Combination product for the treatment of neurological and/or psychiatric disorders

11723,894

16/958226

October 26, 2018

The present application provides a combination product for the treatment and/or prevention of psychiatric and/or neurological disorders. The combination product comprises (i) a compound which promotes neurogenesis and has hallucinogenic and/or psychedelic side effects, and (ii) a 5-HT2A receptor antagonist which alleviates and/or removes the hallucinogenic and/or psychedelic side effects caused by the first compound.

Consejo Superior de Investigaciones Cientificas (CSIC) (Madrid, ES); Universidad Autónoma de Madrid (Madrid, ES); CENTRO DE INVESTIGATIÓN BIOMÉDICA EN RED DE ENFERMEDADES NEURODEGENERATIVAS (Madrid, ES); BlumenTech, S.L. (Barcelona, ES); Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau (Barcelona, ES)

TERRAN BIOSCIENCES, INC. (New York, NY, US)

1. A pharmaceutical combination product consisting of active ingredients (i), (ii) and, optionally, a monoamine oxidase inhibitor: (i) a compound described by the following formula (I), or salt thereof: [chemical expression included] wherein, R 1 is selected from the group consisting of methyl, ethyl, n-propyl, allyl and isopropyl; R 2 is selected from the group consisting of methyl, ethyl, n-propyl, allyl and isopropyl; R 3 is selected from the group consisting of hydrogen, methoxy, methyl, hydroxy and a halogen; and R 4 is selected from the group consisting of hydrogen, hydroxy, phosphoryloxy and acetoxy; R 5 is selected from the group consisting of deuterium (2 H) and protium (1 H); and (ii) a 5-HT2A receptor antagonist.

2. The pharmaceutical combination product of claim 1 , wherein the compound described by formula (I) is selected from the group consisting of N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, N,N-diethyltryptamine, N,N-dipropyltryptamine, N,N-diisopropyltryptamine, 4-phosphoryloxy-N,N-dimethyltryptamine, 4-hydroxy-N,N-dimethyltryptamine and O-acetylpsilocin, or salt thereof.

3. The pharmaceutical combination product of claim 1 , wherein the 5-HT2A receptor antagonist is selected from the group consisting of Methiothepin, Ritanserin, Ketanserin, Flibanserin, Methysergide, Trazodone, Nefazodone, Cinitapride, Cyproheptadine, Brexpiprazole, Cariprazine, Agomelatine, Pimavanserin, Eplivanserin, Volinanserin, Altanserin, Setoperone, LY-367,265, 1-(1-Naphthyl)piperazine, SB 206553, Pirenperone, SB-215505, Metergoline, Deramciclane, Amperozide, Glemanserin, 5-MeO-NBpBrT, Adatanserin, AMOA, Cinanserin, Fananserin, Iferanserin, AC-90179, LY86057, GSK-215083, Cyamemazine, Mesulergine, BF-1, LY215840, Sergolexole, Spiramide, LY53857, Amesergide, LY108742, Pipamperone, LY314228 and 5-I-R91150.

4. The pharmaceutical combination product of claim 1 , wherein the combination product is prepared for oral, sublingual, buccal, intranasal, intravenous, intramuscular, subcutaneous, rectal, transdermal, topical and/or inhalation-mediated administration.

5. The pharmaceutical combination product of claim 1 , wherein the compound described by formula (I), or salt thereof, and the 5-HT2A receptor antagonist are physically separated.

6. The pharmaceutical combination product of claim 1 , wherein the 5-HT2A receptor antagonist alleviates or eliminates the hallucinogenic and/or psychedelic side effects caused by the compound described by formula (I).

7. The pharmaceutical combination product of claim 4 , wherein the combination product prepared for oral, sublingual, or buccal administration is contained within one or two tablets, wherein the one or two tablets comprise a therapeutically effective amount of a compound described by formula (I), or salt thereof, and the 5-HT2A receptor antagonist for the treatment of a psychiatric or neurological disorder in a human.

