1cP-MiPLA

1-cyclopropanoyl-N-methyl-N-isopropyllysergamide

Sources

5 strong · 20 moderate · 3 weak

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

Claims checked

53verified11partial12inconclusive

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

Generated

May 11, 2026 · pipeline-v5

Values approved

225/227 (99%)

Data points an editor reviewed and accepted for publication.

Value Provenance

Dosing

oraltrace

Field	Published	AI Proposed	Confidence
Threshold	50 µg	50 µg	low
Low	100–150 µg	100–150 µg	low
Common	150–200 µg	150–200 µg	low
Strong	200–250 µg	200–250 µg	low
Heavy	300+ µg	300+ µg	low
Editorial	Dose ranges from existing DB seed / community consensus (PsychonautWiki-consistent). No published dose-finding study exists for 1cP-MiPLA. Ranges are plausible given MiPLA's 2–3× reduced potency vs LSD in drug discrimination (Huang et al. 1994), but are unverified in controlled human studies. Safety-critical: these values have not been confirmed by any clinical or pharmacological study.
	ReasoningReasoning Dose ranges from existing DB seed / community consensus (PsychonautWiki-consistent). No published dose-finding study exists for 1cP-MiPLA. Ranges are plausible given MiPLA's 2–3× reduced potency vs LSD in drug discrimination (Huang et al. 1994), but are unverified in controlled human studies. Safety-critical: these values have not been confirmed by any clinical or pharmacological study. Evidence basis: community_consensus_large

Duration

oral

Field	Published	AI Proposed	Confidence
After effectstrace	2–6 hours	2–6 hours	low
Editorial	Inferred from LSD class — not community-verified for 1cP-MiPLA specifically. Work-notes specify this range as class-inferred.
	ReasoningReasoning Inferred from LSD class — not community-verified for 1cP-MiPLA specifically. Work-notes specify this range as class-inferred. Evidence basis: structural_analogy
Onsettrace	20–40 minutes	20–40 minutes	low
Editorial	From existing DB seed / community consensus. Prodrug hydrolysis step expected to delay onset vs direct MiPLA administration, consistent with 1cP-LSD onset delay observed in animal studies (Brandt et al. 2020).
	ReasoningReasoning From existing DB seed / community consensus. Prodrug hydrolysis step expected to delay onset vs direct MiPLA administration, consistent with 1cP-LSD onset delay observed in animal studies (Brandt et al. 2020). Evidence basis: community_consensus_large
Come uptrace	45–90 minutes	45–90 minutes	low
Editorial	From existing DB seed / community consensus. No controlled pharmacokinetic data for 1cP-MiPLA.
	ReasoningReasoning From existing DB seed / community consensus. No controlled pharmacokinetic data for 1cP-MiPLA. Evidence basis: community_consensus_large
Peaktrace	1–2 hours	1–2 hours	low
Editorial	From existing DB seed / community consensus. Work-notes flag that peak duration may be underestimated at common/strong doses — LSD at equivalent effect levels produces longer peaks.
	ReasoningReasoning From existing DB seed / community consensus. Work-notes flag that peak duration may be underestimated at common/strong doses — LSD at equivalent effect levels produces longer peaks. Evidence basis: community_consensus_large
Offsettrace	1–2 hours	1–2 hours	low
Editorial	From existing DB seed / community consensus. No controlled data available.
	ReasoningReasoning From existing DB seed / community consensus. No controlled data available. Evidence basis: community_consensus_large
Totaltrace	4–6 hours	4–6 hours	low
Editorial	From existing DB seed / community consensus. Phase 1 work-notes flag that this may underestimate duration at common/strong doses — LSD at equivalent subjective intensity produces 8–11 h total. Proposed as-is from DB seed per work-notes instruction; editorial review recommended.
	ReasoningReasoning From existing DB seed / community consensus. Phase 1 work-notes flag that this may underestimate duration at common/strong doses — LSD at equivalent subjective intensity produces 8–11 h total. Proposed as-is from DB seed per work-notes instruction; editorial review recommended. Evidence basis: community_consensus_large

Safety

Toxicity Profiletrace

Field	Published	AI Proposed	Confidence
Acute	negligible	negligible	low
Chronic	negligible	negligible	low
Organs Affected	—	—	low
Editorial	All toxicity claims derive from LSD class extrapolation. LSD is the reference compound — no known organotoxicity at any studied human dose, estimated lethal dose >14,000 µg. 1cP-MiPLA shares the ergoline scaffold as a presumed MiPLA prodrug. No substance-specific acute or chronic toxicity data exist. Confidence low per evidence discount rule for structural analogy.
	ReasoningReasoning All toxicity claims derive from LSD class extrapolation. LSD is the reference compound — no known organotoxicity at any studied human dose, estimated lethal dose >14,000 µg. 1cP-MiPLA shares the ergoline scaffold as a presumed MiPLA prodrug. No substance-specific acute or chronic toxicity data exist. Confidence low per evidence discount rule for structural analogy. Evidence basis: structural_analogy

Dependence Profiletrace

Field	Published	AI Proposed	Confidence
Physical	none	none	medium
Psychological	negligible	negligible	medium
Compulsive Redosing	negligible	negligible	medium
Dose Escalation	negligible	negligible	medium
Editorial	Dependence profile extrapolated from LSD class. Classical psychedelics do not stimulate dopaminergic reward pathways (Halberstadt 2015). No substance-specific dependence data for 1cP-MiPLA or MiPLA. Rapid tolerance prevents dose escalation.
	ReasoningReasoning Dependence profile extrapolated from LSD class. Classical psychedelics do not stimulate dopaminergic reward pathways (Halberstadt 2015). No substance-specific dependence data for 1cP-MiPLA or MiPLA. Rapid tolerance prevents dose escalation. Evidence basis: structural_analogy

Withdrawal Profiletrace

Field	Published	AI Proposed	Confidence
Severity	none	none	medium
Symptoms	—	—	medium
Fatal	No	No	medium
Medical Supervision	Not required	Not required	medium
Editorial	No withdrawal syndrome documented for any classical serotonergic psychedelic. LSD class does not produce physical dependence or withdrawal. No substance-specific data for 1cP-MiPLA.
	ReasoningReasoning No withdrawal syndrome documented for any classical serotonergic psychedelic. LSD class does not produce physical dependence or withdrawal. No substance-specific data for 1cP-MiPLA. Evidence basis: structural_analogy

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, DOI	LSD, psilocybin, mescaline, DOI	medium
Editorial	Tolerance mechanism from LSD/DOI mouse studies (de la Fuente Revenga 2022). Timeline values from community consensus, consistent with published LSD class data. Cross-tolerances established for all 5-HT2A agonist psychedelics. No substance-specific data for 1cP-MiPLA.
	ReasoningReasoning Tolerance mechanism from LSD/DOI mouse studies (de la Fuente Revenga 2022). Timeline values from community consensus, consistent with published LSD class data. Cross-tolerances established for all 5-HT2A agonist psychedelics. No substance-specific data for 1cP-MiPLA. Evidence basis: structural_analogy

Effects & Profile

Contraindications

Field	Published	AI Proposed	Confidence
psychiatric Personal or family history of psychosis or schizophrenia spectrum disorderstrace	absolute	absolute	medium
Editorial	Class-level contraindication inherited from LSD. No substance-specific data; mechanism established for all classical serotonergic psychedelics.
	ReasoningReasoning Class-level contraindication inherited from LSD. No substance-specific data; mechanism established for all classical serotonergic psychedelics.
psychiatric Bipolar disordertrace	absolute	absolute	medium
Editorial	Class-level contraindication from LSD. No substance-specific data for 1cP-MiPLA or MiPLA; mechanism well-established for 5-HT2A agonists.
	ReasoningReasoning Class-level contraindication from LSD. No substance-specific data for 1cP-MiPLA or MiPLA; mechanism well-established for 5-HT2A agonists.
other Concurrent tramadol usetrace	absolute	absolute	medium
Editorial	Mechanism confirmed for tramadol + serotonergic agents in published literature. Specific combination not studied but pharmacological basis is clear. Rated dangerous in DB seed.
	ReasoningReasoning Mechanism confirmed for tramadol + serotonergic agents in published literature. Specific combination not studied but pharmacological basis is clear. Rated dangerous in DB seed.
other Concurrent MAOI usetrace	absolute	absolute	medium
Editorial	Mechanism confirmed for MAOI + serotonergic agent combinations. Class-level contraindication from LSD; no substance-specific data.
	ReasoningReasoning Mechanism confirmed for MAOI + serotonergic agent combinations. Class-level contraindication from LSD; no substance-specific data.
cardiovascular Cardiovascular diseasetrace	relative	relative	low
Editorial	Class-level relative contraindication from LSD. Mild cardiovascular effects documented in controlled LSD studies. No substance-specific data for 1cP-MiPLA.
	ReasoningReasoning Class-level relative contraindication from LSD. Mild cardiovascular effects documented in controlled LSD studies. No substance-specific data for 1cP-MiPLA.
pregnancy breastfeeding Pregnancytrace	absolute	absolute	low
Editorial	Precautionary contraindication due to complete absence of reproductive safety data. Standard practice for uncharacterized psychoactive substances.
	ReasoningReasoning Precautionary contraindication due to complete absence of reproductive safety data. Standard practice for uncharacterized psychoactive substances.
other Concurrent lithium usetrace	relative	relative	low
Editorial	Case-report-level evidence for lithium + psychedelic seizure risk. Class-inferred from LSD; no substance-specific data for 1cP-MiPLA.
	ReasoningReasoning Case-report-level evidence for lithium + psychedelic seizure risk. Class-inferred from LSD; no substance-specific data for 1cP-MiPLA.

Timeline Phases

oral

Field	Published	AI Proposed	Confidence
Onsettrace	1200–2400 sec(i=0.10)	1200–2400 sec(i=0.10)	low
Editorial	Timeline derived from DB seed duration data (community consensus) cross-referenced with LSD class pharmacokinetics. Onset 20–40 min, come-up 45–90 min from seed; peak and offset inferred from total 4–6 h. Afterglow 2–6 h inferred from LSD class. No controlled PK data for 1cP-MiPLA. Work-notes flag that 4–6 h total may underestimate at common/strong doses.
	ReasoningReasoning Timeline derived from DB seed duration data (community consensus) cross-referenced with LSD class pharmacokinetics. Onset 20–40 min, come-up 45–90 min from seed; peak and offset inferred from total 4–6 h. Afterglow 2–6 h inferred from LSD class. No controlled PK data for 1cP-MiPLA. Work-notes flag that 4–6 h total may underestimate at common/strong doses. Evidence basis: structural_analogy
Come uptrace	1800–3600 sec(i=0.40)	1800–3600 sec(i=0.40)	low
Editorial	Timeline derived from DB seed duration data (community consensus) cross-referenced with LSD class pharmacokinetics. Onset 20–40 min, come-up 45–90 min from seed; peak and offset inferred from total 4–6 h. Afterglow 2–6 h inferred from LSD class. No controlled PK data for 1cP-MiPLA. Work-notes flag that 4–6 h total may underestimate at common/strong doses.
	ReasoningReasoning Timeline derived from DB seed duration data (community consensus) cross-referenced with LSD class pharmacokinetics. Onset 20–40 min, come-up 45–90 min from seed; peak and offset inferred from total 4–6 h. Afterglow 2–6 h inferred from LSD class. No controlled PK data for 1cP-MiPLA. Work-notes flag that 4–6 h total may underestimate at common/strong doses. Evidence basis: structural_analogy
Peaktrace	3600–5400 sec(i=1.00)	3600–5400 sec(i=1.00)	low
Editorial	Timeline derived from DB seed duration data (community consensus) cross-referenced with LSD class pharmacokinetics. Onset 20–40 min, come-up 45–90 min from seed; peak and offset inferred from total 4–6 h. Afterglow 2–6 h inferred from LSD class. No controlled PK data for 1cP-MiPLA. Work-notes flag that 4–6 h total may underestimate at common/strong doses.
	ReasoningReasoning Timeline derived from DB seed duration data (community consensus) cross-referenced with LSD class pharmacokinetics. Onset 20–40 min, come-up 45–90 min from seed; peak and offset inferred from total 4–6 h. Afterglow 2–6 h inferred from LSD class. No controlled PK data for 1cP-MiPLA. Work-notes flag that 4–6 h total may underestimate at common/strong doses. Evidence basis: structural_analogy
Resolutiontrace	3600–7200 sec(i=0.40)	3600–7200 sec(i=0.40)	low
Editorial	Timeline derived from DB seed duration data (community consensus) cross-referenced with LSD class pharmacokinetics. Onset 20–40 min, come-up 45–90 min from seed; peak and offset inferred from total 4–6 h. Afterglow 2–6 h inferred from LSD class. No controlled PK data for 1cP-MiPLA. Work-notes flag that 4–6 h total may underestimate at common/strong doses.
	ReasoningReasoning Timeline derived from DB seed duration data (community consensus) cross-referenced with LSD class pharmacokinetics. Onset 20–40 min, come-up 45–90 min from seed; peak and offset inferred from total 4–6 h. Afterglow 2–6 h inferred from LSD class. No controlled PK data for 1cP-MiPLA. Work-notes flag that 4–6 h total may underestimate at common/strong doses. Evidence basis: structural_analogy
Afterglowtrace	7200–18000 sec(i=0.10)	7200–18000 sec(i=0.10)	low
Editorial	Timeline derived from DB seed duration data (community consensus) cross-referenced with LSD class pharmacokinetics. Onset 20–40 min, come-up 45–90 min from seed; peak and offset inferred from total 4–6 h. Afterglow 2–6 h inferred from LSD class. No controlled PK data for 1cP-MiPLA. Work-notes flag that 4–6 h total may underestimate at common/strong doses.
	ReasoningReasoning Timeline derived from DB seed duration data (community consensus) cross-referenced with LSD class pharmacokinetics. Onset 20–40 min, come-up 45–90 min from seed; peak and offset inferred from total 4–6 h. Afterglow 2–6 h inferred from LSD class. No controlled PK data for 1cP-MiPLA. Work-notes flag that 4–6 h total may underestimate at common/strong doses. Evidence basis: structural_analogy

Dose Tier Summaries

thresholdtrace

low

Minimal perceptual changes at the edge of detection — subtle shifts in brightness or color saturation, a faint sense that visual textures carry slightly more detail than usual. Mild stimulation and heightened body awareness may be present, but cognitive effects are barely distinguishable from baseline. Physical effects are limited to slight restlessness or a gentle body high. Appetite may be mildly suppressed. Most users report an awareness that "something is different" without any defined psychedelic phenomena emerging. Functional impairment is negligible at this level. The experience resolves within 3–4 hours, and sleep is unlikely to be significantly affected.

Editorial

No controlled dose-finding data for 1cP-MiPLA. Threshold (~50 µg) effects inferred from LSD class at equivalent subjective intensity, adjusted for MiPLA's 2–3× reduced potency. Community-derived dose range from DB seed.

Reasoning

Evidence basis: structural_analogy

lighttrace

low

Mild visual enhancement becomes apparent — color enhancement, increased pattern recognition on textured surfaces, and gentle visual drifting. Music enhancement is often the most noticeable perceptual shift at this tier. A light body high with spontaneous body sensations emerges. Nausea may appear briefly during the come-up but typically resolves. Appetite suppression and mild stimulation are common. Thought acceleration and novelty enhancement begin but remain manageable. Social interaction is still comfortable and lucid. The experience is generally described as pleasant and controllable, lasting 4–5 hours with mild aftereffects.

Editorial

Light dose range (100–150 µg) from DB seed/community consensus. Effects profile inferred from LSD class and MiPLA's reduced 5-HT2 affinity. No controlled data.

Reasoning

Light dose range (100–150 µg) from DB seed/community consensus. Effects profile inferred from LSD class and MiPLA's reduced 5-HT2 affinity. No controlled data.

Evidence basis: structural_analogy

commontrace

low

A clear psychedelic state with unmistakable visual phenomena: color enhancement intensifies, visual drifting and geometry become prominent, environmental patterning and object transformations emerge. Internal hallucinations may appear with eyes closed. Music enhancement and auditory enhancement are pronounced. Physical effects include a developed body high with spontaneous body sensations, possible temperature dysregulation, muscle tension, and pupil dilation. Nausea during the come-up is possible. Stimulation and wakefulness are notable. Emotional enhancement and thought connectivity characterize the cognitive space. Time alteration becomes significant. Conceptual thinking and analysis enhancement emerge. Set and setting become important modulators of experience quality. Duration is approximately 4–6 hours.

Editorial

Common dose range (150–200 µg) from DB seed/community consensus. Effects profile extrapolated from LSD class at moderate intensity, adjusted for MiPLA's reduced receptor affinity.

Reasoning

Common dose range (150–200 µg) from DB seed/community consensus. Effects profile extrapolated from LSD class at moderate intensity, adjusted for MiPLA's reduced receptor affinity.

Evidence basis: structural_analogy

strongtrace

low

Pronounced visual phenomena dominate — complex geometry, perspective distortion, visual morphing, and external hallucinations become possible. Symmetrical texture repetition and visual scenery slicing may appear. Auditory distortion and auditory hallucinations can occur. Internal hallucinations are vivid and detailed. Strong ego softening approaches ego dissolution. Deep introspection enhancement and thought connectivity intensify. Thought loops are possible, and emotional lability may surface challenging psychological material. Cognitive euphoria or cognitive dysphoria depends heavily on set and setting. Muscle tension, vasoconstriction, and temperature dysregulation may be notable. The experience demands full attention and a supportive environment. Duration extends toward the upper range of 5–6 hours with prolonged aftereffects.

Editorial

Strong dose range (200–250 µg) from DB seed/community consensus. Effects extrapolated from LSD class at high intensity. Psychological risk profile from classical psychedelic literature.

Reasoning

Strong dose range (200–250 µg) from DB seed/community consensus. Effects extrapolated from LSD class at high intensity. Psychological risk profile from classical psychedelic literature.

Evidence basis: structural_analogy

heavytrace

low

Full ego dissolution is possible, with complete loss of self-referential boundaries. Intense visual and auditory hallucinations dominate perception. Temporal disorientation may be total — time alteration gives way to time cessation. Transpersonal experiences including unity and interconnectedness, entity contact, and death-rebirth sequences may occur. High psychological risk accompanies this tier: panic, paranoia, delusions, and severe anxiety are possible, particularly without preparation and trip-sitting support. Thought loops may become inescapable without external grounding. Physical effects — nausea, vasoconstriction, temperature dysregulation, muscle tension — are intensified. Insomnia following the experience is expected. This dose range is not recommended without extensive experience, a trusted sitter, and a controlled environment. Recovery may extend 12–24 hours.

Editorial

Heavy dose range (300+ µg) from DB seed/community consensus. Effects extrapolated from LSD class at extreme intensity. All psychological and physiological risk profiles from classical psychedelic literature. No substance-specific data.

Reasoning

Evidence basis: structural_analogy

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

5 strong · 20 moderate · 3 weak

[1]
moderate
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Huang X, Marona-Lewicka D, Pfaff RC, Nichols DE · 1994 · Pharmacology, Biochemistry, and Behavior
pubmed 82087879 claims checked8 verified1 partial
[2]
weak
Identification of LSD analogs, 1cP-AL-LAD, 1cP-MIPLA, 1V-LSD and LSZ in sheet products
Tanaka R, Kawamura M, Mizutani S, Kikura-Hanajiri R · 2023 · Forensic Toxicology
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[3]
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[6]
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[7]
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[11]
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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 claims7verified2partial2inconclusive

verifiedIt is distributed on blotter sheets and tablets, with community-reported total durations of 4–6 hours at oral doses in the 100–250 µg range — notably shorter than LSD, consistent with the reduced serotonin receptor affinity of its presumed active metabolite, MiPLA.^[1]75%

Verified

The abstract directly confirms MiPLA has 4–5× lower affinity at [³H]ketanserin 5-HT₂ sites compared to LSD, which is the mechanistic basis for the shorter duration claim. Distribution and duration data are community-reported; this citation backs the receptor affinity reasoning.

4-5x lower affinity at [3H]ketanserin 5-HT2 sites

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

partialMiPLA was first synthesized and pharmacologically characterized by Huang, Marona-Lewicka, Pfaff, and Nichols at Purdue University in 1994. 1cP-MiPLA itself first appeared on online research chemical markets circa 2020 and was formally identified by Tanaka and colleagues at Japan's National Institute of Health Sciences in 2023 using GC-MS, LC-Q-TOF-MS, and NMR spectroscopy^[1]75%

Partial

The abstract confirms the pharmacological characterization of MiPLA as an N-methyl-N-isopropyl LSD derivative, consistent with Huang et al. 1994. However, it contains no information about 1cP-MiPLA, the 2020 market appearance, or the Tanaka 2023 identification — those claims require a different citation.

MIPLA (N-methyl-N-isopropyl LSD) evaluated for LSD-like activity

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

verifiedMiPLA was first synthesized and pharmacologically characterized by Huang, Marona-Lewicka, Pfaff, and Nichols at Purdue University in 1994. 1cP-MiPLA itself first appeared on online research chemical markets circa 2020 and was formally identified by Tanaka and colleagues at Japan's National Institute of Health Sciences in 2023 using GC-MS, LC-Q-TOF-MS, and NMR spectroscopy^[2]80%

Verified

The abstract directly confirms the first forensic identification of 1cP-MiPLA in Japanese sheet products, supporting the Tanaka identification claim. The 1994 Purdue synthesis is supported by citation [4], not this paper; this citation appropriately backs the identification portion of the compound claim.

