Effect of chemically synthesized psilocybin and psychedelic mushroom extract on molecular and metabolic profiles in mouse brain.


Journal

Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835

Informations de publication

Date de publication:
20 Feb 2024
Historique:
received: 06 07 2023
accepted: 01 02 2024
revised: 24 01 2024
medline: 21 2 2024
pubmed: 21 2 2024
entrez: 21 2 2024
Statut: aheadofprint

Résumé

Psilocybin, a naturally occurring, tryptamine alkaloid prodrug, is currently being investigated for the treatment of a range of psychiatric disorders. Preclinical reports suggest that the biological effects of psilocybin-containing mushroom extract or "full spectrum" (psychedelic) mushroom extract (PME), may differ from those of chemically synthesized psilocybin (PSIL). We compared the effects of PME to those of PSIL on the head twitch response (HTR), neuroplasticity-related synaptic proteins and frontal cortex metabolomic profiles in male C57Bl/6j mice. HTR measurement showed similar effects of PSIL and PME over 20 min. Brain specimens (frontal cortex, hippocampus, amygdala, striatum) were assayed for the synaptic proteins, GAP43, PSD95, synaptophysin and SV2A, using western blots. These proteins may serve as indicators of synaptic plasticity. Three days after treatment, there was minimal increase in synaptic proteins. After 11 days, PSIL and PME significantly increased GAP43 in the frontal cortex (p = 0.019; p = 0.039 respectively) and hippocampus (p = 0.015; p = 0.027) and synaptophysin in the hippocampus (p = 0.041; p = 0.05) and amygdala (p = 0.035; p = 0.004). PSIL increased SV2A in the amygdala (p = 0.036) and PME did so in the hippocampus (p = 0.014). In the striatum, synaptophysin was increased by PME only (p = 0.023). There were no significant effects of PSIL or PME on PSD95 in any brain area when these were analyzed separately. Nested analysis of variance (ANOVA) showed a significant increase in each of the 4 proteins over all brain areas for PME versus vehicle control, while significant PSIL effects were observed only in the hippocampus and amygdala and were limited to PSD95 and SV2A. Metabolomic analyses of the pre-frontal cortex were performed by untargeted polar metabolomics utilizing capillary electrophoresis - Fourier transform mass spectrometry (CE-FTMS) and showed a differential metabolic separation between PME and vehicle groups. The purines guanosine, hypoxanthine and inosine, associated with oxidative stress and energy production pathways, showed a progressive decline from VEH to PSIL to PME. In conclusion, our synaptic protein findings suggest that PME has a more potent and prolonged effect on synaptic plasticity than PSIL. Our metabolomics data support a gradient of effects from inert vehicle via chemical psilocybin to PME further supporting differential effects. Further studies are needed to confirm and extend these findings and to identify the molecules that may be responsible for the enhanced effects of PME as compared to psilocybin alone.

Identifiants

pubmed: 38378926
doi: 10.1038/s41380-024-02477-w
pii: 10.1038/s41380-024-02477-w
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s).

