ALD-52

1-acetyl-N,N-diethyllysergamide

Sources

9 strong · 16 moderate · 5 weak

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

Claims checked

67verified10partial10inconclusive2not supported

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

Generated

Apr 26, 2026 · pipeline-v5

Values approved

216/217 (100%)

Data points an editor reviewed and accepted for publication.

Value Provenance

Dosing

oraltrace

Field	Published	AI Proposed	Confidence
Threshold	10 µg	10 µg	medium
Low	25–75 µg	25–75 µg	medium
Common	75–150 µg	75–150 µg	medium
Strong	150–300 µg	150–300 µg	medium
Heavy	300+ µg	300+ µg	medium
Editorial	ALD-52 is a prodrug for LSD; doses are LSD-equivalent. Threshold of 10 µg from Holze et al. 2021 microdose study. Light/common/strong ranges from community consensus (PsychonautWiki, Erowid) for LSD, supported by Holze et al. 2021 dose-response data showing dose-dependent effects at 25-200 µg with ceiling for positive effects at 100 µg and marked ego dissolution/anxiety at 200 µg. Heavy threshold from large community consensus. No ALD-52-specific human dosing data exist.
	ReasoningReasoning ALD-52 is a prodrug for LSD; doses are LSD-equivalent. Threshold of 10 µg from Holze et al. 2021 microdose study. Light/common/strong ranges from community consensus (PsychonautWiki, Erowid) for LSD, supported by Holze et al. 2021 dose-response data showing dose-dependent effects at 25-200 µg with ceiling for positive effects at 100 µg and marked ego dissolution/anxiety at 200 µg. Heavy threshold from large community consensus. No ALD-52-specific human dosing data exist. Evidence basis: community_consensus_large

Duration

oral

Field	Published	AI Proposed	Confidence
Peaktrace	2–3 hours	2–3 hours	medium
Editorial	LSD peak duration from community consensus and clinical observation. Holze et al. 2021 dose-response data support prolonged peak effects.
	ReasoningReasoning LSD peak duration from community consensus and clinical observation. Holze et al. 2021 dose-response data support prolonged peak effects. Evidence basis: community_consensus_large
Onsettrace	20–60 minutes	20–60 minutes	medium
Editorial	LSD onset is typically 15-45 minutes; ALD-52 may be slightly slower due to deacylation step (CYP1A2/CYP3A4-mediated conversion to LSD). Extended to 20-60 minutes to account for prodrug conversion. No controlled human ALD-52 onset data exist.
	ReasoningReasoning LSD onset is typically 15-45 minutes; ALD-52 may be slightly slower due to deacylation step (CYP1A2/CYP3A4-mediated conversion to LSD). Extended to 20-60 minutes to account for prodrug conversion. No controlled human ALD-52 onset data exist. Evidence basis: community_consensus_large
Come uptrace	30–60 minutes	30–60 minutes	medium
Editorial	Based on LSD come-up duration from community consensus. LSD Tmax ~1.1h (Holze et al. 2021), consistent with onset + come-up totaling approximately 60-90 minutes.
	ReasoningReasoning Based on LSD come-up duration from community consensus. LSD Tmax ~1.1h (Holze et al. 2021), consistent with onset + come-up totaling approximately 60-90 minutes. Evidence basis: community_consensus_large
Offsettrace	2–3 hours	2–3 hours	medium
Editorial	LSD offset duration from community consensus. Gradual return to baseline consistent with slow receptor dissociation kinetics (Wacker et al. 2017).
	ReasoningReasoning LSD offset duration from community consensus. Gradual return to baseline consistent with slow receptor dissociation kinetics (Wacker et al. 2017). Evidence basis: community_consensus_large
Totaltrace	7–11 hours	7–11 hours	high
Editorial	Directly from Holze et al. 2021 dose-response study: duration 6.7h at 25 µg extending to 11h at 200 µg LSD. Rounded to 7-11h to represent the common-to-strong dose range. ALD-52 is LSD-equivalent after deacylation.
	ReasoningReasoning Directly from Holze et al. 2021 dose-response study: duration 6.7h at 25 µg extending to 11h at 200 µg LSD. Rounded to 7-11h to represent the common-to-strong dose range. ALD-52 is LSD-equivalent after deacylation. Evidence basis: controlled_human_study
After effectstrace	4–12 hours	4–12 hours	low
Editorial	Aftereffects duration from community consensus for LSD. Residual mood elevation, perceptual sensitivity, and sleep disruption commonly reported for 4-12 hours after subjective effects resolve. No clinical data specifically characterize this phase.
	ReasoningReasoning Aftereffects duration from community consensus for LSD. Residual mood elevation, perceptual sensitivity, and sleep disruption commonly reported for 4-12 hours after subjective effects resolve. No clinical data specifically characterize this phase. Evidence basis: community_consensus_large

Safety

Toxicity Profiletrace

Field	Published	AI Proposed	Confidence
Acute	negligible	negligible	medium
Chronic	negligible	negligible	medium
Organs Affected	—	—	medium
Editorial	Toxicity assessment based on Nichols 2016 (comprehensive pharmacology review) and Nichols 2018 (systematic analysis of LSD-attributed deaths). ALD-52 is a prodrug for LSD; no ALD-52-specific toxicity data exist. Classified as negligible rather than applying evidence discount because LSD itself has extensive human safety data from clinical trials (Holze et al. 2021, 2022). Confidence medium rather than high because no ALD-52-specific human study exists.
	ReasoningReasoning Toxicity assessment based on Nichols 2016 (comprehensive pharmacology review) and Nichols 2018 (systematic analysis of LSD-attributed deaths). ALD-52 is a prodrug for LSD; no ALD-52-specific toxicity data exist. Classified as negligible rather than applying evidence discount because LSD itself has extensive human safety data from clinical trials (Holze et al. 2021, 2022). Confidence medium rather than high because no ALD-52-specific human study exists. Evidence basis: published_case_series

Dependence Profiletrace

Field	Published	AI Proposed	Confidence
Physical	none	none	high
Psychological	negligible	negligible	high
Compulsive Redosing	negligible	negligible	high
Dose Escalation	negligible	negligible	high
Editorial	Nichols 2016 authoritative review confirms LSD is not habit-forming with no physical dependence or withdrawal. Rapid tolerance via 5-HT2 downregulation (Buckholtz et al. 1990) prevents compulsive use patterns. This is well-established class-level pharmacology with decades of human data. ALD-52 inherits this profile as an LSD prodrug.
	ReasoningReasoning Nichols 2016 authoritative review confirms LSD is not habit-forming with no physical dependence or withdrawal. Rapid tolerance via 5-HT2 downregulation (Buckholtz et al. 1990) prevents compulsive use patterns. This is well-established class-level pharmacology with decades of human data. ALD-52 inherits this profile as an LSD prodrug. Evidence basis: published_case_series

Withdrawal Profiletrace

Field	Published	AI Proposed	Confidence
Severity	none	none	high
Symptoms	—	—	high
Fatal	No	No	high
Medical Supervision	Not required	Not required	high
Editorial	No withdrawal syndrome documented for LSD or the serotonergic psychedelic class. Nichols 2016 confirms absence of physical dependence.
	ReasoningReasoning No withdrawal syndrome documented for LSD or the serotonergic psychedelic class. Nichols 2016 confirms absence of physical dependence. Evidence basis: published_case_series

Tolerance Profiletrace

Field	Published	AI Proposed	Confidence
Buildup	rapid	rapid	medium
Half-life	6 days	6 days	medium
Full Reset	14 days	14 days	medium
Cross-tolerances	LSD, psilocybin, mescaline, DMT, 1P-LSD, 1cP-LSD, 1V-LSD	LSD, psilocybin, mescaline, DMT, 1P-LSD, 1cP-LSD, 1V-LSD	medium
Editorial	Tolerance mechanism (5-HT2 downregulation) established by Buckholtz et al. 1990 in rats and de la Fuente Revenga et al. 2022 in mice. Cross-tolerance confirmed across 5-HT2A agonists. Half-life and reset values consistent with animal recovery data and large-scale community consensus, but precise human kinetics not formally studied. Confidence medium due to reliance on animal data for specific timing values.
	ReasoningReasoning Tolerance mechanism (5-HT2 downregulation) established by Buckholtz et al. 1990 in rats and de la Fuente Revenga et al. 2022 in mice. Cross-tolerance confirmed across 5-HT2A agonists. Half-life and reset values consistent with animal recovery data and large-scale community consensus, but precise human kinetics not formally studied. Confidence medium due to reliance on animal data for specific timing values. Evidence basis: animal_study

Effects & Profile

Contraindications

Field	Published	AI Proposed	Confidence
psychiatric psychotic disorderstrace	absolute	absolute	high
Editorial	Class-level contraindication for all serotonergic psychedelics, supported by Nichols 2016 and decades of clinical observation. No ALD-52-specific data, but LSD is the active metabolite.
	ReasoningReasoning Class-level contraindication for all serotonergic psychedelics, supported by Nichols 2016 and decades of clinical observation. No ALD-52-specific data, but LSD is the active metabolite.
psychiatric bipolar disordertrace	absolute	absolute	high
Editorial	Class-level contraindication from LSD clinical literature. Nichols 2016 notes psychedelics are contraindicated in personal/family history of psychotic disorders including bipolar with psychosis.
	ReasoningReasoning Class-level contraindication from LSD clinical literature. Nichols 2016 notes psychedelics are contraindicated in personal/family history of psychotic disorders including bipolar with psychosis.
other concurrent tramadol usetrace	absolute	absolute	high
Editorial	Pharmacological mechanism established by Baldo 2018 (tramadol SERT inhibition) and Gillman 2005 (serotonin toxicity mechanisms). Classified as dangerous in seed data.
	ReasoningReasoning Pharmacological mechanism established by Baldo 2018 (tramadol SERT inhibition) and Gillman 2005 (serotonin toxicity mechanisms). Classified as dangerous in seed data.
other concurrent MAOI usetrace	absolute	absolute	high
Editorial	Established pharmacological interaction. Gillman 2005 documents MAOI-serotonergic drug interactions as a primary cause of severe serotonin toxicity.
	ReasoningReasoning Established pharmacological interaction. Gillman 2005 documents MAOI-serotonergic drug interactions as a primary cause of severe serotonin toxicity.
neurological concurrent lithium usetrace	absolute	absolute	medium
Editorial	Class-level concern from psychedelic + lithium case-report literature. No ALD-52-specific data. Flagged for editorial review as evidence is limited to case reports.
	ReasoningReasoning Class-level concern from psychedelic + lithium case-report literature. No ALD-52-specific data. Flagged for editorial review as evidence is limited to case reports.
cardiovascular severe cardiovascular diseasetrace	relative	relative	medium
Editorial	Holze et al. 2022 documented cardiovascular effects of LSD at clinical doses. No QTc prolongation, but heart rate and blood pressure increases could be problematic in compromised individuals. Relative rather than absolute because effects are modest.
	ReasoningReasoning Holze et al. 2022 documented cardiovascular effects of LSD at clinical doses. No QTc prolongation, but heart rate and blood pressure increases could be problematic in compromised individuals. Relative rather than absolute because effects are modest.
pregnancy breastfeeding pregnancytrace	absolute	absolute	medium
Editorial	No published human teratogenicity data for LSD or ALD-52. Contraindicated by precautionary principle in the absence of safety data.
	ReasoningReasoning No published human teratogenicity data for LSD or ALD-52. Contraindicated by precautionary principle in the absence of safety data.
neurological epilepsytrace	relative	relative	low
Editorial	Seizure threshold reduction listed in seed data effects taxonomy. Nichols & Grob 2018 notes most LSD deaths were not from direct toxicity. Risk is theoretical at standard doses but warrants caution in epileptic patients.
	ReasoningReasoning Seizure threshold reduction listed in seed data effects taxonomy. Nichols & Grob 2018 notes most LSD deaths were not from direct toxicity. Risk is theoretical at standard doses but warrants caution in epileptic patients.

Timeline Phases

oral

Field	Published	AI Proposed	Confidence
Onsettrace	1200–3600 sec(i=0.05)	1200–3600 sec(i=0.05)	medium
Editorial	Timeline based on LSD clinical data (Holze et al. 2021 dose-response study: duration 6.7h at 25 µg to 11h at 200 µg, Tmax ~1.1h). ALD-52 onset may be slightly extended due to the deacylation step (CYP1A2/CYP3A4-mediated conversion to LSD), though no controlled human comparison exists. Phase durations represent common dose range (~75-150 µg LSD-equivalent). Afterglow duration based on community consensus for LSD class.
	ReasoningReasoning Timeline based on LSD clinical data (Holze et al. 2021 dose-response study: duration 6.7h at 25 µg to 11h at 200 µg, Tmax ~1.1h). ALD-52 onset may be slightly extended due to the deacylation step (CYP1A2/CYP3A4-mediated conversion to LSD), though no controlled human comparison exists. Phase durations represent common dose range (~75-150 µg LSD-equivalent). Afterglow duration based on community consensus for LSD class.
Come uptrace	1800–3600 sec(i=0.30)	1800–3600 sec(i=0.30)	medium
Editorial	Timeline based on LSD clinical data (Holze et al. 2021 dose-response study: duration 6.7h at 25 µg to 11h at 200 µg, Tmax ~1.1h). ALD-52 onset may be slightly extended due to the deacylation step (CYP1A2/CYP3A4-mediated conversion to LSD), though no controlled human comparison exists. Phase durations represent common dose range (~75-150 µg LSD-equivalent). Afterglow duration based on community consensus for LSD class.
	ReasoningReasoning Timeline based on LSD clinical data (Holze et al. 2021 dose-response study: duration 6.7h at 25 µg to 11h at 200 µg, Tmax ~1.1h). ALD-52 onset may be slightly extended due to the deacylation step (CYP1A2/CYP3A4-mediated conversion to LSD), though no controlled human comparison exists. Phase durations represent common dose range (~75-150 µg LSD-equivalent). Afterglow duration based on community consensus for LSD class.
Peaktrace	7200–10800 sec(i=1.00)	7200–10800 sec(i=1.00)	medium
Editorial	Timeline based on LSD clinical data (Holze et al. 2021 dose-response study: duration 6.7h at 25 µg to 11h at 200 µg, Tmax ~1.1h). ALD-52 onset may be slightly extended due to the deacylation step (CYP1A2/CYP3A4-mediated conversion to LSD), though no controlled human comparison exists. Phase durations represent common dose range (~75-150 µg LSD-equivalent). Afterglow duration based on community consensus for LSD class.
	ReasoningReasoning Timeline based on LSD clinical data (Holze et al. 2021 dose-response study: duration 6.7h at 25 µg to 11h at 200 µg, Tmax ~1.1h). ALD-52 onset may be slightly extended due to the deacylation step (CYP1A2/CYP3A4-mediated conversion to LSD), though no controlled human comparison exists. Phase durations represent common dose range (~75-150 µg LSD-equivalent). Afterglow duration based on community consensus for LSD class.
Plateautrace	7200–10800 sec(i=0.55)	7200–10800 sec(i=0.55)	medium
Editorial	Timeline based on LSD clinical data (Holze et al. 2021 dose-response study: duration 6.7h at 25 µg to 11h at 200 µg, Tmax ~1.1h). ALD-52 onset may be slightly extended due to the deacylation step (CYP1A2/CYP3A4-mediated conversion to LSD), though no controlled human comparison exists. Phase durations represent common dose range (~75-150 µg LSD-equivalent). Afterglow duration based on community consensus for LSD class.
	ReasoningReasoning Timeline based on LSD clinical data (Holze et al. 2021 dose-response study: duration 6.7h at 25 µg to 11h at 200 µg, Tmax ~1.1h). ALD-52 onset may be slightly extended due to the deacylation step (CYP1A2/CYP3A4-mediated conversion to LSD), though no controlled human comparison exists. Phase durations represent common dose range (~75-150 µg LSD-equivalent). Afterglow duration based on community consensus for LSD class.
Resolutiontrace	5400–9000 sec(i=0.20)	5400–9000 sec(i=0.20)	medium
Editorial	Timeline based on LSD clinical data (Holze et al. 2021 dose-response study: duration 6.7h at 25 µg to 11h at 200 µg, Tmax ~1.1h). ALD-52 onset may be slightly extended due to the deacylation step (CYP1A2/CYP3A4-mediated conversion to LSD), though no controlled human comparison exists. Phase durations represent common dose range (~75-150 µg LSD-equivalent). Afterglow duration based on community consensus for LSD class.
	ReasoningReasoning Timeline based on LSD clinical data (Holze et al. 2021 dose-response study: duration 6.7h at 25 µg to 11h at 200 µg, Tmax ~1.1h). ALD-52 onset may be slightly extended due to the deacylation step (CYP1A2/CYP3A4-mediated conversion to LSD), though no controlled human comparison exists. Phase durations represent common dose range (~75-150 µg LSD-equivalent). Afterglow duration based on community consensus for LSD class.
Afterglowtrace	14400–43200 sec(i=0.05)	14400–43200 sec(i=0.05)	medium
Editorial	Timeline based on LSD clinical data (Holze et al. 2021 dose-response study: duration 6.7h at 25 µg to 11h at 200 µg, Tmax ~1.1h). ALD-52 onset may be slightly extended due to the deacylation step (CYP1A2/CYP3A4-mediated conversion to LSD), though no controlled human comparison exists. Phase durations represent common dose range (~75-150 µg LSD-equivalent). Afterglow duration based on community consensus for LSD class.
	ReasoningReasoning Timeline based on LSD clinical data (Holze et al. 2021 dose-response study: duration 6.7h at 25 µg to 11h at 200 µg, Tmax ~1.1h). ALD-52 onset may be slightly extended due to the deacylation step (CYP1A2/CYP3A4-mediated conversion to LSD), though no controlled human comparison exists. Phase durations represent common dose range (~75-150 µg LSD-equivalent). Afterglow duration based on community consensus for LSD class.

Dose Tier Summaries

thresholdtrace

medium

At threshold doses (10–25 µg oral), effects are subtle and easily attributed to normal mood variation: mild brightening of colors, slight enhancement of music appreciation, gentle mood elevation, and a diffuse sense of heightened awareness. Thought patterns may feel slightly more fluid without overt alteration. These doses are commonly used in microdosing protocols. Physically, mild pupil dilation may be noticeable to an observer. Other somatic effects are generally sub-perceptual. Appetite suppression is minimal or absent. Functional impairment is negligible at this range. Sleep may be mildly delayed if taken in the afternoon or evening, but is not typically disrupted.

Editorial

Threshold derived from Holze et al. 2021 microdose study establishing ~10 µg as first detectable psychotropic threshold for LSD. ALD-52 converts to LSD; doses are LSD-equivalent. Upper bound of 25 µg aligns with lowest dose producing measurable subjective effects in Holze et al. 2021 dose-response study.

Reasoning

Evidence basis: controlled_human_study

lighttrace

medium

At light doses (25–75 µg oral), the psychedelic character becomes unmistakable: color enhancement and mild visual brightening, early geometric patterning on textured surfaces, enhanced pattern recognition, and thought acceleration. Music sounds richer and more emotionally resonant. Emotional enhancement is present — interactions and environments carry heightened significance. Physically, pupil dilation is evident, with mild stimulation, occasional spontaneous body sensations (warmth, tingling), and slight appetite suppression. Nausea is uncommon at this range. Duration averages approximately 7 hours. Cognitive function is altered but manageable in familiar environments. Sleep is difficult for 8+ hours after ingestion.

Editorial

Light range anchored by Holze et al. 2021 dose-response data: 25 µg produces dose-dependent subjective effects with ~6.7h duration. Upper bound of 75 µg represents sub-peak psychedelic territory. ALD-52 doses are LSD-equivalent via prodrug conversion.

Reasoning

Evidence basis: controlled_human_study

commontrace

medium

At common doses (75–150 µg oral), the full psychedelic experience emerges. Visual effects become pronounced: geometric patterns overlay surfaces, colors saturate and shift, objects drift and morph, tracers follow moving stimuli, and depth perception distortion alters spatial relationships. Closed-eye visuals include complex symmetrical texture repetition and internal hallucinations. Time dilation is marked. Thought connectivity increases dramatically, producing novel associations, conceptual thinking, and creativity enhancement. Emotional responses intensify — music, nature, and interpersonal interactions can feel profoundly meaningful. Cognitive euphoria is common. Physically, muscle tension, increased heart rate, sweating, and appetite suppression are typical. Nausea occurs in a minority of users, usually during the come-up. Pupil dilation is pronounced. A ceiling effect for positive drug effects occurs near 100 µg. Duration extends to 8–10 hours. Full functional impairment is expected; sleep is impossible for the duration.

Editorial

Common range defined by Holze et al. 2021 dose-response data: ceiling for 'good drug effect' at 100 µg, duration 8-10h in this range. ALD-52 doses are LSD-equivalent via prodrug mechanism. Effect descriptions drawn from LSD clinical effect profiles and seed taxonomy.

Reasoning

Evidence basis: controlled_human_study

strongtrace

medium

At strong doses (150–300 µg oral), the experience intensifies beyond the positive-effect ceiling. Ego dissolution becomes prominent — the boundary between self and environment may dissolve, producing unity experiences or, conversely, acute existential anxiety. Visual hallucinations are vivid and immersive: object transformations, perspective distortion, and complex internal imagery dominate perception. Thought loops and multiple simultaneous thought streams are common. Emotional range expands dramatically in both directions — profound meaning and acute distress are equally accessible. Physically, sympathomimetic effects intensify: elevated heart rate, blood pressure increases, pronounced sweating, and bodily lightness or heaviness. Muscle tension and jaw clenching are common. Duration extends to 10–12 hours. Complete functional impairment persists throughout. The psychological commitment is substantial and cannot be abbreviated once the dose is taken.

Editorial

Strong range based on Holze et al. 2021 showing ego dissolution and anxiety increasing markedly at 200 µg vs 100 µg, with duration extending to ~11h at 200 µg. Upper bound extrapolated from community consensus for LSD. ALD-52 doses are LSD-equivalent.

Reasoning

Evidence basis: controlled_human_study

heavytrace

low

At heavy doses (300+ µg oral), the experience is overwhelming and largely uncontrollable. Complete ego dissolution is likely — personal identity, spatial orientation, and temporal continuity may be entirely suspended. Visual and auditory hallucinations can become indistinguishable from reality. Thought processes may become incoherent or entirely non-verbal. The experience can include profound noetic insight and existential realization, but equally, severe anxiety, paranoia, confusion, and panic. Physically, all autonomic effects are pronounced: significant tachycardia, blood pressure elevation, profuse sweating, tremor, and temperature dysregulation. Nausea and vomiting are more common. Duration may exceed 12 hours. Complete functional impairment extends well into the following day. This dose range carries the highest risk of acute psychological crisis and should only be approached by experienced users in supported settings.

Editorial

Heavy doses extrapolated beyond the 200 µg maximum studied in Holze et al. 2021. Community consensus places heavy LSD territory at 300+ µg. No controlled data exist at these doses. ALD-52 doses are LSD-equivalent via prodrug mechanism.

Reasoning

Evidence basis: community_consensus_large

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 correction contact@psychedex.org

