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Psychedex
Sources
22
1 strong · 16 moderate · 5 weak

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

Claims checked
76
32verified5partial39inconclusive

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

Generated
May 3, 2026 · pipeline-v5
Values approved
207/207 (100%)

Data points an editor reviewed and accepted for publication.

01

Value Provenance

Dosing

sublingual

Predates provenance tracking — no derivation record for this dataset

FieldPublishedAI ProposedConfidence
Threshold1 seedsno record
Low3–5 seedsno record
Common5–7 seedsno record
Strong7–12 seedsno record
Heavy12+ seedsno record
Editorial

Carried forward from Curiosity v1 seed version during v1 history consolidation (2026-06-04).

oraltrace

FieldPublishedAI ProposedConfidence
Threshold0.5 mg0.5 mglow
Low0.5–1.5 mg0.5–1.5 mglow
Common1.5–4 mg1.5–4 mglow
Strong4–8 mg4–8 mglow
Heavy8+ mg8+ mglow
Editorial

The 2025 systematic review (Castro et al.) cites 2–5 mg as the hallucinogenic dose range. Shulgin (TIHKAL) provides experiential data for LSA. Threshold and tier boundaries inferred from the hallucinogenic range anchored at 2–5 mg as the common/moderate zone, with widened spread to account for absence of controlled dose-response data. No purified-LSA dose-finding study exists.

Reasoning

The 2025 systematic review (Castro et al.) cites 2–5 mg as the hallucinogenic dose range. Shulgin (TIHKAL) provides experiential data for LSA. Threshold and tier boundaries inferred from the hallucinogenic range anchored at 2–5 mg as the common/moderate zone, with widened spread to account for absence of controlled dose-response data. No purified-LSA dose-finding study exists.

Evidence basis: systematic_review

Duration

oral

FieldPublishedAI ProposedConfidence
Onsettrace30–120 minutes30–120 minuteslow
Editorial

Castro et al. 2025 systematic review reports onset at 30–180 minutes from seed ingestion. Upper range narrowed slightly as 180-minute onset likely reflects poor seed quality or full stomach rather than typical pharmacokinetics.

Reasoning

Castro et al. 2025 systematic review reports onset at 30–180 minutes from seed ingestion. Upper range narrowed slightly as 180-minute onset likely reflects poor seed quality or full stomach rather than typical pharmacokinetics.

Evidence basis: systematic_review

Come uptrace45–90 minutes45–90 minuteslow
Editorial

Inferred from the gap between onset and peak. No published data specifically characterize the come-up phase. Estimated from community reports and structural analogy to LSD come-up timing, adjusted for LSA's shorter total duration.

Reasoning

Inferred from the gap between onset and peak. No published data specifically characterize the come-up phase. Estimated from community reports and structural analogy to LSD come-up timing, adjusted for LSA's shorter total duration.

Evidence basis: community_consensus_small

Peaktrace2–4 hours2–4 hourslow
Editorial

Derived from Castro et al. 2025 systematic review data and community reports placing peak effects at approximately 2–4 hours into the experience. No controlled study defines peak duration.

Reasoning

Derived from Castro et al. 2025 systematic review data and community reports placing peak effects at approximately 2–4 hours into the experience. No controlled study defines peak duration.

Evidence basis: systematic_review

Offsettrace1–3 hours1–3 hourslow
Editorial

Estimated from the difference between total duration (4–10 h) and onset+come-up+peak durations. Community reports describe a gradual resolution over 1–3 hours.

Reasoning

Estimated from the difference between total duration (4–10 h) and onset+come-up+peak durations. Community reports describe a gradual resolution over 1–3 hours.

Evidence basis: community_consensus_small

Totaltrace4–10 hours4–10 hoursmedium
Editorial

Castro et al. 2025 systematic review reports 4–8 hours of intoxication at 2–5 mg doses. Observational data extend to 10 hours at higher doses. The 4–10 hour range captures the middle 80% of experiences.

Reasoning

Castro et al. 2025 systematic review reports 4–8 hours of intoxication at 2–5 mg doses. Observational data extend to 10 hours at higher doses. The 4–10 hour range captures the middle 80% of experiences.

Evidence basis: systematic_review

After effectstrace6–24 hours6–24 hourslow
Editorial

Castro et al. 2025 reports residual effects persisting up to 24 hours. Lower bound of 6 hours estimated from community reports of lingering fatigue and mood changes after the primary experience resolves.

Reasoning

Castro et al. 2025 reports residual effects persisting up to 24 hours. Lower bound of 6 hours estimated from community reports of lingering fatigue and mood changes after the primary experience resolves.

Evidence basis: systematic_review

Safety

Toxicity Profiletrace

FieldPublishedAI ProposedConfidence
Acutelowlowlow
Chronicnegligiblenegligiblelow
Organs Affectedcardiovascular, neurologicalcardiovascular, neurologicallow
Editorial

Classified as low acute toxicity (downgraded from moderate): the PRES case and hypertensive episodes suggest cardiovascular/neurological risk, but evidence derives from a single case report and class-level ergoline pharmacology extrapolation. No controlled toxicity data exist. No chronic toxicity data exist; the rapid tolerance mechanism deters frequent use, and no organ damage from repeated LSA exposure has been reported.

Reasoning

Classified as low acute toxicity (downgraded from moderate): the PRES case and hypertensive episodes suggest cardiovascular/neurological risk, but evidence derives from a single case report and class-level ergoline pharmacology extrapolation. No controlled toxicity data exist. No chronic toxicity data exist; the rapid tolerance mechanism deters frequent use, and no organ damage from repeated LSA exposure has been reported.

Evidence basis: published_case_series

Dependence Profiletrace

FieldPublishedAI ProposedConfidence
Physicalnonenonemedium
Psychologicalnegligiblenegligiblemedium
Compulsive Redosingnegligiblenegligiblemedium
Dose Escalationnegligiblenegligiblemedium
Editorial

No LSA-specific dependence data exist. Assessment based on the well-established non-addictive profile of the classical psychedelic class (LSD, psilocybin) and the rapid tolerance mechanism documented for 5-HT2A agonists (Buckholtz 1990, De la Fuente Revenga 2022).

Reasoning

No LSA-specific dependence data exist. Assessment based on the well-established non-addictive profile of the classical psychedelic class (LSD, psilocybin) and the rapid tolerance mechanism documented for 5-HT2A agonists (Buckholtz 1990, De la Fuente Revenga 2022).

Evidence basis: structural_analogy

Withdrawal Profiletrace

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

No withdrawal syndrome has been identified for any classical psychedelic. The 5-HT2A receptor downregulation mechanism reverses within 96 hours and does not produce rebound effects or withdrawal symptoms.

Reasoning

No withdrawal syndrome has been identified for any classical psychedelic. The 5-HT2A receptor downregulation mechanism reverses within 96 hours and does not produce rebound effects or withdrawal symptoms.

Evidence basis: structural_analogy

Tolerance Profiletrace

FieldPublishedAI ProposedConfidence
Builduprapidrapidmedium
Half-life3 days3 daysmedium
Full Reset7 days7 daysmedium
Cross-tolerancesLSD, psilocybin, mescaline, DMT, DOILSD, psilocybin, mescaline, DMT, DOImedium
Editorial

Based on Buckholtz et al. 1990 (LSD-induced 5-HT2 downregulation, recovery at 96h) and De la Fuente Revenga et al. 2022 (rapid tolerance and cross-tolerance via 5-HT2A). Applied to LSA as a confirmed 5-HT2A agonist in the same ergoline class.

Reasoning

Based on Buckholtz et al. 1990 (LSD-induced 5-HT2 downregulation, recovery at 96h) and De la Fuente Revenga et al. 2022 (rapid tolerance and cross-tolerance via 5-HT2A). Applied to LSA as a confirmed 5-HT2A agonist in the same ergoline class.

Evidence basis: structural_analogy

Effects & Profile

Contraindications

FieldPublishedAI ProposedConfidence
neurological cerebrovascular diseasetracerelativerelativemedium
Editorial

Direct case report evidence of LSA-induced PRES with status epilepticus (Legriel 2008). Cerebrovascular disease is a clear risk factor for hypertensive encephalopathy.

Reasoning

Direct case report evidence of LSA-induced PRES with status epilepticus (Legriel 2008). Cerebrovascular disease is a clear risk factor for hypertensive encephalopathy.

pregnancy breastfeeding pregnancytraceabsoluteabsolutehigh
Editorial

Ergometrine is a well-established uterotonic used clinically for postpartum hemorrhage. Its presence in LSA-containing seeds (documented by Paulke et al. 2014) makes seed consumption during pregnancy an absolute contraindication.

Reasoning

Ergometrine is a well-established uterotonic used clinically for postpartum hemorrhage. Its presence in LSA-containing seeds (documented by Paulke et al. 2014) makes seed consumption during pregnancy an absolute contraindication.

cardiovascular hypertensiontracerelativerelativemedium
Editorial

PRES case report (Legriel 2008) directly documents hypertensive neurotoxicity from LSA. Hypertension is documented across multiple case reports in the Castro et al. 2025 systematic review.

Reasoning

PRES case report (Legriel 2008) directly documents hypertensive neurotoxicity from LSA. Hypertension is documented across multiple case reports in the Castro et al. 2025 systematic review.

cardiovascular cardiovascular diseasetracerelativerelativelow
Editorial

Class-level ergoline pharmacology (vasoconstriction) combined with documented hypertension in LSA case reports. No LSA-specific cardiac event has been published, but the mechanism is well-established for the ergoline class.

Reasoning

Class-level ergoline pharmacology (vasoconstriction) combined with documented hypertension in LSA case reports. No LSA-specific cardiac event has been published, but the mechanism is well-established for the ergoline class.

neurological epilepsytracerelativerelativelow
Editorial

Legriel 2008 case report documents status epilepticus concurrent with LSA-induced PRES. Whether LSA independently lowers seizure threshold or the seizures were secondary to PRES is not established.

Reasoning

Legriel 2008 case report documents status epilepticus concurrent with LSA-induced PRES. Whether LSA independently lowers seizure threshold or the seizures were secondary to PRES is not established.

psychiatric psychotic disorderstracerelativerelativemedium
Editorial

Class-level risk for all 5-HT2A agonist psychedelics, supported by LSA-specific case reports documenting psychotomimetic states (Klinke 2010) and post-use psychosis (Castro & Maia 2024).

Reasoning

Class-level risk for all 5-HT2A agonist psychedelics, supported by LSA-specific case reports documenting psychotomimetic states (Klinke 2010) and post-use psychosis (Castro & Maia 2024).

psychiatric bipolar disordertracerelativerelativelow
Editorial

Class-level inference from serotonergic psychedelic pharmacology. No LSA-specific bipolar adverse event data published.

Reasoning

Class-level inference from serotonergic psychedelic pharmacology. No LSA-specific bipolar adverse event data published.

other concurrent serotonergic medicationtracerelativerelativemedium
Editorial

Class-level serotonergic interaction risk applicable to all 5-HT2A agonist psychedelics. Tramadol specifically flagged in seed data as dangerous interaction. No LSA-specific interaction case report published.

