generation run 2026-05-11
68 min completedmodel pipeline-v5plan not recordedrun/ae9b0e4c…Selection
Verification
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- seen / partial
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The model's own caveats
7 further caveats recorded as free text — readable on the working page
Reproduce
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- 23 source keys (listed under Sources)
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21 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | ClinicalTrials.gov · absence | LSM-775 | 0 | — | — |
| 2 | OpenAlex | LSM-775 lysergic acid morpholide psychedelic serotonin receptor | 10 | 2 | — |
| 3 | PubMed | Return of the lysergamides Brandt Halberstadt NPS | 3 | 3 | — |
| 4 | PubMed | PMID 28585392 full fetch | 1 | — | — |
| 5 | PubMed · absence | LSM-775 lysergamide morpholine | 0 | — | — |
| 6 | PubMed | lysergic acid morpholide pharmacology serotonin | 1 | 1 | — |
| 7 | PubChem | lysergic acid morpholide | 1 | 1 | — |
| 8 | PubChem · absence | LSM-775 | 0 | — | — |
| 9 | PubMed | Gogerty Dille lysergic acid morpholide pharmacology 1957 | 1 | 1 | — |
| 10 | WebSearch | LSM-775 Sandoz Hofmann synthesis history compound 775 | 10 | — | — |
| 11 | WebSearch | LSM-775 legal status Germany UK Psychoactive Substances Act Australia TGA scheduling | 10 | 3 | — |
| 12 | PMC | LSM-775 receptor binding Ki EC50 human effects | 1 | — | — |
| 13 | WebSearch | LSM-775 legal status Germany UK Australia Canada | 10 | — | — |
| 14 | PubChem API | — | 1 | — | — |
| 15 | PubMed | Nichols hallucinogens review Pharmacological Reviews | 1 | 1 | — |
| 16 | PubMed | Halberstadt Geyer head twitch response psilocin 5-HT1A 5-HT2A | 1 | — | — |
| 17 | PubMed | Wacker 2017 LSD serotonin 5-HT2B receptor crystal structure | 1 | 1 | — |
| 18 | PubMed | Holze 2021 LSD pharmacokinetics dose-dependent effects | 4 | 3 | — |
| 19 | Erowid | LSM-775 user experience report effects | 1 | — | — |
| 20 | Multiple | LSM-775 chemical identity verification | 1 | — | — |
| 21 | Cayman Chemical | LSM-775 CAS number physical properties | 1 | — | — |
75 claims by section — every cited sentence, checked against its source
pharmacology19 · 12 ok
LSM-775 is a serotonin receptor agonist that acts simultaneously at 5-HT₁A and 5-HT₂A receptors with near-equal binding affinity but divergent functional profilessupported
Acts as nonselective agonist at 5-HT1A (Ki 31.0 nM) and 5-HT2A (Ki 29.5 nM). 5-HT1A activation masks hallucinogenic HTR. dta.2222
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
The 5-HT₂A receptor mediates the hallucinogenic effects of classical psychedelics through Gq-coupled signaling in neocortical layer V pyramidal neurons, while 5-HT₁A activation exerts an opposing, dampening influence on these behavioral outputs.supported
5-HT2A required for HTR; 5-HT1A activation by 5-MeO-DMT inhibits behavioral patterns; WAY-100635 antagonism reveals 5-HT1A-mediated suppression. 0269881110388326
Claim in pharmacology — inconclusiveinconclusiveworking →
In the mouse head-twitch response (HTR) assay — the standard preclinical proxy for hallucinogenic potential — LSM-775 alone produced no significant responsesupported
Head twitch response only with 5-HT1A antagonist WAY-100,635 pretreatment (ED50 0.34 mg/kg). dta.2222
Only after pretreatment with the selective 5-HT₁A antagonist WAY-100,635 (1 mg/kg s.c.) did LSM-775 induce a clear HTR (ED₅₀ = 0.34 mg/kg; 95% CI: 0.24–0.50 mg/kg)supported
Head twitch response only with 5-HT1A antagonist WAY-100,635 pretreatment (ED50 0.34 mg/kg). dta.2222
This masking phenomenon parallels observations with 5-MeO-DMT and is analogous to the non-hallucinogenic 5-HT₂A agonist lisuride.supported
5-HT1A activation by 5-MeO-DMT inhibits behavioral patterns; WAY-100635 antagonism reveals 5-HT1A-mediated suppression. 0269881110388326
This masking phenomenon parallels observations with 5-MeO-DMT and is analogous to the non-hallucinogenic 5-HT₂A agonist lisuride.supported
Cryo-EM structures of 5-HT1A with 5-MeO-DMT; 5-HT1A-selective analogue devoid of hallucinogenic effects while retaining anxiolytic/antidepressant activity. s41586-024-07403-2