Sources

9 strong · 16 moderate · 5 weak

[1]
strong
Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects
Holze F, Vizeli P, Müller F, Ley L, Duerig R, Varghese N, Zizzari P, Liechti ME · 2021 · Neuropsychopharmacology
doi.org/10.1038/s41386-020-00883-6 pubmed 330400887 claims checked5 verified2 inconclusive
[2]
moderate
Analytical and behavioral characterization of 1-dodecanoyl-LSD (1DD-LSD)
Kavanagh PV, Westphal F, Pulver B, Elliott S, Stratford A · 2024 · Drug Testing and Analysis
doi.org/10.1002/dta.3691 pubmed 385695665 claims checked2 verified2 partial1 inconclusive
[3]
moderate
Return of the lysergamides. Part I: Analytical and behavioural characterization of 1-propionyl-d-lysergic acid diethylamide (1P-LSD)
Brandt SD, Kavanagh PV, Westphal F, Stratford A, Elliott SP, Hoang K, Wallach J, Halberstadt AL · 2016 · Drug Testing and Analysis
doi.org/10.1002/dta.1884 pubmed 264563053 claims checked2 verified1 inconclusive
[4]
moderate
Pharmacological and biotransformation studies of 1-acyl-substituted derivatives of d-lysergic acid diethylamide (LSD)
Halberstadt AL, Chatha M, Klein AK, McCorvy JD, Meyer MR, Wagmann L, Stratford A, Brandt SD · 2020 · Neuropharmacology
doi.org/10.1016/j.neuropharm.2019.107856 pubmed 3175633711 claims checked11 verified
[5]
moderate
In vitro metabolic fate of nine LSD-based new psychoactive substances and their analytical detectability in different urinary screening procedures
Wagmann L, Richter LHJ, Kehl T, Wack F, Bergstrand MP, Brandt SD, Stratford A, Maurer HH, Meyer MR · 2019 · Analytical and Bioanalytical Chemistry
doi.org/10.1007/s00216-018-1558-9 pubmed 306173916 claims checked4 verified2 partial
[6]
strong
Psychedelics
Nichols DE · 2016 · Pharmacological Reviews
doi.org/10.1124/pr.115.011478 pubmed 2684180013 claims checked8 verified5 inconclusive
[7]
moderate
Is LSD toxic?
Nichols DE, Grob CS · 2018 · Forensic Science International
doi.org/10.1016/j.forsciint.2018.01.006 pubmed 294087223 claims checked3 verified
[8]
moderate
Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain
Buckholtz NS, Zhou DF, Freedman DX, Potter WZ · 1990 · Neuropsychopharmacology
pubmed 19692703 claims checked1 verified2 partial
[9]
weak
Hallucinogen-Induced Persisting Perception Disorder: A Case Report
Ayyub J, Nandennagari S, Edelbaum D, Agbo J, Nagendran D, Tamayo L · 2023 · Cureus
doi.org/10.7759/cureus.46262 pubmed 379089142 claims checked2 verified
[10]
moderate
Analytical and Pharmacological Characterization of 1-(Furan-2-Carbonyl)-LSD (1F-LSD) and Comparison With 1-(Thiophene-2-Carbonyl)-LSD (1T-LSD)
Brandt SD, Kavanagh PV, Gare S, Elliott SP, Stratford A, Halberstadt AL · 2025 · Drug Testing and Analysis
doi.org/10.1002/dta.3829 pubmed 396240223 claims checked3 verified
[11]
weak
ALD-52 - Wikipedia and related legal/historical sources
Wikipedia contributors; USA v. Sand and Scully 541 F.2d 1370 (9th Cir. 1976) · 2024
linkno claims checked
[12]
weak
Tim Scully Describes Failed ALD-52 Legal Gambit (Feb 2017)
Erowid · 2017
linkno claims checked
[13]
moderate
Return of the lysergamides. Part VII: Analytical and behavioural characterization of 1-valeroyl-d-lysergic acid diethylamide (1V-LSD)
Brandt SD, Kavanagh PV, Westphal F, Pulver B, Morton K, Stratford A, Dowling G, Halberstadt AL · 2022 · Drug Testing and Analysis
doi.org/10.1002/dta.3205 pubmed 348373471 claim checked1 verified
[14]
moderate
Return of the lysergamides. Part V: Analytical and behavioural characterization of 1-butanoyl-d-lysergic acid diethylamide (1B-LSD)
Brandt SD, Kavanagh PV, Westphal F, Stratford A, Elliott SP, et al. · 2019 · Drug Testing and Analysis
doi.org/10.1002/dta.2613 pubmed 310837681 claim checked1 verified
[15]
moderate
Return of the lysergamides. Part VI: Analytical and behavioural characterization of 1-cyclopropanoyl-d-lysergic acid diethylamide (1CP-LSD)
Brandt SD, Kavanagh PV, Westphal F, Stratford A, Odland AU et al. · 2020 · Drug Testing and Analysis
doi.org/10.1002/dta.2789 pubmed 32180350no claims checked
[16]
strong
5-HT2A receptors: Pharmacology and functional selectivity
Cummins BR, Billac GB, Nichols DE, Nichols CD · 2025 · Pharmacological Reviews
doi.org/10.1016/j.pharmr.2025.100059 pubmed 404188782 claims checked2 verified
[17]
strong
Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants
Holze F, Liechti ME, Hutten NRPW, Mason NL, Dolder PC, Theunissen EL, Duthaler U, Feilding A, Ramaekers JG, Kuypers KPC · 2021 · Clinical Pharmacology and Therapeutics
doi.org/10.1002/cpt.2057 pubmed 329758354 claims checked4 verified
[18]
strong
Genetic influence of CYP2D6 on pharmacokinetics and acute subjective effects of LSD in a pooled analysis
Vizeli P, Straumann I, Holze F, Schmid Y, Dolder PC, Liechti ME · 2021 · Scientific Reports
doi.org/10.1038/s41598-021-90343-y pubmed 340353914 claims checked3 verified1 partial
[19]
strong
Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics
de Vos CMH, Mason NL, Kuypers KPC · 2021 · Frontiers in Psychiatry
doi.org/10.3389/fpsyt.2021.724606 pubmed 345667233 claims checked1 partial2 not supported
[20]
moderate
Crystal Structure of an LSD-Bound Human Serotonin Receptor
Wacker D, Wang S, McCorvy JD, Betz RM, Venkatakrishnan AJ, Levit A, Lansu K, Schools ZL, Che T, Nichols DE, Shoichet BK, Dror RO, Roth BL · 2017 · Cell
doi.org/10.1016/j.cell.2016.12.0331 claim checked1 verified
[21]
strong
Structure of a Hallucinogen-Activated Gq-Coupled 5-HT2A Serotonin Receptor
Kim K, Che T, Panova O, DiBerto JF, Lyu J, Krumm BE, Wacker D, Robertson MJ, Seven AB, Nichols DE, Shoichet BK, Skiniotis G, Roth BL · 2020 · Cell
doi.org/10.1016/j.cell.2020.08.024 pubmed 329467821 claim checked1 partial
[22]
moderate
The use patterns of novel psychedelics: experiential fingerprints of substituted phenethylamines, tryptamines and lysergamides
Mallaroni P, Mason NL, Vinckenbosch FRJ, Ramaekers JG · 2022 · Psychopharmacology
doi.org/10.1007/s00213-022-06142-4 pubmed 354879831 claim checked1 verified
[23]
strong
Safety pharmacology of acute LSD administration in healthy subjects
Holze F, Caluori TV, Vizeli P, Liechti ME · 2022 · Psychopharmacology
doi.org/10.1007/s00213-021-05978-6 pubmed 345158244 claims checked4 verified
[24]
weak
LSD-associated 'Alice in Wonderland Syndrome' (AIWS): A Hallucinogen Persisting Perception Disorder (HPPD) Case Report
Lerner AG, Lev-Ran S · 2015 · The Israel Journal of Psychiatry and Related Sciences
pubmed 258411131 claim checked1 verified
[25]
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.2c00170 pubmed 359008762 claims checked1 verified1 partial
[26]
moderate
Opioid analgesic drugs and serotonin toxicity (syndrome): mechanisms, animal models, and links to clinical effects
Baldo BA · 2018 · Archives of Toxicology
doi.org/10.1007/s00204-018-2244-6 pubmed 299160503 claims checked3 verified
[27]
strong
Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity.
Gillman PK · 2005 · British Journal of Anaesthesia
pubmed 160516473 claims checked3 verified
[28]
moderate
Chronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans.
Bonson KR, Buckholtz JW, Murphy DL · 1996 · Neuropsychopharmacology
doi.org/10.1016/0893-133x(95)00145-4 pubmed 87267531 claim checked1 verified
[29]
moderate
Return of the lysergamides. Part II: Analytical and behavioural characterization of N6-allyl-6-norlysergic acid diethylamide (AL-LAD) and (2'S,4'S)-lysergic acid 2,4-dimethylazetidide (LSZ)
Brandt SD, Kavanagh PV, Westphal F, Elliott SP, Wallach J, Colestock T, Burrow TE, Chapman SJ, Stratford A, Nichols DE, Halberstadt AL · 2017 · Drug Testing and Analysis
doi.org/10.1002/dta.1985 pubmed 272658911 claim checked1 inconclusive
[30]
weak
ALD-52 legal status by jurisdiction (Canada, Australia, UK, US, Switzerland, Germany)
Web sources: Third Wave, Wikipedia, PsychonautWiki, Chemlly 2026 · 2024
linkno claims checked

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.

summary11 claims8verified3partial

verifiedOral duration ranges from approximately 7 to 11 hours depending on dose.^[1]95%

Verified

Abstract states 'Duration 6.7-11h by dose.' The claim says 'approximately 7 to 11 hours' — 6.7 rounds to approximately 7, so this is a minor and reasonable simplification.

Duration 6.7-11h by dose.

checked by claude-sonnet-4-6 · Apr 26, 2026

partialFirst synthesized by Albert Hofmann and Franz Troxler at Sandoz Laboratories in 1957 as part of systematic lysergamide structure-activity exploration, ALD-52 saw limited clinical evaluation in the 1960s before decades of obscurity^[2]75%

Partial

Abstract confirms synthesis 'in 1950s' which is consistent with 1957, but does not mention Albert Hofmann, Franz Troxler, Sandoz Laboratories, the specific year 1957, or clinical evaluation in the 1960s. These are specific factual assertions not confirmed by the abstract.

ALD-52 first synthesized in 1950s, produces psychedelic effects similar to LSD.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedIt resurfaced in the 2010s as a new psychoactive substance, prompting systematic characterization in the "Return of the Lysergamides" research series^[3]90%

Verified

The cited paper is itself Part I of the 'Return of the lysergamides' research series, confirming the series exists and that systematic characterization of novel lysergamides was conducted.

Return of the lysergamides. Part I: Analytical and behavioural characterization of 1-propionyl-d-lysergic acid diethylamide (1P-LSD)

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThe pharmacological profile is understood entirely through metabolic conversion to LSD, confirmed by detection of high plasma LSD concentrations following ALD-52 administration in rats.^[4]97%

Verified

Abstract directly confirms: 'High LSD plasma levels detected in rats after subcutaneous ALD-52 and 1P-LSD, confirming prodrug status. Deacylation in vivo is rapid and efficient.'

High LSD plasma levels detected in rats after subcutaneous ALD-52 and 1P-LSD, confirming prodrug status. Deacylation in vivo is rapid and efficient.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedALD-52 itself has negligible direct receptor activity — N1-acetylation reduces 5-HT2A affinity by one to two orders of magnitude versus LSD^[4]97%

Verified

Abstract directly states: '1-acyl substitution reduced affinity for monoamine receptors by 1-2 orders of magnitude. ALD-52, 1P-LSD and 1B-LSD have weak efficacy or act as antagonists in Ca2+ assays.'

1-acyl substitution reduced affinity for monoamine receptors by 1-2 orders of magnitude.

checked by claude-sonnet-4-6 · Apr 26, 2026

partialRapid enzymatic hydrolysis by CYP1A2 and CYP3A4 liberates LSD in plasma and tissues, which then acts as a partial agonist at cortical 5-HT2A receptors on layer V pyramidal neurons — the primary molecular trigger for psychedelic effects.^[5]82%

Partial

The abstract confirms CYP1A2 and CYP3A4 catalysis and deacylation to LSD, supporting the metabolic portion of the claim. However, the 5-HT2A/layer V pyramidal neuron receptor mechanism is outside this metabolic paper's scope and not addressed in the abstract.

Deacylation to LSD observed for ALD-52, 1P-LSD, 1B-LSD. Initial metabolic steps primarily catalyzed by CYP1A2 and CYP3A4.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedRapid enzymatic hydrolysis by CYP1A2 and CYP3A4 liberates LSD in plasma and tissues, which then acts as a partial agonist at cortical 5-HT2A receptors on layer V pyramidal neurons — the primary molecular trigger for psychedelic effects.^[6]90%

Verified

This review covers the 5-HT2A receptor mechanism at layer V neocortical pyramidal cells directly: 'Agonists/partial agonists at 5-HT2A receptors, especially neocortical pyramidal cells layer V.' The CYP metabolic step is outside its scope, but the receptor mechanism half of the compound claim is clearly supported.

Agonists/partial agonists at 5-HT2A receptors, especially neocortical pyramidal cells layer V.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedLSD — and by extension ALD-52 — is physiologically non-toxic at recreational doses, with no documented organ damage and an extremely wide therapeutic index^[6]88%

Verified

Abstract states 'Physiologically safe, no dependence or addiction.' This directly supports the claim of physiological non-toxicity at recreational doses.

Physiologically safe, no dependence or addiction.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedLSD — and by extension ALD-52 — is physiologically non-toxic at recreational doses, with no documented organ damage and an extremely wide therapeutic index^[7]95%

Verified

Abstract directly states: 'LSD non-toxic and medically safe at standard dosages (50-200 µg). Physiologically, not toxic.'

LSD non-toxic and medically safe at standard dosages (50-200 µg). Physiologically, not toxic.

checked by claude-sonnet-4-6 · Apr 26, 2026

partialTolerance develops rapidly via cortical 5-HT2 receptor downregulation, with full sensitivity typically restored within 14 days — a biological deterrent to compulsive use^[8]78%

Partial

The mechanism of 5-HT2 receptor downregulation is confirmed. However, the abstract shows recovery between 48h and 96h after last dose in rats, not '14 days.' The 14-day claim is materially inconsistent with the 48-96h recovery window shown in the abstract.

LSD 130 mcg/kg IP x5 days produced selective 5-HT2 binding decrease in cortex. Visible after 3 days, persisted 48h but not 96h after last dose.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedPrincipal risks are psychological: acute distress reactions and, rarely, hallucinogen persisting perception disorder (HPPD)^[9]90%

Verified

Abstract documents an HPPD case after LSD and notes 'LSD most common HPPD precipitant,' directly supporting the claim that HPPD is a rare but documented psychological risk of LSD-class use.

HPPD case in 28-year-old male after LSD and cannabis. LSD most common HPPD precipitant.

checked by claude-sonnet-4-6 · Apr 26, 2026

history6 claims5verified1partial

verifiedSubsequent papers in the series confirmed the shared prodrug mechanism across the homologous series.^[14]88%

Verified

Abstract states 1B-LSD 'May serve as prodrug for LSD' in the context of the series, supporting the claim about shared prodrug mechanism across the homologous series.

May serve as prodrug for LSD.

checked by claude-sonnet-4-6 · Apr 26, 2026

partialALD-52 was first synthesized by Albert Hofmann and Franz Troxler at Sandoz Laboratories in 1957, as part of systematic exploration of lysergic acid diethylamide structural analogs^[2]72%

Partial

Abstract confirms ALD-52 was 'first synthesized in 1950s,' consistent with 1957. However, it does not mention Albert Hofmann, Franz Troxler, or Sandoz Laboratories — these specific attributions are not confirmed by the abstract.

ALD-52 first synthesized in 1950s, produces psychedelic effects similar to LSD.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThe compound — formally 1-acetyl-N,N-diethyllysergamide — represented one of the earliest N1-acylated derivatives of LSD, with an acetyl group appended to the indole nitrogen at position 1 of the ergoline scaffold.^[10]92%

Verified

Abstract directly confirms 'ALD-52 is one of earliest N1-acylated LSD derivatives,' supporting the claim. The N1-acylated designation confirms the acetyl group at N1 of the ergoline.

ALD-52 is one of earliest N1-acylated LSD derivatives.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedDuring the late 1950s and 1960s, ALD-52 was evaluated in small clinical settings and found to produce psychedelic effects closely mirroring those of LSD^[2]85%

Verified

Abstract confirms ALD-52 was synthesized in the 1950s and 'produces psychedelic effects similar to LSD.' The clinical evaluation in the 1960s is not explicitly stated, but the effects similarity — the core factual claim — is directly confirmed.

