1cP-AL-LAD

Claim in safety — inconclusiveinconclusiveworking →

LSD at 100–200 µg in controlled human studies produces moderate, self-limiting cardiovascular effects: increased heart rate and blood pressuresupported

100/200 µg LSD comparable subjective effects to 30 mg psilocybin. LSD increases heart rate more; psilocybin increases BP more. s41386-022-01297-2

Claim in safety — inconclusiveinconclusiveworking →

Analytical profiling of a commercial 1cP-AL-LAD sample identified 17 impurities, including confirmed AL-LAD and 1P-AL-LAD (verified against reference standards) and 15 additional compounds tentatively identified by mass spectral data alonesupported

detection of 17 impurities... tentative determination of their identity was based on mass spectral grounds alone, though detection of AL-LAD and 1P-AL-LAD was confirmed using available reference standards. dta.3397

Functional impairment lasting more than one day occurred in 8.9% of respondents, and 2.6% sought medical, psychiatric, or psychological assistancesupported

8.9% had functional impairment lasting >1 day. 2.6% sought medical/psychiatric/psychological assistance. j.jad.2023.01.073

Key modifiable risk factors included negative mindset, disagreeable physical environment, absence of psychological support, and dose exceeding intended level.supported

Risk factors: lithium/mood stabilizer co-use, poor set/setting, dose too large. j.jad.2023.01.073

HPPD — persisting visual disturbances (geometric hallucinations, trailing phenomena, halos) after 5-HT₂A agonist use — is a documented rare adverse outcome attributed to imbalance of inhibitory-excitatory activity in visual processing circuitssupported

Majority of HPPD cases attributed to drugs with 5-HT2A agonistic effects. HPPD symptoms result from inhibitory-excitatory imbalance in low-level visual processing. j.euroneuro.2014.05.008

HPPD — persisting visual disturbances (geometric hallucinations, trailing phenomena, halos) after 5-HT₂A agonist use — is a documented rare adverse outcome attributed to imbalance of inhibitory-excitatory activity in visual processing circuitssupported

HPPD appears genuine but uncommon, sometimes persisting months or years. Most commonly after LSD use. s0376-8716(03)00036-8

Co-use of lithium was identified as the top risk factor for severe adverse psychedelic outcomes in the Simonsson epidemiological survey.partially supported

Risk factors: lithium/mood stabilizer co-use, poor set/setting, dose too large. j.jad.2023.01.073

In rats administered LSD, cortical 5-HT₂ receptor binding decreased significantly within 3 days of repeated dosing and recovered within 4 days of cessationpartially supported

Daily LSD for 5 days produced decrease in 5-HT2 binding in cortex within 3 days. Decreased binding parallels development and loss of behavioral tolerance. pmid:1969270

Claim in safety — inconclusiveinconclusiveworking →

The combination of 1cP-AL-LAD with serotonin transporter inhibitors poses a theoretical risk of serotonergic excess. Tramadol inhibits the serotonin transporter (SERT) in human SERT-transfected HEK293 cells, and the FDA issued a Drug Safety Communication in 2016 concerning the serotonin toxicity potential of the opioid classsupported

Tramadol inhibits SERT in human SERT-transfected HEK293 cells. FDA Drug Safety Communication March 2016 on opioids and serotonin toxicity. s00204-018-2244-6

The combination of 1cP-AL-LAD with serotonin transporter inhibitors poses a theoretical risk of serotonergic excess. Tramadol inhibits the serotonin transporter (SERT) in human SERT-transfected HEK293 cells, and the FDA issued a Drug Safety Communication in 2016 concerning the serotonin toxicity potential of the opioid classsupported

Tramadol inhibits SERT in human SERT-transfected HEK293 cells. FDA Drug Safety Communication March 2016 on opioids and serotonin toxicity. s00204-018-2244-6

Marked and prolonged serotonin toxicity has been documented in tramadol poisoningsupported

Case report of marked and prolonged serotonin toxicity in a tramadol-poisoned patient. 15563650.2021.1955912

Simonsson and colleagues identified lithium as the top medication risk factor for severe adverse psychedelic outcomes in their epidemiological survey.partially supported

Risk factors: lithium/mood stabilizer co-use, poor set/setting, dose too large. j.jad.2023.01.073

Cannabidiol (CBD) has been identified as a negative allosteric modulator of the 5-HT₂A receptor, which could theoretically modulate psychedelic effects, but clinical significance is unknownsupported

CBD acts as negative allosteric modulator of 5-HT2A, potentially modulating psychedelic effects. j.cellsig.2025.111588

The selective 5-HT₂A antagonist ketanserin reverses LSD-induced psychedelic effects when administered after the drugsupported