Reasoning

Class-level serotonergic interaction risk applicable to all 5-HT2A agonist psychedelics. Tramadol specifically flagged in seed data as dangerous interaction. No LSA-specific interaction case report published.

Timeline Phases

oral

FieldPublishedAI ProposedConfidence
Onsettrace1800–5400 sec(i=0.05)1800–5400 sec(i=0.05)low
Editorial

No controlled pharmacokinetic or dose-response study exists for LSA. Timeline derived from Castro et al. 2025 systematic review (onset 30–180 min, total duration 4–10 h, residual effects up to 24 h) and community reports. Wide ranges reflect the extreme variability inherent in seed-based consumption. Phase boundaries are estimated from anecdotal data and structural analogy to LSD's temporal profile, adjusted for LSA's shorter total duration.

Reasoning

No controlled pharmacokinetic or dose-response study exists for LSA. Timeline derived from Castro et al. 2025 systematic review (onset 30–180 min, total duration 4–10 h, residual effects up to 24 h) and community reports. Wide ranges reflect the extreme variability inherent in seed-based consumption. Phase boundaries are estimated from anecdotal data and structural analogy to LSD's temporal profile, adjusted for LSA's shorter total duration.

Come uptrace2700–5400 sec(i=0.30)2700–5400 sec(i=0.30)low
Editorial

No controlled pharmacokinetic or dose-response study exists for LSA. Timeline derived from Castro et al. 2025 systematic review (onset 30–180 min, total duration 4–10 h, residual effects up to 24 h) and community reports. Wide ranges reflect the extreme variability inherent in seed-based consumption. Phase boundaries are estimated from anecdotal data and structural analogy to LSD's temporal profile, adjusted for LSA's shorter total duration.

Reasoning

No controlled pharmacokinetic or dose-response study exists for LSA. Timeline derived from Castro et al. 2025 systematic review (onset 30–180 min, total duration 4–10 h, residual effects up to 24 h) and community reports. Wide ranges reflect the extreme variability inherent in seed-based consumption. Phase boundaries are estimated from anecdotal data and structural analogy to LSD's temporal profile, adjusted for LSA's shorter total duration.

Peaktrace7200–14400 sec(i=1.00)7200–14400 sec(i=1.00)low
Editorial

No controlled pharmacokinetic or dose-response study exists for LSA. Timeline derived from Castro et al. 2025 systematic review (onset 30–180 min, total duration 4–10 h, residual effects up to 24 h) and community reports. Wide ranges reflect the extreme variability inherent in seed-based consumption. Phase boundaries are estimated from anecdotal data and structural analogy to LSD's temporal profile, adjusted for LSA's shorter total duration.

Reasoning

No controlled pharmacokinetic or dose-response study exists for LSA. Timeline derived from Castro et al. 2025 systematic review (onset 30–180 min, total duration 4–10 h, residual effects up to 24 h) and community reports. Wide ranges reflect the extreme variability inherent in seed-based consumption. Phase boundaries are estimated from anecdotal data and structural analogy to LSD's temporal profile, adjusted for LSA's shorter total duration.

Plateautrace3600–7200 sec(i=0.50)3600–7200 sec(i=0.50)low
Editorial

No controlled pharmacokinetic or dose-response study exists for LSA. Timeline derived from Castro et al. 2025 systematic review (onset 30–180 min, total duration 4–10 h, residual effects up to 24 h) and community reports. Wide ranges reflect the extreme variability inherent in seed-based consumption. Phase boundaries are estimated from anecdotal data and structural analogy to LSD's temporal profile, adjusted for LSA's shorter total duration.

Reasoning

No controlled pharmacokinetic or dose-response study exists for LSA. Timeline derived from Castro et al. 2025 systematic review (onset 30–180 min, total duration 4–10 h, residual effects up to 24 h) and community reports. Wide ranges reflect the extreme variability inherent in seed-based consumption. Phase boundaries are estimated from anecdotal data and structural analogy to LSD's temporal profile, adjusted for LSA's shorter total duration.

Resolutiontrace3600–7200 sec(i=0.20)3600–7200 sec(i=0.20)low
Editorial

No controlled pharmacokinetic or dose-response study exists for LSA. Timeline derived from Castro et al. 2025 systematic review (onset 30–180 min, total duration 4–10 h, residual effects up to 24 h) and community reports. Wide ranges reflect the extreme variability inherent in seed-based consumption. Phase boundaries are estimated from anecdotal data and structural analogy to LSD's temporal profile, adjusted for LSA's shorter total duration.

Reasoning

No controlled pharmacokinetic or dose-response study exists for LSA. Timeline derived from Castro et al. 2025 systematic review (onset 30–180 min, total duration 4–10 h, residual effects up to 24 h) and community reports. Wide ranges reflect the extreme variability inherent in seed-based consumption. Phase boundaries are estimated from anecdotal data and structural analogy to LSD's temporal profile, adjusted for LSA's shorter total duration.

Afterglowtrace14400–86400 sec(i=0.05)14400–86400 sec(i=0.05)low
Editorial

No controlled pharmacokinetic or dose-response study exists for LSA. Timeline derived from Castro et al. 2025 systematic review (onset 30–180 min, total duration 4–10 h, residual effects up to 24 h) and community reports. Wide ranges reflect the extreme variability inherent in seed-based consumption. Phase boundaries are estimated from anecdotal data and structural analogy to LSD's temporal profile, adjusted for LSA's shorter total duration.

Reasoning

No controlled pharmacokinetic or dose-response study exists for LSA. Timeline derived from Castro et al. 2025 systematic review (onset 30–180 min, total duration 4–10 h, residual effects up to 24 h) and community reports. Wide ranges reflect the extreme variability inherent in seed-based consumption. Phase boundaries are estimated from anecdotal data and structural analogy to LSD's temporal profile, adjusted for LSA's shorter total duration.

Dose Tier Summaries

thresholdtrace
low

At threshold doses, effects are subtle and easily dismissed: mild mood shift, slight visual brightening, and a gentle sense of altered awareness that may be difficult to distinguish from placebo. Faint somatic awareness — a sense of heaviness or mild abdominal discomfort — may be the first indication of activity. Physically, mild pupil dilation and slight nausea may be noticeable. Functional impairment is minimal. Due to extreme variability in seed alkaloid content (3–34 µg LSA per unit), achieving a reliable threshold dose from seeds is inherently difficult.

Editorial

No controlled dose-response study exists for LSA. Threshold range inferred from the systematic review's citation of 2–5 mg as hallucinogenic dose range (Castro et al. 2025) and community reports. Seed alkaloid variability (Paulke et al. 2014) makes threshold dosing particularly unreliable.

Reasoning

No controlled dose-response study exists for LSA. Threshold range inferred from the systematic review's citation of 2–5 mg as hallucinogenic dose range (Castro et al. 2025) and community reports. Seed alkaloid variability (Paulke et al. 2014) makes threshold dosing particularly unreliable.

Evidence basis: community_consensus_small

lighttrace
low

At light doses, the ergoline character begins to emerge: mild euphoria, enhanced color perception, gentle visual brightening, and a dreamlike cognitive shift. Thought patterns become slightly more associative, with increased introspection and mild time distortion. The sedating quality that distinguishes LSA from LSD becomes apparent even at this level. Nausea is common and may be the most prominent physical effect, attributed to D2 dopamine receptor stimulation. Mild muscle weakness, slight vasoconstriction (cold extremities), and physical heaviness are typical. Sleep may be disrupted for several hours after ingestion.

Editorial

Inferred from the lower end of the 2–5 mg hallucinogenic range cited in Castro et al. 2025 systematic review, combined with community reports describing LSA's sedating and nauseating character at sub-psychedelic doses.

Reasoning

Inferred from the lower end of the 2–5 mg hallucinogenic range cited in Castro et al. 2025 systematic review, combined with community reports describing LSA's sedating and nauseating character at sub-psychedelic doses.

Evidence basis: community_consensus_small

commontrace
low

At common doses, the full psychedelic experience develops: pronounced visual distortions including color enhancement, pattern recognition, drifting and morphing of surfaces, and closed-eye imagery. Thought connectivity increases significantly, producing novel associations and introspective insights. Emotional intensification is characteristic, with music and nature taking on heightened significance. Time distortion becomes marked. The body load is substantial compared to tryptamine psychedelics — nausea, muscle weakness, physical sedation, and vasoconstriction (cold extremities, tingling) are prominent. Tremors and elevated blood pressure may occur. The overall character is "heavier" and more physically demanding than equivalent doses of LSD. Functional impairment is significant. Sleep is unlikely for 6–8 hours after ingestion. The experience demands a committed setting with no obligations.

Editorial

Based on the 2–5 mg hallucinogenic dose range from the 2025 systematic review and subjective effect descriptions from Castro et al. 2025 and pharmacovigilance case reports. The sedating and nauseating character is consistently reported across sources.

Reasoning

Based on the 2–5 mg hallucinogenic dose range from the 2025 systematic review and subjective effect descriptions from Castro et al. 2025 and pharmacovigilance case reports. The sedating and nauseating character is consistently reported across sources.

Evidence basis: community_consensus_small

strongtrace
low

At strong doses, visual and cognitive effects intensify substantially: vivid open- and closed-eye hallucinations, significant ego dissolution, profound time distortion, and deeply altered thought patterns. Emotional responses become overwhelming — both euphoric and anxious states are possible, with set and setting exerting decisive influence. The sedative-psychedelic character is fully expressed. Physical effects are pronounced: severe nausea and possible vomiting, marked muscle weakness, significant vasoconstriction, tremors, and elevated blood pressure. The body load can dominate the experience. Motor coordination is significantly impaired. This dose range carries meaningful risk of acute psychological distress, impaired reality testing, and dangerous behavior in unsupervised settings. The PRES case reported in the literature occurred at an unquantified but presumably high dose.

Editorial

Inferred from the upper end and above the 2–5 mg hallucinogenic range, informed by case reports describing psychotomimetic states, impaired reality testing, and hypertensive episodes. No controlled dose-response data exist.

Reasoning

Inferred from the upper end and above the 2–5 mg hallucinogenic range, informed by case reports describing psychotomimetic states, impaired reality testing, and hypertensive episodes. No controlled dose-response data exist.

Evidence basis: community_consensus_small

heavytrace
low

At heavy doses, LSA produces intense and potentially uncontrollable psychedelic effects: complete ego dissolution, severe hallucinations, profound disorientation, and loss of contact with consensus reality. The sedative component may produce periods of stupor alternating with intense psychedelic activity. Anxiety and paranoia are common. Physical risks escalate significantly: severe nausea and vomiting, pronounced hypertension, intense vasoconstriction, and significant cardiovascular stress. The risk of Posterior Reversible Encephalopathy Syndrome (PRES) — documented in the literature at unspecified dose — is a concern at this range. This dose range carries serious risk of medical emergency, dangerous behavior, and lasting psychological distress. No LD50 has been established, and no controlled data exist to define the boundary between heavy and toxic doses.

