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Psychedex
Sources
23
4 strong · 16 moderate · 3 weak

Studies and references cited across this article, graded by evidence strength.

Claims checked
75
45verified1partial29inconclusive

Inconclusive means the cited source neither confirms nor refutes the claim — a lower-confidence badge, not an error.

Generated
May 11, 2026 · pipeline-v5
Values approved
218/218 (100%)

Data points an editor reviewed and accepted for publication.

01

Value Provenance

Dosing

oraltrace

FieldPublishedAI ProposedConfidence
Threshold250 µg250 µglow
Low500–750 µg500–750 µglow
Common750–1250 µg750–1250 µglow
Strong1250–1500 µg1250–1500 µglow
Heavy1500+ µg1500+ µglow
Editorial

Community consensus from PsychonautWiki. Historical studies (Gogerty & Dille 1957, Abramson et al., Isbell et al.) used 75–150 µg and 4.5–9 µg/kg, producing only threshold effects — corroborating that sub-milligram doses are sub-threshold for most users. Single modern user report at ~1.1 mg (Erowid) produced common-to-strong effects. No controlled dose-finding study exists.

Reasoning

Community consensus from PsychonautWiki. Historical studies (Gogerty & Dille 1957, Abramson et al., Isbell et al.) used 75–150 µg and 4.5–9 µg/kg, producing only threshold effects — corroborating that sub-milligram doses are sub-threshold for most users. Single modern user report at ~1.1 mg (Erowid) produced common-to-strong effects. No controlled dose-finding study exists.

Evidence basis: community_consensus_large

Duration

oral

FieldPublishedAI ProposedConfidence
Onsettrace10–30 minutes10–30 minuteslow
Editorial

Community consensus (PsychonautWiki). Single user report at ~1.1 mg noted effects within ~1 hour total, suggesting relatively rapid onset for a lysergamide.

Reasoning

Community consensus (PsychonautWiki). Single user report at ~1.1 mg noted effects within ~1 hour total, suggesting relatively rapid onset for a lysergamide.

Evidence basis: community_consensus_large

Come uptrace20–45 minutes20–45 minuteslow
Editorial

Inferred from structural analogy with LSD (come-up ~30–60 min), adjusted shorter based on user report suggesting faster onset than typical lysergamides. No direct LSM-775 data for this phase.

Reasoning

Inferred from structural analogy with LSD (come-up ~30–60 min), adjusted shorter based on user report suggesting faster onset than typical lysergamides. No direct LSM-775 data for this phase.

Evidence basis: structural_analogy

Peaktrace1.5–3 hours1.5–3 hourslow
Editorial

Inferred from LSD analogy (peak ~2–4 h), adjusted shorter per historical reports indicating shorter total duration. Erowid report noted peak within ~1 hour, suggesting compressed timeline.

Reasoning

Inferred from LSD analogy (peak ~2–4 h), adjusted shorter per historical reports indicating shorter total duration. Erowid report noted peak within ~1 hour, suggesting compressed timeline.

Evidence basis: structural_analogy

Offsettrace2–4 hours2–4 hourslow
Editorial

Inferred from LSD analogy. No direct LSM-775 data for offset phase. Adjusted proportionally for shorter total duration.

Reasoning

Inferred from LSD analogy. No direct LSM-775 data for offset phase. Adjusted proportionally for shorter total duration.

Evidence basis: structural_analogy

Totaltrace6–10 hours6–10 hourslow
Editorial

Community consensus (PsychonautWiki). Historical data (Gogerty & Dille 1957) noted shorter duration than LSD. Consistent with overall 6–10 hour range. No controlled pharmacokinetic data.

Reasoning

Community consensus (PsychonautWiki). Historical data (Gogerty & Dille 1957) noted shorter duration than LSD. Consistent with overall 6–10 hour range. No controlled pharmacokinetic data.

Evidence basis: community_consensus_large

After effectstrace2–6 hours2–6 hourslow
Editorial

Inferred from LSD analogy. Residual fatigue and sedation expected given LSM-775's prominent 5-HT1A component. No direct data for aftereffects phase.

Reasoning

Inferred from LSD analogy. Residual fatigue and sedation expected given LSM-775's prominent 5-HT1A component. No direct data for aftereffects phase.

Evidence basis: structural_analogy

Safety

Toxicity Profiletrace

FieldPublishedAI ProposedConfidence
Acutelowlowlow
Chroniclowlowlow
Organs Affectedcardiovascular, gastrointestinalcardiovascular, gastrointestinallow
Editorial

Acute toxicity rated 'low' based on class-level evidence from LSD (extremely high therapeutic index per Nichols 2016) and one user report showing reversible somatic effects. Chronic toxicity rated 'low' with a theoretical 5-HT2B valvulopathy flag relevant only to repeated dosing patterns. No controlled toxicity data exist for LSM-775 in any species; toxic dose is unknown.

Reasoning

Acute toxicity rated 'low' based on class-level evidence from LSD (extremely high therapeutic index per Nichols 2016) and one user report showing reversible somatic effects. Chronic toxicity rated 'low' with a theoretical 5-HT2B valvulopathy flag relevant only to repeated dosing patterns. No controlled toxicity data exist for LSM-775 in any species; toxic dose is unknown.

Evidence basis: single_case_report

Dependence Profiletrace

FieldPublishedAI ProposedConfidence
Physicalnonenonemedium
Psychologicalnegligiblenegligiblemedium
Compulsive Redosingnegligiblenegligiblemedium
Dose Escalationnegligiblenegligiblemedium
Editorial

Class-level evidence from Nichols 2016 characterizes serotonergic psychedelics as non-addictive. No LSM-775-specific dependence data, but pharmacological profile (5-HT2A partial agonism, no dopamine reward engagement) and rapid tolerance predict negligible abuse liability. Severe body load further discourages repeated use.

Reasoning

Class-level evidence from Nichols 2016 characterizes serotonergic psychedelics as non-addictive. No LSM-775-specific dependence data, but pharmacological profile (5-HT2A partial agonism, no dopamine reward engagement) and rapid tolerance predict negligible abuse liability. Severe body load further discourages repeated use.

Evidence basis: community_consensus_large

Withdrawal Profiletrace

FieldPublishedAI ProposedConfidence
Severitynonenonemedium
Symptoms——medium
FatalNoNomedium
Medical SupervisionNot requiredNot requiredmedium
Editorial

No withdrawal syndrome documented for any serotonergic psychedelic. Class-level evidence from Nichols 2016.

Reasoning

No withdrawal syndrome documented for any serotonergic psychedelic. Class-level evidence from Nichols 2016.

Evidence basis: community_consensus_large

Tolerance Profiletrace

FieldPublishedAI ProposedConfidence
Builduprapidrapidmedium
Half-life6 days6 daysmedium
Full Reset14 days14 daysmedium
Cross-tolerancesLSD, psilocybin, mescaline, DMT, other lysergamidesLSD, psilocybin, mescaline, DMT, other lysergamidesmedium
Editorial

Community consensus values (PsychonautWiki) for buildup, half-life, and reset. Mechanism confirmed at class level by de la Fuente Revenga et al. 2022 (5-HT2A downregulation). No LSM-775-specific tolerance data exist.

Reasoning

Community consensus values (PsychonautWiki) for buildup, half-life, and reset. Mechanism confirmed at class level by de la Fuente Revenga et al. 2022 (5-HT2A downregulation). No LSM-775-specific tolerance data exist.

Evidence basis: community_consensus_large

Effects & Profile

Contraindications

FieldPublishedAI ProposedConfidence
psychiatric Psychotic disorders or personal history of psychosistraceabsoluteabsolutemedium
Editorial

Class-level contraindication for all serotonergic psychedelics. No LSM-775-specific data, but 5-HT2A partial agonism (89% efficacy) retains the mechanistic basis for psychosis risk.

Reasoning

Class-level contraindication for all serotonergic psychedelics. No LSM-775-specific data, but 5-HT2A partial agonism (89% efficacy) retains the mechanistic basis for psychosis risk.

other Concurrent MAOI usetraceabsoluteabsolutemedium
Editorial

Class-level absolute contraindication for serotonergic psychedelics. LSM-775's potent 5-HT1A full agonism may make this combination particularly dangerous.

Reasoning

Class-level absolute contraindication for serotonergic psychedelics. LSM-775's potent 5-HT1A full agonism may make this combination particularly dangerous.

other Concurrent tramadol usetraceabsoluteabsolutemedium
Editorial

Supported by Beakley 2015 class-level evidence and existing seed interaction data classifying tramadol as 'dangerous'. No LSM-775+tramadol-specific case reports.

Reasoning

Supported by Beakley 2015 class-level evidence and existing seed interaction data classifying tramadol as 'dangerous'. No LSM-775+tramadol-specific case reports.

psychiatric Bipolar disordertracerelativerelativemedium
Editorial

Class-level contraindication for serotonergic psychedelics. No LSM-775-specific data.

Reasoning

Class-level contraindication for serotonergic psychedelics. No LSM-775-specific data.

psychiatric Family history of psychotic disorderstracerelativerelativemedium
Editorial

Class-level contraindication for serotonergic psychedelics. No LSM-775-specific data.

Reasoning

Class-level contraindication for serotonergic psychedelics. No LSM-775-specific data.

other Concurrent SSRI/SNRI usetracerelativerelativemedium
Editorial

Class-level evidence supported by Tap 2025 scoping review. No LSM-775-specific interaction data.

Reasoning

Class-level evidence supported by Tap 2025 scoping review. No LSM-775-specific interaction data.

cardiovascular Cardiovascular diseasetracerelativerelativelow
Editorial

Single user report (Erowid) documents cardiovascular effects at effective doses. Evidence is limited but safety-critical.

Reasoning

Single user report (Erowid) documents cardiovascular effects at effective doses. Evidence is limited but safety-critical.

neurological Concurrent lithium usetracerelativerelativelow
Editorial

Class analogy with lysergamide + lithium seizure risk. No LSM-775-specific data or case reports.

Reasoning

Class analogy with lysergamide + lithium seizure risk. No LSM-775-specific data or case reports.

Timeline Phases

oral

FieldPublishedAI ProposedConfidence
Onsettrace600–1800 sec(i=0.15)600–1800 sec(i=0.15)low
Editorial

Onset and total duration from community consensus (PsychonautWiki). All intermediate phases (come_up, peak, resolution, afterglow) inferred from structural analogy with LSD, adjusted shorter per user reports and historical data (Gogerty & Dille 1957) indicating LSM-775 duration is shorter than LSD. Single Erowid report at ~1.1 mg noted peak within ~1 hour, faster than typical lysergamides.

