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

New York State Psychiatric Institute

Status and phase: Completed; Phase 2

Conditions: Marijuana Use

Treatments: Drug: Placebo + Active Marijuana (3.27% THC); Drug: Naltrexone 100 Mg + Inactive Marijuana (0% THC); Drug: Placebo + Inactive Marijuana (0% THC); Drug: Naltrexone 50 Mg + Inactive Marijuana (0% THC); Drug: Naltrexone 50 Mg+ Active Marijuana (3.27% THC); Drug: Naltrexone 12 Mg + Inactive Marijuana (0% THC); Drug: Naltrexone 25 Mg + Inactive Marijuana (0% THC); Drug: Naltrexone 100 Mg+ Active Marijuana (3.27% THC); Drug: Naltrexone 25 Mg + Active Marijuana (3.27% THC); Drug: Naltrexone 12 Mg+ Active Marijuana (3.27% THC)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00403117

DA09236 (Other Grant/Funding Number)

IRB# 5350

Details and patient eligibility

About

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.

Full 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.

Enrollment: 49 patients

Sex: All

Ages: 21 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Double Blind

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49 participants in 10 patient groups, including a placebo group

Placebo, Marijuana (0% THC)

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo + Inactive Marijuana (0% THC)

Placebo, Marijuana (3.27% THC)

Experimental group

Description:

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.

Treatment:

Drug: Placebo + Active Marijuana (3.27% THC)

Naltrexone (12mg), Marijuana (0% THC)

Experimental group

Description:

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.

Treatment:

Drug: Naltrexone 12 Mg + Inactive Marijuana (0% THC)

Naltrexone (12mg), Marijuana (3.27% THC)

Experimental group

Description:

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.

Treatment:

Drug: Naltrexone 12 Mg+ Active Marijuana (3.27% THC)

Naltrexone (25mg), Marijuana (0% THC)

Experimental group

Description:

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.

Treatment:

Drug: Naltrexone 25 Mg + Inactive Marijuana (0% THC)

Naltrexone (25mg), Marijuana (3.27% THC)

Experimental group

Description:

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.

Treatment:

Drug: Naltrexone 25 Mg + Active Marijuana (3.27% THC)

Naltrexone (50mg), Marijuana (0% THC)

Experimental group

Description:

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.

Treatment:

Drug: Naltrexone 50 Mg + Inactive Marijuana (0% THC)

Naltrexone (50mg), Marijuana (3.27% THC)

Experimental group

Description:

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.

Treatment:

Drug: Naltrexone 50 Mg+ Active Marijuana (3.27% THC)

Naltrexone (100mg), Marijuana (0% THC)

Experimental group

Description:

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.

Treatment:

Drug: Naltrexone 100 Mg + Inactive Marijuana (0% THC)

Naltrexone (100mg), Marijuana (3.27% THC)

Experimental group

Description:

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.

Treatment:

Drug: Naltrexone 100 Mg+ Active Marijuana (3.27% THC)