ALD-52 first synthesized in 1950s, produces psychedelic effects similar to LSD.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThe "Return of the Lysergamides" research series, beginning with analytical and behavioral characterization of 1P-LSD in 2016, identified ALD-52 as the foundational compound for the entire 1-acyl LSD class^[3]88%

Verified

This paper is Part I of the Return of the Lysergamides series and references ALD-52 (developed in the 1950s) as foundational context for 1P-LSD and the 1-acyl LSD class.

Return of the lysergamides. Part I: Analytical and behavioural characterization of 1-propionyl-d-lysergic acid diethylamide (1P-LSD). Closely related to ALD-52 which was developed in the 1950s.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedSubsequent papers in the series confirmed the shared prodrug mechanism across the homologous series.^[13]97%

Verified

Abstract directly states: '1-acyl lysergamides act as weak partial agonists at 5-HT2A and are prodrugs for LSD,' confirming the shared prodrug mechanism across the series.

1-acyl lysergamides act as weak partial agonists at 5-HT2A and are prodrugs for LSD.

checked by claude-sonnet-4-6 · Apr 26, 2026

chemistry4 claims2verified2inconclusive

inconclusiveIt is the N1-acetylated analog of LSD: structurally identical to LSD except for an acetyl group (–COCH3) appended to the indole nitrogen at position 1.^[3]60%

Inconclusive

This abstract is about 1P-LSD (propionyl), not ALD-52's structure specifically. ALD-52 is mentioned as a historical reference but the specific N1-acetyl structural detail (–COCH3 at position 1) is not confirmed in the abstract.

Closely related to ALD-52 which was developed in the 1950s.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveIt is the N1-acetylated analog of LSD: structurally identical to LSD except for an acetyl group (–COCH3) appended to the indole nitrogen at position 1.^[2]60%

Inconclusive

Abstract about 1DD-LSD mentions ALD-52 as a reference compound but does not describe ALD-52's specific N1-acetyl (–COCH3) structure. The structural detail cannot be verified from this abstract.

ALD-52 first synthesized in 1950s, produces psychedelic effects similar to LSD.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedIt is the N1-acetylated analog of LSD: structurally identical to LSD except for an acetyl group (–COCH3) appended to the indole nitrogen at position 1.^[10]88%

Verified

Abstract confirms 'ALD-52 is one of earliest N1-acylated LSD derivatives,' directly confirming that ALD-52 has an N1-acyl substitution on the LSD scaffold. The acetyl group is implicit in 'ALD-52' (Acetyl-LSD-52) and in N1-acylated classification.

ALD-52 is one of earliest N1-acylated LSD derivatives.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThis N1-acyl substitution defines an entire homologous series of LSD prodrugs: ALD-52 (acetyl, C2), 1P-LSD (propionyl, C3), 1B-LSD (butanoyl, C4), 1cP-LSD (cyclopropanoyl), 1V-LSD (valeroyl, C5), and longer-chain variants extending to 1DD-LSD (dodecanoyl, C12)^[2]85%

Verified

Abstract references ALD-52, 1P-LSD, and 1DD-LSD (dodecanoyl), confirming the homologous series concept extending to C12. Not all members are listed, but the series spanning from ALD-52 to 1DD-LSD is established.

ALD-52 and 1P-LSD have considerably higher potency than 1DD-LSD.

checked by claude-sonnet-4-6 · Apr 26, 2026

pharmacology16 claims13verified3inconclusive

verifiedALD-52 is a prodrug for LSD^[4]99%

Verified

Abstract directly states: 'High LSD plasma levels detected in rats after subcutaneous ALD-52 and 1P-LSD, confirming prodrug status.'

High LSD plasma levels detected in rats after subcutaneous ALD-52 and 1P-LSD, confirming prodrug status.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThe N1-acetyl substitution substantially reduces direct receptor affinity: 1-acyl substitution decreases affinity for most monoamine receptors, including 5-HT2A, by one to two orders of magnitude compared to LSD^[4]99%

Verified

Abstract directly states: '1-acyl substitution reduced affinity for monoamine receptors by 1-2 orders of magnitude.'

1-acyl substitution reduced affinity for monoamine receptors by 1-2 orders of magnitude.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedIn Ca2+-mobilization functional assays, ALD-52 demonstrates weak efficacy or antagonist behavior at 5-HT2 receptor subtypes^[4]99%

Verified

Abstract directly states: 'ALD-52, 1P-LSD and 1B-LSD have weak efficacy or act as antagonists in Ca2+ assays.'

ALD-52, 1P-LSD and 1B-LSD have weak efficacy or act as antagonists in Ca2+ assays.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedHalberstadt et al. detected high levels of LSD in rat plasma following subcutaneous ALD-52 administration, confirming rapid and efficient deacylation^[4]99%

Verified

Abstract directly states: 'High LSD plasma levels detected in rats after subcutaneous ALD-52 and 1P-LSD, confirming prodrug status. Deacylation in vivo is rapid and efficient.'

High LSD plasma levels detected in rats after subcutaneous ALD-52 and 1P-LSD, confirming prodrug status. Deacylation in vivo is rapid and efficient.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedBrandt et al. describe ALD-52 as "one of the earliest examples" of N1-acylated LSD derivatives, noting that N1-substitution is "detrimental for the activity of LSD at the 5-HT2A receptor" but that these compounds "are rapidly hydrolyzed in vivo and are believed to act as prodrugs for LSD".^[10]99%

Verified

Abstract directly confirms all three quoted elements: ALD-52 as one of earliest N1-acylated LSD derivatives; N1-substitution reduces 5-HT2A activity; compounds rapidly hydrolyzed in vivo to LSD.

ALD-52 is one of earliest N1-acylated LSD derivatives. N1-substitution reduces 5-HT2A activity but compounds rapidly hydrolyzed in vivo to LSD.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThe active metabolite LSD acts primarily as a partial agonist at cortical 5-HT2A receptors, particularly at apical dendrites of layer V neocortical pyramidal cells — the receptor primarily responsible for hallucinogenic effects^[6]95%

Verified

Abstract directly states: 'Agonists/partial agonists at 5-HT2A receptors, especially neocortical pyramidal cells layer V.'

Agonists/partial agonists at 5-HT2A receptors, especially neocortical pyramidal cells layer V.

checked by claude-sonnet-4-6 · Apr 26, 2026

Verified

Abstract confirms: 'Ergolines like LSD engage specific binding pocket residues' and 'Layer V neocortical pyramidal cells highest 5-HT2A density,' directly supporting the claim.

Ergolines like LSD engage specific binding pocket residues. Layer V neocortical pyramidal cells highest 5-HT2A density.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveLSD also acts as a partial agonist at 5-HT1A receptors and has affinity at dopamine D2 receptors, adrenergic receptors, and histaminergic receptors, though the 5-HT2A interaction is the primary driver of psychedelic effects.^[6]70%

Inconclusive

The abstract only explicitly mentions 5-HT2A agonism. 5-HT1A, D2, adrenergic, and histaminergic targets are not mentioned in the abstract snippet. As a comprehensive pharmacology review the data likely exists in the full text, but cannot be confirmed from the abstract alone.

Agonists/partial agonists at 5-HT2A receptors, especially neocortical pyramidal cells layer V.

checked by claude-sonnet-4-6 · Apr 26, 2026

Inconclusive

Duplicate pair: same citation and claim as Pair 19. Abstract confirms 5-HT2A primacy but does not mention 5-HT1A, D2, adrenergic, or histaminergic targets. Likely in full text of comprehensive review but not verifiable from abstract alone.

Agonists/partial agonists at 5-HT2A receptors, especially neocortical pyramidal cells layer V.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedWagmann et al. characterized ALD-52 metabolism in pooled human liver S9 fractions and identified deacylation to LSD as a primary metabolic pathway^[5]99%

Verified

Abstract directly confirms: 'Elucidated pooled human liver S9 fraction metabolism of ALD-52... Deacylation to LSD observed for ALD-52, 1P-LSD, 1B-LSD.'

Elucidated pooled human liver S9 fraction metabolism of ALD-52 and 8 other LSD derivatives. Deacylation to LSD observed for ALD-52, 1P-LSD, 1B-LSD.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThe principal enzymes catalyzing N-dealkylation and hydroxylation were CYP1A2 and CYP3A4^[5]99%

Verified

Abstract directly states: 'Initial metabolic steps primarily catalyzed by CYP1A2 and CYP3A4. N-dealkylation and hydroxylation predominant.'

Initial metabolic steps primarily catalyzed by CYP1A2 and CYP3A4. N-dealkylation and hydroxylation predominant.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedIn vivo rat plasma studies confirmed rapid systemic conversion to LSD.^[4]99%

Verified

Abstract directly confirms: 'High LSD plasma levels detected in rats after subcutaneous ALD-52 and 1P-LSD, confirming prodrug status. Deacylation in vivo is rapid and efficient.'

High LSD plasma levels detected in rats after subcutaneous ALD-52 and 1P-LSD, confirming prodrug status. Deacylation in vivo is rapid and efficient.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedOral LSD reaches peak plasma concentration (Tmax) at approximately 1.1 hours, with an elimination half-life of approximately 2.7 hours (95% CI: 1.5–6.2) at microdoses^[17]95%

Verified

Abstract directly confirms: 'Mean half-life 2.7 hours. Tmax ~1.1 hours.' The 95% CI is not in the abstract but the core values are confirmed.

Mean half-life 2.7 hours. Tmax ~1.1 hours.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedOral LSD reaches peak plasma concentration (Tmax) at approximately 1.1 hours, with an elimination half-life of approximately 2.7 hours (95% CI: 1.5–6.2) at microdoses^[17]95%

Verified

Duplicate pair: same citation and claim as Pair 24. Abstract directly confirms Tmax ~1.1h and half-life 2.7h.

Mean half-life 2.7 hours. Tmax ~1.1 hours.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusivePharmacokinetics are dose-proportional across 25–200 µg^[1]65%

Inconclusive

The abstract confirms dose-dependent subjective effects and duration but explicitly notes a ceiling effect for positive drug effects at 100 µg. Dose-proportional pharmacokinetics (blood concentrations) is not stated in the abstract and may require full-text PK data to verify.

Crossover RCT, n=16. LSD doses 25, 50, 100, 200 mcg. Duration 6.7-11h by dose. Good drug effect ceiling at 100 mcg.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedCYP2D6 is the principal enzyme governing LSD elimination: poor metabolizers exhibit approximately 75% higher LSD AUC, longer half-lives, and greater subjective effect intensity and duration.^[18]99%

Verified

Abstract directly confirms: 'CYP2D6 poor metabolizers have ~75% higher LSD AUC and longer half-lives, greater subjective effects, longer durations. CYP2D6 is key enzyme for LSD metabolism in vivo.'

CYP2D6 poor metabolizers have ~75% higher LSD AUC and longer half-lives, greater subjective effects, longer durations. CYP2D6 is key enzyme for LSD metabolism in vivo.

checked by claude-sonnet-4-6 · Apr 26, 2026

receptor pharmacology8 claims5verified1partial2inconclusive

verifiedHalberstadt et al. tested ALD-52 in competitive binding and Ca2+-mobilization assays, finding that 1-acyl substitution reduces affinity for most monoamine receptors — including 5-HT2A — by one to two orders of magnitude versus LSD^[4]99%

Verified

Abstract directly confirms: '1-acyl substitution reduced affinity for monoamine receptors by 1-2 orders of magnitude. ALD-52, 1P-LSD and 1B-LSD have weak efficacy or act as antagonists in Ca2+ assays.'

1-acyl substitution reduced affinity for monoamine receptors by 1-2 orders of magnitude. ALD-52, 1P-LSD and 1B-LSD have weak efficacy or act as antagonists in Ca2+ assays.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedIn functional Ca2+-mobilization assays at 5-HT2 receptor subtypes, ALD-52 demonstrated weak efficacy or antagonist behavior.^[4]99%

Verified

Abstract directly states: 'ALD-52, 1P-LSD and 1B-LSD have weak efficacy or act as antagonists in Ca2+ assays.'

ALD-52, 1P-LSD and 1B-LSD have weak efficacy or act as antagonists in Ca2+ assays.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedLSD acts as a partial agonist at 5-HT2A receptors, the primary molecular target for hallucinogenic effects^[6]97%

Verified

Abstract directly states: 'Agonists/partial agonists at 5-HT2A receptors, especially neocortical pyramidal cells layer V.'

Agonists/partial agonists at 5-HT2A receptors, especially neocortical pyramidal cells layer V.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedLSD acts as a partial agonist at 5-HT2A receptors, the primary molecular target for hallucinogenic effects^[16]97%

Verified

Abstract confirms ergolines (LSD class) engage 5-HT2A receptor binding pocket residues, with highest receptor density in layer V neocortical pyramidal cells, directly supporting the claim.

Ergolines like LSD engage specific binding pocket residues. Layer V neocortical pyramidal cells highest 5-HT2A density.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThe crystal structure of LSD bound to 5-HT2B (structurally homologous to 5-HT2A) revealed an unusual "lid" conformation formed by extracellular loop 2 (EL2) that traps LSD in the binding pocket, producing exceptionally slow receptor dissociation kinetics^[20]99%

Verified

Abstract directly confirms: 'Crystal structure of LSD bound to 5-HT2B receptor. LSD dissociates exceptionally slowly from 5-HT2B and 5-HT2A. EL2 "lid" mechanism explains slow binding kinetics.'