Reasoning

Onset and total duration from community consensus (PsychonautWiki). All intermediate phases (come_up, peak, resolution, afterglow) inferred from structural analogy with LSD, adjusted shorter per user reports and historical data (Gogerty & Dille 1957) indicating LSM-775 duration is shorter than LSD. Single Erowid report at ~1.1 mg noted peak within ~1 hour, faster than typical lysergamides.

Evidence basis: structural_analogy

Come uptrace1200–2700 sec(i=0.40)1200–2700 sec(i=0.40)low
Editorial

Onset and total duration from community consensus (PsychonautWiki). All intermediate phases (come_up, peak, resolution, afterglow) inferred from structural analogy with LSD, adjusted shorter per user reports and historical data (Gogerty & Dille 1957) indicating LSM-775 duration is shorter than LSD. Single Erowid report at ~1.1 mg noted peak within ~1 hour, faster than typical lysergamides.

Reasoning

Onset and total duration from community consensus (PsychonautWiki). All intermediate phases (come_up, peak, resolution, afterglow) inferred from structural analogy with LSD, adjusted shorter per user reports and historical data (Gogerty & Dille 1957) indicating LSM-775 duration is shorter than LSD. Single Erowid report at ~1.1 mg noted peak within ~1 hour, faster than typical lysergamides.

Evidence basis: structural_analogy

Peaktrace5400–10800 sec(i=1.00)5400–10800 sec(i=1.00)low
Editorial

Onset and total duration from community consensus (PsychonautWiki). All intermediate phases (come_up, peak, resolution, afterglow) inferred from structural analogy with LSD, adjusted shorter per user reports and historical data (Gogerty & Dille 1957) indicating LSM-775 duration is shorter than LSD. Single Erowid report at ~1.1 mg noted peak within ~1 hour, faster than typical lysergamides.

Reasoning

Onset and total duration from community consensus (PsychonautWiki). All intermediate phases (come_up, peak, resolution, afterglow) inferred from structural analogy with LSD, adjusted shorter per user reports and historical data (Gogerty & Dille 1957) indicating LSM-775 duration is shorter than LSD. Single Erowid report at ~1.1 mg noted peak within ~1 hour, faster than typical lysergamides.

Evidence basis: structural_analogy

Resolutiontrace7200–14400 sec(i=0.35)7200–14400 sec(i=0.35)low
Editorial

Onset and total duration from community consensus (PsychonautWiki). All intermediate phases (come_up, peak, resolution, afterglow) inferred from structural analogy with LSD, adjusted shorter per user reports and historical data (Gogerty & Dille 1957) indicating LSM-775 duration is shorter than LSD. Single Erowid report at ~1.1 mg noted peak within ~1 hour, faster than typical lysergamides.

Reasoning

Onset and total duration from community consensus (PsychonautWiki). All intermediate phases (come_up, peak, resolution, afterglow) inferred from structural analogy with LSD, adjusted shorter per user reports and historical data (Gogerty & Dille 1957) indicating LSM-775 duration is shorter than LSD. Single Erowid report at ~1.1 mg noted peak within ~1 hour, faster than typical lysergamides.

Evidence basis: structural_analogy

Afterglowtrace7200–21600 sec(i=0.10)7200–21600 sec(i=0.10)low
Editorial

Onset and total duration from community consensus (PsychonautWiki). All intermediate phases (come_up, peak, resolution, afterglow) inferred from structural analogy with LSD, adjusted shorter per user reports and historical data (Gogerty & Dille 1957) indicating LSM-775 duration is shorter than LSD. Single Erowid report at ~1.1 mg noted peak within ~1 hour, faster than typical lysergamides.

Reasoning

Onset and total duration from community consensus (PsychonautWiki). All intermediate phases (come_up, peak, resolution, afterglow) inferred from structural analogy with LSD, adjusted shorter per user reports and historical data (Gogerty & Dille 1957) indicating LSM-775 duration is shorter than LSD. Single Erowid report at ~1.1 mg noted peak within ~1 hour, faster than typical lysergamides.

Evidence basis: structural_analogy

Dose Tier Summaries

thresholdtrace
low

Sub-perceptual to barely perceptual alterations. A slight mood shift — mild brightening or introspective coloring — may be noticed, alongside faint somatic awareness such as light nausea or a sense of bodily heaviness. No visual effects or geometry are present at this range. Historical studies at 75–150 µg often produced only threshold responses, with subjects unable to distinguish the experience from placebo or estimating the equivalent of just 25–35 µg LSD. Appetite suppression may be mildly noticeable. Duration is likely shorter than at higher doses. Functional impairment is minimal, though subtle cognitive shifts may be present for 3–5 hours.

Editorial

Based on historical human studies (Gogerty & Dille 1957, Abramson et al.) summarized in Brandt et al. 2018, where 75–150 µg produced only threshold responses. Community consensus places threshold at ~250 µg.

Reasoning

Based on historical human studies (Gogerty & Dille 1957, Abramson et al.) summarized in Brandt et al. 2018, where 75–150 µg produced only threshold responses. Community consensus places threshold at ~250 µg.

Evidence basis: community_consensus_large

lighttrace
low

Mild perceptual loosening becomes apparent — subtle color enhancement, slight brightness alteration, and faint pattern recognition enhancement. Visual effects remain minimal; no formed geometry or drifting. Music enhancement may be gently noticeable. Body load is already present at this range due to 5-HT1A dominance: moderate nausea, mild sedation, and a general sense of bodily heaviness. Appetite suppression is common. Yawning and watery eyes may occur as early somatic markers of serotonergic activity. Cognitive effects are minimal — slight novelty enhancement and mild introspection. Functional impairment is low but sedation may limit productivity. Expect 5–7 hours of noticeable effects.

Editorial

Inferred from community dose ranges (500–750 µg oral) and pharmacological profile: 5-HT1A full agonism produces somatic effects before perceptual threshold is fully crossed. User report and historical data confirm body load precedes visual onset.

Reasoning

Inferred from community dose ranges (500–750 µg oral) and pharmacological profile: 5-HT1A full agonism produces somatic effects before perceptual threshold is fully crossed. User report and historical data confirm body load precedes visual onset.

Evidence basis: community_consensus_large

commontrace
low

A recognizable but attenuated psychedelic state emerges. Color alteration takes on the earthy, sepia-toned quality characteristic of LSM-775. Mild geometry, visual drifting, and internal hallucinations are present but muted relative to LSD at equivalent subjective intensity. Depth perception distortion and perspective distortion may be noticed. Body load is significant and defines the experience at this tier: nausea is persistent, sedation and dreaminess are prominent, and spontaneous body sensations — sweating, temperature dysregulation, cardiovascular awareness — are common. Pupil dilation is expected. Appetite is strongly suppressed. Thought connectivity and conceptual thinking are enhanced. Introspection deepens. Time alteration is noticeable. The experience lasts 6–9 hours with residual fatigue afterward.

Editorial

Community consensus range (750–1250 µg). Single detailed user report at ~1.1 mg (Erowid) provides the primary texture: sepia color alteration, fractal geometry, severe body load, sedation. Pharmacological profile (5-HT1A masking 5-HT2A) explains the attenuated visual ceiling.

Reasoning

Community consensus range (750–1250 µg). Single detailed user report at ~1.1 mg (Erowid) provides the primary texture: sepia color alteration, fractal geometry, severe body load, sedation. Pharmacological profile (5-HT1A masking 5-HT2A) explains the attenuated visual ceiling.

Evidence basis: community_consensus_large

strongtrace
low

Pronounced psychedelic effects are present alongside severe body load. Visual drifting, object transformations, and geometry are clearly visible but remain muted compared to LSD — the 5-HT1A masking effect imposes a ceiling on perceptual intensity. Internal hallucinations may become vivid. Synesthesia is possible but uncommon. Nausea and vomiting are likely at this range. Tachycardia and elevated blood pressure have been documented at ~1.1 mg. Excessive sweating, muscle tension, and strong sedation dominate the physical experience. The body load is frequently described as the worst of any psychedelic. Cognitive effects include deep introspection, thought loops, confusion, and time alteration. Anxiety may arise from the severity of somatic discomfort. Duration is 7–10 hours with significant aftereffects.

Editorial

Community consensus range (1250–1500 µg). User report at ~1.1 mg documents vomiting, tachycardia, elevated blood pressure, and severe body load at this intensity. Pharmacological data (Brandt et al. 2018) confirms 5-HT1A masking limits visual ceiling.

Reasoning

Community consensus range (1250–1500 µg). User report at ~1.1 mg documents vomiting, tachycardia, elevated blood pressure, and severe body load at this intensity. Pharmacological data (Brandt et al. 2018) confirms 5-HT1A masking limits visual ceiling.

Evidence basis: community_consensus_large

heavytrace
low

Maximum psychedelic intensity achievable with LSM-775, though still below the ceiling of LSD or psilocybin due to intrinsic 5-HT1A suppression of 5-HT2A output. Visual effects — geometry, drifting, morphing, internal hallucinations — reach their peak but the experience is overwhelmingly dominated by somatic distress. Vomiting is expected. Severe cardiovascular burden — tachycardia, hypertension, excessive sweating — is likely. Sedation is profound. The gastrointestinal and cardiovascular effects at this range represent the primary safety concern; the psychedelic component, while present, is secondary to the body load. Very few reports exist at this range. User accounts strongly discourage high doses due to the disproportionate increase in body load relative to psychedelic depth. Duration is 8–10+ hours.

Editorial

Community consensus places heavy at 1500+ µg. Very few user reports at this range. Extrapolated from the single detailed report at ~1.1 mg (which already showed severe effects) and the pharmacological profile predicting worsening somatic burden with dose escalation.

Reasoning

Community consensus places heavy at 1500+ µg. Very few user reports at this range. Extrapolated from the single detailed report at ~1.1 mg (which already showed severe effects) and the pharmacological profile predicting worsening somatic burden with dose escalation.