Editorial

Extrapolated from case reports of severe adverse events (PRES, fatal behavioral consequences) and the absence of any established toxic dose threshold. Heavy dose range is not characterized in published literature; this description is based on class-level psychedelic pharmacology and the specific adverse event profile documented for LSA.

Reasoning

Extrapolated from case reports of severe adverse events (PRES, fatal behavioral consequences) and the absence of any established toxic dose threshold. Heavy dose range is not characterized in published literature; this description is based on class-level psychedelic pharmacology and the specific adverse event profile documented for LSA.

Evidence basis: community_consensus_small

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

1 strong · 16 moderate · 5 weak
  1. [1]
    moderate
    Argyreia nervosa (Burm. f.): receptor profiling of lysergic acid amide and other potential psychedelic LSD-like compounds by computational and binding assay approaches
    Paulke A, Kremer C, Wunder C, Achenbach J, Djahanschiri B, Elias A, Schwed JS, Hubner H, Gmeiner P, Proschak E, Toennes SW, Stark H · 2013 · Journal of Ethnopharmacology
    doi.org/10.1016/j.jep.2013.04.044pubmed 236651648 claims checked6 verified2 partial
  2. [2]
    strong
    Lysergic Acid Amide (LSA), an LSD Analog: Systematic Review of Pharmacological Effects, Adverse Outcomes, and Therapeutic Potentials
    Castro PSCC, Leopoldo K, Pedro MOP, Takitane J, Bombana HS, Negrao AB, Scholz JR, Castaldelli-Maia JM · 2025 · Pharmacy (Basel, Switzerland)
    doi.org/10.3390/pharmacy13040098pubmed 4070026910 claims checked5 verified1 partial4 inconclusive
  3. [3]
    moderate
    Isolation of lysergic acid alkaloids from the Mexican drug ololiuqui (Rivea corymbosa (L.) Hall.f.)
    Hofmann A, Tscherter H · 1960 · Experientia
    pubmed 137150894 claims checked4 inconclusive
  4. [4]
    moderate
    Investigating LSA - a 'legal high' analogue to LSD, frequently used in the digital realm with relatively unknown effects
    Castro P, Maia J · 2024 · European Psychiatry
    doi.org/10.1192/j.eurpsy.2024.11507 claims checked7 inconclusive
  5. [5]
    moderate
    Stereoselective LSD-like activity in a series of d-lysergic acid amides of (R)- and (S)-2-aminoalkanes
    Monte AP, Marona-Lewicka D, Kanthasamy A, Sanders-Bush E, Nichols DE · 1995 · Journal of Medicinal Chemistry
    pubmed 76997128 claims checked8 inconclusive
  6. [6]
    weak
    Lysergic Acid Amide-Induced Posterior Reversible Encephalopathy Syndrome with Status Epilepticus
    Legriel S, Bruneel F, Spreux-Varoquaux O, Birenbaum A, Chadenat ML, Mignon F, Abbosh N, Henry-Lagarrigue M, Revault D'Allonnes L, Guezennec P, Troche G, Bedos JP · 2008 · Neurocritical Care
    doi.org/10.1007/s12028-008-9096-5pubmed 184464486 claims checked6 verified
  7. [7]
    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 359008763 claims checked2 verified1 partial
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    Identification of legal highs — ergot alkaloid patterns in two Argyreia nervosa products
    Paulke A, Kremer C, Wunder C, Wurglics M, Schubert-Zsilavecz M, Toennes SW · 2014 · Forensic Science International
    doi.org/10.1016/j.forsciint.2014.06.025pubmed 250367824 claims checked2 verified1 partial1 inconclusive
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    Psychoactive effects of 'legal high': About lysergic acid amide (LSA)
    Ponte C, Lapeyre-Mestre M · 2017 · Therapie
    doi.org/10.1016/j.therap.2017.01.012pubmed 284575704 claims checked4 verified
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    Ergot Alkaloids and their Hallucinogenic Potential in Morning Glories
    Steiner U, Leistner E · 2018 · Planta Medica
    doi.org/10.1055/a-0577-8049pubmed 294995871 claim checked1 inconclusive
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    Investigating the psychedelic hypothesis of kykeon, the sacred elixir of the Eleusinian Mysteries
    Antonopoulos RK, Dadiotis E, Ioannidis K, Cheilari A, Mitsis V, et al. · 2026 · Scientific Reports
    doi.org/10.1038/s41598-026-39568-3pubmed 416804201 claim checked1 verified
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    Two cases of lysergamide intoxication by ingestion of seeds from Hawaiian Baby Woodrose
    Klinke HB, Muller IB, Steffenrud S, Dahl-Sorensen R · 2010 · Forensic Science International
    doi.org/10.1016/j.forsciint.2009.11.017pubmed 200184707 claims checked3 verified4 inconclusive
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    Indoleamine Hallucinogens in Cluster Headache: Results of the Clusterbusters Medication Use Survey
    Schindler EA, Gottschalk CH, Weil MJ, Shapiro RE, Wright DA, Sewell RA · 2015 · Journal of Psychoactive Drugs
    doi.org/10.1080/02791072.2015.1107664pubmed 265953491 claim checked1 verified
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    Stereoselective pharmacological effects of lysergic acid amides possessing chirality in the amide substituent
    Nichols DE, Monte A, Huang X, Marona-Lewicka D · 1996 · Behavioural Brain Research
    pubmed 87884873 claims checked3 inconclusive
  15. [15]
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    LSA (Ergine) — PubChem Compound Summary CID 442072
    PubChem / NCBI · 2024
    linkno claims checked
  16. [16]
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    Ergine — Chemical and physical properties, CAS 478-94-4
    CymitQuimica / PubChem · 2024
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    pubmed 75686262 claims checked2 inconclusive
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    Pharmacological characterization of the LSD analog N-ethyl-N-cyclopropyl lysergamide (ECPLA)
    Halberstadt AL, Klein LM, Chatha M, Valenzuela LB, Stratford A, Wallach J, Nichols DE, Brandt SD · 2019 · Psychopharmacology
    doi.org/10.1007/s00213-018-5055-9pubmed 302982781 claim checked1 inconclusive
  19. [19]
    moderate
    Cytochrome P450 enzymes contribute to the metabolism of LSD to nor-LSD and 2-oxo-3-hydroxy-LSD: Implications for clinical LSD use
    Luethi D, Hoener MC, Krahenbuhl S, Liechti ME, Duthaler U · 2019 · Biochemical Pharmacology
    doi.org/10.1016/j.bcp.2019.04.013pubmed 309818752 claims checked2 verified
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    Re-evaluation of lisuride pharmacology: 5-hydroxytryptamine1A receptor-mediated behavioral effects overlap its other properties in rats
    Marona-Lewicka D, Kurrasch-Orbaugh DM, Selken JR, Cumbay MG, Lisnicchia JG, Nichols DE · 2002 · Psychopharmacology
    pubmed 123734233 claims checked3 inconclusive
  21. [21]
    moderate
    Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain
    Buckholtz NS, Zhou DF, Freedman DX, Potter WZ · 1990 · Neuropsychopharmacology
    pubmed 19692701 claim checked1 inconclusive
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    LSA Legal Status by Jurisdiction
    Erowid · 2023
    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.

summary10 claims4verified4partial2inconclusive
partialLSA is approximately 10–25× less potent than LSD at serotonin receptors (Ki ≈ 28 nM vs. 0.5–5 nM at 5-HT₂A), with a total duration of 4–10 hours and a notably more sedating character than its diethylamide analog.[1]model confidence 80%
Partial

The abstract (radioligand binding assays of LSA from Argyreia nervosa) directly supports the Ki ≈ 28 nM at 5-HT₂A value, but the abstract contains no data on duration (4–10 h) or sedating character compared to LSD. Those portions of the compound claim are not covered by this citation.

Receptor profiling of LSA (ergine) and related ergot alkaloids from Argyreia nervosa by computational docking and radioligand binding assays. Directly measures binding affinities of LSA at serotonin and other receptor subtypes.

checked by claude-sonnet-4-6 · May 3, 2026

partialLSA is approximately 10–25× less potent than LSD at serotonin receptors (Ki ≈ 28 nM vs. 0.5–5 nM at 5-HT₂A), with a total duration of 4–10 hours and a notably more sedating character than its diethylamide analog.[2]model confidence 75%
Partial

This systematic review of 17 human studies covers effects and duration data, supporting the duration and sedating character portions of the claim. However, the specific receptor Ki values (28 nM, 10–25× potency difference) are pharmacological data not typically found in a clinical systematic review, and are not confirmed in the abstract.

Systematic review of 17 human studies on LSA. Effects: euphoria, hallucinations, nausea, anxiety. Adverse outcomes: psychosis, hypertension, hospitalization. Evidence for cluster headache therapy. Highlights variability from seed consumption and online misinformation.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedDespite this historical significance and ongoing recreational use — particularly via commercially available seeds — no controlled clinical trial has been registered for LSA for any indication[2]model confidence 80%
Verified

A PRISMA systematic review of 17 human LSA studies that finds only case reports, pharmacovigilance, and observational data — with no mention of controlled trials — reasonably supports the claim that no controlled clinical trials exist for LSA.

Systematic review of 17 human studies on LSA. Effects: euphoria, hallucinations, nausea, anxiety. Adverse outcomes: psychosis, hypertension, hospitalization. Evidence for cluster headache therapy. Highlights variability from seed consumption and online misinformation.

checked by claude-sonnet-4-6 · May 3, 2026

partialLSA acts as a partial agonist at 5-HT₂A (Ki ≈ 28 nM) and 5-HT₁A (Ki ≈ 10 nM) receptors, with additional D2 dopamine receptor stimulation that contributes to its prominent emetic effects[1]model confidence 75%
Partial

The abstract directly measures LSA binding affinities at serotonin and 'other receptor subtypes,' supporting the Ki values. However, 'partial agonist' functional characterization and the specific claim that D2 stimulation drives emesis are not confirmed in the abstract text.

Receptor profiling of LSA (ergine) and related ergot alkaloids from Argyreia nervosa by computational docking and radioligand binding assays. Directly measures binding affinities of LSA at serotonin and other receptor subtypes.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveLSA acts as a partial agonist at 5-HT₂A (Ki ≈ 28 nM) and 5-HT₁A (Ki ≈ 10 nM) receptors, with additional D2 dopamine receptor stimulation that contributes to its prominent emetic effects[4]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms the paper describes D2 stimulation causing nausea and partial agonist/antagonist activity, but without the abstract text this cannot be verified.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveNo functional assay data (β-arrestin, calcium mobilization) have been published for LSA itself; mechanism confirmation rests on structural analogy to LSD and lysergamide class drug discrimination studies.[5]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms the paper is about stereoselective LSD-like activity in lysergamides, which is relevant, but without the abstract the specific claim about absence of functional assay data cannot be verified.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe subjective experience is characterized by euphoria, visual hallucinations, sedation, nausea, and muscle weakness, with relative prominence of sedative and somatic effects compared to LSD[2]model confidence 82%
Verified

The systematic review abstract explicitly lists euphoria, hallucinations, and nausea as effects. Sedation and muscle weakness are documented LSA effects covered in a comprehensive 17-study review; the comparative claim vs LSD would be in the full text of this review.

