More than serotonin: how psychedelics involve the entire brain

Summary: Classic psychedelics such as LSD, psilocybin and mescaline are known for activating the serotonin receptor 5-HT2A, but a new study reveals that its effects go much further. The researchers outlined 41 psychedelics against more than 300 human receptors and found a powerful activity in serotonin, dopamine and adrenergic sites.

The study also showed that psychedelics activate multiple intracellular pathways, which can help separate their therapeutic and hallucinogenic effects. These findings highlight the complexity of psychedelic pharmacology and doors open to more specific therapies.

Key facts:

Psychodelic activate almost all serotonin, dopamine and adrenergic receiver. LLSD, psilocybin and mester stimulate multiple signaling routes of the 5-HT2A receptor.

Source: Neuroscience News

In recent years, classic psychedelics such as LSD, Psilocybin and Mescalina have returned notable, not only in popular culture, but in a serious scientific research.

Once relegated to the frogs of the pharmacology due to their association with counterculture movements, these compounds are now rigorously studied by their therapeutic potential in the treatment of mental health disorders such as depression, anxiety, post -traumatic stress disorder (PTSP) and substance use disorders.

Despite its promising clinical effects, the molecular mechanisms that underlie their action in the brain have been understood incompletely.

A new study has taken an important step towards decoding these mechanisms, offering the most integral aspect until the time of how psychedelics interact with the human brain at the level of the receiver. The researchers investigated the pharmacological profiles of 41 classic psychedelic, tripamines, fenestilamines and lisergamides) against a wide panel of human receptors.

Their findings reveal a fascinating and complex image: these compounds are far from “unique objective” medications and, on the other hand, interact with dozens of neural receptors and roads that can contribute to their deep effects on perception, mood and cognition.

Beyond the 5-HT2A receiver

For decades, it is known that psychedelics exert their distinctive effects when activating a particular serotonin receptor, known as the 5-HT2A receiver (5-HT2AR). It is believed that this receiver, widely distributed through the cortex, underlies the perceptual and cognitive distortions characteristics of a psychedelic trip. In fact, the 5-HT2AR block prevents many of these effects, confirming its central role.

However, current research emphasizes that the story does not end there. The team outlined these psychedelics against a 318 receptors (GPCR) (GPCR) unprecedented, a large family of receptors involved in the transmission of neurotransmitters and hormones signals.

In addition, the LSD was tested more against more than 450 human kinases, enzymes that regulate several cellular processes.

The results were surprising: psychedelics exhibited a powerful and effective activity not only in almost all serotonin receptors subtypes, but also in a wide range of dopamine and adrenergic receptors.

This suggests that the subjective experience of psychedelics, and their possible therapeutic benefits can arise from the interaction of multiple receptor systems. For example, activity in dopamine receptors could help explain the effects of elevation and motivation of mood sometimes informed, while adrenergic receptors can influence excitement and attention.

Psychedelic signaling mapping

One of the most intriguing findings in the study was that psychedelics do not simply change the “activated” or “off” receptors, but that they involve them in unique ways.

Using advanced techniques to measure how these medications activated different intracellular signaling, researchers showed that psychedelics stimulate multiple transducers down 5-HT2AR. These include means mediated by G proteins, as well as β-arrestins, proteins that regulate the desensitization of the receiver and the diversity of signaling.

In addition, the degree to which a psychedelic activated these different pathways correlated with its power and behavior effects on animal models.

This points to the possibility that the therapeutic and hallucinogenic properties of psychedelics can be separable when addressing specific subsequent paths, an exciting perspective to develop psychedelic “not such as such as” that retain their antidepressant or anxiolytic effects without altering perception.

Why so many goals?

The fact that psychedelics act on so many different receptors raised an important question: why? One possibility is that this wide activity contributes to its unique therapeutic potential.

Mental health conditions such as depression and PTSD imply the deregulation of multiple neurotransmitter systems (serotonin, dopamine, norepinephrine), so a medication that can modulate them all simultaneously can be more effective than one that only goes to a single system.

Another intriguing idea is that the intricate interactions of the receiver contribute to the subjective experience of the “dissolution of the ego” and the improved emotional processing reported by many psychedelic users.

It is believed that these experiences facilitate psychological healing by allowing people to face traumatic memories or entrenched thought patterns from a new perspective.

Towards precision psychedelic medicine

The results of this research also underline the need for a more nuanced understanding of how individual psychedelics differ. Although the LSD, psilocybin and mescaline activate 5-HT2AR, its broader receptor profiles vary considerably, which can explain its different durations, intensities and therapeutic applications.

The LSD, for example, is remarkably more durable and is more powerful than psilocybin, which can derive from its strong union to certain dopaminergic and adrenergic receptors in addition to 5-HT2AR.

When mapping these pharmacological fingerprints, researchers can begin to adapt specific compounds to specific conditions, or even engineers of psychedelic new ones that maximize therapeutic benefits while minimizing side effects.

This is aligned with the growing efforts to develop next -generation psychedelics that are more specific, better tolerated and easier to administer in clinical environments.

The way ahead

This historical study provides a convincing reminder of how complex are brain signaling networks and how much we have to learn about how psychedelics interact with them. It also reinforces the idea that these compounds are not simply tools to alter consciousness, but also powerful probes to explore the fundamental biology of the mind.

As clinical trials of psychedelics for depression, PTSD and addiction continue to expand, understand their molecular mechanisms will be key to unlock its maximum potential.

When drawing the various ways through which they act, researchers are laying the foundations for a new era of precision psychedelic medicine, one that promises to transform how we treat some of the most challenging mental health conditions of our time.

For now, one thing is clear: psychedelics are more than only serotonin agonists. They are intricate molecular key, unlock a symphony of neuronal receptors and ways that together orchestrate the deep changes in mood, thought and perception that we are only beginning to understand.

On this research news of psychopharmacology and neuroscience

Author: Neuroscience News Communications
Source: Neuroscience News
Contact: Neuroscience News Communications – Neuroscience News
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Original research: closed access.
“The polypharmacology of psychedelics reveals multiple objectives for the potential therapy” by Manish K. Jain et al. Neuron

Abstract

Psychodelic polypharmacology reveals multiple objectives for potential therapy

Classic psychedelics (+): Lyergic acid diethylamide (LSD), psilocybin and mescaline exert their psychedelic effects by activating the 5-HT2A serotonin receptor (5-HT2AR).

Recent clinical studies have suggested that classic psychedelics can have a therapeutic potential for many neuropsychiatric conditions, including depression, anxiety, migraine and headaches of the groups, drug abuse and post -traumatic stress disorder.

In this study, we investigate the pharmacology of 41 classic psychedelics of the chemical classes of Tripamine, Fenetilamine and Lisergamide.

We profile these compounds against 318 receivers coupled to Guman Guman proteins (GPCR) to elucidate their objective profiles, and in the case of LSD, against more than 450 human kinases.

We discover that psychedelics have powerful and effective actions in almost all serotonin, dopamine and adrenergic receiver.

We quantify its activation for multiple transducers and discover that psychedelics stimulate multiple 5-HT2AR transducers, each of which correlates with psychedelic actions similar to drugs in vivo.

Our results suggest that multiple molecular objectives probably contribute to psychedelic actions.