1P-ETH-LAD

Claim in pharmacology — inconclusiveinconclusiveworking →

Claim in pharmacology — inconclusiveinconclusiveworking →

In vitro serum hydrolysis studies demonstrated conversion of 1P-ETH-LAD to ETH-LAD in human serum at 37°C within a 24-hour incubation window; the N-1 propionyl group is cleaved under physiological conditions to release the active compoundsupported

Serum incubation at 37°C showed hydrolysis to ETH-LAD suggesting prodrug status. 1P-ETH-LAD still detectable in serum after 24h. dta.2196

For the closest structural analog 1p-lsd, human pharmacokinetic data confirmed that oral administration yields only LSD in serum and urine — the parent 1P-LSD is undetectable — with an effective bioavailability of the active form approaching 100%supported

Oral 1P-LSD: only LSD detectable in serum/urine; LSD t1/2=6.4h. IV 1P-LSD: 1P-LSD detectable up to 4.16h. Bioavailability of LSD from oral 1P-LSD ~100%. dta.2821

Halberstadt and colleagues demonstrated across a range of 1-acyl LSD derivatives (ALD-52, 1P-LSD, 1B-LSD) that the acyl group reduces binding affinity at 5-HT₂A, D2, and other monoamine receptors by one to two orders of magnitude compared to the parent lysergamidesupported

1-acyl substitution reduced affinity for monoamine receptors by 1-2 orders of magnitude compared to LSD. ALD-52, 1P-LSD and 1B-LSD have weak efficacy or act as antagonists. j.neuropharm.2019.107856

Claim in pharmacology — inconclusiveinconclusiveworking →

Claim in pharmacology — inconclusiveinconclusiveworking →

The principal psychedelic mechanism of ETH-LAD (and by extension 1P-ETH-LAD after prodrug conversion) is 5-HT₂A receptor partial agonismsupported

Three scaffold classes (tryptamines, ergolines, phenethylamines) engage different binding pocket residues. j.pharmr.2025.100059

The principal psychedelic mechanism of ETH-LAD (and by extension 1P-ETH-LAD after prodrug conversion) is 5-HT₂A receptor partial agonismsupported

5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response. s41467-023-44016-1

The Gq-coupled signaling pathway — rather than β-arrestin2 recruitment — is the primary driver of psychedelic behavioral effects, as established for the hallucinogen class through functional selectivity studies.supported

5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response. Beta-arrestin-biased ligands block psychedelic effects. s41467-023-44016-1

5-HT₁A partial agonism: modulates and may attenuate 5-HT₂A-mediated psychedelic effects. Brandt and colleagues demonstrated that 5-HT₁A activation can mask 5-HT₂A-mediated head-twitch response in a related lysergamide (LSM-775).supported

LSM-775 acts as nonselective agonist at 5-HT1A and 5-HT2A. Did not induce HTR unless 5-HT1A was blocked. Shows how 5-HT1A activation can mask hallucinogenic effects. dta.2222

D2–5-HT₂A heteroreceptor complex interaction: LSD-class hallucinogens enhance D2 protomer recognition and signaling through allosteric activation of the 5-HT₂A protomer within D2–5-HT₂A heteroreceptor complexes.supported

LSD and DOI (5-HT2A agonists) enhance D2R density and affinity in D2-5-HT2A heteroreceptor complexes. Blocked by ketanserin (5-HT2A antagonist). j.bbrc.2013.11.104

Claim in pharmacology — inconclusiveinconclusiveworking →

Community survey data from the Global Drug Survey 2016, however, found that LSD analogue users (a pooled group including ETH-LAD users) reported slightly lower subjective intensity compared to LSD at equivalent doses.supported

Lower ratings for pleasurable high, strength, value for money vs LSD. hup.2599

Wagmann and colleagues characterized the in vitro metabolism of 1P-ETH-LAD using pooled human liver S9 fractionsupported

Human liver S9 fraction metabolism of nine LSD derivatives including 1P-ETH-LAD. s00216-018-1558-9

A pharmacogenomic consideration: for the closely related lsd, CYP2D6 genotype significantly influences pharmacokinetics — poor metabolizers exhibit approximately 75% higher area under the curve (AUC) and prolonged subjective effectssupported

CYP2D6 poor metabolizers had ~75% higher LSD AUC and longer half-life. CYP2D6 genotype influences subjective effects. s41598-021-90343-y

Claim in pharmacology — inconclusiveinconclusiveworking →

The best available proxy is the human pharmacokinetic study of 1p-lsd: oral 1P-LSD (100 µg) yielded only LSD in serum and urine, with an LSD elimination half-life of approximately 6.4 hourssupported

