Safer than Marijuana, a Natural Chemical Strengthens Memories

by Elizabeth Norton Lasley

June, 2009

When an experience packs an emotional wallop, it burns itself instantly into the memory. A new study shows that endocannabinoids—the brain’s natural equivalents of marijuana—are among the substances that help shore up emotionally charged memories.

“We’re not recommending that anyone smoke pot to enhance memory,” study author Jim McGaugh of the University of California, Irvine, is quick to point out. “But our finding does provide a clue toward developing new compounds that activate the same system [as marijuana] more safely.”

The process takes place in the basolateral complex of the amygdala, a region targeted by a variety of chemical messengers. Stress hormones, for example, activate this region to ensure that we avoid dangerous situations in the future.

Important memories form quickly in the amygdala, and the basolateral complex in particular is a target site for several chemical messengers involved in emotion, stress and memory, such as adrenalin. Other hormones called glucocorticoids, which are important in the body’s response to stress, trigger a biochemical chain of events in the basolateral amygdala and contribute indirectly to memory formation.

Recent research suggests that endocannabinoids, too, work through receptors in this part of the brain. These brain chemicals contribute to many functions, including movement, appetite, mood, and pain control. Full-scale overstimulation of the endocannabinoid receptors—from smoking marijuana, for example—can cause severe memory problems. But in animal experiments, certain receptors known as CB1 receptors have been shown to influence neuronal firing.

In the March 24 Proceedings of the National Academy of Sciences, McGaugh, lead author Patrizia Campolongo and colleagues show that endocannabinoids help solidify emotionally significant memories. In the experiment, rats explored a box with a whitewalled section and a darkened area with a mildly electrified floor. When a rat entered the dark chamber, it got a brief shock. After 48 hours the rats visited the box again; the strength of their memories was measured by their reluctance to enter the darkened area.

Rats with CB1 receptors stimulated with an experimental compound took far longer to re-enter the dark section, indicating that they remembered the shock with more aversion. Conversely, rats treated with a compound that blocked the receptors ventured more readily into the dangerous area.

Another phase of the experiment showed that endocannabinoids bring about the well-known reinforcing effects of glucocorticoids. Normally, animals treated with the hormone corticosterone will form stronger memories, but when rats were given corticosterone along with a CB1 blocker, they showed less aversion to the place where they received the shock.

McGaugh says growing evidence suggests that the basolateral amygdale helps mark recently acquired information as important—good news too. Reporting in the May 12 Proceedings of the National Academy of Sciences, another group led by Campolongo and McGaugh found that a hormone fat cells secrete in response to feelings of satiety or “fullness” also enhances memory in the basolateral amygdala.

“If you’re an animal, remembering where you found something good to eat is as important as remembering where you ran into trouble,” McGaugh says.

The finding that glucocorticoids need the help of endocannabinoids is also significant, says Rafael Roesler, who heads the department of pharmacology at the Federal University of Rio Grande do Sul in Brazil and was not involved in the recent research. Because long-term stress can lead to impairments in memory and cognition, he says, the cannabinoid system might be an avenue to explore in treating stress-related disorders.

“Disruption of the cannabinoid system is also implicated in neurodegenerative disorders affecting memory, such as Alzheimer’s and Parkinson’s disease,” Roesler says. “Drugs acting on the CB1 receptor are potential nextgeneration treatments for these and other disorders.”