1V-LSD

# Research Output: 1V-LSD

## Chemical Identity

**Verified via PubChem (CID 162368540):**
- **Systematic name (IUPAC):** (6aR,9R)-N,N-diethyl-7-methyl-4-pentanoyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide
- **Molecular formula:** C₂₅H₃₃N₃O₂
- **Molecular weight:** 407.5 g/mol
- **InChIKey:** GIIBVGJWUZNECE-XMSQKQJNSA-N
- **PubChem CID:** 162368540
- **SMILES:** Not returned by PubChem API in this query; generation agent should retrieve canonical SMILES directly from CID 162368540 on PubChem.

**Seed data verification:** The brief's systematic name, chemical class designations (Indole, Indoleamine, Tryptamine, Ergoline, Lysergamide), and PubChem CID were all confirmed. The brief lists no molecular formula, SMILES, or InChIKey — all are now populated from PubChem verification. The molecular weight of 407.5 g/mol confirms 1V-LSD is ~70 Da heavier than LSD (MW 323.4 g/mol), consistent with addition of a pentanoyl (C₅H₉O) group at the N1 indole nitrogen.

**Alternative names:** 1-valeroyl-LSD, 1-valeryl-LSD, 1-pentanoyl-LSD; street name "Valerie" (Brandt et al. 2022 [Ref 1]).

**Stereochemistry:** The (6aR,9R) configuration is specified in the IUPAC name and PubChem record, consistent with the d-lysergamide (active) stereochemistry. 1V-LSD is synthesized from d-LSD.

**Physical properties:** No published melting point, solubility, or stability data specific to 1V-LSD. By analogy with 1P-LSD (Grumann et al. 2019 [Ref 29]; Zhang et al. 2023 [Ref 30]), N1-acyl LSD derivatives are susceptible to hydrolysis under acidic conditions and in alcoholic solvents; the valeroyl group may confer greater steric protection than the acetyl group of ALD-52 and comparable stability to 1P-LSD (propanoyl), based on the steric hindrance trend observed in the series [Ref 30].

---

## Pharmacology

### Prodrug Hypothesis and Mechanism of Action

The central pharmacological question for 1V-LSD is whether it acts as a prodrug for LSD. Brandt et al. (2022 [Ref 1]) explicitly state: "1V-LSD is also likely to be hydrolyzed to LSD and serve as a prodrug, but studies to assess the biotransformation and receptor pharmacology of 1V-LSD should be performed to fully elucidate its mechanism of action."

**FLAG (human review required):** No published biotransformation or direct receptor binding data exist for 1V-LSD itself. All mechanistic statements below are inferred from the N1-acyl LSD class.

The prodrug hypothesis rests on three converging lines of evidence from closely related analogs:

1. **Receptor pharmacology:** N1-acyl substitution reduces monoamine receptor affinity by 1–2 orders of magnitude and converts LSD from a 5-HT₂A partial agonist to a weak partial agonist or functional antagonist at 5-HT₂A in calcium flux assays (Halberstadt et al. 2020 [Ref 28]). This explains why these compounds depend on in vivo hydrolysis to generate LSD for their activity.

2. **In vitro hydrolysis:** For 1CP-LSD, incubation with human serum produces LSD, confirming enzymatic hydrolysis (Brandt et al. 2020 [Ref 21]). For 1P-AL-LAD, N1-deacylation is the primary reaction in pooled human liver microsomes (pHLM) (Brandt et al. 2022 [Ref 24]). Temperature-dependent hydrolysis of ALD-52 and 1P-LSD to LSD in serum is documented at room temperature (Zhang et al. 2023 [Ref 30]; Grumann et al. 2019 [Ref 29]).

3. **In vivo human evidence (1P-LSD):** 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 — with LSD t½ ≈ 5.7–6.4h; bioavailability of LSD from oral 1P-LSD was "close to 100%" (Grumann et al. 2020 [Ref 12]). Subjective psychosensory effects were comparable to LSD in other studies, supporting the prodrug conclusion.

4. **In vivo animal evidence:** High LSD plasma levels detected in rats after 1P-LSD administration confirms prodrug conversion in vivo (Halberstadt et al. 2020 [Ref 28]).

5. **1F-LSD and 1T-LSD:** Both compounds hydrolyzed to LSD after in vivo administration to mice (Brandt et al. 2025 [Ref 4]).

