Summary: Researchers report low doses of THC can help restore memory and reverse some of the effects of brain aging in mice. The findings could open new avenues for treating dementia and other neurodegenerative diseases.
Source: University of Bonn.
Researchers at the University of Bonn restore the memory performance of Methuselah mice to a juvenile stage.
Memory performance decreases with increasing age. Cannabis can reverse these ageing processes in the brain. This was shown in mice by scientists at the University of Bonn with their colleagues at The Hebrew University of Jerusalem (Israel). Old animals were able to regress to the state of two-month-old mice with a prolonged low-dose treatment with a cannabis active ingredient. This opens up new options, for instance, when it comes to treating dementia. The results are now presented in the journal Nature Medicine.
Like any other organ, our brain ages. As a result, cognitive ability also decreases with increasing age. This can be noticed, for instance, in that 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 (Israel) have now achieved this in mice. These animals have a relatively short life expectancy in nature and display pronounced cognitive deficits even at twelve months of age. The researchers administered a small quantity of THC, the active ingredient in the hemp plant (cannabis), to mice aged two, twelve and 18 months over a period of four weeks.
Afterwards, they tested learning capacity and memory performance in the animals – including, for instance, orientation skills and the recognition of other mice. Mice who were only given a placebo displayed natural age-dependent learning and memory losses. In contrast, the cognitive functions of the animals treated with cannabis were just as good as the two-month-old control animals. “The treatment completely reversed the loss of performance in the old animals,” reported Prof. 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 of all, the scientists discovered that the brain ages much faster when mice 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 marihuana, which accumulate at the receptor. THC imitates the effect of cannabinoids produced naturally in the body, which fulfil important functions in the brain. “With increasing age, the quantity of the cannabinoids naturally formed in the brain reduces,” says Prof. Zimmer. “When the activity of the cannabinoid system declines, we find rapid ageing in the brain.”
To discover precisely what effect the THC treatment has in old mice, the researchers examined the brain tissue and gene activity of the treated mice. The findings were surprising: the molecular signature no longer corresponded to that of old animals, but was instead very similar to that of young animals. 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 mice. Cannabis products are already permitted as medications, for instance as pain relief. As a next step, the researchers want to conduct a clinical trial to investigate whether THC also reverses ageing processes in the brain in humans and can increase cognitive ability.
The North Rhine-Westphalia science minister Svenja Schulze appeared thrilled by the study: “The promotion of knowledge-led research is indispensable, as it is the breeding ground for all matters relating to application. Although there is a long path from mice to humans, I feel extremely positive about the prospect that THC could be used to treat dementia, for instance.”
Source: Andreas Zimmer – University of Bonn
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice” by Andras Bilkei-Gorzo, Onder Albayram, Astrid Draffehn, Kerstin Michel, Anastasia Piyanova, Hannah Oppenheimer, Mona Dvir-Ginzberg, Ildiko Rácz, Thomas Ulas, Sophie Imbeault, Itai Bab, Joachim L Schultze & Andreas Zimmer in Nature Medicine. Published online May 8 2017 doi:10.1038/nm.4311
A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice
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 lower6. 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.
“A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice” by Andras Bilkei-Gorzo, Onder Albayram, Astrid Draffehn, Kerstin Michel, Anastasia Piyanova, Hannah Oppenheimer, Mona Dvir-Ginzberg, Ildiko Rácz, Thomas Ulas, Sophie Imbeault, Itai Bab, Joachim L Schultze & Andreas Zimmer in Nature Medicine. Published online May 8 2017 doi:10.1038/nm.4311