Clinical trial NCT00373503: Effect of Lofexidine and Oral THC on Marijuana Withdrawal and Relapse
Official title: Effect of Lofexidine and Oral THC on Marijuana Withdrawal and Relapse
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Marijuana Dependence
Keywords: Lofexidine
Oral THC
Cannabinoids
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2006-09-08
Enrollment: 8
Sex: ALL
Minimum age (years): 21
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: marijuana relapse
timeFrame: 4 days
Secondary outcomes:
measure: marijuana withdrawal symptoms
timeFrame: 3 days
Other outcomes:
measure: cardiovascular effects
timeFrame: 7 days
Locations:
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
Study officials:
affiliation: New York State Psychiatric Institute
name: Margaret Haney, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: