Studi preclinici/Farmacologia

In questa sezione sono raccolti gli articoli che esplorano il funzionamento delle sostanze psichedeliche a livello molecolare, cellulare e sistemico, prima dell’applicazione clinica.
Dalla farmacodinamica alla neuroplasticità, dalla modulazione dei circuiti cerebrali agli effetti immunitari, questi approfondimenti si concentrano su ciò che accade “sotto la superficie” dell’esperienza.
Spesso si tratta di studi complessi e poco intuitivi, condotti su modelli animali o in vitro, ma rappresentano una tappa fondamentale per comprendere meglio i meccanismi d’azione, orientare la ricerca clinica e porre le basi di un uso terapeutico più consapevole.

Studi preclinici

Psychedelics promote plasticity by directly binding to BDNF receptor TrkB.
Moliner, Rafael et al. “Psychedelics promote plasticity by directly binding to BDNF receptor TrkB.” Nature neuroscience vol. 26,6 (2023): 1032-1041. doi:10.1038/s41593-023-01316-5

N,N-dimethyltryptamine reduces infarct size and improves functional recovery following transient focal brain ischemia in rats.
Nardai, Sándor et al. “N,N-dimethyltryptamine reduces infarct size and improves functional recovery following transient focal brain ischemia in rats.” Experimental neurology vol. 327 (2020): 113245. doi:10.1016/j.expneurol.2020.113245

Effect of chemically synthesized psilocybin and psychedelic mushroom extract on molecular and metabolic profiles in mouse brain.
Shahar, O., Botvinnik, A., Shwartz, A. et al. Effect of chemically synthesized psilocybin and psychedelic mushroom extract on molecular and metabolic profiles in mouse brain. Mol Psychiatry 29, 2059–2073 (2024). https://doi.org/10.1038/s41380-024-02477-w

The Impact of Psilocybin on High Glucose/Lipid-Induced Changes in INS-1 Cell Viability and Dedifferentiation.
Gojani EG, Wang B, Li D-P, Kovalchuk O, Kovalchuk I. The Impact of Psilocybin on High Glucose/Lipid-Induced Changes in INS-1 Cell Viability and Dedifferentiation. Genes. 2024; 15(2):183. https://doi.org/10.3390/genes15020183

Low nonpsychedelic doses of psilocybin for the therapy of MASLD.
EASL Congress 2024. Poster M. Colognesi et al.

Mind over matter: the microbial mindscapes of psychedelics and the gut-brain axis.
Giorgia Caspani, Simon G.D. Ruffell, WaiFung Tsang, Nigel Netzband, Cyrus Rohani-Shukla, Jonathan R. Swann, Wilfred A. Jefferies, Mind over matter: the microbial mindscapes of psychedelics and the gut-brain axis, Pharmacological Research, Volume 207, 2024, 107338, ISSN 1043-6618, https://doi.org/10.1016/j.phrs.2024.107338.

Psychedelic LSD activates neurotrophic signal but fails to stimulate neural stem cells.
Dong, X., Lin, H., Li, Y. et al. Psychedelic LSD activates neurotrophic signal but fails to stimulate neural stem cells. Stem Cell Res Ther 15, 285 (2024). https://doi.org/10.1186/s13287-024-03909-8

Isolation of psychedelic-responsive neurons underlying anxiolytic behavioral states.
Muir, J et al. “Isolation of psychedelic-responsive neurons underlying anxiolytic behavioral states.” Science (New York, N.Y.) vol. 386,6723 (2024): 802-810. doi:10.1126/science.adl0666

Psychedelic control of neuroimmune interactions governing fear.
Chung, E.N., Lee, J., Polonio, C.M. et al. Psychedelic control of neuroimmune interactions governing fear. Nature 641, 1276–1286 (2025). https://doi.org/10.1038/s41586-025-08880-9

5-Methoxy-2-aminoindane Reverses Diet-Induced Obesity and Improves Metabolic Parameters in Mice: A Potential New Class of Antiobesity Therapeutics.
Baraghithy, Saja et al. “5-Methoxy-2-aminoindane Reverses Diet-Induced Obesity and Improves Metabolic Parameters in Mice: A Potential New Class of Antiobesity Therapeutics.” ACS pharmacology & translational science vol. 7,8 2527-2543. 30 Jul. 2024, doi:10.1021/acsptsci.4c00353

Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA.
Warner-Schmidt, Jennifer et al. “Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA.” Frontiers in neuroscience vol. 18 1353131. 7 Feb. 2024, doi:10.3389/fnins.2024.1353131

Farmacologia

Psychological and physiological effects of extended DMT.
Luan, Lisa X et al. “Psychological and physiological effects of extended DMT.” Journal of psychopharmacology (Oxford, England) vol. 38,1 (2024): 56-67. doi:10.1177/02698811231196877

Overcoming the clinical challenges of traditional ayahuasca: a first-in-human trial exploring novel routes of administration of N,N-Dimethyltryptamine and harmine.
Dornbierer, Dario A et al. “Overcoming the clinical challenges of traditional ayahuasca: a first-in-human trial exploring novel routes of administration of N,N-Dimethyltryptamine and harmine.” Frontiers in pharmacology vol. 14 1246892. 27 Nov. 2023, doi:10.3389/fphar.2023.1246892

Drug–drug interactions involving classic psychedelics: A systematic review.
Halman A, Kong G, Sarris J, Perkins D. Drug–drug interactions involving classic psychedelics: A systematic review. Journal of Psychopharmacology. 2023;38(1):3-18. doi:10.1177/02698811231211219

Acute dose-dependent effects of mescaline in a double-blind placebo-controlled study in healthy subjects.
Klaiber, A., Schmid, Y., Becker, A.M. et al. Acute dose-dependent effects of mescaline in a double-blind placebo-controlled study in healthy subjects. Transl Psychiatry 14, 395 (2024). https://doi.org/10.1038/s41398-024-03116-2

Acute dose-dependent effects and self-guided titration of continuous N,N-dimethyltryptamine infusions in a double-blind placebo-controlled study in healthy participants.
Erne, L., Vogt, S.B., Müller, L. et al. Acute dose-dependent effects and self-guided titration of continuous N,N-dimethyltryptamine infusions in a double-blind placebo-controlled study in healthy participants. Neuropsychopharmacol. 50, 1008–1016 (2025). https://doi.org/10.1038/s41386-024-02041-8

Acute effects of R-MDMA, S-MDMA, and racemic MDMA in a randomized double-blind cross-over trial in healthy participants.
Straumann, I., Avedisian, I., Klaiber, A. et al. Acute effects of R-MDMA, S-MDMA, and racemic MDMA in a randomized double-blind cross-over trial in healthy participants. Neuropsychopharmacol. 50, 362–371 (2025). https://doi.org/10.1038/s41386-024-01972-6

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