The intersectionality of cannabis use and depression symptoms on functional brain topology in adults.
Che Liu, Janna Cousijn, Emese Kroon, Francesca Filbey
Drug and Alcohol Dependence April 1, 2026 DOI: 10.1016/j.drugalcdep.2026.113082 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cross-sectional study Peer reviewed |
|---|---|
| Sample size | 395 |
| Population | 223 individuals who currently use cannabis (mean age 26.8 ± 8.1 years, 61.9% male) and 172 controls (mean age 25.0 ± 6.8 years, 48.3% male) |
| Topics | Cannabis Depression |
| Keywords | Graph theory Interaction Network |
| Key findings | Cannabis use was associated with more globally integrated resting-state brain networks (shorter characteristic path length, higher global efficiency and transitivity), but this association weakened at higher depression scores, suggesting that co-occurring depression and cannabis use may relate to less efficient, less integrated network function than cannabis use alone. Among cannabis users, higher use frequency was associated with shorter path length and higher efficiency and transitivity, with no moderating effect of depression symptoms. |
Abstract
Although behavioral and epidemiological studies demonstrate high co-morbidity between cannabis use and depression, the underlying neurobiological mechanisms of this relationship remain poorly understood. This study evaluated the interaction between cannabis use and depression on brain resting state functional connectivity using graph theory network properties in 223 individuals who currently use cannabis (26.8 ± 8.1 years, 61.9 % males) and 172 controls (25.0 ± 6.8 years, 48.3 % males). Graph theory analyses showed that the cannabis group relative to the control group had shorter characteristic path length, higher global efficiency and transitivity as well as increased local efficiency and clustering coefficient in salience, frontoparietal, and subcortical networks. Depression symptoms significantly moderated the effect of group on global measures, such that the effect of cannabis use status on characteristic path length, global efficiency and transitivity weakened in those with higher depression scores. Post-hoc analyses indicated a dose-response relationship such that the higher cannabis use frequency, the shorter characteristic path length, higher global efficiency, and transitivity; but no significant moderating effect of depression symptoms emerged on these associations. These findings suggest that the co-occurrence of depression symptoms and cannabis use, compared to cannabis use alone, may be associated with less efficient and less integrated brain network function. Among those who use cannabis, the effects of cannabis use frequency on these global measures do not vary with depression symptoms, suggesting that depression's moderating effect is conditional on cannabis use status, not dose. These findings underscore the complex interplay between cannabis use and depression in altering functional brain organization.
Comparable studies
Other cross-sectional and survey studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabis use before age 15 and subsequent executive functioning 104 chronic cannabis users (49 early-onset before age 15, 55 late-onset after age 15)... | 2011 | Observational cross-sectional study | n = 148 |
| Patterns of simultaneous polysubstance use in drug using university students Drug-using university students | 2006 | Cross-sectional survey | n = 149 |
| Persisting Reductions in Cannabis, Opioid, and Stimulant Misuse After Naturalistic Psychedelic Use: An Online Survey Online survey respondents | 2020 | Cross-sectional survey | |
| User perceptions of the benefits and harms of hallucinogenic drug use: A web-based questionnaire study Users of hallucinogenic drugs who completed a web-based questionnaire | 2010 | Cross-sectional survey | n = 600 |
| Illicit Use of LSD or Psilocybin, but not MDMA or Nonpsychedelic Drugs, is Associated with Mystical Experiences in a Dose-Dependent Manner Adults recruited from the MAPS website and newsletter, most reporting use of various... | 2012 | Cross-sectional survey | n = 337 |
Citations in the library
Cites 15
- 20 years of the default mode network: A review and synthesis Neuron May 10, 2023
- Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Archives of General Psychiatry 2009
- Spontaneous Brain Activity in the Default Mode Network Is Sensitive to Different Resting-State Conditions with Limited Cognitive Load PLoS One May 28, 2009
- Shifted balance of dorsal versus ventral striatal communication with frontal reward and regulatory regions in cannabis‐dependent males Human Brain Mapping September 12, 2018
- Associations between regular cannabis use and brain resting-state functional connectivity in adolescents and adults Journal of Psychopharmacology July 29, 2023
and 10 more in the library