A complex systems perspective on psychedelic brain action

Trends in Cognitive Sciences, Journal Year: 2023, Volume and Issue: 27(5), P. 433 - 445

Published: Feb. 3, 2023

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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Uncovering Psychedelics: From Neural Circuits to Therapeutic Applications

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(1), P. 130 - 130

Published: Jan. 19, 2025

Psychedelics, historically celebrated for their cultural and spiritual significance, have emerged as potential breakthrough therapeutic agents due to profound effects on consciousness, emotional processing, mood, neural plasticity. This review explores the mechanisms underlying psychedelics’ effects, focusing ability modulate brain connectivity circuit activity, including default mode network (DMN), cortico-striatal thalamo-cortical (CSTC) loops, relaxed beliefs under psychedelics (REBUS) model. Advanced neuroimaging techniques reveal capacity enhance functional between sensory cerebral areas while reducing connections associative areas, decreasing rigidity rendering more plastic susceptible external changings, offering insights into outcome. The most relevant clinical trials of 3,4-methylenedioxymethamphetamine (MDMA), psilocybin, lysergic acid diethylamide (LSD) demonstrate significant efficacy in treating treatment-resistant psychiatric conditions such post-traumatic stress disorder (PTSD), depression, anxiety, with favorable safety profiles. Despite these advancements, critical gaps remain linking molecular actions efficacy. highlights need further research integrate mechanistic optimize tools both therapy understanding human cognition.

Language: Английский

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In vivo mapping of pharmacologically induced functional reorganization onto the human brain’s neurotransmitter landscape

Science Advances, Journal Year: 2023, Volume and Issue: 9(24)

Published: June 14, 2023

To understand how pharmacological interventions can exert their powerful effects on brain function, we need to they engage the brain's rich neurotransmitter landscape. Here, bridge microscale molecular chemoarchitecture and pharmacologically induced macroscale functional reorganization, by relating regional distribution of 19 receptors transporters obtained from positron emission tomography, changes in magnetic resonance imaging connectivity 10 different mind-altering drugs: propofol, sevoflurane, ketamine, lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), ayahuasca, 3,4-methylenedioxymethamphetamine (MDMA), modafinil, methylphenidate. Our results reveal a many-to-many mapping between psychoactive drugs' function multiple systems. The both anesthetics psychedelics are organized along hierarchical gradients structure function. Last, show that co-susceptibility recapitulates disorder-induced structural alterations. Collectively, these highlight statistical patterns drug-induced reorganization architecture.

Language: Английский

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A synergistic workspace for human consciousness revealed by Integrated Information Decomposition

eLife, Journal Year: 2023, Volume and Issue: 12

Published: July 25, 2023

How is the information-processing architecture of human brain organised, and how does its organisation support consciousness? Here, we combine network science a rigorous information-theoretic notion synergy to delineate ‘synergistic global workspace’, comprising gateway regions that gather synergistic information from specialised modules across brain. This then integrated within workspace widely distributed via broadcaster regions. Through functional MRI analysis, show correspond brain’s default mode network, whereas broadcasters coincide with executive control network. We find loss consciousness due general anaesthesia or disorders corresponds diminished ability integrate information, which restored upon recovery. Thus, coincides breakdown integration work contributes conceptual empirical reconciliation between two prominent scientific theories consciousness, Global Neuronal Workspace Integrated Information Theory, while also advancing our understanding supports through information.

Language: Английский

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Serotonin 2A Receptor (5-HT_2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants

Chemical Reviews, Journal Year: 2023, Volume and Issue: 124(1), P. 124 - 163

Published: Nov. 30, 2023

Psychedelics make up a group of psychoactive compounds that induce hallucinogenic effects by activating the serotonin 2A receptor (5-HT2AR). Clinical trials have demonstrated traditional psychedelic substances like psilocybin as class rapid-acting and long-lasting antidepressants. However, there is pressing need for rationally designed 5-HT2AR agonists possess optimal pharmacological profiles in order to fully reveal therapeutic potential these identify safer drug candidates devoid effects. This Perspective provides an overview structure–activity relationships existing based on their chemical classifications discusses recent advancements understanding molecular pharmacology at structural level. The encouraging clinical outcomes psychedelics depression treatment sparked discovery endeavors aimed developing novel with improved subtype selectivity signaling bias properties, which could serve potentially nonhallucinogenic These efforts can be significantly expedited through utilization structure-based methods functional selectivity-directed screening.

Language: Английский

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Psychedelics for acquired brain injury: a review of molecular mechanisms and therapeutic potential

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(3), P. 671 - 685

Published: Jan. 4, 2024

Language: Английский

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Neural complexity is increased after low doses of LSD, but not moderate to high doses of oral THC or methamphetamine

Neuropsychopharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 29, 2024

Language: Английский

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Exploring mechanisms of psychedelic action using neuroimaging

Nature Mental Health, Journal Year: 2024, Volume and Issue: 2(2), P. 141 - 153

Published: Feb. 9, 2024

Language: Английский

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Unique Psychological Mechanisms Underlying Psilocybin Therapy Versus Escitalopram Treatment in the Treatment of Major Depressive Disorder

International Journal of Mental Health and Addiction, Journal Year: 2024, Volume and Issue: 22(2), P. 806 - 841

Published: March 7, 2024

Abstract The mechanisms by which Psilocybin Therapy (PT) improves depression remain an important object of study, with scientists actively exploring acute psychological experiences and neurobiological processes as candidates. In a phase 2, double-blind, randomized, active comparator controlled trial involving patients moderate-to-severe major depressive disorder, we investigated whether could meaningfully account for the unique efficacy PT versus Escitalopram Treatment over core 6-week period. An exploratory-factor-analysis-derived single-factor was used outcome. Among comprehensive set related to psilocybin, so-called “mystical experience” “ego dissolution” were in mediating effect treatment condition on response high specificity. Higher reported levels mystical experience, emotional breakthrough, intense responses music-listening furthermore associated greater antidepressant response. These results provide qualified support causal mechanistic role via PT.

Language: Английский

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