Substitution profile of the cannabinoid agonist nabilone in human subjects discriminating δ9-tetrahydrocannabinol.
OBJECTIVE
The central effects of Δ-tetrahydrocannabinol (Δ-THC), the primary active constituent of cannabis, are attributed to cannabinoid CB1 receptor activity, although clinical evidence is limited. Drug discrimination has proven useful for examining the neuropharmacology of drugs, as data are concordant with the actions of a drug at the receptor level. The aim of this study was to determine the profile of behavioral and physiological effects of the cannabinoid agonist nabilone in humans trained to discriminate Δ-THC.


METHODS
Six cannabis users learned to identify when they received oral Δ-THC (25 mg) or placebo and then received a range of doses of the cannabinoid agonists nabilone (1, 2, 3, and 5 mg) and Δ-THC (5, 10, 15, and 25 mg). The dopamine reuptake inhibitor methylphenidate (5, 10, 20, and 30 mg) was included as a negative control. Subjects completed the Multiple-Choice Procedure, and self-report, task performance, and physiological measures were collected.


RESULTS
Nabilone shared discriminative-stimulus effects with the training dose of Δ-THC, produced subject-rated drug effects that were comparable to those of Δ-THC, and increased heart rate. Methylphenidate did not engender Δ-THC-like discriminative-stimulus effects.


CONCLUSIONS
These data demonstrate that the interoceptive effects of nabilone are similar to Δ-THC in cannabis users. The overlap in their behavioral effects is likely due to their shared mechanism as CB1 receptor agonists. Given the relative success of agonist replacement therapy to manage opioid, tobacco, and stimulant dependence, these results also support the evaluation of nabilone as a potential medication for cannabis-use disorders.
Lile
Joshua A
JA
Department of Behavioral Science, College of Medicine, University of Kentucky, Lexington, KY 40536-0086, USA. jalile2@email.uky.edu
Kelly
Thomas H
TH
Hays
Lon R
LR
D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000175:diagnosis*; D008774:Methylphenidate / Q000008:administration & dosage; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
D014151:Anti-Anxiety Agents; D008774:Methylphenidate; C011941:nabilone; D013759:Dronabinol