Serotonergic Psychedelics: Experimental Approaches for Assessing Mechanisms of Action

  • Clinton E. CanalEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 252)


Recent, well-controlled – albeit small-scale – clinical trials show that serotonergic psychedelics, including psilocybin and lysergic acid diethylamide, possess great promise for treating psychiatric disorders, including treatment-resistant depression. Additionally, fresh results from a deluge of clinical neuroimaging studies are unveiling the dynamic effects of serotonergic psychedelics on functional activity within, and connectivity across, discrete neural systems. These observations have led to testable hypotheses regarding neural processing mechanisms that contribute to psychedelic effects and therapeutic benefits. Despite these advances and a plethora of preclinical and clinical observations supporting a central role for brain serotonin 5-HT2A receptors in producing serotonergic psychedelic effects, lingering and new questions about mechanisms abound. These chiefly pertain to molecular neuropharmacology. This chapter is devoted to illuminating and discussing such questions in the context of preclinical experimental approaches for studying mechanisms of action of serotonergic psychedelics, classic and new.


α-Adrenergic 5-HT2A 5-HT2C Cingulate cortex Head-twitch Ketanserin Psychedelic mechanisms Receptor binding Receptor conformations Receptor dimers Receptor function Serotonin Signal transduction 



1-Propionyl-lysergic acid diethylamide
















5-Hydroxytryptamine (serotonin)










N6-allyl-6-norlysergic acid diethylamide


α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid




2-Bromo-lysergic acid diethylamide


Cannabinoid 1 receptor














3,4-Dihydroxyphenylacetic acid




Inositol 1,4,5-trisphosphate




Lysergic acid diethylamide


Lysergic acid morpholide


Lysergic acid 2,4-dimethylazetidide






Metabotropic glutamate receptor 2




N6-Propynyl-6-norlysergic acid diethylamide


Positron emission tomography


Serotonin transporter


Trace amine-associated receptor 1









This work was supported by grants from the National Institute on Drug Abuse (R21DA040907) and the Department of Defense (W81XWH-17-1-0329). I express my sincere gratitude to Dr. Nader Moniri and Austen Casey for critically reading and providing feedback on an early draft of this manuscript.