The enzymatic machinery for N1-deacylation in the case of 1P-AL-LAD includes both CYP enzymes and carboxylesterases/esterases in liver and likely plasma. The specific enzymes responsible for 1V-LSD hydrolysis have not been studied.

### In Vivo Activity (Mouse Head-Twitch Response)

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 (Halberstadt et al. 2020 [Ref 19]; r = 0.9448 correlation with human hallucinogenic potency across 41 compounds).

**Key finding (Brandt et al. 2022 [Ref 1]):**
- 1V-LSD induced a **dose-dependent** HTR in mice
- **ED₅₀ = 373 nmol/kg** (approximately 152 µg/kg)
- This is approximately **one-third the potency of LSD** (ED₅₀ = 132.8 nmol/kg under identical conditions)
- The dose-response curve is consistent with other N1-acyl LSD derivatives

**Comparative potency in the N1-acyl LSD series (all tested in C57BL/6J mice by same laboratory):**
| Compound | Acyl chain | ED₅₀ (nmol/kg) | Relative to LSD |
|---|---|---|---|
| LSD | none | 132.8 | reference |
| ALD-52 (1A-LSD) | C2 acetyl | ~387* | ~1/3 |
| 1P-LSD | C3 propanoyl | 349.6 | ~1/3 |
| **1V-LSD** | **C5 pentanoyl (valeroyl)** | **373** | **~1/3** |
| 1H-LSD | C6 hexanoyl | 387 | ~1/3 |
| 1CP-LSD | cyclopropanoyl | 430 | ~1/3 |
| 1B-LSD | C4 butanoyl | 976.7 | ~1/7 |
| 1DD-LSD | C12 dodecanoyl | 3,600 | ~1/27 |

*ALD-52 stated roughly equipotent to 1H-LSD (387 nmol/kg) in Brandt et al. 2024 [Ref 5].

The similar potency of 1V-LSD to 1P-LSD and ALD-52 (all ~1/3 LSD potency) suggests efficient in vivo hydrolysis. The decreased potency relative to LSD likely reflects incomplete hydrolysis efficiency rather than direct 5-HT₂A activity (Brandt et al. 2022 [Ref 1]).

**NOTE:** 1B-LSD (C4 butanoyl) is considerably less potent (~14% of LSD), making 1V-LSD (C5) an anomaly in the series. The reason for this potency jump between 1B-LSD and 1V-LSD is not explained in published literature.

### LSD Receptor Pharmacology (Applicable to 1V-LSD as Prodrug)

Since 1V-LSD is believed to act as a prodrug for LSD, the following LSD receptor pharmacology is directly applicable to its effects. No specific Ki or EC₅₀ data exist for 1V-LSD itself.

**Primary targets (LSD):**
- **5-HT₂A receptor:** Partial agonist; primary mediator of hallucinogenic effects. Ketanserin (5-HT₂A antagonist, 40 mg) completely blocks all subjective LSD effects (Holze et al. 2021 [Ref 16]). Crystal structure shows LSD bound in the orthosteric site of 5-HT₂B; slow dissociation from 5-HT₂A and 5-HT₂B due to extracellular loop 2 (EL2) "lid" mechanism (Wacker et al. 2017 [Ref 13]).
- **5-HT₁A receptor:** Partial agonist at somatodendritic autoreceptors in the dorsal raphe nucleus; contributes to reduced 5-HT neurotransmission and anxiolytic/sedative component (De Gregorio et al. 2016 [Ref 32]; Passie et al. 2008 [Ref 42]).
- **5-HT₂C receptor:** Agonist activity; contributes to anxiogenic and other effects.
- **Dopamine D₂ receptor:** Agonist (primarily at higher doses); modulation of the VTA (De Gregorio et al. 2016 [Ref 32]).
- **TrkB (BDNF receptor):** LSD binds TrkB with ~1,000-fold higher affinity than conventional antidepressants; TrkB-mediated neuroplasticity effects are independent of 5-HT₂A activation (Moliner et al. 2023 [Ref 14]).
- **5-HT₂A–mGluR2 heterodimer:** Required for hallucinogen-specific intracellular signaling patterns; mGluR2 activation abolishes hallucinogen-specific responses (González-Maeso et al. 2008 [Ref 27]).
- **Multiple additional sites:** LSD interacts with adrenergic α₁, dopamine D₁, TAAR1, and multiple other serotonin receptor subtypes at varying affinities (Ray 2010 [Ref 31]; Passie et al. 2008 [Ref 42]).

