1V-LSD

No direct receptor binding or biotransformation data have been published for 1V-LSD itself; the prodrug hypothesis rests on converging evidence from structurally related N1-acyl LSD derivatives.supported

Analytical characterization via MS, GC, LC, NMR, GC-sIR, Raman spectroscopy. HTR ED50 = 373 nmol/kg (~1/3 potency of LSD). Likely prodrug for LSD via hydrolysis. dta.3205

N1-acyl substitution reduces monoamine receptor affinity by 1–2 orders of magnitude relative to LSD and converts the compound from a 5-HT₂A partial agonist to a weak partial agonist or functional antagonist in calcium flux assayssupported

1-acyl substitution reduces monoamine receptor affinity by 1-2 orders of magnitude. ALD-52, 1P-LSD, 1B-LSD show weak efficacy or act as antagonists at 5-HT2A in Ca2+ assays. j.neuropharm.2019.107856

In vitro hydrolysis: Incubation of 1CP-LSD with human serum produces LSD. N1-deacylation is the primary metabolic reaction for 1P-AL-LAD in pooled human liver microsomes. Temperature-dependent hydrolysis of ALD-52 and 1P-LSD to LSD occurs in serum at room temperature.supported

1CP-LSD incubated with human serum -> LSD formation (in vitro prodrug evidence). dta.2789

In vitro hydrolysis: Incubation of 1CP-LSD with human serum produces LSD. N1-deacylation is the primary metabolic reaction for 1P-AL-LAD in pooled human liver microsomes. Temperature-dependent hydrolysis of ALD-52 and 1P-LSD to LSD occurs in serum at room temperature.supported

1P-AL-LAD metabolized to AL-LAD in human liver microsomes (pHLM). N1-deacylation primary metabolic reaction. dta.3281

Claim in pharmacology — inconclusiveinconclusiveworking →

In vitro hydrolysis: Incubation of 1CP-LSD with human serum produces LSD. N1-deacylation is the primary metabolic reaction for 1P-AL-LAD in pooled human liver microsomes. Temperature-dependent hydrolysis of ALD-52 and 1P-LSD to LSD occurs in serum at room temperature.supported

Temperature-dependent hydrolysis of 1P-LSD to LSD (up to 21% in serum at RT). j.jpba.2019.05.062

In vivo human evidence: After oral or intravenous administration of 100 µg 1P-LSD to two human volunteers, only LSD was detected in serum and urine — not 1P-LSD itself — with LSD t½ ≈ 5.7–6.4 h; bioavailability of LSD from oral 1P-LSD was "close to 100%".supported

1P-LSD oral ingestion: only LSD detected in serum/urine (not parent 1P-LSD). LSD t1/2 ≈ 5.7h. 1P-LSD bioavailability of LSD close to 100% via oral prodrug. dta.2821

In vivo animal evidence: High LSD plasma levels were detected in rats after 1P-LSD administration. Both 1F-LSD and 1T-LSD hydrolyzed to LSD after in vivo administration to mice.supported

High LSD plasma levels after 1P-LSD in rats confirms prodrug status. j.neuropharm.2019.107856

In vivo animal evidence: High LSD plasma levels were detected in rats after 1P-LSD administration. Both 1F-LSD and 1T-LSD hydrolyzed to LSD after in vivo administration to mice.supported

1F-LSD and 1T-LSD both serve as prodrugs. N1-acylated LSD derivatives hydrolyzed to LSD in vivo. dta.3829

Claim in pharmacology — inconclusiveinconclusiveworking →

1V-LSD was tested in C57BL/6J mice using the head-twitch response (HTR) assay — a 5-HT₂A-mediated behavior validated as a predictive proxy for hallucinogenic potency in humans (r = 0.9448 across 41 compounds).supported

Strong correlation (r=0.9448) between HTR potency in mice and hallucinogenic potency in humans across 41 compounds. j.neuropharm.2019.107933

1V-LSD induced a dose-dependent HTR with an ED₅₀ of 373 nmol/kg (approximately 152 µg/kg), roughly one-third the potency of LSD (ED₅₀ = 132.8 nmol/kg) under identical conditionssupported

