Chemistry:Serotonin 5-HT2A receptor agonist

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Short description: Drug class


Serotonin 5-HT2A receptor agonist
Drug class
Psilocybin, a well-known non-selective agonist of the serotonin 5-HT2A receptor and other serotonin receptors and a serotonergic psychedelic.
Class identifiers
Synonyms5-HT2A agonist
UseHallucinogenic effects, treatment of psychiatric and other disorders
Mechanism of actionSerotonin 5-HT2A receptor agonism
Biological targetSerotonin 5-HT2A receptor
Chemical classTryptamines, phenethylamines, ergolines, lysergamides, others

A serotonin 5-HT2A receptor agonist, or simply 5-HT2A agonist, is a drug which acts as an agonist of the serotonin 5-HT2A receptor.[1][2] The serotonin 5-HT2A receptor is one of 13 known human serotonin receptors.[3] Serotonin 5-HT2A receptor agonists can be divided into two main groups: (1) serotonergic psychedelics such as LSD, psilocybin, and mescaline; and (2) non-hallucinogenic serotonin 5-HT2A receptor agonists such as lisuride, Ariadne, tabernanthalog, and zalsupindole, among others.[1][4] Psychedelic and non-hallucinogenic serotonin 5-HT2A receptor agonists can be reliably distinguished from each other in scientific research using the head-twitch response assay in animals.[5][4][6]

Agonists of the serotonin 5-HT2A receptor are generally not selective for this receptor and also interact with other serotonin receptors, such as the serotonin 5-HT1A, 5-HT2B, and/or 5-HT2C receptors, among others.[7][8] However, highly selective serotonin 5-HT2A receptor agonists, such as TGF-8027, have also been developed.[9] In addition to degree of selectivity for the serotonin 5-HT2A receptor, the serotonin 5-HT2A receptor activates a variety of different downstream signaling pathways, such as G protein and β-arrestin cascades, and serotonin 5-HT2A receptor agonists can have varying efficacies for activating these pathways, in turn resulting in different effects.[10][11][12][8] Differing efficacies at different downstream signaling pathways relative to serotonin is also known as functional selectivity or biased agonism.[10][11]

Serotonin 5-HT2A receptor agonists are frequently analogues of the neurotransmitter serotonin, and include tryptamines, phenethylamines, and ergolines and lysergamides, among other chemical classes.[1][13][14]

In addition to the recreational and entheogenic use of serotonergic psychedelics, both psychedelic and non-hallucinogenic serotonin 5-HT2A receptor agonists, which act as psychoplastogens and have antidepressant-like effects in animals, may have applications in the treatment of psychiatric disorders such as depression, anxiety, and addiction.[15][16] However, use of psychedelics for such purposes has also been critiqued and their potential adverse effects highlighted.[17][18][19]

Serotonergic psychedelics

Main articles: Chemistry:Psychedelic drug and Serotonin § Psychedelics

Serotonergic psychedelics, also known as hallucinogenic serotonin 5-HT2A receptor agonists, produce hallucinogenic effects including open-eye and closed-eye psychedelic visuals, other perceptual changes, synesthesia, distortions in time perception, ego loss, emotional changes, and mystical experiences, among others.[20][21][22][23][24] Examples of serotonergic psychedelics include the following:[1][13]

It is thought that a certain minimum level of activational efficacy at the Gq pathway of the serotonin 5-HT2A receptor may be required for psychedelic effects.[10][11][12] However, more research is needed, and a role of other pathways, such as the β-arrestin pathway, has not been ruled out.[10][14]

Non-hallucinogenic 5-HT2A receptor agonists

Non-hallucinogenic serotonin 5-HT2A receptor agonists, which have sometimes been referred to as "non-hallucinogenic psychedelics", are a class of drugs which act as agonists of the serotonin 5-HT2A receptor and produce effects mediated by this receptor such as neuroplastic and behavioral changes but do not produce psychedelic effects.[1][4][16][25][26][27] This class of drugs includes the following compounds:[1][4][16][25][28]