8. The pharmaceutical combination product of claim 7 , wherein the psychiatric disorder is selected from the group consisting of panic disorder, agoraphobia, social anxiety disorder, phobias, post-traumatic stress disorder, obsessive compulsive disorder, generalized anxiety disorder, bipolar disorder, depression, anorexia nervosa, binge eating disorder, bulimia nervosa, psychosis, schizophrenia, substance addiction and personality disorders.

9. The pharmaceutical combination product of claim 7 , wherein the psychiatric disorder is depression, addiction, post-traumatic stress disorder, or a personality disorder.

10. The pharmaceutical combination product of claim 7 , wherein the neurological disorder is Parkinson's Disease.

3075992 January 1963 Hofmann et al.
20120289515 November 2012 Migaly
20140350064 November 2014 Chen
20150231126 August 2015 Peters et al.
20170281652 October 2017 Altschul et al.
20190350949 November 2019 Kucuksen et al.
20200179349 June 2020 Yun et al.
20220273680 September 2022 Scott
WO-2018135943 July 2018
WO-2019081764 May 2019
WO-2021030571 February 2021

Kometer et al., Biol. Psyciatry, 2012, 72(11), pp. 898-906. (Year: 2012). cited by examiner
Marta Valle, et al, “Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual affects of ayahuasca in humans”, European Neuropsychopharmacology, 2016, pp. 1161-1175, 26. cited by applicant
Michael Kometer, et al, “Psilocybin Biases Facial Recognition, Goal-Directed Behavior, and Mood State Toward Positive Relative to Negative Emotions Through Different Serotonergic Subreceptors”, Biological Psychiatry, 2012, pp. 898-906, 72. cited by applicant
Filip Tyls, et al, “Sex differences and serotonergic mechanisms in the behavioural effects of psilocin”, Behavioural Pharmacology, 2016, pp. 309-320, vol. 27, No. 4. cited by applicant
Briony J. Catlow, et al, “Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning”, Experimental Brain Research, 2013, pp. 481-491, 228. cited by applicant
Fred H. Gage, Mammalian Neural Stem Cells, Science, 2000, pp. 1433-1438, vol. 287, No. 5457. cited by applicant
Sally Temple, Stem cell plasticity—building the brain of our dreams, Nature Reviews Neuroscience, Jul. 2001, pp. 513-520, vol. 2. cited by applicant
Clara Herrera-Arozamena, et al, Recent Advances in Neurogenic Small Molecules as Innovative Treatments for Neurodegenerative Diseases, Molecules, 2016, pp. 1-21, 1165. cited by applicant
Shih-Jen Chen, et al, Antidepressant Administration Modulates Neural Stem Cell Survival and Serotoninergic Differentiation Through Bel-2, Current Neurovascular Research, 2007, pp. 19-29, 4. cited by applicant
Maura Boldrini et al, Antidepressants increase neural progenitor cells in the human hippocampus, Neuropsychopharmacology, Oct. 2009, pp. 2376-2389, 34 (11). cited by applicant
Benjamin D. Sachs, et al, Chronic Fluoxetine Increases Extra-Hippocampal Neurogenesis in Adult Mice, International Journal of Neuropsychopharmacology, 2015, pp. 1-12. cited by applicant
Jordi Riba, et al, Human Pharmacology of Ayahuasca: Subjective and Cardiovascular Effects, Monoamine Metabolite Excretion, and Pharmacokinetics, The Journal of Pharmacology and Experimental Therapeutics, 2003, pp. 73-83, vol. 306, No. 1. cited by applicant
Rick J. Strassman, MD., et al, Dose-Response Study of N, N-Dimethyltryptamine in Humans, Archives of General Psychiatry, Feb. 1994, pp. 98-108, vol. 51. cited by applicant
D.J. McKenna, et al, Differential Interactions of Indolealkylamines with 5-Hydroxytryptamine Receptor Subtypes, Neuropharmacology, 1990, pp. 193-198, vol. 29 No 3. cited by applicant
Anna Rickli, et al, Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens, European Neuropharmacology, 2016, pp. 1-11. cited by applicant
Dominique Fontanilla et al, The Hallucinogen N, N-Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator, Science, 2009, pp. 934-937, 323 (5916). cited by applicant