HTR ED50 = 373 nmol/kg (~1/3 potency of LSD). dta.3205

The decreased potency relative to LSD likely reflects incomplete hydrolysis efficiency rather than direct 5-HT₂A activity.supported

HTR ED50 = 373 nmol/kg (~1/3 potency of LSD). Likely prodrug for LSD via hydrolysis. dta.3205

Claim in pharmacology — inconclusiveinconclusiveworking →

Oral bioavailability: 80%; base and tartrate formulations are bioequivalentsupported

LSD oral bioavailability confirmed at 80%. All oral formulations bioequivalent. cpt.3726

Half-life: 2.7 h at microdoses; ~5.7–6.4 h at 100 µg; up to 11.6 h in CYP2D6 poor metabolizerssupported

LSD t1/2 ≈ 5.7h. dta.2821

Claim in pharmacology — inconclusiveinconclusiveworking →

Primary metabolizing enzyme: CYP2D6; poor metabolizers exhibit ~75% higher LSD AUC and prolonged subjective effectssupported

CYP2D6 poor metabolizers had ~75% higher LSD AUC and longer half-lives; greater alterations of mind and longer subjective effects. CYP1A2, CYP2C9, CYP2C19, CYP2B6 had no effect. s41598-021-90343-y

Primary urinary metabolite: 2-oxo-3-hydroxy-LSD (OH-LSD); additional metabolites include nor-LSD, nor-iso-LSD, trioxylated-LSD, and 13/14-hydroxy-LSD glucuronidessupported

OH-LSD (2-oxo-3-hydroxy-LSD) main urine metabolite; nor-LSD, nor-iso-LSD, trioxylated-LSD, 13/14-OH-LSD glucuronides also detected. s1570-0232(01)00494-9

By analogy with 1P-LSD — where the parent compound was detectable in serum for only 4.16 h and in urine for 2.7 h post-dose — 1V-LSD itself is expected to have a short plasma half-life, with LSD as the principal detected active species.supported

1P-LSD oral ingestion: only LSD detected in serum/urine (not parent 1P-LSD). dta.2821

No well-documented human fatalities from LSD alone have been reported in the published literaturesupported

Physiologically well tolerated; psychological reactions controllable in supervised settings. j.1755-5949.2008.00059.x

Claim in safety — inconclusiveinconclusiveworking →

An intoxication case involving 1P-LSD was investigated analytically, finding 0.51 ng/mL LSD in urine and 3.4 ng/mL in serum, with 1P-LSD undetected — consistent with complete prodrug conversion.supported

Applied to intoxication case: only LSD detected in urine/serum after oral 1P-LSD ingestion. j.jpba.2019.05.062

Claim in safety — inconclusiveinconclusiveworking →

Claim in safety — inconclusiveinconclusiveworking →

Acute anxiety and distress: In controlled settings, 200 µg LSD produced significant anxiety in healthy volunteerssupported

Greater ego dissolution and anxiety at 200µg. s41386-020-00883-6

Good drug effects plateau at 100 µg while ego dissolution and anxiety continue to increase with dosesupported

Ceiling for good effects at 100µg, greater ego dissolution and anxiety at 200µg. s41386-020-00883-6

Hallucinogen persisting perception disorder (HPPD): A rare complication characterized by re-emergence of perceptual symptoms after drug cessation, without impaired reality testingsupported

HPPD: rare disorder of enduring perceptual symptoms without impaired reality control after psychedelic use. s41598-024-82216-x

Hallucinogen persisting perception disorder (HPPD): A rare complication characterized by re-emergence of perceptual symptoms after drug cessation, without impaired reality testingsupported

39.7% of hallucinogen users reported Type I HPPD symptoms; 4.3% Type II. 02791072.2023.2287081

LSD is the most frequently implicated substance in HPPD case reportssupported

LSD most common hallucinogen causing HPPD. cureus.46262

Prevalence estimates vary widely: up to 39.7% for mild Type I symptoms (brief perceptual disturbances) in one self-report survey, and 4.3% for Type II HPPD with functional impairmentsupported

39.7% of hallucinogen users reported Type I HPPD symptoms; 4.3% Type II. 02791072.2023.2287081

