Abstract
Background and Aims
Cannabis is the most widely used illicit drug worldwide and is often co-used with tobacco, the leading cause of preventable death. Although cannabis and tobacco have distinct neurobiological actions, their associations with brain volumes are unclear. We aimed to review studies investigating cannabis use, tobacco use, their co-use, and brain volume and triangulate evidence across different study designs.
Methods
A systematic review and meta-analysis preregistered on PROSPERO (CRD42022356982) and reported according to PRISMA 2020 guidelines. We searched SCOPUS, PubMed and PsycINFO up to 5th September 2024 for studies investigating cannabis use, tobacco use, co-use and brain volume. Cross-sectional, longitudinal and Mendelian randomisation studies were included. The outcome was brain volume of global, cortical and subcortical regions. We extracted adjusted and unadjusted estimates. Random effects meta-analyses were stratified by exposure and study design across 33 brain regions. Risk of bias was assessed using a modified version of the Newcastle-Ottawa scale.
Results
Searches yielded 103 studies: 57 investigated cannabis use, 45 investigated tobacco use, and one investigated tobacco and cannabis co-use. Seventy-seven studies were included in meta-analysis (n = 72798), 44 (n = 18247) in the cross-sectional cannabis analysis, 30 (n = 51194) for tobacco cross-sectional and four (n = 3357) in the tobacco longitudinal analysis. Meta-analysis of adjusted estimates from cross-sectional studies (k denotes the number of independent studies) indicated smaller amygdala volumes (k = 17, g = 0.13, 95% confidence interval [CI] [0.03, 0.23]) in people who use cannabis compared with controls. Relative to controls, people who smoked tobacco had smaller volumes in the amygdala (k = 5, g = 0.17, 95%CI [0.04, 0.31]), insula (k = 5, g = 0.17, 95%CI [0.06, 0.27]), pallidum (k = 5, g = 0.17, 95%CI [0.13, 0.21]) and total grey matter volume (TGMV) (k = 7, g = 0.17, 95%CI [0.04, 0.30]). Longitudinal studies indicated a larger decrease in TGMV in people who smoke tobacco (k = 5, g = 0.05, 95%CI [0.01, 0.10]) relative to controls.
Conclusions
Cannabis use appears to be associated with smaller volume in the amygdala. Tobacco use appears to be associated with smaller amygdala, insula, pallidum and total grey matter volume.
Cannabis is the most widely used illicit drug worldwide and is often co-used with tobacco, the leading cause of preventable death. Although cannabis and tobacco have distinct neurobiological actions, their associations with brain volumes are unclear. We aimed to review studies investigating cannabis use, tobacco use, their co-use, and brain volume and triangulate evidence across different study designs.
Methods
A systematic review and meta-analysis preregistered on PROSPERO (CRD42022356982) and reported according to PRISMA 2020 guidelines. We searched SCOPUS, PubMed and PsycINFO up to 5th September 2024 for studies investigating cannabis use, tobacco use, co-use and brain volume. Cross-sectional, longitudinal and Mendelian randomisation studies were included. The outcome was brain volume of global, cortical and subcortical regions. We extracted adjusted and unadjusted estimates. Random effects meta-analyses were stratified by exposure and study design across 33 brain regions. Risk of bias was assessed using a modified version of the Newcastle-Ottawa scale.
Results
Searches yielded 103 studies: 57 investigated cannabis use, 45 investigated tobacco use, and one investigated tobacco and cannabis co-use. Seventy-seven studies were included in meta-analysis (n = 72798), 44 (n = 18247) in the cross-sectional cannabis analysis, 30 (n = 51194) for tobacco cross-sectional and four (n = 3357) in the tobacco longitudinal analysis. Meta-analysis of adjusted estimates from cross-sectional studies (k denotes the number of independent studies) indicated smaller amygdala volumes (k = 17, g = 0.13, 95% confidence interval [CI] [0.03, 0.23]) in people who use cannabis compared with controls. Relative to controls, people who smoked tobacco had smaller volumes in the amygdala (k = 5, g = 0.17, 95%CI [0.04, 0.31]), insula (k = 5, g = 0.17, 95%CI [0.06, 0.27]), pallidum (k = 5, g = 0.17, 95%CI [0.13, 0.21]) and total grey matter volume (TGMV) (k = 7, g = 0.17, 95%CI [0.04, 0.30]). Longitudinal studies indicated a larger decrease in TGMV in people who smoke tobacco (k = 5, g = 0.05, 95%CI [0.01, 0.10]) relative to controls.
Conclusions
Cannabis use appears to be associated with smaller volume in the amygdala. Tobacco use appears to be associated with smaller amygdala, insula, pallidum and total grey matter volume.
| Original language | English |
|---|---|
| Journal | Addiction |
| Publication status | Acceptance date - 22 Jan 2026 |
