Cannabis Perturbs Dynamic Brain States
Katharina S Lege, Pablo Mallaroni, Sepehr Mortaheb, Natasha L. Mason, Eef L. Theunissen, Desmond H. Y. Tse, Stefan W. Toennes, Athena Demertzi, Johannes G. Ramaekers
Biological Psychiatry October 21, 2025 DOI: 10.1016/j.biopsych.2025.10.015 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Placebo-controlled neuroimaging trial Peer reviewed |
|---|---|
| Sample size | 43 |
| Population | Occasional (n=23) and chronic (n=20) cannabis users |
| Intervention | vaporized cannabis |
| Topics | Cannabis |
| Keywords | Effects of cannabis Relevance law Cognition Neuroimaging Neural activity Cognitive impairment Cognitive psychology Cannabis sativa Biological neural network |
| Citations | 1 |
| Key findings | Cannabis intoxication reduces a hyperconnected brain state in both user groups, with chronic users showing persisting neuroadaptations and tolerance to attentional impairment. |
Abstract
Background: The impact of acute cannabis exposure on brain function and cognitive performance varies among individuals. Acute effects of cannabis on behavior may be absent or benign in chronic users, while occasional users experience significant impairment in day-to-day operations. It is hypothesized that repeated cannabis use induces neuroadaptations leading to tolerance and desensitization, although the precise mechanisms underlying these adaptations remain unclear.
Methods: In this study, we investigated acute and persistent effects of vaporized cannabis on brain dynamics in a placebo-controlled neuroimaging trial involving occasional ( n = 23) and chronic ( n = 20) cannabis users. Functional resting-state data were collected to assess dynamic functional connectivity changes during intoxication and their association with attentional performance and normative cannabinoid CB 1 receptor density.
Results: Cannabis intoxication induced significant acute alterations in the dynamics of brain network organization, as shown by a reduced occurrence of a hyperconnected brain state in both user groups. Chronic users also displayed decreased segregation of brain networks independent of treatment condition, suggesting persisting neuroadaptations. Dynamic reconfiguration of hyperconnected brain motifs correlated with attentional performance, which was most impaired in occasional users, indicating tolerance in chronic users. Both the acute and persistent effects of cannabis on dynamic brain state organization were significantly associated with spatial CB 1 receptor density.
Conclusions: Acute cannabis-induced cognitive impairment is influenced by (persistent) network reconfigurations and CB 1 receptor density. These findings emphasize the relevance of neural dynamics and individual neuroadaptations to (prolonged) cannabis use when assessing the behavioral effects of cannabis in therapeutic, legal, and societal settings.
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 26
- Human consciousness is supported by dynamic complex patterns of brain signal coordination Science Advances February 1, 2019
- Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Current Biology April 13, 2016
- Increased global integration in the brain after psilocybin therapy for depression. Nature Medicine April 11, 2022
- Human brain effects of DMT assessed via EEG-fMRI. Proceedings of the National Academy of Sciences March 28, 2023
- LSD alters dynamic integration and segregation in the human brain. Neuroimage February 15, 2021
and 21 more in the library