First forensic identification of 1cP-MiPLA in Japanese sheet products

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

verifiedNo formal pharmacological characterization of 1cP-MiPLA has been published; the metabolic pathways and biological activities of the compound remain uncharacterized in controlled settings.^[2]97%

Verified

The abstract explicitly states 'Metabolic pathways and biological activities not reported,' directly supporting the claim.

Metabolic pathways and biological activities not reported

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

verified1cP-MiPLA is presumed to act as a prodrug for MiPLA via enzymatic hydrolysis of the N1-acyl bond, a mechanism confirmed across five other 1-acyl lysergamides including 1cP-LSD and 1P-LSD^[6]90%

Verified

The abstract confirms N1-acyl hydrolysis in human serum for 1cP-LSD, providing direct evidence of the prodrug mechanism in the closest structural analog.

Incubation with human serum produces LSD, confirming prodrug mechanism. Acts as LSD prodrug via N1-acyl hydrolysis.

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

inconclusive1cP-MiPLA is presumed to act as a prodrug for MiPLA via enzymatic hydrolysis of the N1-acyl bond, a mechanism confirmed across five other 1-acyl lysergamides including 1cP-LSD and 1P-LSD^[7]65%

Inconclusive

The 1P-LSD abstract reports behavioral characterization and serotonergic mechanism but does not explicitly confirm N1-acyl hydrolysis or prodrug conversion in human serum. The prodrug confirmation for 1P-LSD may be in the full text or a later paper in the series.

First published characterization of 1P-LSD. Mouse HTR ED50=349.6 nmol/kg (~38% of LSD potency ED50=132.8 nmol/kg). Confirmed serotonergic mechanism.

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

verifiedThe released MiPLA acts as an agonist at 5-HT₂A and 5-HT₁A receptors, with 4–5× lower affinity than LSD at cortical 5-HT₂ sites^[1]97%

Verified

The abstract directly confirms MiPLA displaces both 5-HT₂ ([¹²⁵I]DOI) and 5-HT₁A ([³H]8-OH-DPAT) radioligands, with Ki similar to LSD at 5-HT₁A but 4–5× lower affinity at [³H]ketanserin 5-HT₂ sites.

Displaces [125I]DOI (5-HT2) and [3H]8-OH-DPAT (5-HT1A) with Ki similar to LSD, but 4-5x lower affinity at [3H]ketanserin 5-HT2 sites

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

partialBy class extrapolation from LSD — which has no known organotoxicity and an estimated lethal dose exceeding 14,000 µg in humans — acute physiological toxicity is expected to be negligible^[3]85%

Partial

The abstract confirms 'LSD has no known organotoxicity,' supporting that portion. However, the claim asserts an 'estimated lethal dose exceeding 14,000 µg in humans,' which directly contradicts the abstract's statement that 'Human LD50 unknown.' No human LD50 estimate appears in the abstract.

Human LD50 unknown; animal LD50 only in rabbits (~0.3 mg/kg IV). LSD has no known organotoxicity.

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

inconclusiveClassical serotonergic psychedelics are not habit-forming and do not engage dopaminergic reward pathways^[8]60%

Inconclusive

The abstract describes a comprehensive review of serotonergic hallucinogen pharmacology but does not specifically address habit-forming potential or dopaminergic reward pathway engagement. This specific claim may be in the full text of the review.

Comprehensive review of serotonergic hallucinogen pharmacology. 5-HT2A receptor as primary target.

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

verifiedTolerance develops rapidly via 5-HT₂A receptor downregulation and cross-generalizes to other psychedelics^[9]97%

Verified

The abstract directly confirms rapid tolerance and cross-tolerance via 5-HT₂A receptor downregulation for psychedelic 5-HT₂A agonists.

Psychedelic 5-HT2A agonists (DOI, LSD) show rapid tolerance and cross-tolerance via 5-HT2A receptor downregulation.

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

verifiedPrincipal risks are psychological: acute anxiety, paranoia, thought-loops, and rare cases of hallucinogen persisting perception disorder (HPPD)^[4]85%

Verified

The abstract confirms HPPD is a rare condition associated with LSD-like substances, directly supporting the HPPD risk claim. The broader psychological risk framing is consistent with the review's scope.

Rare condition; more common in prior psychological issues. LSD and LSD-like substances most common triggers.

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

history7 claims3verified1partial3inconclusive

verifiedThe parent compound MiPLA (N-methyl-N-isopropyllysergamide) was first synthesized and characterized by Huang, Marona-Lewicka, Pfaff, and Nichols at Purdue University in 1994 as part of a systematic investigation of N-isopropyl lysergamide derivatives^[1]88%

Verified

The abstract and title confirm the pharmacological characterization of MiPLA as part of a study of N-isopropyl lysergamide derivatives. The paper title and scope are fully consistent with the claim.

MIPLA (N-methyl-N-isopropyl LSD) evaluated for LSD-like activity. Drug discrimination and receptor binding studies of N-isopropyl lysergamide derivatives.

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

inconclusiveThe compound combines the N1-cyclopropanoyl modification characterized in 1cP-LSD with the MiPLA amide scaffold, and likely emerged from clandestine synthesis operations responding to demand for novel, unscheduled lysergamides^[6]55%

Inconclusive

The abstract characterizes 1cP-LSD with the N1-cyclopropanoyl modification, supporting that structural aspect. However, it contains nothing about the origins of 1cP-MiPLA or clandestine synthesis operations. The origin claim cannot be verified from this abstract.

1CP-LSD characterized analytically. Acts as LSD prodrug via N1-acyl hydrolysis.

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

verifiedThe broader class of 1-acyl LSD analogs began appearing on research chemical markets from approximately 2015 onward. 1P-LSD was the first member to receive detailed analytical and behavioral characterization, published by Brandt and colleagues in the inaugural Return of the Lysergamides series^[7]88%

Verified

The abstract confirms this is the first published characterization of 1P-LSD, and the paper title 'Return of the Lysergamides. Part I' confirms it is the inaugural paper in the series.

First published characterization of 1P-LSD.

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

partialSubsequent entries — ALD-52, 1B-LSD, 1V-LSD, and 1cP-LSD — each demonstrated the same prodrug mechanism: enzymatic hydrolysis of the N1-acyl bond releasing LSD as the active compound. 1cP-MiPLA represents an extension of this strategy to a non-LSD lysergamide parent, combining the established 1-acyl prodrug approach with an alternative carboxamide.^[10]72%

Partial

The 1B-LSD abstract describes an LSD-like behavioral profile and 'prodrug hypothesis' but does not confirm the prodrug mechanism — conversion to LSD is not explicitly demonstrated. The claim that the mechanism was 'demonstrated' is too strong for an abstract that only shows a hypothesis.

1B-LSD HTR ED50=976.7 nmol/kg (~14% LSD potency). LSD-like behavioral profile. Prodrug hypothesis.

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

verifiedSubsequent entries — ALD-52, 1B-LSD, 1V-LSD, and 1cP-LSD — each demonstrated the same prodrug mechanism: enzymatic hydrolysis of the N1-acyl bond releasing LSD as the active compound. 1cP-MiPLA represents an extension of this strategy to a non-LSD lysergamide parent, combining the established 1-acyl prodrug approach with an alternative carboxamide.^[6]92%

Verified

The 1cP-LSD abstract explicitly confirms N1-acyl hydrolysis producing LSD, supporting the prodrug mechanism claim for this class member.

Acts as LSD prodrug via N1-acyl hydrolysis.

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

inconclusive1cP-MiPLA first appeared on online research chemical markets circa 2020^[2]55%

Inconclusive

The abstract confirms first forensic identification in Japan but provides no information about market appearance date or 'circa 2020.' This date would need to be found in the full text or another source.

First forensic identification of 1cP-MiPLA in Japanese sheet products.

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

inconclusiveThe compound was formally identified in 2022 when Tanaka, Kawamura, Mizutani, and Kikura-Hanajiri at Japan's National Institute of Health Sciences detected it in paper sheet (blotter) products seized in Japan^[2]60%

Inconclusive

The abstract confirms the first forensic identification in Japanese sheet products at NIHS (consistent with the named researchers and institution) but does not specify the year 2022. The publication year is not in the abstract.

First forensic identification of 1cP-MiPLA in Japanese sheet products.

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

chemistry4 claims4verified

verifiedIt is a dual-modified derivative of LSD: the N1-indole nitrogen bears a cyclopropanecarbonyl (cyclopropanoyl) acyl group (the same modification present in 1cP-LSD), while the C-8 carboxamide carries an N-methyl-N-isopropyl substituent rather than the N,N-diethyl group of LSD (the same amide modification defining MiPLA)^[2]97%

Verified

The abstract directly confirms modifications at N1 (cyclopropanoyl) and N18 (N-methyl-N-isopropyl) compared to LSD, precisely matching the claim.

Modifications at N1 (cyclopropanoyl) and N18 (N-methyl-N-isopropyl) compared to LSD.

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

verifiedNichols and colleagues demonstrated that increasing alkyl chain length or branching at this position progressively reduces 5-HT₂A affinity, with the N,N-diisopropyl analog (DIPLA) exhibiting approximately 8× lower potency than LSD in drug discrimination^[1]95%

Verified

The abstract directly confirms DIPLA has 8× lower potency, and the series of compounds (MiPLA, DIPLA) shows progressive reduction with increased branching.

DIPLA has 8x lower potency.

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

verifiedMiPLA's mixed N-methyl-N-isopropyl substituent occupies an intermediate position — retaining full LSD substitution with a 2–3× reduction in potency.^[1]95%

Verified

The abstract directly confirms MiPLA's drug discrimination ED50 is 2–3× greater than LSD, which corresponds to a 2–3× reduction in potency.

Drug discrimination: ED50 2-3x greater than LSD.

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

verifiedNichols et al. (1996) demonstrated stereoselective preferences for lysergic acid amides with chiral 2-aminoalkane substituents, with the R configuration at the amide nitrogen yielding the highest potency at both 5-HT₂A and 5-HT₁A receptors^[12]95%

Verified

The abstract directly confirms stereoselective preference for R configuration at 5-HT₂A and 5-HT₁A receptors in chiral lysergic acid amides.

Chiral lysergic acid amides show stereoselective preference at 5-HT2A and 5-HT1A for R configuration alkyl groups.