This masking phenomenon parallels observations with 5-MeO-DMT and is analogous to the non-hallucinogenic 5-HT₂A agonist lisuride.supported
lisuride (non-hallucinogenic 5-HT2A agonist) does not induce HTR and shows distinct fingerprint. pmid:14523084
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
The only pharmacological characterization of LSM-775 reports binding at serotonin receptors exclusivelysupported
Acts as nonselective agonist at 5-HT1A (Ki 31.0 nM) and 5-HT2A (Ki 29.5 nM). dta.2222
Claim in pharmacology — inconclusiveinconclusiveworking →
By structural analogy with LSD: lysergamide metabolism involves CYP2D6 (primary), CYP1A2, and CYP2C9supported
CYP2D6, CYP1A2, and CYP2C9 involved in LSD in vitro metabolism. s41598-021-90343-y
CYP2D6 poor metabolizers exhibit approximately 75% higher LSD plasma concentrations and prolonged half-livessupported
Poor metabolizers had 75% higher plasma concentrations and longer half-lives. s41598-021-90343-y
LSD's principal urinary metabolite is 2-oxo-3-hydroxy-LSD, with nor-LSD and glucuronide conjugates also detectedsupported
Main LSD metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD) in urine. Also nor-LSD, lysergic acid ethylamide, trioxylated-LSD, and glucuronide conjugates. s1570-0232(01)00494-9
LSD elimination half-life is approximately 5.7–6.4 hourssupported
LSD terminal t1/2 ≈ 5.7–6.4 h after oral administration. dta.2821
Claim in pharmacology — inconclusiveinconclusiveworking →
safety12 · 9 ok
Claim in safety — inconclusiveinconclusiveworking →
By class analogy, classical serotonergic psychedelics possess extremely high therapeutic indices in animal models, and no acute fatality attributable solely to LSD has been confirmed in the medical literature despite decades of widespread usesupported
Generally physiologically safe; no dependence or addiction. pr.115.011478
Claim in safety — inconclusiveinconclusiveworking →
Risk of hallucinogen persisting perception disorder (HPPD) is a recognized class-level concern, though prevalence estimates remain poorly quantified.supported
HPPD is rarely encountered; two types: brief flashbacks (Type 1) and chronic (Type 2); associated with pre-existing anxiety and visual pathway over-activation. 7854_2016_457
Claim in safety — inconclusiveinconclusiveworking →
Cross-tolerance between psychedelics (confirmed experimentally between DOI and LSD) operates through this shared mechanismsupported
Cross-tolerance between DOI and LSD; no cross-tolerance with nonpsychedelic 5-HT2AR agonist lisuride; DOI caused 5-HT2AR downregulation in frontal cortex. acschemneuro.2c00170
Non-hallucinogenic 5-HT₂A agonists such as lisuride do not induce the tolerance pattern observed with hallucinogenic agonists, suggesting the tolerance mechanism is specifically tied to hallucinogenic-type signaling.supported
No cross-tolerance with nonpsychedelic 5-HT2AR agonist lisuride. acschemneuro.2c00170
Serotonergic psychedelics are generally considered non-addictive as a classsupported
Generally physiologically safe; no dependence or addiction. pr.115.011478
Tramadol — a weak serotonin-norepinephrine reuptake inhibitor with additional µ-opioid agonist activity — is classified as a dangerous interaction, consistent with the established serotonin syndrome risk profile of tramadol combined with serotonergic agentssupported
Tramadol is associated with serotonin syndrome risk, especially with other serotonergic agents. pmid:26218943
A scoping review of antidepressant-psychedelic combinations found no confirmed serotonin syndrome cases in published clinical studies, though the review noted that most studies excluded participants on serotonergic medicationssupported
Concomitant use of ADs and classic psychedelics generally safe and tolerable with no increased serotonin syndrome risk for psilocybin. 02698811251368360
Concurrent tramadol use: Serotonin syndrome risk from combined serotonergic activity.supported
Tramadol is associated with serotonin syndrome risk, especially with other serotonergic agents. pmid:26218943
