TY - JOUR T1 - Plasma cannabinoid concentrations during dronabinol pharmacotherapy for cannabis dependence. AU - Milman,Garry, AU - Bergamaschi,Mateus M, AU - Lee,Dayong, AU - Mendu,Damodara R, AU - Barnes,Allan J, AU - Vandrey,Ryan, AU - Huestis,Marilyn A, PY - 2013/9/27/entrez PY - 2013/9/27/pubmed PY - 2015/2/11/medline SP - 218 EP - 24 JF - Therapeutic drug monitoring JO - Ther Drug Monit VL - 36 IS - 2 N2 - 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. SN - 1536-3694 UR - https://www.unboundmedicine.com/medline/citation/24067260/Plasma_cannabinoid_concentrations_during_dronabinol_pharmacotherapy_for_cannabis_dependence_ L2 - https://doi.org/10.1097/FTD.0b013e3182a5c446 DB - PRIME DP - Unbound Medicine ER -