Chronic cannabis use is associated with alterations in resting-state cerebellar-cortical connectivity.
Ilenia Salsano, Giorgia Picci, Nathan M Petro, Anna T Coutant, Lucy K Horne, Jason A John, Ryan Glesinger, Gaelle E Doucet, Tony W Wilson
Psychopharmacology December 12, 2025 DOI: 10.1007/s00213-025-06981-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 45 |
| Population | Middle-aged adults (mean age 41.64 years) with chronic cannabis use and demographically matched controls who did not use cannabis or other illicit substances |
| Topics | Cannabis |
| Keywords | Cerebellum FMRI Functional connectivity |
| Key findings | Chronic cannabis use was associated with decreased resting-state functional connectivity between the right cerebellar Crus II and left pars triangularis, bilateral pars orbitalis, left superior frontal gyrus, left middle temporal gyrus, and left inferior temporal gyrus, and between the right cerebellar Crus I and left pars triangularis, compared to controls. |
Abstract
Cannabis is one of the most widely used psychoactive drugs in the United States, yet its long-term effects on brain function remain poorly understood. Prior resting-state functional connectivity (rsFC) studies have yielded inconsistent findings, likely due to variability in cannabis use thresholds, a predominant focus on younger populations, and region-of-interest (ROI)-based approaches limited to a small number of a priori brain regions. We aimed to address these limitations by examining rsFC across the entire brain using an atlas-based, whole-brain, ROI-to-ROI approach in a middle-aged sample (mean age = 41.64 years) of individuals with chronic cannabis use (CCU) and a demographically matched group of controls who did not use cannabis or other illicit substances. Based on the known neuroanatomical distribution of type 1 cannabinoid receptors (CB1Rs), we hypothesized that regions with high CB1R density would be the most affected. However, given our whole-brain approach, we were also sensitive to other regions that may exhibit altered connectivity. Using the Automated Anatomical Labeling (AAL) atlas, we computed rsFC matrices across 116 brain regions in 22 adults with CCU and 23 demographically matched controls. The CCU group showed decreased rsFC (pFDR< .05) between the right cerebellar Crus II and the left pars triangularis, bilateral pars orbitalis, left superior frontal gyrus, left middle temporal gyrus, and left inferior temporal gyrus compared with the control group. The CCU group also had lower rsFC (pFDR < .05) between the right cerebellar Crus I and the left pars triangularis compared with controls. Our findings revealed disrupted rsFC between cerebellar and prefrontal-temporal regions in the CCU group. This study advances the literature by using an atlas-based, whole-brain, ROI-to-ROI approach in a middle-aged sample with sustained cannabis use. Future studies should integrate neuropsychological assessments and task-based paradigms to understand how such alterations in rsFC affect behavioral outcomes.
Comparable studies
Other observational and cohort studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| High-potency cannabis and the risk of psychosis People with first episode of psychosis and healthy controls from the local population | 2009 | Case-control study | n = 454 |
| Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population | 2013 | Observational study | |
| Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people | 2000 | Observational | |
| Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study Individuals from the general population in Germany aged 14-24 at baseline | 2011 | Observational cohort | n = 1,923 |
| Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases Patients treated for cannabis-induced psychotic symptoms in Denmark between 1994 and... | 2005 | Observational cohort | n = 535 |
Citations in the library
Cites 22
- Resting-State Functional Connectivity Reflects Structural Connectivity in the Default Mode Network Cerebral Cortex April 9, 2008
- Shifted balance of dorsal versus ventral striatal communication with frontal reward and regulatory regions in cannabis‐dependent males Human Brain Mapping September 12, 2018
- Subcortical Local Functional Hyperconnectivity in Cannabis Dependence Biological Psychiatry: Cognitive Neuroscience and Neuroimaging November 23, 2017
- Attenuated frontal and sensory inputs to the basal ganglia in cannabis users Addiction Biology March 3, 2016
- Is resting-state functional connectivity altered in regular cannabis users? A systematic review of the literature. Psychopharmacology May 2022
and 17 more in the library