**Comprehensive receptor profile:** LSD has broad receptor interactions; in one profiling study (Ray 2010 [Ref 31]), psychedelics including LSD interacted with 42 of 49 broadly assayed receptor sites, emphasizing the complexity of the pharmacological profile.

**FLAG:** No published binding affinity (Ki or EC₅₀) data exist for 1V-LSD at any receptor. All pharmacological characterization is by inference from LSD via the prodrug hypothesis.

### Pharmacokinetics

**For 1V-LSD specifically:** No human or animal pharmacokinetic data have been published. The Brandt et al. 2022 paper explicitly calls for biotransformation studies.

**For LSD (applicable after prodrug conversion):**
- **Oral bioavailability:** 80% (Arikci et al. 2025 [Ref 11]); all oral LSD formulations (base and tartrate) are bioequivalent
- **Tmax:** ~1.1–2.5h after oral administration
- **Half-life:** 2.7h at microdoses; ~5.7–6.4h at 100 µg dose (Grumann et al. 2020 [Ref 12]); up to 11.6h in CYP2D6 poor metabolizers (Vizeli et al. 2021 [Ref 15])
- **Primary metabolizing enzyme:** CYP2D6; poor metabolizers have ~75% higher LSD AUC and longer subjective effects (Vizeli et al. 2021 [Ref 15])
- **Other CYPs:** CYP1A2, CYP2C9 play secondary roles; studied in vitro but no in vivo impact detected at population level
- **Primary urinary metabolite:** 2-oxo-3-hydroxy-LSD (OH-LSD); also nor-LSD, nor-iso-LSD, trioxylated-LSD, 13/14-hydroxy-LSD glucuronides (Canezin et al. 2001 [Ref 43])
- **Detection window:** LSD detectable in urine up to ~80h after 100 µg dose; OH-LSD detectable longer

**Note on 1P-LSD timing:** After oral 1P-LSD, LSD appears rapidly in serum with biphasic elimination; 1P-LSD itself detectable only up to 4.16h in serum and 2.7h in urine (Grumann et al. 2020 [Ref 12]). By analogy, 1V-LSD itself would be expected to have a short plasma half-life, with LSD as the detected active species.

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## History

### Discovery and Synthesis

LSD was synthesized by Albert Hofmann at Sandoz Laboratories, Basel, Switzerland, in 1938, and its psychedelic properties were accidentally discovered during self-experimentation on April 19, 1943 (Passie et al. 2008 [Ref 42]).

The first N1-acyl LSD derivative, ALD-52 (1-acetyl-LSD), was synthesized at Sandoz in the 1950s, reportedly by Stoll and coworkers (as referenced in Kavanagh et al. 2024 [Ref 3]). ALD-52 was found to produce psychedelic effects similar to LSD.

**1V-LSD origin:** 1V-LSD (1-valeroyl-d-lysergic acid diethylamide) first appeared on the online research chemical market around 2020–2021, according to Brandt et al. (2022 [Ref 1]), who describe it as a "new N1-acylated LSD derivative that recently appeared on the online market." The compound can be viewed conceptually as the C5 homolog in the series: ALD-52 (C2) → 1P-LSD (C3) → 1B-LSD (C4) → **1V-LSD (C5)** → 1H-LSD (C6) → 1DD-LSD (C12).

No academic synthesis paper for 1V-LSD has been published. The compound is presumed to be synthesized from d-LSD via acylation of the N1 indole nitrogen with valeric anhydride or valeryl chloride, using the same chemistry applied to other N1-acyl derivatives.

### Nomenclature in Research Series

1V-LSD is the subject of "Return of the Lysergamides. Part VII" (Brandt et al. 2022 [Ref 1]), part of a series by Brandt, Kavanagh, Halberstadt and collaborators covering novel lysergamide NPS:
- Part II: AL-LAD, LSZ (Brandt et al. 2017 [Ref 22])
- Part IV: LSM-775 (Brandt et al. 2018 [Ref 23])
- Part V: 1B-LSD (Brandt et al. 2019 [Ref 20])
- Part VI: 1CP-LSD (Brandt et al. 2020 [Ref 21])
- Part VII: **1V-LSD** (Brandt et al. 2022 [Ref 1])

Parts I and III of this series were not identified in database searches; they likely cover other lysergamides (possibly 1P-LSD and ETH-LAD).