Concurrent SSRI/SNRI use: Theoretical serotonin syndrome risk, though confirmed cases are absent from the literature. Likely attenuation of psychedelic effects.supported
No increased serotonin syndrome risk for psilocybin. Some evidence of attenuated acute subjective effects. 02698811251368360
comparative-pharmacology9 · 6 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
LSM-775 reverses this pattern: full 5-HT₁A agonism masks partial 5-HT₂A agonism, yielding attenuated psychedelia with prominent somatic effects (nausea, sedation, cardiovascular burden).supported
5-HT1A activation masks hallucinogenic HTR. dta.2222
Nichols and colleagues demonstrated that the spatial orientation of the amide substituent dictates receptor complementaritysupported
(S,S)-2,4-dimethylazetidine lysergamide most LSD-like at 5-HT2A; provides structural insight into optimal amide conformation for 5-HT2A binding; substitution of the diethylamide group markedly affects potency. pmid:12213075
The diethyl groups of LSD adopt an optimal conformation within the 5-HT₂A binding pocket, as confirmed by the crystal structure of LSD bound to 5-HT₂Bsupported
Crystal structure of LSD-5-HT2B complex. Diethylamide moiety conformational selectivity. j.cell.2016.12.033
LSM-775 occupies a unique position within the lysergamide NPS series characterized by Brandt and colleagues, which includes AL-LAD, ETH-LAD, and 1CP-LSDsupported
AL-LAD and LSZ appeared on NPS market in 2013. AL-LAD ED50 = 174.9 nmol/kg. dta.1985
LSM-775 occupies a unique position within the lysergamide NPS series characterized by Brandt and colleagues, which includes AL-LAD, ETH-LAD, and 1CP-LSDsupported
ETH-LAD and 1P-ETH-LAD analytical characterization. dta.2196
LSM-775 occupies a unique position within the lysergamide NPS series characterized by Brandt and colleagues, which includes AL-LAD, ETH-LAD, and 1CP-LSDsupported
1CP-LSD ED50 = 430.0 nmol/kg in mouse HTR; confirmed prodrug of LSD in human serum incubation. dta.2789
summary8 · 4 ok
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
The compound received no further clinical investigation until its reappearance on the new psychoactive substances market in 2013, prompting a modern pharmacological characterization in 2018.supported
LSM-775 appeared on the NPS market in 2013. Characterized by X-ray crystallography, NMR, GC-MS, HPLC. dta.2222
Claim in summary — inconclusiveinconclusiveworking →
In the mouse head-twitch response assay, LSM-775 alone produces no significant response; hallucinogenic-type activity emerges only after pharmacological blockade of 5-HT₁A with WAY-100,635, demonstrating that concurrent 5-HT₁A activation masks 5-HT₂A-mediated effects.supported
Head twitch response only with 5-HT1A antagonist WAY-100,635 pretreatment (ED50 0.34 mg/kg). 5-HT1A activation masks hallucinogenic HTR. dta.2222
In the mouse head-twitch response assay, LSM-775 alone produces no significant response; hallucinogenic-type activity emerges only after pharmacological blockade of 5-HT₁A with WAY-100,635, demonstrating that concurrent 5-HT₁A activation masks 5-HT₂A-mediated effects.supported
5-HT1A activation by 5-MeO-DMT inhibits behavioral patterns; WAY-100635 antagonism reveals 5-HT1A-mediated suppression. Confirms 5-HT1A can mask 5-HT2A-dependent hallucinogenic effects. 0269881110388326
As a serotonergic psychedelic, the compound is presumed non-addictive and not habit-forming, with rapid tolerance developing through 5-HT₂A receptor downregulationsupported
DOI caused 5-HT2AR downregulation in frontal cortex; mechanism independent of beta-arrestin-2. acschemneuro.2c00170
receptor-pharmacology7 · 6 ok
Pretreatment with the selective 5-HT₁A antagonist WAY-100,635 (1 mg/kg s.c.) unmasked a robust dose-dependent HTR with ED₅₀ = 0.34 mg/kg (95% CI: 0.24–0.50 mg/kg)supported
Head twitch response only with 5-HT1A antagonist WAY-100,635 pretreatment (ED50 0.34 mg/kg). dta.2222
The receptor binding profile of LSM-775 has been characterized at two serotonin receptor subtypes:supported
Acts as nonselective agonist at 5-HT1A (Ki 31.0 nM) and 5-HT2A (Ki 29.5 nM). dta.2222
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