  1. Abellan MT, Martin-Ruiz R, Artigas F (2000) Local modulation of the 5-HT release in the dorsal striatum of the rat: an in vivo microdialysis study. Eur Neuropsychopharmacol 10:455–462PubMedGoogle Scholar
  2. Abi-Saab WM, Bubser M, Roth RH, Deutch AY (1999) 5-HT2 receptor regulation of extracellular GABA levels in the prefrontal cortex. Neuropsychopharmacology 20:92–96PubMedGoogle Scholar
  3. Acuna-Castillo C, Villalobos C, Moya PR, Saez P, Cassels BK, Huidobro-Toro JP (2002) Differences in potency and efficacy of a series of phenylisopropylamine/phenylethylamine pairs at 5-HT(2A) and 5-HT(2C) receptors. Br J Pharmacol 136:510–519PubMedPubMedCentralGoogle Scholar
  4. Aghajanian GK, Marek GJ (1997) Serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal cells. Neuropharmacology 36:589–599PubMedGoogle Scholar
  5. Amargos-Bosch M, Bortolozzi A, Puig MV, Serrats J, Adell A, Celada P, Toth M, Mengod G, Artigas F (2004) Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex. Cereb Cortex 14:281–299PubMedGoogle Scholar
  6. Appel JB, West WB, Buggy J (2004) LSD, 5-HT (serotonin), and the evolution of a behavioral assay. Neurosci Biobehav Rev 27:693–701PubMedGoogle Scholar
  7. Atasoy S, Roseman L, Kaelen M, Kringelbach ML, Deco G, Carhart-Harris RL (2017) Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD. Sci Rep 7:17661PubMedPubMedCentralGoogle Scholar
  8. Barclay Z, Dickson L, Robertson DN, Johnson MS, Holland PJ, Rosie R, Sun L, Fleetwood-Walker S, Lutz EM, Mitchell R (2011) 5-HT2A receptor signalling through phospholipase D1 associated with its C-terminal tail. Biochem J 436:651–660PubMedGoogle Scholar
  9. Bécamel C, Gavarini S, Chanrion B, Alonso G, Galeotti N, Dumuis A, Bockaert J, Marin P (2004) The serotonin 5-HT2A and 5-HT2C receptors interact with specific sets of PDZ proteins. J Biol Chem 279:20257–20266PubMedGoogle Scholar
  10. Bécamel C, Berthoux C, Barre A, Marin P (2017) Growing evidence for heterogeneous synaptic localization of 5-HT2A receptors. ACS Chem Neurosci 8:897–899PubMedGoogle Scholar
  11. Beliveau V, Ganz M, Feng L, Ozenne B, Hojgaard L, Fisher PM, Svarer C, Greve DN, Knudsen GM (2017) A high-resolution in vivo atlas of the human brain’s serotonin system. J Neurosci 37:120–128PubMedPubMedCentralGoogle Scholar
  12. Benneyworth MA, Smith RL, Barrett RJ, Sanders-Bush E (2005) Complex discriminative stimulus properties of (+)lysergic acid diethylamide (LSD) in C57Bl/6J mice. Psychopharmacology 179:854–862PubMedGoogle Scholar
  13. Benneyworth MA, Xiang Z, Smith RL, Garcia EE, Conn PJ, Sanders-Bush E (2007) A selective positive allosteric modulator of metabotropic glutamate receptor subtype 2 blocks a hallucinogenic drug model of psychosis. Mol Pharmacol 72:477–484PubMedGoogle Scholar
  14. Benneyworth MA, Smith RL, Sanders-Bush E (2008) Chronic phenethylamine hallucinogen treatment alters behavioral sensitivity to a metabotropic glutamate 2/3 receptor agonist. Neuropsychopharmacology 33:2206–2216PubMedGoogle Scholar
  15. Berg KA, Maayani S, Goldfarb J, Scaramellini C, Leff P, Clarke WP (1998) Effector pathway-dependent relative efficacy at serotonin type 2A and 2C receptors: evidence for agonist-directed trafficking of receptor stimulus. Mol Pharmacol 54:94–104PubMedGoogle Scholar
  16. Best AR, Regehr WG (2008) Serotonin evokes endocannabinoid release and retrogradely suppresses excitatory synapses. J Neurosci 28:6508–6515PubMedPubMedCentralGoogle Scholar
  17. Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB (2014) Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes. Psychopharmacology 231:4135–4144PubMedPubMedCentralGoogle Scholar
  18. Boess FG, Martin IL (1994) Molecular biology of 5-HT receptors. Neuropharmacology 33:275–317PubMedGoogle Scholar
  19. Bonhaus DW, Bach C, DeSouza A, Salazar FH, Matsuoka BD, Zuppan P, Chan HW, Eglen RM (1995) The pharmacology and distribution of human 5-hydroxytryptamine2B (5-HT2B) receptor gene products: comparison with 5-HT2A and 5-HT2C receptors. Br J Pharmacol 115:622–628PubMedPubMedCentralGoogle Scholar
  20. Bortolozzi A, Amargos-Bosch M, Adell A, Diaz-Mataix L, Serrats J, Pons S, Artigas F (2003) In vivo modulation of 5-hydroxytryptamine release in mouse prefrontal cortex by local 5-HT(2A) receptors: effect of antipsychotic drugs. Eur J Neurosci 18:1235–1246PubMedGoogle Scholar
  21. Braden MR, Nichols DE (2007) Assessment of the roles of serines 5.43(239) and 5.46(242) for binding and potency of agonist ligands at the human serotonin 5-HT2A receptor. Mol Pharmacol 72:1200–1209PubMedGoogle Scholar
  22. Braden MR, Parrish JC, Naylor JC, Nichols DE (2006) Molecular interaction of serotonin 5-HT2A receptor residues Phe339(6.51) and Phe340(6.52) with superpotent N-benzyl phenethylamine agonists. Mol Pharmacol 70:1956–1964PubMedGoogle Scholar
  23. Brandt SD, Kavanagh PV, Westphal F, Stratford A, Elliott SP, Hoang K, Wallach J, Halberstadt AL (2016) Return of the lysergamides. Part I: Analytical and behavioural characterization of 1-propionyl-d-lysergic acid diethylamide (1P-LSD). Drug Test Anal 8:891–902PubMedGoogle Scholar
  24. Brandt SD, Kavanagh PV, Twamley B, Westphal F, Elliott SP, Wallach J, Stratford A, Klein LM, McCorvy JD, Nichols DE, Halberstadt AL (2017a) Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM-775). Drug Test Anal. PubMedPubMedCentralGoogle Scholar
  25. Brandt SD, Kavanagh PV, Westphal F, Elliott SP, Wallach J, Colestock T, Burrow TE, Chapman SJ, Stratford A, Nichols DE, Halberstadt AL (2017b) Return of the lysergamides. Part II: Analytical and behavioural characterization of N6 -allyl-6-norlysergic acid diethylamide (AL-LAD) and (2’S,4’S)-lysergic acid 2,4-dimethylazetidide (LSZ). Drug Test Anal 9:38–50PubMedGoogle Scholar
  26. Brea J, Castro M, Giraldo J, Lopez-Gimenez JF, Padin JF, Quintian F, Cadavid MI, Vilaro MT, Mengod G, Berg KA, Clarke WP, Vilardaga JP, Milligan G, Loza MI (2009) Evidence for distinct antagonist-revealed functional states of 5-hydroxytryptamine(2A) receptor homodimers. Mol Pharmacol 75:1380–1391PubMedGoogle Scholar
  27. Bucher ES, Wightman RM (2015) Electrochemical analysis of neurotransmitters. Annu Rev Anal Chem (Palo Alto, Calif) 8:239–261Google Scholar
  28. Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, Darland T, Suchland KL, Pasumamula S, Kennedy JL, Olson SB, Magenis RE, Amara SG, Grandy DK (2001) Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor. Mol Pharmacol 60:1181–1188PubMedGoogle Scholar
  29. Burris KD, Breeding M, Sanders-Bush E (1991) (+)Lysergic acid diethylamide, but not its nonhallucinogenic congeners, is a potent serotonin 5HT1C receptor agonist. J Pharmacol Exp Ther 258:891–896PubMedGoogle Scholar
  30. Butelman ER, Rus S, Prisinzano TE, Kreek MJ (2010) The discriminative effects of the kappa-opioid hallucinogen salvinorin A in nonhuman primates: dissociation from classic hallucinogen effects. Psychopharmacology 210:253–262PubMedPubMedCentralGoogle Scholar
  31. Canal CE, Morgan D (2012) 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 4:556–576PubMedPubMedCentralGoogle Scholar
  32. Canal CE, Olaghere da Silva UB, Gresch PJ, Watt EE, Sanders-Bush E, Airey DC (2010) The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen. Psychopharmacology 209:163–174PubMedPubMedCentralGoogle Scholar
  33. Canal CE, Cordova-Sintjago TC, Villa NY, Fang LJ, Booth RG (2011) Drug discovery targeting human 5-HT(2C) receptors: residues S3.36 and Y7.43 impact ligand-binding pocket structure via hydrogen bond formation. Eur J Pharmacol 673:1–12PubMedPubMedCentralGoogle Scholar
  34. Canal CE, Booth RG, Morgan D (2013a) 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. Neuropharmacology 70:112–121PubMedPubMedCentralGoogle Scholar
  35. Canal CE, Cordova-Sintjago T, Liu Y, Kim MS, Morgan D, Booth RG (2013b) Molecular pharmacology and ligand docking studies reveal a single amino acid difference between mouse and human serotonin 5-HT2A receptors that impacts behavioral translation of novel 4-phenyl-2-dimethylaminotetralin ligands. J Pharmacol Exp Ther 347:705–716PubMedPubMedCentralGoogle Scholar
