Chronic synthetic cannabinoid users showed reduced brain volume and impaired working memory neural activity | Research

The takeaway

An MRI study comparing 15 chronic synthetic cannabinoid users to 15 controls found reduced total gray matter volume, reduced volume in multiple cortical regions, and diminished brain activation during a working memory task in the user group.

Neuroscience researchers studying synthetic cannabinoid effects; addiction clinicians; public health officials assessing synthetic cannabinoid harms.

First study showing both structural and functional brain changes in chronic synthetic cannabinoid users

What the researchers found

Fifteen chronic synthetic cannabinoid (SC) users and 15 healthy controls underwent MRI scans while performing cognitive tasks.

SC users showed reduced total gray matter volume compared to controls, along with reduced volume in specific regions: middle frontal gyrus, frontal orbital gyrus, inferior frontal gyrus, insula, anterior cingulate cortex, and precuneus.

On a working memory task (N-back), SC users performed worse behaviorally and showed diminished brain activation in the precuneus, cuneus, lingual gyrus, hippocampus, and cerebellum.

On a response inhibition task (Go-No-Go), no group differences were found in either performance or brain activation.

This was the first study showing both overall and region-specific gray matter volume reductions in chronic SC users, and the first to demonstrate impaired neural mechanisms for working memory specifically.

Why it matters

Synthetic cannabinoids are far more potent than natural cannabis and their brain effects are poorly understood. This study provides the first neuroimaging evidence of structural and functional brain changes in chronic SC users, suggesting vulnerability of the frontal-parietal network that supports working memory.

The numbers in context

15 SC users, 15 controls. Reduced gray matter in middle frontal gyrus, frontal orbital gyrus, inferior frontal gyrus, insula, anterior cingulate, and precuneus. Diminished activation during N-back in precuneus, cuneus, lingual gyrus, hippocampus, and cerebellum.

How the study worked

Cross-sectional neuroimaging study. 15 SC users vs 15 controls. Structural MRI for gray matter volume. Functional MRI during N-back (working memory) and Go-No-Go (response inhibition) tasks.

What this study cannot tell us

Very small sample (15 per group). Cross-sectional design cannot determine whether brain differences preceded or resulted from SC use. SC users likely used other substances as well. No data on specific SC compounds used, doses, or duration.

How to read the evidence

Preliminary. Novel first-of-its-kind findings, but very small sample size limits confidence and generalizability.

When this study was published

Published in 2018. Synthetic cannabinoid neuroimaging research remains limited but continues to develop.

The bigger picture

Synthetic cannabinoids represent a much more potent class of compounds than THC. If 15 chronic users already show measurable brain changes, this raises concerns about the neurological impact of the SC epidemic, particularly among young users.

Questions still open

Are these brain changes reversible with abstinence? Do they differ from changes seen with natural cannabis use? Which specific synthetic cannabinoids cause the most brain damage? Do these structural changes predict functional outcomes?

Common questions

Are synthetic cannabinoids worse for the brain than regular cannabis?

This study cannot directly compare the two, but synthetic cannabinoids are much more potent agonists at cannabinoid receptors than THC. The pattern of widespread gray matter reduction seen in just 15 users is concerning and may reflect the greater potency of these compounds.

What is the N-back task?

The N-back is a standard test of working memory where participants must remember items presented N steps earlier in a sequence. It engages frontal and parietal brain regions. SC users performed worse and showed less brain activation during this task.

Read the original research

The effects of synthetic cannabinoids (SCs) on brain structure and function.

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 28(9), 1047-1057

View on PubMed ↗Publisher’s paper ↗

Citation

Livny, A; Cohen, K; Tik, N; Tsarfaty, G; Rosca, P; Weinstein, A. (2018). The effects of synthetic cannabinoids (SCs) on brain structure and function.. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 28(9), 1047-1057. https://doi.org/10.1016/j.euroneuro.2018.07.095