Psychedelic substances could help stop Alzheimer’s, say two Mexicans

For decades, science has tried to combat Alzheimer’s by attacking proteins that accumulate in the brain: beta-amyloid plaques and tau tangles. But the drugs developed to eliminate them “have been disappointing”: they have not managed to stop the disease. Now, two Mexican scientists propose changing the approach completely.

Doctors of science Fernando Minauro Sanmiguel, from the Mexican Social Security Institute (IMSS), and Héctor Vargas Pérez, from the Nierika Institute of Intercultural Medicine, have just announced the results of their most recent joint research.

They do it in the article Hallucinogenic Therapy in Alzheimer’s Disease targeting Mitochondria Associated Membranes (Hallucinogenic therapy in Alzheimer’s directed at mitochondria-associated membranes), published in the most recent printed version of the magazine Neuroscienceone of the most prestigious in the field of neurosciences worldwide.

In that article, the researchers propose a “mechanistic model”: using psychedelic compounds not for their perceptual effects, but to repair the functioning of mitochondria, the structures that generate energy within cells.

Their proposal has been well received by the international scientific community, but they themselves clarify that it is still a hypothesis based on laboratory experiments.

Mitochondria, “little batteries”

“We are not saying that we already have a treatment,” they explain in an interview with The Day . “What we propose is a hypothesis based on preclinical evidence. At no time do we propose that patients take drugs.”

They emphasize that, to understand their idea, you must first know mitochondria, those tiny structures that are inside cells and function like “small batteries.” In the case of the brain, they specify, they generate the energy that neurons need to think, remember and stay alive.

“For years,” they state, “it was thought that mitochondria only served to provide energy. Today it is known that they also regulate calcium, control cellular stress and decide whether a neuron lives or dies.”

In Alzheimer’s, they reveal, these “batteries” begin to fail long before the first symptoms appear. According to the “Mitochondrial Cascade Hypothesis” – which they take up and develop in their article –, this failure is “the true trigger of the disease.”

The plaques and tangles would come later, as a consequence, not as the main cause, they detail. “Alzheimer’s disease increasingly resembles a metabolic disorder of the brain,” they add. “Mitochondria fail years before the first symptoms. If we could intervene at that moment, perhaps we would change the history of the disease.”

The study reviews experiments in cells and animals that suggest some psychedelic compounds could repair damaged mitochondria. “Not because of their hallucinogenic effects, but because they activate repair mechanisms within the cell,” the authors specify.

Minauro and Vargas identified two main pathways. The first is through serotonin, finding that compounds such as psilocybin (the active substance in certain mushrooms), LSD (lysergic acid diethylamide) or mescaline (contained in peyote) activate receptors called 5 HT2A. By doing so, they say, they reduce inflammation in the brain, help neurons create new connections, and stimulate the production of new mitochondria.

The other route is through the Sigma 1 receptor. “Other molecules, such as DMT (dimethyltryptamine) and 5 MeO DMT, bind to a protein called Sigma 1 receptor,” they explain, adding that this is the key between the mitochondria and another cellular structure known as the endoplasmic reticulum.

Scientists call this contact zone “membranes associated with mitochondria,” which is what the title of the article mentions. There, the Sigma 1 receptor helps calcium flow correctly, improves energy production (ATP) and decreases cellular wear and tear.

“In Alzheimer’s, this communication is broken,” the researchers detail. “In preclinical models, compounds such as DMT bind to the Sigma 1 receptor and restore the dialogue between the two structures. They improve energy production, reduce oxidative stress and neurons become more resistant.”

The authors insist that this whole situation has been seen in the laboratory, not in people. “There is no clinical study that shows that a psychedelic modifies the progression of Alzheimer’s in people,” they emphasize. “That is why we reiterate: we do not propose that patients take drugs. The distance between a biological mechanism and a safe treatment is enormous.”

Vargas and Minauro are very clear about the risks. Many people with Alzheimer’s also suffer from depression, anxiety, agitation or even psychosis. In these cases, a dose that alters perception could cause confusion, distress or worsen behavior, they warn.

“It is not about giving mushrooms to patients at home or taking them to ayahuasca ceremonies, which are so popular today,” they emphasize. “Any clinical approach would have to be extremely careful.”

Given this, they propose that the path towards possible treatments should include the development of microdoses or non-hallucinogenic compounds that act on the Sigma 1 receptor without altering consciousness, a strict selection of patients that avoids those with active psychosis, and the “use of biomarkers”, that is, analyzes that allow measuring whether the mitochondria are really improving.

According to the authors, that this work has been published in the printed version of Neuroscience –a journal of the International Brain Research Organization (IBRO), which brings together neuroscience societies from more than 80 countries– is of great relevance to the national scientific community.

Change paradigms

“It is a recognition that the science done in Mexico can provide disruptive ideas,” they consider. “We not only follow imported lines; we also generate original hypotheses with the potential to change paradigms.”

According to Mexican researchers, Alzheimer’s is a complex disease, and combined strategies are likely to be needed. “But if we manage to demonstrate that restoring mitochondrial function slows down cognitive deterioration, we will have taken a turn as important as the one represented at the time by the amyloid hypothesis (which attempts to explain the cause of this condition). The difference is that now we have much more precise tools to do so,” they conclude.