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Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse.
Psychopharmacology (Berl). 2008 Mar; 197(1):157-68.P

Abstract

INTRODUCTION

Individuals seeking treatment for their marijuana use rarely achieve sustained abstinence.

OBJECTIVES

The objectives of the study are to determine if THC, a cannabinoid agonist, and lofexidine, an alpha(2)-adrenergic receptor agonist, given alone and in combination, decreased symptoms of marijuana withdrawal and relapse, defined as a return to marijuana use after a period of abstinence.

MATERIALS AND METHODS

Nontreatment-seeking, male volunteers (n = 8), averaging 12 marijuana cigarettes/day, were maintained on each of four medication conditions for 7 days: placebo, tetrahydrocannabinol (THC) (60 mg/day), lofexidine (2.4 mg/day), and THC (60 mg/day) combined with lofexidine (2.4 mg/day); each inpatient phase was separated by an outpatient washout phase. During the first three inpatient days, placebo marijuana was available for self-administration (withdrawal). For the next 4 days, active marijuana was available for self-administration (relapse). Participants paid for self-administered marijuana using study earnings. Self-administration, mood, task performance, food intake, and sleep were measured.

RESULTS

THC reversed the anorexia and weight loss associated with marijuana withdrawal, and decreased a subset of withdrawal symptoms, but increased sleep onset latency, and did not decrease marijuana relapse. Lofexidine was sedating, worsened abstinence-related anorexia, and did not robustly attenuate withdrawal, but improved sleep and decreased marijuana relapse. The combination of lofexidine and THC produced the most robust improvements in sleep and decreased marijuana withdrawal, craving, and relapse in daily marijuana smokers relative to either medication alone.

CONCLUSIONS

These data suggest the combination of lofexidine and THC warrant further testing as a potential treatment for marijuana dependence.

Authors+Show Affiliations

Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, Unit 120, New York, NY, 10032, USA. mh235@columbia.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18161012

Citation

Haney, Margaret, et al. "Effects of THC and Lofexidine in a Human Laboratory Model of Marijuana Withdrawal and Relapse." Psychopharmacology, vol. 197, no. 1, 2008, pp. 157-68.
Haney M, Hart CL, Vosburg SK, et al. Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse. Psychopharmacology (Berl). 2008;197(1):157-68.
Haney, M., Hart, C. L., Vosburg, S. K., Comer, S. D., Reed, S. C., & Foltin, R. W. (2008). Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse. Psychopharmacology, 197(1), 157-68.
Haney M, et al. Effects of THC and Lofexidine in a Human Laboratory Model of Marijuana Withdrawal and Relapse. Psychopharmacology (Berl). 2008;197(1):157-68. PubMed PMID: 18161012.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse. AU - Haney,Margaret, AU - Hart,Carl L, AU - Vosburg,Suzanne K, AU - Comer,Sandra D, AU - Reed,Stephanie Collins, AU - Foltin,Richard W, Y1 - 2007/12/27/ PY - 2007/09/24/received PY - 2007/11/07/accepted PY - 2007/12/28/pubmed PY - 2008/8/30/medline PY - 2007/12/28/entrez SP - 157 EP - 68 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 197 IS - 1 N2 - INTRODUCTION: Individuals seeking treatment for their marijuana use rarely achieve sustained abstinence. OBJECTIVES: The objectives of the study are to determine if THC, a cannabinoid agonist, and lofexidine, an alpha(2)-adrenergic receptor agonist, given alone and in combination, decreased symptoms of marijuana withdrawal and relapse, defined as a return to marijuana use after a period of abstinence. MATERIALS AND METHODS: Nontreatment-seeking, male volunteers (n = 8), averaging 12 marijuana cigarettes/day, were maintained on each of four medication conditions for 7 days: placebo, tetrahydrocannabinol (THC) (60 mg/day), lofexidine (2.4 mg/day), and THC (60 mg/day) combined with lofexidine (2.4 mg/day); each inpatient phase was separated by an outpatient washout phase. During the first three inpatient days, placebo marijuana was available for self-administration (withdrawal). For the next 4 days, active marijuana was available for self-administration (relapse). Participants paid for self-administered marijuana using study earnings. Self-administration, mood, task performance, food intake, and sleep were measured. RESULTS: THC reversed the anorexia and weight loss associated with marijuana withdrawal, and decreased a subset of withdrawal symptoms, but increased sleep onset latency, and did not decrease marijuana relapse. Lofexidine was sedating, worsened abstinence-related anorexia, and did not robustly attenuate withdrawal, but improved sleep and decreased marijuana relapse. The combination of lofexidine and THC produced the most robust improvements in sleep and decreased marijuana withdrawal, craving, and relapse in daily marijuana smokers relative to either medication alone. CONCLUSIONS: These data suggest the combination of lofexidine and THC warrant further testing as a potential treatment for marijuana dependence. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/18161012/Effects_of_THC_and_lofexidine_in_a_human_laboratory_model_of_marijuana_withdrawal_and_relapse_ L2 - https://dx.doi.org/10.1007/s00213-007-1020-8 DB - PRIME DP - Unbound Medicine ER -