However, most of the above-listed drugs have been concluded to be non-hallucinogenic based on animal behavioral measures of psychedelic-like effects such as the head-twitch response (HTR) assay in rodents. Many of these drugs have not been tested in humans and their putatively non-hallucinogenic natures have not been confirmed. Although available evidence is limited, some observations suggest that hallucinogenic effects may emerge at higher doses in some cases. For instance, while tabernanthalog has been reported to be non-hallucinogenic based on preclinical research, anecdotal reports suggest that it can produce mild hallucinogenic effects at sufficiently high doses in humans.[29][30][31] Additionally, hallucinations have been observed in humans with high doses of lisuride, which is an often-cited non-hallucinogenic serotonin 5-HT2A receptor agonist related to LSD, although the nature and mechanisms of these apparent hallucinogenic effects are unclear and dopamine D2 receptor agonism might alternatively be involved.[32] Another drug, JRT, is the isoindole analogue of LSD and has reduced or possibly absent psychedelic-like effects in animals.[33][34]

The precise mechanism by which non-hallucinogenic serotonin 5-HT2A receptor agonists lack psychedelic effects is uncertain; it is thought that they may not activate the serotonin 5-HT2A receptor with sufficient efficacy, possibly specifically with regard to the Gq pathway, to produce hallucinogenic effects.[11] However, many of these drugs have nonetheless been found to produce psychoplastogenic effects mediated by serotonin 5-HT2A receptor activation and to an equivalent extent as with psychedelics.[35][36][37][38] This might be involved in the antidepressant-like effects of these drugs per animal studies, and non-hallucinogenic serotonin 5-HT2A receptor agonists may have therapeutic potential similarly to psychedelics.[38][39][40][41][42]

In preclinical models, animals administered non-hallucinogenic serotonin 5-HT2A receptor agonists exhibit fewer hallucinogen-associated behaviors at doses that produce rapid antidepressant-like effects.[43][29] The psychoplastogenic effects of non-hallucinogenic serotonin 5-HT2A receptor agonists appear to coincide with their rapid antidepressant-like effects in animal models.[42] It has been suggested that non-hallucinogenic serotonin 5-HT2A receptor agonists may be more suitable for broader clinical use compared to psychedelics because of their reduced perception-altering effects.[44]

Selective 5-HT2A receptor agonists

Selective serotonin 5-HT2A receptor agonists are known and include 25CN-NBOH, BMB-202, DMBMPP (juncosamine), DOI-NBOMe, LPH-5 ((S)-2C-TFM-3PIP), LPH-48, and TGF-8027.[1][45][46][9][28]

Biased 5-HT2A receptor agonists

The serotonin 5-HT2A receptor is coupled to multiple downstream signaling pathways.[11][47][10][14] A number of biased agonists of the serotonin 5-HT2A receptor are known.[47][11] These include the G protein-biased lisuride,[48] (R)-69,[49] and (R)-70;[49] the β-arrestin-biased LSD,[48] RS130-180,[50] 25CN-NBOH and derivatives,[47][51] 25N-N1-Nap,[12] 25N-NBPh,[12] IHCH-7079,[43] and IHCH-7086;[43] and others like DOI-NBOMe,[28] TCB-2 (2CBCB),[52][53] and 5-phenoxytryptamine (OVT2).[47][54] The functional selectivity of various serotonergic psychedelics at the serotonin 5-HT2A receptor has been studied.[55][56][57][58] Besides the serotonin 5-HT2A receptor, many psychedelics are biased agonists of the serotonin 5-HT2C receptor.[59]

Peripherally selective 5-HT2A receptor agonists

Peripherally selective serotonin 5-HT2A receptor agonists that lack effects on the brain are known.[1][60][32] Aside from serotonin itself,[24] α-methylserotonin,[24][61] and the partially peripherally selective bufotenin (N,N-dimethylserotonin),[60][14][62] another notable example of a peripherally selective serotonin 5-HT2A receptor agonist is AL-34662.[63][64] This drug was investigated for the potential treatment of eye diseases such as ocular hypertension and glaucoma.[63][64] Ergotamine may also be a peripherally selective serotonin 5-HT2A receptor agonist, and is used as an obstetric drug and antimigraine agent.[32][65] Psilocybin and psilocin analogues found in psilocybin-containing mushrooms, including baeocystin, norpsilocin, aeruginascin, and 4-HO-TMT, have been found to be peripherally selective serotonin 5-HT2A receptor agonists as well.[66][67][68][69]