Treatment options include benzodiazepines (clonazepam) or lamotrigine; antipsychotics are generally ineffective.supported

Lamotrigine improved symptoms when antipsychotics failed. cureus.46262

Claim in safety — inconclusiveinconclusiveworking →

Claim in safety — inconclusiveinconclusiveworking →

Claim in safety — inconclusiveinconclusiveworking →

A meta-analysis of psychedelic RCTs found no association between psychedelics and higher all-cause discontinuation.supported

Not associated with higher all-cause discontinuation. j.euroneuro.2025.09.011

CYP2D6 inhibitors: Fluoxetine, paroxetine, and bupropion may increase LSD exposure following 1V-LSD prodrug conversion by inhibiting the primary metabolic clearance pathway.supported

CYP2D6 poor metabolizers had ~75% higher LSD AUC and longer half-lives. CYP1A2, CYP2C9, CYP2C19, CYP2B6 had no effect. s41598-021-90343-y

LSD was synthesized by Albert Hofmann at Sandoz Laboratories in Basel, Switzerland, in 1938; its psychedelic properties were discovered accidentally during self-experimentation on April 19, 1943supported

Synthesized 1938, psychoactive effects discovered 1943. j.1755-5949.2008.00059.x

Claim in history — not_supportednot supportedworking →

Each compound extended the acyl chain by one or more carbons: ALD-52 (C2 acetyl) → 1P-LSD (C3 propanoyl) → 1B-LSD (C4 butanoyl) → 1V-LSD (C5 pentanoyl) → 1H-LSD (C6 hexanoyl) → 1DD-LSD (C12 dodecanoyl)supported

1H-LSD HTR ED50 = 192.4 µg/kg (387 nmol/kg), roughly equipotent to ALD-52. N1-acyl LSD derivative anticipated to be hydrolyzed to LSD in vivo. dta.3767

Each compound extended the acyl chain by one or more carbons: ALD-52 (C2 acetyl) → 1P-LSD (C3 propanoyl) → 1B-LSD (C4 butanoyl) → 1V-LSD (C5 pentanoyl) → 1H-LSD (C6 hexanoyl) → 1DD-LSD (C12 dodecanoyl)supported

1DD-LSD HTR ED50 = 2.17 mg/kg (27-fold less potent than LSD). N1-acyl homolog series. dta.3691

The compounds were systematically characterized in the "Return of the Lysergamides" publication series by Brandt, Kavanagh, Halberstadt, and collaborators: Part II covered AL-LAD and LSZ, Part IV LSM-775, Part V 1B-LSD, Part VI 1CP-LSD, and Part VII — the subject of this article — 1V-LSD.supported

Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM-775) dta.2222

The compounds were systematically characterized in the "Return of the Lysergamides" publication series by Brandt, Kavanagh, Halberstadt, and collaborators: Part II covered AL-LAD and LSZ, Part IV LSM-775, Part V 1B-LSD, Part VI 1CP-LSD, and Part VII — the subject of this article — 1V-LSD.supported

Return of the lysergamides. Part V: Analytical and behavioural characterization of 1-butanoyl-d-lysergic acid diethylamide (1B-LSD) dta.2613

The compounds were systematically characterized in the "Return of the Lysergamides" publication series by Brandt, Kavanagh, Halberstadt, and collaborators: Part II covered AL-LAD and LSZ, Part IV LSM-775, Part V 1B-LSD, Part VI 1CP-LSD, and Part VII — the subject of this article — 1V-LSD.supported

Return of the lysergamides. Part VII: Analytical and behavioural characterization of 1-valeroyl-d-lysergic acid diethylamide (1V-LSD) dta.3205

Claim in history — inconclusiveinconclusiveworking →

A validated forensic LC-MS/MS method for 1V-LSD detection in urine (LOD 0.1 ng/mL) was subsequently developed, though no positive urine specimens were found among 325 samples tested.supported

LC-MS/MS method validated for LSD, OH-LSD, and 9 LSD analogs including 1V-LSD in urine. LOD 0.1 ng/mL. No LSD analogs detected in 325 urine specimens tested. 1556-4029.15572

