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

Registration Number
NCT00403117
Lead Sponsor
New York State Psychiatric Institute
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
49
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Naltrexone (100mg), Marijuana (3.27% THC)Naltrexone 100 Mg+ Active Marijuana (3.27% THC)During each session, one capsule containing naltrexone (100 mg) was administered to the participant in a size 00 opaque capsule with lactose filler. A marijuana cigarette (3.27% THC; ca. 800 mg) provided by the National Institute on Drug Abuse, was administered 45 minutes post capsule administration.
Naltrexone (25mg), Marijuana (3.27% THC)Naltrexone 25 Mg + Active Marijuana (3.27% THC)During each session, one capsule containing naltrexone (25 mg) was administered to the participant in a size 00 opaque capsule with lactose filler. A marijuana cigarette (3.27% THC; ca. 800 mg) provided by the National Institute on Drug Abuse, was administered 45 minutes post capsule administration.
Naltrexone (50mg), Marijuana (0% THC)Naltrexone 50 Mg + Inactive Marijuana (0% THC)During each session, one capsule containing naltrexone (50 mg) was administered to the participant in a size 00 opaque capsule with lactose filler. A marijuana cigarette (0% THC; ca. 800 mg) provided by the National Institute on Drug Abuse, was administered 45 minutes post capsule administration.
Naltrexone (100mg), Marijuana (0% THC)Naltrexone 100 Mg + Inactive Marijuana (0% THC)During each session, one capsule containing naltrexone (100 mg) was administered to the participant in a size 00 opaque capsule with lactose filler. A marijuana cigarette (0% THC; ca. 800 mg) provided by the National Institute on Drug Abuse, was administered 45 minutes post capsule administration.
Naltrexone (12mg), Marijuana (0% THC)Naltrexone 12 Mg + Inactive Marijuana (0% THC)During each session, one capsule containing naltrexone (12 mg) was administered to the participant in a size 00 opaque capsule with lactose filler. A marijuana cigarette (0% THC; ca. 800 mg) provided by the National Institute on Drug Abuse, was administered 45 minutes post capsule administration.
Naltrexone (12mg), Marijuana (3.27% THC)Naltrexone 12 Mg+ Active Marijuana (3.27% THC)During each session, one capsule containing naltrexone (12 mg) was administered to the participant in a size 00 opaque capsule with lactose filler. A marijuana cigarette (3.27% THC; ca. 800 mg) provided by the National Institute on Drug Abuse, was administered 45 minutes post capsule administration.
Naltrexone (50mg), Marijuana (3.27% THC)Naltrexone 50 Mg+ Active Marijuana (3.27% THC)During each session, one capsule containing naltrexone (50 mg) was administered to the participant in a size 00 opaque capsule with lactose filler. A marijuana cigarette (3.27% THC; ca. 800 mg) provided by the National Institute on Drug Abuse, was administered 45 minutes post capsule administration.
Placebo, Marijuana (0% THC)Placebo + Inactive Marijuana (0% THC)During each session, one capsule containing placebo was administered to the participant in a size 00 opaque capsule with lactose filler. A marijuana cigarette (0% THC; ca. 800 mg) provided by the National Institute on Drug Abuse, was administered 45 minutes post capsule administration.
Naltrexone (25mg), Marijuana (0% THC)Naltrexone 25 Mg + Inactive Marijuana (0% THC)During each session, one capsule containing naltrexone (25 mg) was administered to the participant in a size 00 opaque capsule with lactose filler. A marijuana cigarette (0% THC; ca. 800 mg) provided by the National Institute on Drug Abuse, was administered 45 minutes post capsule administration.
Placebo, Marijuana (3.27% THC)Placebo + Active Marijuana (3.27% THC)During each session, one capsule containing placebo was administered to the participant in a size 00 opaque capsule with lactose filler. A marijuana cigarette (3.27% THC; ca. 800 mg) provided by the National Institute on Drug Abuse, was administered 45 minutes post capsule administration.
Primary Outcome Measures
NameTimeMethod
Change in Mean Subjective Mood Scores as a Function of Marijuana Strength and Naltrexone Dose.Baseline compared to 6 week timepoint

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)

Change in Mean Psychomotor Task Performance as a Function of Marijuana Strength and Naltrexone DoseBaseline compared to 6 week timepoint

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.

Change in Mean Heart Rate as a Function of Marijuana Strength and Naltrexone Dose.Baseline compared to 6 week timepoint

Change in mean heart rate as a function of marijuana and naltrexone dose

Secondary Outcome Measures
NameTimeMethod
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