The serotonergic psychedelics psilocybin, LSD and DMT hold great promise for the development of new treatments for psychiatric conditions such as major depressive disorder, addiction and end-of-life anxiety. Previous studies in both animals and humans have confirmed the effects of these drugs on neuronal activity and plasticity. However, the understanding of the mechanisms of action of these substances is limited. Here we show rapid effects of psychedelics on presynaptic properties, using live cell imaging at the level of single synapses in primary rat cortical neurons. Using the genetically encoded reporter of synaptic vesicle fusion synaptopHluorin, we detected a reduced fraction of synaptic vesicles that fused in response to mild or strong electrical stimulation 3-30 min after application of serotonergic psychedelics. These effects were transient and no longer present 24 h after treatment. While DMT only reduced the total recycling pool, LSD and psilocin also reduced the size of the readily releasable vesicle pool. Imaging with the sensors for glutamate, iGluSnFR, and presynaptic calcium, synGCaMP6, showed that while psilocin and DMT increased evoked glutamate release, LSD and psilocin reduced evoked presynaptic calcium levels. Interestingly, psilocin also affected short-term plasticity leading to a depression of responses to paired stimuli. The rapid and drug-specific modulation of glutamatergic neurotransmission described in this study may contribute to distinct anxiolytic and antidepressant properties of serotonergic psychedelics.

3rd Faculty of Medicine Charles University Prague Czech Republic

Department of Biology Animal Physiology Friedrich Alexander Universität Erlangen Nürnberg Erlangen Germany

Department of Psychiatry and Psychotherapy Universitätsklinikum Erlangen Friedrich Alexander Universität Erlangen Nürnberg Erlangen Germany

National Institute of Mental Health Klecany Czech Republic

Zobrazit více v PubMed

Aghajanian, G. K. , and Marek G. J.. 1999. “Serotonin, via 5‐HT2A Receptors, Increases EPSCs in Layer V Pyramidal Cells of Prefrontal Cortex by an Asynchronous Mode of Glutamate Release.” Brain Research 825, no. 1‐2: 161–171. 10.1016/s0006-8993(99)01224-x. PubMed DOI

Alabi, A. A. , and Tsien R. W.. 2012. “Synaptic Vesicle Pools and Dynamics.” Cold Spring Harbor Perspectives in Biology 4, no. 8: a013680–a013680. 10.1101/cshperspect.a013680. PubMed DOI PMC

Altier, C. 2012. “GPCR and Voltage‐Gated Calcium Channels (VGCC) Signaling Complexes.” Sub‐Cellular Biochemistry 63: 241–262. 10.1007/978-94-007-4765-4_13. PubMed DOI

Andersen, K. A. A. , Carhart‐Harris R., Nutt D. J., and Erritzoe D.. 2021. “Therapeutic Effects of Classic Serotonergic Psychedelics: A Systematic Review of Modern‐Era Clinical Studies.” Acta Psychiatrica Scandinavica 143, no. 2: 101–118. 10.1111/acps.13249. PubMed DOI

Anni, D. , Weiss E.‐M., Guhathakurta D., et al. 2021. “Aβ1‐16 Controls Synaptic Vesicle Pools at Excitatory Synapses via Cholinergic Modulation of Synapsin Phosphorylation.” Cellular and Molecular Life Sciences: CMLS 78, no. 11: 4973–4992. 10.1007/s00018-021-03835-5. PubMed DOI PMC

Berg, K. A. , Harvey J. A., Spampinato U., and Clarke W. P.. 2005. “Physiological Relevance of Constitutive Activity of 5‐HT2A and 5‐HT2C Receptors.” Trends in Pharmacological Sciences 26, no. 12: 625–630. 10.1016/j.tips.2005.10.008. PubMed DOI

Berg, K. A. , Maayani S., Goldfarb J., and Clarke W. P.. 1998. “Pleiotropic Behavior of 5‐HT2A and 5‐HT2C Receptor Agonists.” Annals of the New York Academy of Sciences 861: 104–110. 10.1111/j.1749-6632.1998.tb10180.x. PubMed DOI

Besnard, J. , Ruda G. F., Setola V., et al. 2012. “Automated Design of Ligands to Polypharmacological Profiles.” Nature 492, no. 7428: 215–220. 10.1038/nature11691. PubMed DOI PMC