Oral 1P-LSD: only LSD detectable in serum/urine; LSD t1/2=6.4h. dta.2821

Oral bioavailability of LSD as free base or tartrate is approximately 80%, while the effective bioavailability of LSD from the 1P-LSD prodrug approached 100% — suggesting that the 1-acyl prodrug form may paradoxically enhance systemic delivery.supported

All oral LSD formulations bioequivalent; absolute oral bioavailability 80%. cpt.3726

Oral bioavailability of LSD as free base or tartrate is approximately 80%, while the effective bioavailability of LSD from the 1P-LSD prodrug approached 100% — suggesting that the 1-acyl prodrug form may paradoxically enhance systemic delivery.supported

Bioavailability of LSD from oral 1P-LSD ~100%. Psychosensory effects comparable to LSD. dta.2821

The Global Drug Survey 2016 found a modal total duration of 8 hours for LSD analogue users (pooled data including ETH-LAD users), consistent with these estimatessupported

Modal duration 8h, time to peak 2h - not significantly different from LSD. hup.2599

Claim in safety — inconclusiveinconclusiveworking →

Claim in safety — inconclusiveinconclusiveworking →

Claim in safety — inconclusiveinconclusiveworking →

Claim in safety — inconclusiveinconclusiveworking →

Population-level data from a nationally representative sample of 130,152 individuals found no association between lifetime psychedelic use (LSD, psilocybin, mescaline) and increased rates of mental health problems in non-psychotic populations.supported

N=130,152; no increased mental health problems with lifetime psychedelic use. LSD, psilocybin, mescaline regarded as non-addictive. journal.pone.0063972

Two subtypes are distinguished: Type 1 (brief, self-limiting flashback episodes) and Type 2 (chronic, waxing-and-waning perceptual disturbances that may persist for months to years)supported

Two forms: Type 1 (brief flashbacks) and Type 2 (chronic, waxing/waning months to years). 7854_2016_457

HPPD can occur after even a single exposure, and LSD is among the most commonly implicated substancessupported

HPPD review: rare, more often in those with prior psychological issues but can arise in anyone even after single exposure. Reviews etiology, hallucinogens involved. brainsci8030047

HPPD can occur after even a single exposure, and LSD is among the most commonly implicated substancessupported

HPPD case report: 28yo male with LSD use history; symptoms 7 months after cessation. cureus.46262

Flashback phenomena have been documented in controlled LSD administration studies in healthy participants.supported

Reoccurring drug-like experiences after acute LSD/psilocybin effects; HPPD as persistent, distressing manifestation. s00213-022-06066-z

A 2025 systematic review found that clonidine, clonazepam, and levetiracetam produced substantial symptom reductionsupported

Clonidine, clonazepam, levetiracetam showed substantial symptom reduction. hrp.0000000000000439

Benzodiazepines were specifically ineffective when HPPD was triggered by LSD.supported

Benzodiazepines ineffective when triggered by LSD. hrp.0000000000000439

Tolerance to the effects of 1P-ETH-LAD develops almost immediately after ingestion through 5-HT₂A receptor downregulation (tachyphylaxis)partially supported

Beta-arrestin-biased ligands block psychedelic effects and induce receptor downregulation and tachyphylaxis. s41467-023-44016-1

Claim in safety — inconclusiveinconclusiveworking →

A population study of 130,152 participants found no association between psychedelic use and substance use disorderssupported

N=130,152; no increased mental health problems with lifetime psychedelic use. LSD, psilocybin, mescaline regarded as non-addictive. journal.pone.0063972

Tramadol (classified: dangerous): tramadol possesses dual pharmacology — μ-opioid agonism and serotonin/norepinephrine reuptake inhibitionsupported

Tramadol has serotonergic adverse effects including serotonin syndrome risk; both mu-opioid agonism and monoaminergic properties. s40265-021-01515-z

Serotonin syndrome from tramadol–serotonergic agent combinations is well documented in the clinical literature. This classification is based on established class pharmacology, not on case reports specifically involving 1P-ETH-LAD or ETH-LAD.supported

Tramadol-antidepressant interaction concern for serotonin syndrome. Review of evidence for this drug-drug interaction. 0897190013504957

Claim in history — inconclusiveinconclusiveworking →

Its first published scientific characterization appeared in 2017 as Part III of the "Return of the Lysergamides" series by Brandt, Kavanagh, and colleaguessupported

First published analytical characterization of 1P-ETH-LAD. dta.2196

Earlier installments characterized 1p-lsd (Part I), al-lad and LSZ (Part II), LSM-775 (Part IV), and 1b-lsd (Part V)supported

