Lysergic acid 2,4-dimethylazetidide

Last updated
LSZ
LSD-azetidine.svg
Clinical data
Other namesLysergic acid 2,4-dimethylazetidine; Lysergic acid 2S,4S-dimethylazetidine; LSZ; LA-Azetidide; LSD-Azetidide; LA-SS-Az; SS-LSZ; (S,S)-LSZ; Diazedine; λ; Lambda
Routes of
administration 		Oral [1] [2]
Drug class Non-selective serotonin receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen
Legal status
Legal status
  • DE: NpSG (Industrial and scientific use only)
  • UK: Class A
  • Illegal in Denmark, France, [3] Sweden, and Switzerland
Pharmacokinetic data
Duration of action 3–11 hours (median 8 hours) [2]
Identifiers
  • [(6aR,9R)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-yl]-[(2S,4S)-2,4-dimethylazetidin-1-yl]methanone
​
  • freebase:(S,S)-isomer, freebase
  • tartrate salt:(S,S)-isomer, tartrate salt
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C21H25N3O
Molar mass 335.451 g·mol−1
3D model (JSmol)
  • freebase: C[C@H]1C[C@@H](N1C(=O)[C@H]2CN([C@@H]3CC4=CNC5=CC=CC(=C45)C3=C2)C)C
  • freebase: InChI=1S/C21H25N3O/c1-12-7-13(2)24(12)21(25)15-8-17-16-5-4-6-18-20(16)14(10-22-18)9-19(17)23(3)11-15/h4-6,8,10,12-13,15,19,22H,7,9,11H2,1-3H3/t12-,13-,15+,19+/m0/s1 X mark.svgN
  • Key:DUKNIHFTDAXJON-CTQRGLTFSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

LSZ, also known as lysergic acid 2,4-dimethylazetidide or as LA-Azetidide (LA-Az), is a psychedelic drug of the lysergamide family related to lysergic acid diethylamide (LSD). [4] [5] [6] [7] It is taken orally. [1] [2]

Contents

The drug acts as a non-selective serotonin receptor agonist, including of the serotonin 5-HT2A receptor. [4] [7] It also interacts with dopamine receptors. [7] [8] The compound is a close analogue of LSD that has been modified at the amide to be more rigid and to have three diastereomers. [4] [6] [7] LA-SS-Az, the (S,S)- isomer, is the most potent and similar isomer to LSD, and is the typically employed form of LSZ. [5] [6] [7] LA-SS-Az and the other isomers of LSZ produce psychedelic-like effects in animals. [7] [6]

LSZ was first described in the scientific literature by David E. Nichols and colleagues in 2002. [6] [7] It was developed as a tool for studying psychedelic interactions with the serotonin 5-HT2A receptor and followed the earlier unstable compound LA-Aziridine developed by Nichols and Robert Oberlender. [4] [7] [9] [10] [11] LSZ, under the name "diazedine", may have been produced on a small scale by the LSD manufacturers William Leonard Pickard and Gordon Todd Skinner around the year 2000. [12] [13] [14] It was first definitely encountered as a novel designer drug in 2013 and then became a popular psychedelic. [6] [15] [16] [2] LSZ is a controlled substance in several European countries. [17] [18] [19] [20]

Use and effects

LSZ, as the (S,S)- isomer LA-SS-Az, has been reported to have a dose range of 100 to 200 μg or 100 to 300 μg orally, with a typical dose estimate of 150 or 200 μg. [1] [2] [6] This dose range is notably higher than that of LSD, which is 50 to 200 μg with a typical dose of about 100 μg. [21] [22] [23] [24] [1] According to David E. Nichols however, LSZ is approximately equipotent with LSD based on human anecdotal reports. [5] The duration of LSZ is reported to be in the range of 3 to 11 hours, with a median duration of around 8 hours. [2] This was shorter than the duration of the LSD prodrug 1P-LSD, which had a duration range of 6 to 14 hours and a median duration of about 10 hours in the same study. [2] The detailed effects of LSZ, aside from it being a psychedelic similarly to LSD, do not appear to have been reported in the published literature. [1] [2] [4]

