Opioid antagonism enhances marijuana's effects in heavy marijuana smokers.
Ziva D. Cooper, Margaret Haney
Psychopharmacology August 2010 DOI: 10.1007/s00213-010-1875-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 29 |
| Population | Daily marijuana smokers |
| Interventions | Naltrexone Marijuana |
| Dose | 0, 12, 25, 50, or 100 mg naltrexone; 3.27% or 0% THC marijuana |
| Topics | Cannabis |
| Key findings | Naltrexone enhanced the subjective and cardiovascular effects of smoked marijuana in daily smokers, suggesting endogenous opioids dampen cannabinoid effects. For example, naltrexone increased ratings of drug strength, high, good, liking, stimulated, and take again under active marijuana conditions, and further increased heart rate. |
Abstract
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. 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. 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. 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.
Comparable studies
Other randomized controlled trials on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Healthy participants | 2012 | Randomized controlled trial | n = 48 |
| Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Healthy, English-native, right-handed men who had used cannabis 15 times or less in... | 2009 | Double-blind, randomized, placebo-controlled crossover trial | n = 15 |
| Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Healthy male subjects | 2012 | Randomized controlled trial | n = 16 |
| Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Healthy, native English-speaking, right-handed men of white race/ethnicity who had used... | 2009 | Randomized controlled trial | n = 15 |
| Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition Healthy volunteers with a history of light cannabis use | 2019 | Randomized, double-blind, within-subjects crossover | n = 14 |
Citations in the library
Cited by 5
- Investigating sex differences in the acute effects of smoked cannabis: a potency-ranging, controlled administration, human laboratory experiment. Psychopharmacology August 11, 2026
- Potency-related effects of smoked cannabis on simulated driving performance: a randomized, controlled crossover trial. Scientific Reports March 10, 2026
- Are Alcohol Anti-relapsing and Alcohol Withdrawal Drugs Useful in Cannabinoid Users? Neurotoxicity Research November 1, 2016
- Naltrexone does not attenuate the effects of intravenous Δ9-tetrahydrocannabinol in healthy humans. The International Journal of Neuropsychopharmacology October 2012
- Dronabinol for the treatment of cannabis dependence: a randomized, double-blind, placebo-controlled trial. Drug and Alcohol Dependence July 1, 2011
Cites 7
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and 2 more in the library