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

Allen, Josh; Dames, Shannon S.; Foldi, Claire J.; Shultz, Sandy R.

doi:10.1038/s41380-023-02360-0

Cited by 6 publications

(1 citation statement)

References 275 publications

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“…The indications range across an entire spectrum of MDD/TRD, PTSD, GAD, bipolar disorders, pain, substance use and eating disorders, late-stage cancer-related anxiety and depression, autism spectrum disorders and the list keeps increasing. There are multiple generally small scale clinical trials in healthy volunteers or in various indications with psychedelics either as mostly psychological support-assisted monotherapies (Kaelen et al, 2015;Carhart-Harris et al, 2015;2018;Erritzoe et al, 2018;Stroud et al, 2018;Agin-Liebes et al, 2020;Hutten et al, 2020;Mertens et al, 2020;Pokorny et al, 2020;Madsen et al, 2020;Uthaug et al, 2020;Davis et al, 2020;Preller et al, 2020;Spriggs et al, 2020;Verrous et al, 2021;Kaertner et al, 2021;Douglass et al, 2022;Bosch et al, 2022;Duerler et al, 2020;Holze et al, 2021;Family et al, 2020;Müller et al, 2022;Sondergaard et al, 2022;Rucker et al, 2022;Jensen et al, 2022;Burmester et al, 2023;Allen et al, 2024;Eckernas et al, 2023;Good et al, 2023;Ledwos et al, 2023;Mason et al, 2023;Vogt et al, 2023;von Rotz et al, 2023) or as combinations with other psychedelics/entactogens (de Win et al, 2006;Carhart-Harris et al, 2014;Vizeli et al, 2022;Borissova et al, 2024;Heresco-Levy and Lerer, 2023;…”

Section: Discussionmentioning

confidence: 99%

On serotonin, psychedelics, entactogens and psychoplastogens in depression, anxiety, post-traumatic stress, and related disorders.

Hoyer

2024

Preprint

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There is controversy about a causal role of serotonin (5-HT) in depression, some arguing that there is no proof for impaired brain 5-HT function in depressed patients. Major depressive disorder comes with multiple endophenotypes; not surprisingly classical antidepressants (tricyclics, MAO inhibitors, SSRIs, SNRIs) are not universally effective. Most antidepressants target the 5-HT system, partially if not exclusively, but treatment-resistant depression (TRD) remains a major issue. The most recent and heavily investigated class of potential rapid acting antidepressant, anxiolytic, and/or anti PTSD drugs, namely psychedelics (psilocybin, LSD, DMT, ayahuasca, etc..) or entactogens (MDMA, ibogaine), all target the 5-HT system, at least in part. Phase II / III clinical trials support psychedelics- and/or MDMA-assisted psychotherapy as a new class of rapid acting treatments for GAD, MDD, TRD, PTSD, and other disorders. Psilocybin and MDMA have FDA breakthrough status for TRD/MDD and PTSD, respectively, whereas LSD just received FDA breakthrough status for GAD. All psychedelics act as 5-HT2A receptor agonists, although LSD, DMT, psilocybin may also target other 5-HT and/or dopamine receptors. Psychedelics produce rapid onset and long-lasting antidepressant effects after one or two administrations. They all promote synaptogenesis and synaptic plasticity. Neuroinflammation plays a major role in anxiety, depression, PTSD. Interestingly, psychedelic-induced 5-HT2A receptor agonism has profound anti-(neuro)inflammatory effects. Altogether, the 5-HT system plays an essential, but not unique role in MDD and related disorders. MDD, TRD and PTSD may be considered as biochemical, neurological and immune conditions, given the emerging role of neuroplasticity and neuroinflammation, which until recently, have been overlooked.

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Section: Discussionmentioning

confidence: 99%

On serotonin, psychedelics, entactogens and psychoplastogens in depression, anxiety, post-traumatic stress, and related disorders.

Hoyer

2024

Preprint

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Psychedelic 25H-NBOMe attenuates post-sepsis depression in rats

Ferri,

de Novais,

Rojas

et al. 2024

Neuroscience Letters

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The New Frontier in Neurotherapeutics: From Brain Stimulation to Novel Psychotropics

Kargbo

2024

ACS Med. Chem. Lett.

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This Highlight explores significant advancements in neuropharmacology and neurotechnology, emphasizing their transformative impact on treating psychological and neurological disorders. This publication covers recent patents that introduce novel tryptamine derivatives, entactogenic mindstate inducers, and psychoplastogens aimed at promoting neuronal growth. It discusses advanced brain monitoring and stimulation systems integrated with AI to optimize treatment protocols. These innovations represent substantial progress in crafting unique therapeutic approaches and diagnostic tools, heralding a new era of personalized and effective treatment strategies for complex mental health and neurological conditions. ImportantCompound Classes. Titles. Therapeutic Combinations, Compositions, and Methods for Designing and Producing Entactogenic Mindstates; Benzofuran and Benzothiophene Psychoplastogens and Uses Thereof; Tryptamine Derivatives and Their Therapeutic Uses; and Brain Monitoring and Stimulation Devices and Methods Patent Publication Numbers. WO 2023/172701 A2

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

Cited by 6 publications

References 275 publications

On serotonin, psychedelics, entactogens and psychoplastogens in depression, anxiety, post-traumatic stress, and related disorders.

On serotonin, psychedelics, entactogens and psychoplastogens in depression, anxiety, post-traumatic stress, and related disorders.

Psychedelic 25H-NBOMe attenuates post-sepsis depression in rats

The New Frontier in Neurotherapeutics: From Brain Stimulation to Novel Psychotropics

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