Interactions

Pharmacology

Pharmacodynamics

LSZ activities
Target Affinity (Ki, nM)
5-HT1A 0.45
5-HT1B 2.4
5-HT1D 2.4
5-HT1E 276
5-HT1F ND
5-HT2A 0.54–19.2 (Ki)
0.32–957 (EC50 Tooltip half-maximal effective concentration)
56–85% (Emax Tooltip maximal efficacy)
5-HT2B 27 (Ki)
0.4–58.4 (EC50)
57–74% (Emax)
5-HT2C 37 (Ki)
992 (EC50)
39% (Emax)
5-HT3 >10,000
5-HT4 ND
5-HT5A 27.3
5-HT6 14.5
5-HT7 14.3
α1A 850.2
α1B >10,000
α1D–α2C ND
β1 75.8
β2 1,069
β3 ND
D1 292
D2 73.6–110
D3 6.0
D4 36–95.5
D5 402.2
H1 2,504
H2–H4 ND
M1–M5 ND
I1 ND
σ1, σ2 ND
TAAR1 Tooltip Trace amine-associated receptor 1ND
SERT Tooltip Serotonin transporter>10,000 (Ki)
NET Tooltip Norepinephrine transporter>10,000 (Ki)
DAT Tooltip Dopamine transporter>10,000 (Ki)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [25] [26] [27] [7] [8] [28] [29] [30] [4]

LSZ has been found to bind non-selectively to serotonin, dopamine, and certain other receptors. [7] [27] [8] [28] It shows especially high affinity for the serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors, among others. [7] [27] [8] The drug acts as a potent agonist of the serotonin 5-HT2A and 5-HT2C receptors, with potency and efficacy similar to that of LSD. [7] [8] [28] It may be more potent than LSD as an agonist of the serotonin 5-HT1A receptor. [7]

LSZ produces the head-twitch response, a behavioral proxy of psychedelic-like effects, in rodents. [31] [1] [6] It shows about the same potency as LSD and AL-LAD in producing this effect. [31] [1] However, LSZ shows a weaker maximal head-twitch response than LSD or AL-LAD. [6] This might be due to lower efficacy at the serotonin 5-HT2A receptor or stronger actions at other receptors like the serotonin 5-HT1A or 5-HT2C receptor. [6] LSZ also substitutes for LSD in rodent drug discrimination tests. [1] [7] It was about 1.8-fold more potent than LSD in this assay. [1] [7] All three isomers of LSZ fully substituted for LSD in rodent drug discrimination tests, but the (S,S)- isomer was the most potent and was the only isomer that was more potent than LSD. [6] [7] In addition, only the (S,S) isomer fully substituted for the LSD-like selective serotonin 5-HT1A receptor full agonist and partial ergoline LY-293284. [6] [7] In contrast to LSZ, LSD itself does not substitute for LY-293284 in drug discrimination tests. [7]

In addition to its psychedelic effects, LSZ has been found to produce anti-inflammatory effects in preclinical research. [6] [32]

Pharmacokinetics

The in-vitro metabolism of LSZ has been studied. [33]

Chemistry

LSZ, also known as lysergic acid 2,4-dimethylazetidide or as LA-Azetidine (LA-Az), is a substituted lysergamide derivative related to lysergic acid diethylamide (LSD). [34] [6] [7] It is the analogue of LSD in which the N,N-diethyl amide moiety has been replaced with an 2,4-dimethyl azetidine moiety. [34] [6] [7] The compound has three possible diastereomers around the azetidine ring, including the cis-(2RS,4SR)-, trans-(2R,4R)-, and trans-(2S,4S)- 2,4-dimethylazetidine isomers. [35] [6] [7] The (S,S)- isomer, also known as LA-SS-Az, is the most potent diastereomer and is the typically employed form of the compound. [6] [7]

The three isomers of LSZ. Left: cis-LSZ. Center: trans-(R,R)-LSZ. Right: trans-(S,S)-LSZ. Isomers of lysergic acid 2,3-dimethylazetidine (LA-Azetidine or LSZ).png
The three isomers of LSZ. Left: cis-LSZ. Center: trans-(R,R)-LSZ. Right: trans-(S,S)-LSZ.