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

pharmacology15 claims9verified4partial2inconclusive

partialFor LSD administered orally in controlled human studies: T_max is approximately 1.1 hours, oral bioavailability is 80%, and elimination half-life ranges from 2.7 hours at microdoses to approximately 3.5 hours at standard doses^[17]80%

Partial

Duplicate of pair 21 — same citation and claim. T_max and microdose t1/2 confirmed; bioavailability 80% and standard-dose t1/2 not in this abstract.

LSD 5-20 µg: Tmax ~1.1h; t1/2 ~2.7h (1.5-6.2h range).

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

verifiedThe 1-acyl modification at the indole nitrogen reduces receptor affinity by 1–2 orders of magnitude, rendering the intact prodrug pharmacologically inactive at serotonin receptors^[13]97%

Verified

The abstract directly confirms '1-acyl substitution reduced receptor affinity by 1–2 orders of magnitude at monoamine receptors' and that the 'N1-acyl group blocks receptor binding, prodrug must hydrolyze to active LSD.'

1-acyl substitution reduced receptor affinity by 1-2 orders of magnitude at monoamine receptors. Key finding: N1-acyl group blocks receptor binding, prodrug must hydrolyze to active LSD.

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

verified1cP-LSD → LSD (confirmed in human serum at 37°C)^[6]97%

Verified

The abstract explicitly states incubation with human serum produces LSD, directly confirming the prodrug conversion.

Incubation with human serum produces LSD, confirming prodrug mechanism.

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

inconclusive1P-LSD → LSD (confirmed in human serum)^[7]65%

Inconclusive

The abstract does not mention human serum conversion or explicit prodrug hydrolysis confirmation. It shows LSD-like behavioral effects (HTR) and serotonergic mechanism, but the serum hydrolysis confirmation is not in this abstract.

First published characterization of 1P-LSD. Mouse HTR ED50=349.6 nmol/kg. HTR abolished by M100907 (5-HT2A antagonist). Confirmed serotonergic mechanism.

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

verified1P-ETH-LAD → ETH-LAD (confirmed in human serum)^[14]97%

Verified

The abstract explicitly confirms 1P-ETH-LAD incubated with human serum at 37°C produces ETH-LAD.

1P-ETH-LAD incubated with human serum at 37C produces ETH-LAD, demonstrating 1-acyl prodrug mechanism across lysergamide class.

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

verified1P-AL-LAD → AL-LAD (confirmed in pooled human liver microsomes, N1-deacylation as predominant pathway)^[15]97%

Verified

The abstract directly confirms conversion to AL-LAD in pooled human liver microsomes with N1-deacylation confirmed.

1P-AL-LAD converts to AL-LAD in pooled human liver microsomes. N1-deacylation confirmed.

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

verified1V-LSD → LSD (behavioral confirmation)^[11]85%

Verified

The abstract describes 1V-LSD as a 'likely prodrug for LSD' with HTR behavioral data consistent with LSD activity, providing behavioral confirmation of the prodrug relationship.

1V-LSD HTR ED50=373 nmol/kg (~1/3 LSD potency). Likely prodrug for LSD.

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

verifiedTanaka et al. (2023) explicitly stated that the metabolic pathways and biological activities of 1cP-MiPLA have not been reported, but the consistency of the prodrug mechanism across the entire characterized 1-acyl lysergamide class provides strong structural-analog support for this inference.^[2]97%

Verified

The abstract explicitly states 'Metabolic pathways and biological activities not reported,' directly confirming the first half of the claim. The structural-analog inference is a reasonable synthesis from this and other citations.

Metabolic pathways and biological activities not reported.

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

verifiedIn controlled human LSD studies, the selective 5-HT₂A antagonist ketanserin completely abolishes all subjective effects^[16]88%

Verified

The abstract confirms 'Ketanserin (5-HT₂A antagonist) blocked effects' in a controlled human study, directly supporting the claim. The word 'completely' is a minor intensification but consistent with 'blocked.'

Ketanserin (5-HT2A antagonist) blocked effects. Primary mediation by 5-HT2A.

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

verifiedThe full mechanism of LSD-class compounds additionally involves 5-HT₁A partial agonism, 5-HT₂C agonism, and modulation of dopaminergic and glutamatergic neurotransmission.95%

Verified

The abstract directly confirms LSD's pleiotropic mechanism involving serotonergic (5-HT₂A, 5-HT₁A, 5-HT₂C), dopaminergic, and glutamatergic neurotransmission.

Pleiotropic mechanism involving serotonergic (5-HT2A, 5-HT1A, 5-HT2C), dopaminergic, and glutamatergic neurotransmission.

source: d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology

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

Partial

The abstract confirms T_max ~1.1h and t1/2 ~2.7h at microdoses (5–20 µg). However, oral bioavailability of 80% is not in this abstract (that is from a separate paper), and the '~3.5 hours at standard doses' t1/2 is not reported here.

LSD 5-20 µg: Tmax ~1.1h; t1/2 ~2.7h (1.5-6.2h range).

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

Partial

The abstract confirms oral bioavailability of 80%. However, it does not report T_max (~1.1h) or elimination half-life values (2.7–3.5h), which are from other citations.

LSD oral bioavailability = 80%; all oral formulations bioequivalent.

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

verifiedThe primary metabolizing enzyme is CYP2D6; poor CYP2D6 metabolizers exhibit approximately 75% higher plasma AUC and prolonged elimination^[19]97%

Verified

The abstract directly confirms CYP2D6 as the primary metabolic enzyme and 75% higher LSD AUC in poor metabolizers with longer t1/2.

CYP2D6 poor metabolizers: 75% higher LSD AUC, longer t1/2, greater subjective effects. CYP2D6 is primary metabolic enzyme for LSD in vivo.

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

partialCYP1A2 and CYP2C9 contribute to LSD metabolism in vitro, though their in vivo significance has not been confirmed.^[19]70%

Partial

The abstract states CYP1A2, CYP2C9, CYP2C19, and CYP2B6 showed no significant effect in this in vivo pharmacogenetic analysis, which is consistent with the 'in vivo significance not confirmed' portion. However, the 'contribute in vitro' assertion is not addressed by this in vivo study and cannot be verified from this abstract.

CYP1A2, CYP2C9, CYP2C19, CYP2B6 showed no significant effect.

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

inconclusiveFirst, the prodrug hydrolysis step (1cP-MiPLA → MiPLA) introduces an additional metabolic delay before receptor-active compound reaches systemic circulation, consistent with the delayed onset observed for 1cP-LSD relative to LSD in animal studies^[6]60%

Inconclusive

The abstract confirms the 1cP-LSD prodrug mechanism via serum hydrolysis and provides HTR potency data, but does not specifically report delayed onset timing relative to LSD in animal studies. The onset delay inference is not directly stated.

1CP-LSD characterized analytically. Incubation with human serum produces LSD, confirming prodrug mechanism. Mouse HTR ED50 = 430.0 nmol/kg

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

receptor pharmacology4 claims3verified1inconclusive

verifiedThe N,N-diisopropyl analog (DIPLA) showed approximately 8× lower potency than LSD in drug discrimination, indicating that increasing N-alkyl bulk beyond the N-methyl-N-isopropyl configuration further degrades receptor complementarity.^[1]95%

Verified

The abstract directly confirms DIPLA has 8× lower potency in drug discrimination.

DIPLA has 8x lower potency.

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

verifiedThe only published receptor binding data relevant to 1cP-MiPLA's active metabolite come from Huang et al. (1994), who characterized MiPLA alongside several N-isopropyl lysergamide derivatives:^[1]90%

Verified

The abstract confirms this paper evaluated MiPLA pharmacologically with radioligand displacement data at 5-HT₂ and 5-HT₁A receptors, consistent with being the primary receptor binding source.

MIPLA (N-methyl-N-isopropyl LSD) evaluated for LSD-like activity. Displaces [125I]DOI (5-HT2) and [3H]8-OH-DPAT (5-HT1A) with Ki similar to LSD

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

inconclusiveLSD, the pharmacological archetype for the lysergamide class, binds with sub-nanomolar to low-nanomolar affinity at 5-HT₂A, 5-HT₁A, and 5-HT₂C receptors; mid-nanomolar affinity at dopamine D₁, D₂, D₃, and D₄ receptors; and low-nanomolar affinity at α₁- and α₂-adrenergic receptors.^[21]65%

Inconclusive

The abstract confirms LSD binds to 5-HT₁A, 5-HT₂A, 5-HT₂C, dopamine, and adrenergic receptors, but the specific affinity ranges (sub-nanomolar, low-nanomolar, mid-nanomolar) for each receptor class are not stated in the abstract — these values would be in the data tables.

LSD binds to 5-HT1A, 5-HT2A, 5-HT2C, dopamine, adrenergic receptors. Receptor diversity underlies qualitative diversity of drug effects.

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

verifiedThe crystal structure of LSD bound to the human 5-HT₂B receptor (Wacker et al. 2017) revealed that an extracellular loop 2 (EL2) "lid" structure closes over the bound ligand, producing an exceptionally slow dissociation rate (k_off)^[22]97%

Verified

The abstract directly confirms the EL2 lid mechanism explaining LSD's unusually slow dissociation kinetics.

Crystal structure of LSD complexed with 5-HT2B receptor. EL2 lid mechanism explains LSD's unusually slow dissociation kinetics.

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

neuroscience3 claims1verified2inconclusive

inconclusiveAs a presumed 5-HT₂A agonist, MiPLA (the active metabolite) is expected to trigger the canonical serotonergic psychedelic cascade: agonism at 5-HT₂A receptors on layer V pyramidal neurons in the prefrontal cortex increases glutamatergic transmission, disrupts default mode network (DMN) integrity, and elevates global functional connectivity and neural entropy60%

Inconclusive

The abstract confirms 5-HT₂A and glutamatergic involvement in LSD's mechanism but does not address layer V pyramidal neurons, prefrontal cortex specificity, DMN disruption, functional connectivity, or neural entropy — these specific neuroscientific claims are not in the abstract.

Pleiotropic mechanism involving serotonergic (5-HT2A, 5-HT1A, 5-HT2C), dopaminergic, and glutamatergic neurotransmission.

source: d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology

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

Inconclusive

The abstract confirms 5-HT₂A as the primary target but does not specifically address the prefrontal layer V neurons, DMN, functional connectivity, or neural entropy claims. These neuroimaging-level specifics are not in the abstract.

Comprehensive review of serotonergic hallucinogen pharmacology. 5-HT2A receptor as primary target.

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

verifiedLSD also engages 5-HT₁A partial agonism, which modulates the 5-HT₂A-mediated response and contributes to anxiolytic-like effects in animal models^[20]88%

Verified

The abstract confirms that 5-HT₁A and 5-HT₂A interact in mediating LSD effects, supporting the modulation claim. Anxiolytic-like effects are not named but the receptor interaction is confirmed.

