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Article
Biochemistry & Molecular Biology
David E. Olson
Summary: In addition to their profound subjective effects, psychedelic compounds can induce long-lasting beneficial behavioral changes relevant to the treatment of neuropsychiatric disorders. This may be due to their ability to promote neuroplasticity in the prefrontal cortex, leading to synaptic connectivity restoration. Understanding the molecular mechanisms behind psychedelic-induced neuroplasticity is crucial for developing improved alternatives for treating these disorders.
Article
Multidisciplinary Sciences
Dongmei Cao et al.
Summary: This study provides structural insights into the binding of drugs to 5-HT2AR and offers a foundation for the design of safe and effective nonhallucinogenic psychedelic analogs for the treatment of neuropsychiatric diseases.
Review
Pharmacology & Pharmacy
Austen B. Casey et al.
Summary: This review discusses the importance of blockade and activation of the serotonin 5-HT2A G protein-coupled receptor (5-HT2AR) in the treatment of psychiatric disorders, and the limitations and strengths of currently available selective 5-HT2AR antagonists.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Neurosciences
Blazej D. Pedzich et al.
Summary: Psychedelic-assisted psychotherapy has gained attention as a novel treatment strategy for fear-related mental disorders. This study investigated the effect of activating the serotonin 2A (5-HT2A) receptor, a key target for psychedelics, on emotional processing. The findings suggest that activation of 5-HT2A receptors in the amygdala suppresses fear expression and reduces anxiety-like behavior, providing insights into the underlying mechanisms of psychedelic-assisted therapy.
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Neurosciences
Yasmim A. Serra et al.
Summary: The study found that ayahuasca treatment can block the expression of alcohol self-administration in mice, and the activation of 5-HT2A receptors is critical for these effects. This suggests the potential of ayahuasca and other 5-HT2A receptor agonists as adjunctive pharmacotherapies for the treatment of AUD.
PSYCHOPHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Anat Levit Kaplan et al.
Summary: Researchers successfully screened and synthesized molecules that can activate the 5-HT2A receptor using structure-based docking and optimization methods. These molecules exhibited potent antidepressant activity in mouse models without psychedelic effects.
Review
Neurosciences
Alex C. Kwan et al.
Summary: This review focuses on the basic neurobiology of the action of psychedelic drugs. It covers the chemistry and potency of psychoactive molecules, the role of serotonin receptors and their signaling pathways, the impact on neuronal spiking dynamics, transcriptional changes, and structural plasticity. This review also summarizes neuroimaging results that highlight the effects on association cortices and thalamocortical functional connectivity, providing insights into the neural mechanisms responsible for the acute and enduring effects of psychedelics on behavior.
NATURE NEUROSCIENCE
(2022)
Article
Medicine, General & Internal
Guy M. Goodwin et al.
Summary: Psilocybin may be effective in treating treatment-resistant depression, but dosage and adverse effects need further investigation.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Neurosciences
Friederike Holze et al.
Summary: This study evaluated the subjective and autonomic effects of different doses of LSD in healthy subjects. It found that LSD displayed dose-proportional pharmacokinetics and dose-dependently induced subjective responses, with a ceiling effect observed for good drug effects at 100 μg. The results suggest that future LSD research may benefit from dose finding based on these findings, and that the full psychedelic effects of LSD are primarily mediated by serotonin 5-HT2A receptor activation.
NEUROPSYCHOPHARMACOLOGY
(2021)
Review
Clinical Neurology
Bashkim Kadriu et al.
Summary: Ketamine and serotonergic psychedelics may share a common mechanism in generating rapid neuroplastic effects and affecting cortical network activity that lead to antidepressant efficacy. Despite some similarities, the connection between the psychoactive component and antidepressant efficacy of these drugs remains unclear and requires further research. The prototypic nature of ketamine research and recent progress in this area suggest a promising platform for investigating new classes of rapid-acting antidepressants.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Lindsay P. Cameron et al.
