rethinkTHC Search
Menu
Study breakdown

Cannabis use showed limited brain structural changes in schizophrenia and bipolar patients, except for those who started before illness onset

Cross SectionalModerate evidence
The takeaway

An MRI study of 314 patients with schizophrenia or bipolar disorder found no significant brain structural changes associated with cannabis use after controlling for confounders, though patients who began cannabis use before illness onset showed cortical thinning in the frontal gyrus.

Read this if you have schizophrenia or bipolar disorder and use cannabis, or are interested in how cannabis affects brain structure in people with serious mental illness.

Brain effects of cannabis were limited and largely explained by polysubstance use

What the researchers found

Researchers compared brain scans of patients with schizophrenia or bipolar disorder who had used cannabis (132 patients) against those who had not (182 patients) and 277 healthy controls.

After controlling for confounders including tobacco and alcohol use, cannabis-using patients showed reduced cortical thickness in the caudal middle frontal gyrus compared to non-user patients and healthy controls.

However, when patients with co-occurring alcohol and other illicit drug use were excluded, these findings were no longer significant. This suggests the brain differences may have been driven by polysubstance use rather than cannabis alone.

One finding persisted: patients whose cannabis use started before their illness onset showed cortical thinning in the caudal middle frontal gyrus. This supports the idea that early cannabis exposure before psychiatric illness develops may have a specific effect on frontal cortex development.

Overall, the authors concluded that cannabis use is associated with limited brain structural effects in both schizophrenia and bipolar disorder.

Why it matters

This study addresses the question of whether cannabis use worsens the brain changes already present in serious mental illness. The finding that effects are limited, and largely disappear when polysubstance use is controlled for, provides reassurance while highlighting the importance of early use timing.

The numbers in context

314 patients (132 cannabis users, 182 non-users) plus 277 healthy controls. 11 preselected brain regions per hemisphere analyzed. Caudal middle frontal gyrus showed thinning with cannabis use. Effects non-significant after excluding polysubstance users. Pre-illness-onset use associated with persistent cortical thinning.

How the study worked

MRI brain scans from 77 schizophrenia and 55 bipolar patients with cannabis history (lifetime use >10 times in one month or abuse/dependence), 97 schizophrenia and 85 bipolar patients without cannabis use, and 277 healthy controls. Cortical thickness, surface area, and subcortical volumes compared using hypothesis-driven and exploratory analyses.

What this study cannot tell us

Cross-sectional design cannot determine temporal causation. Cannabis use history was retrospective and binary (user vs. non-user) without detailed dose-response data. The loss of significance after excluding polysubstance users may reflect reduced statistical power rather than absence of effect. Sample sizes within subgroups were relatively small.

How to read the evidence

Well-designed cross-sectional MRI study with multiple comparison groups and confounder control provides moderate evidence, limited by cross-sectional design and retrospective cannabis history.

When this study was published

Published in 2018. Neuroimaging methods and understanding of cannabis-brain interactions have continued to advance.

The bigger picture

The distinction between cannabis use before versus after psychiatric illness onset is important for understanding risk. If cannabis primarily affects brain structure when used before illness develops, this supports the hypothesis that early cannabis exposure during critical neurodevelopmental periods may contribute to illness vulnerability rather than simply being a consequence of the disorder.

Questions still open

  • Does the frontal cortical thinning associated with pre-illness cannabis use progressively worsen or stabilize? Would longitudinal tracking of cannabis-using patients show continued brain changes? Is the frontal thinning functionally meaningful for cognitive or clinical outcomes?

Common questions

Does cannabis change the brain in people with schizophrenia?
This study found limited brain structural differences. After controlling for tobacco, alcohol, and other drug use, most apparent cannabis effects on brain structure disappeared. The exception: patients who started cannabis before their illness onset showed frontal cortex thinning.
Does it matter when cannabis use started?
Yes. Cannabis use that began before psychiatric illness onset was associated with cortical thinning in the frontal gyrus, while use after illness onset was not associated with significant structural changes.

Read the original research

Cortical thickness, cortical surface area and subcortical volumes in schizophrenia and bipolar disorder patients with cannabis use.

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 28(1), 37-47

Citation

Hartberg, Cecilie Bhandari; Lange, Elisabeth H; Lagerberg, Trine Vik; Haukvik, Unn K; Andreassen, Ole A; Melle, Ingrid; Agartz, Ingrid. (2018). Cortical thickness, cortical surface area and subcortical volumes in schizophrenia and bipolar disorder patients with cannabis use.. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 28(1), 37-47. https://doi.org/10.1016/j.euroneuro.2017.11.019

Explore the wider topic