Selected effects of 5-HT2A receptor agonists

Anti-inflammatory 5-HT2A receptor agonists

Some serotonergic psychedelics, such as (R)-DOI and psilocybin, show highly potent anti-inflammatory effects mediated by serotonin 5-HT2A receptor activation.[70][71][72][73][74] Other serotonergic psychedelics, such as LSD, are less potent, and yet other psychedelics, like DOTFM, show no anti-inflammatory effects at all.[71][74][75] Conversely, some serotonin 5-HT2A receptor agonists, such as 2,5-DMA, have potent anti-inflammatory effects with no apparent psychedelic effects.[74][76][75] These findings indicate that the psychedelic and anti-inflammatory effects of serotonin 5-HT2A receptor agonists are mediated by different downstream signaling pathways and are fully dissociable.[74][76][75] Serotonin 5-HT2A receptor agonists with reduced psychedelic potential but retained anti-inflammatory effects, such as 2C-iBu (ELE-02), are being studied to treat inflammatory disorders.[77][78][79]

5-HT2A receptor agonists and organ fibrosis

Many serotonin 5-HT2A receptor agonists, due to lack of selectivity and activation of the closely related serotonin 5-HT2B receptor,[80][8][12] may have the potential to produce organ fibrosis and associated complications such as cardiac valvulopathy or pulmonary hypertension with long-term use.[81][82][83][84] This has been observed with pharmaceutical drugs such as fenfluramine, methysergide, ergotamine, cabergoline, and pergolide, among others, which has led to market withdrawal or restrictions on use of such agents.[85][86][87][88][89] Infrequent or occasional use of serotonergic psychedelics is thought to be safe and not pose a significant risk, but very frequent use or microdosing may carry risk.[81][83][90] Not all serotonin 5-HT2A receptor agonists are also potent serotonin 5-HT2B receptor agonists however.[80][8][12] For example, many phenethylamine psychedelics show substantial selectivity for the serotonin 5-HT2A and 5-HT2C receptors over the serotonin 5-HT2B receptor.[80][8][12] In addition, selective serotonin 5-HT2A receptor agonists that show less or no activation of other serotonin receptors such as the serotonin 5-HT2B receptor, such as 25CN-NBOH, DMBMPP, LPH-5, and TGF-8027, have been developed.[1][91][9] Moreover, selective serotonin 5-HT2B receptor antagonists, including peripherally selective drugs like VU0530244, are being developed, and may be able to block the complications of serotonin 5-HT2B receptor agonism.[87][92][93][94][95]

5-HT2A receptor agonists and neurotoxicity

Serotonin 5-HT2A receptor agonists may produce neurotoxicity, for instance serotonergic neurotoxicity, at high concentrations or doses.[96][97][98][99] In addition, they may potentiate the serotonergic neurotoxicity of MDMA.[100][101][102][103]