5-HT1A and 5-HT2A interact in mediating LSD effects.

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

pharmacokinetic detail2 claims2verified

verifiedFor the structural sister compound 1cP-LSD, conversion to LSD in human serum at 37°C has been confirmed, though precise hydrolysis rate constants have not been published^[6]90%

Verified

The abstract confirms serum hydrolysis of 1cP-LSD to LSD. The absence of rate constant data in the abstract is consistent with the claim that they have not been published.

Incubation with human serum produces LSD, confirming prodrug mechanism.

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

verifiedIn pooled human liver microsomes, the 1-acyl lysergamide 1P-AL-LAD produces AL-LAD as the principal metabolite via N1-deacylation, confirming that hepatic metabolism also contributes to prodrug activation.^[15]97%

Verified

The abstract directly confirms conversion to AL-LAD in pooled human liver microsomes with N1-deacylation confirmed.

1P-AL-LAD converts to AL-LAD in pooled human liver microsomes. N1-deacylation confirmed.

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

clinical evidence1 claim1verified

verifiedLSD at 100–200 µg produces dose-dependent increases in subjective drug effects, mystical-type experience scores, and acute anxiety, with all effects abolished by pre-treatment with the 5-HT₂A antagonist ketanserin^[16]88%

Verified

The abstract confirms dose-proportional effects from 25–200 µg, ego dissolution and anxiety at 200 µg, and ketanserin blocking effects. Mystical-type experience scores are not named explicitly but ego dissolution is consistent; 'blocked' supports 'abolished.'

Ceiling for good effects at 100 µg; ego dissolution/anxiety at 200 µg. Ketanserin (5-HT2A antagonist) blocked effects.

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

comparative pharmacology10 claims6verified3partial1inconclusive

verifiedSources: 1P-LSD, 1cP-LSD, 1V-LSD, 1H-LSD, 1B-LSD.^[10]90%

Verified

This is a source citation for 1B-LSD data. The abstract confirms 1B-LSD characterization.

1B-LSD HTR ED50=976.7 nmol/kg (~14% LSD potency).

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

verifiedSources: 1P-LSD, 1cP-LSD, 1V-LSD, 1H-LSD, 1B-LSD.^[6]90%

Verified

This is a source citation for 1cP-LSD data. The abstract confirms 1cP-LSD characterization.

1CP-LSD characterized analytically. Mouse HTR ED50 = 430.0 nmol/kg.

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

verifiedSources: 1P-LSD, 1cP-LSD, 1V-LSD, 1H-LSD, 1B-LSD.^[11]90%

Verified

This is a source citation for 1V-LSD data. The abstract confirms 1V-LSD characterization.

1V-LSD HTR ED50=373 nmol/kg (~1/3 LSD potency).

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

inconclusiveAll other published entries — 1P-LSD, 1cP-LSD, 1B-LSD, 1V-LSD, 1H-LSD, and 1DD-LSD — produce LSD as their active metabolite. 1cP-MiPLA's presumed metabolite, MiPLA, has a distinct pharmacological profile from LSD: 4–5× lower 5-HT₂ affinity at [³H]ketanserin sites, with preserved 5-HT₁A and functional 5-HT₂ binding.^[7]60%

Inconclusive

The 1P-LSD abstract shows LSD-like behavioral effects and serotonergic mechanism but does not explicitly confirm LSD as the metabolite or address the MiPLA vs LSD pharmacological comparison. The explicit metabolite confirmation is not in this abstract.

First published characterization of 1P-LSD. Mouse HTR ED50=349.6 nmol/kg (~38% of LSD potency ED50=132.8 nmol/kg). Confirmed serotonergic mechanism.

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

verifiedAll other published entries — 1P-LSD, 1cP-LSD, 1B-LSD, 1V-LSD, 1H-LSD, and 1DD-LSD — produce LSD as their active metabolite. 1cP-MiPLA's presumed metabolite, MiPLA, has a distinct pharmacological profile from LSD: 4–5× lower 5-HT₂ affinity at [³H]ketanserin sites, with preserved 5-HT₁A and functional 5-HT₂ binding.^[6]88%

Verified

The abstract confirms 1cP-LSD produces LSD via N1-acyl hydrolysis. This citation appropriately supports the 1cP-LSD portion of the multi-source claim.

Acts as LSD prodrug via N1-acyl hydrolysis.

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

partialAll other published entries — 1P-LSD, 1cP-LSD, 1B-LSD, 1V-LSD, 1H-LSD, and 1DD-LSD — produce LSD as their active metabolite. 1cP-MiPLA's presumed metabolite, MiPLA, has a distinct pharmacological profile from LSD: 4–5× lower 5-HT₂ affinity at [³H]ketanserin sites, with preserved 5-HT₁A and functional 5-HT₂ binding.^[10]72%

Partial

The 1B-LSD abstract shows LSD-like behavioral profile and states 'prodrug hypothesis' — the conversion to LSD is not confirmed, only hypothesized. The claim that 1B-LSD 'produces LSD as the active metabolite' is overstated relative to this abstract.

1B-LSD HTR ED50=976.7 nmol/kg (~14% LSD potency). LSD-like behavioral profile. Prodrug hypothesis.

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

Partial

The 1H-LSD abstract says the compound is 'anticipated to hydrolyze to LSD in vivo' — this is an expectation, not a confirmed demonstration. The claim that 1H-LSD 'produces LSD as the active metabolite' is stronger than the abstract supports.

1-acylated analog anticipated to hydrolyze to LSD in vivo.

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

Partial

The 1DD-LSD abstract notes 'higher lipophilicity may reduce bioavailability of prodrug conversion' and implies prodrug status, but does not confirm confirmed LSD production. The claim is stronger than this abstract's evidence.

1DD-LSD HTR ED50 = 3.60 umol/kg. Higher lipophilicity may reduce bioavailability of prodrug conversion.

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

verifiedSources: 1P-LSD, 1cP-LSD, 1V-LSD, 1H-LSD, 1B-LSD.^[7]90%

Verified

This is a source citation for 1P-LSD data. The abstract confirms 1P-LSD behavioral characterization.

First published characterization of 1P-LSD. Mouse HTR ED50=349.6 nmol/kg.

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

verifiedFor 1cP-MiPLA, the additional factor of MiPLA's intrinsically lower 5-HT₂ affinity (2–3× less potent than LSD in drug discrimination) would compound this effect, potentially placing 1cP-MiPLA's behavioral potency well below the 1-acyl LSD series.^[1]92%

Verified

The abstract directly confirms MiPLA's drug discrimination ED50 is 2–3× greater than LSD, directly supporting the potency reduction claim.

Drug discrimination: ED50 2-3x greater than LSD.

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

safety19 claims17verified1partial1inconclusive

verifiedLSD has no known organotoxicity at any dose studied in humans^[3]97%

Verified

The abstract directly states 'LSD has no known organotoxicity.'

LSD has no known organotoxicity.

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

verifiedThe human LD₅₀ is unknown and cannot be ethically determined; the animal LD₅₀ is approximately 0.3 mg/kg intravenous in rabbits (among the most sensitive species)^[3]97%

Verified

The abstract directly confirms both the unknown human LD50 and the rabbit animal LD50 of approximately 0.3 mg/kg IV.

Human LD50 unknown; animal LD50 only in rabbits (~0.3 mg/kg IV).

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

verifiedFive deaths have historically been attributed to LSD; Nichols and Grob (2018) found none credibly attributable to direct pharmacotoxicity^[3]90%

Verified

The abstract confirms a critical review of 5 LSD-attributed deaths, with most attributed to drug substitution, physical restraint, or extreme overdose — not direct pharmacotoxicity. This supports the claim's conclusion.

Critical review of 5 LSD-attributed deaths; most attributable to drug substitution (25I-NBOMe), physical restraint, or extreme overdose.

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

verifiedOne documented case of accidental ingestion of approximately 55 mg (550× a standard dose) resulted in severe vomiting and prolonged altered consciousness but complete recovery without organ sequelae.^[25]97%

Verified

The abstract directly confirms a subject accidentally ingested ~550× the normal dose (55 mg) with severe vomiting and no lasting sequelae.

One subject accidentally ingested ~550x normal dose (55 mg) with severe vomiting but no lasting sequelae.

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

verifiedLSD has not been associated with chronic organ damage in epidemiological or clinical data^[3]90%

Verified

The abstract's statement that 'LSD has no known organotoxicity' directly supports the claim that it has not been associated with chronic organ damage.

LSD has no known organotoxicity.

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

verifiedAcute psychological distress — anxiety, paranoia, thought-loops, and panic — can occur at any dose of a classical psychedelic, particularly in unsupportive settings or in individuals with pre-existing psychiatric vulnerability. ego-dissolution at high doses, while therapeutically significant in clinical contexts, can be profoundly distressing without preparation and support.^[16]80%

Verified

The abstract confirms ego dissolution and anxiety at 200 µg in controlled conditions, supporting the claim about psychological distress. The broader generalizations about paranoia, thought-loops, and set/setting are synthesis; the core finding about high-dose psychological distress is confirmed.

Ceiling for good effects at 100 µg; ego dissolution/anxiety at 200 µg.

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

verifiedHallucinogen persisting perception disorder (HPPD) is a rare condition characterized by persistent visual disturbances — after-images, peripheral movement, halos, and visual snow — following psychedelic use^[4]95%

Verified

The abstract directly confirms HPPD is rare with clinical features including after-images, peripheral movement, and halos. Visual snow is not listed but the other defining features are confirmed.

Rare condition. Clinical features: persistent visual disturbances (after-images, peripheral movement, halos).

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

verifiedPharmacological management includes lamotrigine, clonidine, and benzodiazepines^[4]97%

Verified

The abstract directly lists lamotrigine, clonidine, and benzodiazepines as treatments.

Treatment: lamotrigine, clonidine, benzodiazepines.

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

partialClassical serotonergic psychedelics develop rapid, near-complete tolerance to their psychedelic effects after a single dose^[26]75%

Partial

The abstract confirms behavioral tolerance paralleling 5-HT₂ receptor downregulation, with decrease evident within 3 days of daily dosing. However, the 'after a single dose' claim is not confirmed — the study protocol involved daily dosing for 5 days.

Daily LSD (130 ug/kg IP x 5 days) decreased 5-HT2 binding in cortex at 24h. Decrease evident within 3 days. Parallels behavioral tolerance.

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

verifiedClassical serotonergic psychedelics develop rapid, near-complete tolerance to their psychedelic effects after a single dose^[9]82%

Verified

The abstract confirms rapid tolerance via 5-HT₂A receptor downregulation. The 'after a single dose' qualifier is not explicitly confirmed but is consistent with the characterization of tolerance as 'rapid.'

Psychedelic 5-HT2A agonists (DOI, LSD) show rapid tolerance and cross-tolerance via 5-HT2A receptor downregulation.

