April 24, 2024

Negative experiences with cannabis may be linked to genetics

Differences in how young adults metabolize THC, the main part of cannabis that makes people feel “high,” may influence how they feel after taking the drug, as well as the potential risk of developing use disorder. of cannabis, or CUD.

These findings were recently published in Addictive Behaviors by MUSC researcher Rachel Tomko, Ph.D., and former psychology intern Christal Davis, Ph.D., who is now a postdoctoral fellow at the University of Pennsylvania, as well as others colleagues at MUSC and collaborators at the University of Florida and the University of Colorado. Tomko and Davis also explored whether the effects of a genetic difference in THC metabolism on future outcomes of cannabis use depend on the person’s sex.

CUD, which affects one in five people who use cannabis, leads to problems such as withdrawal symptoms and cravings when not using cannabis, difficulty reducing cannabis use and needing to consume more of the drug to feel the same effects.

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THC metabolism, the process by which this active component is broken down in the body into psychoactive and inactive components, may be influenced by genetic differences in enzymes. About one in four people has a gene that causes these enzymes to break down THC less effectively than others, which can increase the strength and duration of cannabis’ effects.

Differences in metabolism have been linked to an increased risk of substance use disorder for other drugs, but not yet for cannabis.

“Unfortunately, we are just beginning to understand some of the effects of how people metabolize and process cannabis,” Davis explained.

“We are just beginning to understand some of the effects of how people metabolize and process cannabis.”

– Dr.

For the study, researchers recruited 38 young adults ages 18 to 25 with CUD and 16 with non-CUD substance use disorder. This age group was chosen because they are three times more likely to have CUD than teens or adults over 26 who use cannabis. “This age group is very important to study because the brain is still developing during early adulthood,” Tomko said. “So this is a key time for intervention.”

Blood samples were collected from study participants and genetic variants for enzymes that metabolize THC were tested. Participants also completed a questionnaire designed to measure the reported positive and negative effects of cannabis use. Based on the genetic variant, participants were categorized as normal or slow THC metabolizers. The researchers then correlated metabolism with the subjective effects reported by participants.

Davis was surprised by the sex differences evident in the data.

“Looking at our data, we realized very quickly that there were sex-specific effects that we couldn’t ignore.”

Notably, the study showed that young women with CUD were more likely to be slow metabolizers of THC compared to young women with other substance use disorders (non-CUD). This suggests that young women who metabolize cannabis more slowly may be at greater risk of developing CUD.

When looking at young male adults, researchers found that those who had a genetic variant that contributed to slower THC metabolism reported more negative effects during initial cannabis use, such as drowsiness, sluggishness and difficulty concentrating. Overall, participants of both sexes categorized as slow THC metabolizers experienced more negative effects during recent cannabis use.

“This age group [18 to 25] It’s super important to study because the brain is still developing during early adulthood.”

– Dr.

Although the study recruited young adults, the most important implications of its findings may be for teenagers. Many young adults who develop CUD begin using cannabis in their teens. As social acceptance of cannabis increases and its perceived risk decreases, teens may consume more cannabis if they are not aware of the potential harm.

The study highlights that not all young people who use cannabis experience the drug in the same way and that the way people metabolize THC may be a contributing factor to the risk of CUD. Although slower THC metabolizers experience more negative effects, experiencing simultaneous positive effects may lead them to continue consuming cannabis regardless of poor results.

“We might think that if you’re experiencing negative effects, you wouldn’t continue to use, but when faced with positive, rewarding effects, maybe you would,” Tomko said.

Tomko and Davis believe it’s important to educate teens about the differences in how people experience cannabis. For example, educational programs aimed at adolescents can improve their understanding of risk factors for CUD. The Just Say “Know” program, led by Lindsay Squeglia, Ph.D., at MUSC, offers presentations and hands-on training to teach middle and high school students about the neuroscience of drug addiction.

Because most people do not undergo genetic testing for these potential risk factors, it is important to understand how these findings can better inform treatment options for people suffering from CUD.

“Our study opens up new hypotheses and options for exploring medications that can modify THC metabolism as a potential treatment for cannabis use disorder,” Tomko suggested.

The initial findings of this investigation may be particularly important in the context of the continued increase in cannabis potency that has been observed over the past few decades, as well as the availability of high-potency cannabis products in legal markets.

“Increases in THC levels found in cannabis may mimic some of the more pronounced effects we see in people who metabolize more slowly,” Davis said. “The effects of cannabis last longer because it is stronger THC.”

With the lack of regulation of cannabis products, combined with an increase in acceptance of cannabis use, additional research will be needed to identify risk factors for CUD in order to counsel vulnerable groups such as adolescents.

Reference: Davis CN, Markowitz JS, Squeglia LM, et al. Evidence for sex differences in the impact of cytochrome P450 genotypes on the initial subjective effects of cannabis. Addictive behaviors. 2024;153:107996. doi: 10.1016/j.addbeh.2024.107996

This article has been republished from the following materials. Note: Material may have been edited for length and content. For more information, contact the source cited.

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