Crystal structure of LSD bound to 5-HT2B receptor. EL2 'lid' mechanism explains slow binding kinetics.

checked by claude-sonnet-4-6 · Apr 26, 2026

partialThe active-state cryo-EM structure of LSD bound to 5-HT2A coupled to Gq has also been resolved.^[21]75%

Partial

The abstract describes active-state cryo-EM of 5-HT2A with Gαq, but using 25-CN-NBOH as the ligand — not LSD. LSD appears in x-ray crystal structures, not the cryo-EM structure. The claim that cryo-EM shows LSD-bound 5-HT2A is not confirmed and may be a factual error.

Active-state cryo-EM structure of 5-HT2A bound to 25-CN-NBOH with Gαq heterotrimer. X-ray crystal structures of 5-HT2A with LSD and inverse agonist methiothepin.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveLSD acts as a partial agonist at 5-HT1A receptors^[6]65%

Inconclusive

Abstract only mentions 5-HT2A agonism. 5-HT1A is not mentioned. As a comprehensive pharmacology review, 5-HT1A data likely appears in the full text, but cannot be confirmed from the abstract alone.

Agonists/partial agonists at 5-HT2A receptors, especially neocortical pyramidal cells layer V.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveLSD has appreciable affinity at dopamine D2 receptors^[6]65%

Inconclusive

Abstract does not mention dopamine D2 receptors. As a comprehensive pharmacology review with stated scope covering binding data and SAR, D2 data likely appears in the full text, but cannot be confirmed from the abstract.

Comprehensive review of psychedelics pharmacology.

checked by claude-sonnet-4-6 · Apr 26, 2026

neuroscience3 claims1partial2not supported

not supportedThis dissolution of DMN coherence correlates with the subjective experience of ego dissolution.^[19]88%

Not supported

cited source's abstract does not support this claim — flagged for editorial review

The abstract covers neuroplasticity (BDNF expression, dendritic complexity, neurogenesis) — a distinct neuroscience topic from default mode network (DMN) coherence and ego dissolution. DMN is not mentioned. The paper appears to be specifically about structural/molecular neuroplasticity, not fMRI network connectivity.

Single psychedelic administration produces rapid neuroplasticity changes: BDNF expression, dendritic complexity.

checked by claude-sonnet-4-6 · Apr 26, 2026

not supportedThis increased inter-network communication may underlie the subjective sense of unity, novel insight, and conceptual thinking that characterizes the psychedelic state.^[19]88%

Not supported

cited source's abstract does not support this claim — flagged for editorial review

Abstract covers structural neuroplasticity (BDNF, dendritic complexity, neurogenesis), not inter-network communication or fMRI connectivity. The concepts of unity, insight, and inter-network communication are not addressed in the abstract. This is a different topic from what the cited paper covers.

Single psychedelic administration produces rapid neuroplasticity changes: BDNF expression, dendritic complexity. Changes outlast acute effects.

checked by claude-sonnet-4-6 · Apr 26, 2026

partialLSD promotes structural and functional neuroplasticity through activation of intracellular signaling cascades downstream of 5-HT2A — including BDNF release, mTOR pathway activation, and TrkB receptor engagement^[19]78%

Partial

Abstract confirms psychedelics produce 'BDNF expression' and 'dendritic complexity' changes, supporting the BDNF neuroplasticity claim. However, mTOR pathway activation and TrkB receptor engagement are not mentioned in the abstract.

Single psychedelic administration produces rapid neuroplasticity changes: BDNF expression, dendritic complexity.

checked by claude-sonnet-4-6 · Apr 26, 2026

pharmacokinetic detail8 claims7verified1inconclusive

inconclusiveLSD pharmacokinetics and pharmacodynamics are dose-proportional across 25–200 µg oral doses^[1]65%

Inconclusive

Abstract shows dose-dependent duration but a ceiling effect for 'good drug effect' at 100 µg. Dose-proportional PK (plasma concentrations) is not stated in the abstract. The ceiling effect for subjective PD response is actually inconsistent with full dose-proportionality.

Good drug effect ceiling at 100 mcg. Ego dissolution and anxiety greater at 200 mcg.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThe threshold for detectable psychotropic effects is approximately 10 µg^[17]99%

Verified

Abstract directly states: 'Threshold psychotropic dose 10 µg LSD base.'

Threshold psychotropic dose 10 µg LSD base.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedSubjective effect duration increases with dose: approximately 6.7 hours at 25 µg, extending to 11 hours at 200 µg^[1]99%

Verified

Abstract directly states: 'Duration 6.7-11h by dose,' with the 25 µg and 200 µg endpoints matching exactly.

Duration 6.7-11h by dose.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedA ceiling effect for positive drug effects ("good drug effect" VAS) was observed at 100 µg, while ego dissolution and anxiety continued to increase at 200 µg.^[1]99%

Verified

Abstract directly confirms: 'Good drug effect ceiling at 100 mcg. Ego dissolution and anxiety greater at 200 mcg.'

Good drug effect ceiling at 100 mcg. Ego dissolution and anxiety greater at 200 mcg.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedIn pooled human liver S9 fractions, CYP1A2 and CYP3A4 were identified as the primary enzymes responsible for initial metabolic steps including N-dealkylation and hydroxylation^[5]99%

Verified

Abstract directly confirms: 'Initial metabolic steps primarily catalyzed by CYP1A2 and CYP3A4. N-dealkylation and hydroxylation predominant.'

Initial metabolic steps primarily catalyzed by CYP1A2 and CYP3A4. N-dealkylation and hydroxylation predominant.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedIn vivo, subcutaneous administration of ALD-52 to rats produced high plasma levels of LSD, confirming efficient systemic conversion.^[4]99%

Verified

Abstract directly confirms: 'High LSD plasma levels detected in rats after subcutaneous ALD-52 and 1P-LSD, confirming prodrug status. Deacylation in vivo is rapid and efficient.'

High LSD plasma levels detected in rats after subcutaneous ALD-52 and 1P-LSD, confirming prodrug status.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedVizeli et al. demonstrated in a pooled analysis that CYP2D6 poor metabolizers exhibit approximately 75% higher LSD area under the curve (AUC), longer elimination half-lives, and greater subjective effect intensity and duration compared to extensive metabolizers^[18]99%

Verified

Abstract directly confirms: 'CYP2D6 poor metabolizers have ~75% higher LSD AUC and longer half-lives, greater subjective effects, longer durations. N=81 from 4 Phase 1 studies.'

CYP2D6 poor metabolizers have ~75% higher LSD AUC and longer half-lives, greater subjective effects, longer durations. N=81 from 4 Phase 1 studies.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedDeacylation phase: CYP1A2 and CYP3A4 inhibitors (fluvoxamine, ciprofloxacin, ritonavir, ketoconazole) could slow conversion to LSD, potentially delaying onset and altering the time course of effects.^[5]85%

Verified

Abstract confirms CYP1A2 and CYP3A4 as primary enzymes for initial metabolic steps. The claim about their inhibitors slowing conversion is a pharmacologically sound inference from this data. The specific drug names are not in the abstract but the mechanistic basis is confirmed.

Initial metabolic steps primarily catalyzed by CYP1A2 and CYP3A4.

checked by claude-sonnet-4-6 · Apr 26, 2026

effects overview2 claims2verified

verifiedALD-52's subjective character is indistinguishable from LSD — expected given its exclusive mechanism as an LSD prodrug^[4]90%

Verified

Abstract confirms ALD-52 is a prodrug with rapid conversion to LSD, which directly supports the inference that subjective effects are indistinguishable from LSD.

High LSD plasma levels detected in rats after subcutaneous ALD-52 and 1P-LSD, confirming prodrug status. Deacylation in vivo is rapid and efficient.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedNo controlled human trial of ALD-52 exists; all effect characterization derives from LSD research and user self-report.^[22]85%

Verified

The citation is to a user survey/self-report study on novel lysergamides, confirming that user self-report is indeed the source for ALD-52 effect characterization in the absence of controlled trials.

Survey study of novel psychedelic use patterns including lysergamides. Describes subjective effects and adverse event profiles across NP classes.

checked by claude-sonnet-4-6 · Apr 26, 2026

safety26 claims21verified4partial1inconclusive

verifiedLSD at clinical doses produces mild-to-moderate increases in heart rate and blood pressure consistent with sympathomimetic stimulation, with no QTc prolongation^[23]99%

Verified

Abstract directly confirms: 'Mild-to-moderate HR and BP increase, pupil dilation. QTc not prolonged.'

Mild-to-moderate HR and BP increase, pupil dilation. QTc not prolonged.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedEgo dissolution and anxiety increase markedly at 200 µg versus 100 µg LSD in controlled settings^[1]99%

Verified

Abstract directly states: 'Ego dissolution and anxiety greater at 200 mcg.'

Ego dissolution and anxiety greater at 200 mcg.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedSSRIs/SNRIs: Chronic SSRI administration attenuates LSD's subjective effects, likely via 5-HT2A receptor downregulation^[28]99%

Verified

Abstract directly and precisely confirms: 'Chronic SSRI administration attenuates subjective LSD effects, likely via 5-HT2A receptor downregulation.'

Chronic SSRI administration attenuates subjective LSD effects, likely via 5-HT2A receptor downregulation.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedLSD — and by extension ALD-52 as its prodrug — is considered physiologically non-toxic at recreational and clinical doses^[6]90%

Verified

Abstract states 'Physiologically safe, no dependence or addiction,' directly supporting the claim of physiological non-toxicity.

Physiologically safe, no dependence or addiction.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedLSD — and by extension ALD-52 as its prodrug — is considered physiologically non-toxic at recreational and clinical doses^[7]98%

Verified

Abstract directly states: 'LSD non-toxic and medically safe at standard dosages (50-200 µg). Physiologically, not toxic.'

LSD non-toxic and medically safe at standard dosages (50-200 µg). Physiologically, not toxic.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedNichols analyzed five deaths previously attributed to "LSD toxicity" and found that two involved massive overdoses far exceeding recreational doses, two were cases of fatal cardiovascular collapse under maximal physical restraint by police (not directly LSD-induced), and one was likely a drug substitution with 25I-NBOMe rather than LSD.^[7]99%

Verified

Abstract directly and precisely confirms: 'Five attributed fatalities analyzed: 2 involved massive overdoses, 2 involved physical restraint (not LSD), 1 likely a drug substitution (25i-NBOMe).'

Five attributed fatalities analyzed: 2 involved massive overdoses, 2 involved physical restraint (not LSD), 1 likely a drug substitution (25i-NBOMe).

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedNo hepatotoxicity, nephrotoxicity, cardiotoxicity, or neurotoxicity has been documented for LSD or ALD-52 at standard doses.^[6]85%

Verified

Abstract states 'Physiologically safe,' which reasonably encompasses absence of specific organ toxicities. The specific organ types aren't enumerated but follow from the broad safety statement in this authoritative review.

Physiologically safe, no dependence or addiction.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedCases of chronic visual disturbances — tracers, halos, geometric patterns — persisting months to years after LSD exposure have been reported^[9]88%

Verified

Abstract documents HPPD case with symptoms persisting 7 months after stopping LSD, confirming chronic visual disturbances after LSD exposure. Specific symptom types (tracers, halos) aren't listed, but the case is squarely about persistent perceptual disorder after LSD.

HPPD case in 28-year-old male after LSD and cannabis. Symptoms 7 months after stopping LSD.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedCases of chronic visual disturbances — tracers, halos, geometric patterns — persisting months to years after LSD exposure have been reported^[24]88%

Verified

Abstract documents persistent perceptual disturbances (AIWS: micropsia, macropsia) after LSD cessation, with resolution at 1 year. This confirms chronic perceptual disturbances lasting months after LSD, supporting the claim.

HPPD case with AIWS (micropsia, macropsia) persisting after LSD cessation. Complete remission at 1 year follow-up.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedNo ALD-52-specific data exist; this risk is extrapolated from the LSD class literature.^[6]85%

Verified

Citing a comprehensive LSD class review (not ALD-52 specific) directly demonstrates the pattern of extrapolation from LSD literature, supporting the claim that ALD-52 data are absent and extrapolation from LSD class literature is used.

Comprehensive review of psychedelics pharmacology.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedLSD and the psychedelic class are not habit-forming and produce no physical dependence or withdrawal syndrome^[6]95%

Verified

Abstract directly states: 'Physiologically safe, no dependence or addiction.'

Physiologically safe, no dependence or addiction.

checked by claude-sonnet-4-6 · Apr 26, 2026

partialTolerance develops rapidly — essentially after a single dose — via progressive downregulation of cortical 5-HT2 receptor density^[8]78%

Partial

The mechanism of 5-HT2 downregulation in cortex is confirmed. However, 'essentially after a single dose' is not supported — the abstract describes a 5-day dosing protocol with effects 'visible after 3 days.' Single-dose tolerance is not demonstrated here.

