Plasma cannabinoid concentrations during dronabinol pharmacotherapy for cannabis dependence.
BACKGROUND
Recently, high-dose oral synthetic delta-9-tetrahydrocannabinol (THC) was shown to alleviate cannabis withdrawal symptoms. The present data describe cannabinoid pharmacokinetics in chronic, daily cannabis smokers who received high-dose oral THC pharmacotherapy and later a smoked cannabis challenge.


METHODS
Eleven daily cannabis smokers received 0, 30, 60, or 120 mg/d THC for four 5-day medication sessions, each separated by 9 days of ad libitum cannabis smoking. On the fifth day, participants were challenged with smoking one 5.9% THC cigarette. Plasma collected on the first and fifth days was quantified by two-dimensional gas chromatography mass spectrometer for THC, 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH). Linear ranges (ng/mL) were 0.5-100 for THC, 1-50 for 11-OH-THC, and 0.5-200 for THCCOOH.


RESULTS
During placebo dosing, THC, 11-OH-THC, and THCCOOH concentrations consistently decreased, whereas all cannabinoids increased dose dependently during active dronabinol administration. THC increase over time was not significant after any dose, 11-OH-THC increased significantly during the 60- and 120-mg/d doses, and THCCOOH increased significantly only during the 120-mg/d dose. THC, 11-OH-THC, and THCCOOH concentrations peaked within 0.25 hours after cannabis smoking, except after 120 mg/d THC when THCCOOH peaked 0.5 hours before smoking.


CONCLUSIONS
The significant withdrawal effects noted during placebo dronabinol administration were supported by significant plasma THC and 11-OH-THC concentration decreases. During active dronabinol dosing, significant dose-dependent increases in THC and 11-OH-THC concentrations support withdrawal symptom suppression. THC concentrations after cannabis smoking were only distinguishable from oral THC doses for 1 hour, too short a period to feasibly identify cannabis relapse. THCCOOH/THC ratios were higher 14 hours after overnight oral dronabinol abstinence but cannot distinguish oral THC dosing from the smoked cannabis intake.
*Chemistry and Drug Metabolism Section, Intramural Research Program, Biomedical Research Center, National Institute on Drug Abuse, National Institutes of Health; and †Behavioral Pharmacology Research Unit, Johns Hopkins Bayview Medical Center, Baltimore, MD.
Garry
G
Milman
Mateus M
MM
Bergamaschi
Dayong
D
Lee
Damodara R
DR
Mendu
Allan J
AJ
Barnes
Ryan
R
Vandrey
Marilyn A
MA
Huestis
D000293:Adolescent; D000328:Adult; D002186:Cannabinoids / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000097:blood* / Q000188:drug therapy*; D008385:Marijuana Smoking / Q000097:blood / Q000188:drug therapy; D008875:Middle Aged; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000188:drug therapy*; D055815:Young Adult
D002186:Cannabinoids; D013759:Dronabinol