Effect of Lofexidine and Oral THC on Marijuana Withdrawal and Relapse

Study Description

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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

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	8 participants
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 :	August 2005
Actual Primary Completion Date :	June 2007
Actual Study Completion Date :	September 2008

Arms and Interventions

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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 Name: Britlofex Drug: dronabinol; cannabinoid agonist hypothesized to decrease MJ withdrawal; Other Name: THC Drug: Marijuana; marijuana intoxication, withdrawal and relapse assessed; Other Name: cannabis

Outcome Measures

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Primary Outcome Measures :

1. marijuana relapse [ Time Frame: 4 days ]

Secondary Outcome Measures :

1. marijuana withdrawal symptoms [ Time Frame: 3 days ]

Other Outcome Measures:

1. cardiovascular effects [ Time Frame: 7 days ]

Eligibility Criteria

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Ages Eligible for Study:	21 Years to 45 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

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Locations

United States, New York
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

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	New York State Psychiatric Institute
ClinicalTrials.gov Identifier:	NCT00373503 History of Changes
Other Study ID Numbers:	4942; R01DA019239 ( U.S. NIH Grant/Contract )
First Posted:	September 8, 2006
Last Update Posted:	February 5, 2013
Last Verified:	February 2013

Keywords provided by New York State Psychiatric Institute:

Lofexidine; Oral THC; Cannabinoids

Additional relevant MeSH terms:

Marijuana Abuse; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Dronabinol; Clonidine; Lofexidine; Hallucinogens; Physiological Effects of Drugs; Psychotropic Drugs; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents	Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antihypertensive Agents; Narcotic Antagonists; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Sympatholytics; Autonomic Agents