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Dissociable effects of cannabis with and without cannabidiol on the human brain's resting-state functional connectivity.
J Psychopharmacol 2019; 33(7):822-830JP

Abstract

BACKGROUND

Two major constituents of cannabis are Δ9-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.

Authors+Show Affiliations

1 Invicro London, Hammersmith Hospital, London, UK. 2 Clinical Psychopharmacology Unit, University College London, London, UK. 3 Division of Brain Sciences, Imperial College London, London, UK.2 Clinical Psychopharmacology Unit, University College London, London, UK.2 Clinical Psychopharmacology Unit, University College London, London, UK. 4 Addiction and Mental Health Group (AIM), Department of Psychology, University of Bath, Bath, UK. 5 National Addiction Centre, Institute of Psychiatry, Psychology and Neuroscience, London, UK.6 Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.1 Invicro London, Hammersmith Hospital, London, UK. 3 Division of Brain Sciences, Imperial College London, London, UK.2 Clinical Psychopharmacology Unit, University College London, London, UK.2 Clinical Psychopharmacology Unit, University College London, London, UK.2 Clinical Psychopharmacology Unit, University College London, London, UK.2 Clinical Psychopharmacology Unit, University College London, London, UK. 7 Division of Psychiatry, University College London, London, UK. 8 Psychiatric Imaging, MRC London Institute of Clinical Sciences, Imperial College London, Hammersmith Hospital, London, UK.2 Clinical Psychopharmacology Unit, University College London, London, UK.9 The Beckley Foundation, Oxford, UK.3 Division of Brain Sciences, Imperial College London, London, UK.2 Clinical Psychopharmacology Unit, University College London, London, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31013455

Citation

Wall, Matthew B., et al. "Dissociable Effects of Cannabis With and Without Cannabidiol On the Human Brain's Resting-state Functional Connectivity." Journal of Psychopharmacology (Oxford, England), vol. 33, no. 7, 2019, pp. 822-830.
Wall MB, Pope R, Freeman TP, et al. Dissociable effects of cannabis with and without cannabidiol on the human brain's resting-state functional connectivity. J Psychopharmacol (Oxford). 2019;33(7):822-830.
Wall, M. B., Pope, R., Freeman, T. P., Kowalczyk, O. S., Demetriou, L., Mokrysz, C., ... Curran, H. V. (2019). Dissociable effects of cannabis with and without cannabidiol on the human brain's resting-state functional connectivity. Journal of Psychopharmacology (Oxford, England), 33(7), pp. 822-830. doi:10.1177/0269881119841568.
Wall MB, et al. Dissociable Effects of Cannabis With and Without Cannabidiol On the Human Brain's Resting-state Functional Connectivity. J Psychopharmacol (Oxford). 2019;33(7):822-830. PubMed PMID: 31013455.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dissociable effects of cannabis with and without cannabidiol on the human brain's resting-state functional connectivity. AU - Wall,Matthew B, AU - Pope,Rebecca, AU - Freeman,Tom P, AU - Kowalczyk,Oliwia S, AU - Demetriou,Lysia, AU - Mokrysz,Claire, AU - Hindocha,Chandni, AU - Lawn,Will, AU - Bloomfield,Michael Ap, AU - Freeman,Abigail M, AU - Feilding,Amanda, AU - Nutt,David, AU - Curran,H Valerie, Y1 - 2019/04/23/ PY - 2019/4/24/pubmed PY - 2019/4/24/medline PY - 2019/4/24/entrez KW - Cannabis KW - THC KW - cannabidiol KW - default mode network KW - fMRI KW - marijuana KW - resting state KW - salience network SP - 822 EP - 830 JF - Journal of psychopharmacology (Oxford, England) JO - J. Psychopharmacol. (Oxford) VL - 33 IS - 7 N2 - BACKGROUND: Two major constituents of cannabis are Δ9-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. SN - 1461-7285 UR - https://www.unboundmedicine.com/medline/citation/31013455/Dissociable_effects_of_cannabis_with_and_without_cannabidiol_on_the_human_brain's_resting_state_functional_connectivity_ L2 - http://journals.sagepub.com/doi/full/10.1177/0269881119841568?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -