Opioid antagonism of cannabinoid effects: differences between marijuana smokers and nonmarijuana smokers.
Neuropsychopharmacology June 2007 DOI: 10.1038/sj.npp.1301243 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study (within-subject, placebo-controlled) Peer reviewed |
|---|---|
| Sample size | 43 |
| Population | Marijuana smokers (n=22) and nonmarijuana smokers (n=21), men and women |
| Interventions | Naltrexone THC Methadone |
| Dose | Naltrexone 12 mg; THC 0-40 mg; Methadone 0-10 mg |
| Topics | Cannabis |
| Key findings | In marijuana smokers, 12 mg naltrexone blunted intoxication from 20 mg THC and increased anxiety at 40 mg THC; in nonmarijuana smokers, it enhanced intoxication from 2.5 mg THC and decreased anxiety at 10 mg THC. No sex differences were observed, though nonmarijuana-smoking men were more sensitive to THC alone than women. |
Abstract
In non-human animals, opioid antagonists block the reinforcing and discriminative-stimulus effects of Delta(9)-tetrahydrocannabinol (THC), while in human marijuana smokers, naltrexone (50 mg) enhances the reinforcing and subjective effects of THC. The objective of this study was to test a lower, more opioid-selective dose of naltrexone (12 mg) in combination with THC. The influence of marijuana-use history and sex was also investigated. Naltrexone (0, 12 mg) was administered 30 min before oral THC (0-40 mg) or methadone (0-10 mg) capsules, and subjective effects, task performance, pupillary diameter, and cardiovascular parameters were assessed in marijuana smoking (Study 1; n=22) and in nonmarijuana smoking (Study 2; n=21) men and women. The results show that in marijuana smokers, low-dose naltrexone blunted the intoxicating effects of a low THC dose (20 mg), while increasing ratings of anxiety at a higher THC dose (40 mg). In nonmarijuana smokers, low-dose naltrexone shifted THC's effects in the opposite direction, enhancing the intoxicating effects of a low THC dose (2.5 mg) and decreasing anxiety ratings following a high dose of THC (10 mg). There were no sex differences in these interactions, although among nonmarijuana smokers, men were more sensitive to the effects of THC alone than women. To conclude, a low, opioid-selective dose of naltrexone blunted THC intoxication in marijuana smokers, while in nonmarijuana smokers, naltrexone enhanced THC intoxication. These data demonstrate that the interaction between opioid antagonists and cannabinoid agonists varies as a function of marijuana use history.
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 15
- Sex differences in acute cannabis effects revisited: Results from two randomized, controlled trials Addiction Biology December 22, 2021
- Sex differences in the acute effects of oral THC: a randomized, placebo-controlled, crossover human laboratory study. Psychopharmacology October 1, 2024
- Sex Differences in the Safety and Subjective Effects of Two Oral Δ9-Tetrahydrocannabinol-Containing Cannabis Products over Multiple Doses Among Healthy Adults. Cannabis and Cannabinoid Research August 2024
- Sex differences in the acute effects of intravenous (IV) delta-9 tetrahydrocannabinol (THC). Psychopharmacology May 2022
- Tasty THC: Promises and Challenges of Cannabis Edibles November 15, 2016
and 10 more in the library
Cites 6
- Transdermal nicotine alters some of marihuana's effects in male and female volunteers. Drug and Alcohol Dependence August 1, 2005
- Involvement of mu-, delta- and kappa-opioid receptor subtypes in the discriminative-stimulus effects of delta-9-tetrahydrocannabinol (THC) in rats. Psychopharmacology June 2005
- Marijuana and cannabinoid regulation of brain reward circuits. British Journal of Pharmacology September 2004
- Interaction between naltrexone and oral THC in heavy marijuana smokers. Psychopharmacology February 2003
- Chronic treatment with Delta(9)-tetrahydrocannabinol enhances the locomotor response to amphetamine and heroin. Implications for vulnerability to drug addiction. Neuropharmacology July 1, 2001
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