Nabiximols combined with motivational enhancement/cognitive behavioral therapy for the treatment of cannabis dependence: A pilot randomized clinical trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Assessing service and treatment needs of young people who use illicit and non-medical prescription drugs living in Northern Ontario, Canada.

Background: The use of illicit and prescription drugs for non-medical purposes among youth and young adults living in Northern Ontario communities is a major public health concern. This problem is amplified in that there is insufficient knowledge on the types of services and treatment centers available for and utilized by young people with substance use issues in Northern Ontario. This needs assessment study aims to examine the service and treatment needs of youth and young adults who use drugs in Northern Ontario communities. Methods/Design: A mixed-methods study design will be used to assess the service and treatment needs of youth and young adults (aged 14-25) who have used one or more illicit drug (excluding cannabis) and/or psychoactive prescription drug for non-medical purposes for at least 3 months and on at least 10 days in the last month. Participants will be recruited from approximately ten Northern, remote and rural communities across Northern Ontario using a mobile research lab. Eligible study candidates from each community will be asked to partake in a focus group and questionnaire exploring service and treatment utilization and needs. We will additionally collect basic socio-demographic information as well as examine patterns of problematic drug use. Interviews with service providers and community organizers will also be conducted in each community.  Discussion: Findings from our study will highlight the availability, accessibility and utilization of existing services; identify the gaps and barriers in current service provision; and provide insight into the service and treatment needs of youth and young adults who use drugs in Northern Ontario communities. Assessing the needs of young people who use drugs will allow service providers, community organizers and health policymakers to improve addiction-related services and treatment centers in Northern Ontario.

Comparing Medical and Recreational Cannabis Users on Socio-Demographic, Substance and Medication Use, and Health and Disability Characteristics.

BACKGROUND: While recreational cannabis use is common, medical cannabis programs have proliferated across North America, including a federal program in Canada. Few comparisons of medical and recreational cannabis users (RCUs) exist; this study compared these groups on key characteristics. METHODS: Data came from a community-recruited sample of formally approved medical cannabis users (MCUs; n = 53), and a sub-sample of recreational cannabis users (RCUs; n = 169) from a representative adult survey in Ontario (Canada). Samples were telephone-surveyed on identical measures, including select socio-demographic, substance and medication use, and health and disability measures. Based on initial bivariate comparisons, multivariate logistical regression with a progressive adjustment approach was performed to assess independent predictors of group status. RESULTS: In bivariate analyses, older age, lower household income, lower alcohol use, higher cocaine, prescription opioid, depression and anxiety medication use, and lower health and disability status were significantly associated with medical cannabis use. In the multivariate analysis, final model, household income, alcohol use, and disability levels were associated with medical cannabis use. Conclusions/Scientific Significance: Compared to RCUs, medical users appear to be mainly characterized by factors negatively influencing their overall health status. Future studies should investigate the actual impact and net benefits of medical cannabis use on these health problems.

Sativex Associated With Behavioral-Relapse Prevention Strategy as Treatment for Cannabis Dependence: A Case Series.

OBJECTIVES: Cannabis is the most commonly used illicit drug; a substantial minority of users develop dependence. The current lack of pharmacological treatments for cannabis dependence warrants the use of novel approaches and further investigation of promising pharmacotherapy. In this case series, we assessed the use of self-titrated dosages of Sativex (1:1, Δ-tetrahydrocannabinol [THC]/cannabidiol [CBD] combination) and motivational enhancement therapy and cognitive behavioral therapy (MET/CBT) for the treatment of cannabis dependence among 5 treatment-seeking community-recruited cannabis-dependent subjects. METHODS: Participants underwent a 3-month open-label self-titration phase with Sativex (up to 113.4 of THC/105 mg of CBD) and weekly MET/CBT, with a 3-month follow-up. RESULTS: Sativex was well-tolerated by all participants (average dosage 77.5 THC/71.7 mg CBD). The combination of Sativex and MET/CBT reduced the amount of cannabis use and progressively reduced craving and withdrawal scores. THC/CBD metabolite concentration indicated reduced cannabis use and compliance with medication. CONCLUSIONS: In summary, this pilot study found that with Sativex in combination with MET/CBT reduced cannabis use while preventing increases in craving and withdrawal in the 4 participants completing the study. Further systematic exploration of Sativex as a pharmacological treatment option for cannabis dependence should be performed.

Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The results found in this proof of concept study warrant further systematic exploration of Sativex as a treatment option for cannabis withdrawal and dependence.

Addressing the stimulant treatment gap: A call to investigate the therapeutic benefits potential of cannabinoids for crack-cocaine use.

Crack-cocaine use is prevalent in numerous countries, yet concentrated primarily - largely within urban contexts - in the Northern and Southern regions of the Americas. It is associated with a variety of behavioral, physical and mental health and social problems which gravely affect users and their environments. Few evidence-based treatments for crack-cocaine use exist and are available to users in the reality of street drug use. Numerous pharmacological treatments have been investigated but with largely disappointing results. An important therapeutic potential for crack-cocaine use may rest in cannabinoids, which have recently seen a general resurgence for varied possible therapeutic usages for different neurological diseases. Distinct potential therapeutic benefits for crack-cocaine use and common related adverse symptoms may come specifically from cannabidiol (CBD) - one of the numerous cannabinoid components found in cannabis - with its demonstrated anxiolytic, anti-psychotic, anti-convulsant effects and potential benefits for sleep and appetite problems. The possible therapeutic prospects of cannabinoids are corroborated by observational studies from different contexts documenting crack-cocaine users' 'self-medication' efforts towards coping with crack-cocaine-related problems, including withdrawal and craving, impulsivity and paranoia. Cannabinoid therapeutics offer further benefits of being available in multiple formulations, are low in adverse risk potential, and may easily be offered in community-based settings which may add to their feasibility as interventions for - predominantly marginalized - crack-cocaine user populations. Supported by the dearth of current therapeutic options for crack-cocaine use, we are advocating for the implementation of a rigorous research program investigating the potential therapeutic benefits of cannabinoids for crack-cocaine use. Given the high prevalence of this grave substance use problem in the Americas, opportunities for such research should urgently be created and facilitated there.