  36. Canal CE, Felsing DE, Liu Y, Zhu W, Wood JT, Perry CK, Vemula R, Booth RG (2015) An orally active phenylaminotetralin-chemotype serotonin 5-HT7 and 5-HT1A receptor partial agonist that corrects motor stereotypy in mouse models. ACS Chem Neurosci 6:1259–1270PubMedGoogle Scholar
  37. Canton H, Verriele L, Millan MJ (1994) Competitive antagonism of serotonin (5-HT)2C and 5-HT2A receptor-mediated phosphoinositide (PI) turnover by clozapine in the rat: a comparison to other antipsychotics. Neurosci Lett 181:65–68PubMedGoogle Scholar
  38. Carbonaro TM, Eshleman AJ, Forster MJ, Cheng K, Rice KC, Gatch MB (2015) The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice. Psychopharmacology 232:275–284PubMedGoogle Scholar
  39. Carhart-Harris RL, Erritzoe D, Williams T, Stone JM, Reed LJ, Colasanti A, Tyacke RJ, Leech R, Malizia AL, Murphy K, Hobden P, Evans J, Feilding A, Wise RG, Nutt DJ (2012) Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proc Natl Acad Sci 109:2138–2143PubMedGoogle Scholar
  40. Carhart-Harris RL, Leech R, Hellyer PJ, Shanahan M, Feilding A, Tagliazucchi E, Chialvo DR, Nutt D (2014) The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Front Hum Neurosci 8:20PubMedPubMedCentralGoogle Scholar
  41. Carhart-Harris RL, Muthukumaraswamy S, Roseman L, Kaelen M, Droog W, Murphy K, Tagliazucchi E, Schenberg EE, Nest T, Orban C, Leech R, Williams LT, Williams TM, Bolstridge M, Sessa B, McGonigle J, Sereno MI, Nichols D, Hellyer PJ, Hobden P, Evans J, Singh KD, Wise RG, Curran HV, Feilding A, Nutt DJ (2016) Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proc Natl Acad Sci U S A 113:4853–4858PubMedPubMedCentralGoogle Scholar
  42. Carhart-Harris RL, Roseman L, Bolstridge M, Demetriou L, Pannekoek JN, Wall MB, Tanner M, Kaelen M, McGonigle J, Murphy K, Leech R, Curran HV, Nutt DJ (2017) Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Sci Rep 7:13187PubMedPubMedCentralGoogle Scholar
  43. Ceci C, Proietti Onori M, Macri S, Laviola G (2015) Interaction between the endocannabinoid and serotonergic system in the exhibition of head twitch response in four mouse strains. Neurotox Res 27:275–283PubMedGoogle Scholar
  44. Chambers JJ, Nichols DE (2002) A homology-based model of the human 5-HT2A receptor derived from an in silico activated G-protein coupled receptor. J Comput Aided Mol Des 16:511–520PubMedGoogle Scholar
  45. Cheng Y, Prusoff WH (1973) Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50% inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22:3099–3108PubMedGoogle Scholar
  46. Choudhary MS, Sachs N, Uluer A, Glennon RA, Westkaemper RB, Roth BL (1995) Differential ergoline and ergopeptine binding to 5-hydroxytryptamine2A receptors: ergolines require an aromatic residue at position 340 for high affinity binding. Mol Pharmacol 47:450–457PubMedGoogle Scholar
  47. Clark LD, Bliss EL (1957) Psychopharmacological studies of lysergic acid diethylamide (LSD-25) intoxication; effects of premedication with BOL-128 (2-bromo-d-lysergic acid diethylamide), mescaline, atropine, amobarbital, and chlorpromazine. AMA Arch Neurol Psychiatry 78:653–655PubMedGoogle Scholar
  48. Cordova-Sintjago T, Villa N, Fang L, Booth RG (2014) Aromatic interactions impact ligand binding and function at serotonin 5-HT2C G protein-coupled receptors: receptor homology modeling, ligand docking, and molecular dynamics results validated by experimental studies. Mol Phys 112:398–407PubMedGoogle Scholar
  49. Corne SJ, Pickering RW (1967) A possible correlation between drug-induced hallucinations in man and a behavioural response in mice. Psychopharmacologia 11:65–78PubMedGoogle Scholar
  50. Cozzi NV, Daley PF (2016) Receptor binding profiles and quantitative structure-affinity relationships of some 5-substituted-N,N-diallyltryptamines. Bioorg Med Chem Lett 26:959–964PubMedGoogle Scholar
  51. Cussac D, Boutet-Robinet E, Ailhaud MC, Newman-Tancredi A, Martel JC, Danty N, Rauly-Lestienne I (2008) Agonist-directed trafficking of signalling at serotonin 5-HT2A, 5-HT2B and 5-HT2C-VSV receptors mediated Gq/11 activation and calcium mobilisation in CHO cells. Eur J Pharmacol 594:32–38PubMedGoogle Scholar
  52. Dakic V, Minardi Nascimento J, Costa Sartore R, Maciel RM, de Araujo DB, Ribeiro S, Martins-de-Souza D, Rehen SK (2017) Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT. Sci Rep 7:12863PubMedPubMedCentralGoogle Scholar
  53. Darmani NA (1998) Cocaine and selective monoamine uptake blockers (sertraline, nisoxetine, and GBR 12935) prevent the d-fenfluramine-induced head-twitch response in mice. Pharmacol Biochem Behav 60:83–90PubMedGoogle Scholar
  54. Darmani NA (2001) Cannabinoids of diverse structure inhibit two DOI-induced 5-HT(2A) receptor-mediated behaviors in mice. Pharmacol Biochem Behav 68:311–317PubMedGoogle Scholar
  55. Darmani NA, Pandya DK (2000) Involvement of other neurotransmitters in behaviors induced by the cannabinoid CB1 receptor antagonist SR 141716A in naive mice. J Neural Transm (Vienna) 107:931–945Google Scholar
  56. Darmani NA, Reeves SL (1996) The mechanism by which the selective 5-HT1A receptor antagonist S-(-) UH 301 produces head-twitches in mice. Pharmacol Biochem Behav 55:1–10PubMedGoogle Scholar
  57. Darmani NA, Mock OB, Towns LC, Gerdes CF (1994) The head-twitch response in the least shrew (Cryptotis parva) is a 5-HT2- and not a 5-HT1C-mediated phenomenon. Pharmacol Biochem Behav 48:383–396PubMedGoogle Scholar
  58. Darmani NA, Janoyan JJ, Kumar N, Crim JL (2003) Behaviorally active doses of the CB1 receptor antagonist SR 141716A increase brain serotonin and dopamine levels and turnover. Pharmacol Biochem Behav 75:777–787PubMedGoogle Scholar
  59. De Gregorio D, Posa L, Ochoa-Sanchez R, McLaughlin R, Maione S, Comai S, Gobbi G (2016) The hallucinogen d-lysergic diethylamide (LSD) decreases dopamine firing activity through 5-HT1A, D2 and TAAR1 receptors. Pharmacol Res 113:81–91PubMedGoogle Scholar
  60. de Witte WE, Danhof M, van der Graaf PH, de Lange EC (2016) In vivo target residence time and kinetic selectivity: the association rate constant as determinant. Trends Pharmacol Sci 37:831–842PubMedGoogle Scholar
  61. Delille HK, Becker JM, Burkhardt S, Bleher B, Terstappen GC, Schmidt M, Meyer AH, Unger L, Marek GJ, Mezler M (2012) Heterocomplex formation of 5-HT2A-mGlu2 and its relevance for cellular signaling cascades. Neuropharmacology 62:2184–2191PubMedGoogle Scholar
  62. DeVree BT, Mahoney JP, Vélez-Ruiz GA, Rasmussen SGF, Kuszak AJ, Edwald E, Fung J-J, Manglik A, Masureel M, Du Y, Matt RA, Pardon E, Steyaert J, Kobilka BK, Sunahara RK (2016) Allosteric coupling from G protein to the agonist-binding pocket in GPCRs. Nature 535:182PubMedPubMedCentralGoogle Scholar
  63. Di Matteo V, Di Giovanni G, Di Mascio M, Esposito E (2000) Biochemical and electrophysiological evidence that RO 60-0175 inhibits mesolimbic dopaminergic function through serotonin(2C) receptors. Brain Res 865:85–90PubMedGoogle Scholar
  64. Dittrich A (1998) The standardized psychometric assessment of altered states of consciousness (ASCs) in humans. Pharmacopsychiatry 31(Suppl 2):80–84PubMedGoogle Scholar
  65. Domenech T, Beleta J, Palacios JM (1997) Characterization of human serotonin 1D and 1B receptors using [3H]-GR-125743, a novel radiolabelled serotonin 5HT1D/1B receptor antagonist. Naunyn Schmiedeberg’s Arch Pharmacol 356:328–334Google Scholar
  66. Done CJ, Sharp T (1992) Evidence that 5-HT2 receptor activation decreases noradrenaline release in rat hippocampus in vivo. Br J Pharmacol 107:240–245PubMedPubMedCentralGoogle Scholar
  67. Du C, Collins W, Cantley W, Sood D, Kaplan DL (2017) Tutorials for electrophysiological recordings in neuronal tissue engineering. ACS Biomater Sci Eng 3:2235–2246Google Scholar
  68. Dursun SM, Handley SL (1993) The effects of alpha 2-adrenoceptor antagonists on the inhibition of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head shakes by 5-HT1A receptor agonists in the mouse. Br J Pharmacol 109:1046–1052PubMedPubMedCentralGoogle Scholar
  69. Egan CT, Herrick-Davis K, Miller K, Glennon RA, Teitler M (1998a) Agonist activity of LSD and lisuride at cloned 5HT2A and 5HT2C receptors. Psychopharmacology 136:409–414PubMedGoogle Scholar