Indirect 5-HT2A receptor agonists

Serotonergic agents that elevate serotonin levels can act as indirect serotonin 5-HT2A receptor agonists.[104][105] Examples of such agents include serotonin precursors like tryptophan and 5-hydroxytryptophan (5-HTP), serotonin reuptake inhibitors (SRIs) like selective serotonin reuptake inhibitors (SSRIs) and various other antidepressants, monoamine oxidase inhibitors (MAOIs), and serotonin releasing agents (SRAs) like fenfluramine and MDMA.[104][105][106][107][108][109][110][111] Direct serotonin 5-HT2A receptor agonists and serotonin-elevating drugs have differing effects.[37] As an example, whereas serotonin-elevating drugs have a risk of serotonin syndrome, major serotonergic psychedelics like psilocybin and LSD are partial agonists of the serotonin 5-HT2A receptor and have little or no risk of serotonin syndrome even in the context of large overdoses.[112][113][114] However, one notable group of psychedelics, the NBOMe drugs, have higher efficacy at the serotonin 5-HT2A receptor and can produce serotonin syndrome.[113] As another example, serotonin is a highly hydrophilic molecule and is unable to enter neurons and activate intracellular serotonin 5-HT2A receptors, which have been found to mediate the psychoplastogenic effects of exogenous serotonin 5-HT2A receptor agonists.[115][37][116] These intracellular serotonin 5-HT2A receptors may also contribute to the psychedelic effects of serotonin 5-HT2A receptor agonists.[37]

