Biochemical Mechanisms Underlying Psychedelic-Induced Neuroplasticity

Biochemistry, Journal Year: 2022, Volume and Issue: 61(3), P. 127 - 136

Published: Jan. 21, 2022

In addition to producing profound subjective effects following acute administration, psychedelic compounds can induce beneficial behavioral changes relevant the treatment of neuropsychiatric disorders that last long after have been cleared from body. One hypothesis with potential explain remarkable enduring psychedelics is related their abilities promote structural and functional neuroplasticity in prefrontal cortex (PFC). A hallmark many stress-related diseases, including depression, post-traumatic stress disorder (PTSD), addiction, atrophy neurons PFC. Psychedelics appear be particularly effective catalysts for growth these key neurons, ultimately leading restoration synaptic connectivity this critical brain region. Furthermore, evidence suggests hallucinogenic are not directly linked ability neuroplasticity. If we develop improved alternatives treating must fully characterize molecular mechanisms give rise psychedelic-induced Here, I review our current understanding biochemical signaling pathways activated by neuroplasticity-promoting molecules, an emphasis on unanswered questions.

Language: Английский

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5-HT2ARs Mediate Therapeutic Behavioral Effects of Psychedelic Tryptamines

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: 14(3), P. 351 - 358

Published: Jan. 11, 2023

Psychedelic compounds have displayed antidepressant potential in both humans and rodents. Despite their promise, psychedelics can induce undesired effects that pose safety concerns limit clinical scalability. The rational development of optimized psychedelic-related medicines will require a full mechanistic understanding how these molecules produce therapeutic effects. While the hallucinogenic properties are generally attributed to activation serotonin 2A receptors (5-HT2ARs), it is currently unclear if also mediate as several nonhallucinogenic analogues with antidepressant-like been developed. Moreover, many exhibit promiscuous pharmacology, making challenging identify primary target(s). Here, we use combination pharmacological genetic tools demonstrate 5-HT2A essential for tryptamine-based Our results suggest psychedelic tryptamines through same receptor.

Language: Английский

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Psychedelic-Induced Neural Plasticity: A Comprehensive Review and a Discussion of Clinical Implications

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(2), P. 117 - 117

Published: Jan. 25, 2025

Background: Psychedelics are increasingly recognized as a promising and innovative treatment strategy for several mental disorders. However, there is still lively controversy in the medical community regards rationale of their employment, specifically indications potential dangers. Methods: A comprehensive literature search on “MEDLINE/PubMed” “Web Science” was performed from inception to 26 June 2024, cross-checking obtained references. We included all studies, i.e., both clinical preclinical, that supplied original data. Results: initially total 1083 entries, 813 MEDLINE/PubMed 270 Web Science. After duplicate elimination, 903 underwent systematic selection. Primary abstract screening yielded 572 candidates eligibility assessment excluded 331 entries formal grounds. Eligibility led exclusion 501 titles. Finally, 70 articles were this review. Discussion: Preclinical evidence genetic expression, histology behavioral studies soundly consistent with psychedelics possessing neuroplasticity-inducing properties. Despite methodological difficulties, seems be inferentially agreement preclinical findings. it unclear whether “neuroplastic boost” induced by classic might dissociable psychodysleptic effects, thereby reducing psychopathological hazards implied these compounds. Moreover, fact so-called “relaxation priors” should unconditionally beneficial appears debatable, further research clarify possible contraindications psychedelic psychoplastogens within precision medicine perspective.

Language: Английский

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Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression

American Journal of Psychiatry, Journal Year: 2025, Volume and Issue: 182(1), P. 33 - 46

Published: Jan. 1, 2025

Unlike classical antidepressants, psychedelics such as psilocybin have been shown to induce a rapid antidepressant response. In the wake of this development, interest has emerged in ultra-fast, short-acting 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and N,N-dimethyltryptamine (DMT) with expectation that these can produce effects following an intense but brief psychedelic intervention. The current paper reviews clinical pharmacology 5-MeO-DMT DMT their potential benefits challenges treatment depression. Both compounds display affinities for variety monoamine receptors transporters, mostly so serotonergic (5HT) receptors, including 5HT

Language: Английский

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Convergent Mechanisms Underlying Rapid Antidepressant Action

CNS Drugs, Journal Year: 2018, Volume and Issue: 32(3), P. 197 - 227

Published: March 1, 2018

Language: Английский

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P2X7 Receptor Signaling in Stress and Depression

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(11), P. 2778 - 2778

Published: June 6, 2019

Stress exposure is considered to be the main environmental cause associated with development of depression. Due limitations currently available antidepressants, a search for new pharmacological targets treatment depression required. Recent studies suggest that adenosine triphosphate (ATP)-mediated signaling through P2X7 receptor (P2X7R) might play prominent role in regulating depression-related pathology, such as synaptic plasticity, neuronal degeneration, well changes cognitive and behavioral functions. P2X7R an ATP-gated cation channel localized different cell types central nervous system (CNS), playing crucial neuron-glia signaling. may modulate release several neurotransmitters, including monoamines, nitric oxide (NO) glutamate. Moreover, stimulation microglia modulates innate immune response by activating NLR family pyrin domain containing 3 (NLRP3) inflammasome, consistent neuroimmune hypothesis MDD. Importantly, blockade leads antidepressant-like effects animal models, which corroborates findings gene encoding located susceptibility locus relevance humans. This review will discuss recent linked involvement stress MDD neuropathophysiology, special emphasis on neurochemical, neuroimmune, neuroplastic mechanisms.

