Separate and combined effects of the GABA reuptake inhibitor tiagabine and Δ 9-THC in humans discriminating Δ 9-THC

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20 Scopus citations


Background: The involvement of non-cannabinoid neurotransmitter systems in the abuse-related behavioral effects of cannabis has not been well characterized in humans. GABAergic drugs have overlapping effects with cannabis and Δ 9-tetrahydrocannabinol (Δ 9-THC) on certain behavioral measures, but those measures lack the specificity to draw conclusions regarding the involvement of GABA in cannabinoid effects. The aim of this study was to assess the separate and combined effects of the GABA reuptake inhibitor tiagabine and Δ 9-THC using more pharmacologically specific drug-discrimination procedures. Methods: Eight cannabis users learned to discriminate 30mg oral Δ 9-THC from placebo and then received tiagabine (6 and 12mg), Δ 9-THC (5, 15 and 30mg) and placebo, alone and in combination. Self-report, task performance and physiological measures were also collected. Results: Δ 9-THC produced subjective effects typically associated with cannabinoids (e.g., High, Stoned, Like Drug), elevated heart rate and impaired rate and accuracy on psychomotor performance tasks. The higher tiagabine dose substituted for the Δ 9-THC discriminative stimulus and engendered subjective and performance-impairing effects that overlapped with those of Δ 9-THC when administered alone. In combination, tiagabine shifted the discriminative-stimulus effects of Δ 9-THC leftward/upward and enhanced Δ 9-THC effects on other outcomes. Conclusions: These results indicate that GABA is involved in the clinical effects of Δ 9-THC, and by extension, cannabis. Future studies should test selective GABAergic compounds to determine which receptor subtype(s) are responsible for the effects observed when combined with cannabinoids.

Original languageEnglish
Pages (from-to)61-69
Number of pages9
JournalDrug and Alcohol Dependence
Issue number1-2
StatePublished - Apr 1 2012

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 R01 DA025605 ) awarded to Dr. Joshua Lile. 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.


  • Cardiovascular
  • Digit-symbol-substitution task
  • Drug-discrimination
  • Marijuana
  • Repeated acquisition task
  • Subjective effects

ASJC Scopus subject areas

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


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