Δ9-Tetrahydrocannabinol Alters Limbic and Frontal Functional Brain Connectomes Among Young Adult Cannabis Users.
Zachary Anderson, Matthew Gunn, Emily Jones, Olusola Ajilore, K Luan Phan, Harriet de Wit, Heide Klumpp, Vince D Calhoun, Natania A. Crane
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging May 1, 2026 DOI: 10.1016/j.bpsc.2025.09.005 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Within-subject, double-blind, randomized study Peer reviewed |
|---|---|
| Sample size | 33 |
| Population | Healthy occasional cannabis users, young adults |
| Interventions | THC (7.5 mg oral) |
| Dose | 7.5 mg |
| Topics | Cannabis |
| Keywords | Frequency Independent component analysis Resting state FMRI Δ9-tetrahydrocannabinol |
| Key points | THC reduced within-network intrinsic connectivity in corticostriatal circuits and other sensory, interoceptive, and spatial reasoning networks, and reduced connectivity between anterior cingulate/dorsal insula and ventral insula/lingual gyrus networks. |
Abstract
Cannabis use among young adults has reached the highest levels ever recorded. Evidence indicates that acute Δ9-tetrahydrocannabinol (THC) disrupts brain connectivity. Few studies have examined this on a whole-brain level. We examined the effects of a single moderate dose of THC on resting-state functional brain networks among young adult cannabis users. In a within-subject, double-blind, randomized study, 33 healthy occasional cannabis users received THC (7.5 mg, oral) and placebo before completing resting-state functional magnetic resonance imaging (rs-fMRI) during peak intoxication. Group-information-guided independent component analysis was performed on resting-state brain data to identify whole-brain networks associated with each scan. Within-samples t tests assessed for differences in intrinsic network functional connectivity and between-network functional connectivity after THC versus placebo. Additional linear models examined relationships between brain connectivity, subjective drug effects, and past-month cannabis use. THC reduced within-network intrinsic connectivity in corticostriatal circuits and other networks associated with sensory systems, interoceptive experiences, and spatial reasoning. THC reduced connectivity between 2 networks characterized by the anterior cingulate cortex and dorsal insula regions as well as the ventral insula and lingual gyrus, respectively. Network connectivity during THC (vs. placebo) was not related to subjective measures of drug effect or recent cannabis use. Our findings add to a growing literature showing that THC decreases rs-fMRI throughout the brain, impacting networks linked to the many behavioral and perceptual changes associated with THC. Future work is needed to extend these findings to clinical samples and to assess the extent to which these networks are associated with negative outcomes of chronic THC use.
Comparable studies
Other randomized controlled trials on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Healthy participants | 2012 | Randomized controlled trial | n = 48 |
| Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Healthy, English-native, right-handed men who had used cannabis 15 times or less in... | 2009 | Double-blind, randomized, placebo-controlled crossover trial | n = 15 |
| Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Healthy male subjects | 2012 | Randomized controlled trial | n = 16 |
| Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Healthy, native English-speaking, right-handed men of white race/ethnicity who had used... | 2009 | Randomized controlled trial | n = 15 |
| Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition Healthy volunteers with a history of light cannabis use | 2019 | Randomized, double-blind, within-subjects crossover | n = 14 |
Citations in the library
Cites 17
- Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity Journal of Psychopharmacology April 23, 2019
- Cannabis use and cognitive dysfunction Indian Journal of Psychiatry 2011
- Evidence for involvement of the insula in the psychotropic effects of THC in humans: a double-blind, randomized pharmacological MRI study The International Journal of Neuropsychopharmacology April 14, 2011
- Reduced responsiveness of the reward system is associated with tolerance to cannabis impairment in chronic users Addiction Biology December 22, 2019
- Functional brain connectomes reflect acute and chronic cannabis use Scientific Reports February 14, 2022
and 12 more in the library