Références

McClure-Begley TD, Roth BL. The promises and perils of psychedelic pharmacology for psychiatry. Nat Rev Drug Discov. 2022;21:463–73.
pubmed: 35301459 doi: 10.1038/s41573-022-00421-7
Strauss D, Ghosh S, Murray Z, Gryzenhout M. An overview on the taxonomy, phylogenetics and ecology of the psychedelic genera psilocybe, panaeolus, pluteus and gymnopilus. Front For Glob Change. 2022;5:1–9.
Barker SA. N, N-Dimethyltryptamine (DMT), an endogenous hallucinogen: past, present, and future research to determine its role and function. Front Neurosci. 2018;12:536.
pubmed: 30127713 pmcid: 6088236 doi: 10.3389/fnins.2018.00536
Uthaug MV, Lancelotta R, van Oorsouw K, Kuypers KPC, Mason N, Rak J, et al. A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms. Psychopharmacology. 2019;236:2653–66.
pubmed: 30982127 pmcid: 6695371 doi: 10.1007/s00213-019-05236-w
Dinis-Oliveira RJ, Pereira CL, da Silva DD. Pharmacokinetic and pharmacodynamic aspects of peyote and mescaline: clinical and forensic repercussions. Curr Mol Pharm. 2019;12:184–94.
doi: 10.2174/1874467211666181010154139
Schiff PL. Ergot and its alkaloids. Am J Pharm Educ. 2006;70:98.
pubmed: 17149427 pmcid: 1637017 doi: 10.5688/aj700598
Ferber SG, Namdar D, Hen-Shoval D, Eger G, Koltai H, Shoval G, et al. The “Entourage Effect”: terpenes coupled with cannabinoids for the treatment of mood disorders and anxiety disorders. Curr Neuropharmacol. 2020;18:87–96.
pubmed: 31481004 pmcid: 7324885 doi: 10.2174/1570159X17666190903103923
Jikoms N. Do magic mushrooms have ‘strains’ like cannabis? 2022. https://www.leafly.com/news/science-tech/do-magic-mushrooms-have-strains-like-cannabis . Accessed 27 June 2023.
FreshCap Mushrooms. Do All Magic Mushrooms Have The Same Effect? YouTube. 2023. https://www.youtube.com/watch?v=PBEHe5cC9qg . Accessed 27 June 2023.
Gartz J. Analysis of Aeruginascin in fruit bodies of the mushroom inocybe aeruginascens. Int J Crude Drug Res. 1989;27:141–4.
doi: 10.3109/13880208909053954
Matsushima Y, Shirota O, Kikura-Hanajiri R, Goda Y, Eguchi F. Effects of Psilocybe argentipes on marble-burying behavior in mice. Biosci Biotechnol Biochem. 2009;73:1866–8.
pubmed: 19661714 doi: 10.1271/bbb.90095
Zhuk O, Jasicka-Misiak I, Poliwoda A, Kazakova A, Godovan VV, Halama M, et al. Research on acute toxicity and the behavioral effects of methanolic extract from psilocybin mushrooms and psilocin in mice. Toxins. 2015;7:1018–29.
pubmed: 25826052 pmcid: 4417952 doi: 10.3390/toxins7041018
Van Court RC, Wiseman MS, Meyer KW, Ballhorn DJ, Amses KR, Slot JC, et al. Diversity, biology, and history of psilocybin-containing fungi: suggestions for research and technological development. Fungal Biol. 2022;126:308–19.
pubmed: 35314062 doi: 10.1016/j.funbio.2022.01.003
Blei F, Dörner S, Fricke J, Baldeweg F, Trottmann F, Komor A, et al. Simultaneous production of psilocybin and a cocktail of β-carboline monoamine oxidase inhibitors in “Magic” Mushrooms. Chem A Eur J. 2020;26:729–34.
doi: 10.1002/chem.201904363
Leung AY, Paul AG. Baeocystin and norbaeocystin: new analogs of psilocybin from Psilocybe baeocystis. J Pharm Sci. 1968;57:1667–71.
pubmed: 5684732 doi: 10.1002/jps.2600571007
Gotvaldová K, Hájková K, Borovička J, Jurok R, Cihlářová P, Kuchař M. Stability of psilocybin and its four analogs in the biomass of the psychotropic mushroom Psilocybe cubensis. Drug Test Anal. 2021;13:439–46.
pubmed: 33119971 doi: 10.1002/dta.2950
Lenz C, Wick J, Hoffmeister D. Identification of ω-N-Methyl-4-hydroxytryptamine (Norpsilocin) as a Psilocybe natural product. J Nat Prod. 2017;80:2835–8.
pubmed: 28929753 doi: 10.1021/acs.jnatprod.7b00407
