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 Citations (Scopus)

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 - 2014
Externally publishedYes

Fingerprint

Marijuana Abuse
Dronabinol
Cannabinoids
Drug Therapy
Cannabis
Marijuana Smoking
Substance Withdrawal Syndrome

Keywords

  • Cannabinoids
  • Dronabinol
  • Oral administration
  • Plasma
  • Smoking

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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

Plasma cannabinoid concentrations during dronabinol pharmacotherapy for cannabis dependence. / Milman, Garry; Bergamaschi, Mateus M.; Lee, Dayong; Mendu, Damodara R.; Barnes, Allan J.; Vandrey, Ryan; Huestis, Marilyn A.

In: Therapeutic Drug Monitoring, Vol. 36, No. 2, 2014, p. 218-224.

Research output: Contribution to journalArticle

Milman, G, Bergamaschi, MM, Lee, D, Mendu, DR, Barnes, AJ, Vandrey, R & Huestis, MA 2014, 'Plasma cannabinoid concentrations during dronabinol pharmacotherapy for cannabis dependence', Therapeutic Drug Monitoring, vol. 36, no. 2, pp. 218-224. https://doi.org/10.1097/FTD.0b013e3182a5c446
Milman, Garry ; Bergamaschi, Mateus M. ; Lee, Dayong ; Mendu, Damodara R. ; Barnes, Allan J. ; Vandrey, Ryan ; Huestis, Marilyn A. / Plasma cannabinoid concentrations during dronabinol pharmacotherapy for cannabis dependence. In: Therapeutic Drug Monitoring. 2014 ; Vol. 36, No. 2. pp. 218-224.
@article{88ce001262354c8d9b3e2f20e7a6abe3,
title = "Plasma cannabinoid concentrations during dronabinol pharmacotherapy for cannabis dependence",
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.",
keywords = "Cannabinoids, Dronabinol, Oral administration, Plasma, Smoking",
author = "Garry Milman and Bergamaschi, {Mateus M.} and Dayong Lee and Mendu, {Damodara R.} and Barnes, {Allan J.} and Ryan Vandrey and Huestis, {Marilyn A.}",
year = "2014",
doi = "10.1097/FTD.0b013e3182a5c446",
language = "English (US)",
volume = "36",
pages = "218--224",
journal = "Therapeutic Drug Monitoring",
issn = "0163-4356",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

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 - 2014

Y1 - 2014

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.

AB - 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.

KW - Cannabinoids

KW - Dronabinol

KW - Oral administration

KW - Plasma

KW - Smoking

UR - http://www.scopus.com/inward/record.url?scp=84897031414&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897031414&partnerID=8YFLogxK

U2 - 10.1097/FTD.0b013e3182a5c446

DO - 10.1097/FTD.0b013e3182a5c446

M3 - Article

C2 - 24067260

AN - SCOPUS:84897031414

VL - 36

SP - 218

EP - 224

JO - Therapeutic Drug Monitoring

JF - Therapeutic Drug Monitoring

SN - 0163-4356

IS - 2

ER -