Opioid Antagonism of Cannabinoid Effects: Differences between Marijuana Smokers and Nonmarijuana Smokers

Haney, Margaret

doi:10.1038/sj.npp.1301243

Cited by 104 publications

(90 citation statements)

References 61 publications

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“…In rats discriminating THC, intracranial injection of the opioid peptide agonist β-endorphin or systemic administration of morphine or heroin enhanced, whereas administration of naltrexone attenuated, the discriminative stimulus effects of THC (Solinas et al 2004;; however, these interactions have not been unanimously confirmed. For example, in humans naltrexone attenuates, enhances, or has no effect the subjective and physiological effects of THC (Wachtel and de Wit 2000;Greenwald and Stitzer 2000;Haney et al 2003;Haney 2007). These inconsistencies could be related to species, drug, dose, or history.…”

Section: Discussionmentioning

confidence: 99%

“…For example, the μ opioid receptor agonists heroin and morphine enhanced while the opioid receptor antagonist naltrexone attenuated the discriminative stimulus effects of THC in rats . Initial reports indicated that naltrexone did not modify the subjective effects of THC in marijuana users (Wachtel and de Wit 2000;Greenwald and Stitzer 2000); however, more recent studies showed that naltrexone can increase (Haney et al 2003) or decrease (Haney 2007) the subjective effects of THC, depending on the history of marijuana use. Thus, the nature of interactions between cannabinoid and opioid receptor agonists and antagonists appears to vary markedly across conditions.…”

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confidence: 99%

“…These inconsistencies could be related to species, drug, dose, or history. For example, naltrexone attenuated THC intoxication in subjects who regularly smoked marijuana and enhanced THC intoxication in non-smokers (Haney et al 2003;Haney 2007).affect common underlying neurochemical systems (e.g. dopamine; Gardner…”

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confidence: 99%

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Interactions between Δ9-tetrahydrocannabinol and μ opioid receptor agonists in rhesus monkeys: discrimination and antinociception

McMahon

Gerak

et al. 2008

Psychopharmacology

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Rationale-Opioid receptor agonists can enhance some effects of cannabinoid receptor agonists and cannabinoid receptor agonists can enhance some effects of opioid receptor agonists; however, the generality of these interactions is not established.Objective-This study examined interactions between the discriminative stimulus and antinociceptive effects of μ opioid receptor agonists and Δ 9 -tetrahydrocannabinol (THC) in rhesus monkeys.Results-Neither heroin nor morphine (i.v. or s.c.) altered the discriminative stimulus effects of THC in monkeys (n=5) discriminating 0.1 mg/kg THC i.v. In contrast, THC (s.c.) markedly attenuated the discriminative stimulus effect of morphine and heroin in non-dependent monkeys (n=4) discriminating 1.78 mg/kg morphine s.c. Doses of THC that attenuated the discriminative stimulus effects of morphine in non-dependent monkeys failed to modify the discriminative stimulus effects of morphine in morphine-dependent (5.6 mg/kg/12 hr) monkeys (n=4) discriminating 0.0178 mg/kg naltrexone s.c. THC also failed to modify the discriminative stimulus effects of naltrexone in morphine-dependent monkeys or the effects of midazolam in monkeys (n=4) discriminating 0.32 mg/kg midazolam s.c. Doses of THC (s.c.) that attenuated the discriminative stimulus effects of morphine in non-dependent monkeys enhanced the antinociceptive effects of morphine (s.c.) in non-dependent monkeys. While μ receptor agonists did not alter the discriminative stimulus effects of THC, in a context-dependent manner THC altered the effects of μ receptor agonists.Conclusion-That the same doses of THC enhance, attenuate, or do not affect morphine, depending on the condition, suggests that attenuation of morphine by THC can result from perceptual masking rather than common pharmacodynamic mechanisms or pharmacokinetic interactions. Keywordsopioid; THC; drug discrimination; rhesus monkey; perceptual masking; morphine; heroin; midazolam; naltrexone; antinociception Cannabinoid receptor agonists and μ opioid receptor agonists have some effects in common (e.g. antinociception): drugs from both classes have important therapeutic effects and some are abused (e.g., marijuana and heroin). Cannabinoid and opioid systems and drugs interact under a broad range of conditions, from cellular (Rios et al. 2006) to behavioral (e.g. Haney NIH Public AccessAuthor Manuscript Psychopharmacology (Berl). Author manuscript; available in PMC 2012 October 24.Published in final edited form as:Psychopharmacology (Berl). 2008 August ; 199(2): 199-208. doi:10.1007/s00213-008-1157-0. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript2007) measures of drug action. Understanding these interactions could be especially important for developing novel medications that might comprise both cannabinoid and opioid mechanisms and for understanding the factors that contribute to polydrug abuse.Especially relevant to polydrug abuse are studies on the combined effects of opioids and cannabinoids on behavioral measures that are related to and p...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Interactions between Δ9-tetrahydrocannabinol and μ opioid receptor agonists in rhesus monkeys: discrimination and antinociception