1P-LSD characterized. HTR: ~38% potency of LSD. dta.1884

Earlier installments characterized 1p-lsd (Part I), al-lad and LSZ (Part II), LSM-775 (Part IV), and 1b-lsd (Part V)supported

AL-LAD (N6-allyl analog; structurally analogous to ETH-LAD) and LSZ characterized. dta.1985

Earlier installments characterized 1p-lsd (Part I), al-lad and LSZ (Part II), LSM-775 (Part IV), and 1b-lsd (Part V)supported

1B-LSD is constitutional isomer of 1P-ETH-LAD. HTR assay: 1B-LSD ~14% potency of LSD. dta.2613

Claim in history — inconclusiveinconclusiveworking →

A critical finding from this body of work was the confirmation that 1P-ETH-LAD is a constitutional isomer of 1B-LSD — both share the molecular formula C₂₄H₃₁N₃O₂ but differ in the arrangement of their N-1 acyl chain and N⁶ substituents.supported

1B-LSD is constitutional isomer of 1P-ETH-LAD. dta.2613

ETH-LAD itself — the active form — was detected in paper sheet products in Japan between 2014 and 2017, identified via GC-MS, LC-MS, and NMR in a forensic survey. 1P-ETH-LAD, as the later-arriving prodrug variant, appeared somewhat after ETH-LAD on the grey marketsupported

Detected ALD-52, ETH-LAD, AL-LAD, 1P-LSD in Japanese paper sheet products from 2014-2017. ETH-LAD (not 1P-ETH-LAD) detected in Japanese products. yakushi.19-00230

Claim in comparative-pharmacology — inconclusiveinconclusiveworking →

Claim in comparative-pharmacology — inconclusiveinconclusiveworking →

Binding data for ETH-LAD from Hoffman and Nichols 1985; LSD binding from Nichols 2018 and Ray 2010.supported

Receptor affinity data for 25 psychedelic drugs at 51 receptors (NIMH-PDSP). journal.pone.0009019

For 1p-lsd, human data confirm rapid and near-complete conversion to LSD, with no 1P-LSD detectable in serum after oral dosingsupported

Oral 1P-LSD: only LSD detectable in serum/urine. dta.2821

For 1P-ETH-LAD, in vitro data show slower or incomplete conversion at 24 hours in human serum, though in vivo conditions (hepatic esterases, acidic gastric environment) may accelerate hydrolysis substantially.supported

1P-ETH-LAD still detectable in serum after 24h. dta.2196

Claim in comparative-pharmacology — inconclusiveinconclusiveworking →

A recent study confirming that EIPLA (an isomer of ETH-LAD) produces psychedelic effects in humans further validates ETH-LAD's activity in this domain.supported

EIPLA is an isomer of ETH-LAD. ETH-LAD known to produce psychedelic effects in humans. dta.3530

For comparison, the human pharmacokinetic study of oral 1P-LSD (100 µg) found that 1P-LSD was undetectable in serum — only LSD appeared — suggesting rapid and near-complete presystemic hydrolysissupported

Oral 1P-LSD: only LSD detectable in serum/urine; LSD t1/2=6.4h. dta.2821

In vitro serum hydrolysis (human serum, 37°C) demonstrated conversion of 1P-ETH-LAD to ETH-LAD, with the parent compound still detectable at 24 hourssupported

Serum incubation at 37°C showed hydrolysis to ETH-LAD suggesting prodrug status. 1P-ETH-LAD still detectable in serum after 24h. dta.2196

Oral lsd bioavailability is approximately 80% (as free base or tartrate)supported

All oral LSD formulations bioequivalent; absolute oral bioavailability 80%. cpt.3726

The 1-acyl prodrug form may enhance net bioavailability: 1P-LSD delivered an effective LSD bioavailability approaching 100%, possibly by protecting the molecule from presystemic degradationsupported

Bioavailability of LSD from oral 1P-LSD ~100%. dta.2821

In vitro metabolism using pooled human liver S9 fraction identified the following pathways for 1P-ETH-LAD:supported

Human liver S9 fraction metabolism of nine LSD derivatives including 1P-ETH-LAD. N-dealkylation and hydroxylation predominant pathways. s00216-018-1558-9

The principal CYP enzymes responsible are CYP1A2 and CYP3A4supported

CYP1A2 and CYP3A4 are primary metabolizing enzymes. s00216-018-1558-9

CYP2D6 may also contribute to ETH-LAD clearance by analogy with LSD, where poor CYP2D6 metabolizers show approximately 75% higher AUC and prolonged effects.supported

CYP2D6 poor metabolizers had ~75% higher LSD AUC and longer half-life. CYP2D6 genotype influences subjective effects. s41598-021-90343-y