LSD psychedelic effects almost fully blocked by 5-HT2A antagonist ketanserin administered after LSD. pyac075

Absolute contraindications: * Personal history of psychotic disorders (schizophrenia spectrum, bipolar disorder with psychotic features) — psychedelics can trigger acute psychotic episodes and exacerbate underlying conditions * Concurrent lithium use — associated with seizures and dangerously amplified psychedelic effects * Concurrent MAOI therapy — serotonin toxicity riskpartially supported

Risk factors: lithium/mood stabilizer co-use, poor set/setting, dose too large. j.jad.2023.01.073

Relative contraindications: * Personal or family history of HPPD * Serious cardiovascular conditions — moderate sympathomimetic effects expected * Concurrent serotonergic medications (SSRIs, SNRIs, tramadol) — attenuated or unpredictable effects; serotonin toxicity risk with tramadol * Pregnancy or breastfeeding — no safety data exist * Unstable psychiatric conditions — risk of destabilisationsupported

Majority of HPPD cases attributed to drugs with 5-HT2A agonistic effects. j.euroneuro.2014.05.008

Relative contraindications: * Personal or family history of HPPD * Serious cardiovascular conditions — moderate sympathomimetic effects expected * Concurrent serotonergic medications (SSRIs, SNRIs, tramadol) — attenuated or unpredictable effects; serotonin toxicity risk with tramadol * Pregnancy or breastfeeding — no safety data exist * Unstable psychiatric conditions — risk of destabilisationsupported

LSD increases heart rate more; psilocybin increases BP more. s41386-022-01297-2

Relative contraindications: * Personal or family history of HPPD * Serious cardiovascular conditions — moderate sympathomimetic effects expected * Concurrent serotonergic medications (SSRIs, SNRIs, tramadol) — attenuated or unpredictable effects; serotonin toxicity risk with tramadol * Pregnancy or breastfeeding — no safety data exist * Unstable psychiatric conditions — risk of destabilisationsupported

Tramadol inhibits SERT in human SERT-transfected HEK293 cells. FDA Drug Safety Communication March 2016 on opioids and serotonin toxicity. Particularly when combined with MAOIs, SSRIs, SNRIs. s00204-018-2244-6

The metabolic pathways and biological activities of 1cP-AL-LAD have not been reportedsupported

The metabolic pathways and biological activities of 1cP-AL-LAD and 1cP-MIPLA have not been reported. s11419-023-00661-1

N1-cyclopropanoyl hydrolysis: 1cP-LSD (cyclopropanoyl at N1, methyl at N6) undergoes hydrolysis in human serum to yield LSD, confirming that the cyclopropanecarbonyl group is cleaved in vivo.supported

Incubation of 1CP-LSD with human serum led to the formation of LSD, indicating that it may act as a prodrug for LSD in vivo. dta.2789

N1-acyl AL-LAD deacylation: 1P-AL-LAD (propanoyl at N1, allyl at N6) converts to AL-LAD as the most abundant metabolite in pooled human liver microsomes, with N1-deacylation as the primary metabolic step and 14 total metabolites detected.supported

1P-AL-LAD converted to AL-LAD as the most abundant metabolite in pooled human liver microsomes, consistent with prodrug hypothesis. 14 metabolites detected including hydroxylation, N-dealkylation, N1-deacylation, dihydrodiol formation, dehydrogenation. dta.3281

ALD-52, 1P-LSD, and 1B-LSD all show weak efficacy or frank antagonism in functional Ca²⁺ assays at the 5-HT₂A receptor, yet administration to rats produces high plasma concentrations of the deacylated parent — confirming in vivo prodrug conversion rather than intrinsic activitysupported

ALD-52, 1P-LSD and 1B-LSD have weak efficacy or act as antagonists at 5-HT2A. High LSD plasma levels after 1P-LSD in rats confirms prodrug status. j.neuropharm.2019.107856

This pattern extends across all studied N1-acyl lysergamides including 1V-LSD, 1B-LSD, 1P-ETH-LAD, and 1F-LSD/1T-LSD.supported

N1-acyl lysergamides act as weak partial agonists at 5-HT2A and believed to serve as prodrugs for LSD. 1V-LSD ED50 = 373 nmol/kg. dta.3205

This pattern extends across all studied N1-acyl lysergamides including 1V-LSD, 1B-LSD, 1P-ETH-LAD, and 1F-LSD/1T-LSD.supported

1B-LSD ED50 = 976.7 nmol/kg. Behavioral effects reminiscent of LSD. Possible prodrug. dta.2613