  70. Egan CT, Herrick-Davis K, Teitler M (1998b) Creation of a constitutively activated state of the 5-hydroxytryptamine2A receptor by site-directed mutagenesis: inverse agonist activity of antipsychotic drugs. J Pharmacol Exp Ther 286:85–90PubMedGoogle Scholar
  71. Egan C, Grinde E, Dupre A, Roth BL, Hake M, Teitler M, Herrick-Davis K (2000) Agonist high and low affinity state ratios predict drug intrinsic activity and a revised ternary complex mechanism at serotonin 5-HT(2A) and 5-HT(2C) receptors. Synapse 35:144–150PubMedGoogle Scholar
  72. Egashira N, Mishima K, Uchida T, Hasebe N, Nagai H, Mizuki A, Iwasaki K, Ishii H, Nishimura R, Shoyama Y, Fujiwara M (2004) Anandamide inhibits the DOI-induced head-twitch response in mice. Psychopharmacology 171:382–389PubMedGoogle Scholar
  73. Egashira N, Shirakawa A, Okuno R, Mishima K, Iwasaki K, Oishi R, Fujiwara M (2011) Role of endocannabinoid and glutamatergic systems in DOI-induced head-twitch response in mice. Pharmacol Biochem Behav 99:52–58PubMedGoogle Scholar
  74. Fantegrossi WE, Harrington AW, Eckler JR, Arshad S, Rabin RA, Winter JC, Coop A, Rice KC, Woods JH (2005) Hallucinogen-like actions of 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7) in mice and rats. Psychopharmacology 181:496–503PubMedGoogle Scholar
  75. Fantegrossi WE, Harrington AW, Kiessel CL, Eckler JR, Rabin RA, Winter JC, Coop A, Rice KC, Woods JH (2006) Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Pharmacol Biochem Behav 83:122–129PubMedGoogle Scholar
  76. Fantegrossi WE, Reissig CJ, Katz EB, Yarosh HL, Rice KC, Winter JC (2008) Hallucinogen-like effects of N,N-dipropyltryptamine (DPT): possible mediation by serotonin 5-HT1A and 5-HT2A receptors in rodents. Pharmacol Biochem Behav 88:358–365PubMedGoogle Scholar
  77. Fantegrossi WE, Simoneau J, Cohen MS, Zimmerman SM, Henson CM, Rice KC, Woods JH (2010) Interaction of 5-HT2A and 5-HT2C receptors in R(-)-2,5-dimethoxy-4-iodoamphetamine-elicited head twitch behavior in mice. J Pharmacol Exp Ther 335:728–734PubMedPubMedCentralGoogle Scholar
  78. Felder CC, Kanterman RY, Ma AL, Axelrod J (1990) Serotonin stimulates phospholipase A2 and the release of arachidonic acid in hippocampal neurons by a type 2 serotonin receptor that is independent of inositolphospholipid hydrolysis. Proc Natl Acad Sci U S A 87:2187–2191PubMedPubMedCentralGoogle Scholar
  79. Fiorella D, Rabin RA, Winter JC (1995) The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs. I: antagonist correlation analysis. Psychopharmacology 121:347–356PubMedGoogle Scholar
  80. Fontanilla D, Johannessen M, Hajipour AR, Cozzi NV, Jackson MB, Ruoho AE (2009) The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator. Science 323:934–937PubMedPubMedCentralGoogle Scholar
  81. Freedman DX, Giarman NJ (1962) LSD-25 and the status and level of brain serotonin. Ann N Y Acad Sci 96:98–107PubMedGoogle Scholar
  82. Freud S, Byck R (1975) Cocaine papers. Stonehill, New YorkGoogle Scholar
  83. Garcia EE, Smith RL, Sanders-Bush E (2007) Role of G(q) protein in behavioral effects of the hallucinogenic drug 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane. Neuropharmacology 52:1671–1677PubMedPubMedCentralGoogle Scholar
  84. Gatch MB, Rutledge MA, Carbonaro T, Forster MJ (2009) Comparison of the discriminative stimulus effects of dimethyltryptamine with different classes of psychoactive compounds in rats. Psychopharmacology 204:715–724PubMedPubMedCentralGoogle Scholar
  85. Gatch MB, Dolan SB, Forster MJ (2017) Locomotor and discriminative stimulus effects of four novel hallucinogens in rodents. Behav Pharmacol 28:375–385PubMedPubMedCentralGoogle Scholar
  86. Gellman RL, Aghajanian GK (1994) Serotonin2 receptor-mediated excitation of interneurons in piriform cortex: antagonism by atypical antipsychotic drugs. Neuroscience 58:515–525PubMedGoogle Scholar
  87. Ghoneim OM, Legere JA, Golbraikh A, Tropsha A, Booth RG (2006) Novel ligands for the human histamine H1 receptor: synthesis, pharmacology, and comparative molecular field analysis studies of 2-dimethylamino-5-(6)-phenyl-1,2,3,4-tetrahydronaphthalenes. Bioorg Med Chem 14:6640–6658PubMedGoogle Scholar
  88. Giarman NJ, Freedman DX (1965) Biochemical aspects of the actions of psychotomimetic drugs. Pharmacol Rev 17:1–25PubMedGoogle Scholar
  89. Glennon RA (1991) Discriminative stimulus properties of hallucinogens and related designer drugs. NIDA Res Monogr 116:25–44Google Scholar
  90. Glennon RA (1992) Animal models for assessing hallucinogenic agents. In: Boulton AA, Baker GB, Wu PH (eds) Animal models of drug addiction. Humana Press, Totowa, pp 345–381Google Scholar
  91. Glennon RA (2017) The 2014 Philip S. Portoghese Medicinal Chemistry Lectureship: the “Phenylalkylaminome” with a focus on selected drugs of abuse. J Med Chem 60:2605–2628PubMedPubMedCentralGoogle Scholar
  92. Glennon RA, Young R (2011) Drug discrimination: applications to medicinal chemistry and drug studies. Wiley, HobokenGoogle Scholar
  93. Glennon RA, Young R, Rosecrans JA (1983) Antagonism of the effects of the hallucinogen DOM and the purported 5-HT agonist quipazine by 5-HT2 antagonists. Eur J Pharmacol 91:189–196PubMedGoogle Scholar
  94. Glennon RA, Titeler M, McKenney JD (1984) Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sci 35:2505–2511PubMedGoogle Scholar
  95. Glennon RA, Higgs R, Young R, Issa H (1992) Further studies on N-methyl-1(3,4-methylenedioxyphenyl)-2-aminopropane as a discriminative stimulus: antagonism by 5-hydroxytryptamine3 antagonists. Pharmacol Biochem Behav 43:1099–1106PubMedGoogle Scholar
  96. Gobert A, Millan MJ (1999) Serotonin (5-HT)2A receptor activation enhances dialysate levels of dopamine and noradrenaline, but not 5-HT, in the frontal cortex of freely-moving rats. Neuropharmacology 38:315–317PubMedGoogle Scholar
  97. Gonzalez-Maeso J, Weisstaub NV, Zhou M, Chan P, Ivic L, Ang R, Lira A, Bradley-Moore M, Ge Y, Zhou Q, Sealfon SC, Gingrich JA (2007) Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior. Neuron 53:439–452PubMedGoogle Scholar
  98. Gonzalez-Maeso J, Ang RL, Yuen T, Chan P, Weisstaub NV, Lopez-Gimenez JF, Zhou M, Okawa Y, Callado LF, Milligan G, Gingrich JA, Filizola M, Meana JJ, Sealfon SC (2008) Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 452:93–97PubMedPubMedCentralGoogle Scholar
  99. Goodwin GM, Green AR (1985) A behavioural and biochemical study in mice and rats of putative selective agonists and antagonists for 5-HT1 and 5-HT2 receptors. Br J Pharmacol 84:743–753PubMedPubMedCentralGoogle Scholar
  100. Gresch PJ, Barrett RJ, Sanders-Bush E, Smith RL (2007) 5-Hydroxytryptamine (serotonin)2A receptors in rat anterior cingulate cortex mediate the discriminative stimulus properties of d-lysergic acid diethylamide. J Pharmacol Exp Ther 320:662–669PubMedGoogle Scholar
  101. Griebel G, Pichat P, Boulay D, Naimoli V, Potestio L, Featherstone R, Sahni S, Defex H, Desvignes C, Slowinski F, Vige X, Bergis OE, Sher R, Kosley R, Kongsamut S, Black MD, Varty GB (2016) The mGluR2 positive allosteric modulator, SAR218645, improves memory and attention deficits in translational models of cognitive symptoms associated with schizophrenia. Sci Rep 6:35320PubMedPubMedCentralGoogle Scholar
  102. Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA (2016) Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol 30:1181–1197PubMedPubMedCentralGoogle Scholar
  103. Grundmann M, Kostenis E (2017) Temporal bias: time-encoded dynamic GPCR signaling. Trends Pharmacol Sci 38:1110–1124PubMedGoogle Scholar
  104. Gudelsky GA, Yamamoto BK, Nash JF (1994) Potentiation of 3,4-methylenedioxymethamphetamine-induced dopamine release and serotonin neurotoxicity by 5-HT2 receptor agonists. Eur J Pharmacol 264:325–330PubMedGoogle Scholar
  105. Halberstadt AL (2017) Pharmacology and toxicology of N-benzylphenethylamine (“NBOMe”) hallucinogens. Curr Top Behav Neurosci 32:283–311PubMedGoogle Scholar
  106. Halberstadt AL, Geyer MA (2013) Characterization of the head-twitch response induced by hallucinogens in mice: detection of the behavior based on the dynamics of head movement. Psychopharmacology 227:727–739PubMedGoogle Scholar