Bodzęta, A. , Scheefhals N., and MacGillavry H. D.. 2021. “Membrane Trafficking and Positioning of mGluRs at Presynaptic and Postsynaptic Sites of Excitatory Synapses.” Neuropharmacology 200: 108799. 10.1016/j.neuropharm.2021.108799. PubMed DOI

Burrone, J. , Li Z., and Murthy V. N.. 2006. “Studying Vesicle Cycling in Presynaptic Terminals Using the Genetically Encoded Probe synaptopHluorin.” Nature Protocols 1, no. 6: 2970–2978. 10.1038/nprot.2006.449. PubMed DOI

Calder, A. E. , and Hasler G.. 2023. “Towards an Understanding of Psychedelic‐Induced Neuroplasticity.” Neuropsychopharmacology 48, no. 1: 104–112. 10.1038/s41386-022-01389-z. PubMed DOI PMC

Carhart‐Harris, R. L. , Bolstridge M., Day C. M. J., et al. 2018. “Psilocybin With Psychological Support for Treatment‐Resistant Depression: Six‐Month Follow‐Up.” Psychopharmacology 235, no. 2: 399–408. 10.1007/s00213-017-4771-x. PubMed DOI PMC

Carhart‐Harris, R. L. , Bolstridge M., Rucker J., et al. 2016. “Psilocybin With Psychological Support for Treatment‐Resistant Depression: An Open‐Label Feasibility Study.” Lancet. Psychiatry 3, no. 7: 619–627. 10.1016/S2215-0366(16)30065-7. PubMed DOI

Chaudhuri, A. D. , Yelamanchili S. V., and Fox H. S.. 2013. “MicroRNA‐142 Reduces Monoamine Oxidase A Expression and Activity in Neuronal Cells by Downregulating SIRT1.” PLoS One 8, no. 11: e79579. 10.1371/journal.pone.0079579. PubMed DOI PMC

Dolphin, A. C. 2003. “G Protein Modulation of Voltage‐Gated Calcium Channels.” Pharmacological Reviews 55, no. 4: 607–627. 10.1124/pr.55.4.3. PubMed DOI

Egan, C. T. , Herrick‐Davis K., Miller K., Glennon R. A., and Teitler M.. 1998. “Agonist Activity of LSD and Lisuride at Cloned 5HT2A and 5HT2C Receptors.” Psychopharmacology 136, no. 4: 409–414. 10.1007/s002130050585. PubMed DOI

Fontanilla, D. , Johannessen M., Hajipour A. R., Cozzi N. V., Jackson M. B., and Ruoho A. E.. 2009. “The Hallucinogen N,N‐Dimethyltryptamine (DMT) is an Endogenous Sigma‐1 Receptor Regulator.” Science (New York, N.Y.) 323, no. 5916: 934–937. 10.1126/science.1166127. PubMed DOI PMC

Franzen, F. , and Gross H.. 1965. “Tryptamine, N,N‐Dimethyltryptamine, N,N‐Dimethyl‐5‐Hydroxytryptamine and 5‐Methoxytryptamine in Human Blood and Urine.” Nature 206, no. 988: 1052. 10.1038/2061052a0. PubMed DOI

Fuente Revenga, M. , Zhu B., Guevara C. A., et al. 2021. “Prolonged Epigenomic and Synaptic Plasticity Alterations Following Single Exposure to a Psychedelic in Mice.” Cell Reports 37, no. 3: 109. 10.1016/j.celrep.2021.109836. PubMed DOI PMC

Galvão‐Coelho, N. L. , Marx W., Gonzalez M., et al. 2021. “Classic Serotonergic Psychedelics for Mood and Depressive Symptoms: A Meta‐Analysis of Mood Disorder Patients and Healthy Participants.” Psychopharmacology 238, no. 2: 341–354. 10.1007/s00213-020-05719-1. PubMed DOI PMC

Gattuso, J. J. , Perkins D., Ruffell S., et al. 2022. “Default Mode Network Modulation by Psychedelics: A Systematic Review.” International Journal of Neuropsychopharmacology 26, no. 3: 155–188. 10.1093/ijnp/pyac074. PubMed DOI PMC

