Separate and combined effects of the GABA(B) agonist baclofen and Δ9-THC in humans discriminating Δ9-THC.
BACKGROUND
Our previous research with the GABA reuptake inhibitor tiagabine suggested the involvement GABA in the interoceptive effects of Δ9-THC. The aim of the present study was to determine the potential involvement of the GABA(B) receptor subtype by assessing the separate and combined effects of the GABA(B)-selective agonist baclofen and Δ9-THC using pharmacologically specific drug-discrimination procedures.


METHODS
Eight cannabis users learned to discriminate 30 mg oral Δ9-THC from placebo and then received baclofen (25 and 50mg), Δ9-THC (5, 15 and 30 mg) and placebo, alone and in combination. Self-report, task performance and physiological measures were also collected.


RESULTS
Δ9-THC functioned as a discriminative stimulus, produced subjective effects typically associated with cannabinoids (e.g., High, Stoned, Like Drug), elevated heart rate and impaired rate and accuracy on a psychomotor performance task. Baclofen alone (50 mg) substituted for the Δ9-THC discriminative stimulus, and both baclofen doses shifted the discriminative-stimulus effects of Δ9-THC leftward/upward. Similar results were observed on other cannabinoid-sensitive outcomes, although baclofen generally did not engender Δ9-THC-like subjective responses when administered alone.


CONCLUSIONS
These results suggest that the GABA(B) receptor subtype is involved in the abuse-related effects of Δ9-THC, and that GABA(B) receptors were responsible, at least in part, for the effects of tiagabine-induced elevated GABA on cannabinoid-related behaviors in our previous study. Future research should test GABAergic compounds selective for other GABA receptor subtypes (i.e., GABA(A)) to determine the contribution of the different GABA receptors in the effects of Δ9-THC, and by extension cannabis, in humans.
Department of Behavioral Science, University of Kentucky, College of Medicine, Medical Behavioral Sciences Building, Lexington, KY 40536-0086, USA. jalile2@email.uky.edu
Joshua A
JA
Lile
Thomas H
TH
Kelly
Lon R
LR
Hays
D000293:Adolescent; D000328:Adult; D001418:Baclofen / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects; D003710:Demography; D004192:Discrimination, Psychological / Q000187:drug effects*; D013759:Dronabinol / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D018755:GABA Agonists / Q000627:therapeutic use*; D006213:Hallucinogens / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000523:psychology; D011597:Psychomotor Performance / Q000187:drug effects; D018080:Receptors, GABA-B / Q000187:drug effects*; D012959:Socioeconomic Factors; D019966:Substance-Related Disorders / Q000523:psychology; D011795:Surveys and Questionnaires; D013998:Time Perception / Q000187:drug effects; D055815:Young Adult
D018755:GABA Agonists; D006213:Hallucinogens; D018080:Receptors, GABA-B; D013759:Dronabinol; D001418:Baclofen