Effect of Baclofen on Marijuana Withdrawal and Relapse

• ClinicalTrials.gov Identifier: NCT00373295
• Recruitment Status: Completed
• First Posted: September 8, 2006
• Results First Posted: May 10, 2017
• Last Update Posted: May 10, 2017
• Sponsor: New York State Psychiatric Institute
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): New York State Psychiatric Institute

Study Description

Brief Summary:

The purpose of this study is to determine if baclofen dose-dependently decreases marijuana's direct effects and symptoms of marijuana withdrawal and thus decreases marijuana relapse.

Condition or disease	Intervention/treatment	Phase
Marijuana Dependence	Drug: Baclofen; Drug: Marijuana; Drug: Placebo	Phase 2

Detailed Description:

Only a small percentage of dependent-marijuana smokers who are seeking treatment for their marijuana use are able to achieve sustained abstinence. The objective of this study is to investigate the interaction between marijuana and the potential treatment medication, baclofen, with the direct goal of using this information to improve marijuana treatment outcome. GABAB agonists such as baclofen have been shown to attenuate the self-administration of cocaine, heroin, alcohol and nicotine (see Cousins et al., 2002; Haney et al., 2006). Baclofen also appears to decrease withdrawal symptoms in heroin and alcohol abusers (Akhondzadeh et al., 2000; Addolorato et al., 2000). The purpose of this study is to determine if baclofen dose-dependently decreases marijuana's direct effects and symptoms of marijuana withdrawal and thus decreases marijuana relapse in our laboratory model. For the purposes of this model, relapse is defined as a return to marijuana use after a period of abstinence. The study will utilize an inpatient/outpatient, counter-balanced design, with each participant maintained on each of three medication conditions for 16 days: placebo and baclofen (60, 90 mg/day). Participants will begin taking capsules during the outpatient phase so that the dose can be incremented up to the maintenance dose prior to the first inpatient day. Further, clinical studies have shown that baclofen is most effective at decreasing cocaine's effects when administered for several weeks. During the inpatient study phases, participants will have the opportunity to self-administer placebo or active marijuana 6 times per day. This study will provide important information of the effect of baclofen as a potential treatment medication for marijuana dependence.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Effect of Baclofen on Marijuana Withdrawal and Relapse
• Study Start Date: May 2006
• Actual Primary Completion Date: January 2008
• Actual Study Completion Date: January 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Baclofen 60 mg, Placebo, Baclofen 90 mg; Baclofen (60mg/day or 90 mg/day): Packaged medication in size 00 opaque capsules with riboflavin filler. Study capsules (0, 20, 30mg) were administered 3 times per day (0900, 1530, 2200). Marijuana: Participants each received a single marijuana cigarette (provided by the National Institute on Drug Abuse) at each smoking occasion. Marijuana cigarettes were stored frozen in an airtight container and humidified at room temperature for 24 h prior to use.	Drug: Baclofen; Baclofen (60mg/day or 90 mg/day): Packaged medication in size 00 opaque capsules with riboflavin filler. Study capsules (0, 20, 30mg) were administered 3 times per day (0900, 1530, 2200).; Other Name: Lioresal; Drug: Marijuana; Marijuana: Participants each received a single marijuana cigarette (provided by the National Institute on Drug Abuse) at each smoking occasion. Marijuana cigarettes were stored frozen in an airtight container and humidified at room temperature for 24 h prior to use.; Other Name: cannabis; Drug: Placebo
Experimental: Baclofen 90 mg, Placebo, Baclofen 60 mg; Baclofen (60mg/day or 90 mg/day): Packaged medication in size 00 opaque capsules with riboflavin filler. Study capsules (0, 20, 30mg) were administered 3 times per day (0900, 1530, 2200). Marijuana: Participants each received a single marijuana cigarette (provided by the National Institute on Drug Abuse) at each smoking occasion. Marijuana cigarettes were stored frozen in an airtight container and humidified at room temperature for 24 h prior to use.	Drug: Baclofen; Baclofen (60mg/day or 90 mg/day): Packaged medication in size 00 opaque capsules with riboflavin filler. Study capsules (0, 20, 30mg) were administered 3 times per day (0900, 1530, 2200).; Other Name: Lioresal; Drug: Marijuana; Marijuana: Participants each received a single marijuana cigarette (provided by the National Institute on Drug Abuse) at each smoking occasion. Marijuana cigarettes were stored frozen in an airtight container and humidified at room temperature for 24 h prior to use.; Other Name: cannabis; Drug: Placebo
Experimental: Baclofen 60 mg, Baclofen 90 mg, Placebo; Baclofen (60mg/day or 90 mg/day): Packaged medication in size 00 opaque capsules with riboflavin filler. Study capsules (0, 20, 30mg) were administered 3 times per day (0900, 1530, 2200). Marijuana: Participants each received a single marijuana cigarette (provided by the National Institute on Drug Abuse) at each smoking occasion. Marijuana cigarettes were stored frozen in an airtight container and humidified at room temperature for 24 h prior to use.	Drug: Baclofen; Baclofen (60mg/day or 90 mg/day): Packaged medication in size 00 opaque capsules with riboflavin filler. Study capsules (0, 20, 30mg) were administered 3 times per day (0900, 1530, 2200).; Other Name: Lioresal; Drug: Marijuana; Marijuana: Participants each received a single marijuana cigarette (provided by the National Institute on Drug Abuse) at each smoking occasion. Marijuana cigarettes were stored frozen in an airtight container and humidified at room temperature for 24 h prior to use.; Other Name: cannabis; Drug: Placebo
Experimental: Baclofen 90 mg, Baclofen 60 mg, Placebo; Baclofen (60mg/day or 90 mg/day): Packaged medication in size 00 opaque capsules with riboflavin filler. Study capsules (0, 20, 30mg) were administered 3 times per day (0900, 1530, 2200). Marijuana: Participants each received a single marijuana cigarette (provided by the National Institute on Drug Abuse) at each smoking occasion. Marijuana cigarettes were stored frozen in an airtight container and humidified at room temperature for 24 h prior to use.	Drug: Baclofen; Baclofen (60mg/day or 90 mg/day): Packaged medication in size 00 opaque capsules with riboflavin filler. Study capsules (0, 20, 30mg) were administered 3 times per day (0900, 1530, 2200).; Other Name: Lioresal; Drug: Marijuana; Marijuana: Participants each received a single marijuana cigarette (provided by the National Institute on Drug Abuse) at each smoking occasion. Marijuana cigarettes were stored frozen in an airtight container and humidified at room temperature for 24 h prior to use.; Other Name: cannabis; Drug: Placebo
Experimental: Placebo, Baclofen 90 mg, Baclofen 60 mg; Baclofen (60mg/day or 90 mg/day): Packaged medication in size 00 opaque capsules with riboflavin filler. Study capsules (0, 20, 30mg) were administered 3 times per day (0900, 1530, 2200). Marijuana: Participants each received a single marijuana cigarette (provided by the National Institute on Drug Abuse) at each smoking occasion. Marijuana cigarettes were stored frozen in an airtight container and humidified at room temperature for 24 h prior to use.	Drug: Baclofen; Baclofen (60mg/day or 90 mg/day): Packaged medication in size 00 opaque capsules with riboflavin filler. Study capsules (0, 20, 30mg) were administered 3 times per day (0900, 1530, 2200).; Other Name: Lioresal; Drug: Marijuana; Marijuana: Participants each received a single marijuana cigarette (provided by the National Institute on Drug Abuse) at each smoking occasion. Marijuana cigarettes were stored frozen in an airtight container and humidified at room temperature for 24 h prior to use.; Other Name: cannabis; Drug: Placebo
Experimental: Placebo, Baclofen 60 mg, Baclofen 90 mg; Baclofen (60mg/day or 90 mg/day): Packaged medication in size 00 opaque capsules with riboflavin filler. Study capsules (0, 20, 30mg) were administered 3 times per day (0900, 1530, 2200). Marijuana: Participants each received a single marijuana cigarette (provided by the National Institute on Drug Abuse) at each smoking occasion. Marijuana cigarettes were stored frozen in an airtight container and humidified at room temperature for 24 h prior to use.	Drug: Baclofen; Baclofen (60mg/day or 90 mg/day): Packaged medication in size 00 opaque capsules with riboflavin filler. Study capsules (0, 20, 30mg) were administered 3 times per day (0900, 1530, 2200).; Other Name: Lioresal; Drug: Marijuana; Marijuana: Participants each received a single marijuana cigarette (provided by the National Institute on Drug Abuse) at each smoking occasion. Marijuana cigarettes were stored frozen in an airtight container and humidified at room temperature for 24 h prior to use.; Other Name: cannabis; Drug: Placebo

