Cannabis Can Reverse Brain Aging

A new study has found that the low-dose, long-term use of a key component in full-spectrum cannabis oils can reverse aging processes in the brain and has anti-aging effects. The University Hospital of Bonn, in collaboration with Israel’s Hebrew University, examined the effects of THC on aging mice. THC (tetrahydrocannabinol) is one of the main active compounds in the cannabis plant, known for its psychoactive effects, meaning it can cause euphoria and alter consciousness. It is also used medically, for example, for pain relief and appetite stimulation. Full-spectrum cannabis oils and extracts in most EU countries contain THC in amounts below 0.2%, which is not enough to induce psychoactive effects under proper usage, but their therapeutic value can still be significant.

The results published in ACS Pharmacology & Translation Science suggest that THC can rejuvenate cognitive functions in older mice by influencing key molecular pathways in the brain.

Cognitive functions are the fundamental mental abilities of the human brain that enable thinking, problem-solving, decision-making, and adapting to the environment. These functions encompass numerous mental processes that help us process, understand, and apply information. The main cognitive functions include:

1. Attention

2. Memory

3. Language skills

4. Executive functions

Executive functions are higher-level mental processes that enable goal-directed behavior, planning, and decision-making. These include problem-solving, impulse control, self-regulation, flexibility, as well as the ability to process and integrate new information.

5. Perception

Perception is the process by which our sensory organs convert stimuli into understandable information in the brain. This includes sight, hearing, touch, and other senses, through which we recognize objects, sounds, colors, and more in our environment.

6. Spatial orientation

8. Learning

Why are cognitive functions important?

Maintaining and improving cognitive functions is essential for quality of life, as these abilities determine independent living, learning, workplace performance, and social relationships. A healthy lifestyle and regular mental challenges, such as reading, puzzles, or studying, can help preserve brain freshness and improve cognitive functions.

Aging is often accompanied by a decline in cognitive abilities, caused by the deterioration of brain cells and the quality of connections between them. Previous studies have already suggested that the endocannabinoid system—a complex network of receptors and signaling molecules found in the brain and other organs—plays a critical role in this process. This new research clarifies the significance of THC, specifically its impact on the brain’s abundant CB1 receptor. It has been shown that loss of CB1 receptor activity in mice leads to significant age-related learning and memory impairments.

With this in mind, the researchers investigated whether enhancing CB1 activity with low-dose THC could have the opposite effect, potentially reversing certain aspects of brain aging. They were particularly interested in how THC might affect mTOR, a protein that serves as a central regulator of cell growth, metabolism, and aging. mTOR has been linked to both cognitive performance and the aging process, making it a crucial target for interventions aimed at extending healthy lifespan.

For the study, the researchers used groups of young (four-month-old) and old (18-month-old) male mice. The mice were randomly assigned to receive either low-dose THC or a placebo solution without active ingredients for 28 days. THC was administered via mini-pumps, allowing the researchers to control the dosage and ensure continuous delivery.

The study focused on several key areas: brain function, levels of specific proteins involved in signaling between brain cells, and the overall health of the mice. Throughout the experiment, the researchers monitored the mice's body weight, food intake, and activity levels. They also conducted detailed biochemical analyses of the mice's brains, blood plasma, and fat tissue to assess how THC influenced mTOR signaling and the metabolome.

(The metabolome refers to the complete collection of small-molecule substances present in cells, tissues, or organisms, including metabolites—products of metabolism—such as sugars, amino acids, fatty acids, and other compounds. These molecules reflect the current state of an organism’s metabolism and provide information about the physiological processes, environmental influences, and disease-related changes in the cell or organism.)

In the brains of older mice, THC treatment led to a temporary but significant increase in mTOR activity, especially in the hippocampus—a region critical for learning and memory. This rise in mTOR activity was accompanied by elevated levels of key synaptic proteins, such as synaptophysin and PSD-95, which are essential for the formation and maintenance of synapses—the connections between neurons.

Moreover, the researchers observed that THC treatment significantly enhanced hippocampal activity. This was evidenced by increased levels of metabolites involved in energy production pathways, including those related to glycolysis and the citric acid cycle, which provide the energy cells need for their functions. Interestingly, these changes were strongest after 14 days of treatment and normalized by day 28.

István Bilkei-Gorzó

“We have now demonstrated that THC treatment has a tissue-dependent and dual effect on mTOR signaling and the metabolome,” explained András Bilkei-Gorzo, a researcher at the Molecular Psychiatry Institute at the University of Bonn. “We concluded that long-term THC treatment initially enhances cognitive function by increasing brain energy and synaptic protein production, followed by an anti-aging effect characterized by mTOR activity modulating peripheral metabolic processes. Our study suggests that this dual impact on mTOR activity and the metabolome could form the basis of an effective anti-aging and cognitive-enhancing drug.”

While the results are promising, the study has limitations. The research was conducted on mice, which are frequently used as models for human biology, but differences between species must be considered. It remains unclear whether the same effects can be observed in humans, and further research is needed to understand the potential therapeutic applications of THC.
Future studies should focus on determining the optimal treatment protocols to maximize the anti-aging benefits while minimizing potential risks.

Source:
The study titled “Bidirectional Effect of Long-Term Δ9-Tetrahydrocannabinol Treatment on mTOR Activity and Metabolome” was authored by András Bilkei-Gorzo, Britta Schurmann, Marion Schneider, Michael Kraemer, Prakash Nidadavolu, Eva C. Beins, Christa E. Müller, Mona Dvir-Ginzberg, and Andreas Zimmer. The original study can be found here: https://pubs.acs.org/doi/10.1021/acsptsci.4c00002

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