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

February 15, 2018 updated by: New York State Psychiatric Institute

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

49

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo, 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.
One capsule containing placebo was administered to the participant in a size 00 opaque capsules with lactose filler 45 minutes before marijuana administration.
Other Names:
  • treatment type 1
Experimental: Placebo, 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.
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.
Other Names:
  • treatment type 2
Experimental: Naltrexone (12mg), 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.
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.
Other Names:
  • treatment type 7
Experimental: Naltrexone (12mg), 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.
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.
Other Names:
  • Treatment type 3
Experimental: Naltrexone (25mg), 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.
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.
Other Names:
  • treatment type 8
Experimental: Naltrexone (25mg), 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.
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.
Other Names:
  • treatment type 4
Experimental: Naltrexone (50mg), 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.
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.
Other Names:
  • treatment type 9
Experimental: Naltrexone (50mg), 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.
One capsule containing 25mg Naltrexone was administered to the participant in a size 00 opaque capsules with lactose filler 45 minutes before marijuana administration.
Other Names:
  • treatment type 5
Experimental: Naltrexone (100mg), 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.
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.
Other Names:
  • treatment type 10
Experimental: Naltrexone (100mg), 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.
One capsule containing 50mg Naltrexone was administered to the participant in a size 00 opaque capsules with lactose filler 45 minutes before marijuana administration.
Other Names:
  • treatment type 6

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Mean Subjective Mood Scores as a Function of Marijuana Strength and Naltrexone Dose.
Time Frame: 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)

Baseline compared to 6 week timepoint
Change in Mean Psychomotor Task Performance as a Function of Marijuana Strength and Naltrexone Dose
Time Frame: Baseline 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.

Baseline compared to 6 week timepoint
Change in Mean Heart Rate as a Function of Marijuana Strength and Naltrexone Dose.
Time Frame: Baseline compared to 6 week timepoint
Change in mean heart rate as a function of marijuana and naltrexone dose
Baseline compared to 6 week timepoint

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2006

Primary Completion (Actual)

May 1, 2008

Study Completion (Actual)

August 1, 2010

Study Registration Dates

First Submitted

November 21, 2006

First Submitted That Met QC Criteria

November 21, 2006

First Posted (Estimate)

November 23, 2006

Study Record Updates

Last Update Posted (Actual)

March 15, 2018

Last Update Submitted That Met QC Criteria

February 15, 2018

Last Verified

February 1, 2018

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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