Background and aims <p>Cannabis is a widely abuse substance during pregnancy. However, reports of effects on human fetal brain development and implication in brain malformations are scarce in the literature. This study aims to determine the usability of long-term formalin-fixed tissues, highly degraded as a result of long post-mortem delays, collected during post-mortem medical examinations of human fetuses for molecular identification of low-abundance molecular species, namely the cannabinoid receptors, as a prerequisite for studying cannabis role in human fetal brain malformations.</p> Methods <p>This preliminary work describes the experimental approach used to identify the CB1 cannabinoid receptor transcript and protein. For this purpose, the experimental procedure was conducted on reference samples, namely adult hippocampus and placenta (known to express CB1) subjected to minimal chemical fixation. Subsequently, the validated methods were applied to fetal tissues fixed in 4% buffered formaldehyde for extended periods (7 days to 6 months), with placenta serving as the control tissue (known to express CB1) and fetal brain as the experimental target.</p> Results <p>CB1 cannabinoid receptor protein and mRNA are identifiable following long-term formaldehyde fixation, with differences observed across brain regions.</p> Conclusion <p>Our preliminary results confirm that tissues conserved in paraffin blocks following long-term formalin fixation are suitable for medical research. Moreover, identification of CB1 cannabinoid receptors, a low-abundance molecule, by molecular techniques is possible in these samples. Applied to a large cohort of fetal brains at different developmental time points, these methods will enable determination of a precise cannabis toxicity window during pregnancy and provide a better understanding of cannabis involvement in brain malformations.</p>