Researchers were able to restore memory performance, with the next step for clinical trials in humans to see whether THC reverses aging processes and increases cognitive ability.

With increasing age, memory performance decreases. Now, new Hebrew University research shows cannabis can reverse these aging processes in the brain. Scientists at the University of Bonn, with colleagues at the Hebrew University of Jerusalem, showed this in animal models. The older models were able to regress to the state of two-month-olds with a prolonged low-dose treatment with cannabis as an active ingredient. This discovery opens up new options, such as treating dementia. The research results are now presented in the journal Nature Medicine

May 8, 2017 — Like any other organ, our brain ages. As a result, our cognitive abilities decrease with increasing age. Thus, it becomes more difficult to learn new things or devote attention to several things at the same time. This process is normal, but can also promote dementia. Researchers have long been looking for ways to slow down or even reverse this process.

Scientists at the University of Bonn and the Hebrew University of Jerusalem have now achieved a way to restore cognition abilities in animal models. With their short life expectancy, these models display pronounced cognitive deficits even at 12 months of age. The researchers administered a small quantity of THC, the active ingredient in cannabis, to models aged two, twelve and 18 months over a period of four weeks.

Afterward, they tested learning capacity and memory performance in the models – including orientation skills and the recognition of other models. Subjects that were only given a placebo displayed natural age-dependent learning and memory losses. In contrast, the cognitive functions of the models treated with cannabis were just as good as the two-month-old control subjects. “The treatment completely reversed the loss of performance in the old animals,” reported Professor Andreas Zimmer from the Institute of Molecular Psychiatry at the University of Bonn and member of the Cluster of Excellence ImmunoSensation.

Years of meticulous research

This treatment success is the result of years of meticulous research. First, the scientists discovered that the brain ages much faster when animal models do not possess any functional receptors for THC. These cannabinoid 1 (CB1) receptors are proteins to which the substances dock and thus trigger a signal chain. CB1 is also the reason for the intoxicating effect of THC in cannabis products, such as hashish or marijuana, which accumulate at the receptor. THC imitates the effect of cannabinoids produced naturally in the body, which fulfill important functions in the brain. “With increasing age, the quantity of the cannabinoids naturally formed in the brain reduces,” says Professor Zimmer. “When the activity of the cannabinoid system declines, we find rapid aging in the brain.”

To discover precisely what effect the THC treatment has in old animal models, researchers at the Hebrew University of Jerusalem, led by Dr. Mona Dvir-Ginzberg and the late Professor Itai Bab, examined the epigenetic changes in brains of aged models treated with THC.

“The THC treatment induced molecular and epigenetic changes, which no longer corresponded to that of untreated old models, but rather were similar to what we see in young animals,” said Dr. Mona Dvir-Ginzberg from the Institute of Dental Sciences, in the Faculty of Dental Medicine at the Hebrew University of Jerusalem.

Moreover, the number of links between the nerve cells in the brain also increased again, which is an important prerequisite for learning ability. “It looked as though the THC treatment turned back the molecular clock,” says Zimmer.

Next step: clinical trial on humans

A low dose of the administered THC was chosen so that there was no intoxicating effect in the models. Cannabis products are already permitted as medications, with many uses, such as for pain relief. As a next step, the researchers want to conduct a clinical trial to investigate whether THC also reverses aging processes in the brain in humans and can increase cognitive ability.

CITATION: A chronic low dose of delta9-tetrahydrocannabinol (THC) restores cognitive function in old mice, Nature Medicine, DOI: 10.1038/nm.4311