Synthesis

The chemical synthesis of LSZ has been described. [7]

Analogues

Analogues of LSZ include other lysergamides like the 6-substituted lysergamides ETH-LAD, PRO-LAD, AL-LAD, and CE-LAD; the amide-substituted lysergamides LA-3Cl-SB, EcPLA, and MiPLA; the amide-cycilzed lysergamides LA-Aziridine, LA-Pyr (LPD-824), LPN, LA-Pip, LA-Morph (LSM-775), and LA-Azepane; and the ester prodrugs ALD-52 (1A-LSD), 1P-LSD, 1cP-LSD, 1V-LSD, 1B-LSD, 1P-ETH-LAD, and 1cP-AL-LAD, among others.

History

LSZ was developed by David E. Nichols and colleagues at Purdue University and was first described by them in the scientific literature in 2002. [6] [7] It was developed to help better understand the binding orientation of LSD at the serotonin 5-HT2A receptor and to help further map the topography of the receptor. [6] LSZ is a rigid analogue of LSD in which the N,N-diethyl amide moiety has been replaced with and constrained into a 2,4-dimethyl azetidine moiety. [34] [6] [7] Moreover, the compound has two additional chiral centers due to this modification, with three possible diastereomers. [6] [7]

Nichols and colleagues like Robert Oberlender had initially attempted to do this research by employing the closely related and very similar compound LA-Aziridine in the 1980s, but this drug proved to be highly chemically unstable such that in-vivo studies were precluded. [7] [9] [10] [11] With the development of LSZ, the team determined that the (S,S)- isomer, LA-SS-Az, was the most potent and hence most optimal configuration of LSZ in terms of serotonin 5-HT2A receptor activation and psychedelic-like effects in animals. [6] [7] In addition, the conformation of LSD within the crystal structure of the closely related serotonin 5-HT2B receptor was later found to be essentially superimposable with the structure of LA-SS-Az. [4] [35] [29] Similar findings were made with virtual docking studies with the serotonin 5-HT2A receptor. [4] [35] LSZ, as LA-SS-Az, is among the only known analogues of LSD modified at the amide to have similar or greater psychedelic-type potency. [4] [7]

According to Krystle Cole in an interview with journalist and researcher Hamilton Morris, the LSD clandestine manufacturers William Leonard Pickard and Gordon Todd Skinner had synthesized and experimented with a psychedelic drug they called "diazedine" around the year 2000. [12] [13] [14] Per Cole, "[diazedine] was also crazy, but nothing earth-shattering". [12] Pickard and Skinner had high expectations for the drug and intended to produce and distribute it as an LSD alternative, but had difficulty scaling its synthesis due to high production costs and low yields. [12] [36] Pickard was a student of Nichols in his lab at Purdue University and was aware of the work on LSZ before it was published. [13] Morris has speculated that "diazedine" (notably a contraction of "dimethylazetidine") is extremely likely to have been LSZ, although this remains unconfirmed. [12] [13] [14] There have also been rumors for many years that LSZ was distributed for a time on blotter paper under the name "λ" ("lambda"), though this has likewise not been confirmed. [13]

LSZ was first definitely encountered as a novel designer drug, in Europe, in December 2013. [6] [15] [20] It is known to have been produced and sold by the now-defunct psychedelic lysergamide manufacturer Lizard Labs in the 2010s and 2020s. [37] [6] [38] The drug is said to have become a popular psychedelic drug and alternative to other lysergamides like LSD following its initial emergence. [16] [2]

Society and culture

Europe

LSZ is illegal in Switzerland as of December 2015, [17] in Denmark as of May 2015, [18] and in Sweden as of January 2016. [19] It is also illegal in France. [3]

United Kingdom

On June 10, 2014, the United Kingdom Advisory Council on the Misuse of Drugs (ACMD) recommended that LSZ be specifically named in the UK Misuse of Drugs Act as a class A drug despite not identifying any harm associated with its use. [20] The United Kingdom Home office accepted this advice and announced a ban of the substance to be enacted on 6 January 2015 as part of the Misuse of Drugs Act amended in 2014. [20]

