Could THC Help an Aging Brain?

The main psychoactive component of marijuana protects aging mice against cognitive declines. Could it someday do the same for humans?
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The main psychoactive component of marijuana protects aging mice against cognitive declines. Could it someday do the same for humans?
White widow.

White Widow, a hybrid cannabis strain.

Slowly but surely, Americans are coming around to recreational weed.

Roughly 30 million Americans admitted to smoking pot in the last year, and 60 percent now believe it should be legal—the highest percentage since Gallup began polling on the drug almost 50 years ago. At least 28 states and Washington, D.C., have legalized marijuana for recreational or medical use. But while marijuana has steadily grown in popularity, research has consistently raised some concerns on the drug. Some studies, for example, appear to show that THC—the primary psychoactive component in marijuana—can lead to temporary cognitive impairments in young people.

But now, a new study published today in Nature Medicine offers marijuana supporters some good ammunition: At least among mice, THC may actually improve cognitive performance in aging individuals.

"Many, many studies show that, if kids smoke marijuana, cognitive performance goes down," says Andreas Zimmer, a professor of molecular psychiatry at the University of Bonn in Germany, and lead author on the new study. "But there are very few studies, if any, in older individuals."

In order to study the science of getting high, it's important to first understand the neurobiology. The reason marijuana has any effect on us at all is that humans—along with nearly every other animal species, including mice, monkeys, and sea sponges—have receptors throughout the body for the cannabinoid compounds that we naturally produce. Those receptors are involved in mood, appetite, and pain sensation. THC, or Tetrahydrocannabinol, is a cannabinoid in cannabis that links up with those same receptors, leading to the psychoactive effects of smoking weed.

There are many reasons to be optimistic that THC could one day be used to reverse or slow cognitive declines in aging humans.

Zimmer and his colleagues have been studying this endocannabinoid system in mice for years. Previously, he found that, when they blocked those cannabinoid receptors, the cognitive performance of the mutant mice began to rapidly decline—as if they had begun to age faster than usual, which suggested that cannabinoids played a role in cognition. That, coupled with a finding that mice tend to produce less cannabinoids as they age, got Zimmer wondering if they could supplement those declining levels of natural cannabinoids with exogenous ones: in other words, THC.

To find out, the team implanted tiny pumps under the skin of young (two-month-old), mature (12-month-old), and old (18-month-old) mice that delivered a small dose of THC to the animals every day for one month. The researchers then ran the mice through a battery of behavioral tests to assess their learning, memory, and social recognition. As it turns out, restoring levels of cannabinoids back to more youthful levels in the mice improved performance on these tests as well. And those improvements lasted for weeks after the authors cut off the flow of THC through the pumps.

"After treatment of four weeks, the 12- and 18-month-old animals behave like two-month-old animals; we cannot tell them apart anymore. In a way, it's almost a rejuvenating factor in old animals," Zimmer says. "THC is the only substance I know that is able to do that."

The older mice didn't just perform like their younger counterparts—their brains actually looked younger as well. The researchers zeroed in on the hippocampus, a region of the brain critical for memory, and where cannabinoid receptors are abundant. THC appeared to up the productivity of genes associated with longer lifespans, improved cognition, and a lowered risk of Alzheimer's, and reduce the expression of genes involved in aging and cell death.

"The results so far are extremely astounding," Zimmer says. "The next thing that we have to do, and that we want to do, is to see whether we can transfer these results into the clinic." Indeed, there are many reasons to be optimistic that THC could one day be used to reverse or slow cognitive declines in aging humans; the endocannabinoid system in humans works much the same as it does in mice, and the widespread use of medical marijuana has proven that THC, when taken in low doses, is safe and relatively free from side effects.

But don't mistake the study's findings as an endorsement to start smoking weed—medicinal or otherwise. For one thing, that's not how the mice in the study were even exposed to THC. "The problem is that marijuana is widely accessible, and many people smoke it," Zimmer says. "I'm concerned that people may think that by smoking pot they could produce the same effect that we saw, and that could be wrong."

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