Dörner S, Rogge K, Fricke J, Schäfer T, Wurlitzer JM, Gressler M, et al. Genetic survey of psilocybe natural products. ChemBioChem. 2022;23:e202200249.
pubmed: 35583969 pmcid: 9400892 doi: 10.1002/cbic.202200249
Glatfelter GC, Pottie E, Partilla JS, Sherwood AM, Kaylo K, Pham DNK, et al. Structure–activity relationships for psilocybin, baeocystin, aeruginascin, and related analogues to produce pharmacological effects in mice. ACS Pharmacol Transl Sci. 2022;5:1181–96.
pubmed: 36407948 pmcid: 9667540 doi: 10.1021/acsptsci.2c00177
Sherwood AM, Halberstadt AL, Klein AK, McCorvy JD, Kaylo KW, Kargbo RB, et al. Synthesis and biological evaluation of tryptamines found in hallucinogenic mushrooms: norbaeocystin, baeocystin, norpsilocin, and aeruginascin. J Nat Prod. 2020;83:461–7.
pubmed: 32077284 doi: 10.1021/acs.jnatprod.9b01061
Grieco SF, Castrén E, Knudsen GM, Kwan AC, Olson DE, Zuo Y, et al. Psychedelics and neural plasticity: therapeutic implications. J Neurosci. 2022;42:8439–49.
pubmed: 36351821 pmcid: 9665925 doi: 10.1523/JNEUROSCI.1121-22.2022
Calder AE, Hasler G. Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology. 2023;48:104–12.
pubmed: 36123427 doi: 10.1038/s41386-022-01389-z
Ly C, Greb AC, Cameron LP, Wong JM, Barragan EV, Wilson PC, et al. Psychedelics promote structural and functional neural plasticity. Cell Rep. 2018;23:3170–82.
pubmed: 29898390 pmcid: 6082376 doi: 10.1016/j.celrep.2018.05.022
Shao LX, Liao C, Gregg I, Davoudian PA, Savalia NK, Delagarza K, et al. Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo. Neuron. 2021;109:2535–44.
Cao D, Yu J, Wang H, Luo Z, Liu X, He L, et al. Structure-based discovery of nonhallucinogenic psychedelic analogs. Science. 2022;375:403–11.
pubmed: 35084960 doi: 10.1126/science.abl8615
Cameron LP, Tombari RJ, Lu J, Pell AJ, Hurley ZQ, Ehinger Y, et al. A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature. 2021;589:474–9.
pubmed: 33299186 doi: 10.1038/s41586-020-3008-z
Kaplan AL, Confair DN, Kim K, Barros-Álvarez X, Rodriguiz RM, Yang Y, et al. Bespoke library docking for 5-HT(2A) receptor agonists with antidepressant activity. Nature. 2022;610:582–91.
pubmed: 36171289 pmcid: 9996387 doi: 10.1038/s41586-022-05258-z
Shahar O, Botvinnik A, Esh-Zuntz N, Brownstien M, Wolf R, Lotan A, et al. Role of 5-HT2A, 5-HT2C, 5-HT1A and TAAR1 receptors in the head twitch response induced by 5-hydroxytryptophan and psilocybin: translational implications. Int J Mol Sci. 2022;23:14148.
pubmed: 36430623 pmcid: 9698447 doi: 10.3390/ijms232214148
Nazir FH, Becker B, Brinkmalm A, Höglund K, Sandelius Å, Bergström P, et al. Expression and secretion of synaptic proteins during stem cell differentiation to cortical neurons. Neurochem Int. 2018;121:38–49.
pubmed: 30342961 pmcid: 6232556 doi: 10.1016/j.neuint.2018.10.014
Truckenbrodt S, Viplav A, Jähne S, Vogts A, Denker A, Wildhagen H, et al. Newly produced synaptic vesicle proteins are preferentially used in synaptic transmission. EMBO J. 2018;37:e98044.
pubmed: 29950309 pmcid: 6068464 doi: 10.15252/embj.201798044
Courant F, Antignac J-P, Dervilly-Pinel G, Le Bizec B. Basics of mass spectrometry based metabolomics. PROTEOMICS. 2014;14:2369–88.
pubmed: 25168716 doi: 10.1002/pmic.201400255
Mandal PK, Gaur S, Roy RG, Samkaria A, Ingole R, Goel A. Schizophrenia, bipolar and major depressive disorders: overview of clinical features, neurotransmitter alterations, pharmacological interventions, and impact of oxidative stress in the disease process. ACS Chem Neurosci. 2022;13:2784–802.
pubmed: 36125113 doi: 10.1021/acschemneuro.2c00420
Zandonadi FS, Silva AAR, Melo AA, Ignarro RS, Matos TS, Santos EA, et al. Understanding ayahuasca effects in major depressive disorder treatment through in vitro metabolomics and bioinformatics. Anal Bioanal Chem. 2023;415:1–18.