Outcome Measures

Primary Outcome Measures :

1. Measure of Relapse: Change in Money Spent Between Baseline and Relapse Phase [ Time Frame: Days 1-3 (Baseline) and Days 6-8 (Relapse Phase) ]

   This is a measure of marijuana self-administration and relapse since each initial puff costs $7 and is a burden to overcome just to smoke.

   Over each 3 day period, the puffs chosen by each participant is averaged for a single value.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Current marijuana use: average of 3 marijuana cigarettes at least 4 times per week for the past 4 weeks
• Able to perform study procedures
• 21-45 years of age
• Women practicing an effective form of birth control (condoms, diaphragm, birth control pill, IUD)

Exclusion Criteria:

• Current, repeated illicit drug use (other than marijuana)
• Presence of significant medical illness(e.g., diabetes, cardiovascular disease, hypertension, examination, laboratory clinically significant laboratory abnormalities)
• History of heart disease
• Request for drug treatment
• Current parole or probation
• Pregnancy or current lactation
• Recent history of significant violent behavior
• Major current Axis I psychopathology(e.g., major depressive disorder, bipolar disorder, suicide risk, schizophrenia)
• Current use of any prescription or over-the-counter medication

Contacts and Locations

Locations

United States, New York

New York State Psychiatric Institute

New York, New York, United States, 10032

Sponsors and Collaborators

New York State Psychiatric Institute

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Margaret Haney, Ph.D.; New York State Psychiatric Institute

More Information

Publications:

Haney M, Hart CL, Vosburg SK, Comer SD, Reed SC, Cooper ZD, Foltin RW. Effects of baclofen and mirtazapine on a laboratory model of marijuana withdrawal and relapse. Psychopharmacology (Berl). 2010 Aug;211(2):233-44. doi: 10.1007/s00213-010-1888-6. Epub 2010 Jun 3.

• Responsible Party: New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT00373295
• Other Study ID Numbers: 5232; 5P50DA009236 ( U.S. NIH Grant/Contract )
• First Posted: September 8, 2006
• Results First Posted: May 10, 2017
• Last Update Posted: May 10, 2017
• Last Verified: March 2017

Keywords provided by New York State Psychiatric Institute:

Baclofen; Marijuana Dependence; Marijuana Withdrawal

Additional relevant MeSH terms:

Marijuana Abuse; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Baclofen; Muscle Relaxants, Central; Physiological Effects of Drugs; Neuromuscular Agents; Peripheral Nervous System Agents; GABA-B Receptor Agonists; GABA Agonists; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action