Research

LSZ has been patented as a potential anti-inflammatory drug by Charles D. Nichols and colleagues. [39]

See also

References

  1. 1 2 3 4 5 6 7 8 9 Halberstadt AL, Chatha M, Klein AK, Wallach J, Brandt SD (May 2020). "Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species" (PDF). Neuropharmacology. 167 107933. doi:10.1016/j.neuropharm.2019.107933. PMC   9191653 . PMID   31917152. Table 4 Human potency data for selected hallucinogens. [...]
  2. 1 2 3 4 5 6 7 8 9 Mallaroni P, Mason NL, Vinckenbosch FR, Ramaekers JG (June 2022). "The use patterns of novel psychedelics: experiential fingerprints of substituted phenethylamines, tryptamines and lysergamides". Psychopharmacology (Berl). 239 (6): 1783–1796. doi:10.1007/s00213-022-06142-4. PMC   9166850 . PMID   35487983.
  3. 1 2 "Arrêté du 20 mai 2021 modifiant l'arrêté du 22 février 1990 fixant la liste des substances classées comme stupéfiants". www.legifrance.gouv.fr (in French). 20 May 2021.
  4. 1 2 3 4 5 6 7 8 9 10 Nichols DE (2018). Chemistry and Structure-Activity Relationships of Psychedelics. Curr Top Behav Neurosci. Vol. 36. pp. 1–43. doi:10.1007/7854_2017_475. ISBN   978-3-662-55878-2. PMID   28401524. To test the hypothesis that the receptor might have a region that was optimally complementary to the N,N-diethylamide, the synthesis and testing of conformationally constrained 2,3-dimethylazetidine amides of lysergic acid was carried out (Nichols et al. 2002). These dimethylazetidines exist in three isomeric forms: the 2,3-cis meso isomer 27, the R,R-trans 28, and the S,S-trans 29 isomers. The amide of each of these was prepared from lysergic acid and tested. [...] Virtual docking of LSD, 28, and 29 into an in silico agonist-activated model of the 5-HT2A receptor revealed that the diethyl groups of LSD nestle into a region that is bounded by a number of residues near the extracellular face of the receptor (Juncosa 2011). Further, extracellular loop 2 (EL2) was observed to interact with the diethylamide moiety. In particular, Leu-229 in EL2 was found to be critical for this interaction (McCorvy 2012). The conformation of EL2 was very similar after docking either LSD or S,S-isomer 29, whereas EL2 was significantly displaced (ca. 4 Å at Leu-229) by docking of R,R-28. After docking of LSD, followed by molecular dynamics and minimization, the conformations adopted by the ethyl groups were observed to mirror the configurations in S,S-29. Curiously, the receptor appears to have evolved to be complementary to the diethyl moiety of LSD in a specific conformation.{{cite book}}: |journal= ignored (help)
  5. 1 2 3 Nichols DE (October 2018). "Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD)" (PDF). ACS Chemical Neuroscience. 9 (10): 2331–2343. doi:10.1021/acschemneuro.8b00043. PMID   29461039. One analogue of LSD modified in the amide moiety has been reported to have human activity approximately equipotent to LSD. The lysergamide of 2S,4S-dimethylazetidine52 has been sold as "LSZ" and anecdotal reports of its human activity have appeared. Interestingly, the crystal structure of LSD bound within the human serotonin 5-HT2B receptor was recently reported.78 The conformation of the LSD molecule within the crystal structure was essentially superimposable on the structure of the lysergamide of 2S,4S-dimethylazetidine.52