González‐Maeso, J. , Ang R. L., Yuen T., et al. 2008. “Identification of a Serotonin/Glutamate Receptor Complex Implicated in Psychosis.” Nature 452, no. 7183: 93–97. 10.1038/nature06612. PubMed DOI PMC

González‐Maeso, J. , Weisstaub N. V., Zhou M., et al. 2007. “Hallucinogens Recruit Specific Cortical 5‐HT(2A) Receptor‐Mediated Signaling Pathways to Affect Behavior.” Neuron 53, no. 3: 439–452. 10.1016/j.neuron.2007.01.008. PubMed DOI

González‐Maeso, J. , Yuen T., Ebersole B. J., et al. 2003. “Transcriptome Fingerprints Distinguish Hallucinogenic and Nonhallucinogenic 5‐Hydroxytryptamine 2A Receptor Agonist Effects in Mouse Somatosensory Cortex.” Journal of Neuroscience: The Official Journal of the Society for Neuroscience 23, no. 26: 8836–8843. PubMed PMC

Goodwin, G. M. , Aaronson S. T., Alvarez O., et al. 2022. “Single‐Dose Psilocybin for a Treatment‐Resistant Episode of Major Depression.” New England Journal of Medicine 387, no. 18: 1637–1648. 10.1056/NEJMoa2206443. PubMed DOI

Goodwin, G. M. , Aaronson S. T., Alvarez O., et al. 2023. “Single‐Dose Psilocybin for a Treatment‐Resistant Episode of Major Depression: Impact on Patient‐Reported Depression Severity, Anxiety, Function, and Quality of Life.” Journal of Affective Disorders 327: 120–127. 10.1016/j.jad.2023.01.108. PubMed DOI

Gregorio, D. D. , Aguilar‐Valles A., Preller K. H., et al. 2021. “Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine.” Journal of Neuroscience 41, no. 5: 891–900. 10.1523/JNEUROSCI.1659-20.2020. PubMed DOI PMC

Guhathakurta, D. , Petrušková A., Akdaş E. Y., et al. 2024. “Hydroxynorketamine, but Not Ketamine, Acts via α7 Nicotinic Acetylcholine Receptor to Control Presynaptic Function and Gene Expression.” Translational Psychiatry 14, no. 1: 47. 10.1038/s41398-024-02744-y. PubMed DOI PMC

Halberstadt, A. L. , Koedood L., Powell S. B., and Geyer M. A.. 2011. “Differential Contributions of Serotonin Receptors to the Behavioral Effects of Indoleamine Hallucinogens in Mice.” Journal of Psychopharmacology Oxford, England 25, no. 11: 1548–1561. 10.1177/0269881110388326. PubMed DOI PMC

Harvey, J. A. 2003. “Role of the Serotonin 5‐HT(2A) Receptor in Learning.” Learning & Memory (Cold Spring Harbor, N.Y.) 10, no. 5: 355–362. 10.1101/lm.60803. PubMed DOI PMC

Hesselgrave, N. , Troppoli T. A., Wulff A. B., Cole A. B., and Thompson S. M.. 2021. “Harnessing Psilocybin: Antidepressant‐Like Behavioral and Synaptic Actions of Psilocybin Are Independent of 5‐HT2R Activation in Mice.” Proceedings of the National Academy of Sciences of the United States of America 118, no. 17: e2022489118. 10.1073/pnas.2022489118. PubMed DOI PMC

Holze, F. , Avedisian I., Varghese N., Eckert A., and Liechti M. E.. 2021. “Role of the 5‐HT2A Receptor in Acute Effects of LSD on Empathy and Circulating Oxytocin.” Frontiers in Pharmacology 12: 711. 10.3389/fphar.2021.711255. PubMed DOI PMC

Holze, F. , Vizeli P., Ley L., et al. 2021. “Acute Dose‐Dependent Effects of Lysergic Acid Diethylamide in a Double‐Blind Placebo‐Controlled Study in Healthy Subjects.” Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology 46, no. 3: 537–544. 10.1038/s41386-020-00883-6. PubMed DOI PMC

PDSP . 2023. “PDSP Ki Database.” https://pdsp.unc.edu/databases/kidb.php.

