Substitution profile of Δ9-tetrahydrocannabinol, triazolam, hydromorphone, and methylphenidate in humans discriminating Δ9-tetrahydrocannabinol

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30 Scopus citations


Rationale: Preclinical evidence suggests that non-cannabinoid neurotransmitter systems are involved in the behavioral and physiological effects of cannabinoids, but relatively little research has been conducted in humans. Objectives: The aims of this study were to assess whether oral Δ9-tetrahydrocannabinol (Δ9-THC) would function as a discriminative stimulus in humans and to examine the substitution profile of drugs acting at opioid, GABA, and dopamine systems. Methods: Healthy subjects who reported moderate cannabis use were enrolled. Subjects learned to identify when they received oral 25 mg Δ9-THC or placebo under double-blind conditions. Once subjects acquired the discrimination (i.e., ≥80% drug-appropriate responding for four consecutive sessions), multiple doses of Δ9-THC, the GABAA positive modulator triazolam, the μ-opioid agonist hydromorphone and the dopamine reuptake inhibitor methylphenidate were tested to determine if they shared discriminative-stimulus effects with the training dose of Δ9- THC. Results: Eight subjects (N∈=∈8) accurately discriminated Δ9-THC and completed the study. The training dose of Δ9-THC functioned as a discriminative stimulus and produced prototypical subject-rated drug effects. All of the drugs tested produced significant effects on the self-report questionnaires, but only Δ9-THC substituted for the training dose. Conclusion: These results suggest that the discriminative-stimulus effects of Δ9- THC in humans are not directly mediated through central neurotransmitter systems acted upon by the drugs tested in this study.

Original languageEnglish
Pages (from-to)241-250
Number of pages10
Issue number2
StatePublished - Apr 2009

Bibliographical note

Funding Information:
This research and the preparation of this manuscript were supported by grants from the National Institute on Drug Abuse (K01 DA018772) and the University of Kentucky Research Foundation awarded to Dr. Joshua A. Lile. Support was also provided by a Center for Biomedical Research Excellence (P20 RR015592) awarded to Dr. Thomas Curry and a General Clinical Research Center (M01 RR002602) awarded to Dr. Jay Perman by the National Center for Research Resources. The authors do not have any financial relationship with these funding sources.


  • Cannabis
  • Drug-discrimination
  • Hydromorphone
  • Marijuana
  • Methylphenidate
  • Subjective effects
  • Triazolam
  • Δ-THC

ASJC Scopus subject areas

  • Pharmacology


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