Opioid antagonism enhances marijuana's effects in heavy marijuana smokers.
Open accessAbstract
Rationale and objective Studies in laboratory animals strongly suggest reciprocal modulation of the opioidergic and endocannabinoid systems, a relationship that has not been demonstrated in humans. This study sought to clarify this interaction by assessing how a range of naltrexone doses altered the subjective, cognitive, and cardiovascular effects of marijuana.Material and methods Daily marijuana smokers (n = 29) participated in this within-subject, randomized, double-blind, placebo-controlled study. Naltrexone (0, 12, 25, 50, or 100 mg) was administered before active or inactive marijuana (3.27 or 0% THC) was smoked.Results Active marijuana increased subjective ratings of marijuana 'Strength,' 'High,' and positive subjective ratings of marijuana quality and drug effect including 'Liking,' 'Good,' and 'Take Again' compared to inactive marijuana. Naltrexone alone decreased ratings of 'Liking,' 'Take Again,' and 'Stimulated' compared with placebo, but increased ratings of drug 'Strength,' 'High,' 'Good,' 'Liking,' 'Stimulated,' and 'Take Again' when administered under active marijuana conditions. Active marijuana did not affect performance on cognitive tasks relative to inactive marijuana, whereas naltrexone decreased performance when administered alone or in combination with active marijuana. Active marijuana increased heart rate compared to inactive marijuana under placebo naltrexone conditions. Although naltrexone alone decreased heart rate, it further increased marijuana's cardiovascular effect.Conclusions In heavy marijuana smokers opioid-receptor blockade enhanced the subjective and cardiovascular effects of marijuana, suggesting that endogenous opioids dampen cannabinoid effects in this population. These findings demonstrate that a broad range of clinically used doses of naltrexone potentially increases the abuse liability and cardiovascular risks of cannabinoids.
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Acute administration of naltrexone potentiated the positive subjective effects of cannabis, but repeated administration decreased such effects.
“It has been reported that the acute administration of naltrexone potentiated the positive subjective effects of cannabis but that repeated administration decreased such effects 74, 75.”
From Psychosocial and pharmacological interventions for the treatment of cannabis use disorder (2018) · cites this paper as [75]
The Results (Subjective ratings) report that naltrexone generally increased positive subjective ratings when combined with active marijuana in heavy marijuana smokers. The Introduction describes single-dose testing, and Future directions and limitations raises chronic administration as a question; this paper does not establish that repeated administration decreased those effects. (LLM, conf=0.89)
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Cites
Functional interaction between opioid and cannabinoid receptors in drug self-administration.
Navarro, M., Carrera, M. R. A., Fratta, W., Valverde, O., Cossu, G., Fattore, L., Chowen, J. A., Gómez, R., del Arco, I., Villanúa, M. A., et al. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-14-05344.2001 · Cited by 378 · see citing works
Abstinence symptoms following smoked marijuana in humans
Haney, M., Ward, A. S., Comer, S. D., Foltin, R. W., & Fischman, M. W. (1999) · Psychopharmacology · doi:10.1007/s002130050849 · Cited by 354 · see citing works
Self-citationEffects of Acute Smoked Marijuana on Complex Cognitive Performance
Hart, C. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00273-1 · Cited by 272 · see citing works
Marijuana Withdrawal in Humans: Effects of Oral THC or Divalproex
Haney, M., Hart, C. L., Vosburg, S. K., Nasser, J. A., Bennett, A., Zúbaran, C., & Foltin, R. W. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300310 · Cited by 262 · see citing works
Self-citationIntravenous self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-2 in rats
Fattore, L., Cossu, G., Martellotta, C., & Fratta, W. (2001) · Psychopharmacology · doi:10.1007/s002130100734 · Cited by 187 · see citing works
