The use of serotonergic psychedelics has gained increasing attention in research, clinical practice and society. Growing evidence suggests fast-acting, transdiagnostic health benefits of these 5-hydroxytryptamine 2A receptor agonists. Here, we provide a brief overview of their benefits for psychological, cardiovascular, metabolic, neurodegenerative, and immunological pathologies. We then review their effect on mitochondria including mitochondrial biogenesis, functioning and transport. Mitochondrial dysregulation is a transdiagnostic mechanism that contributes to the aforementioned pathologies. Hence, we postulate that psychedelic-induced effects on mitochondria partially underlie their transdiagnostic benefits. Based on this assumption, we propose new treatment indications for psychedelics and that the health benefits induced by psychedelics depend on patient-specific mitochondrial dysregulation.
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http://dx.doi.org/10.1177/02698811231164707 | DOI Listing |
Nervenarzt
January 2025
Abteilung für Molekulares Neuroimaging, Zentralinstitut für Seelische Gesundheit, Medizinische Fakultät Mannheim, Universität Heidelberg, 68159, Mannheim, Deutschland.
Background: Novel antidepressive substances are challenging the explanations for the mechanisms of action of traditional psychopharmacology.
Objective: What could be the shared effects of various antidepressants and in this context what role do extrapharmacological factors, such as the body and environment, play?
Material And Method: The available literature on clinical and preclinical data for assumed combined active factors of serotonergic psychedelic drugs, (es)ketamine, monoaminergic antidepressants and zuranolone are presented and the influence of context factors on the individual mechanisms of action is discussed.
Results: There are many indications that classical and novel pharmacological approaches could share similar mechanisms of action in the treatment of depression.
Curr Pain Headache Rep
January 2025
Northwell Health Department of Neurology, New York, NY, USA.
Purpose Of Review: Exploration of the potential of serotonergic psychedelic drugs, such as psilocybin and LSD, as potential treatments for headache disorders. This review addresses the need for well-informed physician guidelines and discusses mechanisms, safety, and efficacy of these treatments. Further research, including the consideration of combination with psychotherapy, is needed.
View Article and Find Full Text PDFACS Med Chem Lett
January 2025
Smith, Gambrell & Russell LLP, 1105 W. Peachtree Street NE, Suite 1000, Atlanta, Georgia 30309, United States.
Provided herein are novel 3-pyrrolidineindole derivatives as serotonergic psychedelic agents, pharmaceutical compositions, use of such compounds in treating psychosis and mental illnesses such as depression and post-traumatic stress disorder, and processes for preparing such compounds.
View Article and Find Full Text PDFCurr Pain Headache Rep
January 2025
Advanced Wellness and Pain, Scottsdale, AZ, USA.
Purpose Of Review: Chronic pain affects approximately 1.5 billion people worldwide, representing the leading cause of disability and a significant financial burden on healthcare systems. Conventional treatments, such as opioids and non-steroidal anti-inflammatory drugs, are frequently linked to adverse effects, including dependency and gastrointestinal issues, and often offer limited long-term relief.
View Article and Find Full Text PDFAm J Psychiatry
January 2025
Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands.
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 psychedelics such as 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and N,N-dimethyltryptamine (DMT) with the expectation that these can produce rapid antidepressant effects following an intense but brief psychedelic intervention. The current paper reviews the clinical pharmacology of 5-MeO-DMT and DMT and their potential benefits and challenges in the treatment of depression.
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