Hu, L. , Liu C., Dang M., Luo B., Guo Y., and Wang H.. 2016. “Activation of 5‐HT2A/2C Receptors Reduces the Excitability of Cultured Cortical Neurons.” Neuroscience Letters 632: 124–129. 10.1016/j.neulet.2016.08.052. PubMed DOI

Jaster, A. M. , Elder H., Marsh S. A., Negus S. S., and González‐Maeso J.. 2022. “Effects of the 5‐HT2A Receptor Antagonist Volinanserin on Head‐Twitch Response and Intracranial Self‐Stimulation Depression Induced by Different Structural Classes of Psychedelics in Rodents.” Psychopharmacology 239, no. 6: 1665–1677. 10.1007/s00213-022-06092-x. PubMed DOI PMC

Jin, L. E. , Wang M., Galvin V. C., et al. 2018. “mGluR2 Versus mGluR3 Metabotropic Glutamate Receptors in Primate Dorsolateral Prefrontal Cortex: Postsynaptic mGluR3 Strengthen Working Memory Networks.” Cerebral Cortex 28, no. 3: 974–987. 10.1093/cercor/bhx005. PubMed DOI PMC

Kopra, E. I. , Ferris J. A., Winstock A. R., Kuypers K. P., Young A. H., and Rucker J. J.. 2023. “Investigation of Self‐Treatment With Lysergic Acid Diethylamide and Psilocybin Mushrooms: Findings From the Global Drug Survey 2020.” Journal of Psychopharmacology (Oxford, England) 37: 748. 10.1177/02698811231158245. PubMed DOI PMC

Kossatz, E. , Diez‐Alarcia R., Gaitonde S. A., et al. 2024. “G Protein‐Specific Mechanisms in the Serotonin 5‐HT2A Receptor Regulate Psychosis‐Related Effects and Memory Deficits.” Nature Communications 15, no. 1: 4307. 10.1038/s41467-024-48196-2. PubMed DOI PMC

Krebs‐Thomson, K. , and Geyer M. A.. 1996. “The Role of 5‐HT(1A) Receptors in the Locomotor‐Suppressant Effects of LSD: WAY‐100635 Studies of 8‐OH‐DPAT, DOI and LSD in Rats.” Behavioural Pharmacology 7, no. 6: 551–559. PubMed

Kvachnina, E. , Dumuis A., Wlodarczyk J., et al. 2009. “Constitutive Gs‐Mediated, but Not G12‐Mediated, Activity of the 5‐Hydroxytryptamine 5‐HT7(a) Receptor Is Modulated by the Palmitoylation of Its C‐Terminal Domain.” Biochimica et Biophysica Acta 1793, no. 11: 1646–1655. 10.1016/j.bbamcr.2009.08.008. PubMed DOI

Lazarevic, V. , Fieńko S., Andres‐Alonso M., et al. 2017. “Physiological Concentrations of Amyloid Beta Regulate Recycling of Synaptic Vesicles via Alpha7 Acetylcholine Receptor and CDK5/Calcineurin Signaling.” Frontiers in Molecular Neuroscience 10: 221. 10.3389/fnmol.2017.00221. PubMed DOI PMC

Lazarevic, V. , Yang Y., Flais I., and Svenningsson P.. 2021. “Ketamine Decreases Neuronally Released Glutamate via Retrograde Stimulation of Presynaptic Adenosine A1 Receptors.” Molecular Psychiatry 26, no. 12: 7425–7435. 10.1038/s41380-021-01246-3. PubMed DOI PMC

Li, N. , Lee B., Liu R.‐J., et al. 2010. “mTOR‐Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists.” Science (New York, N.Y.) 329, no. 5994: 959–964. 10.1126/science.1190287. PubMed DOI PMC

Lonze, B. E. , and Ginty D. D.. 2002. “Function and Regulation of CREB Family Transcription Factors in the Nervous System.” Neuron 35, no. 4: 605–623. 10.1016/s0896-6273(02)00828-0. PubMed DOI

Ly, C. , Greb A. C., Cameron L. P., et al. 2018. “Psychedelics Promote Structural and Functional Neural Plasticity.” Cell Reports 23, no. 11: 3170–3182. 10.1016/j.celrep.2018.05.022. PubMed DOI PMC