Solinas, M., & Goldberg, S. R. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300720 · Cited by 174 · see citing works
Two brain sites for cannabinoid reward
Zangen, A., Solinas, M., Ikemoto, S., Goldberg, S. R., & Wise, R. A. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.3554-05.2006 · Cited by 174 · see citing works
Huestis, M. A., Boyd, S. J., Heishman, S. J., Preston, K. L., BONNET, D., Fur, G. L., & Gorelick, D. A. (2007) · Psychopharmacology · doi:10.1007/s00213-007-0861-5 · Cited by 166 · see citing works
Braida, D., Iosuè, S., Pegorini, S., & Sala, M. (2004) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.10.043 · Cited by 152 · see citing works
CB1 cannabinoid receptor antagonist-induced opiate withdrawal in morphine-dependent rats
Navarro, M., Chowen, J., Carrera, M. R. A., del Arco, I., Villanúa, M. A., Martin, Y., Roberts, A. J., Koob, G. F., & de Fonseca, F. R. (1998) · NeuroReport · doi:10.1097/00001756-199810260-00012 · Cited by 152 · see citing works
Braida, D., Pozzi, M., Cavallini, R., & Sala, M. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00210-x · Cited by 152 · see citing works
(1978) · Elsevier eBooks · doi:10.1016/c2013-1-15195-7 · Cited by 125 · see citing works
Advances in the field of cannabinoid–opioid cross‐talk
Robledo, P., Berrendero, F., Ozaita, A., & Maldonado, R. J. (2008) · Addiction Biology · doi:10.1111/j.1369-1600.2008.00107.x · Cited by 120 · see citing works
Antinociceptive, subjective and behavioral effects of smoked marijuana in humans
Greenwald, M. K., & Stitzer, M. L. (2000) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(99)00128-3 · Cited by 119 · see citing works
Haney, M. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301243 · Cited by 113 · see citing works
Self-citationMetabolism and disposition of naltrexone in man after oral and intravenous administration.
Wall, M. E., Brine, D. R., & Perez‐Reyes, M. (1981) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(25)06161-6 · Cited by 111 · see citing works
Dependence on tetrahydrocannabinol in rhesus monkeys.
Beardsley, P. M., Balster, R. L., & Harris, L. S. (1986) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)23582-0 · Cited by 111 · see citing works
Tanda, G., Munzar, P., Goldberg, S. R., & Justinova, Z. (2004) · Psychopharmacology · doi:10.1007/s00213-003-1693-6 · Cited by 111 · see citing works
CB1 receptor agonist and heroin, but not cocaine, reinstate cannabinoid‐seeking behaviour in the rat
Spano, M. S., Fattore, L., Cossu, G., Deiana, S., Fadda, P., & Fratta, W. (2004) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705932 · Cited by 95 · see citing works
Naloxone-induced or postwithdrawal abstinence signs in ?9-Tetrahydrocannabinol-Tolerant rats
Kaymak�alan, �., Ayhan, I. H., & Tulunay, F. C. (1977) · Psychopharmacology · doi:10.1007/bf00497855 · Cited by 91 · see citing works
Justinová, Z., Munzar, P., Panlilio, L. V., Yaşar, S., Redhi, G. H., Tanda, G., & Goldberg, S. R. (2008) · Neuropsychopharmacology · doi:10.1038/npp.2008.21 · Cited by 86 · see citing works
Interaction between naltrexone and oral THC in heavy marijuana smokers
Haney, M., Bisaga, A. M., & Foltin, R. W. (2003) · Psychopharmacology · doi:10.1007/s00213-002-1279-8 · Cited by 83 · see citing works
Self-citationSolinas, M., Zangen, A., Thiriet, N., & Goldberg, S. R. (2004) · European Journal of Neuroscience · doi:10.1111/j.0953-816x.2004.03420.x · Cited by 83 · see citing works
Morphine and ?9-tetrahydrocannabinol: Tolerance to the stimulus effects
Hirschhorn, I. D., & Rosecrans, J. A. (1974) · Psychopharmacology · doi:10.1007/bf00421806 · Cited by 79 · see citing works
Behavioral effects of cocaine alone and in combination with ethanol or marijuana in humans
Foltin, R. W., Fischman, M. W., Pippen, P. A., & Kelly, T. H. (1993) · Drug and Alcohol Dependence · doi:10.1016/0376-8716(93)80001-u · Cited by 74 · see citing works
CB1 cannabinoid receptor agonists increase intracranial self-stimulation thresholds in the rat
Vlachou, S., Nomikos, G. G., & Panagis, G. (2004) · Psychopharmacology · doi:10.1007/s00213-004-2050-0 · Cited by 64 · see citing works
Behavioral contingencies modulate alprazolam self-administration by humans.
