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

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.

Individual and combined effects of Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) on striato-cortical connectivity in the human brain

“…Additional data from this study have been published elsewhere; these previous reports did not investigate resting-state striato-cortical connectivity (Bloomfield et al, 2020; Lawn et al, 2020).…”

“…CC-BY-NC-ND 4.0 International license available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made The copyright holder for this preprint this version posted November 21, 2020. ; https://doi.org/10.1101/2020.11.20.391805 doi: bioRxiv preprint 8 Additional data from this study have been published elsewhere; these previous reports did not investigate resting-state striato-cortical connectivity (Bloomfield et al, 2020;Lawn et al, 2020).…”

Identification of Phenotypic Characteristics in Three Chemotype Categories in the Genus Cannabis

“…However, these vernacular categories are unreliable for medical applications due to extensive cross-breeding and unreliable labeling during unrecorded hybridization (McPartland, 2017). CBD dominant and intermediate varieties were also excluded from these studies despite getting increasing attention from the therapeutic potential of CBD (Avraham et al, 2011;Bloomfield et al, 2020;French et al, 2017;McGuire et al, 2018), especially the indication of regulatory-approved prescription CBD (marketed as Epidiolex) to treat epilepsy (Billakota et al, 2019;Kaplan et al, 2017;Szaflarski et al, 2018). In addition to delimiting ''Sativa'' and ''Indica'' plants, recent studies tried to differentiate three chemotypes by profiling secondary metabolites (Jin et al, 2020), developing genetic markers (Borna et al, 2017;Kojoma et al, 2006;Pacifico et al, 2006;Rotherham et al, 2011;Toth et al, 2020), and comparing sequence and copy number variation of THC acid synthase and CBD acid synthase (McKernan et al, 2015;Onofri et al, 2015).…”

The acute effects of cannabidiol on emotional processing and anxiety: a neurocognitive imaging study

“…Critically, our null findings for the effect of CBD on experimentally-induced stress are in contrast to previous findings reporting that CBD attenuated task-induced anxiety (Bergamaschi et al, 2011;Zuardi et al, 1993;Zuardi et al, 2017), and these discrepant findings may be due to the potentially dose-dependent nature of CBD's effects. Recent work suggests that CBD may have an inverted-U shape dose-response curve (Campos & Guimaraes, 2008;Freeman et al, 2020;Hsiao, Yi, Li, & Chang, 2012;Linares et al, 2019;Zuardi et al, 2017) with best efficacy for human anxiety at 300 mg (Linares et al, 2019;Zuardi et al, 1993;Zuardi et al, 2017) compared to our dose of 600 mg. However, the finding that CBD was able to reduce drug-cue-induced craving and anxiety at single doses of 400 mg and 800 mg (Hurd et al, 2019), suggests that our dose of 600 mg still falls within the effective range, and so our negative finding remains important as evidence against the anxiolytic hypothesis of CBD.…”

“…Lastly, three previous studies have found that chronic administration of CBD was anxiolytic: a 21day treatment of 600 mg of CBD was effective at reducing psychosis-related anxiety in patients at high-risk of psychosis, compared to placebo (Bhattacharyya et al, 2018) and a four-week treatment of oil with 300 mg of CBD significantly reduced anxiety in a socially anxious sample, compared to placebo (Masataka, 2019). Additionally, four-week treatment with 800mg CBD reduced anxiety in people with a cannabis use disorder compared to placebo (Freeman et al, 2020). Therefore, repeated dosing of CBD may necessary to produce anxiolytic effects.…”