Street drugs and emotional memory
Studying marijuana and the adolescent brain, opioids and addiction-related memory
One of Canada’s notable brain researchers has significant concerns about the federal advisory board’s recommendation for the age limit of marijuana legalization.
“Eighteen is too young. There’s no way around it,” warns Dr. Steven Laviolette, Professor in the Depts. of Anatomy and Cell Biology and Psychiatry, Schulich School of Medicine & Dentistry at the University of Western Ontario.
“The adolescent brain is developing well into the early 20s, and in my opinion, 18 is far too young. There’s still a lot of important brain maturation going on. To allow an 18-year old access to high THC strains of marijuana is potentially dangerous.”
Laviolette knows what he’s talking about. His research has studied the behavioural and physiological effects of cannabis and its specific phytochemical components on the brain.
The final connectivity between the brain’s prefrontal cortex and subcortical dopamine areas are still developing in young adults. These connections are key to controlling emotional stability.
“We know that’s still happening in the brain into the early 20s,” he says. “The prefrontal cortex serves as a braking mechanism on the subcortical primordial emotional processing centres in the brain. When these brain mechanisms are disturbed, there is an increased risk of developing neuropsychiatric disorders, such as schizophrenia or mood disorders”.
Marijuana and emotional memory
Laviolette’s research explores the complex interaction of biology, psychology and emotion in the brain. He has studied how memories of emotional experiences are formed and how disruptions in this process may be related to mental health problems, such as addiction, mood disorders and schizophrenia.
“I started almost accidentally,” he says.
He has always been curious about how emotional memories form in the brain’s prefrontal cortex. That’s the area of the brain that controls personality, decision-making and complex cognitive and social behaviours. Along with the amygdala, it has the ability to retain memories of life’s salient emotional experiences.
Laviolette knew that people with schizophrenia had abnormal levels of cannabinoid receptors in the prefrontal cortex, and at the University of Pittsburgh, as a postdoctoral fellow, he learned that synthetic cannabinoid compounds were available for laboratory research. Taking advantage of the opportunity, he devised an experiment to study their effects on the formation of emotional memory.
He investigated how laboratory animals reacted to a memory cue paired with a slight, almost unnoticeable foot shock. When given the memory cue, cannabinoid-treated animals had more intense reactions, based on their “highly salient” emotional memories.
This experiment showed how cannabinoid abnormalities in the brain might account for the inabilty of people with schizophrenia to process the emotional importance of incoming information.
As Laviolette explains it, a person with schizophrenia might see something that other people would ignore and form a dysfunctional emotional memory of the sight. It could lead to a faulty interpretation of that visual information, e.g., a paranoid delusion or hallucination.
His next step was to explore the effects of smoking large amounts of marijuana on the prefrontal cortex. His findings showed that a major natural component of marijuana, THC, directly activates the brain’s dopamine system in a way that’s similar to dopamine hyperactivity in people with schizophrenia.
The other major component of marijuana, cannabidiol (CBD), has the opposite effect. It shuts down the dopamine system.
“That’s why we think that strains of marijuana with equal amounts of THC and CBD are much safer than strains with high levels of THC, which are now known to increase the risk of schizophrenia-related symptoms,” he says.
CBD may mitigate the harmful effects of THC; however, most modern strains of marijuana contain high levels of THC, the primary activator of cannabinoid receptors in the prefrontal cortex.
“Because the adolescent brain is so vulnerable, exposure to high levels of THC interferes with the normal connectivity between the frontal cortex and subcortical dopamine areas,” says Laviolette. “These connections are necessary for proper adult cognition and emotional processing. It’s the THC that seems to cause the problems, particularly in individuals with a genetic predisposition to schizophrenia.”
Opioids and addiction-related memory
Laviolette and his team also study how chronic exposure to opioid drugs, e.g., heroin and morphine, change the brain, particularly memories related to the addiction experience. They are examining how chronic opioid exposure alters memory pathways in the prefrontal cortex and amygdala at the molecular level.
Their research has discovered that when a recovered addict – someone who’s been off drugs for years – encounters something in their environment that triggers an addiction-related memory, that person is at high risk of relapse. In other words, the powerful intensity of those emotional memories can steer them back to drug abuse.
This research and similar work in the field have led scientists to believe that addiction is not primarily a disorder of reward, as once thought, but of learning and memory.
Laviolette and his team have found a molecular switch that controls addiction-related memory in the amygdala: calcium/calmodulin-dependent kinase 2 (Camk2).
“Chronic exposure to heroin triggers this addiction switch,” he explains. “Our target is to look at memory changes and figure out if there’s a way to develop a treatment that would either prevent them from being activated or reverse molecular changes that control the memory switch.”
The ultimate goal is to prevent the addiction-related memories from triggering a relapse.
“I’ve got some excellent postdoctoral fellows and talented graduate students working for me who are doing some amazing research,” he says. “That’s one of the rewards of this work. You see brand-new discoveries on almost a weekly basis.”