Maher, P. , and Davis J. B.. 1996. “The Role of Monoamine Metabolism in Oxidative Glutamate Toxicity.” Journal of Neuroscience: The Official Journal of the Society for Neuroscience 16, no. 20: 6394–6401. 10.1523/JNEUROSCI.16-20-06394.1996. PubMed DOI PMC

Martí‐Solano, M. , Iglesias A., de Fabritiis G., et al. 2015. “Detection of New Biased Agonists for the Serotonin 5‐HT2A Receptor: Modeling and Experimental Validation.” Molecular Pharmacology 87, no. 4: 740–746. 10.1124/mol.114.097022. PubMed DOI

Marvin, J. S. , Borghuis B. G., Tian L., et al. 2013. “An Optimized Fluorescent Probe for Visualizing Glutamate Neurotransmission.” Nature Methods 10, no. 2: 162–170. 10.1038/nmeth.2333. PubMed DOI PMC

Marvin, J. S. , Scholl B., Wilson D. E., et al. 2019. “Author Correction: Stability, Affinity, and Chromatic Variants of the Glutamate Sensor iGluSnFR.” Nature Methods 16, no. 4: 351. 10.1038/s41592-018-0171-3. PubMed DOI

Menegon, A. , Bonanomi D., Albertinazzi C., et al. 2006. “Protein Kinase A‐Mediated Synapsin I Phosphorylation Is a Central Modulator of Ca2+−Dependent Synaptic Activity.” Journal of Neuroscience: The Official Journal of the Society for Neuroscience 26, no. 45: 11670–11681. 10.1523/JNEUROSCI.3321-06.2006. PubMed DOI PMC

Mialet, J. , Berque‐Bestel I., Eftekhari P., et al. 2000. “Isolation of the Serotoninergic 5‐HT4(e) Receptor From Human Heart and Comparative Analysis of Its Pharmacological Profile in C6‐Glial and CHO Cell Lines.” British Journal of Pharmacology 129, no. 4: 771–781. 10.1038/sj.bjp.0703101. PubMed DOI PMC

Moliner, R. , Girych M., Brunello C. A., et al. 2023. “Psychedelics Promote Plasticity by Directly Binding to BDNF Receptor TrkB.” Nature Neuroscience 26, no. 6: 1032–1041. 10.1038/s41593-023-01316-5. PubMed DOI PMC

Moreno, J. L. , Holloway T., Albizu L., Sealfon S. C., and González‐Maeso J.. 2011. “Metabotropic Glutamate mGlu2 Receptor Is Necessary for the Pharmacological and Behavioral Effects Induced by Hallucinogenic 5‐HT2A Receptor Agonists.” Neuroscience Letters 493, no. 3: 76–79. 10.1016/j.neulet.2011.01.046. PubMed DOI PMC

Müller, J. A. , Betzin J., Santos‐Tejedor J., et al. 2022. “A Presynaptic Phosphosignaling Hub for Lasting Homeostatic Plasticity.” Cell Reports 39, no. 3: 110–696. 10.1016/j.celrep.2022.110696. PubMed DOI

Muthukumaraswamy, S. D. , Carhart‐Harris R. L., Moran R. J., et al. 2013. “Broadband Cortical Desynchronization Underlies the Human Psychedelic State.” Journal of Neuroscience: The Official Journal of the Society for Neuroscience 33, no. 38: 15171–15183. 10.1523/JNEUROSCI.2063-13.2013. PubMed DOI PMC

Nagy, G. , Reim K., Matti U., et al. 2004. “Regulation of Releasable Vesicle Pool Sizes by Protein Kinase A‐Dependent Phosphorylation of SNAP‐25.” Neuron 41, no. 3: 417–429. 10.1016/s0896-6273(04)00038-8. PubMed DOI

Nicholls, R. E. , Zhang X.‐L., Bailey C. P., Conklin B. R., Kandel E. R., and Stanton P. K.. 2006. “mGluR2 Acts Through Inhibitory Gα Subunits to Regulate Transmission and Long‐Term Plasticity at Hippocampal Mossy Fiber‐CA3 Synapses.” Proceedings of the National Academy of Sciences of the United States of America 103, no. 16: 6380–6385. 10.1073/pnas.0601267103. PubMed DOI PMC

