The Yin and Yang of Cannabis: A Systematic Review of Human Neuroimaging Evidence of the Differential Effects of Δ⁹-Tetrahydrocannabinol and Cannabidiol

TY - JOUR

T1 - The Yin and Yang of Cannabis

T2 - A Systematic Review of Human Neuroimaging Evidence of the Differential Effects of Δ9-Tetrahydrocannabinol and Cannabidiol

AU - Gunasekera, Brandon

AU - Davies, Cathy

AU - Martin-Santos, Rocio

AU - Bhattacharyya, Sagnik

N1 - Funding Information: This work was supported by grants from the National Institute of Health Research Efficacy and Mechanism Evaluation scheme (Grant No. 16/126/53 [to SB]) and Parkinson's UK (Grant No. G-1901 [to SB]). The views expressed are those of the authors and not necessarily those of the National Health Service, the National Institute of Health Research, or the Department of Health. The authors report no biomedical financial interests or potential conflicts of interest. Funding Information: This work was supported by grants from the National Institute of Health Research Efficacy and Mechanism Evaluation scheme (Grant No. 16/126/53 [to SB]) and Parkinson’s UK (Grant No. G-1901 [to SB]). The views expressed are those of the authors and not necessarily those of the National Health Service, the National Institute of Health Research, or the Department of Health. Publisher Copyright: © 2020 Society of Biological Psychiatry Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/6

Y1 - 2021/6

N2 - Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) have been the most investigated cannabinoids at the human and preclinical levels, although the neurobiological mechanisms underlying their effects remain unclear. Human experimental evidence complemented by observational studies suggests that THC may have psychotogenic effects while CBD may have antipsychotic effects. However, whether their effects on brain function are consistent with their opposing behavioral effects remains unclear. To address this, here we synthesize neuroimaging evidence investigating the acute effects of THC and CBD on human brain function using a range of neuroimaging techniques, with an aim to identify the key brain substrates where THC and CBD have opposing effects. After a systematic search, a review of the available studies indicated marked heterogeneity. However, an overall pattern of opposite effect profiles of the two cannabinoids was evident with some degree of consistency, primarily attributed to the head-to-head challenge studies of THC and CBD. While head-to-head comparisons are relatively few, collectively the evidence suggests that opposite effects of THC and CBD may be present in the striatum, parahippocampus, anterior cingulate/medial prefrontal cortex, and amygdala, with opposite effects less consistently identified in other regions. Broadly, THC seems to increase brain activation and blood flow, whereas CBD seems to decrease brain activation and blood flow. Given the sparse evidence, there is a particular need to understand the mechanisms underlying their opposite behavioral effects because it may not only offer insights into the underlying pathophysiological mechanisms of psychotic disorders but also suggest potentially novel targets and biomarkers for drug discovery.

AB - Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) have been the most investigated cannabinoids at the human and preclinical levels, although the neurobiological mechanisms underlying their effects remain unclear. Human experimental evidence complemented by observational studies suggests that THC may have psychotogenic effects while CBD may have antipsychotic effects. However, whether their effects on brain function are consistent with their opposing behavioral effects remains unclear. To address this, here we synthesize neuroimaging evidence investigating the acute effects of THC and CBD on human brain function using a range of neuroimaging techniques, with an aim to identify the key brain substrates where THC and CBD have opposing effects. After a systematic search, a review of the available studies indicated marked heterogeneity. However, an overall pattern of opposite effect profiles of the two cannabinoids was evident with some degree of consistency, primarily attributed to the head-to-head challenge studies of THC and CBD. While head-to-head comparisons are relatively few, collectively the evidence suggests that opposite effects of THC and CBD may be present in the striatum, parahippocampus, anterior cingulate/medial prefrontal cortex, and amygdala, with opposite effects less consistently identified in other regions. Broadly, THC seems to increase brain activation and blood flow, whereas CBD seems to decrease brain activation and blood flow. Given the sparse evidence, there is a particular need to understand the mechanisms underlying their opposite behavioral effects because it may not only offer insights into the underlying pathophysiological mechanisms of psychotic disorders but also suggest potentially novel targets and biomarkers for drug discovery.

KW - Cannabidiol

KW - Cannabis

KW - CBD

KW - Connectivity

KW - fMRI

KW - Neuroimaging

KW - PET

KW - Psychosis

KW - Review

KW - THC

UR - http://www.scopus.com/inward/record.url?scp=85098968251&partnerID=8YFLogxK

U2 - 10.1016/j.bpsc.2020.10.007

DO - 10.1016/j.bpsc.2020.10.007

M3 - Review article

AN - SCOPUS:85098968251

SN - 2451-9022

VL - 6

SP - 636

EP - 645

JO - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

JF - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

IS - 6

ER -