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Plasma Cannabinoid Concentrations During Dronabinol Pharmacotherapy for Cannabis Dependence

Milman, Garry PhD*; Bergamaschi, Mateus M. PhD*; Lee, Dayong MSc*; Mendu, Damodara R. PhD*; Barnes, Allan J. BS*; Vandrey, Ryan PhD; Huestis, Marilyn A. PhD*

doi: 10.1097/FTD.0b013e3182a5c446
Original Article

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.

Correspondence: Marilyn A. Huestis, PhD, Chemistry and Drug Metabolism Section, Intramural Research Program, Biomedical Research Center, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Boulevard, Rm 05A-721, Baltimore, MD 21224 (e-mail:

Supported by grant R01-DA025044 from the US National Institute on Drug Abuse and the National Institutes of Health, Intramural Research Program of the National Institute on Drug Abuse.

The authors declare no conflict of interest.

Received April 19, 2013

Accepted July 18, 2013

© 2014 by Lippincott Williams & Wilkins