Poster No:
1218
Submission Type:
Abstract Submission
Authors:
Daniel Feldman1,2, Molly Prigge2, Jubel Morgan2, Carolyn King2, Lubdha Shah2, Jace King1,2
Institutions:
1Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, 2Department of Radiology & Imaging Sciences, University of Utah, Salt Lake City, UT
First Author:
Daniel Feldman
Department of Biomedical Engineering, University of Utah|Department of Radiology & Imaging Sciences, University of Utah
Salt Lake City, UT|Salt Lake City, UT
Co-Author(s):
Molly Prigge
Department of Radiology & Imaging Sciences, University of Utah
Salt Lake City, UT
Jubel Morgan
Department of Radiology & Imaging Sciences, University of Utah
Salt Lake City, UT
Carolyn King
Department of Radiology & Imaging Sciences, University of Utah
Salt Lake City, UT
Lubdha Shah
Department of Radiology & Imaging Sciences, University of Utah
Salt Lake City, UT
Jace King
Department of Biomedical Engineering, University of Utah|Department of Radiology & Imaging Sciences, University of Utah
Salt Lake City, UT|Salt Lake City, UT
Introduction:
Few studies have investigated the acute roles and interactions of cannabinoid types, namely CBD and THC, on resting-state fMRI connectivity (Lorenzetti et al., 2023). Existing studies have reported that CBD may either counteract or exacerbate the effects of THC on brain connectivity (Ertl et al., 2024, Wall et al., 2019 & 2022). To shed light on the distinct roles of THC, CBD, and their interactions in human brain function, we implemented a high order tensor decomposition to perform pattern discovery on resting-state functional connectivity data across three active cannabinoid drug states: CBD, THC, and CBD + THC. Further, we relate functional connectivity to blood levels of cannabinoid metabolites, introducing new analyses of brain connectivity-cannabis metabolism relationships.
Methods:
37 healthy individuals (18 F | age 30.4 ± 7.3) participated in four MRI scans at the University of Utah. At each scan, study participants received an oral administration (oil) of 10 mg THC, 600 mg CBD, 10 mg THC + 600 mg CBD, or no drug (placebo condition). Drug states were assigned in random order and MRI scans separated by at least 1 month. Blood concentration of levels of CBD, 7OH-CBD, Delta 9 THC, 11OH-THC, and COOH-THC were measured 90 minutes after drug administration, immediately before the MRI scans. Data was processed as reported elsewhere (King et al. 2018), yielding connectivity matrices containing 64,980 edges between 361 unique cortical, subcortical, and cerebellar brain nodes. Data was recompiled into a 3-dimensional tensor with axes of connectivity edges, participants, and unique cannabinoid drug states. The resulting tensor underwent an unsupervised Tucker decomposition, thereby reducing data dimensionality to constituent drug-modulated patterns of brain connectivity. Differences in cannabinoid blood concentrations were determined with Bonferroni-corrected pairwise t-tests. Participant brain-component eigenvalues were related to blood cannabinoid levels using linear models.
Results:
Decomposed components 2 and 4 seemingly identified unique brain connectivity patterns associated with the acute presence of THC and CBD, respectively. Particularly, component 2 replicated previous findings of increased anti-correlation between the default and salience brain networks with acute THC administration (Kruskal-Wallis Test, p < 0.001 | Pairwise Dunn Test, corrected-p < 0.001). In contrast, component 4 yielded the inverse relationship, implying that CBD may attenuate the effects of THC in overlapping brain connectivity networks.
Additionally, brain-based participant eigenvalues were directly related to blood levels of cannabinoid compounds. Component 4 participant weights were positively correlated with blood concentration of CBD (p < 0.05). Component 4 weights also positively correlated with 11OH-THC and COOH-THC metabolites when CBD and THC were co-administered, but not when THC was administered alone. Blood concentrations of THC metabolites 11OH-THC and COOH-THC, but not Delta9-THC, were greater with CBD-THC co-administration compared to THC in isolation (corrected-p<0.001). Taken together, these data suggest that 1) co-administration of CBD and THC impacts THC metabolism and 2) the identified brain state in component 4 is not only related to CBD's neurological effects but also related to the neural underpinnings of CBD-modulated THC metabolism.
Conclusions:
These results suggest that THC administration yields salient effects on brain connectivity and that CBD may modulate these effects. Likewise, tensor decompositions may be a helpful method for characterizing first order and weaker interactions effects of cannabinoids. Further, we suggest that CBD modulates THC metabolism, and that this modulation is correlated to tensor-decomposed brain connectivity states.
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 1
Physiology, Metabolism and Neurotransmission:
Pharmacology and Neurotransmission 2
Keywords:
Data analysis
FUNCTIONAL MRI
Other - Cannabis
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
Resting state
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Healthy subjects
Was this research conducted in the United States?
Yes
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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
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Yes
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Not applicable
Please indicate which methods were used in your research:
Functional MRI
For human MRI, what field strength scanner do you use?
3.0T
Which processing packages did you use for your study?
SPM
FSL
Free Surfer
Provide references using APA citation style.
Ertl, N. (2024). Acute effects of different types of cannabis on young adult and adolescent resting-state brain networks. Neuropsychopharmacology, 1-12.
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-e184777.
Lorenzetti, V. (2023). Effects of cannabinoids on resting state functional brain connectivity: a systematic review. Neuroscience & Biobehavioral Reviews, 145, 105014.
Wall, M. B. (2022). Individual and combined effects of cannabidiol and Δ9-tetrahydrocannabinol on striato-cortical connectivity in the human brain. Journal of Psychopharmacology, 36(6), 732–744.
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.
No