Effect of Lofexidine and Oral THC on Marijuana Withdrawal and Relapse - Full Text View

Purpose

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	Intervention	Phase
Marijuana Dependence	Drug: Lofexidine Drug: dronabinol Drug: Marijuana	Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Basic Science
Official Title:	Effect of Lofexidine and Oral THC on Marijuana Withdrawal and Relapse

Resource links provided by NLM:

MedlinePlus related topics: Marijuana

Drug Information available for: Dronabinol

U.S. FDA Resources

Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:

marijuana relapse [ Time Frame: 4 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

marijuana withdrawal symptoms [ Time Frame: 3 days ] [ Designated as safety issue: No ]

Other Outcome Measures:

cardiovascular effects [ Time Frame: 7 days ] [ Designated as safety issue: No ]


Enrollment:	8
Study Start Date:	August 2005
Study Completion Date:	September 2008
Primary Completion Date:	June 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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


Ages Eligible for Study:	21 Years to 45 Years (Adult)
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00373503

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


Responsible Party:	New York State Psychiatric Institute
ClinicalTrials.gov Identifier:	NCT00373503 History of Changes
Other Study ID Numbers:	4942 R01DA019239
Study First Received:	September 7, 2006
Last Updated:	February 4, 2013
Health Authority:	United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 27, 2016