Cannabis May Combat Age-Related Cognitive Decline

Megan Brooks

May 10, 2017

The long-term administration of low doses of the cannabinoid tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana, ameliorates age-related learning and memory deficits in mice, researchers have observed.

On the basis of this observation, the investigators plan to conduct a clinical trial to determine whether the finding applies to elderly individuals with and those without cognitive impairment, Andras Bilkei-Gorzo, PhD, of the Institute of Molecular Psychiatry, University of Bonn, Germany, told Medscape Medical News.

For the study, the investigators examined the effects of the long-term administration of low-dose THC in young (2 months old), mature (12 months old), and old (18 months old) mice.

They found that THC treatment was associated with impaired behavioral performance on learning and memory tasks in young mice, but with improved learning and memory in mature and old mice.

"THC treatment has practically opposite effect in young and old animals," Dr Bilkei-Gorzo told Medscape Medical News.

"The same treatment rejuvenated old brains, whereas it made the young brains old. The reason of this phenomenon is that the activity of cannabinoid system declines in aging. In old animals, THC treatment restored the failing cannabinoid system activity, whereas it overactivated the normally functioning cannabinoid system in young animals," the researchers write.

The study was published online May 8 in Nature Medicine.

Turning Back the Molecular Clock

These changes in behavior in the older mice were associated with a restoration of global hippocampal gene expression patterns back to a state similar to that observed in young animals, the researchers note.

"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," they write.

"It looked as though the THC treatment turned back the molecular clock," Andras Zimmer, PhD, director of the Institute of Molecular Psychiatry, University of Bonn, said in a news release.

"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," the investigators note.

"The beneficial effect of THC treatment on brain functions persists long after the termination of the treatment suggesting a long lasting effect of THC on the old brain, whereby epigenetic processes play a key role," said Dr Bilkei-Gorzo.

Going forward, "we have to clear the exact mechanism of action of THC and optimize the treatment strategy using animal models. Parallel with it, we will start a clinical trial to test the efficacy of THC treatment on the learning and memory abilities of elderly with and without cognitive impairments – hopefully within a year."

The study had no commercial funding and the authors have declared no relevant financial relationships.

Nat Med. Published online May 8, 2017. Abstract

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