See also

References

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  52. ↑ "TCB-2 [(7R)-3-bromo-2, 5-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-yl]methanamine]: A hallucinogenic drug, a selective 5-HT2A receptor pharmacological tool, or none of the above?". Neuropharmacology 142: 20–29. November 2018. doi:10.1016/j.neuropharm.2017.10.004. PMID 28987938. "TCB-2 has all the characteristics of a biased agonist (functionally selective agonist) at 5-HT2A receptors. (R)-(-)-TCB-2 displays high selectivity (about 65-fold) toward the PLC signalling pathway over PLA2, one displaying EC50s of 18 ± 2.8 nM and 1180 ± 180, respectively (McLean et al., 2006). The racemic, which is commonly used in pharmacological studies, induced IP3 accumulation with an EC50 of 36 ± 3.6 nM. It corresponded to 94% of the maximal response induced by 5-HT indicating that TCB-2 is a full agonist on this pathway (McLean et al., 2006). It has been also reported that TCB-2 enhances intracellular Ca2+ in line with the increase in IP accumulation in HEK293 cells stably expressing 5 human 5-HT2A receptors (Dalwadi et al., 2016). This confers on TCB-2 a unique pharmacological profile compared to other 5-HT2A receptor ligands such as LSD, DOI, or DOB. While LSD displays a slightly higher potency toward IP accumulation, DOB, DOM, DOI, 5-MeO-DMT, or psilocin have a higher potency at AA release (Kurrasch-Orbaugh et al., 2003b; Moya et al., 2007).". 
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  56. ↑ "Identification of psychedelic new psychoactive substances (NPS) showing biased agonism at the 5-HT2AR through simultaneous use of β-arrestin 2 and miniGαq bioassays". Biochem Pharmacol 182. December 2020. doi:10.1016/j.bcp.2020.114251. PMID 32998000. 
  57. ↑ "Structure-Activity Assessment and In-Depth Analysis of Biased Agonism in a Set of Phenylalkylamine 5-HT2A Receptor Agonists". ACS Chem Neurosci 14 (15): 2727–2742. August 2023. doi:10.1021/acschemneuro.3c00267. PMID 37474114. 
  58. ↑ "The psychedelic phenethylamine 25C-NBF, a selective 5-HT2A agonist, shows psychoplastogenic properties and rapid antidepressant effects in male rodents". Mol Psychiatry. November 2025. doi:10.1038/s41380-025-03341-1. PMID 41238841. 
  59. ↑ "Serotonin 5-HT2C Receptor Signaling Analysis Reveals Psychedelic Biased Agonism". ACS Chem Neurosci 16 (19): 3899–3914. October 2025. doi:10.1021/acschemneuro.5c00647. PMID 40944639. 
  60. ↑ 60.0 60.1 "Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions". Curr Drug Metab 11 (8): 659–666. October 2010. doi:10.2174/138920010794233495. PMID 20942780. 
  61. ↑ "Effects of the 5-HT1C/5-5-HT2 receptor agonists DOI and alpha-methyl-5-HT on plasma glucose and insulin levels in the rat". Eur J Pharmacol 187 (3): 435–443. October 1990. doi:10.1016/0014-2999(90)90370-l. PMID 2127400. 
  62. ↑ "Pharmañopo-psychonautics: human intranasal, sublingual, intrarectal, pulmonary and oral pharmacology of bufotenine". J Psychoactive Drugs 33 (3): 273–281. 2001. doi:10.1080/02791072.2001.10400574. PMID 11718320. 
  63. ↑ 63.0 63.1 Sharif, Najam A; May, Jesse A (2011). "Potential for serotonergic agents to treat elevated intraocular pressure and glaucoma: focus on 5-HT 2 receptor agonists". Expert Review of Ophthalmology 6 (1): 105–120. doi:10.1586/eop.10.69. ISSN 1746-9899. http://www.tandfonline.com/doi/full/10.1586/eop.10.69. Retrieved 18 October 2025. 
  64. ↑ 64.0 64.1 "AL-34662: a potent, selective, and efficacious ocular hypotensive serotonin-2 receptor agonist". J Ocul Pharmacol Ther 23 (1): 1–13. February 2007. doi:10.1089/jop.2006.0093. PMID 17341144. 
  65. ↑ "The 5-HT1B and 5-HT1D agonists in acute migraine therapy: Ergotamine, dihydroergotamine, and the triptans". Migraine Management. Handbook of Clinical Neurology. 199. 2024. 17–42. doi:10.1016/B978-0-12-823357-3.00008-2. ISBN 978-0-12-823357-3. 
  66. ↑ "Behavioural and pharmacological evaluation of the psilocybin analogue baeocystin in Wistar rats". Prog Neuropsychopharmacol Biol Psychiatry 140. July 2025. doi:10.1016/j.pnpbp.2025.111439. PMID 40619050. 
