In total, 10 studies used structural MRI techniques, while one used MRS and one used fMRI to examine the differences between cannabis users and non-users (males and females).

Three of the 10 MRI studies (McQueeny et al., 2011; Medina et al., 2009; Sullivan et al., 2020) showed that female cannabis users (n = 25) versus non-users (n = 37) had regional increases in volume of the following cortical areas: left precuneus, left rostral middle frontal region, superior frontal regions and the amygdala. Conversely, male users (n = 49) versus non-users (n = 52) were found to have global decreases in cortical volume in the same cortical regions: left precuneus, left rostral middle frontal region, superior frontal regions and the amygdala (McQueeny et al., 2011; Medina et al., 2009; Sullivan et al., 2020).

Findings from Chye et al. (2017) also found significant reductions in cortical volume between cannabis users and non-users, specifically around the lateral orbital frontal cortex. Unlike previous work (McQueeny et al., 2011; Medina et al., 2009; Sullivan et al., 2020) that reported an increase in cortical volume in females (n = 25), they found that this reduction in cortical volume was most prominent in female cannabis users (n = 46; Chye et al., 2017). In addition, they reported no sex × group interaction (Chye et al., 2017). Similarly, Maple et al. (2019) found no sex effects or interactions between cannabis use and sex.

Similar to work done by Chye et al. (2017), McQueeny et al. (2011), Medina et al. (2009) and Sullivan et al. (2020), French et al. (2015) were interested in examining how global and regional cortical thickness varies within young cannabis users (ages of 12–21 years). They found decreased cortical thickness in cannabis users, specifically those with a genetic high risk for schizophrenia (calculated from polygenic risk scores). The authors did not report any overall sex differences between groups (cannabis user vs non-users; French et al., 2015).

To further examine cannabis use patterns and cortical thickness, French et al. (2015) partitioned cannabis use into the following categories: never users (1–2 occasions), moderate users (3–19 occasions) and frequent users (20+ occasions). Participants were then measured to see if cortical thickness changed as a function of usage. Male cannabis users in the moderate and frequent use categories showed differences in cortical thickness compared with never users; however, this was only true for the genetic high-risk condition, and these findings did not hold up in female users (high or low risk) unless age was adjusted. When age was considered, female (high risk) cannabis users (vs non-users) presented with a decrease in cortical thickness. No other sex by group differences or interactions were reported.

Changes in cerebellar volumes have also been reported in this sample, such that marijuana users were reported to have larger posterior inferior vermal volumes, however sex differences or interactions were found in users (Medina et al., 2010). Sex differences were only reported in controls, with increases in right and total cerebellar hemisphere volumes (controlling for intercranial volume (ICV); Medina et al., 2010) observed in female controls.

While the previously discussed studies found differences between cannabis using males and females in terms of brain structure, Thayer et al. (2020) used diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) to measure the association between neural structure and substance use and found no sex differences. DTI was used to visualise whole-brain skeletonised white matter while VBM was used to measured grey matter volume density. While they found cannabis use was associated with inferior white matter integrity (axonal diffusivity in the left superior longitudinal fasciculus [SLF]), no significant sex differences were reported in this sample and no group (cannabis user vs non-user) by sex (male vs female) interactions shown (Thayer et al., 2020).

In addition to the previously reported findings of cortical and cerebellar differences in male and female cannabis users (Chye et al., 2017; French et al., 2015; McQueeny et al., 2011; Medina et al., 2009, 2010; Sullivan et al., 2020), Sullivan et al. (2020) found that female cannabis users showed increases in local gyrification index (LGI) in the left precentral and supramarginal regions compared with non-user females. This indicates that female cannabis users have a larger difference between the ratio of the length of the inner and outer delineation of the sulcus on coronal slices (Sullivan et al., 2020; Zilles et al., 1988). This increase in surface area and LGI was only present in females whereas the opposite was true for males (reduced surface area and LGI; Sullivan et al., 2020).

Finally, one study used MRI techniques such as phase contrast (PC) MRI to measure CBF, to obtain measures of regional blood flow, the pseudo-continuous arterial spin labelling (pCASL) MRI method was used. They were also interested in using T2-relaxation-under-spin-tagging (TRUST) MRI to obtain measures of total brain oxygenation which was used to provide estimates of oxygenation extraction fraction (OEF) and cerebral metabolic rate (CMRO₂) during periods of rest in cannabis users and non-users (Filbey et al., 2018). Main effects of group (cannabis users vs non-users) were found for OEF and CMRO₂ such that users had higher OEF and CMRO₂ values compared with non-users. Sex differences were present for CBF and CMRO₂ such that females showed higher values than males. Voxel-based analysis indicated cannabis users had significantly higher blood flow in the right pallidum and putamen. There was also a significant effect of sex such that males (vs females) had significantly higher regional CBF in the right insula. Females (vs males) also presented with higher CBF in the left posterior cingulate and bilateral precuneus. No significant interaction between sex and group was found.

Resting state fMRI (rsfMRI) was used in conjunction with local functional connectivity density (IFCD) to observe the influence of cannabis abuse on subcortical functional hub organisation in the brain and their importance to cognitive and mood-related behaviours (Manza et al., 2018). There were no differences between groups (cannabis users and non-users) on measures of cognitive performance using the National Institutes of Health Toolbox measures, part of the Human Connectome Project (e.g. list sorting task, flanker task and pattern completion task). In addition to this, they found no significant differences in the volume of subcortical regions between groups. IFCD analysis revealed significantly higher IFCD in the ventral striatum, dorsal midbrain (substantia nigra and ventral tegmental area), brain stem and lateral thalamus. Higher IFCD was associated with earlier onset of cannabis use; however, they found no effect of sex and no sex by group interactions (Manza et al., 2018).

Blest-Hopley et al. (2019) was the only MRS paper we identified through our search. This group used MRS to determine if chronic cannabis use (n = 22) affected levels of glutamate (neurotransmitter affected by neuronal and glial cannabis receptors (Blest-Hopley et al., 2019)), N-acetyl aspartate (NAA; an indicator of neural integrity Ebisu et al., 1994; Moffett et al., 2007) and myoinositol (metabolic marker of neurons and glia) in the brain at central sites with a high density of cannabinoid receptor 1 (CB1). While there were main effects of cannabis use and sex on hippocampal myoinositol levels (decreased levels in cannabis users; decreased levels in females), there was no sex by group interaction.