title: Pharmacokinetic and pharmacodynamic profile of supratherapeutic oral doses of Δ(9) -THC in cannabis users.
abstract: Oral Δ(9) -tetrahydrocannabinol (Δ(9) -THC) has been evaluated as a medication for cannabis dependence, but repeated administration of acute oral doses up to 40 mg has not been effective at reducing drug-taking behavior. Larger doses might be necessary to affect cannabis use. The purpose of the present study was therefore to determine the physiological and behavioural effects of oral Δ(9) -THC at acute doses higher than those tested previously. The pharmacokinetic and pharmacodynamic profile of oral Δ(9) -THC, administered in ascending order in 15 mg increments across separate sessions, up to a maximum of 90 mg, was determined in seven cannabis users. Five subjects received all doses and two experienced untoward side effects at lower doses. Δ(9) -THC produced a constellation of effects consistent with previous clinical studies. Low cannabinoid concentrations were associated with significant effects on drug-sensitive measures, although progressively greater levels did not lead to proportionately larger drug effects. Considerable variability in Cmax and tmax was observed. Doses of oral Δ(9) -THC larger than those tested previously can be administered to individuals with a history of cannabis use, although given the pharmacokinetic variability of oral Δ(9) -THC and individual differences in sensitivity, individualized dose adjustment is needed to avoid side effects and maximize therapeutic response.
authors.affiliation: Department of Behavioural Science, University of Kentucky College of Medicine, Lexington, KY 40536‐0086, USA. jalile2@email.uky.edu
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Lile
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Kelly
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Charnigo
authors.forename: Audra L
authors.initials: AL
authors.lastname: Stinchcomb
authors.forename: Lon R
authors.initials: LR
authors.lastname: Hays
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002188:Cannabis / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000188:drug therapy* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D013759:Dronabinol