A new peer-reviewed study published in the Journal of Xenobiotics should change how we talk about cannabis safety. Researchers from the University of Western Australia and Edith Cowan University have found that cannabis use, and cannabis legalisation in particular, is strongly associated with a sharp rise in atrial septal defects (ASDs) in newborns across the United States. An atrial septal defect is a hole in the wall between the two upper chambers of the heart.

What makes this research especially difficult to dismiss is not just the scale of the increase. It is the implication that cannabis may be permanently altering genetic material in ways that harm children born to cannabis-exposed parents, and potentially their grandchildren too, even if those grandchildren are never exposed to cannabis at all. This is the science of transgenerational harm, and it reaches well beyond the usual conversation about cannabis and pregnancy. The damage being done today may not finish arriving for two or three generations.

The Scale of the Rise in Atrial Septal Defects

The study drew on 406,893 reported ASD cases across 46 US states between 1989 and 2020. The national rate of atrial septal defects has risen more than fourfold over this period. In some states the increase has been far steeper. Nevada recorded a twelvefold rise between 2005 and 2018. New Mexico matched it. New York saw a sixfold increase. Among Non-Hispanic Asian and Pacific Islander newborns in Nevada, the rate reached 884 cases per 10,000 live births in the 2016 to 2020 period.

For context, the official CDC figure has long been cited as around 10 per 10,000, based on older data from Atlanta. The gap between that figure and what is now being recorded in high-cannabis states is not a statistical quirk. The rate of increase is itself accelerating. Most people are familiar with exponential growth, the kind where something doubles, then doubles again, then doubles again. What researchers are seeing here is worse than that. The rate is growing faster than exponential, meaning each successive period adds more cases than the last, at an increasing pace.

The supra-exponential rise is almost entirely attributable to states with high cannabis use. States with low cannabis use show comparatively flat rates. When states where cannabis was legal were compared with all others, the average ASD rate was 178 per 10,000 in legal states versus 74 per 10,000 elsewhere. And because the genetic damage researchers believe is driving this can be passed from one generation to the next, the children being born with these defects today may themselves pass that inherited disruption on to their own children.

Why ASD Is Used as a Marker

The heart forms in the first weeks of pregnancy, often before a woman knows she is pregnant. An atrial septal defect occurs when the wall between the heart’s two upper chambers fails to close properly. It is the most common congenital heart defect, and because terminations of pregnancy are not performed for ASD as they are for more severe anomalies, the data on its prevalence is unusually reliable. There are no significant reporting gaps distorting the figures.

That reliability is precisely why researchers treat ASD as a population-level signal. When the rate rises sharply and consistently in states with high cannabis use, across multiple ethnic groups and over multiple decades, it warrants a serious investigation of cause.

How Cannabis Disrupts Heart Development

The developing heart is guided into its final shape by molecular signals called morphogens. Think of them as a construction blueprint transmitted at the chemical level. They tell cells where to go, what to become and when to stop growing. Without these signals working in precise sequence, the heart cannot form correctly. Cannabis and its constituent cannabinoids, including THC, cannabidiol (CBD) and cannabigerol (CBG), appear to interfere with at least seven of these major signalling pathways simultaneously.

The specific pathways disrupted have names that mean little outside a biology textbook, but what matters is their function. They control everything from the basic geometry of the heart to the formation of its internal walls. Cannabinoids appear capable of scrambling the molecular instructions the developing heart depends on to close those walls properly.

This is not theoretical. A detailed study of DNA methylation in cannabis-dependent individuals found that cardiogenesis ranked fifth among the biological processes most disrupted by cannabis exposure, with a stronger signal than that seen for brain development. A total of 127 cardiogenic genes were identified as affected, including genes governing atrial development and atrial septal formation directly. Critically, many of these genes sit within the epigenome, meaning the disruption to them is not necessarily confined to the person who used cannabis. It can be transmitted to the next generation through sperm and egg cells before a pregnancy even begins.

Cannabis, Genotoxicity and the Intergenerational Risk

Perhaps the most confronting dimension of this research is what it says about hereditary transmission. Genotoxicity refers to damage to genetic material. When that damage occurs in sperm or egg cells, or alters the epigenome in heritable ways, the consequences extend beyond the person who used cannabis to children and potentially grandchildren who had no exposure at all.

