Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse.
BACKGROUND
Individuals seeking treatment for their marijuana use rarely achieve sustained abstinence.


OBJECTIVE
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.


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.
Haney
Margaret
M
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.edu
Hart
Carl L
CL
Vosburg
Suzanne K
SK
Comer
Sandra D
SD
Reed
Stephanie Collins
SC
Foltin
Richard W
RW
D000316:Adrenergic alpha-Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000339:Affect / Q000187:drug effects; D001066:Appetite / Q000187:drug effects; D001288:Attention / Q000187:drug effects; D002186:Cannabinoids / Q000633:toxicity*; D003000:Clonidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004311:Double-Blind Method; D013759:Dronabinol / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000523:psychology / Q000534:rehabilitation*; D011939:Mental Recall / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D011619:Psychotropic Drugs / Q000009:adverse effects / Q000627:therapeutic use*; D055502:Secondary Prevention; D012890:Sleep / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000523:psychology / Q000534:rehabilitation*
D000316:Adrenergic alpha-Agonists; D002186:Cannabinoids; D011619:Psychotropic Drugs; D013759:Dronabinol; D003000:Clonidine; C025655:lofexidine