Summary: A study from the University of Bonn reports that prolonged low-dose THC treatment restored memory and reversed molecular signs of brain ageing in mice, suggesting potential avenues for treating dementia and other neurodegenerative conditions.
Source: University of Bonn
University of Bonn researchers restore memory performance of elderly mice to a youthful state
As we age, brain function and cognitive performance naturally decline. A team of researchers at the University of Bonn, in collaboration with colleagues from The Hebrew University of Jerusalem, has shown that a prolonged, low-dose treatment with Δ9-tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, can reverse age-related cognitive decline in mice. The study, published in Nature Medicine, found that older mice treated with THC displayed learning and memory abilities similar to those of young adult mice.
Like other organs, the brain undergoes structural and functional changes with age, which often manifest as slower learning, reduced attention, and weaker memory. While this decline is a normal part of ageing, it can contribute to the development of dementia and other neurodegenerative diseases. Scientists have therefore been investigating interventions that might slow or reverse age-related brain decline.
In the study, researchers treated mice at different life stages—two months, twelve months and eighteen months old—with a small daily dose of THC for four weeks. After treatment, the animals underwent behavioural testing to assess learning, spatial orientation and social memory, including their ability to recognize other mice. Mice that received a placebo showed the expected age-dependent cognitive decline, while THC-treated older animals performed comparably to the two-month-old control group. “The treatment completely reversed the loss of performance in the old animals,” said Prof. Andreas Zimmer from the Institute of Molecular Psychiatry at the University of Bonn.
Years of careful research
This result builds on years of systematic investigation into how the endocannabinoid system influences brain ageing. The researchers previously demonstrated that mice lacking functional cannabinoid receptor type 1 (CB1)—the receptor through which THC and natural endocannabinoids act—exhibit accelerated brain ageing. CB1 receptors are proteins on neurons that mediate the effects of cannabinoids. Besides being responsible for THC’s intoxicating effects, the endocannabinoid system plays important roles in maintaining brain function. Prof. Zimmer explains that levels of endocannabinoids produced by the body decline with age, and that reduced cannabinoid signalling appears to accelerate ageing-related changes in the brain.
To understand how THC produced these effects, the team analysed brain tissue and gene expression patterns from treated and untreated animals. They found that gene expression profiles in the hippocampus—a brain region critical for learning and memory—shifted from an “old” pattern toward a “young” one after THC treatment. In addition, markers of synaptic connectivity and the density of dendritic spines, which facilitate communication between neurons, increased in treated animals. These molecular and structural changes provide a plausible biological basis for the restored cognitive performance: the THC treatment appeared to reverse several ageing-related molecular signatures and supported the re-establishment of neuronal connections.
Path toward human trials
The dose of THC used in these experiments was intentionally low, chosen to avoid intoxication in the mice while engaging cannabinoid signalling. THC and other cannabis-derived products are already approved in some settings for medical use, for example to relieve pain or chemotherapy-related symptoms. Building on the promising preclinical data, the researchers plan to initiate clinical trials to determine whether low-dose THC can also counteract age-associated cognitive decline in humans and potentially improve quality of life for those with dementia or milder cognitive impairments.
Svenja Schulze, the science minister of North Rhine-Westphalia, commented positively on the findings, noting that fundamental, knowledge-driven research is essential to developing future applications. Although translating results from mice to humans requires careful, controlled studies, the authors and observers see the study as an encouraging step toward novel therapeutic strategies for age-related cognitive disorders.
Source: Andreas Zimmer, University of Bonn
Original research: Bilkei-Gorzo A., Albayram O., Draffehn A., Michel K., Piyanova A., Oppenheimer H., Dvir-Ginzberg M., Rácz I., Ulas T., Imbeault S., Bab I., Schultze J. L., & Zimmer A. “A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice.” 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
Ageing reflects the balance between harmful, pro-ageing processes and protective, homeostatic mechanisms. The endocannabinoid system (ECS) is implicated in these protective processes: its activity declines with age, including reduced CB1 receptor expression and lower levels of the endocannabinoid 2-arachidonoylglycerol (2-AG). This study reports that a chronic, low dose of THC reversed age-related cognitive decline in mice aged 12 and 18 months. THC treatment was associated with increased expression of synaptic marker proteins and higher hippocampal spine density. Gene transcription patterns in the hippocampus of THC-treated older mice resembled those of young adults, and the beneficial effects depended on glutamatergic CB1 receptor signalling and histone acetylation. These findings suggest that restoring CB1 signalling in older individuals may be a viable strategy to treat age-related cognitive impairments.
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