McMahon

Gerak

et al. 2008

Psychopharmacology

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“…One possible explanation for this lack of replication may involve cannabis strength: the earlier study tested less potent cannabis (3.27% THC), producing lower ratings of 'High' and 'Good Effect' than the higher strength cannabis tested herein (5.5%). The relationship between naltrexone and cannabinoids is complex and appears to be influenced by a variety of experimental parameters including route of administration (oral THC vs smoked cannabis), THC dose, naltrexone dose, outcome measure (reinforcement vs analgesia), and cannabis use patterns (daily vs infrequent; Haney, 2007;Haney et al, 2003;Greenwald and Stitzer, 2000;Wachtel and de Wit, 2000). The underlying mechanism contributing to the variable effects observed across experimental parameters remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers

Haney

Ramesh

Glass

et al. 2015

Neuropsychopharmacol

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Given that cannabis use is increasing in the United States, pharmacological treatment options to treat cannabis use disorder are needed. Opioid antagonists modulate cannabinoid effects and may offer a potential approach to reducing cannabis use. In this double-blind, placebo-controlled human laboratory study, we assessed the effects of naltrexone maintenance on the reinforcing, subjective, psychomotor, and cardiovascular effects of active and inactive cannabis. Nontreatment-seeking, daily cannabis smokers were randomized to receive naltrexone (50 mg: n = 18 M and 5 F) or placebo (0 mg; n = 26 M and 2 F) capsules for 16 days. Before, during, and after medication maintenance, participants completed 10 laboratory sessions over 4-6 weeks, assessing cannabis' behavioral and cardiovascular effects. Medication compliance was verified by observed capsule administration, plasma naltrexone, and urinary riboflavin. Relative to placebo, maintenance on naltrexone significantly reduced both active cannabis self-administration and its positive subjective effects ('good effect'). Participants in the placebo group had 7.6 times (95% CI: 1.1-51.8) the odds of self-administering active cannabis compared with the naltrexone group. This attenuation of reinforcing and positive subjective effects also influenced cannabis use in the natural ecology. Naltrexone had intrinsic effects: decreasing ratings of friendliness, food intake, and systolic blood pressure, and increasing spontaneous reports of stomach upset and headache, yet dropout rates were comparable between groups. In summary, we show for the first time that maintenance on naltrexone decreased cannabis self-administration and ratings of 'good effect' in nontreatment-seeking daily cannabis smokers. Clinical studies in patients motivated to reduce their cannabis use are warranted to evaluate naltrexone's efficacy as a treatment for cannabis use disorder.

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“…Although pioneering studies has recently started to individuate possible useful targets for the treatment of cannabis abuse in humans (Solinas et al, 2007a;Haney et al, 2007), marijuana dependence appears difficult to treat, and its use leads to a risk of relapse as high as those found for other drugs of abuse (Stephens et al, 1994;Spear et al, 1999;Moore and Budney, 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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Opioid Antagonism of Cannabinoid Effects: Differences between Marijuana Smokers and Nonmarijuana Smokers

Cited by 104 publications

References 61 publications

Interactions between Δ9-tetrahydrocannabinol and μ opioid receptor agonists in rhesus monkeys: discrimination and antinociception

Interactions between Δ9-tetrahydrocannabinol and μ opioid receptor agonists in rhesus monkeys: discrimination and antinociception

Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers

Neurobiological mechanisms of cannabinoid addiction

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