title: Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings.
abstract: 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.
authors.affiliation: Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, Canada.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Trigo
authors.affiliation: Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, Canada.
authors.forename: Dina
authors.initials: D
authors.lastname: Lagzdins
authors.affiliation: Social and Epidemiological Research Department, CAMH, Toronto, Canada; Addiction Policy, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada; Institute of Medical Science, University of Toronto, Faculty of Medicine, Toronto, Canada; Department of Psychiatry, University of Toronto, Canada; Institute of Clinical Psychology and Psychotherapy & Center of Clinical Epidemiology and Longitudinal Studies (CELOS), Technische Universität Dresden, Dresden, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rehm
authors.affiliation: Department of Psychiatry, University of Toronto, Canada; Addictions Division, CAMH, Toronto, Canada; Department of Family and Community Medicine, University of Toronto, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Selby
authors.affiliation: Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, Canada; Department of Medical Sciences, Institute of Environmental Studies and Research, Ain Shams University, Cairo, Egypt; Directorate of Poison Control Centres, MOH, Riyadh, Saudi Arabia.
authors.forename: Islam
authors.initials: I
authors.lastname: Gamaleddin
authors.affiliation: Social and Epidemiological Research Department, CAMH, Toronto, Canada; Department of Psychiatry, University of Toronto, Canada; Centre for Applied Research in Mental Health & Addiction, Faculty of Health Sciences, Simon Fraser University, Vancouver, Canada.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Fischer
authors.affiliation: Chemistry and Drug Metabolism, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Baltimore, USA.
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Barnes
authors.affiliation: Chemistry and Drug Metabolism, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Baltimore, USA.
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
authors.affiliation: Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, Canada; Addictions Division, CAMH, Toronto, Canada. Electronic address: bernard.lefoll@camh.ca.
authors.forename: Bernard
authors.initials: B
authors.lastname: Le Foll
mesh_terms: D000328:Adult; D002185:Cannabidiol; D002188:Cannabis / Q000009:adverse effects*; D066249:Craving / Q000187:drug effects*; D004311:Double-Blind Method; D013759:Dronabinol; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000188:drug therapy*; D008385:Marijuana Smoking; D008875:Middle Aged; D010936:Plant Extracts / Q000008:administration & dosage* / Q000627:therapeutic use; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D019966:Substance-Related Disorders / Q000188:drug therapy; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D010936:Plant Extracts; D002185:Cannabidiol; D013759:Dronabinol; C587251:nabiximols
keywords: Cannabidiol; Cannabis; Clinical trials.gov ID# NCT01748799; Marijuana; THC; Withdrawal