### Market Appearance

1V-LSD was detected in sheet products (blotter-type drug products) in Japan, as reported by Tanaka et al. (2023 [Ref 2]), who noted it as the first report of multi-position-modified LSD analogs in Japanese drug markets. The street nickname "Valerie" has been noted in the research chemical community. A forensic LC-MS/MS method validated for 1V-LSD detection in urine (LOD 0.1 ng/mL) was developed by Patton et al. (2024 [Ref 7]), though no positive urine specimens were found in 325 samples tested.

The compound's emergence is consistent with the pattern of designer lysergamide development: each successive NPS ban in Germany prompted development of the next structural homolog (see Legal Status section).

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## Subjective Effects

**No published controlled human studies of 1V-LSD subjective effects exist.** The following is entirely inferred from: (1) the prodrug hypothesis, (2) LSD data, and (3) the Grumann et al. (2020 [Ref 12]) 1P-LSD human study which showed subjective effects "comparable to those seen after uptake of LSD in other studies."

**FLAG (structural analogy inference — requires editorial label):** All subjective effect descriptions for 1V-LSD are based on class inference from LSD, not 1V-LSD-specific data.

**LSD dose-dependent subjective effects (applicable by inference):**
- **25–100 µg LSD:** Visual perceptual changes, ego dissolution (increasing with dose), good drug effects peaking at 100 µg, duration 6.7–11h depending on dose (Holze et al. 2021 [Ref 16])
- **>100 µg LSD:** Greater ego dissolution; significantly increased anxiety; ceiling on "good effects" reached at 100 µg (Holze et al. 2021 [Ref 16])
- **200 µg LSD:** Significant anxiety and ego dissolution (Holze et al. 2021 [Ref 16])
- Duration of subjective effects: 6.7h at 25 µg to 11h at 200 µg LSD

**Duration profile (seed data — consistent with LSD + prodrug lag; no published 1V-LSD-specific data):**
- Onset: 20–60 min (oral)
- Come up: 45–120 min (oral)
- Peak: 3–5 hours (oral)
- Offset: 3–5 hours (oral)
- Total: 8–12 hours (oral)
- Aftereffects: 6–24 hours (oral)

The somewhat prolonged onset and come-up relative to LSD could reflect the time required for prodrug hydrolysis. However, this inference has not been confirmed experimentally. 1P-LSD human self-reports and the Grumann 2020 study suggest onset/duration broadly comparable to LSD.

**Effect taxonomy from brief database:** The listed effects (visual hallucinations, synesthesia, ego inflation/dissolution, cognitive euphoria, thought loops, pattern recognition enhancement, etc.) are consistent with published LSD literature. These are appropriately attributed to LSD class pharmacology mediated via 5-HT₂A agonism.

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## Safety & Toxicity

**No published safety or toxicity data specific to 1V-LSD exist.** The following is inferred from LSD class data.

**FLAG (class inference — human review required):** All toxicity characterizations below apply to LSD, not 1V-LSD specifically.

### Acute Toxicity

LSD has extremely low acute toxicity. There are no well-documented human fatalities from LSD alone (Passie et al. 2008 [Ref 42]). The LD₅₀ data for LSD are from animal studies (rats, mice); the therapeutic index for humans is estimated to be very high. The brief's characterization of "negligible" acute toxicity is consistent with published LSD literature (Omidian and Omidian 2025 [Ref 33]).

### Cardiovascular Effects

LSD moderately increases blood pressure and heart rate in controlled studies (Holze et al. 2021 [Ref 16]). As an ergoline alkaloid, LSD has vasoconstrictive properties, though clinically significant vasoconstriction at psychoactive doses is rarely reported outside of high-dose or combined-drug scenarios (Passie et al. 2008 [Ref 42]). The brief's "vasoconstriction" listing in the effects taxonomy is pharmacologically plausible.

