The effects of acute cannabidiol on cerebral blood flow and its relationship to memory: An arterial spin labelling magnetic resonance imaging study

J Psychopharmacol. 2020 Sep;34(9):981-989. doi: 10.1177/0269881120936419. Epub 2020 Aug 7.

Abstract

Background: Cannabidiol (CBD) is being investigated as a potential treatment for several medical indications, many of which are characterised by altered memory processing. However, the mechanisms underlying these effects are unclear.

Aims: Our primary aim was to investigate how CBD influences cerebral blood flow (CBF) in regions involved in memory processing. Our secondary aim was to determine if the effects of CBD on CBF were associated with differences in working and episodic memory task performance.

Methods: We used a randomised, crossover, double-blind design in which 15 healthy participants were administered 600 mg oral CBD or placebo on separate days. We measured regional CBF at rest using arterial spin labelling 3 h after drug ingestion. We assessed working memory with the digit span (forward, backward) and n-back (0-back, 1-back, 2-back) tasks, and we used a prose recall task (immediate and delayed) to assess episodic memory.

Results: CBD increased CBF in the hippocampus (mean (95% confidence intervals) = 15.00 (5.78-24.21) mL/100 g/min, t14 = 3.489, Cohen's d = 0.75, p = 0.004). There were no differences in memory task performance, but there was a significant correlation whereby greater CBD-induced increases in orbitofrontal CBF were associated with reduced reaction time on the 2-back working memory task ( r= -0.73, p = 0.005).

Conclusions: These findings suggest that CBD increases CBF to key regions involved in memory processing, particularly the hippocampus. These results identify potential mechanisms of CBD for a range of conditions associated with altered memory processing, including Alzheimer's disease, schizophrenia, post-traumatic stress disorder and cannabis-use disorders.

Keywords: ASL; MRI; cannabidiol; hippocampus; memory; perfusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cannabidiol / administration & dosage
  • Cannabidiol / pharmacology*
  • Cannabinoid Receptor Modulators / administration & dosage
  • Cannabinoid Receptor Modulators / pharmacology*
  • Cerebrovascular Circulation / drug effects*
  • Female
  • Hippocampus / diagnostic imaging
  • Hippocampus / drug effects*
  • Hippocampus / physiology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory, Episodic*
  • Memory, Short-Term / drug effects*
  • Memory, Short-Term / physiology
  • Mental Recall / drug effects*
  • Mental Recall / physiology
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / physiology
  • Psychomotor Performance / drug effects*
  • Psychomotor Performance / physiology
  • Spin Labels
  • Young Adult

Substances

  • Cannabinoid Receptor Modulators
  • Spin Labels
  • Cannabidiol