Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration and attenuates MDMA-induced hyperthermia and neurotoxicity in rats.
Erica Y Shen, Syed F. Ali, Jerrold S. Meyer
Neuropharmacology December 2011 DOI: 10.1016/j.neuropharm.2011.07.002 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats |
| Interventions | MDMA THC |
| Dose | MDMA (2 × 10 mg/kg × 4 h) every fifth day; THC (5 mg/kg) once daily |
| Duration | Postnatal day 35 to 60, with testing after drug washout |
| Topics | Cannabis MDMA |
| Key findings | THC co-administration attenuated MDMA-induced hyperthermia, behavioral changes in anxiety and exploration tests, and neurochemical deficits in serotonin levels and SERT binding in frontal cortex, parietal cortex, and striatum, but not hippocampus. THC alone produced modest hyperthermia. |
Abstract
Most recreational users of 3, 4-methylenedioxymethamphetamine (MDMA or "ecstasy") also take cannabis, in part because cannabis can reduce the dysphoric symptoms of the ecstasy come-down such as agitation and insomnia. Although previous animal studies have examined the acute effects of co-administering MDMA and Δ(9)-tetrahydrocannabinol (THC), which is the major psychoactive ingredient in cannabis, research on chronic exposure to this drug combination is lacking. Therefore, the present study was conducted to investigate the effects of chronic adolescent administration of both THC and MDMA on behavior and on regional serotonin transporter (SERT) binding and serotonin (5-HT) concentrations as indices of serotonergic system integrity. Male Sprague-Dawley rats were divided into four drug administration groups: (1) MDMA alone, (2) THC alone, (3) MDMA plus THC, and (4) vehicle controls. MDMA (2 × 10 mg/kg × 4 h) was administered every fifth day from postnatal day (PD) 35 to 60 to simulate intermittent recreational ecstasy use, whereas THC (5mg/kg) was given once daily over the same time period to simulate heavy cannabis use. THC unexpectedly produced a modest hyperthermic effect when administered alone, but in animals co-treated with both THC and MDMA, there was an attenuation of MDMA-induced hyperthermia on dosing days. Subsequent testing conducted after a drug washout period revealed that THC reduced MDMA-related behavioral changes in the emergence and social interaction tests of anxiety-like behavior and also blunted the MDMA-induced decrease in exploratory behavior in the hole-board test. THC additionally attenuated MDMA -induced decreases in 5-HT levels and in SERT binding in the frontal cortex, parietal cortex, and striatum, but not in the hippocampus. These results suggest that chronic co-administration of THC during adolescence can provide some protection against various adverse physiological, behavioral, and neurochemical effects produced by MDMA.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 10
- Sex‐dependent long‐term effects of adolescent exposure to THC and/or MDMA on neuroinflammation and serotoninergic and cannabinoid systems in rats British Journal of Pharmacology November 15, 2013
- Sex-Dependent Psychoneuroendocrine Effects of THC and MDMA in an Animal Model of Adolescent Drug Consumption PLoS One November 4, 2013
- Adolescent MDMA exposure diminishes the physiological and neurotoxic consequences of an MDMA binge in female rats Developmental Psychobiology July 1, 2014
- Long-term effects of adolescent THC exposure on anxiety-like behavior and cognitive function in male rats Psychopharmacology April 23, 2026
- Detrimental effects of adolescent escalating low-dose Δ9 -tetrahydrocannabinol leads to a specific bio-behavioural profile in adult male rats. British Journal of Pharmacology April 2021
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Cites 20
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- Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Journal of Neuroscience July 1, 1998
- Long-Term Neuropsychiatric Consequences of "Ecstasy" (MDMA): A Review Harvard Review of Psychiatry 2002
- Repeated MDMA (“Ecstasy”) exposure in adolescent male rats alters temperature regulation, spontaneous motor activity, attention, and serotonin transporter binding Developmental Psychobiology 2005
- THC Prevents MDMA Neurotoxicity in Mice PLoS One February 10, 2010
and 15 more in the library