Janhavi P, Divyashree S, Sanjailal K, Muthukumar S. DoseCal: a virtual calculator for dosage conversion between human and different animal species. Arch Physiol Biochem. 2022;128:426–30.
pubmed: 31746232 doi: 10.1080/13813455.2019.1687523
de la Fuente Revenga M, Vohra HZ, González-Maeso J. Automated quantification of head-twitch response in mice via ear tag reporter coupled with biphasic detection. J Neurosci methods. 2020;334:108595.
pubmed: 31954738 pmcid: 7363508 doi: 10.1016/j.jneumeth.2020.108595
Jefsen OH, Elfving B, Wegener G, Müller HK. Transcriptional regulation in the rat prefrontal cortex and hippocampus after a single administration of psilocybin. J Psychopharmacol. 2021;35:483–93.
pubmed: 33143539 doi: 10.1177/0269881120959614
Custodio RJ, Ortiz DM, Lee HJ, Sayson LV, Buctot D, Kim M, et al. 5-HT2CR is as important as 5-HT2AR in inducing hallucinogenic effects in serotonergic compounds. SSRN. 2022;4121838:1–49.
Almeida CAF, Pereira-Junior AA, Rangel JG, Pereira BP, Costa KCM, Bruno V, et al. Ayahuasca, a psychedelic beverage, modulates neuroplasticity induced by ethanol in mice. Behav Brain Res. 2022;416:113546.
pubmed: 34437939 doi: 10.1016/j.bbr.2021.113546
Du Y, Li Y, Zhao X, Yao Y, Wang B, Zhang L, et al. Psilocybin facilitates fear extinction in mice by promoting hippocampal neuroplasticity. Chin Med J. 2023;136:2983–92.
pubmed: 37000971 pmcid: 10752473 doi: 10.1097/CM9.0000000000002647
Sugishita T, Tokunaga M, Kami K, Terai K, Yamamoto H, Shinohara H, et al. Determination of the minimum sample amount for Capillary Electrophoresis-Fourier Transform Mass Spectrometry (CE-FTMS)-based metabolomics of colorectal cancer biopsies. Biomedicines. 2023;11:1706.
pubmed: 37371800 pmcid: 10296550 doi: 10.3390/biomedicines11061706
Ruiz-Perez D, Guan H, Madhivanan P, Mathee K, Narasimhan G. So you think you can PLS-DA? BMC Bioinforma. 2020;21:1–10.
doi: 10.1186/s12859-019-3310-7
Jones KA, Srivastava DP, Allen JA, Strachan RT, Roth BL, Penzes P. Rapid modulation of spine morphology by the 5-HT2A serotonin receptor through kalirin-7 signaling. Proc Natl Acad Sci. 2009;106:19575–80.
pubmed: 19889983 pmcid: 2780750 doi: 10.1073/pnas.0905884106
Slocum ST, DiBerto JF, Roth BL. Molecular insights into psychedelic drug action. J Neurochem. 2022;162:24–38.
pubmed: 34797943 doi: 10.1111/jnc.15540
de la Fuente Revenga M, Zhu B, Guevara CA, Naler LB, Saunders JM, Zhou Z, et al. Prolonged epigenomic and synaptic plasticity alterations following single exposure to a psychedelic in mice. Cell Rep. 2021;37:109836.
pubmed: 34686347 doi: 10.1016/j.celrep.2021.109836
Lukasiewicz K, Baker JJ, Zuo Y, Lu J. Serotonergic psychedelics in neural plasticity. Front Mol Neurosci. 2021;14:748359.
pubmed: 34712118 pmcid: 8545892 doi: 10.3389/fnmol.2021.748359
Lohmann C, Kessels HW. The developmental stages of synaptic plasticity. J Physiol. 2014;592:13–31.
pubmed: 24144877 doi: 10.1113/jphysiol.2012.235119
Console-Bram LM, Fitzpatrick-McElligott SG, McElligott JG. Distribution of GAP-43 mRNA in the immature and adult cerebellum: a role for GAP-43 in cerebellar development and neuroplasticity. Dev Brain Res. 1996;95:97–106.
doi: 10.1016/0165-3806(96)00079-X
Cantallops I, Routtenberg A. Activity‐dependent regulation of axonal growth: Posttranscriptional control of the GAP‐43 gene by the NMDA receptor in developing hippocampus. J Neurobiol. 1999;41:208–20.
pubmed: 10512978 doi: 10.1002/(SICI)1097-4695(19991105)41:2<208::AID-NEU4>3.0.CO;2-V
Snipes G, Chan S, McGuire C, Costello B, Norden J, Freeman J, et al. Evidence for the coidentification of GAP-43, a growth-associated protein, and F1, a plasticity-associated protein. J Neurosci. 1987;7:4066–75.
