Effect of cannabis on glutamate signalling in the brain: A systematic review of human and animal evidence

Marco Colizzi, Philip McGuire, Roger G. Pertwee, Sagnik Bhattacharyya*

*Corresponding author for this work

Research output: Contribution to journalLiterature reviewpeer-review

111 Citations (Scopus)


Use of cannabis or delta-9-tetrahydrocannabinol (Delta 9-THC), its main psychoactive ingredient, is associated with psychotic symptoms or disorder. However, the neurochemical mechanism that may underlie this psychotomimetic effect is poorly understood. Although dopaminergic dysfunction is generally recognized as the final common pathway in psychosis, evidence of the effects of Delta 9-THC or cannabis use on dopaminergic measures in the brain is equivocal. In fact, it is thought that cannabis or Delta 9-THC may not act on dopamine firing directly but indirectly by altering glutamate neurotransmission. Here we systematically review all studies examining acute and chronic effects of cannabis or Delta 9-THC on glutamate signalling in both animals and man. Limited research carried out in humans tends to support the evidence that chronic cannabis use reduces levels of glutamate-derived metabolites in both cortical and subcortical brain areas. Research in animals tends to consistently suggest that Delta 9-THC depresses glutamate synaptic transmission via CB1 receptor activation, affecting glutamate release, inhibiting receptors and transporters function, reducing enzyme activity, and disrupting glutamate synaptic plasticity after prolonged exposure. (C) 2016 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)359-381
Number of pages23
JournalNeuroscience & Biobehavioral Reviews
Publication statusPublished - May 2016


  • Cannabis
  • Delta-9-tetrahydrocannabinol
  • Glutamate signalling
  • Glutamatergic synaptic transmission
  • Cannabinoid receptor type 1
  • Functional genetic-variation
  • Long-term depression
  • Rat cerebellum
  • Delta-9-tetrahydrocannabinol exposure
  • Synaptic plasticity
  • Prefrontal Cortex
  • Delta(9)-tetrahydrocannabinol exposure
  • Extracellular glutamate
  • Attentional salience
  • Hippocampal-neurons


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