Evidence basis: community_consensus_large

02

History

current version
published Jun 4, 2026AI-generated—
versions
1 total
publication ledger

backfill Jun 4, 2026

Historical versions do not record which reviewer approved them; editorial accountability is recorded per value in the database and in the publication ledger going forward.

full version history suggest a correctioncontact@psychedex.org
03

Sources

4 strong · 16 moderate · 3 weak
  1. [1]
    moderate
    Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM-775)
    Brandt SD, Kavanagh PV, Twamley B, Westphal F, Elliott SP, Wallach J, Stratford A, Klein LM, McCorvy JD, Nichols DE, Halberstadt AL · 2018 · Drug Testing and Analysis
    doi.org/10.1002/dta.2222pubmed 2858539229 claims checked13 verified16 inconclusive
  2. [2]
    moderate
    Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice
    Halberstadt AL, Koedood L, Powell SB, Geyer MA · 2011 · Journal of Psychopharmacology
    doi.org/10.1177/0269881110388326pubmed 211480214 claims checked4 verified
  3. [3]
    moderate
    Pharmacology of d-lysergic acid morpholide (LSM)
    Gogerty JH, Dille JM · 1957 · The Journal of Pharmacology and Experimental Therapeutics
    pubmed 134763566 claims checked6 inconclusive
  4. [4]
    weak
    LSM-775 Erowid Experience Report: The Most Unique Lysergamide I've Tried
    2013
    linkno claims checked
  5. [5]
    moderate
    Tolerance and Cross-Tolerance among Psychedelic and Nonpsychedelic 5-HT2A Receptor Agonists in Mice
    de la Fuente Revenga M, Jaster AM, McGinn J, Silva G, Saha S, Gonzalez-Maeso J · 2022 · ACS Chemical Neuroscience
    doi.org/10.1021/acschemneuro.2c00170pubmed 359008764 claims checked3 verified1 inconclusive
  6. [6]
    weak
    LSM-775 dosage and effects
    PsychonautWiki contributors · 2024
    linkno claims checked
  7. [7]
    moderate
    Biosynthesis, total synthesis, and biological profiles of Ergot alkaloids
    Tasker NR, Wipf P · 2021 · The Alkaloids: Chemistry and Biology
    doi.org/10.1016/bs.alkal.2020.08.001pubmed 336637511 claim checked1 inconclusive
  8. [8]
    moderate
    Lysergamides of isomeric 2,4-dimethylazetidines map the binding orientation of the diethylamide moiety in the potent hallucinogenic agent N,N-diethyllysergamide (LSD)
    Nichols DE, Frescas S, Marona-Lewicka D, Kurrasch-Orbaugh DM · 2002 · Journal of Medicinal Chemistry
    pubmed 122130753 claims checked2 verified1 inconclusive
  9. [9]
    moderate
    Crystal Structure of an LSD-Bound Human Serotonin Receptor
    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 · Cell
    doi.org/10.1016/j.cell.2016.12.0334 claims checked2 verified2 inconclusive
  10. [10]
    moderate
    Structural pharmacology and therapeutic potential of 5-methoxytryptamines.
    Warren AL, Lankri D, Cunningham MJ, Serrano IC, Parise LF, Kruegel AC, Duggan P, Zilberg G, Capper MJ, Havel V, Russo SJ, Sames D, Wacker D · 2024 · Nature
    doi.org/10.1038/s41586-024-07403-2pubmed 387200723 claims checked2 verified1 inconclusive
  11. [11]
    moderate
    Transcriptome fingerprints distinguish hallucinogenic and nonhallucinogenic 5-hydroxytryptamine 2A receptor agonist effects in mouse somatosensory cortex.
    González-Maeso J, Yuen T, Ebersole BJ, et al. · 2003 · Journal of Neuroscience
    pubmed 145230841 claim checked1 verified
  12. [12]
    strong
    Genetic influence of CYP2D6 on pharmacokinetics and acute subjective effects of LSD in a pooled analysis
    Vizeli P, Straumann I, Holze F, Schmid Y, Dolder PC, Liechti ME · 2021 · Scientific Reports
    doi.org/10.1038/s41598-021-90343-ypubmed 340353914 claims checked4 verified
  13. [13]
    moderate
    Determination of LSD and its metabolites in human biological fluids by HPLC-MS/MS
    Canezin J, Cailleux A, Turcant A, Le Bouil A, Harry P, Allain P · 2001 · Journal of Chromatography B
    doi.org/10.1016/s1570-0232(01)00494-9pubmed 118173052 claims checked2 verified
  14. [14]
    strong
    Psychedelics
    Nichols DE · 2016 · Pharmacological Reviews
    doi.org/10.1124/pr.115.011478pubmed 268418004 claims checked3 verified1 inconclusive
  15. [15]
    moderate
    Pharmacokinetics and subjective effects of 1P-LSD in humans after oral and intravenous administration
    Grumann C, Henkel K, Brandt SD, Stratford A, Passie T, Auwaerter V · 2020 · Drug Testing and Analysis
    doi.org/10.1002/dta.2821pubmed 324157501 claim checked1 verified
  16. [16]
    strong
    Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects
    Holze F, Vizeli P, Müller F, Ley L, Duerig R, Varghese N, Zizzari P, Liechti ME · 2021 · Neuropsychopharmacology
    doi.org/10.1038/s41386-020-00883-6pubmed 330400881 claim checked1 partial
  17. [17]
    moderate
    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)
    Brandt SD, Kavanagh PV, Westphal F, Elliott SP, Wallach J, Colestock T, Burrow TE, Chapman SJ, Stratford A, Nichols DE, Halberstadt AL · 2017 · Drug Testing and Analysis
    doi.org/10.1002/dta.1985pubmed 272658911 claim checked1 verified
  18. [18]
    moderate
    Return of the lysergamides. Part III: Analytical characterization of ETH-LAD and 1P-ETH-LAD
    Brandt SD, Kavanagh PV, Westphal F, Elliott SP, Wallach J, Stratford A, Nichols DE, Halberstadt AL · 2017 · Drug Testing and Analysis
    doi.org/10.1002/dta.2196pubmed 283421781 claim checked1 verified
  19. [19]
    moderate
    Return of the lysergamides. Part VI: Analytical and behavioural characterization of 1-cyclopropanoyl-d-lysergic acid diethylamide (1CP-LSD)
    Brandt SD, Kavanagh PV, Westphal F, Stratford A, Odland AU et al. · 2020 · Drug Testing and Analysis
    doi.org/10.1002/dta.2789pubmed 321803501 claim checked1 verified
  20. [20]
    moderate
    A Review of Hallucinogen Persisting Perception Disorder (HPPD) and an Exploratory Study of Subjects Claiming Symptoms of HPPD
    Halpern JH, Lerner AG, Passie T · 2018 · Current Topics in Behavioral Neurosciences
    doi.org/10.1007/7854_2016_457pubmed 278226791 claim checked1 verified
  21. [21]
    moderate
    Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review
    Beakley BD, Kaye AM, Kaye AD · 2015 · Pain Physician
    pubmed 262189432 claims checked2 verified
  22. [22]
    strong
    Concomitant use of antidepressants and classic psychedelics: A scoping review
    Tap SC, Thomas K, Páleníček T, et al. · 2025 · Journal of Psychopharmacology
    doi.org/10.1177/02698811251368360pubmed 409377322 claims checked2 verified
  23. [23]
    weak
    LSM-775 legal status and pharmacology
    Wikipedia contributors · 2024
    linkno claims checked
04

Claim Verification

Citation-bearing claims in this article were checked by an AI model against the abstract of the source they cite — every safety-critical claim, plus a sample of the rest. Verdicts below are model-issued, not human-issued; when an editor overrides a verdict, the override is recorded alongside it. Claims whose source does not support them are flagged for editorial review.

summary8 claims4verified4inconclusive
inconclusiveActive in the high-microgram to low-milligram range (threshold ~250 µg oral; common 750–1250 µg oral), LSM-775 is approximately 5- to 10-fold less potent than LSD by weight and produces a shorter total duration of 6–10 hours.[1]model confidence 85%
Inconclusive

The abstract confirms LSM-775 pharmacological characterization but contains no dose range, potency ratio vs LSD, or duration data. These specific figures may appear in the full paper but are absent from the abstract.

LSM-775 appeared on the NPS market in 2013. Acts as nonselective agonist at 5-HT1A (Ki 31.0 nM) and 5-HT2A (Ki 29.5 nM).

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveLSM-775 was first synthesized by Albert Hofmann and colleagues at Sandoz Laboratories (Basel, Switzerland) as compound number 775 in the systematic exploration of lysergic acid amide derivatives, with the earliest published pharmacological data appearing in 1957[3]model confidence 90%
Inconclusive

No abstract available in PubMed. The scope confirms this is the earliest published pharmacological study from 1957, but the abstract text cannot verify the specific claims about Hofmann, Sandoz, or compound numbering.

No abstract available in PubMed. Earliest published pharmacological study of LSM-775 including human subject data.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThree small-scale human studies conducted in the late 1950s characterized LSM-775 as markedly weaker than LSD and incapable of producing more than threshold psychedelic responses at the doses tested[1]model confidence 85%
Inconclusive

The abstract covers modern pharmacological characterization and does not include historical human study data from the 1950s. This historical context may appear in the full paper body.

LSM-775 appeared on the NPS market in 2013. Acts as nonselective agonist at 5-HT1A (Ki 31.0 nM) and 5-HT2A (Ki 29.5 nM).

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe compound received no further clinical investigation until its reappearance on the new psychoactive substances market in 2013, prompting a modern pharmacological characterization in 2018.[1]model confidence 90%
Verified

The abstract confirms LSM-775 appeared on the NPS market in 2013, and this paper is itself the modern pharmacological characterization it prompted.

LSM-775 appeared on the NPS market in 2013. Characterized by X-ray crystallography, NMR, GC-MS, HPLC.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveLSM-775 binds 5-HT₁A (Ki = 31.0 ± 7.4 nM) and 5-HT₂A (Ki = 29.5 ± 4.1 nM) with near-equal affinity, but functions as a full agonist at 5-HT₁A (EC₅₀ = 1.03 nM, 98% efficacy) and only a partial agonist at 5-HT₂A (EC₅₀ = 4.9 nM, 89% efficacy)[1]model confidence 85%
Inconclusive

The abstract confirms Ki values for both receptors (31.0 nM 5-HT1A; 29.5 nM 5-HT2A), but the specific EC₅₀ values, efficacy percentages, and full vs. partial agonist distinction are absent from the abstract and require the full text.

Acts as nonselective agonist at 5-HT1A (Ki 31.0 nM) and 5-HT2A (Ki 29.5 nM).

checked by claude-sonnet-4-6 · May 11, 2026

verifiedIn 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.[1]model confidence 98%
Verified

Abstract directly confirms all three elements: no HTR without pretreatment, HTR only with WAY-100,635, and the 5-HT1A masking mechanism.

Head twitch response only with 5-HT1A antagonist WAY-100,635 pretreatment (ED50 0.34 mg/kg). 5-HT1A activation masks hallucinogenic HTR.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedIn 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.[2]model confidence 95%
Verified

Abstract confirms the mechanistic framework: 5-HT1A activation suppresses 5-HT2A-dependent behavioral effects, and WAY-100635 antagonism unmasks this suppression — directly relevant to LSM-775's profile.

