Differential Effects of THC and CBD on Brain Network Timing
Presented During: Poster Session 3
Friday, June 27, 2025: 01:45 PM - 03:45 PM
Friday, June 27, 2025: 01:45 PM - 03:45 PM
Presented During: Poster Session 4
Saturday, June 28, 2025: 01:45 PM - 03:45 PM
Saturday, June 28, 2025: 01:45 PM - 03:45 PM
Poster No:
1259
Submission Type:
Abstract Submission
Authors:
Jace King1, Molly Prigge1, Lubdha Shah1, Jeff Anderson1
Institutions:
1University of Utah, Salt Lake City, UT
First Author:
Co-Author(s):
Introduction:
Introduction: Interest in the use of cannabidiol (CBD) and other cannabis derivatives has increased over the last several years due to reported health benefits. Despite a growing body of literature about efficacy for medical indications, critical questions about the mechanism of action remain unanswered. For example, how cannabinoids such as ∆-9-tetrahydrocannabinol (THC) and CBD influence large-scale brain network activity is poorly understood. Traditional functional connectivity measures synchrony of intrinsic activity between brain regions and identifies resting-state functional networks. Traditional connectivity has been shown to be altered by cannabis use (with and without CBD, Wall et al. 2019); however, effect sizes are small compared to the perceived effects of THC and the temporal dynamics of that synchrony is unknown. Sustained connectivity uses the width of cross correlation curves to reflect the relative duration of synchronous activity between brain regions and may inform how the timing of brain connections is affected. Previous studies have shown a relationship between sustained connectivity and processing speed and other cognitive domains (King et al. 2018, 2019). This study examines how THC and CBD affect traditional and sustained connectivity in healthy adults.
Methods:
Methods: 39 healthy adults (48.7% female, mean age 29.28±7.13) were given 10mg THC (Syndros), 600mg CBD (Epidiolex), both THC and CBD, or placebo across four study visits. At each visit, participants completed MP2RAGE (1x1x1mm, TR=5000ms, TE=2.93ms) structural scan and two 15-minute multiband resting-state fMRI scans (2x2x2mm, TR=800ms, TE=30ms) in a 3T Siemens Vida scanner. Image preprocessing and analyses were completed using SPM12 and MATLAB software. Preprocessing included coregistration to MP2RAGE, segmentation, motion correction, normalization to MNI space, and regression of motion parameters. A 4-way ANOVA examined the effects of THC and CBD controlling for age, sex, and head motion. A 17x17 network parcellation (Yeo, 2011) was used to evaluate traditional functional and sustained connectivity across the brain with each network treated as a single ROI. Results were corrected for multiple comparisons (FDR).
Results:
Results: When under the effects of THC, participants demonstrated increased sustained connectivity in 91 out of 153 network connections whereas traditional functional connectivity found FDR corrected findings in only 4 out of 136. No FDR corrected findings were found in either traditional or sustained connectivity in the CBD condition.
·THC Effects on Sustained Connectivity
·THC Effects on Functional Connectivity
Conclusions:
Conclusions: These findings suggest that the mechanism of action of THC on brain network function may be through alteration of the timing and stability of brain connectivity. Such a mechanism is consistent with slower cognitive and sensorimotor response times. Investigation of how THC alters the timing of synchronous brain connections may facilitate a unified explanation of perceptual and cognitive alterations of brain network function induced by THC, with greater brain network stability and impaired set shifting and traversal of distinct cognitive states.
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 1
Novel Imaging Acquisition Methods:
BOLD fMRI 2
Keywords:
FUNCTIONAL MRI
MRI
Other - Cannabinoids
1|2Indicates the priority used for review
Abstract Information
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Please indicate below if your study was a "resting state" or "task-activation” study.
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Was this research conducted in the United States?
Are you Internal Review Board (IRB) certified? Please note: Failure to have IRB, if applicable will lead to automatic rejection of abstract.
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
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Provide references using APA citation style.
2. King, J. B. (2018). Evaluation of Differences in Temporal Synchrony Between Brain Regions in Individuals With Autism and Typical Development. JAMA Network Open, 1(7), e184777.
3. Wall, M. B. (2019). Dissociable effects of cannabis with and without cannabidiol on the human brain's resting-state functional connectivity. Journal of Psychopharmacology, 33(7), 822-830.
4. Yeo, B. T., (2011). The organization of the human cerebral cortex estimated by intrinsic functional connectivity. Journal of Neurophysiology, 106(3), 1125-1165