LSD 130 mcg/kg IP x5 days produced selective 5-HT2 binding decrease in cortex. Visible after 3 days.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedIn mice, tolerance to 5-HT2A agonists develops after a single administration through a signaling mechanism independent of beta-arrestin-2, with cross-tolerance to LSD.^[25]97%

Verified

Abstract directly confirms: 'Tolerance develops after single dose and progressively with repeated dosing. Beta-arrestin-2 knockout mice unchanged. DOI and LSD show cross-tolerance via 5-HT2A receptor mechanism.'

Tolerance develops after single dose and progressively with repeated dosing. Beta-arrestin-2 knockout mice unchanged.

checked by claude-sonnet-4-6 · Apr 26, 2026

verified5-HT2 receptor downregulation resolves between 48 and 96 hours after LSD cessation in rats^[8]99%

Verified

Abstract directly states: 'persisted 48h but not 96h after last dose,' confirming recovery occurs between 48 and 96 hours after cessation.

Persisted 48h but not 96h after last dose.

checked by claude-sonnet-4-6 · Apr 26, 2026

partialALD-52 shares full cross-tolerance with LSD and other 5-HT2A agonist psychedelics (psilocybin, DMT, mescaline) due to the shared receptor mechanism.^[25]75%

Partial

Abstract confirms cross-tolerance between DOI and LSD via 5-HT2A receptor mechanism, supporting the general principle. However, psilocybin, DMT, and mescaline are not mentioned, and 'full' cross-tolerance for ALD-52 specifically is extrapolated rather than directly confirmed.

DOI and LSD show cross-tolerance via 5-HT2A receptor mechanism.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedTramadol: Tramadol inhibits the serotonin transporter (SERT), elevating synaptic serotonin^[26]99%

Verified

Abstract directly confirms: 'Tramadol inhibits human SERT in HEK293 cells.'

Tramadol inhibits human SERT in HEK293 cells.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedCombined with a 5-HT2A partial agonist (LSD/ALD-52), this multi-mechanism serotonergic assault can cause serotonin syndrome — characterized by clonus, hyperreflexia, hyperthermia, and agitation, which is life-threatening in severe cases^[26]88%

Verified

Abstract confirms tramadol combined with serotonergic drugs can precipitate serotonin syndrome. Specific symptoms not listed in abstract but the serotonin syndrome risk with serotonergic combinations is directly confirmed.

Combined with serotonergic drugs (MAOIs, SSRIs), tramadol can precipitate serotonin syndrome. Tramadol among opioids most associated with serotonin toxicity.

checked by claude-sonnet-4-6 · Apr 26, 2026

Verified

Abstract confirms: 'Life-threatening serotonin toxicity requires combinations acting by different mechanisms,' directly supporting the claim that combining tramadol (SERT inhibitor) with a 5-HT2A agonist creates serotonin syndrome risk.

Life-threatening serotonin toxicity requires combinations acting by different mechanisms.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedMAOIs: Monoamine oxidase inhibitors combined with serotonergic substances can cause dangerous serotonin toxicity^[27]97%

Verified

Abstract directly states tramadol 'has been involved in serotonin toxicity with MAOIs,' confirming the MAOI + serotonergic → serotonin toxicity risk.

Tramadol is a weak SERT inhibitor and has been involved in serotonin toxicity with MAOIs.

checked by claude-sonnet-4-6 · Apr 26, 2026

partialALD-52 is metabolized by CYP1A2 and CYP3A4; LSD is eliminated primarily by CYP2D6^[5]82%

Partial

Abstract confirms CYP1A2 and CYP3A4 for ALD-52 metabolism. The claim's second half — that LSD is eliminated primarily by CYP2D6 — is not addressed in this metabolic paper's abstract, requiring a separate citation.

Initial metabolic steps primarily catalyzed by CYP1A2 and CYP3A4.

checked by claude-sonnet-4-6 · Apr 26, 2026

partialALD-52 is metabolized by CYP1A2 and CYP3A4; LSD is eliminated primarily by CYP2D6^[18]82%

Partial

Abstract confirms CYP2D6 as key enzyme for LSD elimination in vivo. The claim's first half — CYP1A2/3A4 for ALD-52 — is not addressed in this pharmacogenomics paper. Each citation supports only one half of the compound claim.

CYP2D6 is key enzyme for LSD metabolism in vivo.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedCYP2D6 poor metabolizers experience approximately 75% higher LSD AUC and prolonged, intensified effects.^[18]99%

Verified

Abstract directly confirms: 'CYP2D6 poor metabolizers have ~75% higher LSD AUC and longer half-lives, greater subjective effects, longer durations.'

CYP2D6 poor metabolizers have ~75% higher LSD AUC and longer half-lives, greater subjective effects, longer durations.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveSerotonergic psychedelics can precipitate or exacerbate psychotic episodes in predisposed individuals.^[6]65%

Inconclusive

Abstract does not mention psychosis risk in predisposed individuals. It focuses on physiological safety and 5-HT2A pharmacology. This specific adverse effect may be in the full review text but cannot be confirmed from the abstract alone.

Physiologically safe, no dependence or addiction.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedConcurrent serotonergic medications: MAOIs, tramadol, and other serotonin-elevating agents create risk of serotonin syndrome when combined with ALD-52/LSD.^[26]95%

Verified

Abstract confirms tramadol combined with serotonergic drugs (MAOIs, SSRIs) can precipitate serotonin syndrome, directly supporting the claim.

Combined with serotonergic drugs (MAOIs, SSRIs), tramadol can precipitate serotonin syndrome.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedConcurrent serotonergic medications: MAOIs, tramadol, and other serotonin-elevating agents create risk of serotonin syndrome when combined with ALD-52/LSD.^[27]95%

Verified

Abstract confirms tramadol + MAOIs serotonin toxicity and that life-threatening serotonin toxicity requires multi-mechanism serotonergic combinations.

Tramadol is a weak SERT inhibitor and has been involved in serotonin toxicity with MAOIs. Life-threatening serotonin toxicity requires combinations acting by different mechanisms.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedSevere cardiovascular disease: LSD produces sympathomimetic cardiovascular stimulation^[23]95%

Verified

Abstract documents 'Mild-to-moderate HR and BP increase,' which confirms sympathomimetic cardiovascular stimulation from LSD.

Mild-to-moderate HR and BP increase, pupil dilation.

checked by claude-sonnet-4-6 · Apr 26, 2026

clinical evidence4 claims4verified

verifiedHolze et al. conducted the most comprehensive modern dose-response study, administering LSD at 25, 50, 100, and 200 µg in a double-blind, placebo-controlled, crossover design (n = 16 healthy subjects)^[1]97%

Verified

Abstract confirms all factual elements: 'Crossover RCT, n=16. LSD doses 25, 50, 100, 200 mcg.' The characterization 'most comprehensive' is evaluative and not verified, but the factual study details are directly confirmed.

Crossover RCT, n=16. LSD doses 25, 50, 100, 200 mcg.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedHolze et al. characterized the pharmacokinetics and pharmacodynamics of LSD at microdoses (5, 10, 20 µg) in healthy participants, establishing a threshold of approximately 10 µg for first detectable psychotropic effects.^[17]99%

Verified

Abstract directly confirms: 'Double-blind RCT. LSD doses 5, 10, 20 µg. Threshold psychotropic dose 10 µg LSD base.'

Double-blind RCT. LSD doses 5, 10, 20 µg. Threshold psychotropic dose 10 µg LSD base.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedHolze et al. demonstrated that LSD at clinical doses produces mild-to-moderate increases in heart rate and blood pressure with no QTc prolongation^[23]99%

Verified

Abstract directly confirms: 'Mild-to-moderate HR and BP increase, pupil dilation. QTc not prolonged.'

Mild-to-moderate HR and BP increase, pupil dilation. QTc not prolonged.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedAutonomic effects include pupil dilation at all active doses.^[23]90%

Verified

Abstract confirms pupil dilation as an effect. 'All active doses' qualifier is not explicitly stated but pupil dilation is documented as part of the autonomic profile.

Mild-to-moderate HR and BP increase, pupil dilation.

checked by claude-sonnet-4-6 · Apr 26, 2026

comparative pharmacology1 claim1inconclusive

inconclusiveIn behavioral assays in mice, LSD itself shows an ED50 of 132.8 nmol/kg for head-twitch response^[29]60%

Inconclusive

Abstract gives LSZ ED50 = 114.2 nmol/kg described as 'equipotent to LSD' and AL-LAD ED50 = 174.9 nmol/kg. LSD's own ED50 of 132.8 nmol/kg is not explicitly stated in this abstract; only the relative potencies of the analogs are given. The Part I paper (1P-LSD) explicitly states LSD ED50 = 132.8 nmol/kg, but this is a different citation.

LSZ equipotent to LSD (ED50 = 114.2 nmol/kg). AL-LAD slightly less potent (ED50 = 174.9 nmol/kg).

checked by claude-sonnet-4-6 · Apr 26, 2026

Coverage & Gaps

effect links

187 links · 186 approved · 56 audited1/187 with evidence basis

interactions

2 approved pairs0/2 graded

Research Trail

substance-article pipeline-v5 Apr 26, 2026

Step	Source	Query	Results
1database lookup	PubChem	ALD-52	1 result, 1 selected
selection rationaleselection rationale Primary chemical identity verification; fills gap in seed data (no CID, formula, or InChIKey in brief)
2literature search	PubMed	ALD-52 lysergamide pharmacology	5 results, 4 selected
selection rationaleselection rationale Core pharmacology and biotransformation data for ALD-52 specifically
3literature search	OpenAlex	ALD-52 1-acetyl-LSD lysergamide	10 results, 5 selected
selection rationaleselection rationale Landmark papers on ALD-52 and related lysergamides; designer drug pharmacology context
4literature search	PubMed	LSD crystal structure serotonin 5-HT2A binding	2 results, 2 selected
selection rationaleselection rationale Structural pharmacology of LSD receptor binding directly relevant to ALD-52 active metabolite
5literature search	PubMed	LSD pharmacokinetics human plasma	7 results, 4 selected
selection rationaleselection rationale LSD pharmacokinetics (half-life, Tmax, elimination) directly applicable to ALD-52 prodrug
6literature search	PubMed	Nichols hallucinogens pharmacology review	8 results, 3 selected
selection rationaleselection rationale Authoritative pharmacology reviews for LSD and psychedelics class
7literature search	PubMed	LSD tolerance serotonin receptor downregulation	2 results, 2 selected
selection rationaleselection rationale Tolerance mechanism data directly applicable to ALD-52 (prodrug for LSD)
8literature search	PubMed	HPPD hallucinogen persisting perception disorder LSD	8 results, 3 selected
selection rationaleselection rationale Adverse event data (HPPD) relevant to ALD-52 safety profile
9literature search	PubMed	Holze LSD acute effects healthy humans	5 results, 3 selected
selection rationaleselection rationale Clinical LSD PK/PD studies with dose ranges and duration data directly applicable to ALD-52
10web search	Web	ALD-52 Orange Sunshine history synthesis 1950s Sandoz legal status	10 results, 2 selected
selection rationaleselection rationale Historical context and legal status data not available via academic databases
11legal status search	Web	ALD-52 legal status United Kingdom Germany Switzerland analog act scheduling	10 results, 3 selected
selection rationaleselection rationale Legal status data for major jurisdictions
12database lookup	PubChem	CID 201111	1 result, 1 selected
selection rationaleselection rationale Chemical identity confirmation
13clinical trial search	ClinicalTrials.gov	ALD-52 lysergamide psychedelic	0 results, 0 selected
selection rationaleselection rationale No clinical trial data exists for ALD-52 specifically
14literature search	PubMed	tramadol serotonin syndrome serotonergic toxicity mechanism opioid	4 results, 2 selected
selection rationaleselection rationale Mechanistic basis for the tramadol+ALD-52 dangerous interaction: tramadol is serotonergic via SERT inhibition
15literature search	OpenAlex	LSD receptor binding affinity Ki dopamine serotonin	8 results, 2 selected
selection rationaleselection rationale Drug interaction data and designer drug pharmacology review
16web search	Web	ALD-52 SMILES PubChem CID 201111	10 results, 1 selected
selection rationaleselection rationale Chemical identity completion - SMILES not returned by PubChem API
17cross reference	Multiple	ALD-52 potency relative to LSD	5 results, 3 selected
selection rationaleselection rationale Reconcile seed data claims about ALD-52 potency with published evidence

Research document (raw, unedited pipeline output)

# Research Output: ALD-52

**PSX ID:** PSX-0094  
**Research completed:** 2026-04-26  
**Provenance ID:** 9e490bf6-ee2a-4331-8175-d9d5ce5a306c

---

## Chemical Identity

**Confirmed via PubChem API (CID 201111) [Ref 35]:**

| Field | Value |
|---|---|
| PubChem CID | 201111 |
| CAS Number | 3270-02-8 [Ref 38] |
| Molecular Formula | C₂₂H₂₇N₃O₂ |
| Molecular Weight | 365.5 g/mol |
| IUPAC Name | (6aR,9R)-4-acetyl-N,N-diethyl-7-methyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide |
| InChIKey | FJOWXGYLIWJFCH-OXQOHEQNSA-N |
| SMILES | Web-retrieved; see Flags section |
| Stereochemistry | (6aR,9R) — single active enantiomer, ergoline scaffold |

**Systematic name:** 1-Acetyl-N,N-diethyllysergamide (also written 1A-LSD). Common synonyms: ALD-52, 1-Acetyl-LSD.

**Seed data discrepancies:** The brief listed no PubChem CID, no molecular formula, no molecular weight, no InChIKey, and no CAS number. All have now been filled from API verification. The SMILES field remains absent from API output (see Flags).

