By Marcia Hill Gossard
Like many kids her age, Kelli, a 10th-grade high school student, learned about the dangers of using marijuana in health class.
“They teach us not to do it because it is a gateway drug,” she said, “and it can take you down a bad path.”
But despite the educational warnings, she knows many kids in her school are smoking marijuana.
“They don’t worry about it at all,” she said. “They think it is a cool thing to do.”
Although Kelli said she would never try marijuana, she admits that because kids talk about it so openly, she doesn’t think about the dangers of marijuana as much as she does with other drugs.
According to a JAMA Pediatrics article published in December 2016, Washington state eighth- and 10th-graders perceived marijuana as less harmful and reported an increase in use when compared to teens in states where marijuana is not legalized. And that worries Ryan McLaughlin, assistant professor of neuroscience in the College of Veterinary Medicine.
“Since marijuana has legalized for recreational use in Washington state, the concern has been that, with reduced stigma, there may also be a reduction in perceived harm,” he said.
Washington state legalized marijuana for medical use in 1998, and recreational use in 2012. Because of reduced stigma and a growing number of young people who may decide to use the drug, McLaughlin wants to know how marijuana affects the developing brain, particularly in adolescents and during pregnancy.
“When there is any interference during sensitive developmental stages, then it could lead to maladaptive behavior or changes in brain development,” McLaughlin said. “If people smoke marijuana during adolescence, for example, it could lead to changes in how the prefrontal cortex in the brain develops.”
In teens, the prefrontal cortex, which is the rational or reasoning area of the brain, is developing rapidly. It helps to control impulses and regulate emotions, and it is the center for decision-making, organization and working memory.
During adolescence and until the early- to mid-20s, synapses in the prefrontal cortex are pruned to strengthen the connections between other areas in the brain including the amygdala, the emotional center of the brain.
But because the rational part of the brain is underdeveloped in teens, they are less capable of managing their thoughts and impulses, which might lead to more risky behavior, such as taking drugs.
“There is very little research on effects of early-life cannabis use on cognition and emotion in adolescence or adulthood,” McLaughlin said.
To understand the unique effects on the brain, studies must be done in a controlled environment. With humans, McLaughlin said, there are too many other factors such as poor nutrition, early-life stress, use of other drugs or alcohol, or trauma that could also affect brain development.
In his lab, rats self-administer cannabis in a vapor chamber, a system like an e-cigarette. WSU is currently one of a handful of places in the world using vapor chambers to mimic voluntarily smoking marijuana, which, McLaughlin said, could produce more accurate findings.
“There may be different neurobiological effects when taken voluntarily,” McLaughlin said. “There is also a complex interplay of the compounds in the plant that determines the effects.”
One of the questions McLaughlin is trying to answer is how drug use changes the prefrontal cortex structure during adolescence and the effects it has on making decisions or adopting new decision-making strategies later in life.
“If the prefrontal cortex is underdeveloped, there would be less cognitive flexibility and less ability to shift rules,” he said.
For humans, researchers use the Wisconsin Card Sorting Test to measure this mental flexibility. For rats, they train them to press levers and use different strategies to optimize delivery of sugar rewards.
“We want to understand what happens when the brain is exposed to cannabis during sensitive developmental periods,” McLaughlin said.
McLaughlin’s future research will examine whether exposure to marijuana in-utero could increase the risk of addiction to drugs later in life.
“Ultimately,” he said, “the goal of this type of research is to inform people who use marijuana about the potential benefits and risks.”
The persistence of memory
“Exposure to drugs changes the brain,” said Rita Fuchs, associate professor and director of the Alcohol and Drug Abuse Research Program at WSU. “But the experience of taking a drug also changes the brain.”
When someone uses drugs, elements from the environment around them — sights, smells, sounds and colors — go into their memory.
“Learning takes place while someone is using drugs and the associations are stored,” Fuchs said. “For instance, a red house isn’t just a red house, but a crack house.”
And it is one of the reasons it is so difficult for addicts to quit. When a recovering drug user visits a place or a neighborhood where they had taken drugs, it brings back maladaptive memories, such as getting high and enjoying it, and that could trigger a relapse.
Fuchs maps where these maladaptive memories persist in the brain to learn where a memory could be changed. Memory stored in the amygdala, the emotional center of the brain, can influence people’s desire to use more drugs, make poor decisions, or lead to a relapse.
Fuchs said that once a memory is recalled, it becomes destabilized and has to be restored. The hippocampus holds the memories while they are restabilized in the amygdala.
“The brain is like a maze,” she said. “The more that is unveiled and that we can know, the more points of weakness we can find to alter a memory.”
And that could lead to more effective drug treatments.
“By altering the memory, someone would remember going to the crack house, but would not be transported back emotionally,” Fuchs said. “The memories become two-dimensional rather than three-dimensional. They would not emotionally experience the craving, but rather feel detached. It doesn’t get rid of the memory altogether, but could give them an edge on therapy.”
The Centers for Disease Control report that between 2002 and 2015, drug overdose deaths more than doubled in the United States.
Fuchs’ research to understand how drug memories could be manipulated before a relapse could help pharmaceuticals develop advanced treatments such as gene therapy or lead to new behavior techniques that prevent the restorage of maladaptive memories in the brain.
It could also lead to treatments for opioid use, one of the leading causes of drug overdose.
“There is no reason why this type of circuitry mapping wouldn’t have an impact on developing treatments for heroin and opioid addiction,” Fuchs said.
“It is difficult to halt drug-taking once someone has relapsed,” Fuchs said. “It is better to prevent the relapse altogether. And having science-based treatments will likely be more effective.”
(This article originally was published in the Fall 2017 issue of the College of Veternary Medicine’s Advance newsletter)