  6. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Brandt SD, Kavanagh PV, Westphal F, Elliott SP, Wallach J, Colestock T, et al. (January 2017). "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 Testing and Analysis. 9 (1): 38–50. doi:10.1002/dta.1985. PMC   5411264 . PMID   27265891. [...] Powdered samples of (2'S,4'S)-lysergic acid 2,4-dimethylazetidide (LSZ) and N6 -allyl-6-norlysergic acid diethylamide (AL-LAD) tartrate were obtained from Synex Ltd (London, UK). Blotters labelled to contain 150 μg AL-LAD and 150 μg LSZ, and blank blotter paper, were provided by the same vendor. [...]
  7. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 Nichols DE, Frescas S, Marona-Lewicka D, Kurrasch-Orbaugh DM (September 2002). "Lysergamides of isomeric 2,4-dimethylazetidines map the binding orientation of the diethylamide moiety in the potent hallucinogenic agent N,N-diethyllysergamide (LSD)". J Med Chem. 45 (19): 4344–4349. doi:10.1021/jm020153s. PMID   12213075.
  8. 1 2 3 4 5 Braden MR (2007). Towards a biophysical understanding of hallucinogen action (Ph.D. thesis). Purdue University. ProQuest   304838368.
  9. 1 2 Pfaff RC, Huang X, Marona-Lewicka D, Oberlender R, Nichols DE (1994). "Lysergamides revisited" (PDF). NIDA Research Monograph. 146: 52–73. PMID   8742794. Archived from the original (PDF) on August 5, 2023.
  10. 1 2 Nichols DE, Monte A, Huang X, Marona-Lewicka D (1996). "Stereoselective pharmacological effects of lysergic acid amides possessing chirality in the amide substituent" (PDF). Behavioural Brain Research. 73 (1–2): 117–119. doi:10.1016/0166-4328(96)00080-0. PMID   8788487.
  11. 1 2 Oberlender RA (May 1989). "Stereoselective aspects of hallucinogenic drug action and drug discrimination studies of entactogens". Purdue e-Pubs. Purdue University.
  12. 1 2 3 4 5 Morris H (1 May 2011). "Life Is a Cosmic Giggle on the Breath of the Universe". Vice Magazine. Retrieved 2011-06-15. There were other novel substances as well. Leonard made a new LSD analog called "diazedine," though I don't know exactly what that was either. Are you familiar with lysergic acid 2,4-dimethylazetidide?2 No, but they were calling this diazedine. It was also crazy, but nothing earth-shattering. Leonard gave it to Todd in a bottle of Everclear for testing, and we would dose a capful at a time. Apparently, diazedine failed to be doable on a large scale because the production costs were too high and the yields too low. Diazedine caused a lot of stress between Todd and Leonard, because they had high expectations for it as an LSD alternative. [...] 2 Lysergic acid 2,4-dimethylazetidide (aka LSZ) belongs to a very small group of serotonergic psychedelics that surpass LSD in potency. Aside from the fact that "diazedine" is a lexical clipping of dimethylazetidine (diazedine).
  13. 1 2 3 4 5 Morris, Hamilton (28 September 2011). "Getting High on Krystle". VICE. Retrieved 13 October 2025. 2 [LSZ] belongs to a small group of serotonergic psychedelics that are superior in potency to LSD. The first paper describing the pharmacology and composition of LSZ was written by a laboratory at Purdue University, where Leonard had been a student of the renowned chemist David Nichols. Although the research was published after Leonard's arrest, it is still likely that Leonard was aware of its contents. When I asked Dr. Nichols if he thought Pickard had actually produced LSZ, he said, "Leonard knew about our research, I'm sure of that." Rumors have circulated for years that LSZ was distributed on blotter paper (under the name λ), but there are no confirmed reports of its existence. The name diazedine is certainly ambiguous and could refer to pretty much anything, but I would bet a kilo of benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium that LSZ and diazedine are the same thing.