  107. Halberstadt AL, Geyer MA (2014) Effects of the hallucinogen 2,5-dimethoxy-4-iodophenethylamine (2C-I) and superpotent N-benzyl derivatives on the head twitch response. Neuropharmacology 77:200–207PubMedGoogle Scholar
  108. Halberstadt AL, Geyer MA (2017) Effect of hallucinogens on unconditioned behavior. Curr Top Behav Neurosci. Google Scholar
  109. Halberstadt AL, Koedood L, Powell SB, Geyer MA (2011) Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice. J Psychopharmacol 25:1548–1561PubMedGoogle Scholar
  110. Hartman JL, Northup JK (1996) Functional reconstitution in situ of 5-hydroxytryptamine2c (5HT2c) receptors with alphaq and inverse agonism of 5HT2c receptor antagonists. J Biol Chem 271:22591–22597PubMedGoogle Scholar
  111. Herrick-Davis K, Grinde E, Teitler M (2000) Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors. J Pharmacol Exp Ther 295:226–232PubMedGoogle Scholar
  112. Hide I, Kato T, Yamawaki S (1989) In vivo determination of 5-hydroxytryptamine receptor-stimulated phosphoinositide turnover in rat brain. J Neurochem 53:556–560PubMedGoogle Scholar
  113. Hoffmann C, Leitz MR, Oberdorf-Maass S, Lohse MJ, Klotz K-N (2004) Comparative pharmacology of human β-adrenergic receptor subtypes – characterization of stably transfected receptors in CHO cells. Naunyn Schmiedeberg’s Arch Pharmacol 369:151–159Google Scholar
  114. Hua T, Vemuri K, Pu M, Qu L, Han GW, Wu Y, Zhao S, Shui W, Li S, Korde A, Laprairie RB, Stahl EL, Ho JH, Zvonok N, Zhou H, Kufareva I, Wu B, Zhao Q, Hanson MA, Bohn LM, Makriyannis A, Stevens RC, Liu ZJ (2016) Crystal structure of the human cannabinoid receptor CB1. Cell 167(750–762):e14Google Scholar
  115. Hua T, Vemuri K, Nikas SP, Laprairie RB, Wu Y, Qu L, Pu M, Korde A, Jiang S, Ho JH, Han GW, Ding K, Li X, Liu H, Hanson MA, Zhao S, Bohn LM, Makriyannis A, Stevens RC, Liu ZJ (2017) Crystal structures of agonist-bound human cannabinoid receptor CB1. Nature 547:468–471PubMedPubMedCentralGoogle Scholar
  116. Isbell H, Logan CR (1957) Studies on the diethylamide of lysergic acid (LSD-25). II. Effects of chlorpromazine, azacyclonol, and reserpine on the intensity of the LSD-reaction. A M A Arch Neurol Psychiatry 77:350–358Google Scholar
  117. Isberg V, Balle T, Sander T, Jorgensen FS, Gloriam DE (2011) G protein- and agonist-bound serotonin 5-HT2A receptor model activated by steered molecular dynamics simulations. J Chem Inf Model 51:315–325PubMedGoogle Scholar
  118. Iversen L, Gibbons S, Treble R, Setola V, Huang X-P, Roth BL (2013) Neurochemical profiles of some novel psychoactive substances. Eur J Pharmacol 700:147–151PubMedGoogle Scholar
  119. Jensen AA, McCorvy JD, Leth-Petersen S, Bundgaard C, Liebscher G, Kenakin TP, Brauner-Osborne H, Kehler J, Kristensen JL (2017) Detailed characterization of the in vitro pharmacological and pharmacokinetic properties of N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine (25CN-NBOH), a highly selective and brain-penetrant 5-HT2A receptor agonist. J Pharmacol Exp Ther 361:441–453PubMedGoogle Scholar
  120. Johansen A, Hansen HD, Svarer C, Lehel S, Leth-Petersen S, Kristensen JL, Gillings N, Knudsen GM (2017) The importance of small polar radiometabolites in molecular neuroimaging: a PET study with [(11)C]Cimbi-36 labeled in two positions. J Cereb Blood Flow Metab. Google Scholar
  121. Jope RS, Song L, Powers R (1994) [3H]PtdIns hydrolysis in postmortem human brain membranes is mediated by the G-proteins Gq/11 and phospholipase C-beta. Biochem J 304(Pt 2):655–659PubMedPubMedCentralGoogle Scholar
  122. Kadamur G, Ross EM (2013) Mammalian phospholipase C. Annu Rev Physiol 75:127–154PubMedGoogle Scholar
  123. Karaki S, Becamel C, Murat S, Mannoury la Cour C, Millan MJ, Prezeau L, Bockaert J, Marin P, Vandermoere F (2014) Quantitative phosphoproteomics unravels biased phosphorylation of serotonin 2A receptor at Ser280 by hallucinogenic versus nonhallucinogenic agonists. Mol Cell Proteomics 13:1273–1285PubMedPubMedCentralGoogle Scholar
  124. Katritch V, Cherezov V, Stevens RC (2013) Structure-function of the G protein-coupled receptor superfamily. Annu Rev Pharmacol Toxicol 53:531–556PubMedGoogle Scholar
  125. Kehne JH, Baron BM, Carr AA, Chaney SF, Elands J, Feldman DJ, Frank RA, van Giersbergen PL, McCloskey TC, Johnson MP, McCarty DR, Poirot M, Senyah Y, Siegel BW, Widmaier C (1996) Preclinical characterization of the potential of the putative atypical antipsychotic MDL 100,907 as a potent 5-HT2A antagonist with a favorable CNS safety profile. J Pharmacol Exp Ther 277:968–981PubMedGoogle Scholar
  126. Keller DL, Umbreit WW (1956) Permanent alteration of behavior in mice by chemical and psychological means. Science 124:723–724PubMedGoogle Scholar
  127. Kenakin T (2016) Measurement of receptor signaling bias. Curr Protoc Pharmacol 74:2–15PubMedGoogle Scholar
  128. Kennedy RT (2013) Emerging trends in in vivo neurochemical monitoring by microdialysis. Curr Opin Chem Biol 17:860–867PubMedGoogle Scholar
  129. Kometer M, Vollenweider FX (2016) Serotonergic hallucinogen-induced visual perceptual alterations. Curr Top Behav Neurosci. Google Scholar
  130. Kometer M, Schmidt A, Bachmann R, Studerus E, Seifritz E, Vollenweider FX (2012) Psilocybin biases facial recognition, goal-directed behavior, and mood state toward positive relative to negative emotions through different serotonergic subreceptors. Biol Psychiatry 72:898–906PubMedGoogle Scholar
  131. Kometer M, Schmidt A, Jancke L, Vollenweider FX (2013) Activation of serotonin 2A receptors underlies the psilocybin-induced effects on alpha oscillations, N170 visual-evoked potentials, and visual hallucinations. J Neurosci 33:10544–10551PubMedGoogle Scholar
  132. Kraehenmann R, Pokorny D, Vollenweider L, Preller KH, Pokorny T, Seifritz E, Vollenweider FX (2017) Dreamlike effects of LSD on waking imagery in humans depend on serotonin 2A receptor activation. Psychopharmacology 234:2031–2046PubMedGoogle Scholar
  133. Kroeze WK, Hufeisen SJ, Popadak BA, Renock SM, Steinberg S, Ernsberger P, Jayathilake K, Meltzer HY, Roth BL (2003) H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology 28:519–526PubMedGoogle Scholar
  134. Kurrasch-Orbaugh DM, Parrish JC, Watts VJ, Nichols DE (2003a) A complex signaling cascade links the serotonin2A receptor to phospholipase A2 activation: the involvement of MAP kinases. J Neurochem 86:980–991PubMedGoogle Scholar
  135. Kurrasch-Orbaugh DM, Watts VJ, Barker EL, Nichols DE (2003b) Serotonin 5-hydroxytryptamine 2A receptor-coupled phospholipase C and phospholipase A2 signaling pathways have different receptor reserves. J Pharmacol Exp Ther 304:229–237PubMedGoogle Scholar
  136. Lee MY, Chiang CC, Chiu HY, Chan MH, Chen HH (2014) N-acetylcysteine modulates hallucinogenic 5-HT(2A) receptor agonist-mediated responses: behavioral, molecular, and electrophysiological studies. Neuropharmacology 81:215–223PubMedGoogle Scholar
  137. Leysen JE, Eens A, Gommeren W, Van Gompel P, Wynants J, Janssen PA (1987) Non-serotonergic [3H]ketanserin binding sites in striatal membranes are associated with a dopac release system on dopaminergic nerve endings. Eur J Pharmacol 134:373–375PubMedGoogle Scholar
  138. Leysen JE, Janssen PM, Schotte A, Luyten WH, Megens AA (1993) Interaction of antipsychotic drugs with neurotransmitter receptor sites in vitro and in vivo in relation to pharmacological and clinical effects: role of 5HT2 receptors. Psychopharmacology 112:S40–S54PubMedGoogle Scholar
  139. Li JX, Rice KC, France CP (2007) Behavioral effects of dipropyltryptamine in rats: evidence for 5-HT1A and 5-HT2A agonist activity. Behav Pharmacol 18:283–288PubMedGoogle Scholar
  140. Li JX, Rice KC, France CP (2009a) Discriminative stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane in rhesus monkeys: antagonism and apparent pA2 analyses. J Pharmacol Exp Ther 328:976–981PubMedGoogle Scholar
  141. Li JX, Unzeitig A, Javors MA, Rice KC, Koek W, France CP (2009b) Discriminative stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), ketanserin, and (R)-(+)-{alpha}-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-pipidinemetha nol (MDL100907) in rats. J Pharmacol Exp Ther 331:671–679PubMedPubMedCentralGoogle Scholar
