Smoking shrinks key brain regions while cannabis shows weaker effects

By Dr. Liji Thomas, MDReviewed by Lauren HardakerApr 7 2026

Scientists find consistent brain changes linked to tobacco use, but say cannabis research is still too limited to draw firm conclusions.

Study: Associations of cannabis use, tobacco use and co-use with brain volume: A systematic review and meta-analysis. Image credit: nito/Shutterstock.com

Tobacco remains the leading preventable cause of death worldwide, while cannabis use is rising globally. Since both are neuroactive drugs, their effects on brain structure and function need to be established. A study published in Addiction found that both substances are associated with reductions in specific brain regions when used separately.

Cannabis and tobacco use patterns

Cannabis use is widespread and evolving. Around 228 million people used it in 2022, about 4.4 % of the global population, and increasingly potent products are becoming more common. These higher-strength forms are linked to a greater risk of mental health disorders and addiction than less potent variants.

Tobacco use remains even more prevalent. In 2020, an estimated 1.18 billion people, roughly 30 % of the world’s population, used tobacco, contributing to more than eight million deaths each year. Its health burden falls disproportionately on underprivileged populations.

For some, these substances overlap. Cannabis and tobacco may be used together in spliffs or joints, or separately within short time windows. Either way, the brain is exposed to their distinct neurobiological effects, acting through different pathways.

How tobacco and cannabis affect the brain

Nicotine, the main psychoactive compound in tobacco, acts on nicotinic acetylcholine receptors found throughout multiple brain regions. Tetrahydrocannabinol (THC) is the primary psychoactive compound in cannabis. It acts on cannabinoid type 1 (CB1) receptors, abundant in many areas of the brain.

What the study looked at

The study is a systematic review and meta-analysis synthesizing cross-sectional, longitudinal, and Mendelian randomization (MR) studies. MR is a useful technique for testing causal associations, especially in research areas not suitable for randomized trials. The current study aimed to mitigate biases and increase the power to detect small effect sizes.

There is limited research on the concomitant use of both these drugs in relation to brain size. Existing literature suggests that cannabis use has been associated with smaller amygdala volume, with no effects observed in adolescents in earlier meta-analyses.

The cannabis meta-analysis primarily included male participants, while the tobacco cross-sectional studies included mostly female participants. Longitudinal tobacco samples included mostly female participants, though the users were primarily male, but controls were mostly female.

These studies were judged to have a moderate-to-substantial risk of bias. The MR studies were rated as higher quality within the study framework.

Synthesizing the evidence

Cross-sectional analyses showed smaller amygdala volumes among cannabis users compared to controls. Longitudinal studies yielded inconsistent evidence, with reductions mostly in users with schizophrenia or at risk for it. No MR studies were available to assess the causal effects of cannabis use on brain volume.

In tobacco users, smaller volumes were observed in multiple brain regions: the amygdala, insula, pallidum, and total grey matter volume, with weaker evidence for hippocampal differences in cross-sectional analyses. Longitudinal studies showed reduced total gray matter volume in people who smoke tobacco compared to controls. MR studies revealed decreased amygdala volumes linked to smoking initiation and reduced hippocampal volume associated with higher daily cigarette consumption.

These changes might mechanistically underlie the psychoactive effects of these drugs, consistent with their receptor distribution in the brain, although these mechanisms remain hypotheses rather than confirmed causal pathways. Tobacco combustion might also trigger oxidative stress and inflammation, causing neuronal death.

Cannabis combustion also produces toxins, though potentially counteracted by cannabidiol (CBD), which counters oxidation and inflammation.

No longitudinal studies were available on the co-use of these drugs, and only one cross-sectional study examined co-use, finding no significant differences in hippocampal volume compared to controls or nicotine-only users.

Study strengths and limitations

The study included multiple designs and analyzed adjusted versus non-adjusted findings separately. However, some limitations remain.

Cross-sectional meta-analyses cannot provide causal inferences, and observed associations may also reflect confounding factors, such as lifestyle or underlying health differences. Only binary classifications of use were considered, ignoring the potency of the drugs and the severity of use.

Also, using cortical volume as the primary measure of brain structural change overlooks the biological significance of changes in brain surface area relative to cortical thickness.

Implications for action

This is the first systematic review and meta-analysis of its kind to assess separate and combined cannabis and tobacco use in relation to brain volume. These findings suggest reductions in specific brain regions involved in memory and emotional processing associated with tobacco use, with weaker and less consistent evidence for cannabis use.

Tobacco-related findings were strengthened by their consistency across different study designs. However, the authors note that alternative pathways may explain the associations with amygdala volume reduction observed in MR studies.

These observations underline the need for more longitudinal research, especially on their combined use, as cannabis consumption continues to rise globally. They also support public health messaging on the potential harms of these drugs to the brain.

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