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.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedAs a serotonergic psychedelic, the compound is presumed non-addictive and not habit-forming, with rapid tolerance developing through 5-HT₂A receptor downregulation[5]model confidence 90%
Verified

Abstract confirms 5-HT2A receptor downregulation as the tolerance mechanism for psychedelics, supporting the claim that tolerance develops through this pathway.

DOI caused 5-HT2AR downregulation in frontal cortex; mechanism independent of beta-arrestin-2.

checked by claude-sonnet-4-6 · May 11, 2026

history6 claims1verified5inconclusive
inconclusiveThe first published pharmacological study was conducted by Gogerty and Dille in 1957, who reported that 75 µg of LSM-775 produced approximately the same subjective response as 50 µg of LSD in two human subjects, with a shorter duration of action[3]model confidence 90%
Inconclusive

No abstract available. The scope confirms this is the 1957 study with human data, but specific details (Gogerty and Dille, 75 µg dose, 50 µg LSD comparison, two subjects) cannot be verified from the abstract.

No abstract available in PubMed. Earliest published pharmacological study of LSM-775 including human subject data.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveTwo additional early human studies are known through secondary summary: Abramson and colleagues administered 150 µg to three subjects, two of whom estimated they had received 25–35 µg of LSD, while a third believed they had received placebo[1]model confidence 85%
Inconclusive

The abstract covers modern pharmacological characterization and does not contain historical human study data. The Abramson study details may be summarized in the full paper body.

LSM-775 appeared on the NPS market in 2013. Characterized by X-ray crystallography, NMR, GC-MS, HPLC.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThe compound first appeared in the scientific literature in approximately 1955.[1]model confidence 80%
Inconclusive

Abstract does not mention the date of first appearance in scientific literature. Historical context may be in the full paper body.

LSM-775 appeared on the NPS market in 2013.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThe compound first appeared in the scientific literature in approximately 1955.[7]model confidence 75%
Inconclusive

Abstract covers Sandoz ergot alkaloid history and synthesis of unnatural analogs, which is consistent context. However, no specific date of 1955 for LSM-775's first appearance is mentioned.

Several natural ergot alkaloids discovered and unnatural analogs synthesized at Sandoz. Reviews history and therapeutic applications.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveIts emergence was presumably motivated by the historical reports suggesting weak LSD-like effects[1]model confidence 75%
Inconclusive

Abstract confirms NPS market appearance in 2013 but does not discuss the motivation behind its emergence. This inference may be stated in the full paper's historical discussion.

LSM-775 appeared on the NPS market in 2013.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThis 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 series[1]model confidence 92%
Verified

The abstract confirms modern pharmacological characterization (receptor binding, analytical chemistry, HTR). The paper title confirms it is part of the 'Return of the Lysergamides' series.

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).

checked by claude-sonnet-4-6 · May 11, 2026

chemistry3 claims2verified1inconclusive
verifiedThis 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.[8]model confidence 88%
Verified

Abstract confirms that amide conformation matters critically for 5-HT2A binding (optimal amide conformation for 5-HT2A binding) and that substitution markedly affects potency — consistent with the claim that morpholine's rigid conformation has consequences for receptor binding geometry.

Structural insight into optimal amide conformation for 5-HT2A binding; substitution of the diethylamide group markedly affects potency.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThe absolute configuration has been established by X-ray crystallographic analysis of the hemitartrate salt, which crystallizes in the orthorhombic P2₁2₁2₁ space group with anomalous dispersion confirming the stereochemical assignment[1]model confidence 80%
Inconclusive

Abstract confirms X-ray crystallographic characterization, but the specific details (hemitartrate salt, orthorhombic P2₁2₁2₁ space group, anomalous dispersion) are not in the abstract and require the full paper.

Characterized by X-ray crystallography, NMR, GC-MS, HPLC.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe hemitartrate salt has been characterized by X-ray crystallography, GC-MS, NMR, and HPLC-DAD[1]model confidence 90%
Verified

Abstract explicitly lists X-ray crystallography, NMR, GC-MS, and HPLC as characterization methods. The 'hemitartrate salt' and 'HPLC-DAD' specification are not confirmed but the methods are.

Characterized by X-ray crystallography, NMR, GC-MS, HPLC.

checked by claude-sonnet-4-6 · May 11, 2026

pharmacology19 claims12verified7inconclusive
verifiedLSM-775 is a serotonin receptor agonist that acts simultaneously at 5-HT₁A and 5-HT₂A receptors with near-equal binding affinity but divergent functional profiles[1]model confidence 95%
Verified

Abstract directly confirms agonism at both 5-HT1A (Ki 31.0 nM) and 5-HT2A (Ki 29.5 nM) with near-equal affinity. Divergent functional profiles are implied by the HTR masking data showing different behavioral outcomes.

Acts as nonselective agonist at 5-HT1A (Ki 31.0 nM) and 5-HT2A (Ki 29.5 nM). 5-HT1A activation masks hallucinogenic HTR.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveAt 5-HT₁A, it functions as a full agonist (EC₅₀ = 1.03 nM, 98 ± 2% efficacy relative to serotonin), while at 5-HT₂A it operates as a partial agonist (EC₅₀ = 4.9 nM at human receptors, 89 ± 2% efficacy)[1]model confidence 85%
Inconclusive

The abstract only provides Ki binding values and does not contain EC₅₀ potency values, efficacy percentages, or the full vs. partial agonist distinction. These functional data require the full paper.

Acts as nonselective agonist at 5-HT1A (Ki 31.0 nM) and 5-HT2A (Ki 29.5 nM).

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThe 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.[14]model confidence 80%
Inconclusive

Review paper abstract confirms 5-HT2A on neocortical layer V pyramidal cells, supporting that aspect of the claim. However, the Gq-coupling specification and the 5-HT1A dampening mechanism are not mentioned in the abstract and would need to be found in the review body.

Psychedelics are agonists or partial agonists at 5-HT2A receptors on apical dendrites of neocortical pyramidal cells in layer V.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe 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.[2]model confidence 90%
Verified

Abstract confirms 5-HT2A is required for HTR and directly demonstrates that 5-HT1A activation suppresses 5-HT2A-dependent behavioral effects — the opposing/dampening relationship is explicitly confirmed.

5-HT2A required for HTR; 5-HT1A activation by 5-MeO-DMT inhibits behavioral patterns; WAY-100635 antagonism reveals 5-HT1A-mediated suppression.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThe 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.[10]model confidence 80%
Inconclusive

Abstract maps 5-HT1A vs 5-HT2A signaling distinctions and shows 5-HT1A-selective activity is non-hallucinogenic, supporting the opposing roles. However, Gq-coupled signaling and neocortical layer V specifics are not in the abstract.

5-HT1A-selective analogue devoid of hallucinogenic effects while retaining anxiolytic/antidepressant activity; maps molecular basis of 5-HT1A vs 5-HT2A signaling.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedIn the mouse head-twitch response (HTR) assay — the standard preclinical proxy for hallucinogenic potential — LSM-775 alone produced no significant response[1]model confidence 97%
Verified

Abstract directly implies LSM-775 alone produces no HTR by stating HTR occurs only with 5-HT1A antagonist pretreatment.

Head twitch response only with 5-HT1A antagonist WAY-100,635 pretreatment (ED50 0.34 mg/kg).

checked by claude-sonnet-4-6 · May 11, 2026

verifiedOnly 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)[1]model confidence 90%
Verified

Abstract confirms HTR only with WAY-100,635 pretreatment and ED50 = 0.34 mg/kg. The specific WAY dose (1 mg/kg s.c.) and 95% CI are not in the abstract but the core data is confirmed.

Head twitch response only with 5-HT1A antagonist WAY-100,635 pretreatment (ED50 0.34 mg/kg).

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThis masking phenomenon parallels observations with 5-MeO-DMT and is analogous to the non-hallucinogenic 5-HT₂A agonist lisuride.[2]model confidence 95%
Verified

Abstract directly confirms 5-HT1A activation by 5-MeO-DMT suppresses 5-HT2A-mediated behavioral effects — this is the exact parallel claimed.

5-HT1A activation by 5-MeO-DMT inhibits behavioral patterns; WAY-100635 antagonism reveals 5-HT1A-mediated suppression.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThis masking phenomenon parallels observations with 5-MeO-DMT and is analogous to the non-hallucinogenic 5-HT₂A agonist lisuride.[10]model confidence 88%
Verified

Abstract uses 5-MeO-DMT at 5-HT1A and demonstrates that 5-HT1A-selective agonism is devoid of hallucinogenic effects, directly supporting the 5-MeO-DMT parallel in the masking phenomenon.

Cryo-EM structures of 5-HT1A with 5-MeO-DMT; 5-HT1A-selective analogue devoid of hallucinogenic effects while retaining anxiolytic/antidepressant activity.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThis masking phenomenon parallels observations with 5-MeO-DMT and is analogous to the non-hallucinogenic 5-HT₂A agonist lisuride.[11]model confidence 93%
Verified

Abstract directly confirms lisuride as a non-hallucinogenic 5-HT2A agonist that does not produce HTR, supporting the lisuride analogy in the claim.

lisuride (non-hallucinogenic 5-HT2A agonist) does not induce HTR and shows distinct fingerprint.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThe crystal structure of LSD bound to 5-HT₂B demonstrates that the diethyl groups adopt specific conformational arrangements to optimally occupy the receptor binding pocket; the morpholine substitution disrupts these interactions, reducing intrinsic 5-HT₂A potency while leaving 5-HT₁A activity relatively intact.[9]model confidence 80%
Inconclusive

Abstract confirms the LSD-5-HT2B crystal structure and diethylamide moiety conformational selectivity, supporting the first part of the claim. The morpholine substitution effects on 5-HT2A vs 5-HT1A are not in the abstract.

Crystal structure of LSD-5-HT2B complex. Reveals EL2 lid mechanism explaining slow LSD dissociation kinetics. Diethylamide moiety conformational selectivity.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThe crystal structure of LSD bound to 5-HT₂B demonstrates that the diethyl groups adopt specific conformational arrangements to optimally occupy the receptor binding pocket; the morpholine substitution disrupts these interactions, reducing intrinsic 5-HT₂A potency while leaving 5-HT₁A activity relatively intact.[8]model confidence 75%
Inconclusive

Abstract supports the SAR aspect (amide substitution markedly affects 5-HT2A potency), which underpins the morpholine disruption claim. However, the crystal structure reference is not from this paper, and 5-HT1A sparing effects are not addressed in the abstract.

Substitution of the diethylamide group markedly affects potency; structural insight into optimal amide conformation for 5-HT2A binding.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe only pharmacological characterization of LSM-775 reports binding at serotonin receptors exclusively[1]model confidence 88%
Verified

The abstract reports only 5-HT1A and 5-HT2A serotonin receptor data for LSM-775, with no mention of dopamine, adrenergic, or other receptor classes — consistent with serotonin-exclusive characterization.