  142. Liechti ME (2017) Modern clinical research on LSD. Neuropsychopharmacology 42:2114–2127PubMedPubMedCentralGoogle Scholar
  143. Liu Y, Canal CE, Cordova-Sintjago TC, Zhu W, Booth RG (2017) Mutagenesis analysis reveals distinct amino acids of the human serotonin 5-HT2C receptor underlying the pharmacology of distinct ligands. ACS Chem Neurosci 8:28–39PubMedGoogle Scholar
  144. Lopez-Gimenez JF, Vilaro MT, Palacios JM, Mengod G (1998) [3H]MDL 100,907 labels 5-HT2A serotonin receptors selectively in primate brain. Neuropharmacology 37:1147–1158PubMedGoogle Scholar
  145. Lopez-Gimenez JF, Vilaro MT, Palacios JM, Mengod G (2013) Multiple conformations of 5-HT2A and 5-HT 2C receptors in rat brain: an autoradiographic study with [125I](+/−)DOI. Exp Brain Res 230:395–406PubMedGoogle Scholar
  146. Luparini MR, Garrone B, Pazzagli M, Pinza M, Pepeu G (2004) A cortical GABA-5HT interaction in the mechanism of action of the antidepressant trazodone. Prog Neuro-Psychopharmacol Biol Psychiatry 28:1117–1127Google Scholar
  147. Marona-Lewicka D, Thisted RA, Nichols DE (2005) Distinct temporal phases in the behavioral pharmacology of LSD: dopamine D2 receptor-mediated effects in the rat and implications for psychosis. Psychopharmacology 180:427–435PubMedGoogle Scholar
  148. Martin DA, Nichols CD (2017) The effects of hallucinogens on gene expression. Curr Top Behav Neurosci. Google Scholar
  149. Martin-Ruiz R, Puig MV, Celada P, Shapiro DA, Roth BL, Mengod G, Artigas F (2001) Control of serotonergic function in medial prefrontal cortex by serotonin-2A receptors through a glutamate-dependent mechanism. J Neurosci 21:9856–9866PubMedGoogle Scholar
  150. May JA, Sharif NA, Chen HH, Liao JC, Kelly CR, Glennon RA, Young R, Li JX, Rice KC, France CP (2009) Pharmacological properties and discriminative stimulus effects of a novel and selective 5-HT2 receptor agonist AL-38022A [(S)-2-(8,9-dihydro-7H-pyrano[2,3-g]indazol-1-yl)-1-methylethylamine]. Pharmacol Biochem Behav 91:307–314PubMedGoogle Scholar
  151. Mayberg HS, Brannan SK, Mahurin RK, Jerabek PA, Brickman JS, Tekell JL, Silva JA, McGinnis S, Glass TG, Martin CC, Fox PT (1997) Cingulate function in depression: a potential predictor of treatment response. Neuroreport 8:1057–1061PubMedGoogle Scholar
  152. McCreary AC, Filip M, Cunningham KA (2003) Discriminative stimulus properties of (+/−)-fenfluramine: the role of 5-HT2 receptor subtypes. Behav Neurosci 117:212–221PubMedGoogle Scholar
  153. McGrew L, Chang MS, Sanders-Bush E (2002) Phospholipase D activation by endogenous 5-hydroxytryptamine 2C receptors is mediated by Galpha13 and pertussis toxin-insensitive Gbetagamma subunits. Mol Pharmacol 62:1339–1343PubMedGoogle Scholar
  154. McKenna DJ, Saavedra JM (1987) Autoradiography of LSD and 2,5-dimethoxyphenylisopropylamine psychotomimetics demonstrates regional, specific cross-displacement in the rat brain. Eur J Pharmacol 142:313–315PubMedGoogle Scholar
  155. McKenna DJ, Mathis CA, Shulgin AT, Sargent T 3rd, Saavedra JM (1987) Autoradiographic localization of binding sites for 125I-DOI, a new psychotomimetic radioligand, in the rat brain. Eur J Pharmacol 137:289–290PubMedGoogle Scholar
  156. McKinney M, Raddatz R (2006) Practical aspects of radioligand binding. Curr Protoc Pharmacol 1:1.3. CrossRefGoogle Scholar
  157. Milligan G, Kostenis E (2006) Heterotrimeric G-proteins: a short history. Br J Pharmacol 147(Suppl 1):S46–S55PubMedPubMedCentralGoogle Scholar
  158. Montgomery T, Buon C, Eibauer S, Guiry PJ, Keenan AK, McBean GJ (2007) Comparative potencies of 3,4-methylenedioxymethamphetamine (MDMA) analogues as inhibitors of [(3)H]noradrenaline and [(3)H]5-HT transport in mammalian cell lines. Br J Pharmacol 152:1121–1130PubMedPubMedCentralGoogle Scholar
  159. Moreau JJ (1973) Hashish and mental illness. Raven Press, New YorkGoogle Scholar
  160. Moreno JL, Holloway T, Albizu L, Sealfon SC, Gonzalez-Maeso J (2011) Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists. Neurosci Lett 493:76–79PubMedPubMedCentralGoogle Scholar
  161. Moutkine I, Quentin E, Guiard BP, Maroteaux L, Doly S (2017) Heterodimers of serotonin receptor subtypes 2 are driven by 5-HT2C protomers. J Biol Chem 292:6352–6368PubMedPubMedCentralGoogle Scholar
  162. Moya PR, Berg KA, Gutierrez-Hernandez MA, Saez-Briones P, Reyes-Parada M, Cassels BK, Clarke WP (2007) Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors. J Pharmacol Exp Ther 321:1054–1061PubMedGoogle Scholar
  163. Mueller F, Lenz C, Dolder PC, Harder S, Schmid Y, Lang UE, Liechti ME, Borgwardt S (2017) Acute effects of LSD on amygdala activity during processing of fearful stimuli in healthy subjects. Transl Psychiatry 7:e1084PubMedPubMedCentralGoogle Scholar
  164. Muschamp JW, Regina MJ, Hull EM, Winter JC, Rabin RA (2004) Lysergic acid diethylamide and [-]-2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex. Brain Res 1023:134–140PubMedGoogle Scholar
  165. Nair SG, Gudelsky GA (2004) Activation of 5-HT2 receptors enhances the release of acetylcholine in the prefrontal cortex and hippocampus of the rat. Synapse 53:202–207PubMedGoogle Scholar
  166. Navailles S, De Deurwaerdere P, Spampinato U (2006) Clozapine and haloperidol differentially alter the constitutive activity of central serotonin2C receptors in vivo. Biol Psychiatry 59:568–575PubMedGoogle Scholar
  167. Nichols DE (2016) Psychedelics. Pharmacol Rev 68:264–355PubMedPubMedCentralGoogle Scholar
  168. Nichols DE (2017) Chemistry and structure-activity relationships of psychedelics. Curr Top Behav Neurosci. Google Scholar
  169. Nichols DE, Frescas SP, Chemel BR, Rehder KS, Zhong D, Lewin AH (2008) High specific activity tritium-labeled N-(2-methoxybenzyl)-2,5-dimethoxy-4-iodophenethylamine (INBMeO): a high-affinity 5-HT2A receptor-selective agonist radioligand. Bioorg Med Chem 16:6116–6123PubMedPubMedCentralGoogle Scholar
  170. Nichols DE, Sassano MF, Halberstadt AL, Klein LM, Brandt SD, Elliott SP, Fiedler WJ (2015) N-Benzyl-5-methoxytryptamines as potent serotonin 5-HT2 receptor family agonists and comparison with a series of phenethylamine analogues. ACS Chem Neurosci 6:1165–1175PubMedGoogle Scholar
  171. Nichols DE, Johnson MW, Nichols CD (2017) Psychedelics as medicines: an emerging new paradigm. Clin Pharmacol Ther 101:209–219PubMedGoogle Scholar
  172. Pahnke WN, Richards WA (1966) Implications of LSD and experimental mysticism. J Relig Health 5:175–208PubMedGoogle Scholar
  173. Pahnke WN, Kurland AA, Unger S, Savage C, Grof S (1970) The experimental use of psychedelic (LSD) psychotherapy. JAMA 212:1856–1863PubMedGoogle Scholar
  174. Palfreyman MG, Schmidt CJ, Sorensen SM, Dudley MW, Kehne JH, Moser P, Gittos MW, Carr AA (1993) Electrophysiological, biochemical and behavioral evidence for 5-HT2 and 5-HT3 mediated control of dopaminergic function. Psychopharmacology 112:S60–S67PubMedGoogle Scholar
  175. Palhano-Fontes F, Andrade KC, Tofoli LF, Santos AC, Crippa JA, Hallak JE, Ribeiro S, de Araujo DB (2015) The psychedelic state induced by ayahuasca modulates the activity and connectivity of the default mode network. PLoS One 10:e0118143PubMedPubMedCentralGoogle Scholar
  176. Parrish JC, Nichols DE (2006) Serotonin 5-HT(2A) receptor activation induces 2-arachidonoylglycerol release through a phospholipase c-dependent mechanism. J Neurochem 99:1164–1175PubMedGoogle Scholar
  177. Parrish JC, Braden MR, Gundy E, Nichols DE (2005) Differential phospholipase C activation by phenylalkylamine serotonin 5-HT 2A receptor agonists. J Neurochem 95:1575–1584PubMedGoogle Scholar
  178. Pauwels PJ, Van Gompel P, Leysen JE (1993) Activity of serotonin (5-HT) receptor agonists, partial agonists and antagonists at cloned human 5-HT1A receptors that are negatively coupled to adenylate cyclase in permanently transfected HeLa cells. Biochem Pharmacol 45:375–383PubMedGoogle Scholar
  179. Pazos A, Probst A, Palacios JM (1987) Serotonin receptors in the human brain – IV. Autoradiographic mapping of serotonin-2 receptors. Neuroscience 21:123–139PubMedGoogle Scholar
  180. Pehek EA, Hernan AE (2015) Stimulation of glutamate receptors in the ventral tegmental area is necessary for serotonin-2 receptor-induced increases in mesocortical dopamine release. Neuroscience 290:159–164PubMedPubMedCentralGoogle Scholar
