Marijuana rejuvenated the brains of old mice
Oleg Lischuk, N+1
German and Israeli scientists have found that the course administration of the main active substance of marijuana is able to restore cognitive functions (in particular, learning and memory) of elderly mice to the level of young animals. At the same time, in younger mice, the effect was largely the opposite. The results of the work are published in the journal Nature Medicine.
The aging process of the body is caused by the counteraction of accumulating negative changes in cells, tissues and organs and homeostatic mechanisms that hinder this process. To date, a sufficient amount of data has been accumulated indicating that the endocannabinoid system (EX) participates in the regulation of a number of such mechanisms. With age, its activity, the number of cannabinoid CB1 receptors and the level of one of the main endocannabinoids 2-arachidonoylglycerin decreases, but the direct role of these processes in the mechanisms of aging has not been clarified.
To understand this issue, the staff of the University of Bonn and the Hebrew University in Jerusalem prescribed young, mature and elderly mice (respectively, aged 2, 12 and 18 months) a small dose of the main psychoactive ingredient of marijuana delta-9-tetrahydrocannabinol (THC), which serves as a powerful agonist of CB1 receptors. The drug at a dose of three milligrams per kilogram of body weight per day (a similar amount does not produce a pronounced psychoactive effect) or a placebo of the same volume was administered continuously using osmotic micro-pumps for 28 days.
Five days after the end of the experimental therapy, the mice were subjected to three tests for cognitive abilities: the Morris water maze (to assess spatial memory and learning), the task of finding and recognizing a new object (to analyze the ability to assimilate new information) and the partner recognition test (to assess the memorization of unfamiliar representatives of their species).
As expected, with the introduction of placebo, mature and elderly mice coped with all tasks worse than young ones. The administration of THC significantly improved the performance of older animals (their results were almost the same as in younger ones without THC), but worsened them in young mice.
Immunochemical analysis showed that the administration of THC restores the production of synapsin I and synaptophysin — markers of synaptic density — decreased with age in the hippocampal neurons (the brain structure responsible for memory consolidation) of elderly animals, but does not affect it in young animals. Analysis of gene expression in the entire hippocampus on the 50th day after the start of therapy showed that its profile in elderly mice after administration of THC is similar to that in young animals from the control group, and vice versa, THC in young mice caused changes similar to the expression profile of elderly animals receiving placebo.
To the greatest extent, the drug affected the expression of genes associated with morphogenesis, homeostasis, transcription regulation, phosphorylation and conduction of nerve impulses. Thus, THC modulates the molecular processes underlying cellular plasticity and neural impulses in older animals, the authors write.
According to them, restoring the signaling activity of CB1 receptors in elderly individuals can become an effective strategy for the treatment of age-related cognitive disorders. Since a low dose of THC was used in the experiment, and medical marijuana preparations are allowed for use in many countries of the world, the researchers plan to switch to clinical trials of such therapy in the near future.
Earlier, an international research team showed that memory disorders when taking marijuana are caused by the action of cannabinoids on mitochondrial receptors in brain neurons. Scientists have also found that THC contributes to the emergence of so—called brain noise - random electrical activity in the central nervous system.
The authors of a recent report by the National Academies of Science, Technology and Medicine of the United States recognized that there is currently insufficient evidence-based scientific data on cannabis preparations. Nevertheless, statistics show that after the legalization of medical marijuana in a number of states of the country, the use of other prescription drugs and insurance costs for them have significantly decreased.
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11.05.2017