The study identifies two distinct mechanisms. The first is direct genotoxicity, where cannabinoids damage DNA and chromosomes through strand breaks, abnormal cell division and structural chromosomal changes. Think of it as physical damage to the instruction manual inside a cell. The second is epigenotoxicity, which is subtler. The epigenome is a layer of chemical tags that sit on top of DNA and act as switches, controlling which genes are active and which are silent. Cannabinoids alter these switches without changing the underlying DNA sequence itself. The critical point is that these altered switches can be passed from parent to child. A child inherits not just their parent’s DNA but potentially their parent’s disrupted gene-switching patterns too.

Researchers found over 20,000 cannabis-induced perturbations of DNA methylation in human and rodent sperm. That is not an incidental finding. It points to cannabis as a substance capable of altering the genetic legacy a parent passes to their child in ways that may accumulate across generations.

The genotoxic effect appears to apply not just to THC but to a structural feature common to all cannabinoids, including CBD. Every cannabinoid shares a particular chemical building block called the olivetol ring, a molecular structure that researchers now believe is responsible for the DNA damage. Because it is present in every cannabinoid without exception, the damage potential is not limited to the psychoactive component of cannabis. This matters because CBD is widely marketed as safe and is used freely by people who would not go near THC-containing products.

Cannabis as a Greater Threat to the Foetal Heart Than Tobacco or Alcohol

A teratogen is any substance that interferes with normal foetal development. Tobacco and alcohol are the two most widely recognised examples, the subject of decades of public health warnings. The study analysed the relative contributions of cigarettes, binge alcohol and cannabis to the rise in ASD rates. Cannabis accounted for nine per cent of the measurable variance. Tobacco accounted for 1.7 per cent. Alcohol was less significant still, and its relationship with ASD rates was inverse, reflecting its overall decline in the population over the same period.

This finding is consistent with earlier large-scale studies. The link between cannabis and birth defects is, by this measure, a substantially more serious problem than the equivalent risks posed by tobacco or alcohol. Given the decades of public health effort directed at smoking and drinking during pregnancy, this comparison demands a serious rethink of how cannabis is positioned in public health messaging.

Legalisation as an Amplifier of the Cannabis and Birth Defects Problem

Cannabis use in the US has risen 1.9-fold since 2005. But because the cannabis available today is far more potent than in previous decades, a composite exposure index accounting for both use rates and THC concentration rose 6.6-fold between 2009 and 2018. More people are using a stronger product, and the ASD data tracks that trajectory closely. What legalisation has done, in effect, is accelerate the pace at which a population-wide genetic experiment is being conducted on people who have not yet been born and cannot consent to it.

Legal status appears to be a driver in its own right. The statistical analysis found that the departure from normal ASD rate trends was wholly attributable to high-cannabis-use states, which are overwhelmingly states with liberal legal frameworks. The authors applied causal inference tools, including inverse probability weighting, and found the association between cannabis legalisation and elevated ASD rates met the criteria for probable causation.

This is consistent with large population-based studies from Hawaii, Canada, Australia, Colorado and Europe, all of which have identified associations between cannabis exposure and atrial septal defects.

A Debt Being Passed to Children Who Have No Say

The researchers conclude that ASD rates may now serve as a bellwether: a population-level signal of the genetic and epigenetic legacy of widespread cannabis use. The data is clean, consistent and now replicated across multiple countries and methodologies.

What it shows is a society accumulating a biological debt that will not fully arrive for another generation or more. A person who uses cannabis today may not see the full consequences in their own children. They may appear in their grandchildren, or their grandchildren’s children, in the form of heart defects, developmental disorders or other conditions that no one at that future point will be able to trace back to a decision made decades earlier.

The damage travels silently through generations because it is written not in symptoms but in the molecular switches that control how genes behave. It is invisible until it is not.

The authors put it plainly: community genomes and epigenomes are precious but fragile resources. Once altered across a generation of reproductive-age adults, that damage cannot simply be undone. The window for preventing this harm is now, not in the generation that will inherit it.

Source: MDPI