Snyder, S. H. Drugs and the Brain (W. H. Freeman & Co., 1986).
Shulgin, A. T. The background and chemistry of MDMA. J. Psychoactive Drugs 18, 291–304 (1986).
Google Scholar
Griffiths, R. R. et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J. Psychopharmacol. 30, 1181–1197 (2016).
Google Scholar
Noller, G. E., Frampton, C. M. & Yazar-Klosinski, B. Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study. Am. J. Drug Alcohol Abuse 44, 37–46 (2018).
Google Scholar
Johnson, M. W. & Griffiths, R. R. Potential therapeutic effects of psilocybin. Neurotherapeutics 14, 734–740 (2017).
Google Scholar
Mitchell, J. M. et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat. Med. 27, 1025–1033 (2021).
Google Scholar
Mithoefer, M. C. et al. Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. J. Psychopharmacol. 27, 28–39 (2013).
Google Scholar
Carhart-Harris, R. et al. Trial of psilocybin versus escitalopram for depression. N. Engl. J. Med. 384, 1402–1411 (2021).
Google Scholar
Zarate, C. A. et al. A randomized trial of an N-methyl-d-aspartate antagonist in treatment-resistant major depression. Arch. Gen. Psychiatry 63, 856–864 (2006).
Google Scholar
Nichols, D. E. Psychedelics. Pharmacol. Rev. 68, 264–355 (2016).
Google Scholar
Nardou, R. et al. Oxytocin-dependent reopening of a social reward learning critical period with MDMA. Nature 569, 116–120 (2019).
Google Scholar
Russo, S. J. et al. The addicted synapse: mechanisms of synaptic and structural plasticity in nucleus accumbens. Trends Neurosci. 33, 267–276 (2010).
Google Scholar
Bedi, G., Hyman, D. & De Wit, H. Is ecstasy an ‘empathogen’? Effects of 3,4- methylenedioxymethamphetamine on prosocial feelings and identification of emotional states in others. Biol. Psychiatry 68, 1134–1140 (2010).
Google Scholar
Holze, F. et al. Distinct acute effects of LSD, MDMA, and d-amphetamine in healthy subjects. Neuropsychopharmacology 45, 462–471 (2020).
Google Scholar
Niesters, M., Martini, C. & Dahan, A. Ketamine for chronic pain: risks and benefits. Br. J. Clin. Pharmacol. 77, 357–367 (2014).
Google Scholar
MačiIulaitis, R., Kontrimavičiute, V., Bressolle, F. M. M. & Briedis, V. Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. Hum. Exp. Toxicol. 27, 181–194 (2008).
Google Scholar
Halberstadt, A. L., Chatha, M., Klein, A. K., Wallach, J. & Brandt, S. D. Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. Neuropharmacology 167, 107933 (2020).
Google Scholar
Autry, A. E. et al. NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 475, 91–95 (2011).
Google Scholar
Tzschentke, T. M. Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade. Addict. Biol. 12, 227–462 (2007).
Google Scholar
Kolbrich, E. A. et al. Physiological and subjective responses to controlled oral 3,4-methylenedioxymethamphetamine administration. J. Clin. Psychopharmacol. 28, 432–440 (2008).
Google Scholar
Madsen, M. K. et al. Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. Neuropsychopharmacology 44, 1328–1334 (2019).
Google Scholar
Schmid, Y. et al. Acute effects of lysergic acid diethylamide in healthy subjects. Biol. Psychiatry 78, 544–553 (2015).
Google Scholar
Abraham, W. C. & Bear, M. F. Metaplasticity: the plasticity of synaptic plasticity. Trends Neurosci. 19, 126–130 (1996).
Google Scholar
Cho, K. K. A., Khibnik, L., Philpot, B. D. & Bear, M. F. The ratio of NR2A/B NMDA receptor subunits determines the qualities of ocular dominance plasticity in visual cortex. Proc. Natl Acad. Sci. USA 106, 5377–5382 (2009).
Google Scholar
Dölen, G., Darvishzadeh, A., Huang, K. W. & Malenka, R. C. Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin. Nature 501, 179–184 (2013).
Google Scholar
Hung, L. W. L. L. W. et al. Gating of social reward by oxytocin in the ventral tegmental area. Science 357, 1406–1411 (2017).
Google Scholar
Bennett, J. P. & Snyder, S. H. Stereospecific binding of d-lysergic acid diethylamide (LSD) to brain membranes: relationship to serotonin receptors. Brain Res. 94, 523–544 (1975).
