Marijuana Reversed the Effects of Old Age in Mouse Brains

THC helped old mice learn and remember as well as young mice.

What if we told you that a lifetime of smoking pot might actually be good for your aging brain?

Research published Monday in Nature Medicine suggests that one of marijuana’s active ingredients, Δ9-tetrahydrocannabinol (THC), could have the magical power of helping to preserve the memories and learning abilities of mouse brains as they age.

There’s lots of research on how cannabis affects people’s minds while they’re using it. The short-term effects of cannabis can include impaired memory, addictive use, and getting laid. But there’s not as much research on how cannabis affects brains after prolonged use.

Co-lead authors on this study, Onder Albayram, a research fellow at Harvard Medical School and Andreas Zimmer, director of the Institute of Molecular Psychiatry at the University of Bonn, worked with an international team of researchers in Germany and Israel. To perform this study, Albayram, Zimmer, and their colleagues administered low doses of THC to mice for 28 days. These mice ranged in age from young (2 months), mature (12 months), and old (18 months), and a portion of the mice were left untreated as a control group. After giving the mice five days off THC, the team put the mice through cognitive behavioral tests, including the Morris water maze, an object recognition test, and a partner recognition test. These tests were intended to see how well mice can remember features in their environment, as well as how good they are at learning and adapting to changes. The researchers found that the old mice treated with THC performed these tests just as well as the young mice that were untreated. Surprisingly, the young mice that were treated with THC performed just as poorly as the old mice that had not received THC.

So what accounts for these behavioral changes in old mice treated with THC? Albayram says it has to do with the way THC interacts with the brain’s natural cannabinoid system, known as the endocannabinoid system.

“The young brain has lots of endocannabinoids, and an old brain has significantly less,” Albayram tells Inverse. “That’s why when you give THC to a young brain, which can access lots of endocannabinoids, this confuses the brain. But when you give THC to old brains, they have less endocannabinoid binding affinity, so the brain experiences a plasticity change to adapt to high THC.”

Since cannabinoids are involved in normal cognitive processes (not just when you’re getting high), deficiencies or overabundances can cause cognitive processing difficulties. So while THC in young mice makes it harder for them to learn and remember, for the old mice in this study, THC simply helped them restore a lost internal balance of brain chemicals.

The study’s authors have been careful to note that these results only apply to mice. And while there are some obvious differences between mice and humans, like size and lifespan, there are also some really important similarities that suggest this research could apply to humans.

“They’re both mammals. Brain parts, the hippocampus for example, involved with learning and memory, function the same in humans and mice. Humans and mice also have the same proteins and biological systems,” Albayram says, adding: “Their brains use cannabinoids for memory consolidation. We will find a way to move to human studies.”

Albayram also notes that humans and mice both have similar endocannabinoid systems, including two different types of cannabinoid receptors.

“I think studying THC is one of the best ways to understand how the brain works,” says Albayram. “It can manipulate the brain in a good or bad way.”

Abstract: The balance between detrimental, pro-aging, often stochastic processes and counteracting homeostatic mechanisms largely determines the progression of aging. There is substantial evidence suggesting that the endocannabinoid system (ECS) is part of the latter system because it modulates the physiological processes underlying aging. The activity of the ECS declines during aging, as CB1 receptor expression and coupling to G proteins are reduced in the brain tissues of older animals and the levels of the major endocannabinoid 2-arachidonoylglycerol (2-AG) are lower. However, a direct link between endocannabinoid tone and aging symptoms has not been demonstrated. Here we show that a low dose of Δ9-tetrahydrocannabinol (THC) reversed the age-related decline in cognitive performance of mice aged 12 and 18 months. This behavioral effect was accompanied by enhanced expression of synaptic marker proteins and increased hippocampal spine density. THC treatment restored hippocampal gene transcription patterns such that the expression profiles of THC-treated mice aged 12 months closely resembled those of THC-free animals aged 2 months. The transcriptional effects of THC were critically dependent on glutamatergic CB1 receptors and histone acetylation, as their inhibition blocked the beneficial effects of THC. Thus, restoration of CB1 signaling in old individuals could be an effective strategy to treat age-related cognitive impairments.
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