  181. Pehek EA, McFarlane HG, Maguschak K, Price B, Pluto CP (2001) M100,907, a selective 5-HT2A antagonist, attenuates dopamine release in the rat medial prefrontal cortex. Brain Res 888:51–59PubMedGoogle Scholar
  182. Pehek EA, Nocjar C, Roth BL, Byrd TA, Mabrouk OS (2006) Evidence for the preferential involvement of 5-HT2A serotonin receptors in stress- and drug-induced dopamine release in the rat medial prefrontal cortex. Neuropsychopharmacology 31:265–277PubMedGoogle Scholar
  183. Peng Y, McCorvy JD, Harpsøe K, Lansu K, Yuan S, Popov P, Qu L, Pu M, Che T, Nikolajsen LF, Huang X-P, Wu Y, Shen L, Bjørn-Yoshimoto WE, Ding K, Wacker D, Han GW, Cheng J, Katritch V, Jensen AA, Hanson MA, Zhao S, Gloriam DE, Roth BL, Stevens RC, Liu Z-J (2018) 5-HT2C receptor structures reveal the structural basis of GPCR polypharmacology. Cell 172(4):719–730.e14PubMedPubMedCentralGoogle Scholar
  184. Perez-Aguilar JM, Shan J, LeVine MV, Khelashvili G, Weinstein H (2014) A functional selectivity mechanism at the serotonin-2A GPCR involves ligand-dependent conformations of intracellular loop 2. J Am Chem Soc 136:16044–16054PubMedPubMedCentralGoogle Scholar
  185. Petri G, Expert P, Turkheimer F, Carhart-Harris R, Nutt D, Hellyer PJ, Vaccarino F (2014) Homological scaffolds of brain functional networks. J R Soc Interface 11:20140873PubMedPubMedCentralGoogle Scholar
  186. Pokorny T, Preller KH, Kraehenmann R, Vollenweider FX (2016) Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience. Eur Neuropsychopharmacol 26:756–766PubMedGoogle Scholar
  187. Preller KH, Vollenweider FX (2016) Phenomenology, structure, and dynamic of psychedelic states. Curr Top Behav Neurosci. Google Scholar
  188. Preller KH, Herdener M, Pokorny T, Planzer A, Kraehenmann R, Stampfli P, Liechti ME, Seifritz E, Vollenweider FX (2017) The fabric of meaning and subjective effects in LSD-induced states depend on serotonin 2A receptor activation. Curr Biol 27:451–457PubMedGoogle Scholar
  189. Puig MV, Watakabe A, Ushimaru M, Yamamori T, Kawaguchi Y (2010) Serotonin modulates fast-spiking interneuron and synchronous activity in the rat prefrontal cortex through 5-HT1A and 5-HT2A receptors. J Neurosci 30:2211–2222PubMedGoogle Scholar
  190. Quednow BB, Geyer MA, Halberstadt AL (2010) Serotonin and schizophrenia. In: Muller CP, Jacobs B (eds) Handbook of the behavioral neurobiology of serotonin. Academic Press, London, pp 585–620Google Scholar
  191. Quednow BB, Kometer M, Geyer MA, Vollenweider FX (2012) Psilocybin-induced deficits in automatic and controlled inhibition are attenuated by ketanserin in healthy human volunteers. Neuropsychopharmacology 37:630–640PubMedGoogle Scholar
  192. Rabin RA, Regina M, Doat M, Winter JC (2002) 5-HT2A receptor-stimulated phosphoinositide hydrolysis in the stimulus effects of hallucinogens. Pharmacol Biochem Behav 72:29–37PubMedGoogle Scholar
  193. Ranganathan A, Rodríguez D, Carlsson J (2017) Structure-based discovery of GPCR ligands from crystal structures and homology models. Springer, Berlin, Heidelberg, pp 1–35Google Scholar
  194. Raote I, Bhattacharyya S, Panicker MM (2013) Functional selectivity in serotonin receptor 2A (5-HT2A) endocytosis, recycling, and phosphorylation. Mol Pharmacol 83:42–50PubMedGoogle Scholar
  195. Rauser L, Savage JE, Meltzer HY, Roth BL (2001) Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor. J Pharmacol Exp Ther 299:83–89PubMedGoogle Scholar
  196. Reissig CJ, Eckler JR, Rabin RA, Winter JC (2005) The 5-HT1A receptor and the stimulus effects of LSD in the rat. Psychopharmacology 182:197–204PubMedPubMedCentralGoogle Scholar
  197. Richards N, Chapman LF, Goodell H, Wolff HG (1958) LSD-like delirium following ingestion of a small amount of its brom analog (BOL-148). Ann Intern Med 48:1078–1082PubMedGoogle Scholar
  198. Richelson E, Souder T (2000) Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci 68:29–39PubMedGoogle Scholar
  199. Rickli A, Kopf S, Hoener MC, Liechti ME (2015a) Pharmacological profile of novel psychoactive benzofurans. Br J Pharmacol 172:3412–3425PubMedPubMedCentralGoogle Scholar
  200. Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME (2015b) Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs). Neuropharmacology 99:546–553PubMedGoogle Scholar
  201. Rickli A, Moning OD, Hoener MC, Liechti ME (2016) Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. Eur Neuropsychopharmacol 26:1327–1337PubMedGoogle Scholar
  202. Riva-Posse P, Choi KS, Holtzheimer PE, Crowell AL, Garlow SJ, Rajendra JK, McIntyre CC, Gross RE, Mayberg HS (2017) A connectomic approach for subcallosal cingulate deep brain stimulation surgery: prospective targeting in treatment-resistant depression. Mol Psychiatry. PubMedPubMedCentralGoogle Scholar
  203. Ross S, Bossis A, Guss J, Agin-Liebes G, Malone T, Cohen B, Mennenga SE, Belser A, Kalliontzi K, Babb J, Su Z, Corby P, Schmidt BL (2016) Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol 30:1165–1180PubMedPubMedCentralGoogle Scholar
  204. Roth BL, Choudhary MS, Khan N, Uluer AZ (1997) High-affinity agonist binding is not sufficient for agonist efficacy at 5-hydroxytryptamine2A receptors: evidence in favor of a modified ternary complex model. J Pharmacol Exp Ther 280:576–583PubMedGoogle Scholar
  205. Roth BL, Lopez E, Patel S, Kroeze WK (2000) The multiplicity of serotonin receptors: uselessly diverse molecules or an embarrassment of riches? Neuroscientist 6:252–262Google Scholar
  206. Saleh N, Ibrahim P, Saladino G, Gervasio FL, Clark T (2017) An efficient metadynamics-based protocol to model the binding affinity and the transition state ensemble of G-protein-coupled receptor ligands. J Chem Inf Model 57:1210–1217PubMedGoogle Scholar
  207. Sanders-Bush E, Burris KD, Knoth K (1988) Lysergic acid diethylamide and 2,5-dimethoxy-4-methylamphetamine are partial agonists at serotonin receptors linked to phosphoinositide hydrolysis. J Pharmacol Exp Ther 246:924–928PubMedGoogle Scholar
  208. Santana N, Artigas F (2017) Expression of serotonin2c receptors in pyramidal and GABAergic neurons of rat prefrontal cortex: a comparison with striatum. Cereb Cortex 27:3125–3139PubMedGoogle Scholar
  209. Santana N, Mengod G, Artigas F (2013) Expression of alpha(1)-adrenergic receptors in rat prefrontal cortex: cellular co-localization with 5-HT(2A) receptors. Int J Neuropsychopharmacol 16:1139–1151PubMedGoogle Scholar
  210. Schmid CL, Bohn LM (2010) Serotonin, but not N-methyltryptamines, activates the serotonin 2A receptor via a ss-arrestin2/Src/Akt signaling complex in vivo. J Neurosci 30:13513–13524PubMedPubMedCentralGoogle Scholar
  211. Schmid CL, Raehal KM, Bohn LM (2008) Agonist-directed signaling of the serotonin 2A receptor depends on beta-arrestin-2 interactions in vivo. Proc Natl Acad Sci U S A 105:1079–1084PubMedPubMedCentralGoogle Scholar
  212. Schmid CL, Streicher JM, Meltzer HY, Bohn LM (2014) Clozapine acts as an agonist at serotonin 2A receptors to counter MK-801-induced behaviors through a betaarrestin2-independent activation of Akt. Neuropsychopharmacology 39:1902–1913PubMedPubMedCentralGoogle Scholar
  213. Schreiber R, Brocco M, Millan MJ (1994) Blockade of the discriminative stimulus effects of DOI by MDL 100,907 and the ‘atypical’ antipsychotics, clozapine and risperidone. Eur J Pharmacol 264:99–102PubMedGoogle Scholar
  214. Schreiber R, Brocco M, Audinot V, Gobert A, Veiga S, Millan MJ (1995) (1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane)-induced head-twitches in the rat are mediated by 5-hydroxytryptamine (5-HT) 2A receptors: modulation by novel 5-HT2A/2C antagonists, D1 antagonists and 5-HT1A agonists. J Pharmacol Exp Ther 273:101–112PubMedGoogle Scholar
  215. Scruggs JL, Schmidt D, Deutch AY (2003) The hallucinogen 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) increases cortical extracellular glutamate levels in rats. Neurosci Lett 346:137–140PubMedGoogle Scholar
  216. Shulgin A, Shulgin A (1991) Pihkal: a chemical love story. Transform Press, BerkeleyGoogle Scholar
  217. Shulgin A, Shulgin A (1997) Tihkal: the continuation. Transform Press, BerkeleyGoogle Scholar