  67. ↑ "Pharmacological and behavioural effects of tryptamines present in psilocybin-containing mushrooms". Br J Pharmacol 181 (19): 3627–3641. October 2024. doi:10.1111/bph.16466. PMID 38825326. 
  68. ↑ "Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice". ACS Pharmacol Transl Sci 5 (11): 1181–1196. November 2022. doi:10.1021/acsptsci.2c00177. PMID 36407948. 
  69. ↑ "A Review of Aeruginascin and Potential Entourage Effect in Hallucinogenic Mushrooms". European Psychiatry (Royal College of Psychiatrists) 65 (S1): S885. 2022. doi:10.1192/j.eurpsy.2022.2297. ISSN 0924-9338. 
  70. ↑ "Psychedelics as Medicines: An Emerging New Paradigm". Clin Pharmacol Ther 101 (2): 209–219. February 2017. doi:10.1002/cpt.557. PMID 28019026. 
  71. ↑ 71.0 71.1 "Psychedelics and Anti-inflammatory Activity in Animal Models". Disruptive Psychopharmacology. Current Topics in Behavioral Neurosciences. 56. 2022. pp. 229–245. doi:10.1007/7854_2022_367. ISBN 978-3-031-12183-8. 
  72. ↑ "Psychedelics as potent anti-inflammatory therapeutics". Neuropharmacology 219. November 2022. doi:10.1016/j.neuropharm.2022.109232. PMID 36007854. 
  73. ↑ "Psychedelics as anti-inflammatory agents". Int Rev Psychiatry 30 (4): 363–375. August 2018. doi:10.1080/09540261.2018.1481827. PMID 30102081. http://usdbiology.com/cliff/Courses/Advanced%20Seminars%20in%20Neuroendocrinology/Therapeutic%20Effects%20of%20Psychedelics%2019/Flanagan%20Nichols%2018%20IntRevPsychiatry%20Psychedelics%20as%20anti-inflammatory%20agents.pdf. 
  74. ↑ 74.0 74.1 74.2 74.3 "Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore". ACS Pharmacol Transl Sci 4 (2): 488–502. April 2021. doi:10.1021/acsptsci.0c00063. PMID 33860179. PMC 8033619. https://www.researchgate.net/publication/360537036. 
  75. ↑ 75.0 75.1 75.2 "Serotonin-2 Receptor Agonists Produce Anti-inflammatory Effects through Functionally Selective Mechanisms That Involve the Suppression of Disease-Induced Arginase 1 Expression". ACS Pharmacology & Translational Science 7 (2): 478–492. February 2024. doi:10.1021/acsptsci.3c00297. PMID 38357283. "The effects of (R)-DOTFM were examined in the head-twitch response (HTR) assay. (R)-DOTFM produced a strong HTR with a potent ED 50 of 0.60 μmol/kg. These values are equivalent to (R)-DOI, as previously determined.". 
  76. ↑ 76.0 76.1 "Differential Regulation of Inflammatory Responses Following 5-HT 2 Receptor Activation in Pulmonary Tissues". The FASEB Journal 36 (S1). 2022. doi:10.1096/fasebj.2022.36.S1.R2617. ISSN 0892-6638. 
  77. ↑ "Eleusis Draws on Research Into Psychedelics To Develop New Medicines for Inflammation". 8 July 2020. https://www.lucid.news/eleusis-research-on-psychedelics-develop-inflammation-medicines/. 
  78. ↑ Shlomi Raz, Eleusis (February 2020). "Eleusis Drug Development Overview". LSX World Congress 2020. https://www.youtube.com/watch?v=VwblUOQQwMI. 
  79. ↑ ; Gerald Billac & David E. Nichols"Compounds and methods for treating inflammatory disorders" WO patent published 2020210823, published 15 October 2020
  80. ↑ 80.0 80.1 80.2 Luethi, Dino; Liechti, Matthias E. (2021). "Drugs of Abuse Affecting 5-HT2B Receptors". 5-HT2B Receptors. 35. Cham: Springer International Publishing. pp. 277–289. doi:10.1007/978-3-030-55920-5_16. ISBN 978-3-030-55919-9. http://link.springer.com/10.1007/978-3-030-55920-5_16. Retrieved 27 April 2025. 
  81. ↑ 81.0 81.1 "The risk of chronic psychedelic and MDMA microdosing for valvular heart disease". J Psychopharmacol 37 (9): 876–890. September 2023. doi:10.1177/02698811231190865. PMID 37572027. 
  82. ↑ "Cardiovascular safety of psychedelic medicine: current status and future directions". Pharmacol Rep 75 (6): 1362–1380. December 2023. doi:10.1007/s43440-023-00539-4. PMID 37874530. 
  83. ↑ 83.0 83.1 "Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins". J Psychopharmacol 38 (3): 217–224. March 2024. doi:10.1177/02698811231225609. PMID 38214279. 