LSM-775 alone produced no significant HTR at doses up to those testedsupported
Head twitch response only with 5-HT1A antagonist WAY-100,635 pretreatment (ED50 0.34 mg/kg). dta.2222
This pharmacological dissection confirms that LSM-775 possesses intrinsic hallucinogenic potential at 5-HT₂A that is functionally suppressed by its concurrent 5-HT₁A full agonism — a mechanism previously demonstrated for 5-MeO-DMT.supported
5-HT1A activation by 5-MeO-DMT inhibits behavioral patterns; WAY-100635 antagonism reveals 5-HT1A-mediated suppression. 0269881110388326
This pharmacological dissection confirms that LSM-775 possesses intrinsic hallucinogenic potential at 5-HT₂A that is functionally suppressed by its concurrent 5-HT₁A full agonism — a mechanism previously demonstrated for 5-MeO-DMT.supported
Cryo-EM structures of 5-HT1A with 5-MeO-DMT; 5-HT1A-selective analogue devoid of hallucinogenic effects while retaining anxiolytic/antidepressant activity. s41586-024-07403-2
For LSD, the unusually slow k_off at 5-HT₂A (receptor residence time >1 hour) partially explains its prolonged duration; whether LSM-775's shorter reported duration reflects faster dissociation kinetics at 5-HT₂A is unknown.supported
Reveals EL2 lid mechanism explaining slow LSD dissociation kinetics. j.cell.2016.12.033
history6 · 1 ok
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
This prompted the first modern pharmacological characterization by Brandt and colleagues in 2018, who determined the receptor binding profile, functional activity, and behavioral pharmacology of the compound as part of their "Return of the Lysergamides" research seriessupported
Characterized by X-ray crystallography, NMR, GC-MS, HPLC. Acts as nonselective agonist at 5-HT1A (Ki 31.0 nM) and 5-HT2A (Ki 29.5 nM). dta.2222
pharmacokinetic-detail5 · 4 ok
LSD metabolism proceeds primarily via CYP2D6-mediated oxidation, producing 2-oxo-3-hydroxy-LSD as the principal urinary metabolite, with nor-LSD and glucuronide conjugates as minor productssupported
Main LSD metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD) in urine. Also nor-LSD, lysergic acid ethylamide, trioxylated-LSD, and glucuronide conjugates. s1570-0232(01)00494-9
LSD metabolism proceeds primarily via CYP2D6-mediated oxidation, producing 2-oxo-3-hydroxy-LSD as the principal urinary metabolite, with nor-LSD and glucuronide conjugates as minor productssupported
CYP2D6, CYP1A2, and CYP2C9 involved in LSD in vitro metabolism. s41598-021-90343-y
CYP2D6 poor metabolizers show approximately 75% higher LSD plasma concentrations and prolonged subjective effectssupported
Poor metabolizers had 75% higher plasma concentrations and longer half-lives. s41598-021-90343-y
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
LSD, by comparison, peaks at 1.4–2.5 hours and has a total subjective duration of 8–14 hourspartially supported
Duration 6.7-11h at 25-200 µg. s41386-020-00883-6
clinical-evidence4 · 0 ok
chemistry3 · 2 ok
This substitution imposes a rigid conformation on the amide nitrogen that constrains the spatial orientation of the carbonyl-adjacent substituent, a modification with direct consequences for receptor binding geometry.supported
Structural insight into optimal amide conformation for 5-HT2A binding; substitution of the diethylamide group markedly affects potency. pmid:12213075
Claim in chemistry — inconclusiveinconclusiveworking →
The hemitartrate salt has been characterized by X-ray crystallography, GC-MS, NMR, and HPLC-DADsupported
Characterized by X-ray crystallography, NMR, GC-MS, HPLC. dta.2222
neuroscience2 · 2 ok
Classical serotonergic psychedelics produce their characteristic effects through 5-HT₂A agonism on layer V pyramidal neurons in the prefrontal cortexsupported
Psychedelics are agonists or partial agonists at 5-HT2A receptors on apical dendrites of neocortical pyramidal cells in layer V. pr.115.011478
In behavioral assays, this opposition is decisive: LSM-775 produces no head-twitch response unless 5-HT₁A is pharmacologically blockedsupported
Head twitch response only with 5-HT1A antagonist WAY-100,635 pretreatment (ED50 0.34 mg/kg). 5-HT1A activation masks hallucinogenic HTR. dta.2222