Memory impairment following combined exposure to delta(9)-tetrahydrocannabinol and ethanol in rats

Eur J Pharmacol. 2002 Aug 9;449(3):245-52. doi: 10.1016/s0014-2999(02)01999-4.


Cannabis derivatives and alcohol are widely co-abused, particularly among adolescents. Since both ethanol and cannabinoids are known to impair learning and memory, the present study investigated in rats the effects of combined exposure to ethanol and delta(9)-tetrahydrocannabinol (THC) in a memory task, the object recognition test. The results of the present study provide evidence that ethanol, voluntarily ingested in alcohol-preferring rats, and THC, given by intraperitoneal injection, have a synergic action to impair object recognition, when a 15-min interval was adopted between the sample phase and the choice phase of the test. Neither voluntary ethanol ingestion nor 2 or 5 mg/kg of THC were able per se to modify object recognition in these experimental conditions, but when voluntary ethanol ingestion was combined with administration of these doses of THC object recognition was markedly impaired. THC impaired object recognition only at the dose of 10 mg/kg, when its administration was not combined with that of ethanol. The selective cannabinoid CB(1) receptor antagonist SR 141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1(2, 4-dichloro-phenyl)-4-methyl-1H-pyrazole carboxamide.HCl) at the dose of 1 mg/kg reversed the amnesic effect of THC, 10 mg/kg, suggesting that the effect is mediated by this receptor subtype. The synergism of ethanol and THC was not detected when an inter-trial interval of 1 min was adopted. The present findings are in keeping with the notion that Cannabis derivatives impair memory processes and provide evidence for a synergic action of THC and ethanol, thus emphasizing the risks consequent to their co-administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / psychology
  • Animals
  • Central Nervous System Depressants / toxicity*
  • Discrimination, Psychological / drug effects
  • Dronabinol / toxicity*
  • Drug Interactions
  • Ethanol / toxicity*
  • Form Perception / drug effects
  • Hallucinogens / toxicity*
  • Male
  • Memory Disorders / chemically induced*
  • Memory Disorders / psychology
  • Motor Activity / drug effects
  • Rats


  • Central Nervous System Depressants
  • Hallucinogens
  • Ethanol
  • Dronabinol