pubmed: 3694262 pmcid: 6569085 doi: 10.1523/JNEUROSCI.07-12-04066.1987
He Q, Dent EW, Meiri KF. Modulation of actin filament behavior by GAP-43 (neuromodulin) is dependent on the phosphorylation status of serine 41, the protein kinase C site. J Neurosci. 1997;17:3515–24.
pubmed: 9133376 pmcid: 6573702 doi: 10.1523/JNEUROSCI.17-10-03515.1997
Chen X, Levy JM, Hou A, Winters C, Azzam R, Sousa AA, et al. PSD-95 family MAGUKs are essential for anchoring AMPA and NMDA receptor complexes at the postsynaptic density. Proc Natl Acad Sci. 2015;112:E6983–92.
pubmed: 26604311 pmcid: 4687590 doi: 10.1073/pnas.1517045112
Xu T, Bajjalieh SM. SV2 modulates the size of the readily releasable pool of secretory vesicles. Nat cell Biol. 2001;3:691–8.
pubmed: 11483953 doi: 10.1038/35087000
Dore K, Malinow R. Elevated PSD-95 blocks ion-flux independent LTD: a potential new role for PSD-95 in synaptic plasticity. Neuroscience. 2021;456:43–9.
pubmed: 32114099 doi: 10.1016/j.neuroscience.2020.02.020
Coley AA, Gao W-J. PSD95: a synaptic protein implicated in schizophrenia or autism? Prog Neuro-Psychopharmacol Biol Psychiatry. 2018;82:187–94.
doi: 10.1016/j.pnpbp.2017.11.016
Gylys KH, Fein JA, Yang F, Wiley DJ, Miller CA, Cole GM. Synaptic changes in Alzheimer’s disease: increased amyloid-β and gliosis in surviving terminals is accompanied by decreased PSD-95 fluorescence. Am J Pathol. 2004;165:1809–17.
pubmed: 15509549 pmcid: 1618663 doi: 10.1016/S0002-9440(10)63436-0
Shibaguchi H, Takemura K, Kan S, Kataoka Y, Kaibara M, Saito N, et al. Role of synaptophysin in exocytotic release of dopamine from Xenopus oocytes injected with rat brain mRNA. Cell Mol Neurobiol. 2000;20:401–8.
pubmed: 10789836 doi: 10.1023/A:1007022428041
Valtorta F, Pennuto M, Bonanomi D, Benfenati F. Synaptophysin: leading actor or walk‐on role in synaptic vesicle exocytosis? Bioessays. 2004;26:445–53.
pubmed: 15057942 doi: 10.1002/bies.20012
Alder J, Kanki H, Valtorta F, Greengard P, Poo MM. Overexpression of synaptophysin enhances neurotransmitter secretion at Xenopus neuromuscular synapses. J Neurosci. 1995;15:511–9.
pubmed: 7823159 pmcid: 6578326 doi: 10.1523/JNEUROSCI.15-01-00511.1995
Daly C, Ziff EB. Ca2+-dependent formation of a dynamin-synaptophysin complex: potential role in synaptic vesicle endocytosis. J Biol Chem. 2002;277:9010–5.
pubmed: 11779869 doi: 10.1074/jbc.M110815200
Horikawa HP, Kneussel M, El Far O, Betz H. Interaction of synaptophysin with the AP-1 adaptor protein γ-adaptin. Mol Cell Neurosci. 2002;21:454–62.
pubmed: 12498786 doi: 10.1006/mcne.2002.1191
Bartholome O, Van den Ackerveken P, Sánchez Gil J, de la Brassinne Bonardeaux O, Leprince P, Franzen R, et al. Puzzling out synaptic vesicle 2 family members functions. Front Mol Neurosci. 2017;10:148.
pubmed: 28588450 pmcid: 5438990 doi: 10.3389/fnmol.2017.00148
Crowder KM, Gunther JM, Jones TA, Hale BD, Zhang HZ, Peterson MR, et al. Abnormal neurotransmission in mice lacking synaptic vesicle protein 2A (SV2A). Proc Natl Acad Sci. 1999;96:15268–73.
pubmed: 10611374 pmcid: 24809 doi: 10.1073/pnas.96.26.15268
Janz R, Goda Y, Geppert M, Missler M, Südhof TC. SV2A and SV2B function as redundant Ca2+ regulators in neurotransmitter release. Neuron. 1999;24:1003–16.
pubmed: 10624962 doi: 10.1016/S0896-6273(00)81046-6
Raval NR, Johansen A, Donovan LL, Ros NF, Ozenne B, Hansen HD, et al. A single dose of psilocybin increases synaptic density and decreases 5-HT2A receptor density in the pig brain. Int J Mol Sci. 2021;22:835.
pubmed: 33467676 pmcid: 7830000 doi: 10.3390/ijms22020835
Nardai S, László M, Szabó A, Alpár A, Hanics J, Zahola P, et al. N, N-dimethyltryptamine reduces infarct size and improves functional recovery following transient focal brain ischemia in rats. Exp Neurol. 2020;327:113245.