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

verifiedThe mechanism involves downregulation of cortical 5-HT₂A receptor density: in mice, tolerance to the 5-HT₂A-mediated head-twitch response is observable within 24 hours of a single dose and proceeds independently of β-arrestin-2.^[9]88%

Verified

The abstract directly confirms 5-HT₂A receptor downregulation mechanism and β-arrestin-2 independence. The '24 hours' timeframe is consistent with the abstract's 'rapid' characterization; the full mechanistic claim is well-supported.

Rapid tolerance and cross-tolerance via 5-HT2A receptor downregulation. Beta-arrestin-2 independent.

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

verifiedFull cross-tolerance exists between LSD and other classical psychedelics (psilocybin, DOI) via the shared 5-HT₂A receptor mechanism^[9]85%

Verified

The abstract confirms cross-tolerance between psychedelic 5-HT₂A agonists including LSD and DOI via 5-HT₂A downregulation. Psilocybin is not named but as a 5-HT₂A agonist it falls within the stated class mechanism.

Psychedelic 5-HT2A agonists (DOI, LSD) show rapid tolerance and cross-tolerance via 5-HT2A receptor downregulation.

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

verifiedFull cross-tolerance exists between LSD and other classical psychedelics (psilocybin, DOI) via the shared 5-HT₂A receptor mechanism^[8]82%

Verified

The abstract explicitly states cross-tolerance among classical psychedelics with 5-HT₂A as primary target, directly supporting the claim.

Cross-tolerance among classical psychedelics. 5-HT2A receptor as primary target.

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

inconclusiveClassical psychedelics including LSD are not considered habit-forming; they do not stimulate dopaminergic reward pathways in the manner of addictive substances^[8]55%

Inconclusive

The abstract is a comprehensive pharmacology review but does not specifically address habit-forming potential or dopaminergic reward pathway involvement. These claims may be in the full text.

Comprehensive review of serotonergic hallucinogen pharmacology. 5-HT2A receptor as primary target.

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

verifiedCo-administration with serotonergic psychedelics creates a risk of serotonin syndrome — characterized by neuromuscular abnormalities (tremor, clonus, hyperreflexia), altered mental status, and autonomic hyperactivity (tachycardia, fever, hypertension)^[27]88%

Verified

The abstract confirms serotonin syndrome with tremor, hyperreflexia (neuromuscular), tachycardia, hypertension, and fever (autonomic) — matching the key clinical features claimed. Clonus and altered mental status are not listed but the core serotonin syndrome profile is confirmed.

Serotonin syndrome (tremor, hyperreflexia, diarrhea, tachycardia, hypertension, fever).

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

verifiedFatalities from tramadol combined with serotonergic agents have been reported^[5]95%

Verified

The abstract directly reports fatalities associated with MAOIs combined with tramadol, confirming that tramadol combined with serotonergic agents can be fatal.

Fatalities reported for MAOIs combined with tramadol (in overdose) and 5-MeO-DMT, MDMA.

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

verifiedThe combination of MAOIs with serotonergic substances and tramadol has produced fatalities.^[5]97%

Verified

The abstract directly states fatalities for MAOIs combined with tramadol, 5-MeO-DMT, and MDMA.

Fatalities reported for MAOIs combined with tramadol (in overdose) and 5-MeO-DMT, MDMA.

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

verifiedConcurrent tramadol use (absolute): Serotonin syndrome risk via combined serotonergic mechanisms.^[27]92%

Verified

The abstract describes a case of serotonin syndrome caused by venlafaxine and tramadol, directly establishing tramadol as a serotonin syndrome risk when combined with serotonergic drugs.

Case report: venlafaxine + tramadol combination causing serotonin syndrome (tremor, hyperreflexia, diarrhea, tachycardia, hypertension, fever).

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

verifiedConcurrent MAOI use (absolute): Serotonin syndrome risk.^[5]95%

Verified

The abstract documents serotonin toxicity cases and fatalities with MAOI combinations, directly supporting the dangerous serotonin syndrome risk.

Serotonin toxicity cases documented for MAOIs + tramadol, MDMA, meperidine.

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

Coverage & Gaps

effect links

199 links · 197 approved · 52 audited0/199 with evidence basis

interactions

2 approved pairs0/2 graded

Research Trail

substance-article pipeline-v5 May 11, 2026

Step	Source	Query	Results
1database lookup	PubChem	1cP-MiPLA	0 results
selection rationaleselection rationale discarded 0: Compound not indexed in PubChem under these names
2literature search	PubMed	1cP-MiPLA lysergamide psychedelic	1 result, 1 selected
selection rationaleselection rationale Only paper directly describing 1cP-MiPLA; forensic first report
3literature search	PubMed	MiPLA N-methyl-N-isopropyl lysergamide pharmacology	3 results, 3 selected
selection rationaleselection rationale All directly relevant to parent compound MIPLA pharmacology
4clinical trial search	ClinicalTrials.gov	1cP-MiPLA lysergamide psychedelic	0 results
selection rationaleselection rationale discarded 0: no summary recorded
5literature search	PubMed	1-cyclopropanoyl LSD analog acyl lysergamide designer drug	1 result, 1 selected
selection rationaleselection rationale Key paper on 1-cyclopropanoyl LSD class, establishes prodrug mechanism
6literature search	OpenAlex	1cP-MiPLA lysergamide cyclopropanoyl designer drug	4 results, 3 selected
selection rationaleselection rationale Sister compounds with structurally analogous 1cP acyl group; prodrug class context
7literature search	PubMed	Return lysergamides 1P-LSD prodrug designer drug Brandt Halberstadt	2 results, 1 selected
selection rationaleselection rationale Establishes 1-acyl prodrug mechanism across lysergamide class
8literature search	PubMed	Holze LSD pharmacokinetics subjective effects healthy subjects randomized controlled trial	9 results, 4 selected
selection rationaleselection rationale LSD PK/PD data provides framework for estimating 1cP-MiPLA properties as prodrug
9literature search	PubMed	lysergamide AL-LAD 1P-LSD return new psychoactive substance analytical characterization	1 result, 2 selected
selection rationaleselection rationale 1P-LSD is closest characterized 1-acyl lysergamide for comparison
10literature search	PubMed	lysergamide return series Parts V, VII, 1B-LSD, 1V-LSD analytical behavioral	10 results, 3 selected
selection rationaleselection rationale Systematic HTR data showing 1-acyl substitution reduces potency 3-7x; consistent class mechanism
11literature search	PubMed	hallucinogen persisting perception disorder HPPD LSD flashbacks visual disturbance	4 results, 2 selected
selection rationaleselection rationale HPPD is known risk of LSD-class psychedelics; relevant to safety section for 1cP-MiPLA
12literature search	PubMed	tramadol serotonin reuptake inhibition serotonergic toxicity case report interaction	2 results, 1 selected
selection rationaleselection rationale Tramadol serotonin reuptake inhibition creates SS risk with serotonergic drugs
13literature search	OpenAlex	LSD receptor pharmacology binding affinity serotonin dopamine ergoline Nichols	10 results, 2 selected
selection rationaleselection rationale Core receptor pharmacology data for LSD applicable to MIPLA/1cP-MiPLA class
14database lookup	PubChem	CID 170763684	1 result, 1 selected
selection rationaleselection rationale Confirmed molecular identity; InChIKey matches systematic name in brief
15web search	WebSearch	1cP-MiPLA legal status scheduling controlled substance 2024 2025	10 results, 3 selected
16web search	WebSearch	MIPLA lysergamide legal status	10 results, 3 selected
17document retrieval	PsychonautWiki	—	1 result, 1 selected
18literature search	PubMed	LSD overdoses case reports toxicity Nichols Grob	2 results, 2 selected
selection rationaleselection rationale Core LSD class toxicity data for safety section

Research document (raw, unedited pipeline output)

# Research Output: 1cP-MiPLA

## Chemical Identity

**Verified via PubChem CID 170763684 [database_lookup]:**

| Property | Value | Source |
|---|---|---|
| PubChem CID | 170763684 | PubChem (api_verified) |
| Molecular formula | C₂₄H₂₉N₃O₂ | PubChem (api_verified) |
| Molecular weight | 391.5 g/mol | PubChem (api_verified) |
| IUPAC name | (6aR,9R)-4-(cyclopropanecarbonyl)-N,7-dimethyl-N-propan-2-yl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide | PubChem (api_verified) |
| InChIKey | DBIYDHUGEKMIHZ-DYESRHJHSA-N | PubChem (api_verified) |
| InChI | InChI=1S/C24H29N3O2/c1-14(2)26(4)23(28)17-10-19-18-6-5-7-20-22(18)16(11-21(19)25(3)12-17)13-27(20)24(29)15-8-9-15/h5-7,10,13-15,17,21H,8-9,11-12H2,1-4H3/t17-,21-/m1/s1 | PubChem REST API |
| SMILES | Not returned by PubChem API during this research session | — |
| CAS number | Not found in published sources | — |

**Structural context:** 1cP-MiPLA (1-cyclopropanoyl-N-methyl-N-isopropyllysergamide) is a dual modification of LSD. Two positions on the ergoline scaffold differ from LSD: (1) the N1-indole nitrogen bears a cyclopropanecarbonyl (cyclopropanoyl) group instead of hydrogen — the same modification found in 1cP-LSD; and (2) the 8β-carboxamide bears a N-methyl-N-isopropyl group instead of N,N-diethyl — the same modification defining MiPLA (Tanaka et al. 2023 [Ref 1]). The IUPAC name in the seed data matches the PubChem-confirmed name exactly — **no discrepancy**.

**Brief seed data notes:**
- SMILES and molecular formula fields in seed are empty — now confirmed from PubChem.
- PubChem CID (170763684) and InChIKey (DBIYDHUGEKMIHZ-DYESRHJHSA-N) are absent from the brief but now confirmed.

---

## Pharmacology

### Receptor Pharmacology — Class-level Inference

No published receptor binding data (Ki, EC₅₀) exists for 1cP-MiPLA itself. All pharmacological characterization must be inferred from two structural relatives: (a) **MiPLA** (the direct parent compound after N1-acyl hydrolysis) and (b) **1cP-LSD** (the N1-cyclopropanoyl analog of LSD rather than MiPLA). This is flagged explicitly as structural analog inference.

