Cannabis Use Disorder: The Genetic Component

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By Chris Johnston, MD, Chief Medical Officer, Pinnacle Treatment Centers

Marijuana use is not uncommon.

Everyone knows that. And where marijuana is concerned, this common knowledge is not simply an aggregate of anecdotes repeated so often they become accepted as fact. There’s solid evidence backed up by statistics to support the common perception.

In fact, reliable data indicates it’s the most widely used psychoactive substance in the world, with research showing about 9% of users become dependent. Recent studies in the U.S. reveal marijuana use is on the rise among both adolescents and adults. Results from the 2017 Monitoring the Future Survey (MTF) and the National Institutes of Health (NIH) paint a clear picture of current marijuana use in the U.S.:

  • 45% of high school seniors said they’ve tried marijuana
  • 9.5% of adults said they use marijuana
  • 30% of adults who use marijuana meet the criteria for Cannabis Use Disorder (CUD)
  • Only 2.9% of those who meet CUD criteria receive a diagnosis from a mental health professional

All of that seems logical to most adults in the U.S. In high school, we all knew people who tried marijuana. Some tried it and enjoyed it – they started smoking sometimes. Some tried it and hated it – they never touched the stuff again. And some tried it, loved it, started smoking all the time, and never looked back – they may still be regular marijuana users to this day.

All of this – the evidence-based facts and the anecdotal observations – begs the question: why do some people develop a cannabis use disorder (CUD) while others don’t?

A series of recent studies conducted by researchers in Denmark offer a new insight that may help answer this question: there may be a genetic component to marijuana addiction.

New Study: A Gene Correlated with Cannabis Use Disorder

First, we need to take a brief side trip to the land of statistics. No, we won’t go back to the most hated class in mathematics. We’ll just make sure we’re on the same page with regards to the terms correlation and causation.

This is what they mean:

Correlation describes the relationship between two or more variables. Correlation between variables does not mean a change in one variable causes the change in the other variable.

Causation indicates that one variable or event is the result of the other variable or event. This is simple cause and effect.

Here’s a basic example of cause and effect: eating too much sugary food causes an increased risk of diabetes. And here’s a basic example of correlation: people who eat a lot of sugary foods are more likely to lead a sedentary lifestyle. In the first example, the sugary food causes the diabetes. In the second, the sugary food does not cause the sedentary lifestyle.

Make sense?

It’s an important distinction to understand, not only for this article, but for reading any type of scientific paper or news articles based on scientific papers.

Now that we have that cleared up, let’s move on to this study. It’s a big deal for two reasons:

  1. The size of the study: 2,387 cases and 301,041 controls.
  2. They replicated the study, the second time with higher numbers: 5,501 cases and 301,041 controls.

That means in the first study, they compared the genetic information from 2,387 people with CUD against 301,041 without CUD, while in the second, they compared the genetic information from 5,501 people with CUD against 301,041 without CUD.

What did they find?

They found a specific genetic mutation present in all the people with CUD, and absent in the people without CUD.

CHRA2: The Gene Involved in CUD

There’s a third reason this study is significant, related to the high numbers of individuals the study analyzed. The study is/was what’s known as a Genome-Wide Association Survey (GWAS). Here’s the NIH definition of GWAS:

“A GWAS (genome-wide association survey) is a way for scientists to identify inherited genetic variants associated with risk of disease or a particular trait. This method surveys the entire genome for genetic [patterns] that occur more frequently in cases (people with the disease or trait being assessed) than in controls (people without the disease or trait). Also called genome-wide association study.”

In this GWAS, researchers identified a mutation in a gene – called CHRA2 – that holds the code for a specific class of nicotine receptors. They found that the people diagnosed with CUD had lower levels of the nicotine receptor than people not diagnosed with CUD. Researchers did not identify the mechanism by which the decreased expression of this causes CUD, but nevertheless, this is a major step forward in the research effort to link genetic factors and addiction.

So, why does identifying this gene matter?

Identifying genes associated with specific diseases is important for many reasons, the primary three being:

Awareness

Once scientists identify a gene associated with a disease, they can test individuals for its presence, absence, or any abnormalities. If doctors know an individual carries a gene or genetic mutation associated with any disease, it prepares both doctor and patient for the next item on our list.

Prevention

An individual with a gene or mutation associated disease may or may not develop that disease. However, they can take steps that increase their chances of avoiding the condition or mitigating its effects if it develops.

Treatment

While gene therapy is a new development in science and medicine, it has the potential to radically alter the medical landscape. The goal of gene therapy – and this is grossly oversimplified – is to change mutated genes or genes associated with disease to their non-mutated, non-health threatening variations. It’s a complicated process, but in a nutshell, the idea is that when they replace an atypical gene with a typical gene, the associated disease or condition improves or disappears entirely.

It’s easy to see how this may work with regards to Cannabis Use Disorder. At its most basic level, a genetic screening could identify those who have the CHRA2 mutation and those who don’t. That’s the awareness aspect. Those who have the mutation will understand they’re at increased risk of developing a CUD compared to those who don’t and will ideally avoid using marijuana. That’s the prevention aspect. Finally, a successful gene therapy approach to CUD would involve replacing the mutated CHRA2 gene with a typical CHRA2 gene, thereby – theoretically – decreasing risk of developing a CUD.

Gene Therapy: A New Direction for Medication-Assisted Treatment?

In the addiction treatment world, we welcome all three aspects of gene therapy – the awareness, the prevention, and the treatment. We also welcome any new scientific knowledge about the genetic component of addiction, because – for one thing – we believe the more we can identify the precise physiological causes and mechanisms of addiction, the more we can reduce the stigma around addiction. Finally, gene therapy has the potential to add a brand-new component to Medication-Assisted Treatment (MAT): the current mode of MAT happens after someone develops a substance use disorder, but gene-therapy for addiction could happen before someone develops a substance use disorder.

Therefore, gene therapy has the potential to dramatically reduce the number of people who struggle with addiction. This, in turn, would reduce the amount of pain, suffering, heartache, and loss caused by addiction. We see the damage addiction causes every day, first-hand. That’s why this recent discovery of the gene associated with Cannabis Use Disorder gives us hope: we’re committed to using every evidence-based tool at our disposal to heal, restore balance, and help people struggling with addiction live a healthy, productive life, free from the destructive cycles of alcohol and substance use.