Acts as nonselective agonist at 5-HT1A (Ki 31.0 nM) and 5-HT2A (Ki 29.5 nM).

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveDopamine receptor activity is plausible given the shared ergoline scaffold with LSD, which binds D₂ receptors with nanomolar affinity, but this remains experimentally unconfirmed for LSM-775.[9]model confidence 75%
Inconclusive

Abstract is about the LSD-5-HT2B crystal structure and does not address dopamine receptor binding. LSD's D2 affinity and the ergoline scaffold-dopamine relationship are not mentioned.

Crystal structure of LSD-5-HT2B complex. Reveals EL2 lid mechanism explaining slow LSD dissociation kinetics.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedBy structural analogy with LSD: lysergamide metabolism involves CYP2D6 (primary), CYP1A2, and CYP2C9[12]model confidence 95%
Verified

Abstract directly confirms CYP2D6, CYP1A2, and CYP2C9 are involved in LSD in vitro metabolism, supporting this claim by structural analogy.

CYP2D6, CYP1A2, and CYP2C9 involved in LSD in vitro metabolism.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedCYP2D6 poor metabolizers exhibit approximately 75% higher LSD plasma concentrations and prolonged half-lives[12]model confidence 98%
Verified

Abstract directly and precisely confirms both numerical claim and the half-life finding.

Poor metabolizers had 75% higher plasma concentrations and longer half-lives.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedLSD's principal urinary metabolite is 2-oxo-3-hydroxy-LSD, with nor-LSD and glucuronide conjugates also detected[13]model confidence 97%
Verified

Abstract directly confirms 2-oxo-3-hydroxy-LSD as the main metabolite in urine, with nor-LSD and glucuronide conjugates also identified.

Main LSD metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD) in urine. Also nor-LSD, lysergic acid ethylamide, trioxylated-LSD, and glucuronide conjugates.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedLSD elimination half-life is approximately 5.7–6.4 hours[15]model confidence 98%
Verified

Abstract directly confirms LSD terminal t1/2 ≈ 5.7–6.4 h after oral administration.

LSD terminal t1/2 ≈ 5.7–6.4 h after oral administration.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveHistorical human reports describe LSM-775's duration as shorter than LSD at equivalent subjective doses, which could indicate a faster elimination rate or shorter receptor residence time, but neither parameter has been determined[3]model confidence 90%
Inconclusive

No abstract available. Scope confirms this is the 1957 study with human data, but the specific duration comparison cannot be verified from the abstract text.

No abstract available in PubMed. Earliest published pharmacological study of LSM-775 including human subject data.

checked by claude-sonnet-4-6 · May 11, 2026

receptor pharmacology7 claims6verified1inconclusive
verifiedPretreatment 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)[1]model confidence 90%
Verified

Abstract confirms WAY-100,635 pretreatment produces HTR with ED50 = 0.34 mg/kg. The WAY-100,635 dose and CI bounds are not in the abstract but the core finding is confirmed.

Head twitch response only with 5-HT1A antagonist WAY-100,635 pretreatment (ED50 0.34 mg/kg).

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe receptor binding profile of LSM-775 has been characterized at two serotonin receptor subtypes:[1]model confidence 97%
Verified

Abstract directly confirms binding characterized at 5-HT1A and 5-HT2A — exactly two serotonin receptor subtypes.

Acts as nonselective agonist at 5-HT1A (Ki 31.0 nM) and 5-HT2A (Ki 29.5 nM).

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveFunctional potency and intrinsic efficacy were determined using calcium mobilization (5-HT₂A, 5-HT₂B, 5-HT₂C) and cAMP inhibition (5-HT₁A) assays:[1]model confidence 80%
Inconclusive

Abstract does not mention calcium mobilization assays, cAMP inhibition assays, or 5-HT2B/5-HT2C receptor subtypes. These methodological and receptor coverage details are in the full paper only.

Acts as nonselective agonist at 5-HT1A (Ki 31.0 nM) and 5-HT2A (Ki 29.5 nM).

checked by claude-sonnet-4-6 · May 11, 2026

verifiedLSM-775 alone produced no significant HTR at doses up to those tested[1]model confidence 97%
Verified

Abstract directly implies this by stating HTR occurs only with WAY-100,635 pretreatment.

Head twitch response only with 5-HT1A antagonist WAY-100,635 pretreatment (ED50 0.34 mg/kg).

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThis 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.[2]model confidence 95%
Verified

Abstract directly confirms that 5-HT1A activation by 5-MeO-DMT suppresses 5-HT2A behavioral effects, which is the mechanism cited as precedent for LSM-775.

5-HT1A activation by 5-MeO-DMT inhibits behavioral patterns; WAY-100635 antagonism reveals 5-HT1A-mediated suppression.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThis 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.[10]model confidence 88%
Verified

Abstract demonstrates with 5-MeO-DMT cryo-EM structures that 5-HT1A-selective activity produces no hallucinogenic effects, directly supporting the masking mechanism precedent from 5-MeO-DMT.

Cryo-EM structures of 5-HT1A with 5-MeO-DMT; 5-HT1A-selective analogue devoid of hallucinogenic effects while retaining anxiolytic/antidepressant activity.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedFor 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.[9]model confidence 92%
Verified

Abstract directly confirms the EL2 lid mechanism explains LSD's slow dissociation kinetics, which is the structural basis for the slow k_off referenced in the claim.

Reveals EL2 lid mechanism explaining slow LSD dissociation kinetics.

checked by claude-sonnet-4-6 · May 11, 2026

neuroscience2 claims2verified
verifiedClassical serotonergic psychedelics produce their characteristic effects through 5-HT₂A agonism on layer V pyramidal neurons in the prefrontal cortex[14]model confidence 88%
Verified

Abstract confirms 5-HT2A agonism on neocortical pyramidal cells in layer V as the mechanism for psychedelic effects. 'Prefrontal cortex' is a common specification of neocortex that is a reasonable inference from the broader 'neocortical' description.

Psychedelics are agonists or partial agonists at 5-HT2A receptors on apical dendrites of neocortical pyramidal cells in layer V.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedIn behavioral assays, this opposition is decisive: LSM-775 produces no head-twitch response unless 5-HT₁A is pharmacologically blocked[1]model confidence 98%
Verified

Abstract directly confirms LSM-775 produces HTR only with 5-HT1A antagonist pretreatment, meaning no HTR occurs without 5-HT1A blockade.

Head twitch response only with 5-HT1A antagonist WAY-100,635 pretreatment (ED50 0.34 mg/kg). 5-HT1A activation masks hallucinogenic HTR.

checked by claude-sonnet-4-6 · May 11, 2026

pharmacokinetic detail5 claims3verified1partial1inconclusive
verifiedLSD 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 products[13]model confidence 93%
Verified

Abstract directly confirms 2-oxo-3-hydroxy-LSD as the main urinary metabolite, with nor-LSD and glucuronide conjugates also identified.

Main LSD metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD) in urine. Also nor-LSD, lysergic acid ethylamide, trioxylated-LSD, and glucuronide conjugates.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedLSD 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 products[12]model confidence 92%
Verified

Abstract confirms CYP2D6, CYP1A2, and CYP2C9 involvement in LSD in vitro metabolism, directly supporting the CYP2D6-primary claim.

CYP2D6, CYP1A2, and CYP2C9 involved in LSD in vitro metabolism.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedCYP2D6 poor metabolizers show approximately 75% higher LSD plasma concentrations and prolonged subjective effects[12]model confidence 95%
Verified

Abstract confirms 75% higher plasma concentrations and longer half-lives in poor metabolizers. 'Prolonged subjective effects' is a reasonable inference from longer half-lives.

Poor metabolizers had 75% higher plasma concentrations and longer half-lives.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveHistorical human data report LSM-775's duration as shorter than LSD at equivalent subjective doses[3]model confidence 90%
Inconclusive

No abstract available. Cannot verify duration comparison from the abstract.

No abstract available in PubMed. Earliest published pharmacological study of LSM-775 including human subject data.

checked by claude-sonnet-4-6 · May 11, 2026

partialLSD, by comparison, peaks at 1.4–2.5 hours and has a total subjective duration of 8–14 hours[16]model confidence 85%
Partial

Abstract reports LSD duration as 6.7–11 h at 25–200 µg, which does not match the claimed 8–14 h range — the upper bound of 14 h is materially higher than the 11 h maximum reported, and the lower bound of 8 h is higher than the 6.7 h reported. Peak time (1.4–2.5 h) is not mentioned in the abstract.

Duration 6.7-11h at 25-200 µg.

checked by claude-sonnet-4-6 · May 11, 2026

clinical evidence4 claims4inconclusive
inconclusiveGogerty and Dille (1957) administered 75 µg to two subjects and compared the response to LSD[3]model confidence 90%
Inconclusive

No abstract available. Cannot verify specific claim details from the abstract.

No abstract available in PubMed. Earliest published pharmacological study of LSM-775 including human subject data.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveAbramson and colleagues administered 150 µg to three subjects[1]model confidence 80%
Inconclusive

Abstract does not contain historical human study data. The Abramson study details may be summarized in the full paper's historical context section.

LSM-775 appeared on the NPS market in 2013.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveIsbell and colleagues administered 4.5 and 9 µg/kg to subjects, observing only threshold responses.[1]model confidence 80%
Inconclusive

Abstract does not contain historical human study data. The Isbell study details may be in the full paper's historical context section.

LSM-775 appeared on the NPS market in 2013.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThese studies employed minimal sample sizes, lacked placebo controls and blinding protocols by contemporary standards, and are available only through secondary summary[1]model confidence 75%
Inconclusive

Abstract contains no discussion of historical study methodology, sample sizes, or blinding. This methodological critique may be discussed in the full paper's historical context section.

LSM-775 appeared on the NPS market in 2013.

checked by claude-sonnet-4-6 · May 11, 2026

comparative pharmacology9 claims6verified3inconclusive
inconclusiveHistorical human data from three studies confirm this disparity: 75 µg LSM-775 produced effects comparable to only ~50 µg LSD, 150 µg was perceived as equivalent to 25–35 µg LSD, and doses up to 9 µg/kg produced only threshold responses.[3]model confidence 90%
Inconclusive

No abstract available. Scope confirms this is the first study with human data, but the specific numerical comparisons cannot be verified.

No abstract available in PubMed. Earliest published pharmacological study of LSM-775 including human subject data.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveHistorical human data from three studies confirm this disparity: 75 µg LSM-775 produced effects comparable to only ~50 µg LSD, 150 µg was perceived as equivalent to 25–35 µg LSD, and doses up to 9 µg/kg produced only threshold responses.[1]model confidence 80%
Inconclusive

Abstract contains no historical human study data. The three studies and their dose/response comparisons may be summarized in the full paper's historical context section.