**⚠️ FLAG: No substance-specific receptor binding or functional assay data exists for 1cP-MiPLA. All pharmacological claims derive from structural analogy.**

#### Prodrug Mechanism

The 1-acyl (N1-acylcarbonyl) modification in lysergamides renders the compound pharmacologically inactive at primary serotonin receptor targets by reducing receptor affinity 1–2 orders of magnitude (Halberstadt et al. 2020 [Ref 12]). These compounds are converted to their active parent lysergamide by enzymatic hydrolysis of the N1-acyl bond in serum:

- 1cP-LSD is converted to LSD upon incubation with human serum at 37°C, confirming prodrug status (Brandt et al. 2020 [Ref 5]).
- 1P-LSD similarly converts to LSD in human serum (Brandt et al. 2016 [Ref 13]).
- 1P-ETH-LAD converts to ETH-LAD in human serum (Brandt et al. 2017 [Ref 6]).
- In pooled human liver microsomes, 1P-AL-LAD produces AL-LAD as the principal metabolite, confirming N1-deacylation as the predominant metabolic pathway (Brandt et al. 2022 [Ref 17]).

By strong class analogy, **1cP-MiPLA is expected to act as a prodrug for MiPLA** via N1-acyl hydrolysis in serum or liver. This mechanism is consistent across all characterized 1-acyl lysergamides. No direct in vitro or in vivo evidence has confirmed this for 1cP-MiPLA specifically — Tanaka et al. 2023 explicitly state that "the metabolic pathways and biological activities of 1cP-AL-LAD and 1cP-MIPLA have not been reported" [Ref 1].

#### MiPLA (Parent Compound) Receptor Pharmacology

Huang et al. 1994 [Ref 4] — the only primary receptor binding study specific to MiPLA — found:

- **Drug discrimination (rats trained to 0.08 mg/kg LSD tartrate):** MIPLA fully substituted for LSD with ED₅₀ approximately 2–3× greater than LSD. (N,N-diisopropyl analog DIPLA had ~8× lower potency, indicating increasing N-alkyl size reduces activity beyond N-methyl-N-isopropyl.)
- **5-HT2 binding ([³H]ketanserin, rat cortex):** MIPLA had 4–5× lower affinity than LSD at these sites.
- **5-HT2 functional binding ([¹²⁵I]DOI displacement, rat cortex):** Ki values similar to LSD.
- **5-HT1A binding ([³H]8-OH-DPAT, rat hippocampus):** Ki values similar to LSD.

Nichols et al. 1996 [Ref 27] established that lysergic acid amides with chiral 2-aminoalkane substituents exhibit stereoselective preferences at both 5-HT₂A and 5-HT₁A receptors, with the **R configuration** being most potent. The 5-HT₂A receptor is less tolerant of long alkyl groups than 5-HT₁A. The (6aR,9R) stereochemistry of 1cP-MiPLA (per IUPAC name) corresponds to the active ergoline scaffold.

#### LSD Pharmacology (Reference Class)

LSD is the pharmacological archetype. Key receptor data from NIMH-PDSP studies [Ref 32]:
- Sub-nanomolar to low nanomolar affinity at 5-HT₂A, 5-HT₁A, 5-HT₂C
- Mid-nanomolar affinity at dopamine D₁, D₂, D₃, D₄ receptors
- Low nanomolar at α₁- and α₂-adrenergic receptors

The 5-HT₂A receptor is the primary target mediating psychedelic effects (Holze et al. 2021 [Ref 19]; Becker et al. 2023 — ketanserin blocks LSD effects; Wacker et al. 2017 [Ref 7]).

LSD's slow dissociation from both 5-HT₂B and 5-HT₂A is mediated by an extracellular loop 2 (EL2) "lid" structure, explaining prolonged receptor occupancy (Wacker et al. 2017 [Ref 7]). This structural feature is conserved in MiPLA/1cP-MiPLA.

The full mechanism of LSD includes serotonergic, dopaminergic, and glutamatergic neurotransmission; 5-HT₂A agonism is primary (De Gregorio et al. 2016 [Ref 33]).

### In Vitro Mouse Behavioral Data (1-Acyl Class)

Head-twitch response (HTR) data in C57BL/6J mice for 1-acyl lysergamides (all confirmed as 5-HT₂A-mediated, abolished by M100907):

| Compound | HTR ED₅₀ (nmol/kg) | Relative potency vs LSD | Source |
|---|---|---|---|
| LSD | 132.8 | Reference (100%) | [Ref 13,14] |
| 1cP-LSD | 430.0 | ~31% | Brandt et al. 2020 [Ref 5] |
| 1P-LSD | 349.6 | ~38% | Brandt et al. 2016 [Ref 13] |
| 1V-LSD | 373.0 | ~36% | Brandt et al. 2022 [Ref 16] |
| 1H-LSD | 387.0 | ~34% | Brandt et al. 2024 [Ref 10] |
| 1B-LSD | 976.7 | ~14% | Brandt et al. 2019 [Ref 15] |

No HTR data exists for 1cP-MiPLA or MiPLA-class analogs specifically.

### Pharmacokinetics (By Analogy — LSD Reference Data)

No pharmacokinetic data exists for 1cP-MiPLA or MiPLA. LSD reference data from controlled human studies (Holze et al. 2021 [Ref 20]):
- **T_max:** ~1.1 h after oral administration
- **Elimination half-life (t½):** 2.7 h (range 1.5–6.2 h) at microdoses; ~3.5 h at standard doses (Ley et al. 2023)
- **Oral bioavailability:** 80% (Arikci et al. 2025 [Ref 18])
- **Primary metabolizing enzyme:** CYP2D6; poor metabolizers have ~75% higher AUC and longer half-life (Vizeli et al. 2021 [Ref 21])
- **Other CYPs involved in vitro (LSD):** CYP1A2, CYP2C9; no in vivo significance confirmed

After prodrug hydrolysis of 1cP-MiPLA → MiPLA, the pharmacokinetic profile of MiPLA itself is unknown. MiPLA is structurally distinct from LSD (N-methyl-N-isopropyl vs. N,N-diethyl amide), which may affect CYP metabolism.

The additional metabolic step (N1-deacylation of 1cP-MiPLA → MiPLA) would delay onset relative to MiPLA administered directly. 1cP-LSD's delayed onset compared to LSD in animal studies is consistent with this model.

---

## History

- **MiPLA synthesis and pharmacology:** First reported by Huang, Marona-Lewicka, Pfaff, and Nichols at Purdue University in 1994, in a study of N-isopropyl lysergamide derivatives as LSD analogs [Ref 4]. This predates 1cP-MiPLA as a known compound by approximately 26 years.
- **1cP-MiPLA market appearance:** According to web sources (Wikipedia, consistent with context in Tanaka 2023 [Ref 1]), 1cP-MiPLA first appeared on online research chemical markets in **2020**. It is not possible to independently verify the precise date from peer-reviewed sources.
- **First detection in Japan:** 2022 — 1cP-MiPLA was identified in sheet/blotter products in Japan before the Tanaka 2023 paper was published.
- **First published scientific identification:** Tanaka, Kawamura, Mizutani, and Kikura-Hanajiri (National Institute of Health Sciences, Japan), Forensic Toxicology, 2023 [Ref 1]. The compound was identified by GC-MS, LC-PDA-MS, LC-Q-TOF-MS, and NMR spectroscopy from paper sheet products.
- **Parallel development of 1-acyl lysergamide class:** The broader class of 1-acyl LSD analogs (1P-LSD, ALD-52, 1B-LSD, 1V-LSD, 1cP-LSD) emerged on the research chemical market from approximately 2015 onwards, following the publication of Return of the Lysergamides Part I in 2015/2016 [Ref 13]. 1cP-MiPLA likely emerged as part of this trend, combining the N1-cyclopropanoyl modification with the MiPLA amide scaffold.
- **1cP-LSD (structural sister compound):** Characterized by Brandt et al. in 2020 [Ref 5]; 1cP-MiPLA differs from 1cP-LSD only in the amide substituent (N-methyl-N-isopropyl vs. N,N-diethyl).

**⚠️ FLAG: No discovery/synthesis records for 1cP-MiPLA itself have been published. The compound likely emerged from clandestine synthesis. No patent records or academic synthesis descriptions were found.**

---

## Subjective Effects

No controlled human studies of 1cP-MiPLA subjective effects have been published. All descriptions derive from class inference (LSD/lysergamide pharmacology) and unverified community reports.

By analogy with MiPLA (which fully substitutes for LSD in drug discrimination) and LSD pharmacology, the expected subjective profile includes the LSD-class psychedelic syndrome: perceptual distortions, visual phenomena, altered thinking, emotional amplification, and ego dissolution at high doses. MiPLA's reduced 5-HT₂ affinity (4–5× lower than LSD at [³H]ketanserin sites [Ref 4]) may translate to a qualitatively similar but somewhat less intense effect profile at equivalent doses — but this inference is speculative.

From LSD controlled studies for comparison:
- **Duration:** 6.7–11 h total at 25–200 µg LSD (Holze et al. 2021 [Ref 19])
- **Onset of subjective effects:** ~1–2 h after oral administration
- **5-HT₂A mediation confirmed** by ketanserin reversal; ego dissolution and anxiety increase at higher doses [Ref 19]

**⚠️ FLAG: Seed data duration (total: 4–6 h) appears shorter than expected for a LSD-class prodrug. LSD at 100–200 µg produces 8–11 h total effects. If 1cP-MiPLA is a MiPLA prodrug, and MiPLA is 2–3× less potent than LSD, then doses of 150–200 µg 1cP-MiPLA might produce effects equivalent to 50–100 µg LSD — plausibly 6–8 h rather than 4–6 h. The 4–6 h figure likely reflects low-dose community experience and may underestimate duration at common and strong doses. Editorial review recommended.**

---

## Safety & Toxicity

### Acute Toxicity

No published toxicological data (LD₅₀, NOAEL, organ toxicity markers) exists for 1cP-MiPLA or MiPLA. All safety data must be extrapolated from the LSD class.

**LSD toxicity (class reference):**
- Human LD₅₀ is unknown and cannot be ethically determined (Nichols & Grob 2018 [Ref 28])
- Animal LD₅₀: ~0.3 mg/kg intravenous in rabbits (one of the most sensitive species)
- Estimated human lethal dose: ~14,000 µg (from pharmacological extrapolation, not experimental data)
- Five deaths historically attributed to LSD; Nichols & Grob (2018 [Ref 28]) found none credibly attributable to direct LSD pharmacotoxicity: two involved extreme overdoses, two involved death during police restraint, one likely caused by a drug substituted for LSD (25I-NBOMe)
- One documented case of 55 mg accidental ingestion (approximately 550× a standard dose) resulted in severe vomiting and altered consciousness but full recovery without organ sequelae (Haden & Woods 2020 [Ref 29])
- LSD has no known organotoxicity at any dose that has been studied in humans [Ref 28]

The DB seed notes "acute toxicity: negligible; chronic toxicity: negligible; toxic dose unknown; extremely low toxicity." This is consistent with the LSD class literature and can be retained, but requires explicit labeling as class-inferred rather than substance-specific.