Summary: The study identifies key structural elements of the potential therapeutic pharmacophore of ibogaine and designs tabernanthalog, a safer, non-hallucinogenic analogue of ibogaine. Tabernanthalog is found to promote neural plasticity, reduce addiction-related behavior, and produce antidepressant effects in rodents. Through careful chemical design, it is possible to modify psychedelic compounds to produce safer, non-hallucinogenic variants with therapeutic potential.
Review
Pharmacology & Pharmacy
Antonio Inserra et al.
Summary: Psychedelic compounds are emerging as potential novel therapeutics in psychiatry, with their main effects mediated through the modulation of neurotransmitter systems, immunity, and neuroplasticity. Promising results suggest an opportunity for improvement in the treatment of psychiatric disorders, an area that has seen limited advancement in the past 20 years. Studies are underway to separate the psychedelic effects from the therapeutic effects of these compounds, aiming to provide more effective treatment options.
PHARMACOLOGICAL REVIEWS
(2021)
Article
Multidisciplinary Sciences
Danilo De Gregorio et al.
Summary: Clinical studies have shown that LSD can enhance empathy and social behavior in humans. This study in male mice found that LSD promotes social behavior by potentiating glutamatergic neurotransmission in the medial prefrontal cortex through the 5-HT2A/AMPA receptors and mTOR signaling. The results suggest that activating these pathways with psychedelic drugs could be explored for treating mental disorders characterized by social behavior impairments.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Neurosciences
Neil K. Savalia et al.
Summary: Studies have shown that serotonergic psychedelics like psilocybin and ketamine may relieve depression by promoting neural plasticity. Despite targeting distinct molecular receptors in the brain, the behavioral and neural effects of these compounds are similar, possibly by enhancing and suppressing membrane excitability at dendrites.
TRENDS IN NEUROSCIENCES
(2021)
Article
Cell Biology
Mario de la Fuente Revenga et al.
Summary: Clinical evidence shows that rapid and sustained antidepressant effects can be achieved with a single exposure to psychedelics. The study found that a single dose of the psychedelic DOI has fast-acting effects on the frontal cortex dendritic spine structure and accelerates fear extinction through the 5-HT2A receptor. Furthermore, DOI induces changes in chromatin organization, particularly at enhancer regions of genes involved in synaptic assembly, which overlap with genetic loci associated with schizophrenia, depression, and attention deficit hyperactivity disorder.
Review
Neurosciences
Eero Castren et al.
Summary: Neurotrophic factors, especially BDNF, are associated with depression and the action of antidepressant drugs, with impaired BDNF signaling linked to mood disorders. Increased BDNF expression and signaling have been linked to the mechanisms of antidepressant drugs, and BDNF regulates various types of neuronal plasticities in the brain, which are connected to antidepressant action. The hypothesis of a connection between neurotrophic factors and neuronal plasticity with mood disorders and antidepressant action has been further supported by recent evidence.
BIOLOGICAL PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Chunyang Dong et al.
Summary: The study introduces psychLight, a genetically encoded fluorescent sensor based on the structure of 5-HT2AR, which can detect behaviorally relevant serotonin release and predict the effects of different 5-HT2AR ligands. This new technology identified a non-hallucinogenic psychedelic analog with rapid-onset and long-lasting antidepressant-like effects.
Article
Neurosciences
Lynette A. Desouza et al.
Summary: The hallucinogenic 5-HT2A receptor agonist DOI rapidly upregulates neuronal plasticity-associated genes in the rat neocortex through activation of the CREB transcription factor. This upregulation was confirmed in both in vitro and in vivo studies, and has significant implications for psychoplastic changes.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Review
Psychiatry
Maxemiliano V. Vargas et al.
Summary: Psychedelics offer new hope for treating brain disorders due to their sustained therapeutic effects and broad potential, but face challenges in clinical scalability. Research on psychoplastogens provides insight into neural plasticity and offers a new paradigm for addressing the underlying pathophysiology of mental illness. Effectively deploying psychoplastogenic medicines at scale will be a key consideration for future development in the field.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Medicine, General & Internal
Robin Carhart-Harris et al.
