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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
15
Administered orally. Participants will place the liquid in their mouth for 45 seconds before swallowing it.
Administered orally. Participants will place the liquid in their mouth for 45 seconds before swallowing it.
Auburn University MRI Research Center
Auburn, Alabama, United States
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.