Odland, A. U. , Kristensen J. L., and Andreasen J. T.. 2022. “Animal Behavior in Psychedelic Research.” Pharmacological Reviews 74, no. 4: 113093. 10.1016/j.bbr.2020.113093. PubMed DOI

Oleskevich, S. , Clements J., and Walmsley B.. 2000. “Release Probability Modulates Short‐Term Plasticity at a Rat Giant Terminal.” Journal of Physiology 524, no. Pt 2: 513–523. 10.1111/j.1469-7793.2000.00513.x. PubMed DOI PMC

Ostadkarampour, M. , and Putnins E. E.. 2021. “Monoamine Oxidase Inhibitors: A Review of Their Anti‐Inflammatory Therapeutic Potential and Mechanisms of Action.” Frontiers in Pharmacology 12: 676239. 10.3389/fphar.2021.676239. PubMed DOI PMC

Patzke, C. , Brockmann M. M., Dai J., et al. 2019. “Neuromodulator Signaling Bidirectionally Controls Vesicle Numbers in Human Synapses.” Cell 179, no. 2: 498–513. 10.1016/j.cell.2019.09.011. PubMed DOI PMC

Pieri, L. , Keller H. H., and Burkard W.. 1978. “Effects of Lisuride and LSD on Cerebral Monoamine Systems and Hallucinosis.” Nature 272, no. 5650: 278–280. 10.1038/272278a0. PubMed DOI

Ponimaskin, E. G. , Heine M., Joubert L., et al. 2002. “The 5‐Hydroxytryptamine(4a) Receptor Is Palmitoylated at Two Different Sites, and Acylation Is Critically Involved in Regulation of Receptor Constitutive Activity.” Journal of Biological Chemistry 277, no. 4: 2534–2546. 10.1074/jbc.M106529200. PubMed DOI

Preller, K. H. , Herdener M., Pokorny T., et al. 2017. “The Fabric of Meaning and Subjective Effects in LSD‐Induced States Depend on Serotonin 2A Receptor Activation.” Current Biology: CB 27, no. 3: 451–457. 10.1016/j.cub.2016.12.030. PubMed DOI

Qin, N. , Platano D., Olcese R., Stefani E., and Birnbaumer L.. 1997. “Direct Interaction of Gβγ With a C‐Terminal Gβγ‐Binding Domain of the Ca2+ Channel α1 Subunit Is Responsible for Channel Inhibition by G Protein‐Coupled Receptors.” Proceedings of the National Academy of Sciences of the United States of America 94, no. 16: 8866–8871. PubMed PMC

Ray, T. S. 2010. “Psychedelics and the Human Receptorome.” PLoS One 5, no. 2: e9019. 10.1371/journal.pone.0009019. PubMed DOI PMC

Regehr, W. G. 2012. “Short‐Term Presynaptic Plasticity.” Cold Spring Harbor Perspectives in Biology 4, no. 7: a005702. 10.1101/cshperspect.a005702. PubMed DOI PMC

Riba, J. , McIlhenny E. H., Bouso J. C., and Barker S. A.. 2015. “Metabolism and Urinary Disposition of N,N‐Dimethyltryptamine After Oral and Smoked Administration: A Comparative Study.” Drug Testing and Analysis 7, no. 5: 401–406. 10.1002/dta.1685. PubMed DOI

Rickli, A. , Moning O. D., Hoener M. C., and Liechti M. E.. 2016. “Receptor Interaction Profiles of Novel Psychoactive Tryptamines Compared With Classic Hallucinogens.” European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology 26, no. 8: 1327–1337. 10.1016/j.euroneuro.2016.05.001. PubMed DOI

Rose, T. , Schoenenberger P., Jezek K., and Oertner T. G.. 2013. “Developmental Refinement of Vesicle Cycling at Schaffer Collateral Synapses.” Neuron 77, no. 6: 1109–1121. 10.1016/j.neuron.2013.01.021. PubMed DOI

Roth, B. L. , Lopez E., Patel S., and Kroeze W. K.. 2000. “The Multiplicity of Serotonin Receptors: Uselessly Diverse Molecules or an Embarrassment of Riches?” Neuroscientist 6, no. 4: 252–262. 10.1177/107385840000600408. DOI