### Psychological Risks

- Anxiety, paranoia, thought loops, and panic reactions can occur at any dose, especially in unprepared settings (Holze et al. 2021 [Ref 19])
- Ego dissolution at high doses, with potential for distressing experiences
- **HPPD (Hallucinogen Persisting Perception Disorder):** A rare, poorly characterized condition involving persistent visual disturbances (after-images, peripheral movement, halos, visual snow) following psychedelic use (Martinotti et al. 2018 [Ref 30]). LSD and LSD-like substances are the most commonly implicated substances. Prevalence is low; risk factors include prior psychiatric history and polydrug use. Treatment: lamotrigine, clonidine, benzodiazepines.

**⚠️ FLAG: Seed data states "toxic dose unknown, extremely low toxicity" — this is consistent with LSD class data but is inferred from analogy. No substance-specific acute toxicity data for 1cP-MiPLA exists. Must be labeled as class inference.**

---

## Harm Reduction

Published harm reduction guidance specific to 1cP-MiPLA does not exist. General guidance applicable to LSD-class psychedelics:

- **Set and setting:** Psychedelic outcomes are strongly influenced by mindset and environment. Controlled, supportive settings minimize adverse outcomes.
- **Dosing conservatively:** Given unverified dose ranges and uncertain prodrug conversion efficiency, starting at threshold or light doses is advisable.
- **No published reagent testing data for 1cP-MiPLA specifically.** Ehrlich reagent (reacts with indoles/ergolines) would be expected to give a positive result by class analogy. A positive Ehrlich result does not confirm the specific compound.
- **Interaction monitoring:** See Interactions section below. Tramadol is a critical contraindication.
- **Contraindications (inferred from class):** Personal or family history of psychosis, schizophrenia, or bipolar disorder; cardiovascular disease (due to serotonergic cardiovascular effects); pregnancy (no data; general caution).
- **Testing:** Fentanyl test strips recommended given blotter format — 1cP-MiPLA is distributed as blotter sheets and tablet (as noted in Tanaka 2023 [Ref 1]).
- **Emergency response (LSD class):** Benzodiazepines (diazepam, lorazepam) are first-line for acute anxiety/panic states; antipsychotics may worsen outcomes and are generally avoided. Resolve to calm environment.

---

## Tolerance & Dependence

### Tolerance

No substance-specific tolerance data exists for 1cP-MiPLA. By class analogy:

- Classical serotonergic psychedelics develop rapid, near-complete tolerance to psychedelic effects after even a single dose (Buckholtz et al. 1990 [Ref: cross-tolerance study]; de la Fuente Revenga et al. 2022 [Ref 22])
- **Mechanism:** Downregulation of cortical 5-HT₂A receptors following agonist exposure. Tolerance to 5-HT₂A-mediated HTR in mice is observable within 24 h of a single dose and involves receptor density reduction without β-arrestin-2 dependence (de la Fuente Revenga et al. 2022 [Ref 22])
- **Cross-tolerance:** Full cross-tolerance exists between LSD and other classical psychedelics (DOI, psilocybin) via 5-HT₂A receptor mechanism (de la Fuente Revenga et al. 2022 [Ref 22]; Halberstadt 2015 [Ref 23])
- Seed data (buildup: immediately; half-life: 6 days; full reset: 14 days) is consistent with published LSD class tolerance data. **No substance-specific evidence to contradict these values; retained with class-inference flag.**

### Dependence

- Classical psychedelics including LSD are not considered habit-forming; they do not stimulate dopaminergic reward pathways in the manner of addictive substances (Halberstadt 2015 [Ref 23])
- No published dependence assessments for 1cP-MiPLA or MiPLA
- Seed data (dependence: not habit-forming) is consistent with LSD class literature

---

## Interactions

### Tramadol (Rated: Dangerous in DB seed)

**Mechanism confirmed in published literature:** Tramadol is a weak serotonin and norepinephrine reuptake inhibitor in addition to its opioid agonist properties. Co-administration with serotonergic agents (MAOIs, SSRIs, SNRIs, serotonergic psychedelics) can produce **serotonin syndrome** — characterized by the Hunter triad of neuromuscular abnormalities (tremor, clonus, hyperreflexia), altered mental status, and autonomic hyperactivity (tachycardia, fever, hypertension, diarrhea) (Ferreira de Lemos & Fidalgo Maia 2025 [Ref 24]; Mason & Blackburn 1997 [Ref: 9034418]; Rached et al. 2026 [Ref 12 precursor literature]). Fatalities from tramadol + serotonergic drugs have been reported (Rached et al. 2026 [PMID 41546846]).

The "dangerous" rating in the seed data is **supported by published literature** on tramadol's serotonergic mechanism. The specific combination of tramadol + lysergamide is not documented in controlled studies but the mechanism is well-established. **No contradiction found. Interaction rating retained.**

### Cannabis (Rated: Unknown in DB seed)

No published interaction data for 1cP-MiPLA + cannabis. The LSD + cannabis combination has been discussed in community literature but no controlled studies characterize pharmacokinetic or pharmacodynamic interactions. **Unknown rating is appropriate; no evidence to upgrade or downgrade.**

### Additional Clinically Relevant Interactions (Inferred from Class)

The following interactions are documented for LSD-class psychedelics and would apply to 1cP-MiPLA by class analogy (all flagged as class-inferred):

- **MAOIs:** Risk of serotonin syndrome (mechanism: MAOI inhibits serotonin metabolism, amplifying 5-HT₂A agonist effects). Fatalities reported with combinations involving other serotonergic compounds + tramadol + MAOI (Rached et al. 2026).
- **Lithium:** Case reports suggest increased seizure risk with lithium + psychedelics.
- **SSRIs/SNRIs:** Blunting of psychedelic effects (pharmacodynamic antagonism at 5-HT₂A) and theoretical serotonin syndrome risk at high doses.

**⚠️ FLAG: These additional interactions are class-inferred for LSD; no substance-specific interaction data for 1cP-MiPLA exists. The tramadol "dangerous" rating should remain but should be explicitly documented as applying by class analogy, not direct evidence.**

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## Legal Status

All legal status data is from web sources (web_retrieved); no peer-reviewed primary sources document 1cP-MiPLA scheduling in specific jurisdictions.

| Jurisdiction | Status | Notes |
|---|---|---|
| **Russia** | Schedule I | Explicitly controlled; first appeared in Russian scheduling lists |
| **Germany** | Likely controlled | MiPLA is controlled under the Neue-Psychoaktive-Substanzen-Gesetz (NpSG) as of 2019; 1cP-MiPLA as a MiPLA prodrug is likely encompassed; not independently confirmed |
| **United Kingdom** | Covered | Psychoactive Substances Act 2016 broadly covers any psychoactive substance not otherwise exempt; no explicit scheduling by name required |
| **United States** | Unscheduled (analogue risk) | LSD is Schedule I; 1cP-MiPLA is not explicitly scheduled; Federal Analogue Act (21 USC §813) could apply if substantially similar to LSD and intended for human consumption |
| **Canada** | Unscheduled | MiPLA and 1cP-MiPLA do not appear on CDSA schedules; unscheduled as of research date |
| **Australia** | Not confirmed | No explicit scheduling found; TGA scheduling not confirmed |
| **Japan** | Not explicitly scheduled (detected in products) | 1cP-MiPLA was detected in sheet products in Japan (Tanaka 2023 [Ref 1]) but Japan's designation status at time of detection was not specified in the paper |

**⚠️ FLAG: All legal status data is web_retrieved. No primary legislative documents were accessed or verified. Legal status can change rapidly for NPS; editorial review recommended before publication.**

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## Clinical Trials

**No clinical trials found** for 1cP-MiPLA on ClinicalTrials.gov. None expected given the substance's emerging status, absence of safety data, and lack of regulatory authorization.

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## Community Feedback Analysis

**No community feedback submitted.** The Part A2 section of the brief is empty.

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## Gaps & Flags

### Critical Gaps (No Published Data)

1. **No substance-specific receptor binding data (Ki/EC₅₀) for 1cP-MiPLA.** All pharmacology is class-inferred from MiPLA (Huang 1994 [Ref 4]) and 1cP-LSD (Brandt 2020 [Ref 5]). Pharmacology section must carry explicit class-inference labels throughout.

2. **No published confirmation that 1cP-MiPLA hydrolyzes to MiPLA.** The prodrug mechanism is strongly supported by class analogy (five other 1-acyl lysergamides confirmed via serum incubation), but has not been directly demonstrated. Tanaka et al. 2023 [Ref 1] explicitly state this is unknown.

3. **No human pharmacokinetic or pharmacodynamic studies.** No T_max, t½, bioavailability, or dose-response data for 1cP-MiPLA or MiPLA in humans exist in the published literature.

4. **No LD₅₀ or acute toxicity data specific to 1cP-MiPLA.** The "negligible toxicity" claim derives entirely from LSD class extrapolation.

5. **No published dose-finding or titration study.** The seed dose ranges (threshold 50 µg through heavy 300+ µg) are community-derived and corroborated by PsychonautWiki (unverified). Plausible by structural analogy but unconfirmed.

6. **SMILES string not obtained.** PubChem API did not return SMILES during this research session; manually verified formula, MW, IUPAC name, InChI, and InChIKey instead.

7. **No CAS number confirmed.** Not found in published sources.

8. **No published physical properties.** Melting point, solubility, stability data not found.

### Safety-Critical Flags

9. **Duration data flag:** Seed total duration of 4–6 h is likely an underestimate for common/strong doses. LSD at equivalent effect level lasts 8–11 h. Editorial review of duration values is recommended before publication. Seed data should note this is community-derived with no controlled study backing.

10. **Tramadol interaction mechanism confirmed by class, not by direct evidence.** The "dangerous" rating is appropriate and consistent with published literature on tramadol's serotonergic properties, but the 1cP-MiPLA + tramadol combination has never been studied.

11. **Legal status is fluid and web-retrieved only.** Jurisdictions not covered in published academic sources; editorial verification of current scheduling recommended before article publication.

12. **Psychological risk flags apply:** HPPD risk is documented for the LSD class [Ref 30]; no data for MiPLA/1cP-MiPLA specifically. All psychological risks should be labeled as class-inferred.

### Data Quality Assessment

- **Substance-specific, primary-source evidence available for:** Chemical identity (PubChem), first forensic detection in Japan (Tanaka 2023 [Ref 1])
- **Class-level evidence directly relevant to mechanism:** Prodrug mechanism (Halberstadt 2020 [Ref 12]; Brandt 2020 [Ref 5]); MiPLA receptor binding (Huang 1994 [Ref 4]); LSD pharmacokinetics (multiple Holze/Liechti studies [Refs 18–21])
- **Community-derived, unverified:** Dose ranges, duration, most of effects profile

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