Google Scholar
Preller, K. H. et al. The fabric of meaning and subjective effects in LSD-induced states depend on serotonin 2A receptor activation. Curr. Biol. 27, 451–457 (2017).
Google Scholar
Kometer, M., Schmidt, A., Jäncke, L. & Vollenweider, F. X. Activation of serotonin 2A receptors underlies the psilocybin-induced effects on α oscillations, N170 visual-evoked potentials, and visual hallucinations. J. Neurosci. 33, 10544–10551 (2013).
Google Scholar
Rudnick, G. & Wall, S. C. The molecular mechanism of ‘ecstasy’ [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Proc. Natl Acad. Sci. USA 89, 1817–1821 (1992).
Google Scholar
Murphy, T. J. & Murnane, K. S. The serotonin 2C receptor agonist WAY-163909 attenuates ketamine-induced hypothermia in mice. Eur. J. Pharmacol. 842, 255–261 (2019).
Google Scholar
McClure-Begley, T. D. & Roth, B. L. The promises and perils of psychedelic pharmacology for psychiatry. Nat. Rev. Drug Discov. 21, 463–473 (2022).
Google Scholar
Kim, K. et al. Structure of a hallucinogen-activated Gq-coupled 5-HT2A serotonin receptor. Cell 182, 1574–1588.e19 (2020).
Google Scholar
Maillet, E. L. et al. Noribogaine is a G-protein biased κ-opioid receptor agonist. Neuropharmacology 99, 675–688 (2015).
Google Scholar
Suzuki, K., Nosyreva, E., Hunt, K. W., Kavalali, E. T. & Monteggia, L. M. Effects of a ketamine metabolite on synaptic NMDAR function. Nature 546, E1–E3 (2017).
Google Scholar
Esterlis, I. et al. Ketamine-induced reduction in mGluR5 availability is associated with an antidepressant response: an [11C]ABP688 and PET imaging study in depression. Mol. Psychiatry 23, 824–832 (2018).
Google Scholar
Lau, L. W., Cua, R., Keough, M. B., Haylock-Jacobs, S. & Yong, V. W. Pathophysiology of the brain extracellular matrix: a new target for remyelination. Nat. Rev. Neurosci. 14, 722–729 (2013).
Google Scholar
Oh, S. Y., Lee, S.-J., Jung, Y. H., Lee, H. J. & Han, H. J. Arachidonic acid promotes skin wound healing through induction of human MSC migration by MT3-MMP-mediated fibronectin degradation. Cell Death Dis. 6, e1750 (2015).
Google Scholar
Cussac, L.-A. et al. TRPV4 channel mediates adventitial fibroblast activation and adventitial remodeling in pulmonary hypertension. Am. J. Physiol. 318, L135–L146 (2020).
Google Scholar
Shan, Z.-G. et al. Upregulation of tubulointerstitial nephritis antigen like 1 promotes gastric cancer growth and metastasis by regulating multiple matrix metallopeptidase expression. J. Gastroenterol. Hepatol. 36, 196–203 (2021).
Google Scholar
Chakraborty, S. & Ain, R. Nitric-oxide synthase trafficking inducer is a pleiotropic regulator of endothelial cell function and signaling. J. Biol. Chem. 292, 6600–6620 (2017).
Google Scholar
Uckelmann, H. et al. Extracellular matrix protein Matrilin-4 regulates stress-induced HSC proliferation via CXCR4. J. Exp. Med. 213, 1961–1971 (2016).
Google Scholar
Tjong, W.-Y. & Lin, H.-H. The role of the RGD motif in CD97/ADGRE5-and EMR2/ADGRE2-modulated tumor angiogenesis. Biochem. Biophys. Res. Commun. 520, 243–249 (2019).
Google Scholar
Cai, H. et al. Roundabout 4 regulates blood-tumor barrier permeability through the modulation of ZO-1, occludin, and claudin-5 expression. J. Neuropathol. Exp. Neurol. 74, 25–37 (2015).
Google Scholar
Carulli, D., de Winter, F. & Verhaagen, J. Semaphorins in adult nervous system plasticity and disease. Front. Synaptic Neurosci. 13, 672891 (2021).
Google Scholar
Hesselgrave, N., Troppoli, T. A., Wulff, A. B., Cole, A. B. & Thompson, S. M. Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice. Proc. Natl Acad. Sci. USA 118, e2022489118 (2021).