Medical Marijuana programs: implications for cannabis control policy--observations from Canada.

While prohibition has been the dominant regime of cannabis control in most countries for decades, an increasing number of countries have been implementing cannabis control reforms recently, including decriminalization or even legalization frameworks. Canada has held out from this trend, although it has among the highest cannabis use rates in the world. Cannabis use is universally criminalized, and the current (conservative) federal government has vowed not to implement any softening reforms to cannabis control. As a result of several higher court decisions, the then federal government was forced to implement a 'medical marijuana access regulations' program in 2001 to allow severely ill patients therapeutic use and access to therapeutic cannabis while shielding them from prosecution. The program's regulations and approval processes were complex and subject to extensive criticism; initial uptake was low and most medical marijuana users continued their use and supply outside the program's auspices. This year, the government introduced new 'marijuana for medical purposes regulations', which allow physicians to 'authorize' medical marijuana use for virtually any health condition for which this is considered beneficial; supply is facilitated by licensed commercial producers. It is expected that some 500,000 users, and dozens of commercial producers will soon be approved under the program, arguably constituting - as with medical marijuana schemes elsewhere, e.g. in California--de facto 'legalization'. We discuss the question whether the evolving scope and realities of 'medical cannabis' provisions in Canada offer a 'sneaky side door' or a 'better third way' to cannabis control reform, and what the potential wider implications are of these developments.

Comparing key characteristics of young adult crack users in and out-of-treatment in Rio de Janeiro, Brazil.

BACKGROUND: Crack use is prevalent among street drug users in Brazilian cities, yet despite recent help system reforms and investments, treatment utilization is low. Other studies have identified a variety of - often inconsistent - factors associated with treatment status among crack or other drug users. This study compared socio-economic, drug use, health and service use characteristics between samples of young adult crack users in- and out-of-treatment in Rio de Janeiro, Brazil. FINDINGS: Street-involved crack users (n = 81) were recruited by community-based methods, and privately assessed by way of an anonymous interviewer-administered questionnaire as well as biological methods, following informed consent. In-treatment users (n = 30) were recruited from a public service in-patient treatment facility and assessed based on the same protocol. Key indicators of interest were statistically cross-compared. Not-in-treatment users were less likely to: be white, educated, stably housed, to be involved in drug dealing, to report lifetime marijuana and current alcohol use, to report low mental health status and general health or addiction/mental health care; they were more likely to: be involved in begging and utilize social services, compared to the in-treatment sample (statistical significance for differences set at p < .05). CONCLUSIONS: In-treatment and not-in-treatment crack users differed on several key characteristics. Overall, in-treatment users appeared to be more socio-economically integrated and connected to the health system, yet not acutely needier in terms of health or drug problems. Given overall low treatment utilization but high need, efforts are required to facilitate improved treatment access and use for marginalized crack users in Brazil.

Public opinion towards supervised injection facilities and heroin-assisted treatment in Ontario, Canada.

In recent years, controversial interventions such as 'heroin-assisted treatment' (HAT) and 'supervised injection facilities' (SIFs) have been established in attempts to minimise the high morbidity and mortality consequences of illicit drug use. This paper examines public opinion towards HAT and SIF using data from the 2003 Centre for Addiction and Mental Health (CAMH) Monitor, a representative population survey conducted among adults residing in Ontario, Canada. Data relating specifically to SIFs and HAT were isolated from the main database (n=885); agreement scores were collapsed to create a scale and analysed using independent sample t-tests and ANOVAs. Results revealed that 60 percent (n=530) of the sample agreed that SIFs should be made available to injection drug users, while 40 percent (n=355) disagreed. When asked about the provision of HAT, a similar pattern emerged. Variables significantly associated with positive opinions toward SIFs and HAT were: income; higher education; the use of cocaine or cannabis within the last 12 months; being in favour of cannabis decriminalisation; support of needle exchange in prison; view of illicit drug users as ill people; and agreement that drug users are in need of public support. Given the current political climate and the tentative position of SIFs and HAT in Canada, understanding the public's opinion is crucial for the feasibility and long-term sustainability of these interventions.

Treatment for hepatitis C virus and cannabis use in illicit drug user patients: implications and questions.

Illicit drug users are the primary risk group for HCV transmission, and will form the largest HCV treatment population for years to come. Sylvestre et al.'s study suggests that cannabis use may benefit treatment retention and outcomes in illicit drug users undergoing HCV treatment. In fact, there is substantial evidence that cannabis use may help address key challenges faced by drug users in HCV treatment (e.g., nausea, depression), especially when such treatment occurs in the context of methadone maintenance treatment which may amplify these consequences. While further research is required on the biological and clinical aspects of the benefits of cannabis use for HCV treatment, and the effectiveness of cannabis use for HCV treatment needs to be explored in larger study populations, we advocate that in the interim existing barriers to cannabis use are removed for drug users undergoing HCV treatment until the conclusive empirical basis for evidence-based guidance is available.