pubmed: 32067950 doi: 10.1016/j.expneurol.2020.113245
De Vos CM, Mason NL, Kuypers KP. Psychedelics and neuroplasticity: a systematic review unraveling the biological underpinnings of psychedelics. Front psychiatry. 2021;12:724606.
pubmed: 34566723 pmcid: 8461007 doi: 10.3389/fpsyt.2021.724606
Martin DA, Marona-Lewicka D, Nichols DE, Nichols CD. Chronic LSD alters gene expression profiles in the mPFC relevant to schizophrenia. Neuropharmacology. 2014;83:1–8.
pubmed: 24704148 pmcid: 4098645 doi: 10.1016/j.neuropharm.2014.03.013
Colaço CS, Alves SS, Nolli LM, Pinheiro WO, de Oliveira DGR, Santos BWL, et al. Toxicity of ayahuasca after 28 days daily exposure and effects on monoamines and brain-derived neurotrophic factor (BDNF) in brain of Wistar rats. Metab Brain Dis. 2020;35:739–51.
pubmed: 32103409 doi: 10.1007/s11011-020-00547-w
Moliner R, Girych M, Brunello CA, Kovaleva V, Biojone C, Enkavi G, et al. Psychedelics promote plasticity by directly binding to BDNF receptor TrkB. Nat Neurosci. 2023;26:1032–41.
pubmed: 37280397 pmcid: 10244169 doi: 10.1038/s41593-023-01316-5
Kozlowska U, Nichols C, Wiatr K, Figiel M. From psychiatry to neurology: Psychedelics as prospective therapeutics for neurodegenerative disorders. J Neurochem. 2022;162:89–108.
pubmed: 34519052 doi: 10.1111/jnc.15509
Ishida A, Noda Y, Ueda T. Synaptic vesicle-bound pyruvate kinase can support vesicular glutamate uptake. Neurochem Res. 2009;34:807–18.
pubmed: 18751889 doi: 10.1007/s11064-008-9833-3
Sagar NA, Tarafdar S, Agarwal S, Tarafdar A, Sharma S. Polyamines: functions, metabolism, and role in human disease management. Med Sci. 2021;9:44.
Xu T-T, Li H, Dai Z, Lau GK, Li B-Y, Zhu W-L, et al. Spermidine and spermine delay brain aging by inducing autophagy in SAMP8 mice. Aging. 2020;12:6401.
pubmed: 32268299 pmcid: 7185103 doi: 10.18632/aging.103035
Fernandez CO, Hoyer W, Zweckstetter M, Jares‐Erijman EA, Subramaniam V, Griesinger C, et al. NMR of α‐synuclein–polyamine complexes elucidates the mechanism and kinetics of induced aggregation. EMBO J. 2004;23:2039–46.
pubmed: 15103328 pmcid: 424375 doi: 10.1038/sj.emboj.7600211
Calabresi P, Mechelli A, Natale G, Volpicelli-Daley L, Di Lazzaro G, Ghiglieri V. Alpha-synuclein in Parkinson’s disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction. Cell Death Dis. 2023;14:176.
pubmed: 36859484 pmcid: 9977911 doi: 10.1038/s41419-023-05672-9
Gotvaldová K, Borovička J, Hájková K, Cihlářová P, Rockefeller A, Kuchař M. Extensive collection of psychotropic mushrooms with determination of their tryptamine alkaloids. Int J Mol Sci. 2022;23:14068.
pubmed: 36430546 pmcid: 9693126 doi: 10.3390/ijms232214068
Nkadimeng SM, Nabatanzi A, Steinmann CM, Eloff JN. Phytochemical, cytotoxicity, antioxidant and anti-inflammatory effects of Psilocybe natalensis magic mushroom. Plants. 2020;9:1127.
pubmed: 32878164 pmcid: 7570254 doi: 10.3390/plants9091127
Zanikov T, Gerasymchuk M, Ghasemi Gojani E, Robinson GI, Asghari S, Groves A, et al. The effect of combined treatment of psilocybin and eugenol on lipopolysaccharide-induced brain inflammation in mice. Molecules. 2023;28:2624.
pubmed: 36985596 pmcid: 10056123 doi: 10.3390/molecules28062624
Ignjatović Đ, Tovilović-Kovačević G, Mićić B, Tomić M, Djordjevic A, Macut D, et al. Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome. Hormones Behav. 2023;153:105392.
doi: 10.1016/j.yhbeh.2023.105392
Berthoux C, Barre A, Bockaert J, Marin P, Bécamel C. Sustained activation of postsynaptic 5-HT2A Receptors Gates Plasticity at Prefrontal Cortex Synapses. Cereb Cortex. 2018;29:1659–69.
doi: 10.1093/cercor/bhy064

