Separate and combined effects of the cannabinoid agonists nabilone and Δ 9-THC in humans discriminating Δ 9-THC

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31 Scopus citations


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 Δ 9-tetrahydrocannabinol (Δ 9-THC) using drug-discrimination procedures, which are sensitive to drug interactions. Testing the concurrent administration of nabilone and Δ 9-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 30mg oral Δ 9-THC from placebo and then received nabilone (0, 1 and 3mg) and Δ 9-THC (0, 5, 15 and 30mg), 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: Δ 9-THC and nabilone alone shared discriminative-stimulus effects with the training dose of Δ 9-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 Δ 9-THC leftward/upward and enhanced Δ 9-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.

Original languageEnglish
Pages (from-to)86-92
Number of pages7
JournalDrug and Alcohol Dependence
Issue number1-3
StatePublished - Jul 1 2011

Bibliographical note

Funding Information:
This research and the preparation of this manuscript were supported by grant from the National Institute on Drug Abuse (K01 DA018772 and R01 DA025605) awarded to Dr. Joshua Lile. Support was also provided in part by a Center for Biomedical Research Excellence (P20 RR015592) awarded to Dr. Thomas Curry from the National Center for Research Resources and a grant from the University of Kentucky Center for Clinical and Translational Science. These funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.


  • Agonist replacement
  • Cardiovascular
  • Digit-symbol-substitution task
  • Drug discrimination
  • Marijuana
  • Multiple-choice procedure
  • Repeated acquisition task
  • Subjective effects
  • Temperature
  • Time reproduction

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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