Summary: The study compared the efficacy of psilocybin and escitalopram in treating patients with major depressive disorder. While there was no significant difference in antidepressant effects between the two drugs at week 6, secondary outcomes generally favored psilocybin over escitalopram, though these results were not adjusted for multiple comparisons. Larger and longer trials are needed to further compare psilocybin with established antidepressants.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Multidisciplinary Sciences
Natalie Hesselgrave et al.
Summary: Psilocybin has shown promising rapid and persistent antidepressant effects in mice, possibly through enhancing excitatory synapses in the hippocampus, independent of 5-HT2A receptor activation. Further research is needed to explore the potential combination of psychedelic compounds and 5-HT2AR antagonists for clinical utility in human depression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Psychiatry
Alan K. Davis et al.
Summary: The study showed that psilocybin therapy with psychological support is effective in treating MDD, building on previous findings in patients with cancer and depression, as well as in a nonrandomized study in patients with treatment-resistant depression.
Article
Neurosciences
Ling-Xiao Shao et al.
Summary: The study showed that psilocybin can induce rapid and lasting synaptic rewiring in the cortex, increasing spine size and density. This structural change may have potential implications for long-term integration of experiences and lasting beneficial actions.
Review
Pharmacology & Pharmacy
Lily R. Aleksandrova et al.
Summary: The emerging therapeutic efficacy of ketamine and classical psychedelics for depression has sparked considerable interest in the mechanisms underlying neuroplasticity. Preclinical and clinical evidence suggests that these drugs induce synaptic, structural, and functional changes, particularly in pyramidal neurons in the prefrontal cortex, resulting in adaptive rewiring of pathological neurocircuitry.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2021)
Article
Chemistry, Medicinal
Calvin Ly et al.
Summary: Cortical neuron atrophy is a hallmark of depression, and psychoplastogens like ketamine and LSD have been shown to promote sustained growth of cortical neurons after short periods of stimulation. These psychoplastogens induce cortical neuron growth through distinct phases, with early TrkB activation and later sustained mTOR and AMPA receptor activation being crucial. It is suggested that rapidly excreted psychoplastogens may have unique advantages as neurotherapeutics compared to compounds like ketamine and LSD.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2021)
Article
Chemistry, Medicinal
David E. Olson
Summary: Psychedelics have shown promise for treating neuropsychiatric disorders due to their ability to promote neural plasticity and produce rapid and sustained therapeutic effects, but evidence suggests that the subjective effects induced by these drugs may not be necessary for long-lasting changes in mood and behavior. Understanding the role of subjective effects in the therapeutic mechanisms of psychedelics will have important implications for basic neuroscience and patient access to future medicines developed from psychedelic research.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2021)
Article
Chemistry, Medicinal
David B. Yaden et al.
Summary: The subjective effects of psychedelics are crucial for their lasting benefits, accounting for the majority of their therapeutic outcomes.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Meghan Hibicke et al.
ACS CHEMICAL NEUROSCIENCE
(2020)
Article
Chemistry, Medicinal
Lee E. Dunlap et al.
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
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Neurosciences
Adam L. Halberstadt et al.
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Multidisciplinary Sciences
R. N. Moda-Sava et al.
Article
Neurosciences
R. L. Carhart-Harris et al.
PSYCHOPHARMACOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Lindsay P. Cameron et al.
ACS CHEMICAL NEUROSCIENCE
(2018)
Article
Cell Biology
Calvin Ly et al.
Article
Multidisciplinary Sciences
Jonathan T. Ting et al.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2018)
Article
Biology
Katrin H. Preller et al.
Review
Biochemistry & Molecular Biology
E. Castren et al.
MOLECULAR PSYCHIATRY
(2017)
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Victoria Phoumthipphavong et al.
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Amy F. T. Arnsten et al.
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(2015)
Editorial Material
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(2013)
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Adam L. Halberstadt et al.
JOURNAL OF PSYCHOPHARMACOLOGY
(2011)
Review
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Rita Z. Goldstein et al.
NATURE REVIEWS NEUROSCIENCE
(2011)
Review
Biochemistry & Molecular Biology
Hong-Wu Shen et al.
CURRENT DRUG METABOLISM
(2010)
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JOURNAL OF PSYCHOPHARMACOLOGY
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