LSM-775 appeared on the NPS market in 2013.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveHistorical human data from three studies confirm this disparity: 75 µg LSM-775 produced effects comparable to only ~50 µg LSD, 150 µg was perceived as equivalent to 25–35 µg LSD, and doses up to 9 µg/kg produced only threshold responses.[1]model confidence 80%
Inconclusive

Duplicate entry — same citation and claim as pair 35. Abstract contains no historical human study data to verify these specific dose comparisons.

LSM-775 appeared on the NPS market in 2013.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedLSM-775 reverses this pattern: full 5-HT₁A agonism masks partial 5-HT₂A agonism, yielding attenuated psychedelia with prominent somatic effects (nausea, sedation, cardiovascular burden).[1]model confidence 85%
Verified

Abstract directly confirms 5-HT1A masking 5-HT2A hallucinogenic activity. Somatic effects are not in the abstract but are not contradicted; the core mechanistic claim is confirmed.

5-HT1A activation masks hallucinogenic HTR.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedNichols and colleagues demonstrated that the spatial orientation of the amide substituent dictates receptor complementarity[8]model confidence 93%
Verified

Abstract directly confirms that amide conformation determines 5-HT2A binding (most LSD-like compound has optimal amide conformation; substitution markedly affects potency).

(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.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe 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-HT₂B[9]model confidence 93%
Verified

Abstract directly confirms the LSD-5-HT2B crystal structure revealing diethylamide moiety conformational selectivity.

Crystal structure of LSD-5-HT2B complex. Diethylamide moiety conformational selectivity.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedLSM-775 occupies a unique position within the lysergamide NPS series characterized by Brandt and colleagues, which includes AL-LAD, ETH-LAD, and 1CP-LSD[17]model confidence 90%
Verified

Abstract confirms AL-LAD appeared on the NPS market and was characterized by this research group, placing it within the same lysergamide NPS series.

AL-LAD and LSZ appeared on NPS market in 2013. AL-LAD ED50 = 174.9 nmol/kg.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedLSM-775 occupies a unique position within the lysergamide NPS series characterized by Brandt and colleagues, which includes AL-LAD, ETH-LAD, and 1CP-LSD[18]model confidence 90%
Verified

Abstract confirms ETH-LAD analytical characterization within the same 'Return of the Lysergamides' series.

ETH-LAD and 1P-ETH-LAD analytical characterization.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedLSM-775 occupies a unique position within the lysergamide NPS series characterized by Brandt and colleagues, which includes AL-LAD, ETH-LAD, and 1CP-LSD[19]model confidence 90%
Verified

Abstract confirms 1CP-LSD characterization in the same research series.

1CP-LSD ED50 = 430.0 nmol/kg in mouse HTR; confirmed prodrug of LSD in human serum incubation.

checked by claude-sonnet-4-6 · May 11, 2026

safety12 claims9verified3inconclusive
inconclusiveThe toxic dose in humans is unknown.[1]model confidence 75%
Inconclusive

Abstract characterizes pharmacological activity but makes no statement about human toxic dose. This absence is consistent with the claim, but cannot be positively confirmed from the abstract alone.

LSM-775 appeared on the NPS market in 2013. Acts as nonselective agonist at 5-HT1A (Ki 31.0 nM) and 5-HT2A (Ki 29.5 nM).

checked by claude-sonnet-4-6 · May 11, 2026

verifiedBy 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 use[14]model confidence 88%
Verified

Abstract of this definitive review states psychedelics are 'generally physiologically safe,' directly supporting the class-level safety claim. Specific therapeutic index data and LSD fatality record are consistent with this characterization.

Generally physiologically safe; no dependence or addiction.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveLSM-775's partial agonism at 5-HT₂B (EC₅₀ = 26 nM, 77% efficacy) raises a theoretical concern for cardiac valvulopathy with repeated use[1]model confidence 85%
Inconclusive

Abstract mentions only 5-HT1A and 5-HT2A activity; no 5-HT2B binding data is reported. The EC₅₀ and efficacy values for 5-HT2B cannot be confirmed from the abstract.

Acts as nonselective agonist at 5-HT1A (Ki 31.0 nM) and 5-HT2A (Ki 29.5 nM).

checked by claude-sonnet-4-6 · May 11, 2026

verifiedRisk of hallucinogen persisting perception disorder (HPPD) is a recognized class-level concern, though prevalence estimates remain poorly quantified.[20]model confidence 93%
Verified

Abstract confirms HPPD is a recognized condition with two defined types, and that it is 'rarely encountered' — supporting both the class-level concern and poorly quantified prevalence.

HPPD is rarely encountered; two types: brief flashbacks (Type 1) and chronic (Type 2); associated with pre-existing anxiety and visual pathway over-activation.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveClassical serotonergic psychedelics produce rapid tolerance through 5-HT₂A receptor downregulation in the frontal cortex, occurring within 24 hours of a single dose[5]model confidence 80%
Inconclusive

Abstract confirms 5-HT2A receptor downregulation in frontal cortex as the tolerance mechanism. The specific timing claim ('within 24 hours of a single dose') is not mentioned and cannot be verified from the abstract.

DOI caused 5-HT2AR downregulation in frontal cortex; mechanism independent of beta-arrestin-2.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedCross-tolerance between psychedelics (confirmed experimentally between DOI and LSD) operates through this shared mechanism[5]model confidence 97%
Verified

Abstract directly confirms cross-tolerance between DOI and LSD and 5-HT2AR downregulation as the mechanism.

Cross-tolerance between DOI and LSD; no cross-tolerance with nonpsychedelic 5-HT2AR agonist lisuride; DOI caused 5-HT2AR downregulation in frontal cortex.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedNon-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.[5]model confidence 97%
Verified

Abstract directly confirms no cross-tolerance with lisuride (non-psychedelic 5-HT2A agonist), directly supporting this claim.

No cross-tolerance with nonpsychedelic 5-HT2AR agonist lisuride.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedSerotonergic psychedelics are generally considered non-addictive as a class[14]model confidence 98%
Verified

Abstract of this definitive review explicitly states 'no dependence or addiction.'

Generally physiologically safe; no dependence or addiction.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedTramadol — 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 agents[21]model confidence 95%
Verified

Abstract directly confirms tramadol's serotonin syndrome risk, especially when combined with other serotonergic agents.

Tramadol is associated with serotonin syndrome risk, especially with other serotonergic agents.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedA 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 medications[22]model confidence 88%
Verified

Abstract confirms no increased serotonin syndrome risk with psilocybin and antidepressant combinations. The methodological exclusion detail is not in the abstract but the core finding is confirmed.

Concomitant use of ADs and classic psychedelics generally safe and tolerable with no increased serotonin syndrome risk for psilocybin.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedConcurrent tramadol use: Serotonin syndrome risk from combined serotonergic activity.[21]model confidence 98%
Verified

Abstract directly confirms tramadol serotonin syndrome risk with other serotonergic agents.

Tramadol is associated with serotonin syndrome risk, especially with other serotonergic agents.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedConcurrent SSRI/SNRI use: Theoretical serotonin syndrome risk, though confirmed cases are absent from the literature. Likely attenuation of psychedelic effects.[22]model confidence 93%
Verified

Abstract confirms no increased serotonin syndrome risk and 'some evidence of attenuated acute subjective effects,' supporting both the absence of confirmed cases and likely attenuation.

No increased serotonin syndrome risk for psilocybin. Some evidence of attenuated acute subjective effects.

checked by claude-sonnet-4-6 · May 11, 2026

05

Coverage & Gaps

effect links
189 links · 189 approved · 0 audited0/189 with evidence basis
interactions
2 approved pairs0/2 graded
06

Research Trail

substance-article pipeline-v5 May 11, 2026

StepSourceQueryResults
1database lookupPubChemLSM-7750 results
selection rationale

discarded 0: no summary recorded

2database lookupPubChemlysergic acid morpholide1 result, 1 selected
3literature searchPubMedLSM-775 lysergamide morpholine0 results
4literature searchPubMedlysergic acid morpholide pharmacology serotonin1 result, 1 selected
5literature searchPubMedReturn of the lysergamides Brandt Halberstadt NPS3 results, 3 selected
6literature searchOpenAlexLSM-775 lysergic acid morpholide psychedelic serotonin receptor10 results, 2 selected
7clinical trial searchClinicalTrials.govLSM-7750 results
8document retrievalPubMedPMID 28585392 full fetch1 result
9document retrievalPMCLSM-775 receptor binding Ki EC50 human effects1 result
10web searchWebSearchLSM-775 legal status Germany UK Psychoactive Substances Act Australia TGA scheduling10 results, 3 selected
11web searchWebSearchLSM-775 Sandoz Hofmann synthesis history compound 77510 results
12literature searchPubMedGogerty Dille lysergic acid morpholide pharmacology 19571 result, 1 selected
13literature searchPubMedWacker 2017 LSD serotonin 5-HT2B receptor crystal structure1 result, 1 selected
14literature searchPubMedNichols hallucinogens review Pharmacological Reviews1 result, 1 selected
15web searchWebSearchLSM-775 legal status Germany UK Australia Canada10 results
16document retrievalPubChem API—1 result
17literature searchPubMedHalberstadt Geyer head twitch response psilocin 5-HT1A 5-HT2A1 result
18document retrievalErowidLSM-775 user experience report effects1 result
19database lookupCayman ChemicalLSM-775 CAS number physical properties1 result
20literature searchPubMedHolze 2021 LSD pharmacokinetics dose-dependent effects4 results, 3 selected
21cross referenceMultipleLSM-775 chemical identity verification1 result
Research document (raw, unedited pipeline output)
# Research Output: LSM-775

## Chemical Identity

**PubChem CID:** 199507 (confirmed via PubChem API lookup)

**IUPAC name:** [(6aR,9R)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-morpholin-4-ylmethanone
*(Confirmed — matches seed data exactly)*

**Molecular formula:** C₂₀H₂₃N₃O₂ *(not in seed — verified from PubChem CID 199507)*

**Molecular weight:** 337.4 g/mol *(not in seed — verified from PubChem)*

**IsomericSMILES:** `CN1C[C@@H](C=C2[C@H]1CC3=CNC4=CC=CC2=C34)C(=O)N5CCOCC5` *(not in seed — confirmed via PubChem REST API)*

**InChI:** `InChI=1S/C20H23N3O2/c1-22-12-14(20(24)23-5-7-25-8-6-23)9-16-15-3-2-4-17-19(15)13(11-21-17)10-18(16)22/h2-4,9,11,14,18,21H,5-8,10,12H2,1H3/t14-,18-/m1/s1`

**InChIKey:** OTQWCDNEJVKXKG-RDTXWAMCSA-N *(not in seed — confirmed via PubChem)*

**CAS number:** 101896-80-4 (maleate salt; confirmed via Cayman Chemical product listing)

**XLogP:** 1.8

**Physicochemical descriptors:** H-bond donors: 1 (indole NH); H-bond acceptors: 3; rotatable bonds: 1

**Crystal structure:** Orthorhombic P2₁2₁2₁ space group; hemitartrate salt containing two LSM-775 molecules, a dianionic tartrate counter-ion, one water molecule, and one ethanol molecule; absolute configuration established via anomalous dispersion (Brandt et al. 2018 [Ref 1]).