  218. Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME (2016) In vitro characterization of psychoactive substances at rat, mouse, and human trace amine-associated receptor 1. J Pharmacol Exp Ther 357:134–144PubMedGoogle Scholar
  219. Snyder SH, Faillace L, Hollister L (1967) 2,5-Dimethoxy-4-methyl-amphetamine (STP): a new hallucinogenic drug. Science 158:669–670PubMedGoogle Scholar
  220. Spindle MS, Thomas MP (2014) Activation of 5-HT2A receptors by TCB-2 induces recurrent oscillatory burst discharge in layer 5 pyramidal neurons of the mPFC in vitro. Physiol Rep 2:e12003. CrossRefPubMedPubMedCentralGoogle Scholar
  221. Strassman R (2001) DMT: the spirit molecule: a doctor’s revolutionary research into the biology of near-death and mystical experiences. Park Street Press, RochesterGoogle Scholar
  222. Studerus E, Gamma A, Kometer M, Vollenweider FX (2012) Prediction of psilocybin response in healthy volunteers. PLoS One 7:e30800PubMedPubMedCentralGoogle Scholar
  223. Sykes DA, Dowling MR, Charlton SJ (2010) Measuring receptor target coverage: a radioligand competition binding protocol for assessing the association and dissociation rates of unlabeled compounds. Curr Protoc Pharmacol 9:14. CrossRefPubMedGoogle Scholar
  224. Tagliazucchi E, Carhart-Harris R, Leech R, Nutt D, Chialvo DR (2014) Enhanced repertoire of brain dynamical states during the psychedelic experience. Hum Brain Mapp 35:5442–5456PubMedGoogle Scholar
  225. Tagliazucchi E, Roseman L, Kaelen M, Orban C, Muthukumaraswamy SD, Murphy K, Laufs H, Leech R, McGonigle J, Crossley N, Bullmore E, Williams T, Bolstridge M, Feilding A, Nutt DJ, Carhart-Harris R (2016) Increased global functional connectivity correlates with LSD-induced ego dissolution. Curr Biol 26:1043–1050PubMedGoogle Scholar
  226. Thal DM, Sun B, Feng D, Nawaratne V, Leach K, Felder CC, Bures MG, Evans DA, Weis WI, Bachhawat P, Kobilka TS, Sexton PM, Kobilka BK, Christopoulos A (2016) Crystal structures of the M1 and M4 muscarinic acetylcholine receptors. Nature 531:335–340PubMedPubMedCentralGoogle Scholar
  227. Thomsen WJ, Grottick AJ, Menzaghi F, Reyes-Saldana H, Espitia S, Yuskin D, Whelan K, Martin M, Morgan M, Chen W, Al-Shamma H, Smith B, Chalmers D, Behan D (2008) Lorcaserin, a novel selective human 5-hydroxytryptamine2C agonist: in vitro and in vivo pharmacological characterization. J Pharmacol Exp Ther 325:577–587PubMedGoogle Scholar
  228. Tian MK, Schmidt EF, Lambe EK (2016) Serotonergic suppression of mouse prefrontal circuits implicated in task attention. eNeuro 3.
  229. Valle M, Maqueda AE, Rabella M, Rodriguez-Pujadas A, Antonijoan RM, Romero S, Alonso JF, Mananas MA, Barker S, Friedlander P, Feilding A, Riba J (2016) Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans. Eur Neuropsychopharmacol 26:1161–1175PubMedGoogle Scholar
  230. Verhoeff NP, Visser WH, Ferrari MD, Saxena PR, van Royen EA (1993) Dopamine D2-receptor imaging with 123I-iodobenzamide SPECT in migraine patients abusing ergotamine: does ergotamine cross the blood brain barrier? Cephalalgia 13:325–329PubMedGoogle Scholar
  231. Viol A, Palhano-Fontes F, Onias H, de Araujo DB, Viswanathan GM (2017) Shannon entropy of brain functional complex networks under the influence of the psychedelic Ayahuasca. Sci Rep 7:7388PubMedPubMedCentralGoogle Scholar
  232. Vollenweider FX (2001) Brain mechanisms of hallucinogens and entactogens. Dialogues Clin Neurosci 3:265–279PubMedPubMedCentralGoogle Scholar
  233. Vollenweider FX, Vollenweider-Scherpenhuyzen MF, Babler A, Vogel H, Hell D (1998) Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport 9:3897–3902PubMedGoogle Scholar
  234. Wacker D, Fenalti G, Brown MA, Katritch V, Abagyan R, Cherezov V, Stevens RC (2010) Conserved binding mode of human β2 adrenergic receptor inverse agonists and antagonist revealed by X-ray crystallography. J Am Chem Soc 132:11443–11445PubMedPubMedCentralGoogle Scholar
  235. Wacker D, Wang C, Katritch V, Han GW, Huang XP, Vardy E, McCorvy JD, Jiang Y, Chu M, Siu FY, Liu W, Xu HE, Cherezov V, Roth BL, Stevens RC (2013) Structural features for functional selectivity at serotonin receptors. Science 340:615–619PubMedPubMedCentralGoogle Scholar
  236. Wacker D, Wang S, McCorvy JD, Betz RM, Venkatakrishnan AJ, Levit A, Lansu K, Schools ZL, Che T, Nichols DE, Shoichet BK, Dror RO, Roth BL (2017) Crystal structure of an LSD-bound human serotonin receptor. Cell 168:377–389.e12PubMedPubMedCentralGoogle Scholar
  237. Walker SJ, Brown HA, Molecular and Cellular Biology CUINYUSA (2004) Measurement of G protein-coupled receptor-stimulated phospholipase D activity in intact cells. Methods Mol Biol 237:89–97PubMedGoogle Scholar
  238. Wang C, Jiang Y, Ma J, Wu H, Wacker D, Katritch V, Han GW, Liu W, Huang XP, Vardy E, McCorvy JD, Gao X, Zhou XE, Melcher K, Zhang C, Bai F, Yang H, Yang L, Jiang H, Roth BL, Cherezov V, Stevens RC, Xu HE (2013) Structural basis for molecular recognition at serotonin receptors. Science 340:610–614PubMedPubMedCentralGoogle Scholar
  239. Wang S, Wacker D, Levit A, Che T, Betz RM, McCorvy JD, Venkatakrishnan AJ, Huang XP, Dror RO, Shoichet BK, Roth BL (2017) D4 dopamine receptor high-resolution structures enable the discovery of selective agonists. Science 358:381–386PubMedPubMedCentralGoogle Scholar
  240. Weber ET, Andrade R (2010) Htr2a gene and 5-HT(2A) receptor expression in the cerebral cortex studied using genetically modified mice. Front Neurosci 4:36. CrossRefPubMedPubMedCentralGoogle Scholar
  241. Wenthur CJ, Lindsley CW (2013) Classics in chemical neuroscience: clozapine. ACS Chem Neurosci 4:1018–1025PubMedPubMedCentralGoogle Scholar
  242. Willins DL, Meltzer HY (1997) Direct injection of 5-HT2A receptor agonists into the medial prefrontal cortex produces a head-twitch response in rats. J Pharmacol Exp Ther 282:699–706PubMedGoogle Scholar
  243. Willins DL, Deutch AY, Roth BL (1997) Serotonin 5-HT2A receptors are expressed on pyramidal cells and interneurons in the rat cortex. Synapse 27:79–82PubMedGoogle Scholar
  244. Winter JC (2009) Hallucinogens as discriminative stimuli in animals: LSD, phenethylamines, and tryptamines. Psychopharmacology 203:251–263PubMedGoogle Scholar
  245. Winter CA, Flataker L (1956) Effects of lysergic acid diethylamide upon performance of trained rats. Proc Soc Exp Biol Med 92:285–289PubMedGoogle Scholar
  246. Winter JC, Rice KC, Amorosi DJ, Rabin RA (2007) Psilocybin-induced stimulus control in the rat. Pharmacol Biochem Behav 87:472–480PubMedPubMedCentralGoogle Scholar
  247. Wright IK, Garratt JC, Marsden CA (1990) Effects of a selective 5-HT2 agonist, DOI, on 5-HT neuronal firing in the dorsal raphe nucleus and 5-HT release and metabolism in the frontal cortex. Br J Pharmacol 99:221–222PubMedPubMedCentralGoogle Scholar
  248. Xia Z, Gray JA, Compton-Toth BA, Roth BL (2003) A direct interaction of PSD-95 with 5-HT2A serotonin receptors regulates receptor trafficking and signal transduction. J Biol Chem 278: 21901–21908PubMedGoogle Scholar
  249. Yang KC, Stepanov V, Martinsson S, Ettrup A, Takano A, Knudsen GM, Halldin C, Farde L, Finnema SJ (2017) Fenfluramine reduces [11C]Cimbi-36 binding to the 5-HT2A receptor in the nonhuman primate brain. Int J Neuropsychopharmacol 20:683–691PubMedPubMedCentralGoogle Scholar
  250. Zhang ZW, Arsenault D (2005) Gain modulation by serotonin in pyramidal neurones of the rat prefrontal cortex. J Physiol 566:379–394PubMedPubMedCentralGoogle Scholar
  251. Zhelyazkova-Savova M, Giovannini MG, Pepeu G (1997) Increase of cortical acetylcholine release after systemic administration of chlorophenylpiperazine in the rat: an in vivo microdialysis study. Neurosci Lett 236:151–154PubMedGoogle Scholar
  252. Zhelyazkova-Savova M, Giovannini MG, Pepeu G (1999) Systemic chlorophenylpiperazine increases acetylcholine release from rat hippocampus-implication of 5-HT2C receptors. Pharmacol Res 40:165–170PubMedGoogle Scholar

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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Pharmaceutical SciencesCollege of Pharmacy, Mercer UniversityAtlantaUSA

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