  84. ↑ "Serotonin 5-HT2B receptor agonism and valvular heart disease: implications for the development of psilocybin and related agents". Expert Opin Drug Saf 22 (10): 881–883. 2023. doi:10.1080/14740338.2023.2248883. PMID 37581427. 
  85. ↑ "Drug-induced valvulopathy: an update". Toxicol Pathol 38 (6): 837–848. October 2010. doi:10.1177/0192623310378027. PMID 20716786. 
  86. ↑ "Serotonin receptors and heart valve disease--it was meant 2B". Pharmacol Ther 132 (2): 146–157. November 2011. doi:10.1016/j.pharmthera.2011.03.008. PMID 21440001. 
  87. ↑ 87.0 87.1 "2B Determined: The Future of the Serotonin Receptor 2B in Drug Discovery". J Med Chem 66 (16): 11027–11039. August 2023. doi:10.1021/acs.jmedchem.3c01178. PMID 37584406. 
  88. ↑ "Serotonergic drugs and valvular heart disease". Expert Opin Drug Saf 8 (3): 317–329. May 2009. doi:10.1517/14740330902931524. PMID 19505264. 
  89. ↑ "Parallel functional activity profiling reveals valvulopathogens are potent 5-hydroxytryptamine(2B) receptor agonists: implications for drug safety assessment". Mol Pharmacol 76 (4): 710–722. October 2009. doi:10.1124/mol.109.058057. PMID 19570945. 
  90. ↑ Roihuvuo, Elias (31 January 2022). "Classical psychedelics and NBOMes as serotonin 2B receptor agonists: Valvulopathogenic signaling pathways and cardiac safety concerns". Itä-Suomen yliopisto. https://erepo.uef.fi/items/09fb2e57-a98e-4ec0-9de5-90e5267c6ed6. 
  91. ↑ Peplow, Mark (2024). "Next-generation psychedelics: should new agents skip the trip?". Nature Biotechnology 42 (6): 827–830. doi:10.1038/s41587-024-02285-1. ISSN 1087-0156. PMID 38831049. "Another problem is that some classical psychedelics are also agonists of the 5-HT2B receptor, which is expressed in heart tissue and can cause long-term cardiac problems. Kristensen's company Lophora aims to solve that with its lead compound LPH-5, a phenylethylamine derivative with an extra molecular ring that makes it less flexible. LPH-5 has a 60-fold higher selectivity for 5-HT2A over 5-HT2B.". 
  92. ↑ "Cardiovascular Concern of 5-HT2B Receptor and Recent Vistas in the Development of Its Antagonists". Cardiovasc Hematol Disord Drug Targets 17 (2): 86–104. 2017. doi:10.2174/1871529X17666170703115111. PMID 28676029. 
  93. ↑ "Pathological Insight into 5-HT2B Receptor Activation in Fibrosing Interstitial Lung Diseases". Int J Mol Sci 22 (1): 225. December 2020. doi:10.3390/ijms22010225. PMID 33379351. 
  94. ↑ "Reintroducing Fenfluramine as a Treatment for Seizures: Current Knowledge, Recommendations and Gaps in Understanding". Neuropsychiatric Disease and Treatment 19: 2013–2025. 2023. doi:10.2147/NDT.S417676. PMID 37790801. 
  95. ↑ "The role of 5-HT2B receptors in mitral valvulopathy: bone marrow mobilization of endothelial progenitors". British Journal of Pharmacology 174 (22): 4123–4139. November 2017. doi:10.1111/bph.13981. PMID 28806488. 
  96. ↑ "Molecular and clinical aspects of potential neurotoxicity induced by new psychoactive stimulants and psychedelics". Exp Neurol 343. September 2021. doi:10.1016/j.expneurol.2021.113778. PMID 34090893. 
  97. ↑ "Serotonin 2C receptors are also important in head-twitch responses in male mice". Psychopharmacology (Berl) 242 (7): 1585–1605. July 2025. doi:10.1007/s00213-023-06482-9. PMID 37882810. 
  98. ↑ "Ecstasy-induced cell death in cortical neuronal cultures is serotonin 2A-receptor-dependent and potentiated under hyperthermia". Neuroscience 139 (3): 1069–1081. 2006. doi:10.1016/j.neuroscience.2006.01.007. PMID 16504407. 
