Effects of a Range of Naltrexone Doses in Combination With Smoked Marijuana

Opioid Antagonism Enhances Marijuana's Effects in Heavy Marijuana Smokers

The purpose of this study is to determine if the subjective effects of marijuana will be decreased by low-doses (< 25 mg) of naltrexone and increased by high-doses (> 50 mg) of naltrexone.

Laboratory animal studies demonstrate that endogenous cannabinoids and opioids are closely inter-related. We have completed a series of studies in marijuana smokers showing that a clinically-utilized dose of naltrexone (50 mg) enhanced the reinforcing and subjective effects of orally-administered tetrahydrocannabinol (THC), while a low naltrexone dose (12 mg) blunted the effects of THC. A better understanding of the effects of a range of naltrexone doses in combination with smoked marijuana has important implications for the following reasons: (1) Alcohol- and opioid-dependent patients receive high doses of naltrexone (50-150 mg), which may increase the abuse liability of marijuana, (2) Low-dose naltrexone blunts THC's intoxicating effects, suggesting potential utility as a treatment medication for marijuana dependence. This study will determine if naltrexone (0, 12, 25, 50, 100 mg) administration 45 min prior to marijuana administration (0, 3.27% THC) alters marijuana's subjective, cognitive or physiological effects. Marijuana smokers will spend approximately 5h/day for a total of 10 days in the outpatient laboratory. Participants will visit the outpatient laboratory 2-3 times per week, with a minimum 48-hr interval between sessions to allow for naltrexone clearance. These data will provide important information regarding the clinical use of naltrexone.

Inclusion Criteria:

• Current marijuana use
• Able to perform study procedures
• 21-45 years of age
• Women practicing an effective form of birth control

Exclusion Criteria:

• Current, repeated illicit drug use (other than marijuana)
• Presence of significant medical illness (e.g., diabetes, cardiovascular disease, hypertension, examination, laboratory hepatitis, clinically significant laboratory abnormalities, tests, 12-lead ECG, Mantoux test LFTs > 3x upper limit of normal)
• History of heart disease
• Request for drug treatment
• Current parole or probation
• Pregnancy or current lactation
• Recent history of significant violent behavior
• Previous adverse reaction to naltrexone
• Major current Axis I psychopathology Psychiatric interview (e.g., major depressive disorder, bipolar disorder, suicide risk, schizophrenia)
• Current use of any prescription or over-the-counter medication