### Psychological Risks

**HPPD (Hallucinogen Persisting Perception Disorder):** A rare but documented complication of hallucinogen use, most commonly associated with LSD. Characterized by re-emergence of perceptual symptoms after drug cessation, without impaired reality testing (Leistenschneider et al. 2024 [Ref 34]; Hadley et al. 2025 [Ref 35]). LSD is the most frequently implicated substance in HPPD case reports (Ayyub et al. 2023 [Ref 36]). Treatment: clonazepam or lamotrigine; antipsychotics generally ineffective (Christensen et al. 2023). Prevalence estimates vary widely (up to 39.7% for mild Type I symptoms in one self-report survey; 4.3% for Type II HPPD with impairment) (Hadley et al. 2025 [Ref 35]).

**Acute anxiety and psychological distress:** 200 µg LSD produced significant anxiety in healthy volunteers (Holze et al. 2021 [Ref 16]). Uncontrolled settings increase risk of adverse psychological reactions.

**Risk in predisposed individuals:** Individuals with personal or family history of psychotic disorders should avoid LSD-class compounds. This risk applies by inference to 1V-LSD.

**Seizure threshold:** The brief lists "Seizure threshold reduction" in the effects taxonomy. Pharmacological basis: LSD's complex serotonergic/glutamatergic effects may modulate seizure threshold. No published seizure case reports specifically attributed to 1V-LSD.

### Reproductive/Developmental Toxicity

LSD prenatal exposure studies are limited and methodologically constrained; clinicians should counsel with explicit acknowledgment of uncertainty (Albert and Arthur 2026). No data exist for 1V-LSD.

### Case Reports

**No published case reports of 1V-LSD adverse events, overdose, or intoxication are identifiable in the literature.** The Grumann et al. (2019 [Ref 29]) 1P-LSD paper applied their analytical method to an intoxication case (finding 0.51 ng/mL LSD in urine, 3.4 ng/mL in serum, with 1P-LSD undetected), which is relevant by analogy for understanding 1V-LSD intoxication presentation.

---

## Harm Reduction

**FLAG:** The following is based on LSD literature and general psychedelic harm reduction guidance, not 1V-LSD-specific data.

### Testing and Identification

Forensic identification of 1V-LSD requires specific analytical methods:
- **GC-MS:** 1V-LSD elutes between 1B-LSD and 1cP-LSD under standard GC conditions (Tusiewicz et al. 2024 [Ref 9]). Methanol extraction causes artifact hydrolysis to LSD (Zhang et al. 2023 [Ref 30]); isopropyl alcohol or acetonitrile are preferred solvents.
- **LC-MS/MS:** Validated method for urine detection at LOD 0.1 ng/mL (Patton et al. 2024 [Ref 7]).
- **NMR, Raman, GC-sIR:** Used in Brandt et al. 2022 [Ref 1] for full analytical characterization.
- Colorimetric reagent tests (Ehrlich, Hofmann) will react with 1V-LSD (ergoline ring), but cannot distinguish it from LSD or other lysergamides.

### Detection in Biological Matrices

Because 1V-LSD is likely rapidly converted to LSD in vivo, drug testing should target LSD and its primary metabolite OH-LSD, not 1V-LSD itself. Standard LSD immunoassays may detect 1V-LSD or its conversion product (Patton et al. 2024 [Ref 7]).

### Clinical Harm Reduction Considerations

Standard LSD harm reduction principles apply:
- Set and setting (mindset and environment) are primary determinants of adverse experience
- Having a sober companion for high doses
- Benzodiazepines (e.g., diazepam, lorazepam) are the primary intervention for acute anxiety or agitation; they reduce subjective intensity without precipitating adverse interactions
- Antipsychotics (haloperidol) are used in emergency settings but may worsen psychological distress and carry their own risks
- For HPPD management: benzodiazepines or lamotrigine (Ayyub et al. 2023 [Ref 36])

---

## Tolerance & Dependence

### Tolerance

**Mechanism:** LSD and classical 5-HT₂A psychedelics produce rapid tachyphylaxis (functional tolerance) primarily through 5-HT₂A receptor downregulation and desensitization. Tolerance develops "almost immediately after ingestion" (brief seed data) and is consistent with published literature on classical hallucinogens (Passie et al. 2008 [Ref 42]).

**Cross-tolerance:** Well-established within the classical psychedelic class (5-HT₂A agonists). Cross-tolerance exists between LSD, psilocybin, mescaline, and other serotonergic psychedelics (Passie et al. 2008 [Ref 42]).