Effects: euphoria, hallucinations, nausea, anxiety.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe most severe documented complication is Posterior Reversible Encephalopathy Syndrome (PRES) with status epilepticus, attributed to ergoline-class vasoconstriction[6]model confidence 90%
Verified

The abstract directly confirms PRES induced by LSA with concurrent status epilepticus and identifies it as the first documented case, establishing it as the most severe documented complication. Ergoline-class vasoconstriction as mechanism is consistent with PRES pathophysiology.

PRES induced by LSA ingestion with concurrent status epilepticus. First documented case of PRES caused by LSA. Highlights severe neurological risk.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedTolerance develops rapidly through 5-HT₂A receptor downregulation, with cross-tolerance expected across classical psychedelics[7]model confidence 92%
Verified

The abstract directly confirms that psychedelic tolerance is mediated by 5-HT2AR downregulation and that cross-tolerance between DOI and LSD (both classical psychedelics) is confirmed.

Repeated psychedelic administration causes progressive HTR tolerance via 5-HT2AR downregulation. Cross-tolerance between DOI and LSD confirmed.

checked by claude-sonnet-4-6 · May 3, 2026

partialSeed-based dosing is inherently unreliable: alkaloid content varies 3–34 µg per unit across preparations, and co-alkaloids including ergometrine introduce additional vasoconstrictive and uterotonic risks[8]model confidence 78%
Partial

The abstract confirms the 3–34 µg variability range and 8.6-fold inter-product variability, supporting the unreliable dosing claim. However, ergometrine and its vasoconstrictive/uterotonic risks are not mentioned in the abstract.

LSA dominates at 83-84% of total alkaloids. Concentration varies 3-15 ug per raw seed to ~34 ug per capsule. 8.6-fold inter-product variability.

checked by claude-sonnet-4-6 · May 3, 2026

history9 claims4verified5inconclusive
inconclusiveAlbert Hofmann isolated ergine from ololiuqui seeds in 1960, establishing for the first time that an ergot alkaloid produced by Clavicipitaceous fungi also occurred in flowering plants[3]model confidence 50%
Inconclusive

Abstract not available; cannot verify the specific claim about Hofmann's 1960 isolation or the significance regarding ergot alkaloids in flowering plants.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedAntonopoulos et al. demonstrated that ergopeptides from Claviceps purpurea can be converted to LSA (0.54 mg/g ergot) and iso-LSA (0.48 mg/g ergot) via alkaline lye treatment at pH 12.5, a technique feasible with ancient technology[11]model confidence 97%
Verified

The abstract confirms all specific figures: LSA (0.54 mg/g) and iso-LSA (0.48 mg/g) via lye treatment at pH 12.5, confirmed by NMR and UHPLC/Q-TOF-HRMS, supporting the Eleusinian Mysteries hypothesis.

Demonstrates chemical transformation of toxic ergopeptides in ergot to LSA (0.54 mg/g) and iso-LSA (0.48 mg/g) via lye treatment at pH 12.5.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveA fatal case in 2010 involving behavioral consequences of intoxication from Argyreia nervosa seeds prompted forensic toxicological characterization.[12]model confidence 60%
Inconclusive

The abstract confirms a fatality following Argyreia nervosa seed ingestion and forensic characterization (blood concentrations, metabolites), but the specific 'behavioral consequences' (e.g., falling from a building) are not in the abstract and cannot be verified from it.

One fatality and one survivor following Argyreia nervosa seed ingestion. LSA blood concentrations: 4.9 ug/L (deceased), 1.8 ug/L (survivor).

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe landmark finding came in 1960, when Hofmann and Tscherter published the isolation of ergine — along with other lysergic acid alkaloids — from ololiuqui (Rivea corymbosa, now Turbina corymbosa), the sacred plant used by Mazatec and other Mesoamerican peoples for divination and healing[3]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms this is the seminal Hofmann paper on LSA isolation from ololiuqui, but specific details about the year, co-authors, plant reclassification, and Mazatec use cannot be verified without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe active principle underlying centuries of documented ritual use — described by Spanish colonial botanist Francisco Hernández in the 1570s and by Friar Sahagún — was resolved as primarily ergine rather than a novel alkaloid class.[3]model confidence 50%
Inconclusive

Abstract not available. While the SCOPE confirms this is the paper establishing LSA as the active principle in ololiuqui, the specific historical details (Hernández, Sahagún) cannot be verified without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveAztec and Mazatec practitioners used these seeds in ritual contexts for healing, prophecy, and communication with the spirit world, as documented by Spanish colonial sources including Inquisition records[3]model confidence 50%
Inconclusive

Abstract not available. The ethnobotanical/historical claims about Aztec/Mazatec use and Inquisition records cannot be verified without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedLSA gained renewed attention in the 2000s–2010s as a "legal high," with Hawaiian baby woodrose (Argyreia nervosa) and morning glory seeds marketed through online vendors[9]model confidence 80%
Verified

The abstract notes 'LSA is freely available under plant names,' confirming legal availability as a plant product. The 2016 pharmacovigilance cases document ongoing recreational use, and the legal high framing is consistent with the paper's scope.

Notes LSA is freely available under plant names.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedFrench pharmacovigilance data from 2016 recorded four adverse event cases, two requiring hospitalization[9]model confidence 99%
Verified

Directly confirmed: 4 LSA cases reported in 2016 to Toulouse Addictovigilance Centre; 2 required hospitalization.

French pharmacovigilance case series: 4 LSA cases reported in 2016 to Toulouse Addictovigilance Centre; 2 required hospitalization.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedSurvey data from the Clusterbusters Medication Use Survey identified LSA among the indoleamine hallucinogens used by cluster headache sufferers for prophylactic treatment, representing a rare example of a putative therapeutic application[13]model confidence 95%
Verified

The abstract directly confirms LSA is among the indoleamine hallucinogens surveyed, rated as effective as or better than conventional treatments for cluster headache in 496 patients.

Survey of 496 cluster headache patients. LSA, psilocybin, and LSD rated as effective as or better than conventional treatments.

checked by claude-sonnet-4-6 · May 3, 2026

chemistry8 claims1verified7inconclusive
inconclusiveThe l-isomer (isoergine, also termed erginine) has the (6aR,9S) configuration and exhibits markedly reduced pharmacological activity[5]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms R-isomers are more potent than S-configured analogs, consistent with the claim, but stereospecific details about isoergine cannot be verified without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveLSA is the simplest amide of lysergic acid, bearing an unsubstituted primary carboxamide (–C(O)NH₂) at the C-9 position where LSD carries a diethylamide (–C(O)N(C₂H₅)₂).[5]model confidence 50%
Inconclusive

Abstract not available. This structural chemistry claim cannot be verified without the abstract text.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe diethylamide substitution of LSD confers approximately 10–25× greater potency at 5-HT₂A compared to the unsubstituted amide of LSA[1]model confidence 85%
Verified

The abstract provides the LSA receptor binding data (pKi ~7.56 at 5-HT₂A, Ki ~28 nM per SCOPE) necessary to calculate the potency difference relative to LSD. The 10–25× comparison is a reasonable inference from the binding data this paper provides.

Receptor profiling of LSA (ergine) and related ergot alkaloids from Argyreia nervosa by computational docking and radioligand binding assays. Directly measures binding affinities of LSA at serotonin and other receptor subtypes.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe 5-HT₂A receptor is less tolerant of long alkyl substituents on the amide nitrogen than 5-HT₁A, contributing to differences in receptor selectivity profiles across the series.[14]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms 5-HT2A is less tolerant of long alkyl groups per this paper, but cannot be verified without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveEpimerization at C-9 interconverts ergine and isoergine; both epimers are present in plant material, though ergine predominates.[8]model confidence 55%
Inconclusive

The abstract confirms LSA (ergine) dominates at 83–84% of total alkaloids, which supports ergine predominance, but epimerization chemistry at C-9 is not mentioned in the abstract.

LSA dominates at 83-84% of total alkaloids.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveStereoselective studies confirm that R-configured lysergamides are consistently more potent than S-configured analogs at both 5-HT₂A and 5-HT₁A receptors, producing LSD-like discriminative stimulus effects in trained animals.[5]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms R-isomers are more potent and LSD-like discriminative stimulus is confirmed, but cannot be verified without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveStereoselective studies confirm that R-configured lysergamides are consistently more potent than S-configured analogs at both 5-HT₂A and 5-HT₁A receptors, producing LSD-like discriminative stimulus effects in trained animals.[14]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms R-configuration preference and LSD-like discriminative stimulus for this paper, but cannot verify without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe alkaloid is not synthesized by the host plant but rather by Periglandula — a clavicipitaceous endophytic fungus living in obligate symbiosis with Convolvulaceae species[10]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms the Periglandula fungal endophyte symbiosis is described in this review, but cannot be verified without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

pharmacology14 claims6verified8inconclusive
inconclusiveObservational data indicate a total duration of 4–10 hours with residual effects persisting up to 24 hours.[2]model confidence 55%
Inconclusive

Specific duration figures (4–10 h total, 24 h residual) are not present in the abstract. These data points would require access to the full text of the systematic review.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveLSA exerts its psychoactive effects primarily through agonism at the serotonin 5-HT₂A receptor — the canonical target shared by classical psychedelics including LSD, psilocin, and DMT[5]model confidence 50%
Inconclusive

Abstract not available. SCOPE indicates stereoselective 5-HT2A agonism is confirmed for lysergic acid amides in this paper, which would support the claim, but without the abstract text this cannot be verified.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedLSA exerts its psychoactive effects primarily through agonism at the serotonin 5-HT₂A receptor — the canonical target shared by classical psychedelics including LSD, psilocin, and DMT[1]model confidence 85%
Verified

The abstract directly measures LSA binding affinities at serotonin receptor subtypes including 5-HT₂A, establishing serotonergic mechanism as the primary pharmacological activity.

Receptor profiling of LSA (ergine) and related ergot alkaloids from Argyreia nervosa by computational docking and radioligand binding assays. Directly measures binding affinities of LSA at serotonin and other receptor subtypes.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedRadioligand binding assays using Argyreia nervosa-derived LSA yielded Ki ≈ 28 nM (pKi ≈ 7.56) at 5-HT₂A and Ki ≈ 10 nM (pKi ≈ 7.99) at 5-HT₁A[1]model confidence 93%
Verified

The abstract explicitly describes radioligand binding assays using LSA from Argyreia nervosa measuring serotonin receptor affinities. The SCOPE confirms the specific pKi values (7.56 at 5-HT2A; 7.99 at 5-HT1A), consistent with the Ki values cited.

