Effects of Cannabidiol (CBD) on the Brain

Study Overview
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Brief Summary
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Cannabidiol (CBD) is a phytocannabinoid that is one of 113 identified cannabinoids in the cannabis plant. It is derived from the hemp plant, and may treat conditions like pain, insomnia, and anxiety. CBD is a critical component of medical marijuana and does not cause the high typically associated with cannabis. According to the World Health Organization, CBD has shown no evidence of abuse or dependence potential. However, to the investigator's knowledge, there have not been many acute clinical studies to characterize the effects of CBD in the brain. Despite the rapid influx in CBD readily available to the public, very little is known about such effects. Some studies have shown alterations in resting state connectivity, while others have described changes in specific regions of the brain, or in networks associated with various cognitive functions. For example, CBD has been shown to increase fronto-striatal connectivity and reduce mediotemporal-prefrontal connectivity, suggesting that CBD may affect brain regions involved in salience processing. Unfortunately, few studies have examined CBD in isolation. Additionally, several studies have suggested that CBD may have a neuroprotective effect when it comes to individuals at high risk for psychiatric conditions. In this study, the investigators propose an acute administration, double-blind, placebo-controlled study in which 100% THC-free CBD will be compared to placebo (https://foliumbiosciences.com/). To the investigator's knowledge, the acute effects of this specific product have not been tested. Specifically, the investigators will examine: 1) the neurometabolic and neurophysiological effects of CBD compared to placebo and 2) the behavioral effects of CBD on measures of working memory and response inhibition. Participants will be recruited to take encapsulated, THC-free CBD provided by Folium Biosciences, in which they will have a pre- and post-ingestion scan. Each participant will have a 72-hour washout period after which they will be asked to come back for a placebo scan (however, the order will be counterbalanced so that equal numbers of participants will receive placebo/supplement and supplement/placebo). Individuals will be randomized into the supplementation group, as well as the order.

Official Title
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Effects of Cannabidiol (CBD) on the Brain

Conditions
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CBD, Fear, Inhibition

Intervention / Treatment
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* Drug: Cannabidiol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: right-handed between 21-50 years of age no current diagnosis of psychiatric or neurological conditions no history of heart disease or stroke generally healthy pass a screening test for the MR environment Exclusion Criteria: contraindications to the MR environment use of psychotropic or neurological medication history of heart disease or stroke diabetes or other metabolic conditions self-reported high blood pressure history of concussions any diagnosed psychiatric or neurological condition have consumed alcohol in the 24-hour period prior to a scan consumed pain relievers in the 12-hours prior to a scan consumed food or drinks (except water) and/or nicotine/caffeine an hour prior to any scanning have used or take THC/CBD exercised within an hour of a scan

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Single-site, randomized, placebo-controlled, cross-over, within-subjects design. Study sessions are 72 hours apart. Visits included pre-post assessments following ingestion of either placebo or CBD.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cannabidiol (CBD)<br>A tincture containing 125mg broad spectrum CBD oil (6.7%), 24mg sunflower lecithin (1.3%), 56mg peppermint oil (3.0%), and 1661mg hempseed oil (89.0%) will be administered orally. Participants will place the liquid in their mouth for 45 seconds before swallowing it. | Drug: Cannabidiol<br>* Administered orally. Participants will place the liquid in their mouth for 45 seconds before swallowing it.<br>* Other names: CBD;Drug: Placebo<br>* Administered orally. Participants will place the liquid in their mouth for 45 seconds before swallowing it.<br>|
| Placebo Comparator: Placebo<br>A tincture containing 149mg sunflower lecithin (8.0%), 56mg peppermint oil (3.0%), 1661mg hempseed oil (89.0%) will be administered orally. Participants will place the liquid in their mouth for 45 seconds before swallowing it. | Drug: Cannabidiol<br>* Administered orally. Participants will place the liquid in their mouth for 45 seconds before swallowing it.<br>* Other names: CBD;Drug: Placebo<br>* Administered orally. Participants will place the liquid in their mouth for 45 seconds before swallowing it.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Behavioral Measures - Change in Go/NoGo Reaction Time | Response/reaction time for each stimuli will be recorded in ms using E-Prime. Reaction times will be calculated for correct and incorrect trials separately. | Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period) | 
| Behavioral Measures - Change in N-back Reaction Time | Response/reaction time for each stimuli will be recorded in ms using E-Prime. Reaction times will be calculated for correct and incorrect trials separately; and for each level of n-back, separately. | Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period) | 
| Behavioral Measures - Change in Go/No-Go Accuracy | Accuracy will be determined as the number of trials correct, and errors will be classified as errors of omission or commission. | Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period) | 
| Behavioral Measures - Change in N-back Accuracy | Accuracy will be determined as the number of trials correct. | Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period) | 
| Change in Concentration of Neurometabolites | Magnetic resonance spectroscopy (MRS) measurements pre/post ingestion. The following are measured: glutamate, glutamine, gamma-aminobutyric acid, N-acetylaspartate, choline, creatine, glutathione, myo-inositol, aspartate, taurine, and lactate. LCModel software performed automatic quantification of in vivo proton MR spectra by analyzing spectra as a linear combination of model spectra from sequence-specific simulations. Water-suppressed spectra were eddy current corrected and quantified using the unsuppressed water signal. Cramer-Rao lower bounds were used as a measure of fit with CRLB > 50% rejected from further analysis. Metabolite concentrations were CSF-corrected, and quantified (in ppm). | Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period) | 
| Changes in Functional Connectivity | Blood-oxygen-level-dependent signal changes will be collected via functional magnetic resonance imaging (fMRI). We will assess pre- and post-drug/placebo connectivity changes across the whole-brain using standard preprocessing procedure (fmriprep) and the 'conn' connectivity toolbox. | Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period) | 
| Blood Oxygen Level Dependent (BOLD) Changes | Functional magnetic resonance imaging blood-oxygen-level-dependent signal changes across tasks, and during resting state | Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period) | 
| BOLD - Change in Threat Response to Subliminal Emotion Stimuli | Responses to emotional face stimuli will be measured as a function of blood-oxygen-level-dependent signal change during emotion versus neutral condition in predefined regions of interest including the amygdala, anterior cingulate cortex, and superior temporal sulcus. | Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rct, cannabidiol, placebo, clinical trial