David E. Nichols, Hallucinogens, Pharmacology & Therapeutics 101, 2004, pp. 131-181. cited by applicant
Teruo Hayashi, et al, Sigma-1 Receptor Chaperones at the ER-Mitochondrion Interface Regulate Ca2+ Signaling and Cell Survival, Cell, 2007, pp. 596-610, 131. cited by applicant
Tomohisa Mori et al, Sigma-1 Receptor Chaperone at the ER-Mitochondrion Interface Mediates the Mitochondrion-ER-Nucleus Signaling for Cellular Survival, Plos One, 2013, pp. 1-13, vol. 8 Issue 10. cited by applicant
Arin Dam Pal, et al, The sigma-1 receptor protects against cellular oxidative stress and activates antioxidant response elements, European Journal of Pharmacology, 2012, pp. 12-20, 682 (1-3). cited by applicant
T Omi, et al, Fluvoxamine alleviates ER stress via induction of Sigma-1 receptor, Cell Death and Disease, 2014, 5, e1332. cited by applicant
Atilla Szabo et al, Psychedelic N,N-Dimethyltryptamine and 5-Methoxy-N,N-Dimetheyltryptamine Modulate Innate and Adaptive Inflammatory Responses through the Sigma-1 Receptor of Human Monocyte-Derived Dendritic Cells, Plos One, 2014, pp. 1-12, vol. 9 Issue 8 e106533. cited by applicant
Karsten Ruscher, et al., The involvement of the sigma-1 receptor in neurodegeneration and neurorestoration, Journal of Pharmacological Sciences, 2015, pp. 30-35, 127. cited by applicant
Atilla Szabo, et al, Dimethyltryptamine (DMT): a biochemical Swiss Army knife in neuroinflammation and neuroprotection?, Neural Regeneration Research, 2016, pp. 396-397, vol. 11 Issue 3. cited by applicant
Ede Frecska, et al, The Therapeutic Potentials of Ayahuasca: Possible Effects again Various Diseases of Civlization, Frontiers in Pharmacology, 2016, pp. 1-17, vol. 7 Article 35. cited by applicant
Atilla Szabo, et al, The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells, Frontiers in Neuroscience, 2016, pp. 1-11, vol. 10 Article 423. cited by applicant
Flavia De L Osorio et al, Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report, Revista Brasileira de Psiquiatria, 2015 pp. 13-20, 37. cited by applicant
Roberta Tittarelli et al., Recreational Use, Analysis and Toxicity of Tryptamines, Current Neuropharmacology, 2015 pp. 26-46, 13. cited by applicant
Thomas S. Ray, Psychedelics and the Human Receptorome, Plos One, 2010, pp. 1-17, vol. 5, Issue 2 e9019. cited by applicant
Franz X. Vollenweider, et al, Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action, Neuroreport, 1998, pp. 3897-3902, vol. 9 No 17. cited by applicant
Katrin H. Preller, et al., The Fabric of Meaning and Subjective Effects in LSD Induced States Depend on Serotonin 2A Receptor Activation, Current Biology, 2017, pp. 451-457, 27. cited by applicant
Ya-Zhu Xu, et al, Synthesis of deuterium labeled standards of 5-methoxy-N,N-dimethyltryptamine (5-Meo-DMT), Journal of Labelled Compounds and Radiopharmaceuticals, 2006, pp. 897-902, 49. cited by applicant
Hofmann et al., 168. Psilocybin und Psilocin, Helvetica Chimica Acta, 1959, pp. 1557-1572, vol. 42 No. 5. cited by applicant
Nicholas V. Cozzi, et al, Receptor binding profiles and quantitative structure-affinity relationships of some 5-substituted-N,N-diallyltryptamines, Bioorganic & Medicinal Chemistry Letters, 2016, pp. 959-964, vol. 26 No. 3. cited by applicant
Adam L. Halberstadt et al., Behavioral effects of α,α,β,β-tetradeutero-5-MeO-DMT in rats: comparison with 5-MeO-DMT administered in combination with a monoamine oxidase inhibitor, Psychopharmacology, 2012, pp. 709-718, vol. 221 No. 4. cited by applicant
John M. Beaton et al., A Comparison of the Behavioral Effects of Proteo- and Deutero-N, N-Dimethyltryptamine, Pharmacology Biochemistry & Behavior, 1982, pp. 811-814, vol. 16 No. 5. cited by applicant
Jose A. Morales-Garcia et al., Phosphodiesterase7 Inhibition Activates Adult Neurogenesis in Hippocampus and Subventricular Zone in Vitro and in Vivo, Stem Cells, 2017, pp. 458-472, vol. 35. cited by applicant