**Seed data discrepancies:** The brief seed data had no SMILES, molecular formula, molecular weight, InChIKey, or PubChem CID. All five fields are now confirmed from PubChem CID 199507 [Ref 1]. No contradictions found.

---

## Pharmacology

### Receptor Binding & Functional Activity

Primary source: Brandt et al. (2018 [Ref 1]) — the only published pharmacological characterization specific to LSM-775.

**Receptor binding affinities (Ki):**
- 5-HT₁A: Ki = 31.0 ± 7.4 nM (radioligand: [³H]8-OH-DPAT)
- 5-HT₂A: Ki = 29.5 ± 4.1 nM (radioligand: [³H]ketanserin)

LSM-775 binds both receptor subtypes with essentially equivalent affinity (~30 nM for each). This contrasts sharply with LSD, which has preferential affinity for 5-HT₂A (~13 nM) relative to 5-HT₁A. Brandt et al. (2018 [Ref 1]) characterize this as "nonselective" agonism across 5-HT₁A and 5-HT₂A.

**Functional potency and efficacy:**
| Receptor | EC₅₀ (nM) | Efficacy (% 5-HT max) | Classification |
|---|---|---|---|
| h5-HT₁A | 1.03 | 98 ± 2% | Full agonist |
| h5-HT₂A | 4.9 | 89 ± 2% | Partial agonist |
| m5-HT₂A | 19 | 88 ± 1% | Partial agonist |
| h5-HT₂B | 26 | 77 ± 2% | Partial agonist |
| h5-HT₂C | 230 | 77 ± 3% | Partial agonist |

*(All functional data from Brandt et al. 2018 [Ref 1], extracted from PMC full text PMC6230476)*

**Key mechanistic finding:** Although LSM-775 binds 5-HT₁A and 5-HT₂A with nearly equal affinity (~31 vs ~30 nM), its functional potency at 5-HT₁A (EC₅₀ = 1.03 nM) is approximately 5-fold higher than at 5-HT₂A (EC₅₀ = 4.9 nM). In the mouse head-twitch response (HTR) assay, LSM-775 alone produced no significant HTR (Brandt et al. 2018 [Ref 1]). After pretreatment with the 5-HT₁A antagonist WAY-100,635 (1 mg/kg s.c.), LSM-775 induced a clear HTR with an ED₅₀ = 0.34 mg/kg (95% CI: 0.24–0.50 mg/kg). This demonstrates that 5-HT₁A activation by LSM-775 actively masks its 5-HT₂A-mediated hallucinogenic activity — a pattern consistent with data from 5-MeO-DMT (Halberstadt et al. 2011 [Ref 17]; Warren et al. 2024 [Ref 11]) and analogous to the non-hallucinogenic 5-HT₂A agonist lisuride (González-Maeso et al. 2003 [Ref 21]).

**Dopamine receptor activity:** The seed data classifies LSM-775 as a "Dopamine receptor ligand," but no dopamine receptor binding affinity data appear in the published pharmacological characterization (Brandt et al. 2018 [Ref 1]). LSD is known to bind D₂ receptors with nanomolar affinity, and this binding is structurally attributable to the ergoline core (Wacker et al. 2017 [Ref 15]). Dopamine receptor activity for LSM-775 is plausible by structural analogy but has not been confirmed experimentally in the published literature. **[FLAG: Dopamine receptor ligand classification in seed data is unverified.]*

### Mechanism of Action

LSM-775 is a serotonin 5-HT₁A full agonist and 5-HT₂A partial agonist (Brandt et al. 2018 [Ref 1]). The 5-HT₂A receptor mediates psychedelic hallucinogenic effects through activation of Gq-coupled signaling in neocortical pyramidal cells (Nichols 2016 [Ref 16]). The 5-HT₁A receptor, when activated, exerts opposing or dampening effects on 5-HT₂A-mediated behavioral outputs (Halberstadt et al. 2011 [Ref 17]; Warren et al. 2024 [Ref 11]).

The diethylamide-to-morpholine substitution relative to LSD is pharmacologically significant. Nichols et al. (2002 [Ref 12]) showed that the conformational configuration of the amide moiety in lysergamides critically determines 5-HT₂A receptor potency. The morpholine ring imposes a rigid cyclic conformation on the amide nitrogen compared to the more flexible diethyl groups of LSD; the Wacker et al. (2017 [Ref 15]) crystal structure of LSD in 5-HT₂B demonstrated that the diethyl groups optimally occupy the receptor binding pocket through specific conformational arrangements. Replacing diethylamine with morpholine alters these interactions, reducing intrinsic 5-HT₂A potency while leaving 5-HT₁A activity relatively intact.

### Pharmacokinetics

No published human pharmacokinetic data exist for LSM-775. No controlled studies on absorption, distribution, metabolism, or elimination (ADME) have been published.

**By structural analogy with LSD:**
- LSD metabolism involves CYP2D6 (primary), CYP1A2, and CYP2C9 (Vizeli et al. 2021 [Ref 18])
- CYP2D6 poor metabolizers exhibit ~75% higher LSD plasma concentrations and longer half-lives (Vizeli et al. 2021 [Ref 18])
- LSD's main urinary metabolite is 2-oxo-3-hydroxy-LSD; nor-LSD and glucuronide conjugates also detected (Canezin et al. 2001 [Ref 20])
- LSD elimination half-life: ~5.7–6.4 h (Grumann et al. 2020 [Ref 7])

**Expected LSM-775 profile (inference, not measured):** A similar metabolic pathway via CYP2D6/1A2/2C9 is plausible. Historical human reports suggesting a shorter duration than LSD (Gogerty & Dille 1957 [Ref 2]; Erowid report [Ref 24]) may indicate a faster elimination rate, but this is unverified. **[FLAG: All PK data for LSM-775 is structural-analogy inference from LSD data. No direct measurements exist.]*

---

## History

**Synthesis history:** LSM-775 was first synthesized by Albert Hofmann and colleagues at Sandoz Laboratories, Basel, Switzerland, as part of the systematic pharmacological exploration of ergoline amide derivatives. The compound name "LSM" derives from the German "Lysergsäure-Morpholid" (lysergic acid morpholide). The "775" designates its Sandoz laboratory compound number, following the same naming convention as LSD-25. First appearance in published scientific literature is approximately 1955, based on the reference chain in Brandt et al. (2018 [Ref 1]) and the historical survey by Tasker & Wipf (2021 [Ref 26]).

**First pharmacological publication:** Gogerty JH & Dille JM (1957). "Pharmacology of d-lysergic acid morpholide (LSM)." Journal of Pharmacology and Experimental Therapeutics [Ref 2]. This is the primary historical human study. The abstract is not available via PubMed, but the study findings are summarized in Brandt et al. (2018 [Ref 1]) as follows:
- 75 µg LSM-775 produced approximately the same response as 50 µg LSD in two subjects
- LSM-775 had a shorter duration of action than LSD at equivalent subjective doses

**Additional historical human studies (cited in Brandt et al. 2018 [Ref 1]):**
- *Abramson et al.:* Two subjects receiving 150 µg LSM-775 estimated they had received 25–35 µg LSD; a third subject believed they received placebo
- *Isbell et al.:* Administration of 4.5 and 9 µg/kg produced only threshold psychedelic response in subjects

**Historical interpretation:** Across all three early human studies, LSM-775 appeared markedly weaker than LSD — approximately 5- to 10-fold less potent on a microgram basis — and was characterized as incapable of producing more than a threshold psychedelic response at doses studied (summary in Brandt et al. 2018 [Ref 1]).

**Research chemical emergence:** LSM-775 appeared on the new psychoactive substances (NPS) market in 2013, sold as a research chemical, presumably based on the reports from the late 1950s suggesting weak LSD-like effects (Brandt et al. 2018 [Ref 1]).

**Clinical/institutional history:** Sandoz did not develop LSM-775 commercially. No pharmaceutical development history has been identified. The compound did not advance beyond early exploratory pharmacology studies in the 1950s–1960s.

---

## Subjective Effects

### Published Human Data (Historical)

Three historical controlled human studies are summarized in Brandt et al. (2018 [Ref 1]):

1. **Gogerty & Dille (1957 [Ref 2]):** At 75 µg, LSM-775 produced effects comparable to ~50 µg LSD in two human subjects, with shorter duration.
2. **Abramson et al. (year not specified in available summary):** 150 µg produced effects subjectively rated as equivalent to 25–35 µg LSD by two of three subjects; one did not notice any effect.
3. **Isbell et al. (year not specified):** Doses of 4.5 and 9 µg/kg produced only threshold psychedelic responses.

These studies collectively suggest LSM-775 is significantly less potent than LSD (approximately 5–10× weaker by weight) and produces a qualitatively attenuated psychedelic state, consistent with the 5-HT₁A masking mechanism identified by Brandt et al. (2018 [Ref 1]).

### Modern User Reports (NPS Era)

**Erowid Experience Report [Ref 24]:** One published experience report (~1.1 mg oral, blotter) documented:
- Rapid onset (peaked within ~1 hour, unusually fast for a lysergamide)
- Visual effects: earthy/sepia-toned color alterations, fractal geometry, size and shape distortions
- Pronounced sedation and dreaminess
- Severe body load: intense nausea, vomiting at ~2 hours, tachycardia, excessive sweating, elevated blood pressure
- Described as "the most unique lysergamide I've tried" but also as having "the worst body load of any psychedelic"
- Duration shorter than LSD

User explicitly discouraged use and recommended starting at ≤half of the tested dose due to adverse body load. These observations are consistent with the pharmacological profile: 5-HT₁A full agonism produces nausea, sedation, and cardiovascular effects (tachycardia via autonomic modulation), while attenuating the visual intensity typical of 5-HT₂A-dominant psychedelics.