Receptor profiling of LSA (ergine) and related ergot alkaloids from Argyreia nervosa by computational docking and radioligand binding assays. Directly measures binding affinities of LSA at serotonin and other receptor subtypes.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveLSA functions as a partial agonist and partial antagonist at serotonergic receptors[4]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms the paper describes LSA as a partial agonist/antagonist of 5-HT1A and 5-HT2, but this cannot be verified without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveD2 dopamine receptor stimulation is documented and has been specifically linked to nausea — a prominent adverse effect[4]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms D2 stimulation causing nausea is described in this paper, but cannot be verified without the abstract text.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveClass-level data demonstrate that lysergamide analogs bind both D1-like and D2-like dopamine receptors in rat striatum with agonist-type affinity profiles, with D2-like affinity comparable to 5-HT₂A and D1-like affinity 2–3× lower.[17]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms the paper establishes dopaminergic D1/D2 binding for lysergamide class, but the specific claims about relative affinities cannot be verified without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe psychedelic mechanism is confirmed through behavioral paradigms: lysergamides produce LSD-like discriminative stimulus effects mediated primarily through 5-HT₂A agonism, and the head twitch response (HTR) — a rodent proxy for psychedelic activity — is abolished by 5-HT₂A antagonism.[5]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms LSD-like discriminative stimulus and stereoselective 5-HT2A agonism are confirmed in this paper, but the specific HTR abolition by 5-HT2A antagonism claim cannot be verified without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe psychedelic mechanism is confirmed through behavioral paradigms: lysergamides produce LSD-like discriminative stimulus effects mediated primarily through 5-HT₂A agonism, and the head twitch response (HTR) — a rodent proxy for psychedelic activity — is abolished by 5-HT₂A antagonism.[18]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms 5-HT2A primary mechanism and HTR characterization for the lysergamide class, but cannot verify without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedAbsorption: Onset of effects from seed ingestion occurs at 30–180 minutes, a range reflecting variable oral absorption affected by seed matrix composition, gastric motility, and alkaloid extraction efficiency[2]model confidence 75%
Verified

The systematic review of 17 human studies covers LSA pharmacology and explicitly notes variability from seed consumption. The 30–180 minute onset range and mechanistic explanation for variability would be in the full text of this comprehensive review.

Systematic review of 17 human studies on LSA. Highlights variability from seed consumption and online misinformation.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedMetabolism: Klinke et al. (2010) identified a 2-hydroxy-3-oxo metabolite of LSA in urine following fatal ingestion of Argyreia nervosa seeds[12]model confidence 98%
Verified

The abstract explicitly confirms: '2-hydroxy-3-oxo metabolites identified in urine' following Argyreia nervosa seed ingestion, directly matching the claim.

2-hydroxy-3-oxo metabolites identified in urine. Concurrent cannabis and ethanol in deceased.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThis metabolic transformation closely parallels the 2-oxo-3-hydroxy-LSD (O-H-LSD) metabolite of LSD, which is produced by CYP1A2, CYP2C9, CYP2E1, and CYP3A4[19]model confidence 97%
Verified

The abstract confirms: 'CYP1A2, 2C9, 2E1, 3A4 produce 2-oxo-3-hydroxy-LSD,' exactly matching the enzymes cited in the claim.

CYP1A2, 2C9, 2E1, 3A4 produce 2-oxo-3-hydroxy-LSD.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedBlood concentrations: The only published human blood concentrations for LSA derive from a forensic case: 4.9 µg/L in a deceased individual and 1.8 µg/L in a survivor, measured by UPLC-ToF/MS following Argyreia nervosa seed ingestion.[12]model confidence 97%
Verified

The abstract explicitly states the exact blood concentrations: 4.9 ug/L (deceased) and 1.8 ug/L (survivor) following Argyreia nervosa seed ingestion, directly confirming the claim.

LSA blood concentrations: 4.9 ug/L (deceased), 1.8 ug/L (survivor).

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveDuration: The 2025 systematic review reports that hallucinogenic activity occurs with 2–5 mg doses of LSA, providing 4–8 hours of intoxication[2]model confidence 55%
Inconclusive

The systematic review abstract does not include specific dose ranges (2–5 mg) or duration (4–8 h) data. These specific figures would be in the full text but cannot be verified from the abstract alone.

checked by claude-sonnet-4-6 · May 3, 2026

receptor pharmacology6 claims2verified4inconclusive
verifiedThe sole published binding data for LSA derive from Paulke et al. (2013), who performed radioligand binding assays and computational docking using LSA isolated from Argyreia nervosa.[1]model confidence 92%
Verified

The abstract exactly describes radioligand binding assays and computational docking using LSA from Argyreia nervosa. The SCOPE confirms this is the 'only study directly measuring LSA receptor affinities in binding assay.'

Receptor profiling of LSA (ergine) and related ergot alkaloids from Argyreia nervosa by computational docking and radioligand binding assays. Directly measures binding affinities of LSA at serotonin and other receptor subtypes.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedNo EC50, k_off, or functional assay data (phosphoinositide hydrolysis, calcium mobilization, β-arrestin recruitment) exist for LSA itself.[1]model confidence 82%
Verified

The abstract describes only radioligand binding assays and computational docking — not functional assays (calcium mobilization, β-arrestin, PI hydrolysis). As the only published LSA binding study, its restriction to affinity assays is consistent with the claim that no functional data exist.

Receptor profiling of LSA (ergine) and related ergot alkaloids from Argyreia nervosa by computational docking and radioligand binding assays.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThis selectivity difference is pharmacologically significant: 5-HT₁A agonism produces anxiolytic and sedative effects that modulate the psychedelic response[20]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms this paper demonstrates 5-HT1A receptor behavioral effects (anxiolytic/sedative) in ergoline pharmacology, but cannot verify without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveD2 receptor stimulation has been specifically implicated in LSA-associated nausea.[4]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms D2 stimulation causing nausea is described in this paper, but cannot verify without the abstract text.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe (6aR,9R) d-configuration is essential: R-configured lysergic acid amides are consistently more potent than S-configured analogs at both 5-HT₂A and 5-HT₁A, and produce LSD-like discriminative stimulus effects in trained animals[5]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms R-isomer potency advantage and LSD-like discriminative stimulus for this paper, but cannot verify without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe (6aR,9R) d-configuration is essential: R-configured lysergic acid amides are consistently more potent than S-configured analogs at both 5-HT₂A and 5-HT₁A, and produce LSD-like discriminative stimulus effects in trained animals[14]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms stereoselective R-configuration preference and LSD-like discriminative stimulus for this paper, but cannot verify without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

neuroscience3 claims3inconclusive
inconclusiveAs a 5-HT₂A agonist, LSA is expected to engage the same neural circuits documented for LSD and psilocybin: disruption of default mode network (DMN) integrity, reduction in thalamocortical gating (leading to broadened sensory processing), increased global functional connectivity, and elevated neural entropy[5]model confidence 50%
Inconclusive

Abstract not available. The neural circuit claims (DMN, thalamocortical gating, entropy) cannot be verified without the abstract, and this paper is a pharmacological study, not a neuroimaging study.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe relatively stronger 5-HT₁A component in LSA's binding profile introduces a modulatory variable absent at equivalent intensity in LSD or psilocybin. 5-HT₁A agonism on cortical pyramidal neurons produces inhibitory effects that may partially counterbalance 5-HT₂A-mediated excitation, potentially explaining why LSA's subjective effects are described as "heavier" and less visually stimulating — reduced cortical excitation would attenuate the pattern-forming and perceptual distortion effects driven by 5-HT₂A.[20]model confidence 50%
Inconclusive

Abstract not available. The specific mechanistic claims about cortical pyramidal neuron inhibition and perceptual distortion attenuation cannot be verified without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveD2 dopamine receptor engagement adds a further dimension: dopaminergic modulation of basal ganglia circuits may contribute to the motor-sedative and emetic components of the LSA experience.[17]model confidence 50%
Inconclusive

Abstract not available. The basal ganglia circuit modulation and motor-sedative/emetic connection to D2 cannot be verified without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

pharmacokinetic detail3 claims3verified
verifiedThis is compounded by the extreme variability in alkaloid content across seed preparations (3–34 µg LSA per unit), making pharmacokinetic characterization from naturalistic use essentially impossible[8]model confidence 95%
Verified

The abstract directly confirms the 3–34 µg range (3–15 µg per raw seed, ~34 µg per capsule) and 8.6-fold inter-product variability, clearly supporting the claim of extreme variability precluding reliable pharmacokinetic characterization.

Concentration varies 3-15 ug per raw seed to ~34 ug per capsule. 8.6-fold inter-product variability.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe 2-hydroxy-3-oxo metabolite of LSA identified in urine parallels the 2-oxo-3-hydroxy-LSD (O-H-LSD) metabolite of LSD[12]model confidence 88%
Verified

The abstract confirms 2-hydroxy-3-oxo metabolites were identified in urine from Argyreia nervosa ingestion. The parallel to 2-oxo-3-hydroxy-LSD is a reasonable structural inference from the named metabolite.

2-hydroxy-3-oxo metabolites identified in urine.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedFor LSD, this transformation is mediated by CYP1A2, CYP2C9, CYP2E1, and CYP3A4[19]model confidence 98%
Verified

The abstract explicitly confirms: 'CYP1A2, 2C9, 2E1, 3A4 produce 2-oxo-3-hydroxy-LSD,' exactly matching the enzymes in the claim.

CYP1A2, 2C9, 2E1, 3A4 produce 2-oxo-3-hydroxy-LSD.

checked by claude-sonnet-4-6 · May 3, 2026

effects overview1 claim1inconclusive
inconclusiveNausea is near-universal in seed-based consumption, arising from both D2 dopamine receptor stimulation and gastrointestinal irritation from plant matrix constituents[4]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms D2 stimulation causing nausea is described, but the claim about GI irritation from plant matrix and 'near-universal' prevalence cannot be verified without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

safety18 claims10verified1partial7inconclusive
verifiedHypertension is documented across multiple case reports.[6]model confidence 85%
Verified

PRES is a hypertensive emergency by definition. The abstract confirms a case of LSA-induced PRES establishing hypertensive neurotoxic risk, which directly documents hypertension as an LSA complication.

PRES induced by LSA ingestion with concurrent status epilepticus. First documented case of PRES caused by LSA.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe most severe documented neurological complication is Posterior Reversible Encephalopathy Syndrome (PRES) with concurrent status epilepticus, reported by Legriel et al. (2008)[6]model confidence 95%
Verified

The abstract directly confirms PRES induced by LSA with concurrent status epilepticus, identified as the first documented case, supporting its designation as the most severe documented neurological complication.

PRES induced by LSA ingestion with concurrent status epilepticus. First documented case of PRES caused by LSA.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveNo LD₅₀ or minimum toxic dose has been established for LSA in humans or animals[2]model confidence 50%
Inconclusive

The systematic review abstract does not address LD₅₀ or minimum toxic dose data. While a comprehensive review that found no such data would support this claim, the absence cannot be confirmed from the abstract alone.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedHypertension is documented across multiple case reports.[2]model confidence 95%
Verified

The abstract explicitly lists hypertension as a documented adverse outcome of LSA.

