Interaction between naltrexone and oral THC in heavy marijuana smokers

Psychopharmacology (Berl). 2003 Feb;166(1):77-85. doi: 10.1007/s00213-002-1279-8. Epub 2002 Dec 19.


Rationale: Studies in non-human animals suggest that opioid antagonists block the reinforcing effects of cannabinoids.

Objective: The present studies in humans investigated how naltrexone modulates (1) the subjective and physiological effects of oral THC in comparison to methadone, (2) the reinforcing effects of oral THC, and (3) plasma levels of oral THC.

Methods: In study 1, marijuana smokers (n=9) received naltrexone (0, 50 mg) followed 30 min later by THC (0, 15, 30 mg) or methadone (5, 10 mg). Subjective effects, task performance, pupillary diameter, and cardiovascular parameters were measured repeatedly. In study 2a, marijuana smokers (n=23) were randomly assigned to one THC dose condition (0, 15 or 30 mg). One set of color-coded capsules containing THC and active naltrexone (50 mg) was given in one session, while another set of color-coded capsules containing THC and placebo naltrexone was given in another session. In the final three sessions, participants chose which color capsules they would receive. In study 2b, a subset of participants from study 2a (n=7) received naltrexone (0, 50 mg) 30 min prior to oral THC (30 mg) administration, and blood was drawn repeatedly.

Results: Pretreatment with naltrexone significantly increased many of the "positive" subjective effects of oral THC (30 mg) e.g. ratings of Good Drug Effect and Capsule Liking. Naltrexone tended to increase the reinforcing effects of oral THC (30 mg), as indicated by performance in a drug choice test. Naltrexone did not alter plasma THC levels.

Conclusions: These studies demonstrate that naltrexone increases the subjective effects of oral THC. Thus, oral THC's effects are enhanced rather than antagonized by opioid receptor blockade in heavy marijuana smokers.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adult
  • Analgesics, Non-Narcotic / adverse effects
  • Analgesics, Non-Narcotic / pharmacokinetics*
  • Analysis of Variance
  • Choice Behavior / drug effects
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Dronabinol / adverse effects
  • Dronabinol / pharmacokinetics*
  • Drug Interactions*
  • Female
  • Heart Rate / drug effects
  • Humans
  • Male
  • Marijuana Smoking / blood
  • Marijuana Smoking / metabolism*
  • Marijuana Smoking / psychology
  • Methadone / pharmacology
  • Naltrexone / adverse effects
  • Naltrexone / pharmacology*
  • Narcotic Antagonists / adverse effects
  • Narcotic Antagonists / pharmacology*
  • Pain Measurement / drug effects
  • Psychomotor Performance / drug effects
  • Reaction Time / drug effects


  • Analgesics, Non-Narcotic
  • Narcotic Antagonists
  • Naltrexone
  • Dronabinol
  • Methadone