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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
49
One capsule containing placebo was administered to the participant in a size 00 opaque capsules with lactose filler 45 minutes before marijuana administration.
One capsule containing placebo was administered to the participant in a size 00 opaque capsules with lactose filler 45 minutes before administration of a marijuana cigarette containing 3.27% THC (ca. 800 mg) provided by the National Institute on Drug Abuse.
One capsule containing 12mg Naltrexone was administered to the participant in a size 00 opaque capsules with lactose filler 45 minutes before active marijuana administration.
Change in Mean Subjective Mood Scores as a Function of Marijuana Strength and Naltrexone Dose.
All subjective effects were measured using visual analog scales (VAS), a series of 100 mm long lines labeled 'not at all' at one end (0 mm) and 'extremely' at the other end (100 mm). Participants were instructed to rate their subjective experiences on the line according to how they felt at that particular moment. Subjective assessments included measures of perceived marijuana strength, marijuana "high", "good effects" of marijuana, and how much marijuana was "liked". Marijuana's effects were determined by comparing the active and inactive marijuana conditions when paired with the placebo naltrexone condition (one comparison). Naltrexone's intrinsic effects were assessed by comparing placebo and each active dose of naltrexone (12, 25, 50, and 100 mg) under the inactive marijuana condition (four comparisons). Finally, the active marijuana- placebo naltrexone condition was compared to the active marijuana-active naltrexone conditions (four comparisons)
Time frame: Baseline compared to 6 week timepoint
Change in Mean Psychomotor Task Performance as a Function of Marijuana Strength and Naltrexone Dose
Change in Digit Symbol Substitution Test (DSST) scores. Increasing scores indicate improvement, on a scale of 0-90. The task batteries included total correct attempts on a 3-min DSST.
Time frame: Baseline compared to 6 week timepoint
Change in Mean Heart Rate as a Function of Marijuana Strength and Naltrexone Dose.
Change in mean heart rate as a function of marijuana and naltrexone dose
Time frame: Baseline compared to 6 week timepoint
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
One capsule containing 12mg Naltrexone was administered to the participant in a size 00 opaque capsules with lactose filler 45 minutes before active marijuana administration.
One capsule containing 25mg Naltrexone was administered to the participant in a size 00 opaque capsules with lactose filler 45 minutes before marijuana administration.
One capsule containing 50mg Naltrexone was administered to the participant in a size 00 opaque capsules with lactose filler 45 minutes before marijuana administration.
One capsule containing 12mg Naltrexone was administered to the participant in a size 00 opaque capsules with lactose filler 45 minutes before inactive marijuana administration.
One capsule containing 25mg Naltrexone was administered to the participant in a size 00 opaque capsules with lactose filler 45 minutes before inactive marijuana administration.
One capsule containing 50mg Naltrexone was administered to the participant in a size 00 opaque capsules with lactose filler 45 minutes before inactive marijuana administration.
One capsule containing 100mg Naltrexone was administered to the participant in a size 00 opaque capsules with lactose filler 45 minutes before inactive marijuana administration.