Michael T. Heneka, et al., Neuroinflammation in Alzheimer's Disease, Lancet Neurol., 2015, pp. 388-405, vol. 14 No. 4. cited by applicant
Simon D. Brandt, et al, Characterization of the synthesis of N,N-dimethyltryptamine by reductive amination using gas chromatography ion trap mass spectrometry, Drug Testing and Analysis, 2010, pp. 330-338, 2. cited by applicant
Masanori Somei, et al, The Chemistry of Indoles. CVII.1) A Novel Synthesis of 3,4,5,6-Tetrahydro-7-hydroxy-1H-azepino[5,4,3-cd]indoles and a New Finding on Pictet-Spengler Reaction, Chemical and Pharmaceutical Bulletin (Tokyo), 2001, pp. 1159-1165, 49 (9). cited by applicant
Arnt et al. Facilitation of 8-OHDPAT-induced forepaw treading of rats by the 5-HT2 agonist DOI. Eur. J. Pharmacol., 161:45 (1989). cited by applicant
Barrett et al. Emotions and brain function are altered up to one month after a single high dose of psilocybin. Sci. Rep. 10:2214 (2020). cited by applicant
Belmaker et al. Major depressive disorder. N Engl J Med 358:55-68 (2008). cited by applicant
Billings et al. Social-environmental factors in unipolar depression; comparisons of depressed patients and nondepressed controls. J Abnormal Psychol 92:119-133 (1983). cited by applicant
Boulenguez et al. Modulation of dopamine release in the nucleus accumbens by 5-HT1E1 agonists: involvement of the hippocampo-accumbens pathway. Neuropharmacology 35:1521-1529 (1996). cited by applicant
Brun et al. Place cells and place recognition maintained by direct entorhinal-hippocampal circuitry. Science 296:2243-2246 (2002). cited by applicant
Burgdorf et al. Extinction of contextual cocaine memories requires Ca(v)1.2 within D1R-expressing cells and recruits hippocampal Ca(v)1,2-dependent signaling mechanisms. J Neurosci 37:11894-11911 (2017). cited by applicant
Burmeister et al. Differential roles of 5-HT receptor subtypes in cue and cocaine reinstatement of cocaine-seeking behavior in rats. Neuropsychopharmacology 29:660-668 (2004). cited by applicant
Cai et al. Local potentiation of excitatory synapses by serotonin and its alteration in rodent models of depression. Nat Neurosci 16:464-472 (2013). cited by applicant
Canal et al. Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model. Drug Test Anal., 4:556-576 (2012). cited by applicant
Canel et al. Support for 5-HT2C receptor functional selectivity in vivo utilizing structurally diverse, selective 5-HT2C receptor ligands and the 2,5-dimethoxy-4-iodoamphetamine elicited head-twitch response model. Neuropharmacol 70:112-121 (2013). cited by applicant
Carhart-Harris et al. Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Sci. Rep. 7:13187 (2017). cited by applicant
Carhart-Harris et al.: Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry 3: 619-627. Published Online May 17, 2016 (2016). cited by applicant
Carhart-Harris et al.: Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology (Berl). 235(2):399-408 doi:10.1007/s00213-017-4771-x (2018). cited by applicant
Carr et al. The role of serotonin receptor subtypes in treating depression: a review of animal studies, Psychopharmacology (Berl.) 213:265-287 (2011). cited by applicant
Chan et al. Strained in Planning Your Mouse Background? Using the HPA Stress Axis as a Biological Readout for Backcrossing Strategies. Neuropsychopharmacology 42:1749-1751 (2017). cited by applicant
Compass Pathways. Compass Pathways Receives FDA Breakthrough Therapy Designation for Psilocybin Therapy for Treatment-resistant Depression. Available at https://www.prnewswire.com/news-releases/compass-pathways-receives-fda-breakthrough-therapy-designation-for-psilocybin-therapy-for-treatment-resistant-depression-834088100.html (Oct. 23, 2018). cited by applicant
