The Genetic Component of Cannabis-Induced Schizophrenia

By Laura Stack

Modern marijuana is an insidious drug, in part because its proponents and users operate under a set of assumptions that no longer apply. Once upon a time—ironically, during the period when government agencies quashed it most severely—marijuana wasn’t much of a threat to most people. The concentration of tetrahydrocannabinol (THC), the chemical that generates its high, was typically in the low single digits.

But due to selective breeding and various chemical processes, the THC content in today’s marijuana products has increased by up to 30+ times, and concentrates can be 90%+ THC. Even as many states have legalized or decriminalized marijuana, and fewer people consider it a threat, the danger has grown with the THC concentration—to the point where modern marijuana is a totally different drug. Today, marijuana IS a hard drug with narcotic strength. Excessive marijuana use, especially in young people, can cause not just cancer, but numerous other physical and mental disorders.

One of the most alarming is schizophrenia. Mental health professionals have long recognized a relationship between marijuana use and schizophrenia, but what came first, the chicken or the egg? Can marijuana trigger schizophrenia in some users, or did schizophrenics just use marijuana at a higher rate than non-schizophrenics? It took a while, but researchers eventually established the causal direction as marijuana to schizophrenia. Individuals who begin using marijuana during adolescence are much more likely to develop adulthood schizophrenia than non-users.

We’ve also learned that first-episode marijuana psychoses are more likely to occur after high potency marijuana use. The cutoff is for high potency is anything above 10% THC content.  The average THC content for modern marijuana products exceeds 15%.

What’s Happening Here?

The big question then became, “Why is marijuana a significant risk factor for developing schizophrenia?”

Recent evidence suggests that in some cases, your genes can play a big role—more specifically, it involves how one’s genes interact with the environment. There’s no single “schizophrenia gene”; we know that many different genes can cause someone to become schizophrenic if triggered. Dr. Erik Messamore, a member of Johnny’s Ambassadors Scientific Advisory Board, says there are over 100 genes that can contribute to the condition. Most of these genetic vulnerabilities result from mutations, and they most likely activate because of multiple small changes accumulating over time.

Genes that we know can interact with cannabis to cause schizophrenia include catechol-O-methyltransferase(COMT), AKT1, and neuregulin 1 (NRG1). Typically, genes have multiple variants, and some combinations aren’t as risky. Researchers are still in the process of determining which variants react to marijuana use; a recent study suggests carriers with the COMT variant called valine158 (VAL/VAL) are most likely to develop schizophrenia when exposed to marijuana.

Interactions between marijuana and other genes may also cause schizophrenia; researchers are still delving into this. Clearly, multiple variants of multiple genes can interact with cannabis to trigger schizophrenia.

How This Hurts Us

Even with an average 500% increase over the norm for marijuana users, the number of “schizophreniform” cases remains statistically small. An average of only about one in a hundred people in the general has schizophrenia. Among daily marijuana users, the frequency increases to around five cases per 100. This is a small increase, but a significant one when multiplied by the number of adolescent marijuana users. As of 2020, roughly 4.4% of the estimated 24 million Americans aged 12-17 used marijuana daily or near-daily (the percentage varied from 1.1% for eight graders to 6.9% for 12th graders).

This yields about 1,056,000 adolescent daily users.  About 1% of the general population develops adult schizophrenia, so the total number of cases for this cohort would normally come to about 10,560. However, we must multiply this number by five, due to their heavy marijuana use. Thus, the number of cases for this cohort alone rises to almost 53,000, burdening families and the medical system with tens of thousands of new cases of a terrible disorder characterized by psychosis, paranoia, and other distortions of reality—most of which needn’t have occurred.

A Crucial Disclaimer

I feel we require a warning here, because I suspect some marijuana advocates will take the news of a genetic vulnerability for cannabis-induced schizophrenia exactly wrong. They might think, “They would have had this happen with or without smoking weed, so what’s the big deal if they do?”

The big deal is this: that statement is completely false. First, we’re not sure yet whether everyone who develops schizophrenia after marijuana use has one of the vulnerability genes. As far as we know at this point, people with no genetic tendencies toward schizophrenia can still acquire it after using marijuana as adolescents. Other factors, like the cannabinoid tendency to lock certain neurotransmitters out of brain cells, may also be in play; we don’t know yet. Johnny was tested after his marijuana use began, and his COMT genes were normal, so that particular gene wasn’t the cause of his schizophrenia.

Second, not everyone with a genetic risk for schizophrenia will develop it; in fact, most don’t. The risk doesn’t rise higher than 50% under normal circumstances, and that occurs only if one has an identical twin with the disorder (it’s 40% if both parents have it). Something may trigger it along the way, but it’s likely nothing will, especially if the person at risk is careful to avoid risk factors. So, having these harmful genes DOES NOT automatically cause schizophrenia. They just make someone more vulnerable to it. They usually require a trigger—an environmental change that “switches on” the gene. Marijuana can provide that trigger.

The point? We know marijuana use is a significant and independent risk factor that may trigger schizophrenia. High-potency marijuana use alone can increase the risk of schizophrenia in later life by a factor of about five times on average. Various studies have pegged the risk at four to seven times the normal rate for long-term and high-potency pot users.

These figures make the normal familial risk factors pale in comparison.

The Lessons Here

Schizophrenia does seem to have a component caused by the environmental triggering of specific genes. Heavy marijuana use can serve as one of those triggers. But never assume that just because someone’s genes might cause them to become schizophrenic that they will. Assuming that someone who has acquired cannabis-induced schizophrenia would have manifested it anyway is NOT a fact. More importantly, if we can identify the genes that confer vulnerability to cannabis-induced psychosis, we can warn the people and put extra protective factors in place to avoid marijuana use altogether.

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