Central Executive Network drives delta-9-tetrahydrocannabinol (THC)-induced nonlinear changes in large-scale functional connectivity in adolescent nonhuman primates.
Andrew Jin Soo Byun, Harshawardhan U Deshpande, Jessi Stover, Brian D Kangas, Stephen J Kohut
Neuropsychopharmacology October 1, 2025 DOI: 10.1038/s41386-025-02068-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled animal experiment Peer reviewed |
|---|---|
| Population | Adolescent squirrel monkeys (aged 2.0 years female, 2.5 years male) |
| Intervention | delta-9-tetrahydrocannabinol (THC) |
| Dose | 0.32 or 3.2 mg/kg |
| Duration | 6-month chronic dosing, 60-day discontinuation follow-up |
| Topics | Cannabis |
| Key findings | Low-dose (0.32 mg/kg) chronic THC exposure during adolescence increased default mode–central executive network functional connectivity during the exposure period, an effect not seen with high-dose (3.2 mg/kg) or vehicle. |
Abstract
Adolescent cannabinoid exposure has been implicated in enduring modifications to adult brain circuitry; however, well-controlled, systematic analyses investigating dose-dependent effects of chronic delta-9-tetrahydrocannabinol (THC) exposure on brain connectivity are lacking. It is hypothesized that large-scale intrinsic networks, such as default mode (DMN), central executive (CEN), and salience networks (SN), are critically involved in vulnerability to deficits in cognitive processing often associated with adolescent cannabis use. The present study aimed to elucidate the effects of chronic THC exposure on functional connectivity (FC) of these putative large-scale networks in nonhuman primates. Separate groups of adolescent squirrel monkeys (aged 2.0-yrs [female] and 2.5-yrs [male]) were administered intramuscular injections of vehicle or THC daily (0.32 or 3.2mg/kg) for 6-months during adolescence. Resting state functional connectivity from scans conducted in awake subjects was measured before dosing, at 6-months of chronic dosing, and 60-days following discontinuation of daily THC exposure. Utilizing two distinct analytical methodologies, we observed a non-linear, dosage-dependent alteration in DMN-CEN FC across scan intervals. Specifically, exposure to a low THC dosage increased FC during chronic exposure compared to both the pre-dosing and discontinuation periods. This pattern, however, was not observed in either the vehicle or high THC dosage groups. Dual-regression unveiled a similar non-linear effect within the CEN, but not DMN, suggesting the effect on DMN-CEN FC may be driven by modifications within the CEN. Taken together, these results suggest adolescent THC exposure differentially affects large-scale brain networks and contributes to a nuanced understanding of CEN's role in disrupting brain connectivity following chronic THC exposure.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cites 12
- Long-term consequences of adolescent cannabinoid exposure in adult psychopathology Frontiers in Neuroscience November 10, 2014
- Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity Journal of Psychopharmacology April 23, 2019
- Associations between regular cannabis use and brain resting-state functional connectivity in adolescents and adults Journal of Psychopharmacology July 29, 2023
- Chronic Δ9-tetrahydrocannabinol exposure in adolescent nonhuman primates: persistent abnormalities in economic demand and brain functional connectivity. Neuropsychopharmacology February 1, 2025
- An evolutionary gap in primate default mode network organization Cell Reports March 16, 2021
and 7 more in the library