Claim in summary — inconclusiveinconclusiveworking →

1V-LSD first appeared on the online research chemical market around 2020–2021 and was analytically and pharmacologically characterized by Brandt et al. in 2022 as Part VII of the "Return of the Lysergamides" seriessupported

Return of the lysergamides. Part VII: Analytical and behavioural characterization of 1-valeroyl-d-lysergic acid diethylamide (1V-LSD) dta.3205

N1-acyl substitution reduces monoamine receptor affinity by 1–2 orders of magnitude relative to LSD, converting the compound from an active 5-HT₂A agonist to a functionally inert precursor that requires in vivo hydrolysis to liberate LSDsupported

1-acyl substitution reduces monoamine receptor affinity by 1-2 orders of magnitude. ALD-52, 1P-LSD, 1B-LSD show weak efficacy or act as antagonists at 5-HT2A in Ca2+ assays. High LSD plasma levels after 1P-LSD in rats confirms prodrug status. j.neuropharm.2019.107856

In mice, 1V-LSD produces a dose-dependent head-twitch response (ED₅₀ = 373 nmol/kg), approximately one-third the potency of LSD (ED₅₀ = 132.8 nmol/kg), consistent with incomplete but efficient prodrug conversionsupported

HTR ED50 = 373 nmol/kg (~1/3 potency of LSD). Likely prodrug for LSD via hydrolysis. dta.3205

Following conversion, LSD acts primarily as a 5-HT₂A partial agonist; ketanserin (40 mg) completely blocks all subjective LSD effectssupported

Ketanserin blocked all effects. 5-HT2A primary mediator. s41386-020-00883-6

As a prodrug for LSD, 1V-LSD inherits LSD's negligible acute toxicity profile: no well-documented human fatalities from LSD alone have been reportedsupported

Physiologically well tolerated; psychological reactions controllable in supervised settings. j.1755-5949.2008.00059.x

Claim in summary — inconclusiveinconclusiveworking →

No biotransformation data, human pharmacokinetic parameters, or controlled dose-response studies have been published for 1V-LSD specifically — all safety and efficacy characterizations rest on LSD class inference pending direct investigation.supported

Analytical characterization via MS, GC, LC, NMR, GC-sIR, Raman spectroscopy. HTR ED50 = 373 nmol/kg (~1/3 potency of LSD). Likely prodrug for LSD via hydrolysis. dta.3205

This receptor is the primary mediator of hallucinogenic effects — the selective 5-HT₂A antagonist ketanserin (40 mg oral) completely blocks all subjective LSD effects in healthy volunteerssupported

Ketanserin blocked all effects. 5-HT2A primary mediator. s41386-020-00883-6

N1-acyl substitution itself reduces monoamine receptor affinity by 1–2 orders of magnitude relative to LSDsupported

1-acyl substitution reduces monoamine receptor affinity by 1-2 orders of magnitude. j.neuropharm.2019.107856

Crystallographic analysis of LSD bound to 5-HT₂B reveals a slow-dissociation mechanism mediated by extracellular loop 2 (EL2), which forms a "lid" over the binding pocket; the same mechanism is inferred at 5-HT₂A and may explain the prolonged duration of action.supported

Crystal structure of LSD bound to 5-HT2B receptor. EL2 'lid' mechanism explains slow LSD dissociation from 5-HT2A and 5-HT2B. j.cell.2016.12.033

Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

TrkB-mediated neuroplasticity effects are independent of 5-HT₂A activation, representing a mechanistically distinct pathway.supported

TrkB-mediated neuroplasticity is independent of 5-HT2A; head-twitch (hallucinogenic proxy) is TrkB-independent. s41593-023-01316-5

5-HT₂A–mGluR2 heterodimer: The 5-HT₂A–mGluR2 receptor complex is required for hallucinogen-specific intracellular signaling; mGluR2 activation abolishes hallucinogen-specific downstream responses.supported

5-HT2A-mGluR2 heterodimer forms functional complex in brain cortex. Hallucinogenic drugs trigger unique cellular responses via this complex. mGluR2 activation abolishes hallucinogen-specific signaling. nature06612

Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

Claim in comparative-pharmacology — inconclusiveinconclusiveworking →

Claim in comparative-pharmacology — inconclusiveinconclusiveworking →

ALD-52 potency is stated as roughly equipotent to 1H-LSD (387 nmol/kg).supported

1H-LSD HTR ED50 = 192.4 µg/kg (387 nmol/kg), roughly equipotent to ALD-52. dta.3767

Long-chain collapse: 1DD-LSD (C12) retains only ~4% of LSD potency, consistent with steric impedance of hydrolysis or reduced bioavailability of the long-chain derivative.supported

1DD-LSD HTR ED50 = 2.17 mg/kg (27-fold less potent than LSD). N1-acyl homolog series; increased lipophilicity may reduce enzymatic hydrolysis efficiency. dta.3691

The only human PK data in the series come from 1P-LSD, where oral bioavailability of the liberated LSD approached 100%supported

1P-LSD bioavailability of LSD close to 100% via oral prodrug. dta.2821

By analogy with other N1-acyl LSD derivatives, the compound is expected to be susceptible to hydrolysis under acidic conditions and in alcoholic solventssupported

Temperature-dependent hydrolysis of 1P-LSD to LSD (up to 21% in serum at RT). j.jpba.2019.05.062

The compound is derived from d-LSD by acylation of the N1 indole nitrogen with a pentanoyl (valeroyl, C₅H₉O) group, making it the C5 homolog in the series of N1-acylated LSD derivatives.supported

1V-LSD (also known as 1-valeryl-LSD, 1-pentanoyl-LSD, or 'Valerie') is a new N1-acylated LSD derivative. dta.3205

The pentanoyl group may confer greater steric protection of the N1-acyl bond than the shorter acetyl group of ALD-52, and comparable stability to the propanoyl group of 1P-LSD, based on the steric hindrance trend observed across the series.supported

1P-LSD more stable than ALD-52 due to steric hindrance from propanoyl group. 1556-4029.15224

In a pooled analysis of 83 participants, CYP2D6 poor metabolizers exhibited approximately 75% higher LSD area under the curve (AUC) and prolonged subjective effects compared to normal metabolizerssupported

CYP2D6 poor metabolizers had ~75% higher LSD AUC and longer half-lives; greater alterations of mind and longer subjective effects. s41598-021-90343-y

For the structurally analogous 1P-LSD, oral administration to two human volunteers produced rapidly detectable serum LSD, with 1P-LSD itself detectable for only 4.16 h in serum and 2.7 h in urine; LSD then followed biphasic elimination with t½ ≈ 5.7–6.4 hsupported

1P-LSD oral ingestion: only LSD detected in serum/urine (not parent 1P-LSD). LSD t1/2 ≈ 5.7h. dta.2821

Bioavailability of LSD from oral 1P-LSD was "close to 100%", suggesting highly efficient prodrug conversion.supported

1P-LSD bioavailability of LSD close to 100% via oral prodrug. dta.2821

The second, recently characterized, involves direct binding to the TrkB (BDNF) receptor with approximately 1,000-fold higher affinity than conventional antidepressants; this TrkB-mediated pathway is independent of 5-HT₂A activationsupported

LSD and psilocin bind TrkB ~1,000-fold higher affinity than other antidepressants. TrkB-mediated neuroplasticity is independent of 5-HT2A. s41593-023-01316-5

The psychoplastogen framework predicts that LSD-class compounds may have therapeutic effects that persist beyond the acute pharmacological window, mediated by structural remodeling of neural circuits.supported

LSD and psilocin bind TrkB ~1,000-fold higher affinity than other antidepressants. TrkB-mediated neuroplasticity is independent of 5-HT2A. s41593-023-01316-5

A living systematic review and meta-analysis of serotonergic psychedelic RCTs found no association between psychedelics and higher all-cause discontinuation, supporting a favorable tolerability profile for the classsupported

30 RCTs (n=1480). Not associated with higher all-cause discontinuation. j.euroneuro.2025.09.011

Onset may be slightly more gradual than LSD itself, plausibly reflecting the hydrolysis step, though this has not been confirmed in controlled settings.supported

Likely prodrug for LSD via hydrolysis. dta.3205