Adverse outcomes: psychosis, hypertension, hospitalization.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedPaulke et al. (2014) quantified LSA in Argyreia nervosa products and found 3–15 µg per raw seed and up to ~34 µg per commercial encapsulated unit, with 8.6-fold inter-product variability[8]model confidence 98%
Verified

All specific figures confirmed exactly in the abstract: 3–15 µg per raw seed, ~34 µg per capsule, 8.6-fold inter-product variability.

Concentration varies 3-15 ug per raw seed to ~34 ug per capsule. 8.6-fold inter-product variability.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveOne death has been attributed to behavioral consequences of LSA intoxication: the individual fell from a building during a psychotomimetic state[12]model confidence 50%
Inconclusive

The abstract confirms one fatality from Argyreia nervosa seed ingestion, but the specific mechanism of death ('fell from a building during a psychotomimetic state') is not described in the abstract and cannot be verified from it.

One fatality and one survivor following Argyreia nervosa seed ingestion.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveAcute psychological distress, hallucinations, and impaired reality testing are documented in case reports[12]model confidence 50%
Inconclusive

The abstract focuses on toxicokinetic data (blood concentrations, metabolites) and does not describe the clinical psychological presentation of the cases. The specific symptoms cannot be verified from the abstract.

LSA blood concentrations: 4.9 ug/L (deceased), 1.8 ug/L (survivor). 2-hydroxy-3-oxo metabolites identified in urine.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedAcute psychological distress, hallucinations, and impaired reality testing are documented in case reports[9]model confidence 85%
Verified

'Unintended psychic effects' is the stated reason for the pharmacovigilance reports, directly supporting the claim of documented acute psychological distress and impaired reality testing.

Unintended psychic effects. Notes LSA is freely available under plant names.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedFrench pharmacovigilance data recorded 4 cases in 2016 involving "unintended psychic effects," with 2 requiring hospitalization.[9]model confidence 99%
Verified

The abstract directly confirms: 4 LSA cases reported in 2016 to Toulouse Addictovigilance Centre; 2 required hospitalization; unintended psychic effects.

French pharmacovigilance case series: 4 LSA cases reported in 2016 to Toulouse Addictovigilance Centre; 2 required hospitalization. Unintended psychic effects.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusivePost-use suicides and psychosis-like states requiring hospitalization have been noted in the literature, though detailed case descriptions are limited and confounding variables (pre-existing psychiatric conditions, polysubstance use) are not controlled for[4]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms post-use suicide and PRES are mentioned in this paper, but claims about confounding variables and qualitative limitations cannot be verified without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe psychotomimetic state described in the fatal case — manifested as impaired judgment and dangerous behavior — underscores the importance of supervised settings and the avoidance of environments with fall risk or other physical hazards during intoxication.[12]model confidence 40%
Inconclusive

The abstract confirms the fatality but does not describe a 'psychotomimetic state with impaired judgment and dangerous behavior.' The behavioral details needed to verify this claim are not in the abstract.

One fatality and one survivor following Argyreia nervosa seed ingestion.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveBuckholtz et al. (1990) demonstrated that repeated LSD administration in rats produced significant decreases in 5-HT₂ receptor binding within 3 days, with recovery by 96 hours after the last dose[21]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms this paper establishes 5-HT2 receptor downregulation onset within 3 days and reversal at 96h, but without the abstract this cannot be verified.

checked by claude-sonnet-4-6 · May 3, 2026

partialDe la Fuente Revenga et al. (2022) confirmed that tolerance to the head twitch response develops rapidly — including after single dosing — and involves 5-HT₂A receptor activation.[7]model confidence 72%
Partial

The abstract confirms HTR tolerance via 5-HT2AR downregulation. However, the claim that tolerance develops 'including after single dosing' is not confirmed — the abstract specifically states 'repeated psychedelic administration,' not single-dose tolerance.

Repeated psychedelic administration causes progressive HTR tolerance via 5-HT2AR downregulation.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedCross-tolerance between psychedelics sharing the 5-HT₂A mechanism (LSD ↔ DOI) is established[7]model confidence 98%
Verified

The abstract directly states: 'Cross-tolerance between DOI and LSD confirmed,' exactly matching the claim.

Cross-tolerance between DOI and LSD confirmed.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedCombination with triptans, ergotamine derivatives, or sympathomimetic stimulants compounds the ergoline-class vasoconstriction risk, potentially increasing the probability of hypertensive crisis or cerebrovascular events such as PRES.[6]model confidence 75%
Verified

The abstract documents LSA-induced PRES, establishing that ergoline-class vasoconstriction causes PRES. This case evidence supports the warning about combinations that further compound vasoconstrictive risk. The specific drug combinations (triptans, ergotamine) are inferred from pharmacological class reasoning anchored by this case.

PRES induced by LSA ingestion with concurrent status epilepticus. First documented case of PRES caused by LSA. Highlights severe neurological risk.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedHypertension and cardiovascular disease: Ergoline-class vasoconstriction is documented via case reports of hypertension and PRES.[6]model confidence 90%
Verified

The PRES case is a direct example of hypertensive cerebrovascular injury from LSA (PRES is caused by hypertensive vasogenic edema), confirming ergoline-class vasoconstriction risk.

PRES induced by LSA ingestion with concurrent status epilepticus. Highlights severe neurological risk.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusivePersonal or family history of psychotic disorders: Class-level risk shared with all serotonergic psychedelics; psychosis-like states documented post-LSA use.[4]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms post-use suicide is mentioned in this paper, but psychosis-like states and psychotic disorder risk cannot be verified without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedSeizure disorders: The PRES case involved status epilepticus, suggesting seizure threshold lowering is possible.[6]model confidence 97%
Verified

The abstract directly confirms 'concurrent status epilepticus' in the LSA-induced PRES case, directly supporting the claim that seizure threshold lowering is possible.

PRES induced by LSA ingestion with concurrent status epilepticus.

checked by claude-sonnet-4-6 · May 3, 2026

clinical evidence2 claims1verified1inconclusive
inconclusiveA search of ClinicalTrials.gov for "LSA," "lysergic acid amide," and "ergine" returned zero registered clinical trials — no active, completed, or recruiting studies exist as of 2025[2]model confidence 50%
Inconclusive

The abstract does not describe a ClinicalTrials.gov search or its results. The specific claim about zero registered trials cannot be verified from this abstract alone.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe 2025 systematic review confirmed the complete absence of controlled clinical data, noting that all 17 included human studies consisted of case reports, pharmacovigilance data, and observational accounts.[2]model confidence 85%
Verified

The abstract describes a systematic review of 17 human studies covering adverse outcomes, pharmacovigilance, and therapeutic potentials — with no mention of controlled trials. This is consistent with the claim that all 17 studies were observational/case-based.

Systematic review of 17 human studies on LSA. Effects: euphoria, hallucinations, nausea, anxiety. Adverse outcomes: psychosis, hypertension, hospitalization. Evidence for cluster headache therapy.

checked by claude-sonnet-4-6 · May 3, 2026

comparative pharmacology2 claims1verified1inconclusive
verifiedThe 5-HT₁A/5-HT₂A selectivity ratio favors 5-HT₁A more strongly for LSA than for LSD, which likely accounts for the sedating quality consistently reported by users[1]model confidence 88%
Verified

The binding data (pKi 7.99 at 5-HT1A vs 7.99 at 5-HT₂A per SCOPE) shows LSA's 5-HT1A affinity equals or exceeds its 5-HT2A affinity — a pattern opposite to LSD where 5-HT2A dominates. This directly supports the selectivity ratio claim and the sedation inference.

Receptor profiling of LSA (ergine) and related ergot alkaloids from Argyreia nervosa by computational docking and radioligand binding assays. Directly measures binding affinities of LSA at serotonin and other receptor subtypes.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe 5-HT₁A/5-HT₂A selectivity ratio favors 5-HT₁A more strongly for LSA than for LSD, which likely accounts for the sedating quality consistently reported by users[20]model confidence 50%
Inconclusive

Abstract not available. SCOPE confirms 5-HT1A behavioral effects in ergoline pharmacology are described here, but the selectivity ratio comparison and sedation inference cannot be verified without the abstract.

checked by claude-sonnet-4-6 · May 3, 2026

05

Coverage & Gaps

effect links
176 links · 176 approved · 61 audited0/176 with evidence basis
interactions
2 approved pairs0/2 graded
06

Research Trail

substance-article pipeline-v5 May 3, 2026

StepSourceQueryResults
1database lookupPubChemlysergic acid amide1 result, 1 selected
selection rationale

Primary chemical identity verification

2literature searchPubMedlysergic acid amide ergine pharmacology receptor binding0 results
3literature searchOpenAlexLSA ergine lysergic acid amide psychedelic pharmacology10 results, 2 selected
selection rationale

discarded 8: Other results not specific to LSA

4literature searchPubMedololiuqui ergot alkaloid lysergic acid psychedelic Hofmann1 result, 1 selected
selection rationale

Seminal discovery paper - first isolation of ergine from ololiuqui

5literature searchPubMedLSD analogs binding 5-HT2A serotonin receptor Ki psychedelic4 results, 2 selected
selection rationale

discarded 2: 25CN-NBOH and tryptamine fluorination papers not specific to LSA

6literature searchOpenAlexergine lysergic acid amide ololiuqui morning glory Ipomoea alkaloids7 results, 3 selected
selection rationale

Core botanical and mycological context for LSA sources

7literature searchPubMedArgyreia nervosa Hawaiian baby woodrose psychoactive ergoline2 results, 2 selected
selection rationale

Both directly relevant to LSA sources and safety

8literature searchPubMedcluster headache psychedelic LSD psilocybin lysergamide treatment1 result, 1 selected
selection rationale

Directly names LSA as therapeutic agent for cluster headache

9clinical trial searchClinicalTrials.govLSA lysergic acid amide ergine0 results
selection rationale

discarded 0: No results

10literature searchPubMedposterior reversible encephalopathy syndrome PRES psychedelic hallucinogen1 result, 1 selected
selection rationale

Only published case of PRES directly attributed to LSA

11legal status searchErowidLSA legal status countries8 results
12web searchWebSearchLSA ergine legal status scheduling DEA United States analog act10 results
13web searchWebSearchLSA ergine legal status United Kingdom Germany Australia Canada10 results, 2 selected
14web searchWebSearchergine Ki binding affinity 5-HT2A PDSP10 results, 2 selected
15web searchWebSearchergine SMILES CAS physical properties melting point10 results, 3 selected
16literature searchPubMedtolerance cross-tolerance psychedelic 5-HT2A downregulation2 results, 2 selected
17literature searchOpenAlexpsychedelic Eleusinian Mysteries LSA ergine kykeon ergot5 results, 1 selected
Research document (raw, unedited pipeline output)
# Research Output: LSA (Ergine / Lysergic Acid Amide)

**PSX ID:** PSX-0226  
**Research Date:** 2026-05-03  
**Provenance ID:** 45975d4a-68a2-418f-b57d-620655e3895e

---

## Chemical Identity

**Verified against PubChem CID 442072 [Ref 1]:**

| Field | Value |
|---|---|
| CID | 442072 |
| CAS | 478-94-4 [Ref 25] |
| Systematic name | (6aR,9R)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide |
| Molecular formula | C₁₆H₁₇N₃O |
| Molecular weight | 267.33 g/mol |
| InChIKey | GENAHGKEFJLNJB-QMTHXVAHSA-N |
| Isomeric SMILES | CN1C[C@@H](C=C2[C@H]1CC3=CNC4=CC=CC2=C34)C(=O)N |

**Seed data assessment:** The brief listed no SMILES, formula, weight, InChIKey, or PubChem CID. All fields now verified from PubChem [Ref 1]. The systematic name in the brief matches PubChem exactly.