This pattern extends across all studied N1-acyl lysergamides including 1V-LSD, 1B-LSD, 1P-ETH-LAD, and 1F-LSD/1T-LSD.supported

1P-ETH-LAD incubated with human serum led to formation of ETH-LAD, suggesting prodrug mechanism. dta.2196

This pattern extends across all studied N1-acyl lysergamides including 1V-LSD, 1B-LSD, 1P-ETH-LAD, and 1F-LSD/1T-LSD.supported

1F-LSD and 1T-LSD induced HTR in mice and were hydrolyzed to LSD after in vivo administration. Both substances exhibit LSD-like properties as prodrugs for LSD. dta.3829

Claim in pharmacology — inconclusiveinconclusiveworking →

Grumann and colleagues administered 100 µg oral 1P-LSD to human volunteers and detected only LSD in serum and urine, with no intact 1P-LSD measurable, indicating essentially complete presystemic hydrolysis and an apparent bioavailability of the active species approaching 100%supported

Oral 1P-LSD (100 µg): only LSD detected in serum/urine... Bioavailability of LSD from oral 1P-LSD ~100%. dta.2821

LSD itself has an absolute oral bioavailability of approximately 80%.supported

Absolute oral bioavailability of LSD was 80% across all tested formulations. cpt.3726

Subsequent phase I metabolism of AL-LAD proceeds via CYP1A2 and CYP3A4, producing hydroxylated metabolites, dihydrodiols, N-dealkylated products, and dehydrogenated speciespartially supported

N-dealkylation and hydroxylation predominantly catalyzed by CYP1A2 and CYP3A4. s00216-018-1558-9

Brandt and colleagues identified 14 total metabolites from 1P-AL-LAD incubation in human liver microsomes, with a similar profile expected for 1cP-AL-LAD.supported

14 metabolites detected including hydroxylation, N-dealkylation, N1-deacylation, dihydrodiol formation, dehydrogenation. dta.3281

The terminal elimination half-life of LSD derived from oral 1P-LSD is approximately 6.4 hourssupported

LSD elimination t1/2=6.4h. dta.2821

For comparison, 1P-LSD was administered at 100 µg in the only controlled human study of an N1-acyl lysergamide.supported

Oral 1P-LSD (100 µg): only LSD detected in serum/urine. dta.2821

The mouse head-twitch response (HTR) is a 5-HT₂A-dependent behaviour that correlates strongly with human hallucinogenic potency (r = 0.9448)supported

Strong positive correlation (r=0.9448) between HTR potencies in mice and reported hallucinogenic potencies in humans (n=36). j.neuropharm.2019.107933

N1-acylation reduces potency relative to the unsubstituted parent, consistent with the prodrug model: the N1-acyl compound must first be hydrolysed before the active species engages the receptor. The magnitude of reduction is 2–3× for short-chain acyl groups and up to 7× for butanoyl.supported

1B-LSD ED50 = 976.7 nmol/kg (~14% potency of LSD at 132.8 nmol/kg). dta.2613

N6-allyl substitution reduces potency modestly relative to N6-methyl: AL-LAD (174.9 nmol/kg) versus LSD (132.8 nmol/kg), and 1P-AL-LAD (491 nmol/kg) versus 1cP-LSD (430 nmol/kg).supported

AL-LAD ED50 = 174.9 nmol/kg; LSZ ED50 = 114.2 nmol/kg vs LSD ED50 = 132.8 nmol/kg. dta.1985

N6-allyl substitution reduces potency modestly relative to N6-methyl: AL-LAD (174.9 nmol/kg) versus LSD (132.8 nmol/kg), and 1P-AL-LAD (491 nmol/kg) versus 1cP-LSD (430 nmol/kg).supported

1P-AL-LAD ED50 = 491 nmol/kg vs AL-LAD 174.9 nmol/kg in mouse HTR assay. dta.3281

The reported total duration of 1cP-AL-LAD (7–10 hours, oral) is comparable to LSD's mean subjective duration of 8.2 hours in a controlled crossover studysupported

LSD effect duration mean 8.2h. s41386-023-01607-2

A review covering this body of work appeared in the NIDA Research Monograph 146 ("Lysergamides revisited", Pfaff, Huang, Marona-Lewicka, Oberlender, and Nichols, 1994).supported

NIDA Research Monograph 146: Hallucinogens: An Update. Historical review of lysergamide pharmacology. AL-LAD and related N6-substituted nor-LSD analogs described. pmid:8742794

AL-LAD entered the novel psychoactive substance (NPS) market in 2013, appearing in both powdered and blotter formsupported

AL-LAD and LSZ appeared on the NPS market in 2013 in both powdered and blotter form. dta.1985

