Effect of Baclofen on Marijuana Withdrawal and Relapse

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00373295
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 13
• Location: 1
• Arms: 6
• Duration (Months): 44.1
• Patients Per Site Per Month: 0.3

Study Details

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
• 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 1, 2006
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: cannabis ; Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Measure of Relapse: Change in Money Spent Between Baseline and Relapse Phase [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

Criteria

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

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

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

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
• First Posted: Sep 8, 2006
• Last Update Posted: May 10, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by New York State Psychiatric Institute: Baclofen; Marijuana Dependence; Marijuana Withdrawal
• Additional relevant MeSH terms: Marijuana Abuse; Baclofen

Study Results

Participant Flow

Pre-assignment Detail	13 participants were enrolled, but 10 participants were randomized. Three volunteers (1 female, 2 male) dropped out of the study during the marijuana abstinence phase (two were on baclofen and one was on placebo).

Arm/Group Title	Baclofen 60 mg, Placebo, Baclofen 90 mg	Baclofen 90 mg, Placebo, Baclofen 60 mg	Baclofen 60 mg, Baclofen 90 mg, Placebo	Baclofen 90 mg, Baclofen 60 mg, Placebo	Placebo, Baclofen 90 mg, Baclofen 60 mg	Placebo, Baclofen 60 mg, Baclofen 90 mg
Arm/Group Description	participants received baclofen (60 mg/day) for 8 days, followed by placebo for 8 days, then baclofen (90mg/day) for 8 days.	participants received baclofen (90mg/day) for 8 days, followed by placebo for 8 days, then baclofen (60mg/day) for 8 days.	participants received baclofen (60mg/day) for 8 days, followed by baclofen (90mg/day) for 8 days, then placebo for 8 days.	participants received baclofen (90mg/day) for 8 days, followed by baclofen (60mg/day) for 8 days, and then placebo for 8 days.	participants received placebo for 8 days, followed by baclofen (90mg/day) for 8 days, then baclofen (60mg/day) for 8 days.	participants received placebo for 8 days, followed by baclofen (60mg/day) for 8 days, then baclofen (90mg/day) for 8 days.
Period Title: Intervention 1 (8 Days)
STARTED	2	3	1	2	3	2
COMPLETED	2	1	1	2	2	2
NOT COMPLETED	0	2	0	0	1	0
Period Title: Intervention 1 (8 Days)
STARTED	2	1	1	2	2	2
COMPLETED	2	1	1	2	2	2
NOT COMPLETED	0	0	0	0	0	0
Period Title: Intervention 1 (8 Days)
STARTED	2	1	1	2	2	2
COMPLETED	2	1	1	2	2	2
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Participants received placebo, baclofen (60mg) and baclofen (90mg) and smoked Marijuana (5.3% THC).
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	1 10%
Male	9 90%
Region of Enrollment (Count of Participants)
United States	10 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baclofen 60, Marijuana	Placebo, Marijuana	Baclofen 90, Marijuana
Arm/Group Description	baclofen (60 mg)/day Baclofen: measured baclofen's effects on marijuana withdrawal and relapse relative to placebo Marijuana: measured baclofen's effects on marijuana withdrawal and relapse	baclofen (90 mg)/day Baclofen: measured baclofen's effects on marijuana withdrawal and relapse relative to placebo Marijuana: measured baclofen's effects on marijuana withdrawal and relapse
Measure Participants	13	13	13
Mean (Standard Deviation) [dollars spent on marijuana]	7.15 (1.85)	9.77 (2.30)	7.25 (2.10)

Adverse Events

Arm/Group Title	Baclofen 60, Marijuana		Baclofen 90, Marijuana		Placebo, Marijuana
Arm/Group Description	baclofen (60 mg)/day Baclofen: measured baclofen's effects on marijuana withdrawal and relapse relative to placebo Marijuana: measured baclofen's effects on marijuana withdrawal and relapse		baclofen (90 mg)/day Baclofen: measured baclofen's effects on marijuana withdrawal and relapse relative to placebo Marijuana: measured baclofen's effects on marijuana withdrawal and relapse		Marijuana: measured baclofen's effects on marijuana withdrawal and relapse
All Cause Mortality
	Baclofen 60, Marijuana		Baclofen 90, Marijuana		Placebo, Marijuana
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Baclofen 60, Marijuana		Baclofen 90, Marijuana		Placebo, Marijuana
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/13 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Baclofen 60, Marijuana		Baclofen 90, Marijuana		Placebo, Marijuana
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/13 (15.4%)		0/13 (0%)		0/13 (0%)
Social circumstances
mild headache	2/13 (15.4%)	2	0/13 (0%)	0	0/13 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.