Brain imaging shows THC and CBD have opposite effects in key brain regions linked to psychosis

What the researchers found

Despite heterogeneous methods, an overall pattern of opposite THC and CBD effects was evident, primarily from head-to-head challenge studies. THC increased and CBD decreased brain activation and blood flow, with opposing effects most consistent in the striatum, parahippocampus, anterior cingulate/medial prefrontal cortex, and amygdala.

Why it matters

The brain regions where THC and CBD have opposing effects overlap with regions implicated in psychosis (striatum, parahippocampus). This may explain why THC increases psychosis risk while CBD has antipsychotic potential, and identifies specific neural targets for research.

The numbers in context

Opposite effects identified in: striatum, parahippocampus, anterior cingulate/medial prefrontal cortex, amygdala; THC generally increased activation and blood flow; CBD generally decreased both; head-to-head studies provided strongest evidence

How the study worked

Systematic search and synthesis of human neuroimaging studies investigating acute effects of THC and CBD on brain function, using fMRI, PET, SPECT, ASL, MRS, and EEG techniques.

What this study cannot tell us

Marked heterogeneity across studies in design, dosing, imaging modality, and analysis methods. Relatively few head-to-head THC vs. CBD comparison studies. Acute effects may not reflect chronic use patterns. Publication bias possible.

How to read the evidence

Systematic review of heterogeneous neuroimaging evidence with a consistent overall pattern, though limited by few head-to-head studies.

When this study was published

Published in 2021.

The bigger picture

Understanding where THC and CBD have opposing brain effects could guide development of cannabinoid-based medicines and explain individual variation in cannabis response based on THC:CBD ratios.

Questions still open

• Could CBD-dominant products protect against THC-induced brain changes when used together? Are the opposing brain effects dose-dependent?

Common questions

Read the original research

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

Biological psychiatry. Cognitive neuroscience and neuroimaging, 6(6), 636-645

Citation

Gunasekera, Brandon; Davies, Cathy; Martin-Santos, Rocio; Bhattacharyya, Sagnik. (2021). The Yin and Yang of Cannabis: A Systematic Review of Human Neuroimaging Evidence of the Differential Effects of Δ9-Tetrahydrocannabinol and Cannabidiol.. Biological psychiatry. Cognitive neuroscience and neuroimaging, 6(6), 636-645. https://doi.org/10.1016/j.bpsc.2020.10.007

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