Its mouse head-twitch response (HTR) ED₅₀ of 174.9 nmol/kg confirmed hallucinogenic activity broadly comparable to LSD (ED₅₀ = 132.8 nmol/kg).supported

AL-LAD ED50 = 174.9 nmol/kg... vs LSD ED50 = 132.8 nmol/kg. AL-LAD slightly less potent than LSD in mice. dta.1985

Claim in history — inconclusiveinconclusiveworking →

Kavanagh and colleagues described the full analytical profile (HPLC-ESI-QTOF-MS, NMR) of 1cP-AL-LAD purchased from an online vendor, identified 17 impurities including confirmed AL-LAD and 1P-AL-LAD, and detected the compound on commercial blotters.supported

using various chromatographic, mass spectrometric, and spectroscopic methods... 17 impurities... detection of AL-LAD and 1P-AL-LAD was confirmed using available reference standards... detected in samples of blotters sold online for recreational use. dta.3397

Tanaka and colleagues independently identified 1cP-AL-LAD in sheet products monitored or seized in Japan using GC-MS, LC-PDA-MS, LC-Q-TOF-MS, and NMR — the first forensic report from an Asian jurisdiction.supported

The structures of the compounds were determined by GC-MS, LC-PDA-MS, LC-Q-TOF-MS and NMR spectroscopy... This is the first report showing that LSD analogs converted at multiple positions have been detected in sheet products in Japan. s11419-023-00661-1

1cP-AL-LAD first appeared in the scientific literature in 2023, when two independent forensic studies characterised its analytical profile: Kavanagh and colleagues published HPLC-ESI-QTOF-MS impurity data from a commercial sample, and Tanaka and colleagues reported its identification in sheet products monitored in Japansupported

Analysis of a powdered sample of 1cP-AL-LAD, obtained from an online vendor, by HPLC-ESI-QTOF-MS in full scan/AutoMS/MS mode revealed the detection of 17 impurities based on high-resolution tandem mass spectral data dta.3397

1cP-AL-LAD first appeared in the scientific literature in 2023, when two independent forensic studies characterised its analytical profile: Kavanagh and colleagues published HPLC-ESI-QTOF-MS impurity data from a commercial sample, and Tanaka and colleagues reported its identification in sheet products monitored in Japansupported

This is the first report showing that LSD analogs converted at multiple positions have been detected in sheet products in Japan. s11419-023-00661-1

The prodrug hypothesis rests on convergent structural analog evidence: the N1-cyclopropanoyl group is hydrolysed to yield the parent lysergamide in human serum (demonstrated for 1cP-LSD), and N1-acyl AL-LAD analogs undergo deacylation to AL-LAD as the primary metabolite in human liver microsomes (demonstrated for 1P-AL-LAD)supported

Incubation of 1CP-LSD with human serum led to the formation of LSD, indicating that it may act as a prodrug for LSD in vivo. dta.2789

The prodrug hypothesis rests on convergent structural analog evidence: the N1-cyclopropanoyl group is hydrolysed to yield the parent lysergamide in human serum (demonstrated for 1cP-LSD), and N1-acyl AL-LAD analogs undergo deacylation to AL-LAD as the primary metabolite in human liver microsomes (demonstrated for 1P-AL-LAD)supported

1P-AL-LAD converted to AL-LAD as the most abundant metabolite in pooled human liver microsomes, consistent with prodrug hypothesis. dta.3281

Claim in summary — inconclusiveinconclusiveworking →

Tolerance develops almost immediately via 5-HT₂A receptor downregulation and resets over approximately 14 days; dependence liability is negligiblepartially supported

Daily LSD for 5 days produced decrease in 5-HT2 binding in cortex within 3 days. Decreased binding parallels development and loss of behavioral tolerance. pmid:1969270

N1-acyl axis: A cyclopropanecarbonyl group is appended at the N1 (indole nitrogen) position, following the same prodrug design as 1cP-LSD.supported

1-Cyclopropanoyl-LSD (1CP-LSD)... Incubation of 1CP-LSD with human serum led to the formation of LSD, indicating that it may act as a prodrug for LSD in vivo. dta.2789

N6-allyl axis: The N6-methyl group of LSD is replaced by an allyl (prop-2-en-1-yl) group, yielding the AL-LAD (N6-allyl-6-nor-LSD) scaffold.supported

N6-allyl-6-norlysergic acid diethylamide (AL-LAD) dta.1985

Claim in chemistry — inconclusiveinconclusiveworking →

The alternate IUPAC representation uses the ergoline ring numbering system as given in the primary analytical paper.supported

