A small study found that a gene specifically associated with autism appears to change the sperm of men who use cannabis. The genetic mutation occurs through a process called DNA methylation and could eventually be passed on to subsequent generations.
Published in the journal Epigenetics, the researchers note that the results of this study do not establish a definitive link between cannabis use and autism, but the possibility of further links and the need for urgent studies in countries that legalize the medical and/or recreational use of cannabis.
Susan Murphy, the principal author, and doctoral student, and her colleagues conducted studies in animal and human models and analyzed differences in semen between male users (by smoking or ingestion) and non-users.
In earlier work, published in December, the researchers noted several changes in the semen of men who smoke cannabis. The current study focuses on specific genes, particularly one called Discs-Large Associated Protein 2, or DLGAP2. This gene is involved in the transmission of neural signals in the brain and is strongly implicated in autism, schizophrenia, and post-traumatic stress disorder.
We have identified significant hypomethylation of the DLGAP2 gene in the semen of men who have used cannabis compared to the control group, as well as in the semen of rats exposed to THC compared to the control group,” said Schrott. “This hypomethylated state was also detected in the forebrain region of rats born to THC-exposed fathers, supporting the potential for the intergenerational inheritance of a modified sperm DNA methylation model.
The Duke University team has discovered a sex-based difference between DNA methylation and gene expression in human brain tissue. In both male and female brain tissue, increased DNA methylation was associated with decreased gene activity. This relationship was stronger in females and appeared to be less well maintained in males, although the reason for this is unknown at this time. This anomaly was notable, with a 4:1 ratio of boys to girls with autism. There were also gender differences in neurobehavioural symptoms.
The relationship between methylation and expression may be altered if the change in methylation we see in the sperm is inherited by the offspring,” Murphy said. “Either way, it is clear that the DNA methylation region within the DLGAP2 gene, modified in association with cannabis use, is functionally important in the brain.
Murphy explained that the sample size for the study was small – 24 men, half of whom had used cannabis and half of who had not – and did not take into account confounding factors such as diet, sleep, and exercise, but that the results should be an incentive for further research.
Given the growing prevalence of cannabis in the United States and the increasing number of states that have legalized its use, we need more research to understand how the drug affects not only smokers but also their unborn children,” Murphy said. “There is a perception that cannabis is benign. More studies are needed to determine if this is true.