title: Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Cannabis use disorder is associated with substantial morbidity and, after alcohol, is the most common drug bringing adolescents and adults into treatment. At present, there are no FDA-approved medications for cannabis use disorder. Combined pharmacologic interventions might be particularly useful in mitigating withdrawal symptoms and promoting abstinence.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, and lofexidine, an alpha-2 agonist, in treating cannabis dependence.
  
  
  METHODS
  One hundred fifty six cannabis-dependent adults were enrolled and following a 1-week placebo lead-in phase 122 were randomized in a double-blind, placebo-controlled, 11-week trial. Participants were randomized to receive dronabinol 20mg three times a day and lofexidine 0.6 mg three times a day or placebo. Medications were maintained until the end of week eight, were then tapered over two weeks and patients were monitored off medications during the last study week. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow-back method.
  
  
  RESULTS
  There was no significant difference between treatment groups in the proportion of participants who achieved 3 weeks of abstinence during the maintenance phase of the trial (27.9% for the medication group and 29.5% for the placebo group), although both groups showed a reduction over time.
  
  
  CONCLUSIONS
  Based on this treatment study, the combined intervention did not show promise as a treatment for cannabis use disorder.
authors.affiliation: New York State Psychiatric Institute, Division of Substance Abuse, 1051 Riverside Drive, New York, NY 10032, United States; Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, New York, NY 10032, United States. Electronic address: frl2@columbia.edu.
authors.forename: Frances R
authors.initials: FR
authors.lastname: Levin
authors.affiliation: New York State Psychiatric Institute, Division of Substance Abuse, 1051 Riverside Drive, New York, NY 10032, United States; Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, New York, NY 10032, United States.
authors.forename: John J
authors.initials: JJ
authors.lastname: Mariani
authors.affiliation: Department of Biostatistics, Columbia University, 722 West 168th Street, New York, NY 10032, United States.
authors.forename: Martina
authors.initials: M
authors.lastname: Pavlicova
authors.affiliation: New York State Psychiatric Institute, Division of Substance Abuse, 1051 Riverside Drive, New York, NY 10032, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Brooks
authors.affiliation: New York State Psychiatric Institute, Division of Biostatistics, 1051 Riverside Drive, New York, NY 10032, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Glass
authors.affiliation: New York State Psychiatric Institute, Division of Substance Abuse, 1051 Riverside Drive, New York, NY 10032, United States.
authors.forename: Amy
authors.initials: A
authors.lastname: Mahony
authors.affiliation: New York State Psychiatric Institute, Division of Substance Abuse, 1051 Riverside Drive, New York, NY 10032, United States; Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, New York, NY 10032, United States.
authors.forename: Edward V
authors.initials: EV
authors.lastname: Nunes
authors.affiliation: New York State Psychiatric Institute, Division of Substance Abuse, 1051 Riverside Drive, New York, NY 10032, United States; Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, New York, NY 10032, United States.
authors.forename: Adam
authors.initials: A
authors.lastname: Bisaga
authors.affiliation: New York State Psychiatric Institute, Division of Substance Abuse, 1051 Riverside Drive, New York, NY 10032, United States; Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, New York, NY 10032, United States.
authors.forename: Elias
authors.initials: E
authors.lastname: Dakwar
authors.affiliation: New York State Psychiatric Institute, Division of Substance Abuse, 1051 Riverside Drive, New York, NY 10032, United States; Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, New York, NY 10032, United States.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Carpenter
authors.affiliation: New York State Psychiatric Institute, Division of Substance Abuse, 1051 Riverside Drive, New York, NY 10032, United States; Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, New York, NY 10032, United States.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Sullivan
authors.affiliation: New York State Psychiatric Institute, Division of Biostatistics, 1051 Riverside Drive, New York, NY 10032, United States.
authors.forename: Jean C
authors.initials: JC
authors.lastname: Choi
mesh_terms: D000293:Adolescent; D000328:Adult; D063386:Cannabinoid Receptor Agonists / Q000627:therapeutic use; D003000:Clonidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D066249:Craving / Q000187:drug effects; D004311:Double-Blind Method; D013759:Dronabinol / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000188:drug therapy* / Q000517:prevention & control; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000627:therapeutic use; D055502:Secondary Prevention; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy; D016903:Drug Monitoring
chemical_list: D063386:Cannabinoid Receptor Agonists; D009292:Narcotic Antagonists; D013759:Dronabinol; D003000:Clonidine; C025655:lofexidine
keywords: Cannabis use disorder; Cannabis withdrawal; Dronabinol; Lofexidine; Marijuana dependence; Marinol