IUPAC name: 1-(cyclopropanecarbonyl)-N,N-diethyl-6-(prop-2-en-1-yl)-9,10-didehydroergoline-8β-carboxamide dta.3397

Commercial samples have been analysed as powder and on blotter papersupported

Analysis of a powdered sample of 1cP-AL-LAD... 1cP-AL-LAD was also detected in samples of blotters sold online for recreational use. dta.3397

As an N1-acyl prodrug, 1cP-AL-LAD itself is expected to have negligible direct receptor activity; pharmacological effects depend on in vivo conversion to AL-LAD.supported

1-acyl substitution reduced affinity for monoamine receptors by 1-2 orders of magnitude vs LSD. ALD-52, 1P-LSD and 1B-LSD have weak efficacy or act as antagonists at 5-HT2A. High LSD plasma levels after 1P-LSD in rats confirms prodrug status. j.neuropharm.2019.107856

For structural context: LSD binds 5-HT₂A with Ki in the 1–3 nM range and was co-crystallised with the 5-HT₂B receptor, revealing deep orthosteric binding with extracellular loop 2 (EL2) "lid" closure responsible for slow dissociation kinetics and prolonged receptor occupancypartially supported

Crystal structure of LSD in complex with 5-HT2B receptor. LSD dissociates exceptionally slowly. EL2 'lid' mechanism for slow kinetics. j.cell.2016.12.033

The Gq-coupled active-state structure of the 5-HT₂A receptor bound to a hallucinogen further elucidates the structural basis for psychedelic signalling.supported

Determined active-state structure of HTR2A bound to 25-CN-NBOH in complex with engineered Gαq heterotrimer by cryo-EM. j.cell.2020.08.024

The selective 5-HT₂A antagonist ketanserin completely abolishes all subjective effects of LSD in humans, confirming 5-HT₂A as the necessary receptor for lysergamide psychedelic activitypartially supported

LSD psychedelic effects almost fully blocked by 5-HT2A antagonist ketanserin administered after LSD. pyac075

Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

Claim in neuroscience — inconclusiveinconclusiveworking →

The ketanserin blocking study confirms that 5-HT₂A is the necessary and sufficient receptor for LSD-type psychedelic effects; this finding presumably extends to AL-LAD.partially supported

LSD psychedelic effects almost fully blocked by 5-HT2A antagonist ketanserin administered after LSD. Effect reversal supports 5-HT2A as primary site of psychedelic action. pyac075

LSD and other serotonergic psychedelics promote structural and functional neuroplasticity via BDNF-TrkB-mTOR signalling cascades, producing rapid dendritic spine growth in cortical neuronssupported

Psychedelic compounds act primarily through 5-HT2A receptor agonism activating BDNF/TrkB/mTOR pathway. Neuroplasticity, synaptogenesis. ph18040499

A comparative study of mescaline, LSD, and psilocybin in healthy volunteers (Phase 1, Basel; NCT04227756) established LSD's mean subjective effect duration at 8.2 hours and characterised its autonomic effects.supported

Mescaline (500mg), LSD (100µg), psilocybin (20mg) compared in RCT... LSD effect duration mean 8.2h. s41386-023-01607-2

A direct comparison of LSD and psilocybin (double-blind, placebo-controlled, Phase 1) documented the full subjective and cardiovascular effect profiles at controlled doses.supported

100 and 200 µg LSD vs psilocybin 15/30 mg in 28 healthy subjects... LSD increases heart rate more; psilocybin increases BP more. s41386-022-01297-2

The metabolic profile is expected to mirror that of 1P-AL-LAD, for which Brandt and colleagues identified the following reaction classes in human liver microsomes: N1-deacylation (primary), hydroxylation of the ergoline ring and allyl side chain, dihydrodiol formation, N-dealkylation of the diethylamide group, and dehydrogenation, including combination reactions yielding 14 total metabolitessupported

14 metabolites detected including hydroxylation, N-dealkylation, N1-deacylation, dihydrodiol formation, dehydrogenation. dta.3281

AL-LAD itself is further metabolised by CYP1A2 and CYP3A4.supported

Elucidate pooled human liver S9 fraction metabolism of nine LSD derivatives including AL-LAD. N-dealkylation and hydroxylation predominantly catalyzed by CYP1A2 and CYP3A4. s00216-018-1558-9

Set and setting exert outsized influence on the qualitative character of any given experience — the same dose can produce profoundly different outcomes depending on mindset, physical environment, and social contextsupported

Risk factors: lithium/mood stabilizer co-use, poor set/setting, dose too large. j.jad.2023.01.073

Claim in legal-status — inconclusiveinconclusiveworking →