Effects of Low-dose Naltrexone in Combination With a Range of Smoked Marijuana

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00743145
• Collaborator: Research Foundation for Mental Hygiene, Inc. (Other), National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 23
• Location: 1
• Arms: 6
• Duration (Months): 16
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

In heavy marijuana smokers, opioid receptor blockade increases the subjective and cardiovascular effects of marijuana. The current study was designed to clarify opioid-cannabinoid interactions by assessing how naltrexone shifts the dose-response function for marijuana-elicited effects in heavy marijuana smokers. For this within-subject, double-blind study, a marijuana smoking procedure was designed to characterize a dose-response relationship for marijuana's subjective and cardiovascular effects under blinded conditions.

Condition or Disease	Intervention/Treatment	Phase
Marijuana Smoking	Drug: Inactive Marijuana (0% THC); Drug: Active Marijuana (5.5% THC); Drug: Active Marijuana (6.2% THC); Drug: Naltrexone; Drug: Placebo naltrexone	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Double-blind, placebo-controlled
• Primary Purpose: Basic Science
• Official Title: Effects of Low-dose Naltrexone in Combination With a Range of Smoked Marijuana
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Sep 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo naltrexone + Inactive marijuana Placebo naltrexone capsules (0mg), inactive marijuana (0% THC). Each study participant underwent 8 conditions in a randomized order.	Drug: Inactive Marijuana (0% THC); Marijuana cigarette containing 0% THC; Other Names: Cannabis ; Drug: Placebo naltrexone; Naltrexone (0mg); Other Names: PBO
Placebo Comparator: Placebo naltrexone + Active marijuana (5.5% THC) Placebo naltrexone capsules (0mg), active marijuana (5.5% THC). Each study participant underwent 8 conditions in a randomized order.	Drug: Active Marijuana (5.5% THC); Marijuana cigarette containing 5.5% THC; Other Names: Cannabis ; Drug: Placebo naltrexone; Naltrexone (0mg); Other Names: PBO
Placebo Comparator: Placebo naltrexone + Active marijuana (6.2% THC) Placebo naltrexone capsules (0mg), active marijuana (6.2% THC). Each study participant underwent 8 conditions in a randomized order.	Drug: Active Marijuana (6.2% THC); Marijuana cigarette containing 6.2% THC; Other Names: Cannabis ; Drug: Placebo naltrexone; Naltrexone (0mg); Other Names: PBO
Experimental: Naltrexone + Active marijuana (5.5% THC) Naltrexone capsules (12mg), active marijuana (5.5% THC). Each study participant underwent 8 conditions in a randomized order.	Drug: Active Marijuana (5.5% THC); Marijuana cigarette containing 5.5% THC; Other Names: Cannabis ; Drug: Naltrexone; Naltrexone (12mg/70kg); Other Names: Revia
Experimental: Naltrexone + Active marijuana (6.2% THC) Naltrexone capsules (0mg), active marijuana (6.2% THC). Each study participant underwent 8 conditions in a randomized order.	Drug: Active Marijuana (6.2% THC); Marijuana cigarette containing 6.2% THC; Other Names: Cannabis ; Drug: Naltrexone; Naltrexone (12mg/70kg); Other Names: Revia
Placebo Comparator: Naltrexone + Inactive marijuana Naltrexone capsules (12mg), inactive marijuana (0% THC). Each study participant underwent 8 conditions in a randomized order.	Drug: Inactive Marijuana (0% THC); Marijuana cigarette containing 0% THC; Other Names: Cannabis ; Drug: Naltrexone; Naltrexone (12mg/70kg); Other Names: Revia

Outcome Measures

Primary Outcome Measures

1. Subjective Marijuana Effects [180 minutes after marijuana administration, during each of 8 outpatient sessions over the course of 3-6 weeks.]

   Subjective ratings of marijuana's quality and effect ('Strength', 'Good Effect', 'High', 'Stimulation') and craving ('Want Marijuana') as a function of active puffs and naltrexone, using a visual analogue scale with 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 indicate how they felt at that particular moment. Higher ratings indicate more agreement with the statement.