Singer, J. H. , Bellingham M. C., and Berger A. J.. 1996. “Presynaptic Inhibition of Glutamatergic Synaptic Transmission to Rat Motoneurons by Serotonin.” Journal of Neurophysiology 76, no. 2: 799–807. 10.1152/jn.1996.76.2.799. PubMed DOI

Stenbæk, D. S. , Madsen M. K., Ozenne B., et al. 2021. “Brain Serotonin 2A Receptor Binding Predicts Subjective Temporal and Mystical Effects of Psilocybin in Healthy Humans.” Journal of Psychopharmacology 35, no. 4: 459–468. 10.1177/0269881120959609. PubMed DOI

Strassman, R. J. , Qualls C. R., Uhlenhuth E. H., and Kellner R.. 1994. “Dose–Response Study of N,N‐Dimethyltryptamine in Humans: II. Subjective Effects and Preliminary Results of a New Rating Scale.” Archives of General Psychiatry 51, no. 2: 98–108. 10.1001/archpsyc.1994.03950020022002. PubMed DOI

Szára, S. 1956. “Dimethyltryptamin: Its Metabolism in Man; the Relation of Its Psychotic Effect to the Serotonin Metabolism.” Experientia 12, no. 11: 441–442. 10.1007/BF02157378. PubMed DOI

Tanaka, E. , and North R. A.. 1993. “Actions of 5‐Hydroxytryptamine on Neurons of the Rat Cingulate Cortex.” Journal of Neurophysiology 69, no. 5: 1749–1757. 10.1152/jn.1993.69.5.1749. PubMed DOI

Thanawala, M. S. , and Regehr W. G.. 2013. “Presynaptic Calcium Influx Controls Neurotransmitter Release in Part by Regulating the Effective Size of the Readily Releasable Pool.” Journal of Neuroscience 33, no. 11: 4625–4633. 10.1523/JNEUROSCI.4031-12.2013. PubMed DOI PMC

Tylš, F. , Vejmola Č., Koudelka V., et al. 2023. “Underlying Pharmacological Mechanisms of Psilocin‐Induced Broadband Desynchronization and Disconnection of EEG in Rats.” Frontiers in Neuroscience 17: 1. 10.3389/fnins.2023.1152578. PubMed DOI PMC

Vargas, M. V. , Dunlap L. E., Dong C., et al. 2023. “Psychedelics Promote Neuroplasticity Through the Activation of Intracellular 5‐HT2A Receptors.” Science (New York, N.Y.) 379, no. 6633: 700–706. 10.1126/science.adf0435. PubMed DOI PMC

Vollenweider, F. X. , Vollenweider‐Scherpenhuyzen M. F., Bäbler A., Vogel H., and Hell D.. 1998. “Psilocybin Induces Schizophrenia‐Like Psychosis in Humans via a Serotonin‐2 Agonist Action.” Neuroreport 9, no. 17: 3897–3902. PubMed

Wang, Y. , Wang C., Ranefall P., et al. 2020. “SynQuant: An Automatic Tool to Quantify Synapses From Microscopy Images.” Bioinformatics (Oxford, England) 36, no. 5: 1599–1606. 10.1093/bioinformatics/btz760. PubMed DOI PMC

Weiner, D. M. , Burstein E. S., Nash N., et al. 2001. “5‐Hydroxytryptamine2A Receptor Inverse Agonists as Antipsychotics.” Journal of Pharmacology and Experimental Therapeutics 299, no. 1: 268–276. 10.1016/S0022-3565(24)29327-7. PubMed DOI

West, A. E. , Griffith E. C., and Greenberg M. E.. 2002. “Regulation of Transcription Factors by Neuronal Activity.” Nature Reviews. Neuroscience 3, no. 12: 921–931. 10.1038/nrn987. PubMed DOI

Zanos, P. , Moaddel R., Morris P. J., et al. 2016. “NMDAR Inhibition‐Independent Antidepressant Actions of Ketamine Metabolites.” Nature 533, no. 7604: 481–486. 10.1038/nature17998. PubMed DOI PMC

Zucker, R. S. , and Regehr W. G.. 2002. “Short‐Term Synaptic Plasticity.” Annual Review of Physiology 64: 355–405. 10.1146/annurev.physiol.64.092501.114547. PubMed DOI