Haney, M., Comer, S. D., Ward, A. S., Foltin, R. W., & Fischman, M. W. (1997) · PubMed · Cited by 63 · see citing works
Self-citationLi, J., McMahon, L. R., Gerak, L. R., Becker, G. L., & France, C. P. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1157-0 · Cited by 57 · see citing works
Naltrexone does not block the subjective effects of oral Δ9-tetrahydrocannabinol in humans
Wachtel, S. R., & de Wit, H. (2000) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(99)00127-1 · Cited by 56 · see citing works
Effects of smoked marijuana on social interaction in small groups
Foltin, R. W., Brady, J. V., Fischman, M. W., Emurian, C. S., & Dominitz, J. A. (1987) · Drug and Alcohol Dependence · doi:10.1016/0376-8716(87)90079-2 · Cited by 52 · see citing works
Antagonism of discriminative stimulus effects of Δ9-THC and (R)-methanandamide in rats
Järbe, T. U. C., Liu, Q., & Makriyannis, A. (2005) · Psychopharmacology · doi:10.1007/s00213-005-0225-y · Cited by 39 · see citing works
Lile, J. A., Kelly, T. H., Pinsky, D. J., & Hays, L. R. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1393-3 · Cited by 32 · see citing works
Behavioral contingencies modulate alprazolam self-administration by humans
Haney, M., Comer, S. D., Foltin, R. W., et al. (1997) · Behavioural Pharmacology · doi:10.1097/00008877-199702000-00009 · Cited by 30 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Haney M Comer SD Ward AS Foltin RW Fischman MW Factors influencing marijuana self-administration by humans Behav Pharmacol 1997 8 101 112 9833006
Cited by
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Cannabis use and cannabis use disorder
Connor, J. P., Stjepanović, D., Le Foll, B., Hoch, E., Budney, A. J., & Hall, W. D. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00247-4 · Cited by 552 · see citing works
Levin, F. R., Mariani, J. J., Brooks, D. J., Pavlicova, M., Cheng, W., & Nunes, E. V. (2011) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2010.12.010 · Cited by 232 · see citing works
Levin, F. R., Mariani, J. J., Pavlicova, M., Brooks, D., Glass, A., Mahony, A., Nunes, E. V., Bisaga, A., Dakwar, E., Carpenter, K. M., et al. (2016) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2015.11.025 · Cited by 109 · see citing works
Haney, M., Ramesh, D., Glass, A., Pavlicova, M., Bedi, G., & Cooper, Z. D. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.108 · Cited by 73 · see citing works
Self-citationPsychosocial and pharmacological interventions for the treatment of cannabis use disorder
Sabioni, P., & Le Foll, B. (2018) · F1000Research · doi:10.12688/f1000research.11191.1 · Cited by 37 · see citing works
- Authors
- Cooper, Z. D., & Haney, M.
- Affiliations
- Columbia University (US)
- Corresponding author
- Cooper, Ziva D.
- Venue
- Psychopharmacology
- Published
- 2010-05-19
- Volume
- 211
- Issue
- 2
- Pages
- 141-148
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- PMC
- PMC2923559
- OpenAlex
- W2022083093
- Cited by
- 58
- References
- 33
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 7 · 2014: 9 · 2013: 2 · 2012: 4
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (DA-09236, P50DA009236)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Keywords
- naltrexone, cannabis, opioid antagonism, endocannabinoid system, opioid-cannabinoid interaction, subjective drug effects, drug liking, cognitive performance, heart rate, cardiovascular effects, abuse liability, opioid receptor blockade
- MeSH terms
- Adult, Marijuana Abuse, Dose-Response Relationship, Drug, Double-Blind Method, Drug Interactions, Female, Heart Rate, Humans, Male, Marijuana Smoking, Naltrexone, Narcotic Antagonists, Psychomotor Performance, Dronabinol
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