February 26, 2024

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Why can “poisonous mushrooms” cure depression?

Why can “poisonous mushrooms” cure depression?


Science: Why can “poisonous mushrooms” cure depression? New study reveals key mechanism of hallucinogen antidepressant.

When it comes to mushrooms , we believe most people will immediately think of delicious food. But not all mushrooms are non-toxic and edible.

There are not a few people who are admitted to hospital every year due to eating poisonous wild mushrooms. Not only that, some mushrooms also contain hallucinogenic toxins , which make people have colorful and dreamlike hallucinations .

Audiovisual hallucinations are neurotoxins with neuropsychiatric effects.


Several previous clinical trials have shown that psilocybin can effectively treat depression, but the mechanism behind this therapeutic effect is not fully understood.


On February 16, 2023 , the team of Professor David E. Olson of the University of California, Davis , published an article entitled: Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors ( psilocybin through the Activation of intracellular 5-HT2A receptors to promote neuroplasticity) .


This study shows that psilocybin may treat mental diseases by rapidly rebuilding the connection between neurons, and the location of the receptor is the key to the therapeutic effect of psilocybin, which is related to 5 neurons .

Exposure to the serotonin 2A receptor (5-HT2AR) promotes the growth of new connections between neurons, but exposure to the same receptor on the neuron’s surface does not.


The discovery could help guide the development of new drugs to treat depression , post-traumatic stress disorder (PTSD) and other mental illnesses.


Why can "poisonous mushrooms" cure depression?



Hallucinogens such as lysergic acid diethylamine (LSD) , MDMA, and psilocybin show potential promise for treating a wide range of psychiatric disorders characterized by loss of neural connections.

Decreased density of cortical dendritic spines is a hallmark of several neuropsychiatric disorders, and the ability to promote cortical neuronal growth is thought to underlie the rapid onset and sustained efficacy of these hallucinogenic drugs in the treatment of depression.


For example, in April 2022, researchers from Imperial College London published a research paper entitled: Increased global integration in the brain after psilocybin therapy for depression in the top international medical journal Nature Medcine .


The study shows that psilocybin can induce treatment response in patients with treatment-resistant depression by increasing functional network connectivity in the brain.

This mechanism was not observed with the traditional antidepressant escitalopram .

This finding advances our understanding of the pathways behind treatment-resistant depression and the mechanism by which psilocybin treats depression.


Why can "poisonous mushrooms" cure depression?



In the study, published in Science , the team found that just one dose of these hallucinogens caused neurons to rapidly grow new dendrites and form new spines on those dendrites.

David E. Olson called these compounds psychoplastogens because of their ability to regenerate and remodel neural connections in the brain.

And this quick action appears to be different from drugs like selective serotonin reuptake inhibitors (SSRIs) , which take longer to work.


Earlier studies by David E. Olson and others showed that hallucinogens work by engaging serotonin 2A receptors (5-HT2AR) , which have the same receptors as serotonin (5-HT, also called element ) , but did not play the role of the former in promoting neuronal connections.


The research team believes that the reason why it is different from hallucinogens is related to the physical and chemical properties of 5-hydroxytryptamine itself. plasma membrane.

Hallucinogens, on the other hand, are much less polar and can easily pass through cell membranes and enter the interior of cells.


Therefore, the research team reasoned that location bias might explain the differences in neuronal signaling induced by serotonin and hallucinogenic drugs.

The research team further found that the ability of these hallucinogens to promote neuronal connections is related to their ability to cross cell membranes .


Drug receptors are generally thought to be located on the surface of the cell membrane and face outward, but this study showed that in nerve cells, serotonin 2A receptors (5-HT2AR) are concentrated inside the cell, mainly around the Golgi apparatus, with only some located in The cell surface, while other receptors of the same type are localized on the surface of the cell membrane .


These findings suggest that there is a location bias in the mode of action of these drugs , with intracellular activation of the serotonin 2A receptor (5-HT2AR) producing different effects than extracellular activation.

This research provides a better understanding of how to promote neuroplasticity, which could help us design better drugs .


Activation of serotonin (5-hydroxytryptamine) 2A receptors (5-HT2ARs) is critical for hallucinogen-induced cortical plasticity, but it is unclear why some 5-HT2AR agonists promote neuroplasticity while others do not. No.


Overall, this study demonstrates that intracellular serotonin 2A receptors (5-HT2AR) mediate neuronal plasticity in the hallucinogen psilocybin, which explains why serotonin (serotonin ) have no such plasticity effect.

This study highlights the role of location bias in 5-HT2AR signaling, identifies intracellular 5-HT2AR as a therapeutic target for depression and other psychiatric diseases, and raises an interesting possibility— Serotonin (serotonin) may not be an endogenous ligand for the intracellular 5-HT2AR in the cortex .



Professor David E. Olson , the corresponding author of the paper , founded a company called Delix Therapeutics in 2019 to develop hallucinogen-based neuroplasticity drugs for the treatment of psychiatric disorders, including treatment-resistant depression, substance use disorders, Post-traumatic stress disorder, schizophrenia, neurodegenerative diseases, etc.

The company has currently completed more than US$100 million in financing, and it is expected that two R&D pipelines will enter clinical trials this year.


Why can "poisonous mushrooms" cure depression?






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Why can “poisonous mushrooms” cure depression?

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