Cannabis (Cannabis sativa)
Interaction between naltrexone and oral THC in heavy marijuana smokers
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Rationale: Studies in non-human animals sug- gest 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 perfor- mance, pupillary diameter, and cardiovascular parameters were measured repeatedly. In study 2a, marijuana smok- ers (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 signif- icantly 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 demon- strate 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.
1 . Effect of naltrexone on THC concentration (id=NPDI-Rsay5Q)
In Vivo Interaction Study
No Effect (based on bioequivalence limits) was detected.
(Table 2)
Results
Table 2. Cmax of control at t = 240 min; Cmax of test at t = 120 min. P value significance extrapolated from statement within the text: "Table 2, which portrays plasma levels of D9-THC and the metabolite THC-C as a function of naltrexone dose, demonstrates that naltrexone had no significant effect on plasma levels of either compound."
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
(Table 1, Study 2b)
Fixed-sequence
Placebo-controlled
Healthy volunteers
Males
Regular marijuana use
Smokers
Black or African American
Hispanic or Latino
White
7
African American: 3
Caucasian: 1
Hispanic: 3
Marijuana use (days per week): 5 (2)
Marijuana cigarettes/day: 5 (3)
Cigarette smokers: 7
Cigarettes per day: 12 (9)
(mean ± SD)
(Table 1)
0, 30, 60, 120, 180 min
Drug or Natural Product Administration
Oral
Capsule
30 mg
Once
Oral
tablet
50 mg
Once
Not specified
Pharmacodynamics (PD) & Adverse Events
A subset of participants experienced side effects such as nausea, stomach cramping, vomiting, and headache. Specifically, following placebo naltrexone administration, the only dose condition associated with side effects was methadone (10 mg), in which three of the nine partici- pants experienced one of the above symptoms. Active naltrexone increased the likelihood participants would experience side effects in each condition except metha- done (10 mg). Following active naltrexone administra- tion, two participants had side effects in the 15 mg THC condition, while five experienced side effects in the 30 mg THC condition. Four participants had side effects follow- ing 5 mg methadone, while two had side effects following 10 mg methadone.