title: Separate and combined effects of the cannabinoid agonists nabilone and Δ⁹-THC in humans discriminating Δ⁹-THC.
abstract: BACKGROUND
  Agonist replacement treatment is a promising strategy to manage cannabis-use disorders. The aim of this study was to assess the combined effects of the synthetic cannabinoid agonist nabilone and Δ⁹-tetrahydrocannabinol (Δ⁹-THC) using drug-discrimination procedures, which are sensitive to drug interactions. Testing the concurrent administration of nabilone and Δ⁹-THC was also conducted to provide initial safety and tolerability data, which is important because cannabis users will likely lapse during treatment.
  
  
  METHODS
  Six cannabis users learned to discriminate 30 mg oral Δ⁹-THC from placebo and then received nabilone (0, 1 and 3mg) and Δ⁹-THC (0, 5, 15 and 30 mg), alone and in combination. Subjects completed the multiple-choice procedure to assess drug reinforcement, and self-report, task performance and physiological measures were collected.
  
  
  RESULTS
  Δ⁹-THC and nabilone alone shared discriminative-stimulus effects with the training dose of Δ⁹-THC, increased crossover point on the multiple-choice procedure, produced overlapping subject ratings and decreased skin temperature. Nabilone alone also elevated heart rate. In combination, nabilone shifted the discriminative-stimulus effects of Δ⁹-THC leftward/upward and enhanced Δ⁹-THC effects on the other outcome measures.
  
  
  CONCLUSIONS
  These results replicate a previous study demonstrating that nabilone shares agonist effects with the active constituent of cannabis in cannabis users, and contribute further by indicating that nabilone would likely be safe and well tolerated when combined with cannabis. These data support the conduct of future studies to determine if nabilone treatment would produce cross-tolerance to the abuse-related effects of cannabis and reduce cannabis use.
authors.affiliation: Department of Behavioral Science, University of Kentucky College of Medicine, College of Medicine Office Building, Lexington, KY 40536-0086, USA. jalile2@email.uky.edu
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Lile
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Kelly
authors.forename: Lon R
authors.initials: LR
authors.lastname: Hays
mesh_terms: D000046:Academic Medical Centers; D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids / Q000008:administration & dosage / Q000819:agonists / Q000494:pharmacology / Q000627:therapeutic use; D004193:Discrimination Learning; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000188:drug therapy*; D010045:Outpatients; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D011619:Psychotropic Drugs / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014151:Anti-Anxiety Agents; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids; D010919:Placebos; D011619:Psychotropic Drugs; C011941:nabilone; D013759:Dronabinol