The Memory Divide: Why Cannabinoids Have a Greater Influence on Adolescents

December 11, 2024
Science Magazine

With marijuana being marketed as a harmless recreational drug, more and more teens are falling into its trap. Historically, marijuana has been the most abused illegal drug. But with 48 states now allowing some form of medical use or full legalization, teen marijuana use may rise as access increases. What is marijuana doing to them? Beyond the buzz, marijuana is having a bigger impact on their brains and even their future. Is it worth the risk?

Scientists Against Addiction

Dr. Cynthia M. Kuhn is on a mission to understand how drugs like marijuana affect the brain and to help reduce its use among teenagers. As a Professor of Pharmacology and Cancer Biology at the Duke University School of Medicine, Dr. Kuhn focuses on the neurobiology and neuropharmacology of addiction. According to Dr. Kuhn, she has more recently been studying “how the brain responds to the ongoing presence of drugs.”

When she was younger, Dr. Kuhn was fascinated by what alcohol could do to the brain—a curiosity that grew in college after taking a course on the impact of drugs on the brain. This led her to graduate school to “pursue research that [she] developed, not just work for somebody.” Her first paper on the effects of long-term amphetamine use on animals cemented her interest in this field of research. Now, she enjoys teaching graduate students at Duke about the very topics that first captivated her.

Dr. Kuhn approaches a question first behaviorally and then mechanically. In her 2010 study, Dr. Kuhn examined the effects and mechanisms of cannabis in adolescent and adult rats.

About the Research

THC, or ∆9-tetrahydrocannabinol, is the substance in marijuana that directly affects the brain. Many professionals are concerned about the long-term consequences of marijuana on adolescents, especially as it is well-researched that marijuana leads to impaired memory, anxiety, depressive behavior, and altered sensitivity. These memory impairments affect spatial learning, causing affected individuals to struggle to absorb, process, and recall information about the space of the world around them. For example, they might have difficulty remembering the location of objects and navigating unfamiliar environments.

The hippocampus controls memory in the brain and contains type 1 cannabinoid receptors (CB1). CB1 is a protein that interacts with cannabis-related substances, like THC. When activated by these substances, CB1 receptors can contribute to significant spatial learning impairments.

THC is known to cause greater impairments in adolescents than in adults, but why? Dr. Kuhn hypothesized that THC might impair learning in adolescents more than adults because of a slower response in the adolescent hippocampus that typically allows the body to tolerate the effects of cannabinoids. By uncovering why THC has a stronger effect on adolescents, Dr. Kuhn hoped to provide information to demote the use of marijuana during teenage years, ultimately preventing permanent harm. 

The Path to Discovery

To tackle their question, the researchers used a water maze test, in which both THC-treated rats and untreated rats had to use visual cues to find a platform in the water. This paradigm tests spatial learning because typically over multiple trials, rats get faster and swim less to find the platform.

Dr. Kuhn’s team found untreated adolescent rats were able to swim to the platform in less time and a shorter distance compared to adolescent rats that they treated chronically with THC. However, the adult rats pretreated with THC swam less than those without the treatment, showing signs of unaffected spatial learning and desensitization to THC treatment. The adolescent rats, on the other hand, did not show signs of desensitization, causing THC to impair learning in adolescents more than adults.

Morris Water Maze Test | BioRender Science Templates

Above: Rat in the Morris water maze before and after training. Image courtesy of Nima Vaezzadeh and BioRender.

After finding this behavioral effect, the scientists turned their attention to understanding how long it took for the receptor’s response to THC to decrease. To do that, they examined the time for CB1 desensitization in the adolescent versus adult rats’ brains. The results suggested that—compared to adults—CB1s in the adolescent hippocampus desensitize more slowly in response to THC treatment, supporting their original hypothesis that THC effects last longer in adolescents.

Above: CB1 in the brain under a microscope. Image courtesy of Kuhn et al., 2010.

Overcoming Obstacles

“There are always, always, always failures in research,” Dr. Kuhn said. “You can always screw up a batch of reagents or give the wrong dose.” Specifically, Dr. Kuhn highlighted challenges with animal care because animals in high stress do not perform normally, making environment control a constant struggle. “You just have to persevere in research,” she said.

So What?

Simply put, “kids shouldn’t be smoking pot because it’s going to be more memory impairing to them than adults,” Dr. Kuhn explained. Furthermore, teenagers are more likely to be diagnosed as psychotic compared to adults when addicted to marijuana. Scientists are also concerned that marijuana affects the final maturation of the cortex during adolescence, stopping the brain before it has finished developing.

Dr. Kuhn appreciates that her “line of work gets a more direct line from research to real-world health implications” and that her research can help prevent harmful behaviors in teens. The more researchers explore, learn, and discover how drugs affect our brains, the more prevention and treatment methods improve.

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