Neonatal MRI scans showed that infants exposed to cannabis in utero had lower total brain volume compared to unexposed infants in the first month of life — in a study that carefully excluded alcohol, tobacco, and other drugs.
Read this if you're interested in the effects of prenatal cannabis exposure — this is one of the most carefully designed studies on the topic, finding measurable brain differences in the first month of life.
What the researchers found
Studying prenatal cannabis exposure is extremely difficult because most pregnant cannabis users also use tobacco, alcohol, or other substances, making it nearly impossible to isolate cannabis's independent effects. This study addressed that problem directly by enrolling only mother-infant pairs where cannabis was used without concurrent alcohol, tobacco, or illegal drug use.
Cannabinoid exposure was confirmed objectively using ultra-high performance liquid chromatography-tandem mass spectrometry in both maternal and neonatal biological samples — no reliance on self-report alone. Then neonatal brain MRIs were performed in the first month of life for 18 exposed and 21 unexposed infants.
The finding: cannabis-exposed neonates had lower total brain volume compared to unexposed infants. This global brain volume difference was present even after using inverse probability of treatment weighting to control for structural confounding between exposure groups.
The study also examined subcortical regions specifically — the amygdala and hippocampus — which are critical for emotional regulation and memory formation and are rich in cannabinoid receptors during development.
This is one of the cleanest studies of prenatal cannabis exposure and brain development, but it's still an observational study. The brain volume difference could be caused by cannabis exposure, or by unmeasured factors that differ between women who use cannabis during pregnancy and those who don't. What it does is flag a measurable structural brain difference that demands further investigation.
Why it matters
Cannabis use during pregnancy is increasing — in some U.S. surveys, up to 7% of pregnant women report use, often for nausea. If prenatal cannabis exposure affects brain development, the public health implications are significant. This study's careful exclusion of other substances and objective exposure verification make it one of the most methodologically rigorous investigations of this question.
The numbers in context
18 exposed, 21 unexposed neonates. MRI in first month of life. Cannabis-exposed infants had lower total brain volume. Exposure confirmed by LC-MS/MS in maternal and neonatal samples. No concurrent alcohol, tobacco, or illicit drug use in the exposed group. Inverse probability of treatment weighting used for confounding control. Registered clinical trial: NCT03718520.
How the study worked
Prospective pre-birth cohort study selecting mother-infant pairs based on prenatal cannabis use without alcohol, tobacco, or illegal drug use. Cannabinoid exposure quantified in maternal and neonatal biological samples using LC-MS/MS. Neonatal MRI conducted in the first month of life: 18 exposed, 21 unexposed infants. Inverse probability of treatment weighting in a generalized linear model framework controlled for structural confounding. Evaluated global brain volume and subcortical volumes (amygdala, hippocampus). Registered: NCT03718520.
Who was studied
N=39 mother-infant pairs, 43% female neonates, US-based cohort study.
What this study cannot tell us
Small sample (39 total neonates). Observational design — even with careful confounder control, unmeasured differences between cannabis-using and non-using pregnant women may explain the findings. Brain volume at one month is a structural measure, not a functional one — whether the volume difference translates to developmental or cognitive differences later in childhood is unknown. Single time point — no longitudinal follow-up to see if differences persist, widen, or resolve. Cannabis product type, dose, timing, and duration of use during pregnancy weren't precisely characterized.
How to read the evidence
Prospective cohort with objective exposure verification, careful exclusion criteria, and neonatal MRI. Methodologically strong for an observational study but limited by small sample size and single time point. Cannot establish causation despite the rigorous design.
When this study was published
Published in 2025. Longitudinal follow-up of these infants would be invaluable for understanding whether early brain volume differences predict later developmental outcomes.
The bigger picture
This is the prenatal exposure study in the database, connecting to the broader neuroscience of the endocannabinoid system's role in brain development. The endocannabinoid system is active during fetal brain development — regulating neuronal migration, synapse formation, and circuit organization. External cannabinoids (from cannabis use) could disrupt these precisely timed developmental processes, which is the biological rationale for why brain volume differences might occur.
Replication
Not stated in abstract.
Funding
Not reported in abstract.
Conflicts of interest
Not reported in abstract.
Questions still open
- Do the brain volume differences persist or resolve as the child develops? Do they translate to measurable cognitive, behavioral, or emotional differences in childhood? Which trimester of exposure is most critical? Would the findings be replicated in a larger cohort with even more rigorous confounder control? Do specific cannabinoids (THC vs. CBD) drive the effect differently?
Read the original research
In utero chronic cannabis exposure is associated with lower total brain volume in the first month of postnatal life.
The American journal of drug and alcohol abuse, 51(4), 458-470
The American Journal of Drug and Alcohol Abuse is a peer-reviewed journal focusing on substance use and its effects.
Citation
Crume, Tessa L; Kim, Pilyoung; Shen, Xinyi; Iisa, Erika; Huestis, Marilyn A; Fried, Peter; Stickrath, Elaine H; Conageski, Christine; Phipers, Jocelyn E; Kinney, Gregory; Sempio, Cristina; Klawitter, Jost; Dufford, Alexander J. (2025). In utero chronic cannabis exposure is associated with lower total brain volume in the first month of postnatal life.. The American journal of drug and alcohol abuse, 51(4), 458-470. https://doi.org/10.1080/00952990.2025.2506112
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