Google Scholar
Moda-Sava, R. N. et al. Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation. Science 364, eaat8078 (2019).
Google Scholar
Vargas, M. V. et al. Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors. Science 379, 700–706 (2023).
Google Scholar
Young, M. B. et al. Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA). Psychopharmacology 234, 2883–2895 (2017).
Google Scholar
Flanagan, T. W. & Nichols, C. D. Psychedelics as anti-inflammatory agents. Int. Rev. Psychiatry 30, 363–375 (2018).
Google Scholar
Schindler, E. A. D. Psychedelics in the treatment of headache and chronic pain disorders. Curr. Top. Behav. Neurosci. 56, 261–285 (2022).
Google Scholar
Ly, C. et al. Psychedelics promote structural and functional neural plasticity. Cell Rep. 23, 3170–3182 (2018).
Google Scholar
Shao, L.-X. et al. Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo. Neuron 109, 2535–2544.e4 (2021).
Google Scholar
Ali, F. et al. Ketamine disinhibits dendrites and enhances calcium signals in prefrontal dendritic spines. Nat. Commun. 11, 72 (2020).
Google Scholar
Castrén, E. & Monteggia, L. M. Brain-derived neurotrophic factor signaling in depression and antidepressant action. Biol. Psychiatry 90, 128–136 (2021).
Google Scholar
Crawford, D. C., Ramirez, D. M. O., Trauterman, B., Monteggia, L. M. & Kavalali, E. T. Selective molecular impairment of spontaneous neurotransmission modulates synaptic efficacy. Nat. Commun. 8, 14436 (2017).
Google Scholar
Kim, J.-W. et al. Sustained effects of rapidly acting antidepressants require BDNF-dependent MeCP2 phosphorylation. Nat. Neurosci. 24, 1100–1109 (2021).
Google Scholar
Kuypers, K. P. C. et al. Ayahuasca enhances creative divergent thinking while decreasing conventional convergent thinking. Psychopharmacology 233, 3395–3403 (2016).
Google Scholar
Davis, A. K., Barrett, F. S. & Griffiths, R. R. Psychological flexibility mediates the relations between acute psychedelic effects and subjective decreases in depression and anxiety. J. Context. Behav. Sci. 15, 39–45 (2020).
Google Scholar
Agin-Liebes, G. et al. Prospective examination of the therapeutic role of psychological flexibility and cognitive reappraisal in the ceremonial use of ayahuasca. J. Psychopharmacol. 36, 295–308 (2022).
Google Scholar
Lorenz, K. Der Kumpan in der Umwelt des Vogels. J. Ornithol. 83, 137–213 (1935).
Google Scholar
Woolley, S. M. N. & Rubel, E. W. Vocal memory and learning in adult Bengalese finches with regenerated hair cells. J. Neurosci. 22, 7774–7787 (2002).
Google Scholar
Hartshorne, J. K., Tenenbaum, J. B. & Pinker, S. A critical period for second language acquisition: evidence from 2/3 million English speakers. Cognition 177, 263–277 (2018).
Google Scholar
Hensch, T. K. & Quinlan, E. M. Critical periods in amblyopia. Vis. Neurosci. 35, E014 (2018).
Google Scholar
Dromerick, A. W. et al. Critical Period after Stroke Study (CPASS): a phase II clinical trial testing an optimal time for motor recovery after stroke in humans. Proc. Natl Acad. Sci. USA 118, e2026676118 (2021).
Google Scholar
Fawcett, J. W., Oohashi, T. & Pizzorusso, T. The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function. Nat. Rev. Neurosci. 20, 451–465 (2019).
Google Scholar
Venturino, A. et al. Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain. Cell Rep. 36, 109313 (2021).
Google Scholar
Grieco, S. F. et al. Subanesthetic ketamine reactivates adult cortical plasticity to restore vision from amblyopia. Curr. Biol. 30, 3591–3603.e8 (2020).
Google Scholar
Berry, M. & Linder, C. in The Mouse in Biomedical Research 2nd edn (eds Fox, J. G. et al.) 53–78 (Elsevier, 2007).
Bohn, L. M. et al. Enhanced morphine analgesia in mice lacking β-arrestin 2. Science 286, 2495–2498 (1999).
Google Scholar
Frankish, A. et al. GENCODE reference annotation for the human and mouse genomes. Nucleic Acids Res. 47, D766–D773 (2019).
Google Scholar