Effect of Lofexidine and Oral THC on Marijuana Withdrawal and Relapse

Sponsor

New York State Psychiatric Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00373503

Collaborator

National Institute on Drug Abuse (NIDA) (NIH)

Enrollment

Location

Arm

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the interaction between marijuana and two potential treatment medications: lofexidine and oral THC, with the direct goal of using this information to improve marijuana treatment outcome.

Condition or Disease	Intervention/Treatment	Phase
Marijuana Dependence	Drug: Lofexidine Drug: dronabinol Drug: Marijuana	Phase 2

Detailed Description

Only a small percentage of dependent-marijuana smokers who are seeking treatment for their marijuana use is able to achieve sustained abstinence. The objective of this study is to investigate the interaction between marijuana and two potential treatment medications: lofexidine and oral THC, with the direct goal of using this information to improve marijuana treatment outcome. In mice, the α2-receptor agonist, clonidine, reversed symptoms of cannabinoid withdrawal (Lichtman et al., 2001). The purpose of this study is to determine if lofexidine, an α2-receptor agonist with a more favorable side-effect profile than clonidine, decreases symptoms of marijuana withdrawal and thus decreases marijuana relapse, as compared to placebo. Oral THC is FDA-approved for appetite enhancement. Lofexidine, which is currently not FDA-approved, is used in Europe to treat symptoms of heroin withdrawal, and to treat hypertension. For the purposes of this model, relapse is defined to a return to marijuana use after a period of abstinence. We have shown that oral THC reduces symptoms of marijuana withdrawal at doses that produce minimal intoxication (Haney et al., 2004). Thus, the effects of oral THC alone and in combination with lofexidine will be determined. The study will utilize an inpatient/outpatient, counter-balanced design, with each participant maintained on each of four medication conditions for 8 days each: placebo, lofexidine, oral THC, and oral THC combined with lofexidine. During the inpatient study phases, participants will have the opportunity to self-administer placebo or active marijuana 6 times per day. Outpatient phases are for medication clearance so no medications will be administered. This study will provide important information of the effect of these potential treatment medications on both marijuana withdrawal symptoms, and on subsequent marijuana self-administration.

Study Design

Study Type:

Interventional

Actual Enrollment :

8 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

Effect of Lofexidine and Oral THC on Marijuana Withdrawal and Relapse

Study Start Date :

Aug 1, 2005

Actual Primary Completion Date :

Jun 1, 2007

Actual Study Completion Date :

Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: lofexidine, dronabinol, marijuana lofexidine (.6 mg qid), dronabinol (20 mg tid)	Drug: Lofexidine alpha 2 adrenergic agonist, hypothesized to decrease noradrenergic activity Other Names: Britlofex Drug: dronabinol cannabinoid agonist hypothesized to decrease MJ withdrawal Other Names: THC Drug: Marijuana marijuana intoxication, withdrawal and relapse assessed Other Names: cannabis

Arm

Intervention/Treatment

Experimental: lofexidine, dronabinol, marijuana

lofexidine (.6 mg qid), dronabinol (20 mg tid)

Drug: Lofexidine

alpha 2 adrenergic agonist, hypothesized to decrease noradrenergic activity

Other Names:

Britlofex

Drug: dronabinol

cannabinoid agonist hypothesized to decrease MJ withdrawal

Other Names:

THC

Drug: Marijuana

marijuana intoxication, withdrawal and relapse assessed

Other Names:

cannabis

Outcome Measures

Primary Outcome Measures

marijuana relapse [4 days]

Secondary Outcome Measures

marijuana withdrawal symptoms [3 days]

Other Outcome Measures

cardiovascular effects [7 days]

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, clinically significant laboratory abnormalities)
Bradycardia (55 beats/minute), hypotension (< 90 mmHg) including orthostatic hypotension (> 20 mmHg decrease in SP, or > 10 mmHg decrease in DP upon standing
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