THC Slows Aging and Cognitive Decline in Geriatric Rodents, While Adolescent Rodents Just Get Wasted

Like our skin and other organs, our brain ages—and it’s harder to hide as our cognitive abilities, memory and the ability for new learning slowly decline with age. Although this is normal, researchers have long been looking for ways to slow down or even reverse this process, particularly for those with degenerative brain diseases.

Recently scientists at the University of Bonn and The Hebrew University of Jerusalem have slowed the aging process in the brains of mice. Mice make great subjects because we share many of the same brain structures, processes and function as they do.

So, with mice as subjects in this well-designed experiment, researchers administered a small quantity of THC, which is the psychoactive ingredient in cannabis to mice who were two months, twelve months and 18 months old, over a period of four weeks. Afterwards, the learning capacity and memory performance in the subjects were tested – including orientation skills (where am I) and the ability to recognize other mice (long term memory). Mice who were only given a placebo displayed natural age-dependent learning and memory deficits. In contrast, the cognitive functions of the older mice treated with cannabis were on par with the two-month-old control animals. Cannabis reversed the loss of cognitive performance in these aged animals.

But How?

To answer this question, the researchers examined brain tissue and gene activity of the treated mice. The findings were amazing. The molecular signature on the older, THC using mice no longer looked or performed like an older animal. On the contrary, it was very similar to that of a younger animal. In addition, the number of links, or synapses between the nerve cells in the brain of the older mice increased significantly, allowing nerve impulses to travel freely, which is a prerequisite for learning something new or remembering something old. In essence, it appeared that cannabis turned back the molecular clock older mice.

In addition, 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. This study shows that a low dose of D9-tetrahydrocannabinol (THC) reversed the age-related decline in cognitive performance of mice aged 12 and 18 months. Thus, the effects of THC on cognitive performance, synap-togenesis, histone acetylation and the expression of age-related genes were all dependent on the CB1 signaling of forebrain glutamatergic neurons. The results do not exclude the possibility that CB1 receptors on other neurons are also involved.

However, in young mice, THC treatment worsened performance, in good agreement with the known detrimental effects of THC on cognition in young animals and humans. Attempts to reverse age-related epigenetic processes through a phar¬macological blockade of histone deacetylases have shown some promise in rodents, but the deleterious side-effects have prevented applica¬tion in humans. Consequently, the generalized inhibition of histone deacetylation is not further considered to be a suitable treatment of age-related pathologies.

Why Does This Matter?

Drug effects are highly dependent on dose, route of administration, pre-morbid illness, trauma, and a host of other factors including age or neurodevelopmental status. Cannabis preparations and THC are currently used for medicinal purposes. They have a good safety record and do not produce too many adverse side-effects when administered at a low dose to older individuals. Thus, chronic, low-dose treatment with THC or cannabis extracts could be a potential research trial and eventually, if successful, a strategy to slow down or even to reverse cognitive decline in the elderly.