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

Michael A P Bloomfield,Oliver D Howes,H Valerie Curran,Hannah R Walker,Tom P Freeman,Pawel Tokarczuk,Jocelyn Lok Ling Yim,Ben Statton,Yumeya Yamamori,Augustus P M Jones,Sebastian F Green,Chandni Hindocha

doi:10.1177/0269881120936419

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.

Highlights

Cannabidiol (CBD) is one of the main constituents of cannabis and is gaining interest for its broad therapeutic potential (Campos et al, 2016; Devinsky et al, 2014; Freeman et al, 2019; Zuardi, 2008)
In addition to antipsychotic (Leweke et al, 2012; McGuire et al, 2018; Zuardi et al, 2012) and anxiolytic properties (Bergamaschi et al, 2011; Blessing et al, 2015; Crippa et al, 2011; Soares and Campos, 2017), there is some evidence to suggest that CBD may improve memory impairment across multiple domains, including working and episodic memory, as demonstrated in several preclinical models (Avraham et al, 2011; Barichello et al, 2012; Campos et al, 2015; Cassol et al, 2010; Cheng et al, 2014a, 2014b; Fagherazzi et al, 2012; Magen et al, 2009, 2010; Martin-Moreno et al, 2011; Pazos et al, 2012; Schiavon et al, 2014; Wright et al, 2013), cannabis users
We defined regions of interest (ROIs) in the medial temporal lobe (MTL) and prefrontal cortex (PFC) a priori, which are differentially involved in both memory domains, including the hippocampus (Leszczynski, 2011; Squire and Zolamorgan, 1991), parahippocampal gyrus (Luck et al, 2010; Zolamorgan et al, 1989), amygdala (Hamann et al, 1999; Peinadomanzano, 1990; Phelps, 2004), dorsolateral PFC (Mars and Grol, 2007; Nyberg et al, 1996), orbitofrontal cortex (OFC) (Barbey et al, 2011; Brand and Markowitsch, 2006) and ventromedial PFC (Bechara et al, 1998; Bonnici et al, 2012)

Summary

Introduction

Cannabidiol (CBD) is one of the main constituents of cannabis and is gaining interest for its broad therapeutic potential (Campos et al, 2016; Devinsky et al, 2014; Freeman et al, 2019; Zuardi, 2008). Our secondary aim was to investigate the relationship between CBF and memory performance in episodic and working memory tasks. Our secondary aim was to determine if the effects of CBD on CBF were associated with differences in working and episodic memory task performance. 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, 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

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