**Recovery:** Published data and community consensus (brief seed data) indicate: half-life of tolerance approximately 6 days; full reset approximately 14 days. These values are consistent with LSD literature. No specific published tolerance recovery timeline data for 1V-LSD exist; values are inferred from LSD class.

**FLAG (tolerance data — class inference):** The specific tolerance parameters in the brief (half-life 6 days, full reset 14 days) are not verified against a published source. They represent reasonable consensus for LSD class; editorial confirmation of source is recommended.

### Dependence

LSD has low abuse potential. No physical dependence has been documented in humans (Passie et al. 2008 [Ref 42]). Psychological dependence has been reported but is uncommon. The WHO assessed LSD as having low dependence potential. The brief's characterization of "non-addictive with low abuse potential" is consistent with published literature on LSD class compounds. The meta-analysis of psychedelic RCTs (Høylund et al. 2025 [Ref 41]) did not find psychedelics associated with higher all-cause discontinuation, further supporting low dependence liability.

---

## Interactions

### Tramadol — DANGEROUS

**Seed data flags this interaction as "dangerous."**

**Mechanism (inferred, not 1V-LSD-specific):** Tramadol is a weak µ-opioid agonist and serotonin/norepinephrine reuptake inhibitor (SNRI). Combined with a serotonergic psychedelic (which would, as LSD, robustly activate 5-HT₂A and other serotonin receptors), the risk of serotonin syndrome is elevated. Additionally, tramadol lowers the seizure threshold — a risk that may be additive with any seizure threshold reduction from psychedelic use. The "dangerous" classification in the brief is pharmacologically plausible and well-founded for the LSD class.

**FLAG (safety-critical, unverified against published primary source):** No published case report, controlled study, or pharmacokinetic interaction study specifically documenting a tramadol–LSD or tramadol–lysergamide interaction was identified. The "dangerous" classification represents a pharmacologically reasoned harm reduction consensus that should be clearly attributed to class-inference rather than direct evidence for 1V-LSD.

### Cannabis — UNKNOWN

**Seed data flags this interaction as "unknown."**

Preliminary evidence suggests cannabis/THC may enhance the pro-hallucinogenic signaling of 5-HT₂A receptors via Akt/mTOR pathway changes (Ibarra-Lecue et al. 2018), which could potentiate or alter psychedelic effects. The interaction is pharmacologically complex and its practical significance with 1V-LSD is unstudied.

### General Serotonergic Interactions

By class inference from LSD:
- **SSRIs/SNRIs:** May blunt psychedelic effects (pharmacodynamic antagonism at 5-HT₂A); risk of serotonin syndrome with high SSRI doses + serotonergic psychedelic.
- **MAOIs:** Risk of serotonin syndrome; also may potentiate and prolong LSD effects.
- **Lithium:** Anecdotal reports of seizures and cardiac events with LSD + lithium combinations; flagged in harm reduction literature.
- **CYP2D6 inhibitors:** May increase LSD exposure after 1V-LSD conversion; clinically relevant for co-administration of fluoxetine, paroxetine, bupropion.

---

## Legal Status

**Germany:** 1V-LSD was initially targeted by an amendment to the Neue-psychoaktive-Stoffe-Gesetz (NpSG) in September 2022; however, due to a punctuation error in the legislative text, the ban did not take legal effect. The NpSG was successfully amended in March 2023, definitively scheduling 1V-LSD (Ref 39, web-retrieved from Chemical Collective; confirmed by multiple vendor sources). The broader pattern: each lysergamide analogue has been successively banned under NpSG, with vendors pivoting to the next unscheduled derivative (1B-LSD → 1V-LSD → 1D-LSD → 1S-LSD).

**United Kingdom:** Covered by the Psychoactive Substances Act 2016, which prohibits all substances "capable of producing a psychoactive effect" with limited exemptions (alcohol, nicotine, caffeine, medicinal products). 1V-LSD falls within this prohibition (Ref 40, web-retrieved).

**United States:** 1V-LSD is not explicitly scheduled under the Controlled Substances Act (CSA). However, it may be subject to prosecution under the Federal Analogue Act (21 U.S.C. § 813), which treats substances substantially similar to Schedule I/II drugs as Schedule I when intended for human consumption. LSD is Schedule I; 1V-LSD's structural similarity makes Federal Analogue Act prosecution legally possible (Ref 40).

