Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity
Matthew B. Wall, Rebecca Pope, Tom P. Freeman, Olivia S. Kowalczyk, Lysia Demetriou, Claire Mokrysz, Chandni Hindocha, Will Lawn, Michael Bloomfield, Abigail M. Freeman, Amanda Feilding, David Nutt, H. Valerie Curran
Journal of Psychopharmacology April 23, 2019 DOI: 10.1177/0269881119841568 via OpenAlex
Summary
Two strains of cannabis—one containing only THC (8 mg) and another containing THC plus CBD (8 mg THC + 10 mg CBD)—were compared with placebo in seventeen healthy, experienced but non-regular cannabis users. Using resting-state fMRI, both strains reduced functional connectivity in the default mode and salience networks relative to placebo, but with distinct spatial patterns. The THC-only strain specifically disrupted the posterior cingulate cortex within the default mode network, and this disruption correlated with subjective feelings of being 'stoned' and 'high'. The THC-plus-CBD strain produced less disruption of the salience network, suggesting CBD may buffer THC's effects on salience processing, which could underlie its potential therapeutic role in disorders like psychosis and addiction.
Study at a glance
| Characteristics | Within-subjects experimental design Peer reviewed |
|---|---|
| Sample size | 17 |
| Population | Healthy volunteers experienced with cannabis but not regular users |
| Intervention | matched placebo cannabis |
| Dose | 8 mg THC; 8 mg THC + 10 mg CBD |
| Duration | Single session per treatment, scanning session after each treatment |
| Topics | Cannabis |
| Keywords | Functional connectivity Neuroscience Resting State FMRI Psychology |
| Citations | 89 |
| Key finding | THC disrupts the default mode network and the posterior cingulate cortex is key to subjective intoxication, while CBD may restore THC-induced disruption of the salience network. |
Abstract
BACKGROUND: -tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the main psychoactive component; CBD may buffer the user against the harmful effects of THC. AIMS: We examined the effects of two strains of cannabis and placebo on the human brain's resting-state networks using fMRI. METHODS: Seventeen healthy volunteers (experienced with cannabis, but not regular users) underwent three drug treatments and scanning sessions. Treatments were cannabis containing THC (Cann-CBD; 8 mg THC), cannabis containing THC with CBD (Cann+CBD; 8 mg THC + 10 mg CBD), and matched placebo cannabis. Seed-based resting-state functional connectivity analyses were performed on three brain networks: the default mode (DMN; defined by positive connectivity with the posterior cingulate cortex: PCC+), executive control (ECN; defined by negative connectivity with the posterior cingulate cortex: PCC-) and salience (SAL; defined by positive connectivity with the anterior insula: AI+) network. RESULTS: Reductions in functional connectivity (relative to placebo) were seen in the DMN (PCC+) and SAL (AI+) networks for both strains of cannabis, with spatially dissociable effects. Across the entire salience network (AI+), Cann-CBD reduced connectivity relative to Cann+CBD. The PCC in the DMN was specifically disrupted by Cann-CBD, and this effect correlated with subjective drug effects, including feeling 'stoned' and 'high'. CONCLUSIONS: THC disrupts the DMN, and the PCC is a key brain region involved in the subjective experience of THC intoxication. CBD restores disruption of the salience network by THC, which may explain its potential to treat disorders of salience such as psychosis and addiction.