Sex-Dependent Psychoneuroendocrine Effects of THC and MDMA in an Animal Model of Adolescent Drug Consumption
Alvaro Llorente‐berzal, Emma Puighermanal, Aurelijus Burokas, Andrés Ozaita, Rafaël Maldonado, Eva M. Marco, María‐paz Viveros
PLoS One November 4, 2013 DOI: 10.1371/journal.pone.0078386 (opens in new tab)
The journal has published a correction to this paper. Read the correction (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | Male and female Wistar rats |
| Interventions | THC MDMA |
| Dose | THC: 2.5, 5, 10 mg/kg i.p.; MDMA: 10 mg/kg s.c. twice daily every 5 days |
| Duration | From postnatal day 28 to 45 (THC) and from postnatal day 30 to 45 (MDMA); tested on postnatal day 46 and later |
| Measures | holeboard test, elevated plus maze, novel object test, prepulse inhibition |
| Topics | Cannabis MDMA |
| Keywords | Prepulse inhibition Hallucinogen Endocrinology Hippocampal formation Pharmacology Delta-9-tetrahydrocannabinol |
| Citations | 43 |
| Key findings | Adolescent exposure to THC and/or MDMA induces long-term, sex-dependent psychophysiological alterations and reveals functional interactions between the two drugs. |
Abstract
Ecstasy is a drug that is usually consumed by young people at the weekends and frequently, in combination with cannabis. In the present study we have investigated the long-term effects of administering increasing doses of delta-9-tetrahydrocannabinol [THC; 2.5, 5, 10 mg/kg; i.p.] from postnatal day (pnd) 28 to 45, alone and/or in conjunction with 3,4-methylenedioxymethamphetamine [MDMA; two daily doses of 10 mg/kg every 5 days; s.c.] from pnd 30 to 45, in both male and female Wistar rats. When tested one day after the end of the pharmacological treatment (pnd 46), MDMA administration induced a reduction in directed exploration in the holeboard test and an increase in open-arm exploration in an elevated plus maze. In the long-term, cognitive functions in the novel object test were seen to be disrupted by THC administration to female but not male rats. In the prepulse inhibition test, MDMA-treated animals showed a decrease in prepulse inhibition at the most intense prepulse studied (80 dB), whereas in combination with THC it induced a similar decrease at 75 dB. THC decreased hippocampal Arc expression in both sexes, while in the frontal cortex this reduction was only evident in females. MDMA induced a reduction in ERK1/2 immunoreactivity in the frontal cortex of male but not female animals, and THC decreased prepro-orexin mRNA levels in the hypothalamus of males, although this effect was prevented when the animals also received MDMA. The results presented indicate that adolescent exposure to THC and/or MDMA induces long-term, sex-dependent psychophysiological alterations and they reveal functional interactions between the two drugs.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 14
- Long-term consequences of adolescent cannabinoid exposure in adult psychopathology Frontiers in Neuroscience November 10, 2014
- 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
- Modulation of Gut Microbiome in Ecstasy/MDMA-Induced Behavioral and Biochemical Impairment in Rats and Potential of Post-Treatment with Anacyclus pyrethrum L. Aqueous Extract to Mitigate Adverse Effects. International Journal of Molecular Sciences May 22, 2023
- The antioxidant N-acetylcysteine prevents cortical neuropathological phenotypes caused by adolescent Δ-9-tetrahydrocannabinol exposure in male rats. Translational Psychiatry October 6, 2025
- Long-term effects of adolescent THC exposure on anxiety-like behavior and cognitive function in male rats Psychopharmacology April 23, 2026
and 9 more in the library
Cites 36
- 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
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- Cognitive performance in recreational users of MDMA or 'ecstasy': evidence for memory deficits Journal of Psychopharmacology 1998
- Neurotoxicity of methylenedioxyamphetamines (MDMA; ecstasy) in humans: how strong is the evidence for persistent brain damage? Addiction February 27, 2006
- MDMA (3,4-Methylenedioxymethamphetamine) or Ecstasy: The Neuropsychobiological Implications of Taking It at Dances and Raves Neuropsychobiology 2004
and 31 more in the library