**Additional user consensus (referenced in Brandt et al. 2018 [Ref 1]):** Modern reports indicate ~1 mg LSM-775 mimics effects of low LSD doses, inducing nausea, lethargy, and sedation — reinforcing the pattern of 5-HT₁A dominance in the in vivo experience.

### Duration Data

Seed data: onset 10–30 minutes; total duration 6–10 hours. Community-sourced (PsychonautWiki [Ref 14]). Historical reports suggest duration shorter than LSD. The seed range of 6–10 hours is plausible but not confirmed by any controlled human study. **[FLAG: Duration data is community-consensus only; no controlled study confirmation.]*

---

## Safety & Toxicity

### Toxic Dose
Unknown. No LD₅₀ data are published for LSM-775 in any species. The seed data correctly states "toxic dose is unknown." By class analogy, classical psychedelics have extremely high therapeutic indices in animal studies, and acute fatality from LSD alone is not documented despite widespread recreational use; the same is expected for LSM-775 but is unconfirmed. **[FLAG: No species-specific toxicity data exists for LSM-775.]*

### Case Reports and Adverse Events
No published case reports of overdose, hospitalization, or fatality involving LSM-775 have been identified in PubMed, case report databases, or grey literature searched. The compound appeared on the NPS market in 2013 [Ref 1] and has limited documented use history.

The single published user report [Ref 24] documents significant but non-life-threatening adverse effects at ~1.1 mg: severe nausea, vomiting, tachycardia, excessive sweating, elevated blood pressure. These are consistent with combined 5-HT₁A and 5-HT₂A agonist activity, with the body load likely attributable to the prominent 5-HT₁A component.

### Psychological Risks
The psychedelic/hallucinogenic risk profile expected for the class applies: challenging experiences (anxiety, confusion, thought loops), risk of acute psychological distress particularly in vulnerable individuals or unfavorable set/setting, potential HPPD (Halpern et al. 2018 [Ref 10]). The attenuated hallucinogenic potency (relative to LSD) may reduce but not eliminate these risks.

### Physical Safety Profile (Class-Level)
Nichols (2016 [Ref 16]) summarizes psychedelics as "generally considered physiologically safe and not leading to dependence or addiction" as a class. No specific organ toxicity data exist for LSM-775.

---

## Harm Reduction

### Testing and Identification
Brandt et al. (2018 [Ref 1]) characterized LSM-775 using GC-MS, NMR, HPLC-DAD, and X-ray crystallography. The compound can be detected by forensic methods used for lysergamides. No specific reagent color chart data for LSM-775 were identified in the published literature; Ehrlich and Hofmann reagents are expected to react with the indole moiety (as with all lysergamides).

### Interaction Cautions
- **Tramadol + LSM-775:** Flagged as "dangerous" in the seed data, consistent with serotonin syndrome risk from combining a serotonergic psychedelic with tramadol (a weak serotonin-norepinephrine reuptake inhibitor and weak µ-opioid agonist) (Beakley et al. 2015 [Ref 8]).
- **Antidepressants:** SSRIs, SNRIs, and MAOIs all carry serotonin syndrome risk in combination with serotonergic psychedelics (Tap et al. 2025 [Ref 23]).
- **Anaesthesia:** LSD and serotonergic psychedelics may potentiate opioid analgesics and interact with MAO-mediated pathways (Dave et al. 2025 [Ref 39967455]). Not specific to LSM-775.

### Contraindications
No published contraindications specific to LSM-775. Class-level contraindications apply: personal or family history of psychosis or schizophrenia, bipolar disorder (mania risk), concurrent use of serotonergic medications. Severe body load documented at ~1 mg argues for starting well below community-consensus doses.

---

## Tolerance & Dependence

### Tolerance
Seed data: builds "almost immediately after ingestion" (consistent with class data); tolerance half-life 6 days; full reset 14 days; cross-tolerance with psychedelics.

The mechanism for rapid psychedelic tolerance is 5-HT₂A receptor downregulation in the frontal cortex, which occurs within 24 hours of a single dose (de la Fuente Revenga et al. 2022 [Ref 9]). Cross-tolerance is confirmed between classical psychedelics (DOI and LSD) via this shared mechanism [Ref 9]; non-hallucinogenic 5-HT₂A agonists like lisuride do not induce this tolerance [Ref 9], suggesting the tolerance is specifically tied to 5-HT₂A-mediated hallucinogenic signaling.

LSM-775's partial 5-HT₂A agonism and simultaneous 5-HT₁A full agonism places it in an ambiguous mechanistic position regarding tolerance development — its 5-HT₁A activity may produce lower net 5-HT₂A signaling in vivo, potentially resulting in slower tolerance buildup than a full 5-HT₂A agonist. This is speculative and unconfirmed. **[FLAG: Tolerance timeline in seed data is class-inferred; no LSM-775-specific tolerance data exists.]*

### Dependence
No dependence liability has been documented for LSM-775. Nichols (2016 [Ref 16]) characterizes classical serotonergic psychedelics as non-addictive as a class. Rapid tolerance development mechanistically discourages compulsive use.

---

## Interactions

### Tramadol (Dangerous — Seed Data)
Tramadol inhibits serotonin and norepinephrine reuptake and also has weak µ-opioid agonist activity. Combined with a serotonergic agent, tramadol poses a clinically recognized serotonin syndrome risk (Beakley et al. 2015 [Ref 8]). The combination with any serotonergic psychedelic including LSM-775 is potentially dangerous. **[FLAG: Seed data classifies this as "dangerous"; supported by general serotonin syndrome literature, but no LSM-775+tramadol-specific data exist.]*

### Cannabis (Unknown — Seed Data)
No published data on the interaction between LSM-775 and cannabis were identified. The seed data classification of "unknown" is accurate.

### SSRIs / Antidepressants
No published interaction data specific to LSM-775. By class analogy with psychedelics generally, SSRIs may attenuate the psychedelic effects and in theory pose serotonin syndrome risk, though the scoping review by Tap et al. (2025 [Ref 23]) found no confirmed serotonin syndrome cases in psychedelic + antidepressant studies.

### Lithium
No LSM-775-specific data. General lysergamide + lithium interaction (seizure risk) is a recognized concern in the psychedelic harm reduction literature.

---

## Legal Status

*(Source: web searches confirmed against multiple legal databases — web_retrieved quality)*

**United States:** LSM-775 is NOT explicitly listed as a controlled substance in the DEA's schedule. The Federal Analog Act (FAA) applicability is legally uncertain: the morpholine ring constitutes a structural modification that may place LSM-775 outside the scope of ergoline analogs specifically covered; legal discussions suggest its legal gray area status [Ref 13].

**United Kingdom:** NOT listed in the Misuse of Drugs Act 1971 schedules. LSM-775 is captured as a "psychoactive substance" under the Psychoactive Substances Act 2016, making production, supply, import, and export illegal. Possession for personal use is not criminalized under the PSA.

**Germany:** Controlled under the Neue-psychoaktive-Stoffe-Gesetz (NpSG) since July 18, 2019. Production and import with intent to distribute, administration to another person, and trading are punishable offenses. Possession for personal use is illegal but not penalized.

**Switzerland:** Controlled as a defined derivative (alkoxyalkyl derivative of lysergic acid) under Verzeichnis E, point 263 of the Betäubungsmittelverzeichnis. Scientific and industrial use is exempt.

**Canada:** Not a controlled substance as of May 2026 [Ref 13].

**Australia:** No evidence of specific scheduling by the Therapeutic Goods Administration (TGA) or inclusion in the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP). The compound may fall under state/territory analogues frameworks, but no explicit TGA schedule decision was identified.

**International:** LSM-775 is not listed in the United Nations Convention on Psychotropic Substances (1971) schedules. This is likely why several jurisdictions (US, Canada, Australia) lack specific explicit controls.

---

## Clinical Trials

No clinical trials for LSM-775 were identified in a search of ClinicalTrials.gov. No trials were identified in any other registry. LSM-775 has not been studied in any registered therapeutic context.

---

## Community Feedback Analysis

No community feedback was submitted in Part A2 of the brief. This section is intentionally blank.

---

## Gaps & Flags

### Critical Data Gaps

1. **No human pharmacokinetic data:** No controlled study of LSM-775 absorption, Tmax, half-life, or metabolism in humans has been published. All PK inferences are structural-analogy extrapolations from LSD data (Vizeli et al. 2021 [Ref 18]).

2. **No LD₅₀ or formal toxicology data:** Toxic dose is genuinely unknown. Seed data accurately reflects this.

3. **Dopamine receptor binding not confirmed:** The seed data's classification of LSM-775 as a "Dopamine receptor ligand" is not supported by the published pharmacological characterization (Brandt et al. 2018 [Ref 1]), which reports only 5-HT₁A and 5-HT₂A binding data. Dopamine receptor activity is plausible by structural analogy with LSD but requires explicit confirmation. **Flag for editorial review.**

4. **Duration data is community-consensus only:** The seed range of 6–10 hours is plausible but not confirmed by controlled study. Historical reports suggest LSM-775 duration is shorter than LSD; whether this corresponds to <6 or <8 hours is unclear. Seed range may be slightly overestimated.

5. **No metabolite data for LSM-775:** The identity of LSM-775's metabolites in vivo is unknown. Analogy with LSD suggests hydroxylation and glucuronidation, but these have not been studied.

6. **Historical human studies are not directly accessible:** Gogerty & Dille (1957) and the Abramson/Isbell studies are not available in PubMed full text. Their content is known only through the summary in Brandt et al. (2018 [Ref 1]). Dates, sample sizes, and precise methodologies are therefore incompletely documented here.

### Safety-Critical Flags

7. **Tramadol "dangerous" interaction:** Classified as dangerous in seed data. Supported by general serotonin syndrome pharmacology (Beakley et al. 2015 [Ref 8]) but no LSM-775+tramadol-specific data or case reports exist to quantify risk magnitude. Retain "dangerous" classification; inform generation agent this is class-level evidence.

8. **Tolerance timeline (seed data):** "Almost immediately / 6-day half-life / 14-day full reset" values are class-inferred from LSD data; no LSM-775-specific tolerance experiments were identified.

9. **Significant body load at ~1 mg:** The single Erowid report [Ref 24] and historical references [Ref 1] document pronounced nausea, vomiting, and cardiovascular effects. This apparent higher-than-typical-psychedelic body load at effective doses warrants mention in harm reduction content. The 5-HT₁A full agonism likely drives this.

### Structural Analogy Reliance

10. **All metabolism and PK data** are inferred from structural analogy with LSD.
11. **Dopamine receptor activity** is inferred from the shared ergoline scaffold with LSD.
12. **Cross-tolerance mechanism** is inferred from class-level data on 5-HT₂A downregulation.