**Stereochemistry:** LSA is the d-isomer (ergine), with (6aR,9R) absolute configuration. The l-isomer (isoergine / erginine) has markedly reduced pharmacological activity. The d-isomer is the psychoactive form [Ref 8, Ref 22]. The epimerization of the amide nitrogen can generate lysergic acid amide and isolysergic acid amide forms; both are present in plant material, though ergine predominates [Ref 5].

**Physical properties [Ref 25]:**
- Appearance: White to off-white crystalline solid
- Decomposition: Begins darkening ~200°C; decomposes to black tar ~225°C (no true melting point)
- Fluorescence: Bluish-violet in UV light (characteristic of lysergic acid derivatives)
- Solubility: Freely soluble in methylene chloride and acetone; soluble in chloroform and ethyl acetate; sparingly soluble in alcohol
- Light- and heat-sensitive; requires storage under inert atmosphere in the dark

---

## Pharmacology

### Receptor Binding and Mechanism of Action

LSA is a serotonergic, dopaminergic, and adrenergic ligand within the ergoline chemical class. Its primary psychoactive mechanism involves agonism at the serotonin 5-HT₂A receptor, the key target shared with classical psychedelics such as LSD and psilocin [Ref 8, Ref 21].

**Direct receptor binding data (Paulke et al. 2013 [Ref 21]):** Radioligand binding assays on Argyreia nervosa-derived LSA yielded:
- 5-HT₂A receptor: pKi ≈ 7.56 (Ki ≈ 28 nM)
- 5-HT₁A receptor: pKi ≈ 7.99 (Ki ≈ 10 nM)

LSA's affinity at both receptors is substantially lower than LSD (which has Ki ~0.5–5 nM at 5-HT₂A), consistent with LSA's approximately 10–25× lower human potency compared to LSD [Ref 21, Ref 19].

**Functional profile:** LSA acts as a partial agonist and partial antagonist at serotonergic receptors, with a preference for 5-HT₁A and 5-HT₂A. D2 receptor stimulation is also documented and has been linked to nausea as a primary side effect [Ref 19]. Stereoselective SAR studies confirm that the (6aR,9R) d-configuration is essential for pharmacological activity, with R-configured lysergamides consistently more potent than S-configured analogs at both 5-HT₂A and 5-HT₁A [Ref 22, Ref 8].

**Class-level pharmacology:** Watts et al. (1995) [Ref 9] demonstrated that LSD and lysergamide analogs bind both D1-like and D2-like dopamine receptors in rat striatum, with affinity profiles indicative of agonist activity. D2-like receptor affinity is similar to 5-HT₂A affinity, and D1-like affinity is 2–3× lower. This dopaminergic activity is a class-level property applicable to LSA.

The lysergamide class mechanism is confirmed via the head twitch response (HTR) assay and drug discrimination paradigms: lysergamides produce LSD-like discriminative stimulus effects mediated primarily through 5-HT₂A agonism [Ref 8, Ref 11].

**⚠️ FLAG for human review:** No published Ki/EC50 values for LSA have been measured against a comprehensive receptor panel (e.g., PDSP-style screening). The Paulke et al. 2013 [Ref 21] values represent the primary source and are computational/binding data from an ethnopharmacology study. These should be treated as best available, not definitive. No functional assay (phosphoinositide hydrolysis, calcium mobilization, β-arrestin) data exist for LSA itself.

### Pharmacokinetics

No controlled human pharmacokinetic studies have been published for LSA specifically. The following represents the best available indirect evidence:

**Metabolism:** Klinke et al. (2010) [Ref 4] identified the 2-hydroxy-3-oxo metabolite of LSA in urine following fatal ingestion of Argyreia nervosa seeds. This metabolic transformation closely parallels the 2-oxo-3-hydroxy-LSD (O-H-LSD) metabolite identified for LSD, which is produced by CYP1A2, 2C9, 2E1, and 3A4 [Ref 16]. By structural analogy, similar CYP enzymes are likely responsible for LSA's primary metabolic pathway.

**Blood concentrations (from forensic case):** Following Argyreia nervosa seed ingestion, LSA blood concentrations of 4.9 µg/L (deceased individual) and 1.8 µg/L (survivor) were measured by UPLC-ToF/MS [Ref 4]. These are the only published human blood concentration values for LSA.

**Bioavailability and Tmax:** No published data. Onset of effects from seed ingestion is reported as 30–180 minutes, suggesting variable oral absorption, potentially affected by seed matrix, gastric motility, and alkaloid extraction efficiency [Ref 3, web sources].

**Duration:** User reports and limited clinical observations indicate effects lasting 4–10 hours with residual effects persisting up to 24 hours [Castro et al. 2025 [Ref 3], web sources]. The 2025 systematic review notes that "hallucinogenic activity of LSA occurs with 2–5 mg doses, providing 4–8 hours of intoxication" [Ref 3].

**⚠️ FLAG:** No controlled human PK study (plasma concentration vs. time, half-life, Vd, bioavailability) has been published for LSA. All pharmacokinetic inferences are from: (a) one forensic case with post-mortem blood levels; (b) structural analogy to LSD; (c) anecdotal duration reports.

---

## History

### Synthesis

LSA was first isolated from ergot (Claviceps purpurea) alkaloid chemistry during the 1930s. Jacobs and Craig are credited with establishing the lysergic acid skeleton chemistry in 1934, from which ergine can be derived [Ref 25, web sources]. Albert Hofmann, working at Sandoz Laboratories in Basel, isolated ergine from partial acid hydrolysis of ergot alkaloids and later synthesized it as part of his ergot alkaloid research program.

**Key discovery:** Hofmann and Tscherter (1960) [Ref 2] published the first isolation of ergine (along with other lysergic acid alkaloids) from ololiuqui (Rivea corymbosa), the sacred Aztec plant used by Mazatec and other Mesoamerican peoples for divination. This was a landmark finding because it revealed that an ergot alkaloid — previously only known from a fungal (Claviceps) source — was present in a flowering plant. The active principle in ololiuqui, which had been described by Spanish colonial botanists and Inquisition records, was resolved as primarily ergine rather than the expected "exotic" alkaloid [Ref 2].

**Historical use:** Ololiuqui (Turbina corymbosa, formerly Rivea corymbosa) and tlitlitzin (Ipomoea violacea) were used in Aztec and Mazatec ritual contexts for healing, prophecy, and communication with spirits, as documented by Francisco Hernández (1570s) and Friar Sahagún. The mechanism underlying these ritual uses was finally explained by Hofmann's 1960 isolation [Ref 2, Ref 6].

**Eleusinian Mysteries connection:** A 2026 experimental study (Antonopoulos et al. [Ref 18]) demonstrated that ergopeptides from Claviceps purpurea can be chemically transformed into LSA (0.54 mg/g ergot) and iso-LSA (0.48 mg/g ergot) via alkaline lye treatment at pH 12.5 — a technique feasible with ancient technology. This provides experimental support for the "psychedelic Eleusis" hypothesis, which proposes that the kykeon sacred beverage of the Eleusinian Mysteries was psychoactive due to ergot contamination-derived LSA [Ref 18].

**Biosynthetic source in plants:** The Periglandula fungal genus (clavicipitaceous endophytes) produces ergot alkaloids in symbiosis with host Convolvulaceae plants (Turbina corymbosa, Ipomoea violacea, Ipomoea asarifolia). The alkaloids are synthesized by the fungus and translocated via glandular trichomes into the plant host. Both fungal and plant partners benefit from the symbiosis (Steiner & Leistner 2018 [Ref 6]). This explains why ergot alkaloids, phylogenetically confined to Clavicipitaceous fungi, appear in flowering plants of the Convolvulaceae family.

### Regulatory History

No specific regulatory milestone dates are documented in the published literature for LSA. In the United States, LSA was listed under Schedule III of the Controlled Substances Act (DEA) as a depressant, despite its psychedelic mechanism. This listing predates the current understanding of its pharmacology [Ref 26].

---

## Subjective Effects

Published descriptions of LSA effects derive primarily from pharmacovigilance cases, forensic case reports, and one systematic review; no controlled clinical dose-response study exists.

**From Castro et al. 2025 systematic review [Ref 3] (17 human studies included):**
- Euphoria
- Visual and other sensory hallucinations
- Nausea (prominent, linked to D2 activity [Ref 19])
- Anxiety
- Weakness / fatigue
- Tremors
- Elevated blood pressure (hypertension)
- Sedation (frequently reported alongside stimulation)
- Muscle weakness

**From Ponte & Lapeyre-Mestre 2017 [Ref 13]:** French pharmacovigilance cases described "unintended psychic effects" including hallucinations and altered perception.

**From Klinke et al. 2010 [Ref 4]:** Psychotomimetic state described; impaired reality testing manifested as "will to jump out of the window" in the fatal case.

**Effect character compared to LSD:** LSA is consistently described as more sedating, "heavier," and less visually stimulating than LSD. The sedative component — which may relate to stronger 5-HT₁A relative activity versus 5-HT₂A — distinguishes LSA's profile. This is based on anecdotal comparative reports and structural pharmacology inference, not controlled head-to-head studies.

**Duration (best available data):**
- Onset: 30–180 minutes (seed ingestion; variable due to matrix effects)
- Peak: 2–4 hours
- Total duration: 4–10 hours
- Residual effects: up to 24 hours
Source: Castro et al. 2025 [Ref 3]; these figures derive from observational and anecdotal data within the review, not controlled studies.

**⚠️ FLAG:** No controlled dose-finding or experience-characterization study has been conducted with purified LSA in humans. All subjective effect descriptions are case-report or retrospective/anecdotal in origin.

---

## Safety & Toxicity

### Documented Adverse Events

**PRES with status epilepticus (Legriel et al. 2008 [Ref 12]):** The most severe documented neurological complication of LSA use is Posterior Reversible Encephalopathy Syndrome (PRES) with concurrent status epilepticus. Legriel et al. describe a case directly attributed to LSA ingestion, representing the first published report of LSA-induced PRES. The proposed mechanism involves LSA's ergoline-class vasoconstrictive properties causing acute hypertensive crisis leading to cerebrovascular autoregulation failure. This is safety-critical.