Co-pending U.S. Appl. No. 17/940,950, inventor Thompson; Scott, filed Sep. 8, 2022. cited by applicant
Co-pending U.S. Appl. No. 17/945,865, inventor Clark; Sam, filed Sep. 15, 2022. cited by applicant
Darmani et al., Do functional relationships exist between 5-HT1A and 5-HT2 receptors?. Pharmacol. Biochem. Behav., 36:901-606 (1990). cited by applicant
Dolen et al. Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin. Nature 501:179-184 (2013). cited by applicant
Drysdale et al. Resting-state connectivity biomarkers define neurophysiological subtypes of depression. Nature Med 23:28-38 (2017). cited by applicant
Duman et al. Altered connectivity in depression: GABA and glutamate neurotransmitter deficits and reversal by novel treatments. Neuron 102:75-90 (2019). cited by applicant
Engel et al. Identity of inhibitory presynaptic 5-hydroxytryptamine (5-1-IT) autoreceptors in the rat brain cortex with 5-HT1B binding sites Naunyn Schmiedebergs Arch Pharmacol 332:1-7 (1986). cited by applicant
Evans et al. Default mode connectivity in major depressive disorder measured up to 10 days after ketamine administration. Biol Psychiatry 84:582-590 (2018). cited by applicant
Fava et al. Major depressive disorder. Neuron 28:335-341 (2000). cited by applicant
Furay et al. 5-HT1B mRNA expression after chronic social stress. Behav Brain Res 224:350-357 (2011). cited by applicant
Gaynes et al. What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression. Psychiart Serv. 60:1439-1445 (2009). cited by applicant
Gerfen et al. D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science 250(4986):1429-1432 (1990). cited by applicant
Gothert et al. Classification of serotonin receptors. J Cardiovasc Pharmacol 10 Suppl 3:S3-S7 (1987). cited by applicant
Halberstadt et al. Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Neuropharmacol 61:364-381 (2011). cited by applicant
Hamet et al. Genetics and genomics of depression. Metabolism 54:10-15 (2005). cited by applicant
Hasler et al.: Determination of psilocin and 4-hydroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man. Pharm Acta Helv. 72(3):175-184 (1997). cited by applicant
Hibicke et al. Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression. ACS Chem Neurosci. 11(6):864-871 (2020). cited by applicant
Hoyer et al. International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol Rev 46:157-203 (1994). cited by applicant
Jefsen et al. Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat. Acta Neuropsychiatr. 31:213-219 (2019). cited by applicant
Johnson et al. The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act. Neuropharmacology 142:143-166 (2018). cited by applicant
Kallarackal et al. Chronic stress induces a selective decrease in AIVIPA receptor-mediated synaptic excitation at hippocampal temporoammonic-CA1 synapses. Neurosci 33:15669-15674 (2013). cited by applicant
Keller et al. Permanent alteration of behavior in mice by chemical and psychological means. Science 124:723 (1956). cited by applicant
Kennett et al., In vivo properties of SB 200646A, a 5-HT2C/2B receptor antagonist. J. Pharmacol., 111:797-802 (1994). cited by applicant
Kessler et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 62:593-602 (2005). cited by applicant
Kessler, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. Jun. 18, 2003;289(23):3095-105. cited by applicant
Lee et al. Specific roles of AMPA receptor subunit GluR1 (GluAl) phosphorylation sites in regulating synaptic plasticity in the CA1 region of hippocampus. J Neurephysiol 103:479-489 (2010). cited by applicant
Legates et al. Reward behaviour is regulated by the strength of hippocampus-nucleus accumbens synapses. Nature 564:258-262 (2018). cited by applicant
Legates et al. Sex differences in antidepressant efficacy. Neuropsychopharmacol 44:140-154 (2019). cited by applicant