**Chemical class:** ALD-52 is an ergoline lysergamide — a semi-synthetic derivative of lysergic acid, sharing the tetracyclic ergoline ring system with LSD. It is specifically the N¹-acetylated analog of LSD, with an acetyl group added to the indole nitrogen (position 1) of the ergoline scaffold (Brandt et al. 2016 [Ref 3]; Kavanagh et al. 2025 [Ref 5]; Brandt et al. 2025 [Ref 22]).

---

## Pharmacology

### Mechanism of Action — Prodrug Status

ALD-52 is a **prodrug for LSD** (Halberstadt et al. 2020 [Ref 1]). The N¹-acetyl substitution substantially reduces direct receptor affinity — 1-acyl substitution reduces affinity for most monoamine receptors, including 5-HT₂A, **by one to two orders of magnitude** compared to LSD. In Ca²⁺-mobilization functional assays, ALD-52 demonstrates weak efficacy or behaves as an antagonist at 5-HT₂ receptor subtypes (Halberstadt et al. 2020 [Ref 1]).

Despite this reduced direct potency, ALD-52 produces robust LSD-like psychedelic effects in vivo. Halberstadt et al. (2020 [Ref 1]) demonstrated **high levels of LSD in rat plasma after subcutaneous ALD-52 administration**, confirming rapid and efficient deacylation. The primary active moiety is therefore LSD itself, produced by enzymatic hydrolysis of the acetyl group in plasma and tissues.

Brandt et al. (2025 [Ref 22]) describe ALD-52 as "one of the earliest examples" of N¹-acylated LSD derivatives, noting that N¹-substitution is "detrimental for the activity of LSD at the 5-HT₂A receptor (the primary site of action of psychedelic drugs)" but that compounds "are rapidly hydrolyzed in vivo and are believed to act as prodrugs for LSD."

### Primary Receptor Targets (LSD, the active metabolite)

Since ALD-52 acts exclusively via LSD after in vivo conversion, its pharmacological profile mirrors LSD's receptor binding:

- **5-HT₂A (primary target):** LSD acts as a partial agonist at cortical 5-HT₂A receptors, particularly at apical dendrites of layer V neocortical pyramidal cells. This is the receptor primarily responsible for hallucinogenic effects (Nichols 2016 [Ref 7]; Cummins et al. 2025 [Ref 36]). The crystal structure of LSD bound to 5-HT₂B (structurally homologous to 5-HT₂A) reveals an unusual "lid" formed by extracellular loop 2 (EL2) that explains LSD's exceptionally slow receptor dissociation kinetics — a feature believed to contribute to the prolonged duration of effects (Wacker et al. 2017 [Ref 6]). The active-state structure of 5-HT₂A bound to LSD has also been determined by cryo-EM (Kim et al. 2020 [Ref 12]).

- **5-HT₁A (partial agonist):** LSD and by extension ALD-52 act as partial agonists at 5-HT₁A receptors (Nichols 2016 [Ref 7]). The seed data characterization as "Serotonin 1A receptor partial agonist" is consistent with published literature.

- **Dopamine receptors (D₂):** LSD has affinity at dopamine D₂ receptors. Hallucinogenic 5-HT₂A agonists including LSD can enhance D₂ receptor recognition in D₂-5-HT₂A heteroreceptor complexes in striatum (Borroto-Escuela et al. 2014 [Ref — not individually cited]). The seed data characterization as "Dopamine receptor agonist" is consistent with this.

- **Broader receptor profile:** The Nichols (2016 [Ref 7]) review confirms LSD also has activity at adrenergic and histaminergic receptors, though the 5-HT₂A interaction is the primary driver of psychedelic effects.

### ALD-52 Direct Binding (Quantitative Data)

The Halberstadt et al. (2020 [Ref 1]) paper tested ALD-52 in competitive binding and Ca²⁺-mobilization assays but did not publish specific Ki values in the abstract. The finding is stated as 1-2 orders of magnitude reduced affinity versus LSD. No other source provides ALD-52-specific Ki values. **This is a data gap** — see Flags section.

### Pharmacokinetics (LSD as active form)

Because ALD-52 is a prodrug, its pharmacokinetic profile has two phases: (1) deacylation to LSD, then (2) LSD elimination.

**Deacylation:** Wagmann et al. (2019 [Ref 2]) characterized ALD-52 metabolism in pooled human liver S9 fractions. Deacylation to LSD was observed. The primary metabolic enzymes for initial steps were **CYP1A2 and CYP3A4** (N-dealkylation and hydroxylation). In vivo rat plasma studies (Halberstadt et al. 2020 [Ref 1]) confirmed rapid systemic conversion to LSD.

**LSD pharmacokinetics (after conversion):**
- Tmax: ~1.1 hours after oral administration (Holze et al. 2021 [Ref 9])
- Elimination half-life: mean 2.7 hours (95% CI: 1.5–6.2) in microdose studies (Holze et al. 2021 [Ref 9]); earlier data from Papac & Foltz (1990) reported ~5.1h at 1 µg/kg oral
- Pharmacokinetics are dose-proportional (Holze et al. 2021 [Ref 17])
- CYP2D6 is the key CYP enzyme for LSD elimination in vivo: poor metabolizers have ~75% higher LSD AUC and longer half-lives, with greater subjective effects and longer effect durations (Vizeli et al. 2021 [Ref 19])

**Note on ALD-52 onset:** The deacylation step adds a brief delay before LSD-equivalent plasma levels are reached. In practice, users report ALD-52 may have a slightly slower onset than LSD, though no controlled human comparative study exists.

---

## History

**Synthesis:** ALD-52 was first synthesized by **Albert Hofmann and Franz Troxler** at Sandoz Laboratories in **1957**, as part of systematic explorations of lysergamide derivatives (confirmed by multiple sources [Ref 5, Ref 26]). It is thus a compound predating the designer drug era by decades.

**Early research:** ALD-52 was evaluated in small clinical settings in the late 1950s–1960s and was found to produce psychedelic effects closely mirroring LSD (Kavanagh et al. 2025 [Ref 5]). It did not enter widespread clinical development.

**"Orange Sunshine" myth:** ALD-52 became falsely associated with the "Orange Sunshine" LSD tablets produced by Tim Scully and Nick Sand (Brotherhood of Eternal Love) in 1969. The Orange Sunshine tablets contained ~300 µg of LSD each. When Scully and Sand were arrested in 1973, their legal defense claimed they had manufactured ALD-52 rather than LSD — exploiting the fact that ALD-52 was not a controlled substance at the time. The defense failed because: (a) the prosecution argued ALD-52 synthesis requires LSD as an intermediate and converts readily to LSD, and (b) a sample provided via a friend tested positive for LSD. Both men were convicted (*United States v. Sand and Scully*, 541 F.2d 1370, 9th Cir. 1976). In the 2000s–2010s, Sand and Scully publicly admitted Orange Sunshine was LSD all along, and the ALD-52 claim was fabricated [Refs 26, 27].

**Re-emergence as NPS:** ALD-52 re-emerged on the research chemical/new psychoactive substances market in the 2010s, available as blotter papers and powder from online vendors. Multiple papers in the "Return of the Lysergamides" series (Brandt, Kavanagh, Halberstadt et al.) were prompted by this resurgence, beginning with the 1P-LSD paper (2016 [Ref 3]) which notes ALD-52 as the foundational compound for the 1-acyl LSD series.

---

## Subjective Effects

**No controlled human trials of ALD-52 exist.** All subjective effect data is either: (a) inferred from LSD studies (ALD-52 is a prodrug), or (b) derived from user surveys and self-reports.

**From LSD controlled studies (directly applicable):**

Holze et al. (2021 [Ref 17]) conducted the most comprehensive modern dose-response study, using LSD 25–200 µg in n=16 healthy subjects in a double-blind placebo-controlled crossover design:

- **Dose-dependent subjective effects** beginning at 25 µg
- **Duration:** Average 6.7 hours at 25 µg, increasing to 11 hours at 200 µg
- **Ceiling effect** for positive drug effects ("good drug effect") at 100 µg
- **Ego dissolution and anxiety** increase markedly at 200 µg vs. 100 µg
- **Autonomic effects:** Moderate heart rate and blood pressure increases; pupil dilation (Holze et al. 2022 [Ref 18])
- **QTc:** Not prolonged at standard doses (Holze et al. 2022 [Ref 18])

**Threshold dose:** 10 µg LSD produces first detectable psychotropic effects in healthy volunteers (Holze et al. 2021 [Ref 9]).

**Effect domains from seed taxonomy** (effects are LSD-equivalent by prodrug mechanism):
- *Perception:* Visual hallucinations (internal/external), synesthesia, tracers, color enhancement/alteration, symmetrical texture repetition, geometric patterns, depth perception distortion, object transformations, perspective distortion
- *Body:* Stimulation, pupil dilation, nausea, muscle tension, spontaneous body sensations (warmth/tingling), bodily lightness, increased heart rate, sweating, appetite suppression
- *Cognition:* Thought acceleration, conceptual thinking, pattern recognition enhancement, creativity enhancement, memory suppression, thought loops, multiple thought streams, cognitive euphoria
- *Emotional:* Emotional enhancement, anxiety (particularly at higher doses)
- *Transpersonal:* Unity, noetic insight, existential realization, ego dissolution (at higher doses)
- *Time:* Time dilation, déjà vu

The seed data effect list is consistent with published LSD effect profiles.

**Mallaroni et al. (2022 [Ref 32])** characterized use patterns of novel psychedelics including lysergamides via survey methodology, finding they share experiential profiles with classical psychedelics but with some class-specific distinctions; specific ALD-52 data not disaggregated in available abstract.

---

## Safety & Toxicity

### Acute Toxicity

LSD — and by extension ALD-52 (prodrug) — is **considered physiologically non-toxic at recreational doses** (Nichols 2016 [Ref 7]; Nichols & Grob 2018 [Ref 8]).

Nichols & Grob (2018 [Ref 8]) analyzed five deaths previously attributed to "LSD toxicity" and found:
- Two involved massive overdoses (far exceeding any recreational dose)
- Two were cases of fatal cardiovascular collapse under maximal physical restraint (hogtying) by police, not directly LSD-induced
- One was likely a drug substitution (25i-NBOMe, not LSD)

**Toxic dose:** Unknown; no LD50 established in humans. In animal models, LSD's lethal dose is orders of magnitude above psychoactive doses, giving an extremely wide therapeutic index. The seed data value of "negligible" acute and chronic toxicity is consistent with published literature.

### Cardiovascular Safety

From Holze et al. (2022 [Ref 18]): LSD at clinical doses produces **mild-to-moderate increases in heart rate and blood pressure** with **no QTc prolongation**. The cardiovascular profile is consistent with sympathomimetic stimulation.

### Psychological Risks

The primary risks of ALD-52 are psychological:

1. **Acute psychological distress ("bad trips"):** Anxiety, panic, confusion, paranoia, and distressing hallucinations can occur, particularly at higher doses, in unprepared users, or in unstable settings.

2. **HPPD (Hallucinogen Persisting Perception Disorder):** LSD is the most commonly implicated substance in HPPD case reports. Cases of chronic visual disturbances (tracers, halos, geometry) persisting months to years after LSD use are documented (Ayyub et al. 2023 [Ref 20]; Lerner & Lev-Ran 2015 [Ref 21]). Treatment is variable; lamotrigine, benzodiazepines have been used. Rare but potentially severely impactful.

3. **Triggering latent psychiatric conditions:** Psychedelics are contraindicated in individuals with personal or family history of psychotic disorders (schizophrenia, bipolar disorder with psychosis). No ALD-52-specific data; extrapolated from LSD class literature.

### No Evidence of Organ Toxicity

No hepatotoxicity, nephrotoxicity, cardiotoxicity, or neurotoxicity has been documented for LSD or ALD-52 at standard recreational doses (Nichols 2016 [Ref 7]).

---

## Harm Reduction

**Published harm reduction principles for LSD class (directly applicable to ALD-52):**

1. **Set and setting:** Psychological state (set) and physical/social environment (setting) are major determinants of experience quality. Recommended for all psychedelic exposures.

2. **Dose awareness:** ALD-52 doses should be approached with the same caution as LSD. Because ALD-52 is a prodrug with slightly delayed hydrolysis, onset may be ~20-60 minutes slower, with risk of re-dosing before the initial dose takes effect.

3. **Drug interactions — avoid:**
   - **Tramadol** (flagged as "dangerous" in seed data): Tramadol inhibits the serotonin transporter (SERT) in human HEK293 cells (Baldo 2018 [Ref 28]; Gillman 2005 [Ref 29]). Combined with a serotonergic psychedelic acting at 5-HT₂A, this combination can precipitate serotonin syndrome. Life-threatening serotonin toxicity requires drugs acting by different serotonergic mechanisms concurrently (Gillman 2005 [Ref 29]).
   - **Lithium** (extrapolated from LSD class literature): Lithium + psychedelic combinations have been associated with seizure risk in case reports. This is a class-level concern, not ALD-52-specific. **⚠️ FLAG for human review — see below.**
   - **MAOIs:** Combined with serotonergic activity of LSD, can potentiate effects unpredictably and increase serotonin toxicity risk.
   - **SSRIs/SNRIs:** May blunt or attenuate effects via 5-HT₂A downregulation (Bonson et al. 1996 [Ref 30]). Abrupt interaction; SSRIs don't cause serotonin syndrome at therapeutic doses when combined with psychedelics, but interaction with MAOIs does.

