Abstinence symptoms following oral THC administration to humans

Haney, Margaret; Ward, Amie S.; Comer, Sandra D.; Foltin, Richard W.; Fischman, Marian W.

doi:10.1007/s002130050848

Cited by 244 publications

(209 citation statements)

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“…In marijuana smokers, 20-30 mg given 4 times/day produced intoxication, while 10 mg given 5 times/day decreased symptoms of marijuana withdrawal without producing intoxication (Haney et al, 1999a(Haney et al, , 2004. A study objective was to decrease the number of capsule administrations per day from five to three.…”

Section: Capsule Administrationmentioning

confidence: 99%

Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse

et al. 2007

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Individuals seeking treatment for their marijuana use rarely achieve sustained abstinence.Objectives-To determine if THC, a cannabinoid agonist, and lofexidine, an α 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, 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 3 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. KeywordsMarinol; Britlofex; dependence; withdrawal; treatment; cannabinoid; norepinephrine Marijuana use is prevalent in American society, and the number of individuals who currently meet DSM-IV criteria for cannabis abuse or dependence has steadily increased since the 1990s (Compton et al., 2004). Although marijuana is less likely to produce dependence than drugs such as nicotine, alcohol or heroin (Anthony et al., 1994), the sheer number of marijuana smokers combined with the increasing potency of marijuana has NIH Public AccessAuthor Manuscript Psychopharmacology (Berl). Author manuscript; available in PMC 2012 June 12.Published in final edited form as:Psychopharmacology (Berl). 2008 March ; 197(1): 157-168. doi:10.1007/s00213-007-1020-8. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript resulted in a significant number of individuals developing cannabis use disorders, i.e., approximately 1.5% of the U.S. population (Compton et al., 2004).A number of studies have demonstrated that there is a personal (i.e., not court-mandated) demand for marijuana treatment, particularly when marijuana-specific treatment programs are offered (Roffman et al., 1988;Stephens et al., 1993;Lang et al., 2000). Treatmentseekers report distress about their marijuana use, and repeatedly ...

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Section: Capsule Administrationmentioning

confidence: 99%

Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse

et al. 2007

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“…The residential laboratory consists of 11 rooms in the New York State Psychiatric Institute: four private participant rooms, a common recreational area, two single-occupancy bathrooms, two single-occupancy shower rooms, and two vestibules used for exchanging supplies (see Haney et al, 1999a, for a more detailed description).…”

Section: Laboratorymentioning

confidence: 99%

Marijuana Withdrawal in Humans: Effects of Oral THC or Divalproex

Haney

Hart

Vosburg

et al. 2003

Neuropsychopharmacol

239

228

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Abstinence following daily marijuana use can produce a withdrawal syndrome characterized by negative mood (eg irritability, anxiety, misery), muscle pain, chills, and decreased food intake. Two placebo-controlled, within-subject studies investigated the effects of a cannabinoid agonist, delta-9-tetrahydrocannabinol (THC: Study 1), and a mood stabilizer, divalproex (Study 2), on symptoms of marijuana withdrawal. Participants (n ¼ 7/study), who were not seeking treatment for their marijuana use, reported smoking 6-10 marijuana cigarettes/day, 6-7 days/week. Study 1 was a 15-day in-patient, 5-day outpatient, 15-day in-patient design. During the in-patient phases, participants took oral THC capsules (0, 10 mg) five times/day, 1 h prior to smoking marijuana (0.00, 3.04% THC). Active and placebo marijuana were smoked on in-patient days 1-8, while only placebo marijuana was smoked on days 9-14, that is, marijuana abstinence. Placebo THC was administered each day, except during one of the abstinence phases (days 9-14), when active THC was given. Mood, psychomotor task performance, food intake, and sleep were measured. Oral THC administered during marijuana abstinence decreased ratings of 'anxious', 'miserable', 'trouble sleeping', 'chills', and marijuana craving, and reversed large decreases in food intake as compared to placebo, while producing no intoxication. Study 2 was a 58-day, outpatient/in-patient design. Participants were maintained on each divalproex dose (0, 1500 mg/day) for 29 days each. Each maintenance condition began with a 14-day outpatient phase for medication induction or clearance and continued with a 15-day in-patient phase. Divalproex decreased marijuana craving during abstinence, yet increased ratings of 'anxious', 'irritable', 'bad effect', and 'tired.' Divalproex worsened performance on psychomotor tasks, and increased food intake regardless of marijuana condition. Thus, oral THC decreased marijuana craving and withdrawal symptoms at a dose that was subjectively indistinguishable from placebo. Divalproex worsened mood and cognitive performance during marijuana abstinence. These data suggest that oral THC, but not divalproex, may be useful in the treatment of marijuana dependence.

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“…Behavioral and physiological abstinence phenomena after frequent administration of doses as high as 210 mg/day of oral THC were also described (Haney et al, 1999). Over the past decade, demand for treatment for cannabis abuse has grown dramatically, and a large proportion of heavy users of hashish or ganja have difficult achieving and maintaining abstinence from the drug (McRae et al, 2003).…”

Section: Cannabinoids and Drug Addictionmentioning

confidence: 99%

Neurobiological mechanisms of cannabinoid addiction

Fattore

Fadda

Spano

et al. 2008

Molecular and Cellular Endocrinology

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Please cite this article as: Fattore, L., Fadda, P., Spano, M.S., Pistis, M., Fratta, W., Neurobiological mechanisms of cannabinoid addiction, Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 2 AbstractThe endocannabinoid system is implicated in the regulation of a variety of physiological processes, among which conditioning, motivation, habit forming, memory, learning, and cognition play pivotal roles in drug reinforcement and reward. In this article we will give a synopsis of last developments in research on cannabinoid actions on brain reward circuits coming from behavioral, neurochemical and electrophysiological studies. Central cannabinoid-induced effects as measured by animal models of addiction, in vivo cerebral microdialysis, in vitro and in vivo electrophysiological recording techniques, will be reviewed.Brain sites that have been implicated in the mediation of addictive cannabinoid properties include primarily the ventral tegmental area, the nucleus accumbens, and the medial prefrontal cortex, although the amygdala, the substantia nigra, the globus pallidus, and the hippocampus have also been shown to be critical structures mediating motivational and reinforcing effects of cannabinoids. Putative neurobiological mechanisms underlying these effects will be delineated.

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Abstinence symptoms following oral THC administration to humans

Cited by 244 publications

References 31 publications

Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse

Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse

Marijuana Withdrawal in Humans: Effects of Oral THC or Divalproex

Neurobiological mechanisms of cannabinoid addiction

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