Effect of Lofexidine and Oral THC on Marijuana Withdrawal and Relapse

NCT ID: NCT00373503

Last Updated: 2013-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-08-31
• Study Completion Date: 2008-09-30

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.

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.

Conditions

Marijuana Dependence

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

lofexidine, dronabinol, marijuana

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

Group Type: EXPERIMENTAL

Lofexidine

Intervention Type: DRUG

alpha 2 adrenergic agonist, hypothesized to decrease noradrenergic activity

dronabinol

Intervention Type: DRUG

cannabinoid agonist hypothesized to decrease MJ withdrawal

Marijuana

Intervention Type: DRUG

marijuana intoxication, withdrawal and relapse assessed

Interventions

Lofexidine

alpha 2 adrenergic agonist, hypothesized to decrease noradrenergic activity

Intervention Type: DRUG

dronabinol

cannabinoid agonist hypothesized to decrease MJ withdrawal

Intervention Type: DRUG

Marijuana

marijuana intoxication, withdrawal and relapse assessed

Intervention Type: DRUG

Other Intervention Names

Britlofex; THC; cannabis

Eligibility 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, 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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

New York State Psychiatric Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Margaret Haney, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

New York State Psychiatric Institute

Locations

New York State Psychiatric Institute

New York, New York, United States

Countries

United States

Other Identifiers

R01DA019239

Identifier Type: NIH

Identifier Source: secondary_id

View Link

4942

Identifier Type: -

Identifier Source: org_study_id