  14. 1 2 3 Hamilton Morris (28 September 2011). "Getting High on Krystle: Underground LSD Palace". Hamilton's Pharmacopeia [web series]. Episode S0E3. Vice Media. [Web article].
  15. 1 2 European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). EMCDDA-Europol 2013 Annual Report on the implementation of Council Decision 2005/387/JHA. EMCDDA, Lisbon, 2014. http://www.emcdda.europa.eu/system/files/publications/814/TDAN14001ENN_475519.pdf "74. Lysergic acid 2,4-dimethylazetidide (‘LSZ’) ([(2S,4S)-2,4-dimethylazetidin-1-yl]-[(9R)- 7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-yl]methanone) — 10 December 2013, Slovenia."
  16. 1 2 Brandt SD, Kavanagh PV, Westphal F, Stratford A, Elliott SP, Dowling G, Halberstadt AL (October 2020). "Analytical profile of N-ethyl-N-cyclopropyl lysergamide (ECPLA), an isomer of lysergic acid 2,4-dimethylazetidide (LSZ)". Drug Test Anal. 12 (10): 1514–1521. doi:10.1002/dta.2911. PMC   9191644 . PMID   32803833.
  17. 1 2 "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in German). Der Bundesrat.
  18. 1 2 "Bekendtgørelse om euforiserende stoffer - ni nye stoffer tilføjet" (in Danish). Lægemiddelstyrelsen. 31 August 2015.
  19. 1 2 "31 nya ämnen kan klassas som narkotika eller hälsofarlig vara" (in Swedish). Folkhälsomyndigheten. November 2015.
  20. 1 2 3 4 ACMD (10 June 2014). "Update of the Generic Definition for Tryptamines" (PDF). UK Home Office. p. 12. Retrieved 10 June 2014.
  21. ↑ Liechti ME, Holze F (2022). "Dosing Psychedelics and MDMA". Disruptive Psychopharmacology. Curr Top Behav Neurosci. Vol. 56. pp. 3–21. doi:10.1007/7854_2021_270. ISBN   978-3-031-12183-8. PMID   34734392.
  22. ↑ Alexander T. Shulgin; Ann Shulgin (1997). "#26. LSD-25 Acid; Lysergide; D-Lysergic Acid Diethylamide; Meth-LAD; D-Lysergamide, N,N-Diethyl; N,N-Diethyl-D-Lysergamide; 9,10-Didehydro-N,N-Diethyl-6-Methylergoline-8b-Carboxamide". TiHKAL: The Continuation (1st ed.). Berkeley, CA: Transform Press. pp. 490–499. ISBN   978-0-9630096-9-2. OCLC   38503252.
  23. ↑ Shulgin AT (2003). "Basic Pharmacology and Effects". In Laing RR (ed.). Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. pp. 67–137. ISBN   978-0-12-433951-4 . Retrieved 1 February 2025.
  24. ↑ Jacob P, Shulgin AT (1994). "Structure-activity relationships of the classic hallucinogens and their analogs" (PDF). NIDA Res Monogr. 146: 74–91. PMID   8742795. Archived from the original (PDF) on August 5, 2023.
  25. ↑ "Kᵢ Database". PDSP. 1 April 2025. Retrieved 1 April 2025.
  26. ↑ Liu, Tiqing. "BindingDB BDBM50118576 (2,4-Dimethyl-azetidin-1-yl)-(7-methyl-4,6,6a,7,8,9-hexahydro-indolo[4,3-fg]quinolin-9-yl)-methanone::CHEMBL137781". BindingDB. Retrieved 1 April 2025.
  27. 1 2 3 Ray TS (February 2010). "Psychedelics and the human receptorome". PLOS ONE. 5 (2) e9019. Bibcode:2010PLoSO...5.9019R. doi: 10.1371/journal.pone.0009019 . PMC   2814854 . PMID   20126400.
  28. 1 2 3 McCorvy JD (16 January 2013). "Mapping the binding site of the 5-HT2A receptor using mutagenesis and ligand libraries: Insights into the molecular actions of psychedelics". Purdue e-Pubs. Archived from the original on 26 March 2025. Alt URL
  29. 1 2 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 (January 2017). "Crystal Structure of an LSD-Bound Human Serotonin Receptor". Cell. 168 (3): 377–389.e12. doi:10.1016/j.cell.2016.12.033. PMC   5289311 . PMID   28129538.
  30. 1 2 Nichols DE (2012). "Structure–activity relationships of serotonin 5-HT2A agonists". Wiley Interdisciplinary Reviews: Membrane Transport and Signaling. 1 (5): 559–579. doi: 10.1002/wmts.42 . ISSN   2190-460X.