**Canada:** Not specifically listed under the Controlled Drugs and Substances Act (CDSA). Grey area legally; LSD is Schedule III under CDSA and structurally related compounds may be treated analogously (Ref 40).

**Australia:** LSD is a prohibited import under the Customs (Prohibited Imports) Regulations. Lysergamide derivatives are broadly controlled; 1V-LSD is likely prohibited as an LSD analog (Ref 40).

**FLAG:** Legal status data are from web-retrieved sources (vendor blogs, search compilations), not from official government legislative databases. Independent verification against official government schedules is recommended before publication.

---

## Clinical Trials

**No registered clinical trials for 1V-LSD were found on ClinicalTrials.gov** (search conducted April 2026; zero results for "1V-LSD" and "lysergamide" combined).

No institutional clinical research program for 1V-LSD has been announced in the published literature.

For context: active clinical trials for LSD itself include studies of LSD-assisted psychotherapy for anxiety, depression, and alcohol use disorder. These are not directly relevant to 1V-LSD as an independent research target, but establish the broader therapeutic research context (Høylund et al. 2025 [Ref 41]; Omidian and Omidian 2025 [Ref 33]).

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## Community Feedback Analysis

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

No community feedback items to analyze.

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## Gaps & Flags

### Critical Gaps (Safety-Relevant)

1. **No human pharmacokinetic data for 1V-LSD.** Dose-response, onset, duration, and all PK parameters are inferred from LSD and the 1P-LSD human study. The generation agent must clearly label all duration and dose data as class-inference pending 1V-LSD-specific studies.

2. **No receptor binding (Ki/EC₅₀) data for 1V-LSD.** The pharmacological characterization section of any article must clearly state this gap. All receptor pharmacology is via LSD by prodrug inference.

3. **Tramadol interaction classification "dangerous" is unverified against a published primary source.** The pharmacological rationale is sound (serotonin syndrome risk + seizure threshold lowering), but no published case report or study documents this interaction for LSD or 1V-LSD specifically. Must be labeled as class-inference in any article.

4. **No published biotransformation data for 1V-LSD.** Whether and how efficiently 1V-LSD hydrolyzes to LSD in humans has not been studied. Brandt et al. 2022 [Ref 1] explicitly calls for such studies.

5. **Dose range data (15–300+ µg) are not verified against a published source.** These values appear in PsychonautWiki and are consistent with 1V-LSD's likely ~3× lower potency than LSD in mice (suggesting equivalent human potency to LSD at similar doses, if complete hydrolysis occurs). However, no human controlled study has established these values. Must be labeled "community consensus / structural analog inference" per the pipeline's editorial hierarchy.

6. **Duration data (8–12h total) not verified against a published source.** Consistent with LSD class (6.7–11h in Holze 2021 at 25–200 µg), but unconfirmed for 1V-LSD. Label similarly.

7. **SMILES string not returned by PubChem API** in this research run. The generation agent should retrieve canonical SMILES directly from PubChem CID 162368540.

### Discrepancies (Seed Data vs. Published Sources)

- **Pharmacological class in brief:** Lists "Serotonin 1A receptor partial agonist, Serotonin 2A receptor agonist, Serotonin 2C receptor agonist, Dopamine receptor agonist" — these are accurate for LSD (the prodrug target) but technically incorrect for 1V-LSD itself, which at the N1-acyl level has dramatically reduced receptor affinity (Halberstadt et al. 2020 [Ref 28]). This should be clarified in the article: these are the receptor activities of LSD after prodrug conversion, not of 1V-LSD at the N1-acyl level.

- **Brief's characterization:** Lists "emerging" — confirmed accurate; only one peer-reviewed study exists specifically for 1V-LSD (Brandt et al. 2022).

### Legal Status Flags

- Legal status data are web-retrieved from vendor/community sources, not official government databases. Germany's NpSG ban (March 2023) is well-documented but not verified against the primary legislative text.

### Areas Relying Primarily on Structural Analogy

The following content sections are primarily or entirely based on structural analogy with LSD (via prodrug hypothesis) rather than 1V-LSD-specific data:
- All pharmacology beyond HTR ED₅₀
- All pharmacokinetics
- All subjective effects descriptions
- All toxicity and safety data
- Tolerance and dependence characterization
- Drug interaction mechanisms
- Dose ranges
- Duration estimates