Auteurs

Orr Shahar (O)

Biological Psychiatry Laboratory and Hadassah BrainLabs Center for Psychedelic Research, Hadassah Medical Center, Hebrew University, Jerusalem, Israel.

Alexander Botvinnik (A)

Biological Psychiatry Laboratory and Hadassah BrainLabs Center for Psychedelic Research, Hadassah Medical Center, Hebrew University, Jerusalem, Israel.

Amit Shwartz (A)

Biological Psychiatry Laboratory and Hadassah BrainLabs Center for Psychedelic Research, Hadassah Medical Center, Hebrew University, Jerusalem, Israel.

Elad Lerer (E)

Biological Psychiatry Laboratory and Hadassah BrainLabs Center for Psychedelic Research, Hadassah Medical Center, Hebrew University, Jerusalem, Israel.
Israel Institute for Biology, Nes Ziona, Israel.

Peretz Golding (P)

Biological Psychiatry Laboratory and Hadassah BrainLabs Center for Psychedelic Research, Hadassah Medical Center, Hebrew University, Jerusalem, Israel.

Alex Buko (A)

Human Metabolome Technologies, Boston, MA, USA.

Ethan Hamid (E)

Biological Psychiatry Laboratory and Hadassah BrainLabs Center for Psychedelic Research, Hadassah Medical Center, Hebrew University, Jerusalem, Israel.

Dani Kahn (D)

Biological Psychiatry Laboratory and Hadassah BrainLabs Center for Psychedelic Research, Hadassah Medical Center, Hebrew University, Jerusalem, Israel.

Miles Guralnick (M)

Biological Psychiatry Laboratory and Hadassah BrainLabs Center for Psychedelic Research, Hadassah Medical Center, Hebrew University, Jerusalem, Israel.

Karin Blakolmer (K)

Parow Entheobiosciences (ParowBio), Chicago, IL, USA.

Gilly Wolf (G)

Biological Psychiatry Laboratory and Hadassah BrainLabs Center for Psychedelic Research, Hadassah Medical Center, Hebrew University, Jerusalem, Israel.
Achva Academic College, Beer Tuvia, Israel.

Amit Lotan (A)

Biological Psychiatry Laboratory and Hadassah BrainLabs Center for Psychedelic Research, Hadassah Medical Center, Hebrew University, Jerusalem, Israel.

Leonard Lerer (L)

Parow Entheobiosciences (ParowBio), Chicago, IL, USA.
Back of the Yards Algae Sciences (BYAS), Chicago, IL, USA.

Bernard Lerer (B)

Biological Psychiatry Laboratory and Hadassah BrainLabs Center for Psychedelic Research, Hadassah Medical Center, Hebrew University, Jerusalem, Israel. lerer@mail.huji.ac.il.

Tzuri Lifschytz (T)

Biological Psychiatry Laboratory and Hadassah BrainLabs Center for Psychedelic Research, Hadassah Medical Center, Hebrew University, Jerusalem, Israel. tzuri.lifschytz@mail.huji.ac.il.

Classifications MeSH