MDMA attenuates THC withdrawal syndrome in mice.
BACKGROUND
3, 4-Methylenedioxymethamphetamine (MDMA) and cannabis are widely abused illicit drugs that are frequently consumed in combination. Interactions between these two drugs have been reported in several pharmacological responses observed in animals, such as body temperature, anxiety, cognition, and reward. However, the interaction between MDMA and cannabis in addictive processes such as physical dependence has not been elucidated yet.


CONCLUSIONS
In this study, the effects of acute and chronic MDMA were evaluated on the behavioral manifestations of Delta(9)-tetrahydrocannabinol (THC) abstinence in mice. THC withdrawal syndrome was precipitated by injecting the cannabinoid antagonist rimonabant (10 mg/kg, i.p.) in mice chronically treated with THC and receiving MDMA (2.5, 5 and 10 mg/kg i.p.) or saline just before the withdrawal induction or chronically after the THC administration.


RESULTS
Both chronic and acute MDMA decreased in a dose-dependent manner the severity of THC withdrawal. In vivo microdialysis experiments showed that acute MDMA (5 mg/kg, i.p.) administration increased extracellular serotonin levels in the prefrontal cortex, but not dopamine levels in the nucleus accumbens. Our results also indicate that the attenuation of THC abstinence symptoms was not due to a direct interaction between rimonabant and MDMA nor to the result of the locomotor stimulating effects of MDMA.


CONCLUSIONS
The modulation of the cannabinoid withdrawal syndrome by acute or chronic MDMA suggests a possible mechanism to explain the associated consumption of these two drugs in humans.
Touriño
Clara
C
Grup de Recerca de Neurobiologia del Comportament, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, PRBB, C/ Dr. Aiguader 80, 08003, Barcelona, Spain.
Maldonado
Rafael
R
Valverde
Olga
O
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D063387:Cannabinoid Receptor Antagonists; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000627:therapeutic use*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D000077285:Rimonabant; D012701:Serotonin / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000503:physiopathology
D063387:Cannabinoid Receptor Antagonists; D010880:Piperidines; D011720:Pyrazoles; D012701:Serotonin; D013759:Dronabinol; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D000077285:Rimonabant; D004298:Dopamine