Association of cannabis and tobacco use with brain volume: a systematic review and meta-analysis

Background
Tobacco is the leading cause of preventable death worldwide and cannabis, the most used drug under international control worldwide, is increasing in prevalence. Tobacco and cannabis have been associated with mental health problems and one mechanism for this association could be changes in brain structure. However, evidence for the associations of tobacco and cannabis with changes in brain structure is heterogenous and inconsistent. Tobacco and cannabis are often co-used; however, the co-use of tobacco and cannabis is often poorly measured and understood. We present, to our knowledge, the first systematic review and meta-analysis of the association between tobacco use, cannabis use and/or co-use with brain volume, across different populations and different study methods. 

Methods and results 
This review was preregistered on PROSPERO (CRD42022356982). We searched SCOPUS, PubMed and PsycINFO identifying 20209 studies. Studies were eligible if they investigated the association between current tobacco use, cannabis use and/or co-use and global or regional brain volume, measured using t1-weighted structural MRI. After duplicates were removed, 14754 title/abstracts were screened, with 109 studies included. One study investigated tobacco and cannabis co-use, 59 studies investigated cannabis use and 51 investigated tobacco use, across 37 different outcomes. Meta-analysis is on-going and due to be completed by spring 2024. 

Conclusions 
There is limited research investigating the association of current tobacco and cannabis co-use with brain volume and consideration of possible confounding of each substance on each other, limiting understanding of the true effects of these substances on brain structure and thus, mental ill-health.