1P-LSD

# Research Output: 1P-LSD

## Chemical Identity

**Verified via PubChem (CID 119025985):**

| Field | Value |
|-------|-------|
| PubChem CID | 119025985 |
| Molecular formula | C₂₃H₂₉N₃O₂ |
| Molecular weight | 379.5 g/mol |
| IUPAC name | (6aR,9R)-N,N-diethyl-7-methyl-4-propanoyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide |
| InChIKey | JSMQOVGXBIDBIE-OXQOHEQNSA-N |
| Stereochemistry | (6aR,9R) — same absolute configuration as d-LSD |

**Note on seed data discrepancies:** The brief listed blank values for molecular formula, molecular weight, SMILES, InChIKey, and PubChem CID. All of these are now confirmed from PubChem. The CID is 119025985. The IUPAC name in the brief is confirmed correct. SMILES was not returned directly by the PubChem API in this session but the formula, weight, and InChIKey are verified.

**Systematic name:** 1-propionyl-d-lysergic acid diethylamide (also written 1-propanoyl-LSD). Common abbreviations: 1P-LSD, 1-prop-LSD. The hemitartrate salt is the form typically sold on research chemical markets, as noted in Brandt et al. (2016 [Ref 1]) and Grumann et al. (2020 [Ref 37]).

**Physical properties:** No published peer-reviewed data on melting point, aqueous solubility, or photostability specific to 1P-LSD was located in the academic literature. LSD is known to be sensitive to UV light and oxygen; by structural analogy, 1P-LSD is likely similar. The hemitartrate salt is typically encountered as a white or off-white crystalline powder and on blotter paper (Brandt et al. 2016 [Ref 1]).

---

## Pharmacology

### Prodrug Status — Primary Mechanism

The weight of evidence from both animal and human studies establishes that 1P-LSD functions primarily as a **prodrug for LSD** rather than exhibiting significant direct pharmacological activity.

**Receptor binding:** The 1-acyl substitution reduces 1P-LSD's affinity for most monoamine receptors, including 5-HT₂A sites, by one to two orders of magnitude compared to LSD. Although LSD acts as an agonist at 5-HT₂ subtypes, 1P-LSD, ALD-52, and 1B-LSD have weak efficacy or act as antagonists in calcium mobilization assays (Halberstadt et al. 2020 [Ref 2]).

**Deacylation to LSD:** High plasma concentrations of LSD were detected in Sprague-Dawley rats after subcutaneous administration of 1P-LSD, demonstrating rapid and efficient deacylation in vivo (Halberstadt et al. 2020 [Ref 2]). In vitro, pooled human liver S9 fraction incubation confirmed deacylation of 1P-LSD to LSD, catalyzed primarily by CYP1A2 and CYP3A4 (Wagmann et al. 2019 [Ref 3]).

**Human confirmation (Grumann et al. 2020 [Ref 37]):** In the only published controlled human study of 1P-LSD (n=2 volunteers, self-administration design), oral ingestion of 100 µg 1P-LSD hemitartrate produced no detectable 1P-LSD in serum or urine — only LSD was found, with biphasic elimination and a terminal elimination half-life of approximately 6.4 hours. This confirms near-complete first-pass deacylation to LSD in humans. After IV administration, 1P-LSD was detectable in serum for up to 4.16 hours, with LSD appearing in all samples and detectable up to ~24 hours in serum and ~80 hours in urine (t1/2 ~5.7h IV). Bioavailability of LSD after oral 1P-LSD ingestion was close to 100% (Grumann et al. 2020 [Ref 37]).

### LSD Receptor Pharmacology (Active Metabolite)

All downstream pharmacology of 1P-LSD is mediated via LSD following deacylation. LSD's pharmacology is well characterized:

**Primary target — 5-HT₂A receptor:** LSD is an agonist/partial agonist at brain serotonin 5-HT₂A receptors, particularly those expressed on apical dendrites of neocortical pyramidal cells in layer V (Nichols 2016 [Ref 26]). 5-HT₂A activation mediates the hallucinogenic and psychedelic effects; these are blocked by the 5-HT₂A antagonist ketanserin (Becker et al. 2023 [Ref 40]). In mice, 1P-LSD induces the head-twitch response (HTR) — an established 5-HT₂A-mediated behavior — with an ED₅₀ of 349.6 nmol/kg, approximately 38% of LSD's potency (ED₅₀ = 132.8 nmol/kg), consistent with its role as a prodrug (Brandt et al. 2016 [Ref 1]).

**5-HT₁A receptor:** LSD acts as an agonist/partial agonist at 5-HT₁A receptors, mediating inhibition of raphe serotonin firing at low doses (De Gregorio et al. 2016 [Ref 15]).

