Rivastigmine but not vardenafil reverses cannabis-induced impairment of verbal memory in healthy humans

Psychopharmacology (Berl). 2015 Jan;232(2):343-53. doi: 10.1007/s00213-014-3667-2. Epub 2014 Jul 8.


Rationale: One of the most often reported cognitive deficits of acute cannabis administration is an impaired recall of previously learned information.

Objective: The aim of the present study was to determine whether cannabis-induced memory impairment in humans is mediated via glutamatergic or cholinergic pathways.

Methods: Fifteen occasional cannabis users participated in a double-blind, placebo-controlled, six-way cross-over study. On separate test days, subjects received combinations of pretreatment (placebo, vardenafil 20 mg or rivastigmine 3 mg) and treatment (placebo or 1,376 mg cannabis/kg body weight). Cognitive tests were administered immediately after inhalation of treatment was finished and included measures of memory (visual verbal learning task, prospective memory test, Sternberg memory test), perceptual-motor control (critical tracking task), attention (divided attention task) and motor impulsivity (stop signal task).

Results: The results of this study demonstrate that subjects under the influence of cannabis were impaired in all memory tasks, in critical tracking, divided attention and the stop signal task. Pretreatment with rivastigmine attenuated the effect of cannabis on delayed recall and showed a trend towards significance on immediate recall. When cannabis was given in combination with vardenafil, there were no significant interaction effects in any of the tasks.

Conclusions: The present data therefore suggest that acetylcholine plays an important role in cannabis-induced memory impairment, whereas similar results for glutamate have not been demonstrated in this study.

Publication types

  • Clinical Trial

MeSH terms

  • Acetylcholine / metabolism
  • Adult
  • Attention / drug effects
  • Cannabinoids / administration & dosage
  • Cannabinoids / blood
  • Cannabis*
  • Cognition / drug effects
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Glutamic Acid / metabolism
  • Humans
  • Imidazoles / therapeutic use*
  • Male
  • Marijuana Smoking / adverse effects*
  • Marijuana Smoking / drug therapy
  • Marijuana Smoking / metabolism*
  • Marijuana Smoking / psychology
  • Memory / drug effects
  • Memory Disorders / drug therapy
  • Memory Disorders / etiology*
  • Memory Disorders / metabolism*
  • Memory, Short-Term / drug effects
  • Phenylcarbamates / therapeutic use*
  • Piperazines / therapeutic use*
  • Prospective Studies
  • Rivastigmine
  • Sulfones / therapeutic use
  • Triazines / therapeutic use
  • Vardenafil Dihydrochloride
  • Verbal Learning / drug effects
  • Young Adult


  • Cannabinoids
  • Imidazoles
  • Phenylcarbamates
  • Piperazines
  • Sulfones
  • Triazines
  • Glutamic Acid
  • Vardenafil Dihydrochloride
  • Acetylcholine
  • Rivastigmine