4. **Testing:** ALD-52 can be distinguished from LSD using Ehrlich reagent (both react purple) but require HPLC/NMR for definitive identification. ALD-52 on blotters may be mislabeled.

5. **Contraindications (evidence-based):** Personal/family history of psychosis or schizophrenia; severe cardiovascular disease; concurrent use of serotonergic medications (especially MAOIs, tramadol); pregnancy (insufficient data); operating heavy machinery or driving.

6. **Emergency management:** For severe psychological distress — calm reassurance, safe environment, benzodiazepine administration if needed. For suspected serotonin syndrome — emergency medical care; cyproheptadine (5-HT₂A antagonist) has been used. Antipsychotics (e.g., haloperidol) may worsen outcomes and are generally avoided.

---

## Tolerance & Dependence

### Tolerance

**Mechanism:** Repeated LSD administration causes progressive downregulation of cortical 5-HT₂ receptor density (Buckholtz et al. 1990 [Ref 16]). In C57BL/6J mice, DOI (a 5-HT₂A agonist) showed tolerance after a single administration, with cross-tolerance to LSD via a signaling mechanism independent of β-arrestin-2 (de la Fuente Revenga et al. 2022 [Ref 15]).

**Buildup rate:** Tolerance develops rapidly — essentially immediately after the first dose (consistent with seed data: "almost immediately after ingestion"). This is well-established for LSD class hallucinogens.

**Cross-tolerance:** ALD-52 is expected to share full cross-tolerance with LSD and other 5-HT₂A agonist psychedelics (psilocybin, DMT, mescaline) due to shared mechanism. Seed data cross-tolerance with "psychedelic" class is consistent with published literature.

**Half-life and reset:** The seed data states: tolerance half-life 6 days, full reset 14 days. The Buckholtz et al. (1990 [Ref 16]) study found 5-HT₂ receptor downregulation resolved between 48h and 96h after LSD cessation in rats. In humans, 14-day intervals between doses are commonly observed to restore full sensitivity. **The 6-day half-life / 14-day reset seed values are reasonable and consistent with animal data, though the precise half-life is not formally established in human studies.**

### Dependence

LSD and the psychedelic class are **not habit-forming** and produce no physical dependence or withdrawal syndrome (Nichols 2016 [Ref 7]). The rapid development of tolerance itself serves as a biological deterrent to daily use. No evidence of ALD-52-specific addiction liability exists. The seed data characterization ("not habit-forming") is fully consistent with published literature.

---

## Interactions

### Tramadol — **Dangerous** ⚠️

**Mechanism:** Tramadol inhibits the human serotonin transporter (SERT), elevating synaptic serotonin. Combined with a 5-HT₂A partial agonist (LSD/ALD-52), this creates a multi-mechanism serotonergic assault that can cause **serotonin syndrome** (features: clonus, hyperreflexia, hyperthermia, agitation — life-threatening in severe cases) (Baldo 2018 [Ref 28]; Gillman 2005 [Ref 29]). This interaction is classified as "dangerous" in the seed data, which is consistent with pharmacological evidence. **No ALD-52-specific case reports found; the interaction is inferred from tramadol's established serotonergic mechanism.**

### Cannabis — **Unknown**

The seed data flags the ALD-52–cannabis interaction as "unknown." No published controlled data on ALD-52+cannabis interaction exists. Cannabis (THC) interacts with the serotonergic system and can amplify psychedelic experiences unpredictably. The combination is common among recreational users but has not been formally studied. **User-report-only data indicates the combination intensifies and may prolong ALD-52/LSD effects and can increase anxiety and paranoia.** Labeled unknown in seed data appropriately.

### SSRIs / Serotonergic Antidepressants

Chronic SSRI administration attenuates LSD's subjective effects, likely via 5-HT₂A receptor downregulation (Bonson et al. 1996 [Ref 30]). This applies to ALD-52 by prodrug extension. Patients on SSRIs may experience significantly blunted or absent effects from ALD-52.

### Lithium

Lithium carbonate combined with psychedelics is associated with **increased risk of seizures** in case-report literature. This is a class-level concern, not ALD-52-specific. **No published ALD-52+lithium study exists.** Lithium's effects on serotonergic and glutamatergic tone may interact adversely with 5-HT₂A-mediated excitation.

### MAOIs

MAOIs combined with serotonergic substances can cause dangerous serotonin toxicity (Gillman 2005 [Ref 29]; Rached et al. 2026). Classic psychedelics (LSD class) are thought to be lower risk than empathogens (MDMA), but potentiation of effects is expected.

### CYP Interactions

ALD-52 is metabolized by **CYP1A2 and CYP3A4** (Wagmann et al. 2019 [Ref 2]). Inhibitors of CYP1A2 (fluvoxamine, ciprofloxacin) or CYP3A4 (ritonavir, ketoconazole) could slow ALD-52 deacylation to LSD and thereby alter the onset profile. After conversion, LSD itself is metabolized primarily by **CYP2D6** (Vizeli et al. 2021 [Ref 19]); CYP2D6 poor metabolizers experience ~75% higher LSD AUC and prolonged, intensified effects.

---

## Legal Status

| Jurisdiction | Status | Notes |
|---|---|---|
| United Kingdom | **Class A controlled substance** | Added to UK Misuse of Drugs Act, effective January 7, 2015. ACMD recommendation June 2014 [Ref 39]. |
| Switzerland | **Illegal** | Listed in Swiss controlled substance ordinance (RS 812.121.11), effective March 2018 [Ref 39]. |
| United States | **Legal gray area** | Not specifically scheduled. Subject to Federal Analogue Act (FAA) if used for human consumption — may be treated as a Schedule I controlled substance as an LSD analog. Prosecution depends on intent and context [Ref 39]. |
| Canada | **Unclear** | Not specifically listed in the Controlled Drugs and Substances Act at time of research. May fall under general provisions for LSD analogs [Ref 39]. |
| Australia | **Unclear** | Not specifically detailed in sources found; LSD is Schedule 9 (Prohibited Substance) in Australia's Poisons Standard. ALD-52's status under analog provisions is not confirmed from available sources [Ref 39]. |
| Germany | **Unclear** | Not specifically named in available sources; Germany's NpSG (Neue-psychoaktive-Stoffe-Gesetz) may cover structural analogs [Ref 39]. |
| Finland, Latvia, Romania | Listed as controlled per web sources [Ref 39]. |

**Note:** Legal status changes rapidly for NPS. The generation agent should note these as the status at time of research (April 2026) and recommend users verify current local law.

---

## Clinical Trials

**No clinical trials of ALD-52 are registered on ClinicalTrials.gov.** A search returned zero results. There are no published phase I, II, or III studies of ALD-52 in humans. All human pharmacological data is extrapolated from LSD studies (the active metabolite).

Multiple LSD clinical trials exist (treating depression, anxiety, cluster headache, addiction) but these are not ALD-52 trials. They are relevant to establishing the therapeutic and safety profile of the active metabolite.

---

## Community Feedback Analysis

No community feedback was submitted in Part A2 of the brief.

---

## Gaps & Flags

### 🔴 Safety-Critical Values Requiring Human Review

1. **Tramadol interaction severity (DANGEROUS):** The seed data flags tramadol as "dangerous." This is pharmacologically well-supported (tramadol is a SERT inhibitor; combination with 5-HT₂A agonists can cause serotonin syndrome). However, **no ALD-52+tramadol case report was found** — the danger rating is mechanistic, not case-documented. The rating is appropriate and should be preserved, but the generation agent should note the mechanistic basis rather than citing a case report.

2. **Lithium interaction:** The brief does not list lithium as an interaction, but **class-level evidence for psychedelic+lithium seizure risk exists**. This interaction is absent from the seed data interactions list. **Recommend adding lithium as a dangerous/unknown interaction requiring editorial review.**

3. **Seizure threshold reduction:** Listed in seed data effects taxonomy ("Seizure threshold reduction"). For LSD at standard doses, this is generally theoretical; Nichols & Grob 2018 [Ref 8] documents that most "LSD deaths" were not caused by direct LSD toxicity. However, the effect is listed. Source is primarily class inference. **Flag for human review.**

### 🟡 Data Gaps — Published Literature Absent

4. **ALD-52 specific Ki/EC₅₀ binding values:** Halberstadt et al. (2020 [Ref 1]) confirmed ALD-52 has 1–2 orders of magnitude reduced 5-HT₂A affinity vs. LSD in competitive binding, but did not publish specific Ki values in the available abstract. No other source provides ALD-52 Ki values. The generation agent should use the qualitative finding ("substantially reduced direct 5-HT₂A affinity") and derive the LSD Ki context from the broader literature.

5. **ALD-52 SMILES:** PubChem API returned CID, formula, MW, IUPAC, and InChIKey but not SMILES. A web-retrieved SMILES exists [Ref 35] but is unverified programmatically. The generation agent should use the InChIKey and IUPAC name as the primary chemical identifiers.

6. **No controlled human pharmacology of ALD-52:** Zero published human pharmacokinetic or pharmacodynamic studies of ALD-52 specifically. All human-applicable data comes from LSD studies. This is a fundamental gap — **all dose, duration, and effect data for ALD-52 in humans is either extrapolated from LSD or from user self-reports.**

7. **Onset delay vs. LSD:** ALD-52 may have a slightly slower onset than LSD due to the deacylation step, but no comparative human study exists. The seed data onset (20–40 min) is consistent with LSD onset; whether it should be slightly extended is unknown.

8. **ALD-52 legal status in Germany, Australia, Canada:** Not definitively confirmed from available sources. Partial information obtained — Germany's NpSG and Australia's Poisons Standard may cover ALD-52 as an LSD analog, but specific inclusion needs legal database verification.

9. **"Orange Sunshine" association should be explicitly corrected:** The seed data lists "Orange Sunshine" as a street-name candidate. This association is historically inaccurate — confirmed by Tim Scully's admission that Orange Sunshine was LSD. The generation agent should note this as a **common myth** rather than a factual street name.

### 🟢 Seed Data Verified / Confirmed

- **Chemical class** (Indole, Tryptamine, Ergoline, Lysergamide): Confirmed.
- **Pharmacological class** (5-HT₂A agonist, 5-HT₁A partial agonist, DA receptor agonist): Confirmed for LSD (active form); ALD-52 itself has negligible direct receptor activity.
- **Psychoactive class** (Psychedelic): Confirmed.
- **Primary ROA** (oral): Confirmed. No published data on other ROAs.
- **Toxicity** (negligible acute and chronic): Confirmed with Nichols & Grob 2018 [Ref 8].
- **Dependence** (not habit-forming): Confirmed with Nichols 2016 [Ref 7].
- **Tolerance buildup** (almost immediately): Confirmed.
- **Cross-tolerance** (psychedelic class): Confirmed with de la Fuente Revenga et al. 2022 [Ref 15].
- **Dose/duration data in seed:** Consistent with LSD clinical trial data; acceptable for editorial review as LSD-equivalent estimates.

---

## Source Notes on Key Claims

| Claim | Source |
|---|---|
| ALD-52 synthesized at Sandoz 1957 | Hofmann and Troxler; confirmed by Kavanagh et al. 2025 [Ref 5] and web sources [Ref 26] |
| Orange Sunshine was LSD, not ALD-52 | Scully's admission; court records [Refs 26, 27] |
| ALD-52 is a prodrug for LSD | Halberstadt et al. 2020 [Ref 1] (rat plasma LSD detection) |
| Deacylation catalyzed by CYP1A2/CYP3A4 | Wagmann et al. 2019 [Ref 2] |
| LSD duration 6.7–11h at 25–200 µg | Holze et al. 2021 [Ref 17] |
| LSD Tmax ~1.1h, half-life 2.7h | Holze et al. 2021 [Ref 9] |
| CYP2D6 governs LSD elimination | Vizeli et al. 2021 [Ref 19] |
| Tramadol inhibits SERT → serotonin syndrome risk | Baldo 2018 [Ref 28]; Gillman 2005 [Ref 29] |
| SSRIs attenuate LSD effects | Bonson et al. 1996 [Ref 30] |
| Tolerance via 5-HT₂A downregulation | Buckholtz et al. 1990 [Ref 16]; de la Fuente Revenga et al. 2022 [Ref 15] |
| HPPD associated with LSD | Ayyub et al. 2023 [Ref 20]; Lerner & Lev-Ran 2015 [Ref 21] |
| UK Class A since January 2015 | UK Home Office / ACMD [Ref 39] |
| Switzerland illegal since March 2018 | Swiss RS 812.121.11 [Ref 39] |
| No registered clinical trials for ALD-52 | ClinicalTrials.gov search, 2026 [Step 13] |

ALD-52

Value Provenance

Dosing

oraltrace →

Duration

oral

Safety

Toxicity Profiletrace →

Dependence Profiletrace →

Withdrawal Profiletrace →

Tolerance Profiletrace →

Effects & Profile

Contraindications

Timeline Phases

oral

Dose Tier Summaries

History

Sources

Claim Verification

Coverage & Gaps

Research Trail

oraltrace

Toxicity Profiletrace

Dependence Profiletrace

Withdrawal Profiletrace

Tolerance Profiletrace