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

• Able to perform study procedures

• 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, hepatitis, clinically significant laboratory abnormalities, LFTs

3x upper limit of normal, blood pressure > 140/90

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
• Research Foundation for Mental Hygiene, Inc.
• 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

None provided.

• Responsible Party: Margaret Haney, Clinical Psychaitrist, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT00743145
• Other Study ID Numbers: IRB# 5693; DA19239
• First Posted: Aug 28, 2008
• Last Update Posted: Sep 14, 2018
• Last Verified: Aug 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Margaret Haney, Clinical Psychaitrist, New York State Psychiatric Institute: naltrexone; smoked marijuana; marijuana use
• Additional relevant MeSH terms: Marijuana Abuse; Marijuana Use; Naltrexone

Study Results

Participant Flow

Arm/Group Title	Placebo, Naltrexone, Marijuana
Arm/Group Description	A total of 23 participants enrolled but only 19 completed. All patients participated in all conditions; they were randomized to placebo or naltrexone treatment in a counterbalanced fashion, and underwent all smoking conditions in separate, counterbalanced sessions.
Period Title: Overall Study
STARTED	23
COMPLETED	19
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Placebo, Naltrexone, Marijuana
Arm/Group Description	During each of the 8 outpatient sessions, participants smoked a total of 6 puffs from 3 marijuana cigarettes (2 puffs from each cigarette). Marijuana administration occurred 45 minutes after capsule administration. The number of active versus inactive cigarettes smoked during each session varied, according to active puff conditions (i.e., 0 puffs = 3 inactive cigarettes; 2 puffs = 1 active + 2 inactive cigarette; 4 puffs = 2 active + 1 inactive cigarette; 6 puffs = 3 active + 0 inactive cigarette). Cigarettes were color coded, indicating the order in which they were to be smoked and active cigarettes were always smoked before inactive. A within-subject design was used in which all participants were exposed to each of the puff conditions in combination with naltrexone or placebo. The order of naltrexone dosing and puff condition was randomized within the session and across participants.
Overall Participants	19
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	19 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	27.0 (4.0)
Sex: Female, Male (Count of Participants)
Female	1 5.3%
Male	18 94.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	10 52.6%
White	8 42.1%
More than one race	0 0%
Unknown or Not Reported	1 5.3%
Region of Enrollment (Count of Participants)
United States	19 100%

Outcome Measures

1. Primary Outcome

Title	Subjective Marijuana Effects
Description	Subjective ratings of marijuana's quality and effect ('Strength', 'Good Effect', 'High', 'Stimulation') and craving ('Want Marijuana') as a function of active puffs and naltrexone, using a visual analogue scale with 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 indicate how they felt at that particular moment. Higher ratings indicate more agreement with the statement.
Time Frame	180 minutes after marijuana administration, during each of 8 outpatient sessions over the course of 3-6 weeks.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo Naltrexone + Inactive Marijuana	Placebo Naltrexone + Active Marijuana (5.5% THC)	Placebo Naltrexone + Active Marijuana (6.2% THC)	Naltrexone + Active Marijuana (5.5% THC)	Naltrexone + Active Marijuana (6.2% THC)	Naltrexone + Inactive Marijuana
Arm/Group Description	Placebo naltrexone capsules (0mg), inactive marijuana (0% THC). Each study participant underwent 8 conditions in a randomized order. Inactive Marijuana (0% THC): Marijuana cigarette containing 0% THC Placebo naltrexone: Naltrexone (0mg)	Placebo naltrexone capsules (0mg), active marijuana (5.5% THC). Each study participant underwent 8 conditions in a randomized order. Active Marijuana (5.5% THC): Marijuana cigarette containing 5.5% THC Placebo naltrexone: Naltrexone (0mg)	Placebo naltrexone capsules (0mg), active marijuana (6.2% THC). Each study participant underwent 8 conditions in a randomized order. Active Marijuana (6.2% THC): Marijuana cigarette containing 6.2% THC Placebo naltrexone: Naltrexone (0mg)	Naltrexone capsules (12mg), active marijuana (5.5% THC). Each study participant underwent 8 conditions in a randomized order. Active Marijuana (5.5% THC): Marijuana cigarette containing 5.5% THC Naltrexone: Naltrexone (12mg/70kg)	Naltrexone capsules (0mg), active marijuana (6.2% THC). Each study participant underwent 8 conditions in a randomized order. Active Marijuana (6.2% THC): Marijuana cigarette containing 6.2% THC Naltrexone: Naltrexone (12mg/70kg)	Naltrexone capsules (12mg), inactive marijuana (0% THC). Each study participant underwent 8 conditions in a randomized order. Inactive Marijuana (0% THC): Marijuana cigarette containing 0% THC Naltrexone: Naltrexone (12mg/70kg)
Measure Participants	19	19	19	19	19	19
"Marijuana Strength"	13 (1)	15 (1)	16 (2)	16 (2)	20 (2)	16 (2)
"Marijuana Good Effect"	14 (2)	37 (3)	30 (2.5)	31 (3)	46 (2)	26 (2)
"Marijuana High"	10 (1)	10.5 (0.5)	10 (1)	11 (1.5)	16 (1.5)	10 (1.5)
"Marijuana Stimulation"	16 (2)	20 (2)	16 (2)	20 (1.5)	30 (2)	22 (2)
"Want Marijuana"	50 (1.5)	48 (1)	37 (1.5)	49 (1)	45 (1.5)	50 (1.5)

