Plasma cannabinoid concentrations during dronabinol pharmacotherapy for cannabis dependence

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

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)218-224
Number of pages7
JournalTherapeutic Drug Monitoring
Volume36
Issue number2
DOIs
StatePublished - Apr 2014

Keywords

  • Cannabinoids
  • Dronabinol
  • Oral administration
  • Plasma
  • Smoking

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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  • Cite this

    Milman, G., Bergamaschi, M. M., Lee, D., Mendu, D. R., Barnes, A. J., Vandrey, R., & Huestis, M. A. (2014). Plasma cannabinoid concentrations during dronabinol pharmacotherapy for cannabis dependence. Therapeutic Drug Monitoring, 36(2), 218-224. https://doi.org/10.1097/FTD.0b013e3182a5c446