**5-HT₂C receptor:** LSD is an agonist at 5-HT₂C receptors (Nichols 2016 [Ref 26]).

**Dopaminergic effects:** At higher doses, LSD decreases VTA dopamine firing via D₂, 5-HT₁A, and TAAR₁ receptor activation (De Gregorio et al. 2016 [Ref 16]).

**TAAR₁:** LSD interacts with trace amine-associated receptor 1 (TAAR₁), contributing to dopaminergic modulation (De Gregorio et al. 2016 [Ref 16]).

**TrkB (BDNF receptor):** LSD binds TrkB with approximately 1,000-fold higher affinity than classical antidepressants. This TrkB binding promotes BDNF signaling and neuroplasticity independent of 5-HT₂A activation, and may contribute to LSD's antidepressant-like effects (Moliner et al. 2023 [Ref 10]).

**Receptor selectivity:** LSD has low selectivity and binds a broad panel of serotonin, dopamine, and adrenergic receptors. The crystal structure of LSD bound to the 5-HT₂B receptor revealed an extracellular loop 2 (EL2) "lid" mechanism that slows LSD's dissociation, explaining its prolonged receptor residence time and sustained effects (Wacker et al. 2017 [Ref 4]).

**Signal transduction:** LSD activates 5-HT₂A-Gq/PLC signaling; Gq efficacy (not β-arrestin2 recruitment) predicts psychedelic activity. Hallucinogens also uniquely recruit Gi/o proteins and Src kinases downstream of 5-HT₂A (González-Maeso et al. 2007). The Carhart-Harris/Friston REBUS model proposes that psychedelics relax high-level predictive priors via 5-HT₂A activation, accounting for the breadth of altered-state phenomena (Carhart-Harris & Friston 2019 [Ref 31]).

### Pharmacokinetics

The following PK data is for 1P-LSD as characterized in humans (Grumann et al. 2020 [Ref 37]), supplemented by extensive LSD PK data applicable to the active metabolite:

| Parameter | Value | Source |
|-----------|-------|--------|
| Prodrug conversion | Near-complete to LSD (oral route) | Grumann 2020 [Ref 37] |
| LSD t1/2 (from oral 1P-LSD) | ~6.4h (terminal) | Grumann 2020 [Ref 37] |
| LSD t1/2 (from IV 1P-LSD) | ~5.7h | Grumann 2020 [Ref 37] |
| LSD bioavailability (from oral 1P-LSD) | ~100% | Grumann 2020 [Ref 37] |
| LSD oral bioavailability (direct) | ~80% | Arikci et al. 2025 [Ref 11] |
| LSD Tmax (direct oral) | ~1.1–1.5h | Holze 2021 [Ref 7]; Dolder 2015 [Ref 6] |
| LSD t1/2 (microdose study) | ~2.7h | Holze 2021 [Ref 7] |
| LSD t1/2 (100 µg oral) | ~3.5h | Ley et al. 2023 [Ref 13] |

**Note on t1/2 variation:** The Grumann 2020 study found a longer t1/2 (~6.4h) compared to studies using direct LSD formulations (~2.7–3.5h). This may reflect methodological differences, small sample size (n=2), or the ongoing deacylation of 1P-LSD during absorption contributing additional LSD over time (slightly extending apparent t1/2). The Grumann value may overestimate LSD t1/2 because ongoing prodrug conversion creates a "depot" effect.

**Onset delay:** 1P-LSD requires initial deacylation before LSD reaches target receptors; this is expected to slightly delay onset relative to direct LSD administration. Grumann et al. noted 5D-ASC scores were higher after oral compared to IV administration, suggesting oral bioavailability was actually somewhat higher than IV (possibly due to more efficient GI-mediated hydrolysis or first-pass conversion).

### CYP Enzyme Involvement

Primary: CYP1A2, CYP3A4 (N-dealkylation, hydroxylation, deacylation) (Wagmann et al. 2019 [Ref 3]). CYP2D6 also involved in LSD metabolism; CYP2D6 inhibition by paroxetine increased LSD Cmax by 1.4× and AUC by 1.5× (Becker et al. 2025 [Ref 22]).

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## History

**LSD background:** Lysergic acid diethylamide (LSD) was first synthesized by Albert Hofmann at Sandoz Laboratories, Basel, Switzerland, in November 1938 during systematic exploration of ergot alkaloid derivatives. Its profound psychedelic properties were discovered accidentally by Hofmann on April 19, 1943 (now commemorated as "Bicycle Day"). LSD was marketed by Sandoz as "Delysid" from 1947 to 1966, used in psychiatric research and experimental psychotherapy.

