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Cited by 111Cannabis and Cannabinoid ResearchNeurotransmitter Receptor Influence on BehaviorNeuropeptides and Animal Physiology

The opioid antagonist naltrexone reduces the reinforcing effects of ? 9 -tetrahydrocannabinol (THC) in squirrel monkeys

Tanda, Gianluigi, Munzar, Patrik, Goldberg, Steven R., Justinova, Zuzana·2004·Psychopharmacology
DOI 10.1007/s00213-003-1693-6
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Abstract

Rationale Experimental evidence from animal studies suggests reciprocal functional interactions between endogenous brain cannabinoid and opioid systems. There is recent evidence for a role of the opioid system in the modulation of the reinforcing effects of synthetic cannabinoid CB1 receptor agonists in rodents. Since Delta(9)-tetrahydrocannabinol (THC), the natural psychoactive ingredient in marijuana, is actively and persistently self-administered by squirrel monkeys, this provides an opportunity to directly study involvement of opioid systems in the reinforcing effects of THC in non-human primates.Objectives To study the effects of naltrexone, an opioid antagonist, on THC self-administration behavior in squirrel monkeys.Methods Monkeys pressed a lever for intravenous injections of THC under a ten-response, fixed-ratio (FR) schedule with a 60-s time-out after each injection. Effects of pre-session treatment with naltrexone (0.03-0.3 mg/kg intramuscularly, 15 min before session) for 5 consecutive days on self-administration of different doses of THC (2-8 microg/kg per injection) were studied.Results Self-administration responding for THC was significantly reduced by pretreatment with 0.1 mg/kg naltrexone for five consecutive daily sessions. Naltrexone pretreatment had no significant effect on cocaine self-administration responding under identical conditions.Conclusions Self-administration behavior under a fixed-ratio schedule of intravenous THC injection was markedly reduced by daily pre-session treatment with naltrexone, but remained above saline self-administration levels. These findings demonstrate for the first time the modulation of the reinforcing effects of THC by an opioid antagonist in a non-human primate model of marijuana abuse.

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  • Antagonists of opioid receptors reduced discriminative stimulus and reinforcing effects produced by activation of CB1 receptors in preclinical studies.

    “Evidence from pre-clinical studies demonstrates that antagonists of opioid receptors were able to reduce discriminative stimulus and reinforcing effects produced by the activation of CB1 receptors 71, 72.”

    From Psychosocial and pharmacological interventions for the treatment of cannabis use disorder (2018) · cites this paper as [72]

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Authors
Tanda, G., Munzar, P., Goldberg, S. R., & Justinova, Z.
Affiliations
National Institutes of Health (US)
Corresponding author
Goldberg, Steven R.
ORCID
Tanda, Gianluigi
Venue
Psychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2004-04-01
Volume
173
Issue
1-2
Pages
186-194
ISSN
  • 0033-3158 (ISSN-L)
  • 1432-2072
DOI
10.1007/s00213-003-1693-6
OpenAlex
W2060123538
Cited by
111
References
52
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2022: 2 · 2021: 3 · 2020: 5 · 2019: 1 · 2018: 4 · 2017: 7 · 2016: 7 · 2015: 5 · 2014: 4 · 2013: 2 · 2012: 4
FWCI
6.28
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Psychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute on Drug Abuse
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
naltrexone, delta-9-tetrahydrocannabinol, opioid antagonists, opioid-cannabinoid interaction, CB1 receptor, drug reinforcement, squirrel monkey, cocaine self-administration, cannabis use disorder, fixed-ratio schedules
MeSH terms
Anesthetics, Local, Animals, Behavior, Animal, Cocaine, Conditioning, Operant, Dose-Response Relationship, Drug, Drug Interactions, Male, Naltrexone, Narcotic Antagonists, Reinforcement, Psychology, Reinforcement Schedule, Saimiri, Self Administration, Dronabinol, Analgesics, Non-Narcotic

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