Claim in summary — inconclusiveinconclusiveworking →

1P-ETH-LAD first appeared on the research chemical market in the mid-2010s and received its first published analytical characterization in 2017, when Brandt and colleagues confirmed its identity and demonstrated prodrug conversion to ETH-LAD in human serumsupported

First published analytical characterization of 1P-ETH-LAD. GC-MS, NMR, LC-MS. Serum incubation at 37°C showed hydrolysis to ETH-LAD suggesting prodrug status. dta.2196

Claim in summary — inconclusiveinconclusiveworking →

Claim in summary — inconclusiveinconclusiveworking →

The 1-propionyl group itself reduces receptor affinity by one to two orders of magnitude relative to the parent lysergamide, rendering 1P-ETH-LAD pharmacologically inert until hydrolysis occurssupported

1-acyl substitution reduced affinity for monoamine receptors by 1-2 orders of magnitude compared to LSD. ALD-52, 1P-LSD and 1B-LSD have weak efficacy or act as antagonists. Confirmed prodrug status with high LSD plasma levels post-1P-LSD administration. j.neuropharm.2019.107856

Claim in summary — inconclusiveinconclusiveworking →

Tolerance develops almost immediately through 5-HT₂A receptor downregulation and resets within approximately seven days; the compound is not habit-formingpartially supported

Beta-arrestin-biased ligands block psychedelic effects and induce receptor downregulation and tachyphylaxis. s41467-023-44016-1

The following profile reflects the active metabolite ETH-LAD, to which 1P-ETH-LAD is converted in vivo.supported

Serum incubation at 37°C showed hydrolysis to ETH-LAD suggesting prodrug status. dta.2196

Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

This conclusion derives from systematic study of 1-acyl LSD derivatives (ALD-52, 1P-LSD, 1B-LSD), where the 1-acyl modification consistently abolished or dramatically reduced binding at 5-HT₂A, D2, and related receptors. 1P-ETH-LAD is therefore expected to have negligible intrinsic activity at monoamine receptors, functioning exclusively as a delivery vehicle for ETH-LAD.supported

1-acyl substitution reduced affinity for monoamine receptors by 1-2 orders of magnitude compared to LSD. ALD-52, 1P-LSD and 1B-LSD have weak efficacy or act as antagonists. Confirmed prodrug status. j.neuropharm.2019.107856

ETH-LAD's psychedelic effects are mediated through 5-HT₂A receptor activation of the Gq-coupled signaling pathwaysupported

5-HT2A-Gq (not beta-arrestin2) efficacy predicts psychedelic potential via head-twitch response. s41467-023-44016-1

Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

The D2–5-HT₂A heteroreceptor complex interaction, whereby 5-HT₂A agonism allosterically enhances D2 protomer signaling, may contribute to the stimulant, cognitive, and perceptual aspects of the experience that distinguish ergolines from simple tryptamine psychedelics.supported

LSD and DOI (5-HT2A agonists) enhance D2R density and affinity in D2-5-HT2A heteroreceptor complexes. Allosteric biased agonism at 5-HT2A may contribute to psychotic effects. j.bbrc.2013.11.104

The compound is a constitutional isomer of 1B-LSD (1-butanoyl-LSD): both possess the molecular formula C₂₄H₃₁N₃O₂ and molecular weight 393.5 g/mol, but the four additional carbons and hydrogens beyond the LSD core are distributed differently — in 1P-ETH-LAD, a three-carbon propionyl chain at N-1 and an ethyl group at N⁶; in 1B-LSD, a four-carbon butanoyl chain at N-1 with the standard N-methyl at N⁶.supported

1B-LSD is constitutional isomer of 1P-ETH-LAD. dta.2613

This dual modification produces a compound that is pharmacologically inert at serotonin and dopamine receptors until the N-1 propionyl group is hydrolyzed in vivo, releasing the active metabolite eth-lad.supported

Serum incubation at 37°C showed hydrolysis to ETH-LAD suggesting prodrug status. dta.2196

Key functional groups include the N,N-diethylcarboxamide at C-9 (providing the amide pharmacophore essential for serotonergic activity), the N⁶-ethyl substituent on the piperidine nitrogen, and the N-1 propionyl group that confers prodrug character.supported

First published analytical characterization of 1P-ETH-LAD. GC-MS, NMR, LC-MS. Serum incubation at 37°C showed hydrolysis to ETH-LAD suggesting prodrug status. dta.2196

The only systematic data on human use of ETH-LAD-class compounds comes from the Global Drug Survey 2016 (N = 96,894), which included a module on LSD analogue usesupported

Global Drug Survey 2016 (n=96,894). LSD analogue users (AL-LAD, 1P-LSD, ETH-LAD). hup.2599