Language: Английский

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Transient Stimulation with Psychoplastogens Is Sufficient to Initiate Neuronal Growth

ACS Pharmacology & Translational Science, Journal Year: 2020, Volume and Issue: 4(2), P. 452 - 460

Published: Sept. 11, 2020

Cortical neuron atrophy is a hallmark of depression and includes neurite retraction, dendritic spine loss, decreased synaptic density. Psychoplastogens, small molecules capable rapidly promoting cortical growth, have been hypothesized to produce long-lasting positive effects on behavior by rectifying these deleterious structural functional changes. Here we demonstrate that ketamine LSD, psychoplastogens from two structurally distinct chemical classes, promote sustained growth neurons after only short periods stimulation. Furthermore, show psychoplastogen-induced can be divided into epochs: an initial stimulation phase requiring TrkB activation period involving mTOR AMPA receptor activation. Our results provide important temporal details concerning the molecular mechanisms which next-generation antidepressants persistent changes in structure, they suggest excreted might still effective neurotherapeutics with unique advantages over compounds like LSD.

Language: Английский

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The Neurobiological Effects of Electroconvulsive Therapy Studied Through Magnetic Resonance: What Have We Learned, and Where Do We Go?

Biological Psychiatry, Journal Year: 2021, Volume and Issue: 91(6), P. 540 - 549

Published: May 31, 2021

Language: Английский

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Neurotrophic Factors in Parkinson’s Disease: Clinical Trials, Open Challenges and Nanoparticle-Mediated Delivery to the Brain

Frontiers in Cellular Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: June 2, 2021

Neurotrophic factors (NTFs) are small secreted proteins that support the development, maturation and survival of neurons. NTFs injected into brain rescue regenerate certain neuronal populations lost in neurodegenerative diseases, demonstrating potential to cure diseases rather than simply alleviating symptoms. (as vast majority molecules) do not pass through blood–brain barrier (BBB) therefore, delivered directly patients using costly risky intracranial surgery. The delivery efficacy poor diffusion some inside considered major problems behind their modest effects clinical trials. Thus, there is a great need for be systemically thereby avoiding Nanoparticles (NPs), particles with size dimensions 1-100 nm, can used stabilize facilitate transport BBB. Several studies have shown loaded or attached onto NPs, administered transported brain. To improve NP-mediated NTF BBB, surface NPs functionalized specific ligands such as transferrin, insulin, lactoferrin, apolipoproteins, antibodies short peptides will recognized internalized by respective receptors on endothelial cells. In this review, we elaborate most suitable methods envision “ideal” Parkinson’s disease (PD) trial thereof. We shortly summarize trials four NTFs, glial cell line-derived neurotrophic factor (GDNF), neurturin (NRTN), platelet-derived growth (PDGF-BB), cerebral dopamine (CDNF), were tested PD patients, focusing mainly GDNF CDNF. current possibilities discuss whether impact improving properties across Emerging approaches future directions NTF-based nanomedicine also discussed.

Language: Английский

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Neuromodulation of Hippocampal-Prefrontal Cortical Synaptic Plasticity and Functional Connectivity: Implications for Neuropsychiatric Disorders

Frontiers in Cellular Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Oct. 11, 2021

The hippocampus-prefrontal cortex (HPC-PFC) pathway plays a fundamental role in executive and emotional functions. Neurophysiological studies have begun to unveil the dynamics of HPC-PFC interaction both immediate demands long-term adaptations. Disruptions functional connectivity can contribute neuropsychiatric symptoms observed mental illnesses neurological conditions, such as schizophrenia, depression, anxiety disorders, Alzheimer’s disease. Given dysfunctional physiology, it is crucial understand mechanisms that modulate communication. Two main regulate interactions are synaptic plasticity modulatory neurotransmission. Synaptic be investigated inducing potentiation or while spontaneous inferred by statistical dependencies between local field potentials regions. In turn, several neurotransmitters, acetylcholine, dopamine, serotonin, noradrenaline, endocannabinoids, fine-tuning connectivity. Despite experimental evidence, effects neuromodulation on neuronal from cellular behavioral levels not fully understood. current literature lacks review focuses neurotransmitter with activity. Here we reviewed showing systems long- short-term plasticity. We also looked for neuromodulatory oscillatory coordination. Finally, implications disruption cognition disorders. comprehensive overview these impairments could help better communication generate insights into etiology physiopathology clinical conditions.

Language: Английский

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