; Placebos; Plant Extracts; Substance Withdrawal Syndrome

Cannabis addiction is worldwide one of the most prevalent addictions, without any effective pharmacotherapeutic options. Nabiximols spray, consisting of 2.7 mg tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD), could serve as an effective substitution therapy for cannabis addiction. Researchers reported that patients who were treated for 12 weeks with nabiximols significantly reduced the number of days on which they used cannabis (18.6 days less compared to placebo users; 95% CI: 3.5-33.7). There was no difference between groups regarding general health, the use of other substances, cannabis craving, withdrawal symptoms or achieving abstinence.

Topics: Analgesics; Cannabidiol; Cannabis; Clinical Trials as Topic; Dronabinol; Drug Combinations; Female; Humans; Male; Marijuana Abuse; Nasal Sprays; Substance Withdrawal Syndrome