  99. ↑ "Molecular and cellular mechanisms of ecstasy-induced neurotoxicity: an overview". Mol Neurobiol 39 (3): 210–271. June 2009. doi:10.1007/s12035-009-8064-1. PMID 19373443. "To further corroborate the fact that MDMA agonistic properties at the 5-HT2A receptor could produce neuronal death, DOI, a prototypical agonist of that receptor was added to cortical neurons [289]. DOI (10 to 100 μM for 24 or 48 h) also induced a dose- and time-dependent apoptotic cortical neuronal apoptosis, which was attenuated by ketanserin and R-96544 [289]. Ketanserin and R-96544 are competitive selective 5-HT2A receptor antagonists and only attenuated MDMA-induced cortical neurodegeneration. However, an antibody raised against the 5-HT2A-receptor, an “irreversible” non-competitive 5-HT2A receptor blocker, prevented almost completely MDMA- and DOI-induced cortical neurotoxicity [289, 290]. Neuronal apoptosis mediated by MDMA is accompanied by activation of caspase 3, which could be blocked by the antibody raised against the 5-HT2A receptor [290]. Therefore, it is likely that DOI- and MDMA-induced neuronal apoptosis arises from direct stimulation of the 5-HT2A receptor [289, 290].". 
  100. ↑ "The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy")". Pharmacol Rev 55 (3): 463–508. September 2003. doi:10.1124/pr.55.3.3. PMID 12869661. 
  101. ↑ "Potentiation of 3,4-methylenedioxymethamphetamine-induced dopamine release and serotonin neurotoxicity by 5-HT2 receptor agonists". Eur J Pharmacol 264 (3): 325–330. November 1994. doi:10.1016/0014-2999(94)90669-6. PMID 7698172. 
  102. ↑ "Methylenedioxymethamphetamine-induced hyperthermia and neurotoxicity are independently mediated by 5-HT2 receptors". Brain Res 529 (1–2): 85–90. October 1990. doi:10.1016/0006-8993(90)90813-q. PMID 1980848. 
  103. ↑ "Potentiation of (DL)-3,4-methylenedioxymethamphetamine (MDMA)-induced toxicity by the serotonin 2A receptior partial agonist d-lysergic acid diethylamide (LSD), and the protection of same by the serotonin 2A/2C receptor antagonist MDL 11,939". Neuroscience Research Communications 35 (2): 83–95. 2004. doi:10.1002/nrc.20023. 
  104. ↑ 104.0 104.1 "Serotonin and beyond: therapeutics for major depression". Philos Trans R Soc Lond B Biol Sci 368 (1615). 2013. doi:10.1098/rstb.2012.0536. PMID 23440470. 
  105. ↑ 105.0 105.1 "The Roles of Serotonin in Neuropsychiatric Disorders". Cell Mol Neurobiol 42 (6): 1671–1692. August 2022. doi:10.1007/s10571-021-01064-9. PMID 33651238. 
  106. ↑ "Serotonin releasing agents. Neurochemical, therapeutic and adverse effects". Pharmacol Biochem Behav 71 (4): 825–836. April 2002. doi:10.1016/s0091-3057(01)00669-4. PMID 11888573. 
  107. ↑ "Therapeutic and adverse actions of serotonin transporter substrates". Pharmacol Ther 95 (1): 73–88. July 2002. doi:10.1016/s0163-7258(02)00234-6. PMID 12163129. 
  108. ↑ "Neurochemical mechanisms of phentermine and fenfluramine: Therapeutic and adverse effects". Drug Development Research 51 (2): 52–65. 2000. doi:10.1002/1098-2299(200010)51:2<52::AID-DDR2>3.0.CO;2-H. ISSN 0272-4391. 
  109. ↑ "Therapeutic potential of monoamine transporter substrates". Curr Top Med Chem 6 (17): 1845–1859. 2006. doi:10.2174/156802606778249766. PMID 17017961. 
  110. ↑ "Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine". ACS Chem Neurosci 9 (10): 2408–2427. October 2018. doi:10.1021/acschemneuro.8b00155. PMID 30001118. PMC 6197894. https://shaunlacob.com/wp-content/uploads/2020/12/DC-MDMA.pdf. 
  111. ↑ "Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy". J Psychopharmacol 35 (5): 512–536. May 2021. doi:10.1177/0269881120920420. PMID 32909493. 
  112. ↑ "Serotonin toxicity of serotonergic psychedelics". Psychopharmacology (Berl) 239 (6): 1881–1891. June 2022. doi:10.1007/s00213-021-05876-x. PMID 34251464. 
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  114. ↑ "Concomitant use of antidepressants and classic psychedelics: A scoping review". J Psychopharmacol 39 (10): 2698811251368360. September 2025. doi:10.1177/02698811251368360. PMID 40937732. 
  115. ↑ "The Key Role of Intracellular 5-HT2A Receptors: A Turning Point in Psychedelic Research?". Psychoactives 2 (4): 287–293. 13 October 2023. doi:10.3390/psychoactives2040018. ISSN 2813-1851. 
  116. ↑ "Animal Models and Hallucinogenic Drugs". The Neuroscience of Hallucinations. New York, NY: Springer New York. 2013. pp. 253–277. doi:10.1007/978-1-4614-4121-2_14. ISBN 978-1-4614-4120-5. 



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