  31. 1 2 Halberstadt AL, Geyer MA (2018). "Effect of Hallucinogens on Unconditioned Behavior". Behavioral Neurobiology of Psychedelic Drugs. Curr Top Behav Neurosci. Vol. 36. pp. 159–199. doi:10.1007/7854_2016_466. ISBN   978-3-662-55878-2. PMC   5787039 . PMID   28224459. Two other lysergamides sold as "research chemicals," N6 -allyl-6-nor-LSD (AL-LAD) and (2′ S,4′S)-lysergic acid 2,4-dimethylazetidide (LSZ), have also been shown to induce the HTR (Brandt et al. 2017). The potency of LSZ (ED50 = 114 nmol/kg) is approximately the same as LSD, whereas AL-LAD is slightly less potent (ED50 = 175 nmol/kg).
  32. ↑ Yu B, Becnel J, Zerfaoui M, Rohatgi R, Boulares AH, Nichols CD (November 2008). "Serotonin 5-hydroxytryptamine(2A) receptor activation suppresses tumor necrosis factor-alpha-induced inflammation with extraordinary potency". J Pharmacol Exp Ther. 327 (2): 316–323. doi:10.1124/jpet.108.143461. PMID   18708586.
  33. ↑ Wagmann L, Richter LH, Kehl T, Wack F, Bergstrand MP, Brandt SD, Stratford A, Maurer HH, Meyer MR (July 2019). "In vitro metabolic fate of nine LSD-based new psychoactive substances and their analytical detectability in different urinary screening procedures". Anal Bioanal Chem. 411 (19): 4751–4763. doi:10.1007/s00216-018-1558-9. PMID   30617391.
  34. 1 2 3 Duan W, Cao D, Wang S, Cheng J (January 2024). "Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants". Chem Rev. 124 (1): 124–163. doi:10.1021/acs.chemrev.3c00375. PMID   38033123. Replacing the diethylamino group of LSD with a conformationally restricted ((2S,4S)-2,4-dimethylazetidinyl group, which has been demonstrated to be able to mimic the active conformation of the diethylamino group bound to the 5- HT2AR,155 afforded compound LSZ (70). Compound LSZ could induce significant HTR effects in mice with an ED50 of 52 μg/kg.163
  35. 1 2 3 Gumpper RH, Nichols DE (October 2024). "Chemistry/structural biology of psychedelic drugs and their receptor(s)". Br J Pharmacol bph.17361. doi:10.1111/bph.17361. PMID   39354889. To gain a better understanding of the diethylamide function, three rigid analogues of LSD were prepared where the diethylamide was replaced by trans-2R,4R-, 2S,4S- and cis-2RS,4SR-dimethylazetidines (Figure 4). Only the 2S,4S-dimethylazetidide had potency nearly comparable to LSD in drug discrimination assays in LSD-trained rats (Nichols et al., 2002). Virtual docking of LSD into a homology model of the 5-HT2A receptor suggested that the diethylamide of LSD might interact with residues in extracellular loop 2 of the 5-HT2A receptor (Juncosa, 2011). [...] When the crystal structure of LSD in the 5-HT2B receptor was subsequently determined, it was observed that only the 2S,4Sdimethylazetine analogue mimicked the conformation of the diethyl groups of LSD (Wacker et al., 2017). This stereoisomer has appeared on the illicit drug market as 'LSZ'. [...]
  36. ↑ Cole K (2005). Lysergic. Indianapolis: Dog Ear Publishing. ISBN   978-1598580075. [...] Diazadine [LSD analog] fails to be do-able big stress lines. [...]
  37. ↑ Niesporek, Tom (17 August 2022). Der Hype um legales LSD in Deutschland: Wie das Verbot umgangen wird [The hype surrounding legal LSD in Germany: How the ban is circumvented]. YouTube (in German). VICE auf Deutsch. Event occurs at 2:10–8:12, 20:05–20:41. Retrieved 29 September 2025.
  38. ↑ "The End of An Era: Lizard Labs to Permanently Close on 31st December 2024". GetResponse. Lizard Labs. November 2024. Retrieved 29 September 2025.
  39. ↑ "Low Dosage Serotonin 5-HT2A Receptor Agonist To Suppress Inflammation". Google Patents. 10 July 2009. Retrieved 13 October 2025.
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