Interaction between naltrexone and oral THC in heavy marijuana smokers.
BACKGROUND
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.
Haney
Margaret
M
New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA. mh235@columbia.edu
Bisaga
Adam
A
Foltin
Richard W
RW
D000284:Administration, Oral; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D002755:Choice Behavior / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000009:adverse effects / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008385:Marijuana Smoking / Q000097:blood / Q000378:metabolism* / Q000523:psychology; D008691:Methadone / Q000494:pharmacology; D009271:Naltrexone / Q000009:adverse effects / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects
D018712:Analgesics, Non-Narcotic; D009292:Narcotic Antagonists; D009271:Naltrexone; D013759:Dronabinol; D008691:Methadone