Brain volume loss in polysubstance users was linked to total number of substances, not cannabis specifically
A study of 169 men found that medial prefrontal cortex volume loss was associated with the total number of substances used rather than any single drug, though tobacco and cocaine showed specific effects in other brain regions after controlling for polysubstance use.
Quick Facts
What This Study Found
Researchers measured gray matter volume in 169 men across six groups ranging from non-users to heavy polysubstance users (alcohol, tobacco, cocaine, and cannabis).
The number of substances used was negatively associated with volume in the dorsal and ventral medial prefrontal cortex (mPFC). More substances used correlated with less volume in these regions.
Without controlling for other substances, alcohol, tobacco, and cocaine all showed negative associations with dorsal mPFC volume. But after controlling for polysubstance use, these associations disappeared for the mPFC.
Substance-specific effects did emerge in other regions: tobacco was specifically associated with reduced thalamic volume, and cocaine with reduced ventrolateral PFC volume, even after accounting for other substance use.
Cannabis did not show independent effects on gray matter volume after controlling for other substance use.
Key Numbers
169 males: 15 non-users, 89 moderate drinkers, 27 drinkers + tobacco, 13 drinkers + tobacco + cocaine, 10 heavy drinkers + tobacco + cocaine, 15 heavy drinkers + tobacco + cannabis + cocaine. Dorsal and ventral mPFC volume negatively correlated with number of substances.
How They Did This
Cross-sectional neuroimaging study of 169 males in six substance use groups. Voxel-based morphometry for gray matter volume. Regression analyses with and without controlling for co-occurring substance use.
Why This Research Matters
Most brain imaging studies of cannabis users do not adequately control for polysubstance use. This study demonstrates that brain volume differences often attributed to individual substances may actually reflect cumulative polysubstance exposure, which changes how we interpret neuroimaging findings.
The Bigger Picture
This challenges the common approach of studying single-substance effects on the brain without accounting for polysubstance use. The mPFC findings suggest a general "substance burden" effect, while specific substances may affect distinct brain regions beyond this general effect.
What This Study Doesn't Tell Us
Cross-sectional design cannot establish causation. All-male sample limits generalizability. Cannabis users were only in the heaviest polysubstance group, making it hard to isolate cannabis-specific effects. No pre-substance-use baseline measurements.
Questions This Raises
- ?Would cannabis show independent brain effects in a sample of cannabis-only users?
- ?Does the cumulative substance burden effect reverse with abstinence?
- ?Are the mPFC changes a cause or consequence of polysubstance use?
Trust & Context
- Key Stat:
- Prefrontal volume loss tracked with number of substances used, not any individual drug
- Evidence Grade:
- Moderate. Well-designed neuroimaging study with appropriate controls for polysubstance use, but cross-sectional design and all-male sample limit causal inference.
- Study Age:
- Published in 2018. The importance of controlling for polysubstance use in neuroimaging research has been increasingly recognized.
- Original Title:
- The relation between gray matter volume and the use of alcohol, tobacco, cocaine and cannabis in male polysubstance users.
- Published In:
- Drug and alcohol dependence, 187, 186-194 (2018)
- Authors:
- Kaag, A M(2), Schulte, M H J, Jansen, J M, van Wingen, G, Homberg, J, van den Brink, W, Wiers, R W, Schmaal, L, Goudriaan, A E, Reneman, L
- Database ID:
- RTHC-01708
Evidence Hierarchy
A snapshot of a population at one point in time.
What do these levels mean? →Frequently Asked Questions
Does this mean cannabis does not damage the brain?
This study found no independent cannabis effect on gray matter volume after controlling for other substance use. However, cannabis users were only in the heaviest polysubstance group, making it difficult to isolate cannabis-specific effects. It does not prove cannabis is harmless to the brain.
Why does the number of substances matter more than which ones?
The medial prefrontal cortex may be vulnerable to a general "toxic burden" from substance use rather than responding to specific pharmacological effects. Each additional substance adds stress to brain regions involved in decision-making and impulse control.
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Cite This Study
https://rethinkthc.com/research/RTHC-01708APA
Kaag, A M; Schulte, M H J; Jansen, J M; van Wingen, G; Homberg, J; van den Brink, W; Wiers, R W; Schmaal, L; Goudriaan, A E; Reneman, L. (2018). The relation between gray matter volume and the use of alcohol, tobacco, cocaine and cannabis in male polysubstance users.. Drug and alcohol dependence, 187, 186-194. https://doi.org/10.1016/j.drugalcdep.2018.03.010
MLA
Kaag, A M, et al. "The relation between gray matter volume and the use of alcohol, tobacco, cocaine and cannabis in male polysubstance users.." Drug and alcohol dependence, 2018. https://doi.org/10.1016/j.drugalcdep.2018.03.010
RethinkTHC
RethinkTHC Research Database. "The relation between gray matter volume and the use of alcoh..." RTHC-01708. Retrieved from https://rethinkthc.com/research/kaag-2018-the-relation-between-gray
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.