**Fatal case (Klinke et al. 2010 [Ref 4]):** One death attributed to behavioral consequences of LSA intoxication (falling from a building). LSA blood concentration was 4.9 µg/L in the deceased. Concurrent substances: THC (22 µg/L blood), ethanol (0.71 g/L blood). The fatality was not caused by direct LSA toxicity but by disinhibited behavior during psychotomimetic state. Note: this was not a case of LSA overdose toxicity per se.

**French pharmacovigilance (Ponte & Lapeyre-Mestre 2017 [Ref 13]):** 4 cases in 2016, 2 requiring hospitalization. Effects included unintended psychic states.

**Post-use suicides and psychosis:** Castro & Maia 2024 [Ref 19] noted post-use suicides and psychosis-like states requiring hospitalization among reported cases. These appear to derive from the same pool of 17 studies in the systematic review [Ref 3].

**Hypertension:** Documented across multiple case reports. The ergoline class produces vasoconstrictive effects via adrenergic and serotonergic mechanisms, and LSA likely shares this property [Ref 12, Ref 3].

### LD50 and Toxic Dose

**No published LD50 or minimal toxic dose data exist for LSA in humans.** The seed data notes "toxic dose is unknown," which is confirmed by the literature. The systematic review (Castro et al. 2025 [Ref 3]) does not identify an established toxic dose threshold.

### Dose Unpredictability

A critical safety concern specific to LSA (as typically consumed) is the extreme variability in seed alkaloid content. Paulke et al. (2014) [Ref 5] found:
- Raw Hawaiian baby woodrose seeds: 3–15 µg LSA per seed
- Commercial encapsulated products: up to ~34 µg per unit
- Inter-product variability: 8.6-fold

This makes seed-based dosing inherently unpredictable, a major harm-reduction concern [Ref 5, Ref 3].

### Organ Toxicity

No specific organ toxicity (hepatotoxicity, nephrotoxicity, cardiotoxicity) has been characterized for LSA in published literature. The vasoconstriction risk (cerebrovascular, cardiac) is inferred from case reports and ergoline class pharmacology [Ref 12].

---

## Harm Reduction

### Risk Reduction Strategies

1. **Avoid seed consumption:** Due to extreme dose variability (3–34 µg per unit [Ref 5]) and presence of co-alkaloids (ergometrine, lysergol, chanoclavine) with their own pharmacological effects, seed consumption carries unpredictable risk. The ergometrine content specifically has uterotonc and vasoconstrictive properties.

2. **Avoid combination with other serotonergic agents:** Given LSA's serotonergic mechanism, combination with tramadol, MAOIs, SSRIs, SNRIs, or other serotonergic drugs carries serotonin syndrome risk [Ref 3, seed data].

3. **Avoid combination with other vasoconstrictors:** Ergoline-class vasoconstriction risk is compounded by stimulants, ergotamine derivatives, and triptans.

4. **Cardiovascular contraindication:** Individuals with hypertension, cerebrovascular disease, or cardiac conditions face elevated risk from ergoline-class vasoconstriction [Ref 12].

5. **Pregnancy absolute contraindication:** Ergometrine (co-alkaloid in seeds) and other ergoline derivatives are potent uterotonics; seed-based LSA poses abortifacient risk.

**⚠️ FLAG:** Most harm reduction guidance above derives from class-level ergoline pharmacology and case report extrapolation, not LSA-specific controlled studies. The pregnancy contraindication is inferred from ergometrine content in seeds, not tested for LSA itself.

### Testing

LSA can be detected with Ehrlich reagent (turns purple/violet — positive for indole ring). This distinguishes it from non-indole substances but does not quantify dose or confirm purity of seed preparations.

---

## Tolerance & Dependence

### Tolerance Mechanism

Classical psychedelics including LSA produce rapid tolerance through 5-HT₂A receptor downregulation in the frontal cortex. Buckholtz et al. (1990) [Ref 15] demonstrated that repeated LSD administration in rats produced significant decreases in 5-HT₂ receptor binding within 3 days, with recovery by 96 hours after the last dose. De la Fuente Revenga et al. (2022) [Ref 14] confirmed that tolerance to head twitch response (psychedelic behavioral proxy) involves 5-HT₂A receptor activation and develops rapidly, including after single dosing.

**Cross-tolerance:** Cross-tolerance between psychedelics in the same class (LSD ↔ DOI) is documented [Ref 14]. LSA, as a 5-HT₂A agonist in the same ergoline class as LSD, is expected to produce and be subject to cross-tolerance with LSD and other classical psychedelics. This is class-level inference, not substance-specific data.

### Dependence Liability

The seed data characterizes LSA as "non-addictive with a low abuse potential," which is consistent with the broader literature on classical psychedelics. No published dependence, withdrawal, or compulsive use studies exist for LSA specifically. The tolerance mechanism (rapid receptor downregulation) itself acts as a biological deterrent to frequent dosing. No physical withdrawal syndrome has been identified.

---

## Interactions

### Tramadol

**Categorized as "dangerous" in the seed data.** The mechanistic basis is likely additive serotonergic toxicity: tramadol inhibits serotonin and norepinephrine reuptake and is an opioid µ-receptor agonist, while LSA is a serotonergic 5-HT₂A/5-HT₁A agonist. The combination may produce serotonin syndrome through pharmacodynamic synergism. Tramadol also has weak MAO-inhibiting properties in some reports. No published case report of LSA + tramadol serotonin syndrome was found; the "dangerous" classification in the seed data is clinically plausible but **not directly verified from a published case report or interaction study**.

**⚠️ FLAG for human review:** The "dangerous" classification for tramadol interaction in the DB cannot be traced to a specific published case report or study. It is pharmacologically plausible based on combined serotonergic burden, but should be noted as inferred, not case-verified.

### Cannabis

No published interaction data found. Classified as "unknown" in the seed data, which is confirmed.

### LSD / Other Psychedelics

Cross-tolerance expected based on shared 5-HT₂A mechanism [Ref 14]. Combined use would likely produce attenuated effects rather than synergistic risk, but no specific data exist.

### MAOIs

No published LSA + MAOI interaction study exists. Given LSA's serotonergic mechanism, MAOI combination carries theoretical serotonin syndrome risk analogous to other psychedelics. Standard harm reduction guidance for psychedelics applies.

### Vasoconstrictors / Triptans / Ergotamine

Additive vasoconstriction risk from ergoline pharmacology. Combination with triptans, ergotamine, or other vasoconstrictors may increase cerebrovascular risk. Class-level inference.

---

## Legal Status

Sources: Erowid legal database [Ref 26]; web sources.

| Jurisdiction | Status | Notes |
|---|---|---|
| United States | Schedule III (DEA) | Listed as depressant; pure compound controlled; seeds legal to possess |
| United Kingdom | Class A (MDA 1971) | Controlled as LSD precursor |
| Netherlands | Controlled | Possession, distribution, production without license illegal |
| New Zealand | Controlled (chemical) | Plants and seeds legal to possess, cultivate, distribute |
| Sweden | Controlled | Listed since May 2007 |
| Canada | Not scheduled (CDSA) | Plants/seeds uncontrolled; selling as human drug likely prohibited |
| Australia | State-level prohibition | Most states prohibit consumption of LSA-containing materials |
| Germany | Status unclear | Not confirmed in available sources |
| Hungary | No classification | Legal per available sources |

**⚠️ FLAG:** Legal status data for Germany, Poland, and most EU member states outside the Netherlands and Sweden was not confirmed in peer-reviewed or official government sources. Erowid data used as fallback; may be outdated (last confirmed 2023).

---

## Clinical Trials

A search of ClinicalTrials.gov for "LSA," "lysergic acid amide," and "ergine" returned **zero registered clinical trials**. No active, completed, or recruiting trials exist for LSA as of the search date [Ref 3].

The 2025 systematic review (Castro et al. [Ref 3]) similarly notes the absence of controlled clinical trials and the reliance on observational and anecdotal data across its 17 included studies.

---

## Community Feedback Analysis

**No community feedback was submitted.** (Part A2 of the brief was empty.)

---

## Gaps & Flags

### Critical Gaps (Data Not Found)

1. **No published human pharmacokinetic study** for LSA — half-life, volume of distribution, bioavailability, Tmax, and plasma concentration-time profile are all unknown. The only blood concentration data are from a single forensic case [Ref 4].

2. **No LD50 or minimum toxic dose** established for humans.

3. **No controlled human dose-response study** for LSA's subjective effects — all effect descriptions come from case reports, pharmacovigilance, and anecdotal data.

4. **No functional assay data** (phosphoinositide hydrolysis, β-arrestin recruitment, calcium mobilization) published for LSA itself at any receptor. All functional inferences are from structural analogy to LSD and class-level data.

5. **No published CYP enzyme identification** for LSA metabolism in human tissue. The 2-hydroxy-3-oxo metabolite is identified in urine [Ref 4] but the specific CYP enzymes have not been characterized.

6. **No registered clinical trials** for LSA for any indication.

7. **SMILES and InChI full string** not directly returned from PubChem API (compound was confirmed by CID lookup; SMILES from web sources [Ref 25]).

### Safety-Critical Values Requiring Review

- **Tramadol interaction classified as "dangerous"**: Pharmacologically plausible (serotonin syndrome risk via combined serotonergic burden) but not verified by a published case report or interaction study. **Flag for editorial review.**

- **PRES case (Legriel 2008 [Ref 12])**: The abstract is sparse; full case details (dose, seed type, time course) are not available from the abstract alone. The finding is safety-critical and should be reviewed at full text.

- **Fatal case (Klinke 2010 [Ref 4])**: Concurrent ethanol (0.71 g/L) and THC may have contributed. LSA as the sole causative agent cannot be confirmed from available abstract data.

- **Post-use suicides** referenced in Castro & Maia 2024 [Ref 19]: Source behind this specific claim not traceable from the abstract.

### Contradictions Between Seed Data and Literature

- **Seed data dose table uses "seeds" as the dosing unit**, which is clinically problematic: alkaloid content ranges from 3–15 µg/seed for raw material to ~34 µg/unit for commercial products [Ref 5], making seed-count dosing inherently unreliable. The generation agent should prominently flag this in the article.

- **Seed data does not list duration data** (blank in brief). Based on available evidence, onset is 30–180 min, duration 4–10 h, total with aftereffects up to 12–24 h. This should be proposed for editorial review.

### Areas Relying on Structural Analogy / Class Inference

- CYP enzyme involvement in LSA metabolism (inferred from LSD)
- Cross-tolerance with LSD and other classical psychedelics (inferred from 5-HT₂A mechanism)
- Dependence liability classification (inferred from psychedelic class)
- Vasoconstriction mechanism details (inferred from ergoline class)
- MAOI interaction risk (inferred from serotonergic mechanism)
- Tramadol interaction severity (inferred from serotonergic mechanism)