Li et al. Synaptic potentiation onto habenula neurons in the learned helplessness model of depression. Nature 470:535-539 (2011). cited by applicant
Lim et al. Anhedonia requires MC4R-mediated synaptic adaptations in nucleus act umbens. Nature 87:183-189 (2012). cited by applicant
Ly et al., Psychedelics promote structural and functional neural plasticity. Cell Rep. 23(11):3170-3182 (2018). cited by applicant
Madsen et al.: Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. Neuropsychopharmacology 44(7):1328-1334 (2019). cited by applicant
Mathur et al. Serotonin induces long-term depression at corticostriatal synapses. J Neurosci 31:7402-7411 (2011). cited by applicant
Maura et al. Serotonin autoreceptor in rat hippocampus: pharmacological characterization as a subtype of the 5-HT1 receptor. Naunyn Schmiedebergs Arch Pharmacol 334:323-326 (1986). cited by applicant
McEwen. Stress and hippocampal plasticity. Ann Rev Neurosci 22:105-122 (1999). cited by applicant
Moda-Sava et al. Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation. Science 364(6436):eaaat8078 (2019). cited by applicant
Nautiyal et al. Distinct circuits underlie the effects of 5-HT1B receptors on aggression and impulsivity. Neuron 86:813-826 (2015). cited by applicant
Nestler, et al. Neurobiology of depression. Neuron. Mar. 28, 2002;34(1):13-25. cited by applicant
Nestler et al. The mesolimbic dopamine reward circuit in depression. Biol Psychiatry 59:1151-1159 (2006). cited by applicant
Neumaier et al. Chronic fluoxetine reduces serotonin transporter mRNA and 5-HT1B mRNA in a sequential manner in the rat dorsal raphe nucleus. Neuropsychopharmacology 15:515-522 (1996). cited by applicant
Nichols. Psychedelics. Pharmacol Rev. 68:264-35 (2016). cited by applicant
Nutt et al. Independent Scientific Committee on Drugs. Drug harms in the UK: a multicriteria decision analysis. Lancet 376:1558-1565 (2010). cited by applicant
Nutt et al. Psychedelic Psychiatry's Brave New World. Cell 181:24-28 (2020). cited by applicant
PCT/EP2018/079503 International Search Report and Written Opinion dated Feb. 1, 2019. cited by applicant
PCT/US2020/046149 International Search Report and Written Opinion dated Jan. 11, 2021. cited by applicant
PCT/US2022/023067 International Search Report and Written Opinion dated Jun. 21, 2022. cited by applicant
Remondes et al. Role for a cortical input to hippocampal area CA1 in the consolidation of a long-term memory. Nature 431:699-703 (2004). cited by applicant
Roseman et al. Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Front. Pharmacol. 8:974 (2018). cited by applicant
Roth et al. Serotonin 5-HT2A receptors: molecular biology and mechanisms of regulation. Crit Rev. Neurobiol 12:319-338 (1998). cited by applicant
Svenningsson et al. Alterations in 5-HT(1B) receptor function by p11 in depression-like states. Science 311:77-80 (2006). cited by applicant
Thompson et al. An excitatory synapse hypothesis of depression. Trends Neurosci 38:279-294 (2015). cited by applicant
Tye et al. Dopamine neurons modulate neural encoding and expression of depression-related behaviour. Nature 493:537-541 (2013). cited by applicant
Van Dyke et al. Chronic fluoxetine treatment in vivo enhances excitatory synaptic transmission in the hippocampus. Neumpharmacology 150:38-45 (2019). cited by applicant
Weisstaub et al. Cortical 5-HT2A receptor signaling modulates anxiety-like behaviors in mice. Science 313:536-540 (2006). cited by applicant
Willner. The chronic mild stress (CMS) model of depression: History, evaluation and usage. Neurobiol Stress 6:78-93 (2016). cited by applicant
Winter et al. Psilocybin-induced stimulus control in the rat. Pharmacol Biochem Behav. 87:472-480 (2007). cited by applicant
Yuen et al. Repeated stress causes cognitive impairment by suppressing glutamate receptor expression and function in prefrontal cortex. Neuron 73:962-977 (2012). cited by applicant

edspgr.11723894