Cannabidiol attenuates deficits of visuospatial associative memory induced by Δ(9) tetrahydrocannabinol

Br J Pharmacol. 2013 Dec;170(7):1365-73. doi: 10.1111/bph.12199.


Background and purpose: Recent human studies suggest that recreational cannabis strains that are relatively high in cannabidiol (CBD) content produce less cognitive impairment than do strains with negligible CBD and similar Δ(9) tetrahydrocannabinol (THC) content. Self-selection in such studies means it is impossible to rule out additional variables which may determine both cannabis strain selection and basal cognitive performance level. Controlled laboratory studies can better determine a direct relationship.

Experimental approach: In this study, adult male rhesus monkeys were assessed on visuospatial Paired Associates Learning and Self-Ordered Spatial Search memory tasks, as well as additional tests of motivation and manual dexterity. Subjects were challenged with THC (0.2, 0.5 mg·kg(-1) , i.m.) in randomized order and evaluated in the presence or absence of 0.5 mg·kg(-1) CBD.

Key results: CBD attenuated the effects of THC on paired associates learning and a bimanual motor task without affecting the detrimental effects of THC on a Self-Ordered Spatial Search task of working memory. CBD did not significantly reverse THC-induced impairment of a progressive ratio or a rotating turntable task.

Conclusions and implications: This study provides direct evidence that CBD can oppose the cognitive-impairing effects of THC and that it does so in a task-selective manner when administered simultaneously in a 1:1 ratio with THC. The addition of CBD to THC-containing therapeutic products may therefore help to ameliorate unwanted cognitive side-effects.

Linked article: This article is commented on by Mechoulam and Parker, pp 1363-1364 of this issue. To view this commentary visit

Keywords: Macaca mulatta; cannabis; marijuana; working memory.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Cannabidiol / pharmacology*
  • Cognition / drug effects*
  • Dronabinol / toxicity*
  • Functional Laterality / drug effects
  • Macaca mulatta
  • Male
  • Memory / drug effects*
  • Memory Disorders / chemically induced
  • Memory Disorders / prevention & control*
  • Memory Disorders / psychology
  • Models, Animal
  • Molecular Sequence Data
  • Motivation / drug effects
  • Motor Activity / drug effects
  • Time Factors


  • Cannabidiol
  • Dronabinol

Associated data

  • GENBANK/AA007456
  • GENBANK/DA024194