May 27, 2024

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Unexpected mechanism of hallucinogenic drugs to reduce depression discovered

Unexpected mechanism of hallucinogenic drugs to reduce depression discovered



 

Unexpected mechanism of hallucinogenic drugs to reduce depression discovered. 

When it comes to mushrooms , I 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.

 

Previous clinical trials have shown that hallucinogenic substances such as psilocybin and lysergic acid diethylamide (LSD) can effectively treat depression, but the mechanism behind this therapeutic effect is not fully understood.

 

On June 5, 2023, researchers from the University of Helsinki in Finland published a research paper titled: Psychedelics promote plasticity by directly binding to BDNF receptor TrkB in Nature Neuroscience, a sub-journal of Nature .

 

This study shows that the psychedelic drug LSD and psilocin (psilocin, a metabolite of psilocybin) directly bind to a specific receptor TrKB with an affinity 1000 times stronger than other antidepressant drugs and can induce antidepressant effects.

 

This study identified a new mechanism for the specific antidepressant-like effect of psychedelic drugs, and this mechanism is independent of the mechanism related to its hallucinogenic effect, confirming that TrKB is a common main target of antidepressants, providing a basis for the development of new drugs. A drug that treats depression in humans without hallucinogenic effects opens the way.

 

Unexpected mechanism of hallucinogenic drugs to reduce depression discovered

 

 

Hallucinogenic drugs have the potential to alleviate depression, but their hallucinogenic effects limit their clinical application. The hallucinogenic effects and depression-relieving effects of hallucinogenic drugs are considered to be activated by serotonin receptors in the brain . of.

 

On February 16, 2023 , the team of Professor David E. Olson from the University of California, Davis published a research paper entitled: Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors in the journal Science [2] .

 

This Science paper 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 the neuron Serotonin 2A receptor (5-HT2AR) contacts can promote the growth of new connections between neurons.

 

Unexpected mechanism of hallucinogenic drugs to reduce depression discovered

 

In this latest study, the research team found that in neurons in a dish, lysergic acid diethylamide (LSD) and dephosphorylated psilocin (psilocin) interact with the receptor TrkB (neurotrophic receptor tyrosine Acid kinase) binds strongly.

 

Unexpected mechanism of hallucinogenic drugs to reduce depression discovered

Hallucinogenic drugs bind to TrkB

 

The research team had previously found that typical antidepressant drugs also bind and activate TrkB, but to a much lesser extent. Binding of TrKB potentiated the effect of a protein called brain-derived neurotrophic factor (BDNF) on the receptor; this led to increased connections between neurons, implying neuroplasticity.

 

In a mouse model of chronic stress, a single dose of LSD produced sustained antidepressant-like effects. These behavioral effects depend on the binding of LSD to TrkB and are independent of serotonin receptors.

 LSD has also been associated with a head-twitch response, which is thought to be indicative of hallucinogenic effects, but this response relies on activation of serotonin receptors, not TrkB.

 

Unexpected mechanism of hallucinogenic drugs to reduce depression discovered

Hallucinogenic drug-induced neuroplasticity depends on activation of TrkB and BDNF, but not 5-HT2A


These findings suggest that hallucinogenic drugs bind to TrkB much more strongly than general antidepressants, and that their antidepressant-like behavior depends on TrkB binding and enhancement of endogenous BDNF signaling rather than 5-HT2A activation .

This implies that hallucinogenic drugs can induce antidepressant effects independent of their hallucinogenic effects, suggesting that high-affinity TrkB-positive allosteric modulators lacking 5-HT2A activity may retain the antidepressant potential of hallucinogenic drugs without producing hallucinogenic effects effect.

 

 

 

 

 

Paper link :

https://www.nature.com/articles/s41593-023-01316-5

Unexpected mechanism of hallucinogenic drugs to reduce depression discovered

(source:internet, reference only)


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