Adverse Events

Time Frame	4 weeks for each treatment and 1 week after receiving last treatment.
Adverse Event Reporting Description	Safety population included all participants who received at least one intervention. Research staff routinely asked participants to report any adverse events occurring during study sessions and during outpatient washout periods.
Arm/Group Title	Placebo Naltrexone + Inactive Marijuana (0.0% THC)		Placebo Naltrexone + Active Marijuana (5.5% THC)		Placebo Naltrexone + Active Marijuana (6.2% THC)		Naltrexone + Inactive Marijuana (0.0% THC)		Naltrexone + Active Marijuana (5.5% THC)		Naltrexone + Active Marijuana (6.2% THC)
Arm/Group Description	0mg naltrexone + 0.0% THC marijuana		0mg naltrexone + 5.5% THC marijuana		0mg naltrexone + 6.2% THC marijuana		12mg naltrexone + 0.0% THC marijuana		12mg naltrexone + 5.5% THC marijuana		12mg naltrexone + 6.2% THC marijuana
All Cause Mortality
	Placebo Naltrexone + Inactive Marijuana (0.0% THC)		Placebo Naltrexone + Active Marijuana (5.5% THC)		Placebo Naltrexone + Active Marijuana (6.2% THC)		Naltrexone + Inactive Marijuana (0.0% THC)		Naltrexone + Active Marijuana (5.5% THC)		Naltrexone + Active Marijuana (6.2% THC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/23 (0%)		0/23 (0%)		0/23 (0%)		0/23 (0%)		0/23 (0%)
Serious Adverse Events
	Placebo Naltrexone + Inactive Marijuana (0.0% THC)		Placebo Naltrexone + Active Marijuana (5.5% THC)		Placebo Naltrexone + Active Marijuana (6.2% THC)		Naltrexone + Inactive Marijuana (0.0% THC)		Naltrexone + Active Marijuana (5.5% THC)		Naltrexone + Active Marijuana (6.2% THC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/23 (0%)		0/23 (0%)		0/23 (0%)		0/23 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	Placebo Naltrexone + Inactive Marijuana (0.0% THC)		Placebo Naltrexone + Active Marijuana (5.5% THC)		Placebo Naltrexone + Active Marijuana (6.2% THC)		Naltrexone + Inactive Marijuana (0.0% THC)		Naltrexone + Active Marijuana (5.5% THC)		Naltrexone + Active Marijuana (6.2% THC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/23 (0%)		0/23 (0%)		0/23 (0%)		0/23 (0%)		0/23 (0%)

Limitations/Caveats

This study is limited by its small sample size, and portion of males to females.

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.