Co-administration of THC and MDMA ('ecstasy') synergistically disrupts memory in rats

Neuropsychopharmacology. 2005 Aug;30(8):1475-82. doi: 10.1038/sj.npp.1300692.


3,4-Methylenedioxymethamphetamine (MDMA, 'Ecstasy') and cannabis are two of the most commonly used illicit drugs in the western world, and are often used in combination. Very little research has examined their effect on cognitive function or behavior when combined, The present study used a double Y-maze task to examine the acute effect of MDMA and delta9-tetrahydrocannabinol (THC, the principal psychoactive ingredient of cannabis) on mnemonic function in rats, at a range of doses representative of common human use. Experiment I (low doses) examined the effect of 0.25 mg/kg THC and 1.25 mg/kg MDMA alone and together. At these doses MDMA or THC given alone had no effect on working memory, but the co-administered drugs significantly disrupted working memory. Experiment 2 (medium doses) examined the effect of 0.5 mg/kg THC and 2.5 mg/kg MDMA given alone or together. At these doses THC, but not MDMA, impaired working memory. Although MDMA alone had no effect, it exacerbated the impairment due to THC when the drugs were co-administered. Experiment 3 (high doses) examined the effects of 1 mg/kg THC and 5 mg/kg MDMA alone and together. Both drugs significantly impaired memory when given alone, although the impairment due to MDMA was less than that caused by THC. When co-administered at these doses, the drugs caused a major disruption of behavior and this precluded ascribing a mnemonic cause to poor performance on the double Y-maze task Taken together, these experiments demonstrate a synergistic disruption of working memory by acute co-administration of THC and MDMA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Discrimination, Psychological / drug effects
  • Dronabinol / administration & dosage*
  • Drug Combinations
  • Drug Synergism
  • Hallucinogens / administration & dosage*
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects*
  • Memory Disorders / chemically induced*
  • N-Methyl-3,4-methylenedioxyamphetamine / administration & dosage*
  • Rats
  • Rats, Wistar
  • Spatial Behavior / drug effects


  • Drug Combinations
  • Hallucinogens
  • Dronabinol
  • N-Methyl-3,4-methylenedioxyamphetamine