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This study investigates brain response to single acute dose of cannabidiol, cannabidivarin, and placebo in healthy men with and without autism spectrum disorder
Previous research suggests that cannabidiol (CBD) and cannabidivarin (CBDV) could have the potential to shift brain excitation and inhibition (E-I) in the healthy brain and in neurodevelopmental psychiatric conditions, where this balance is disrupted, such as autism spectrum disorder (ASD). However, no study to date has investigated this. Therefore, in this study, we invited 20 healthy men with and without ASD. Each participant received each drug once (600mg CBD/CBDV, or matched placebo) and magnetic resonance imaging was used to obtain measures of brain biochemistry, activity, and connectivity. We further obtained questionnaires, task data, saliva, urine and blood samples, and conducted visual tasks using eye tracking, electroencephalography, and retinal imaging.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PLC, CBD, CBDV | Experimental | Dose order: PLC, CBD, CBDV |
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| PLC, CBDV, CBD | Experimental | Dose order: PL, CBDV, CBD |
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| CBD, PLC, CBDV | Experimental | Dose order: CBD, PLC, CBDV |
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| CBD, CBDV, PLC | Experimental | Dose order: CBD, CBDV, PLC |
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| CBDV, PLC, CBD | Experimental | Dose order: CBDV, PLC, CBD |
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| CBDV, CBD, PLC | Experimental | Dose order: CBDV, CBD, PLC |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PLC | Drug | Single oral dose of PLC. |
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| Measure | Description | Time Frame |
|---|---|---|
| Brain biochemistry response to pharmacological stimulation | The measure of brain biochemistry response to PLC, CBD, and CBDV includes the following: Assessment of the ratio of brain excitation and inhibition (measured as the balance of excitatory and inhibitory neurotransmitters) using using proton magnetic resonance spectroscopy [1H]MRS. | In the months 1-2 following the last day of scanning. |
| Measure | Description | Time Frame |
|---|---|---|
| Measurement of low frequency brain activity using resting state fMRI | In the third and fourth month following the day of the last scan, we will measure whole brain low frequency brain activity using resting state functional magnetic resonance imaging. Measure of activity: fractional amplitude of low frequency fluctuations. | In the months 3-4 following the last day of scanning |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Grainne McAlonan, PhD | King's College London | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| King's College London | London | SE5 8AF | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34210360 | Derived | Pretzsch CM, Floris DL, Voinescu B, Elsahib M, Mendez MA, Wichers R, Ajram L, Ivin G, Heasman M, Pretzsch E, Williams S, Murphy DGM, Daly E, McAlonan GM. Modulation of striatal functional connectivity differences in adults with and without autism spectrum disorder in a single-dose randomized trial of cannabidivarin. Mol Autism. 2021 Jul 1;12(1):49. doi: 10.1186/s13229-021-00454-6. |
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| ID | Term |
|---|---|
| D000067877 | Autism Spectrum Disorder |
| ID | Term |
|---|---|
| D002659 | Child Development Disorders, Pervasive |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D002185 | Cannabidiol |
| C580853 | cannabidivarin |
| ID | Term |
|---|---|
| D002186 | Cannabinoids |
| D013729 | Terpenes |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
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Repeated-measures cross-over study, where each subject received each of three pharmacological probes once (order of drug administration was pseudorandomised)
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Participants and investigators were blinded to the drug condition.
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| CBD | Drug | Single oral dose of cannabidiol (CBD) - 600mg. |
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| CBDV | Drug | Single oral dose of cannabidivarin (CBDV) - 600mg. |
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| Measurement of brain functional connectivity using resting state fMRI | In the fifth and sixth month following the day of the last scan, we will measure whole brain resting state functional connectivity using resting state functional magnetic resonance imaging. Measure of connectivity: correlation between pairs of regions. | In the months 5-6 following the last day of scanning |