**ALD-52 precedent:** 1-Acetyl-LSD (ALD-52), the closest structural analog of 1P-LSD, was synthesized at Sandoz in the 1950s and reported to produce psychedelic effects in humans similar to LSD. ALD-52 served as the template from which 1P-LSD and related N1-acyl lysergamide research chemicals were derived.

**1P-LSD emergence:** 1P-LSD was not described in the published scientific literature prior to its appearance on the research chemical market. It first became commercially available as a "research chemical" via online vendors in approximately early 2015, marketed in blotter and powder form (Brandt et al. 2016 [Ref 1]). The Brandt et al. (2016) paper — submitted 2015 — represents the first peer-reviewed documentation of its existence.

**Who synthesized it:** Unknown. The compound has not been attributed to any academic laboratory in the literature. As noted in Brandt et al. (2016 [Ref 1]), 1P-LSD "has previously not been described in the published literature despite being closely related to 1-acetyl-LSD."

**Regulatory history:** 
- Germany placed 1P-LSD under the NpSG (Neue-psychoaktive-Stoffe-Gesetz) in July 2019 [Ref 23]
- UK: covered by the Psychoactive Substances Act 2016 [Ref 23]
- No known specific scheduling actions by US DEA
- Multiple successor compounds (1B-LSD, 1cP-LSD, 1V-LSD, 1T-LSD) followed on the research chemical market as bans were enacted, each confirmed as LSD prodrugs by the "Return of the Lysergamides" paper series (Brandt et al.)

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## Subjective Effects

### Human Evidence — Direct 1P-LSD Studies

**Grumann et al. 2020 [Ref 37]** (n=2 self-experiments, controlled setting, 100 µg oral and IV): Psychosensory effects and their time course were described as comparable to those seen after LSD administration in published LSD studies. 5D-ASC (Five Dimensions of Altered States of Consciousness) scores were notably higher after oral compared to IV administration, suggesting complete and potentially enhanced prodrug conversion via the oral route. This is the only published controlled human subjective effects data for 1P-LSD.

**Coney et al. 2017 [Ref 27]** (Global Drug Survey subset, self-report, n not specified): Survey comparing self-reported effects of LSD and lysergamide analogues (1P-LSD, AL-LAD, ETH-LAD). Users described 1P-LSD effects as qualitatively similar to LSD. This is user-report data, not a controlled study; see Gaps & Flags.

### LSD Reference Data (Applicable via Prodrug)

Since 1P-LSD is fully converted to LSD in humans, LSD's characterized effect profile provides the relevant reference. Controlled studies at 100–200 µg LSD in healthy volunteers document:

**Perceptual effects:** Visual alterations including patterns, tracers, enhanced color saturation, and at higher doses frank visual hallucinations; synesthesia; auditory enhancement. Effects are dose-dependent (Holze et al. 2022 [Ref 14]; Vizeli et al. 2024 [Ref 39]).

**Cognitive effects:** Altered thinking patterns, loosened associations, enhanced pattern recognition, altered sense of time, ego dissolution (increased with dose), enhanced creativity and openness, thought loops (Nichols 2016 [Ref 26]; Holze et al. 2022 [Ref 14]).

**Emotional effects:** Emotional enhancement (positive and negative), anxiety potential (dose-dependent, increased at 200 µg vs 100 µg), catharsis; the high-BDI group showed greater positive mood effects at low dose (Molla et al. 2024).

**Transpersonal/mystical effects:** Ego dissolution, oceanic boundlessness, sense of unity and interconnectedness — more pronounced at 200 µg (Holze et al. 2022 [Ref 14]).

**Somatic effects:** Pupil dilation, modest heart rate increase, mild blood pressure elevation, appetite suppression, wakefulness/stimulation, muscle tension, nausea possible (Ley et al. 2023 [Ref 13]; Holze et al. 2022 [Ref 14]).

**Duration:** Mean total effect duration approximately 8.2 hours at 100 µg LSD (Ley et al. 2023 [Ref 13]); dose-dependent. Effect duration clearly longer than psilocybin at equiactive doses (Holze et al. 2022 [Ref 14]).

**Dose-effect relationship at LSD doses (applicable to 1P-LSD):** 100 µg LSD and 200 µg LSD produced comparable qualitative effects, with 200 µg producing greater ego-dissolution, anxiety, and impairment of control (Holze et al. 2022 [Ref 14]). LSD dose is the primary predictor of subjective intensity across subjects (Vizeli et al. 2024 [Ref 39]).

**Onset delay relative to LSD:** 1P-LSD oral onset is expected to be slightly delayed vs direct LSD oral due to required prodrug conversion. No published comparative onset data in humans is available.

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## Safety & Toxicity

### Acute Toxicity

No published LD50 data for 1P-LSD was located. Given confirmed near-complete conversion to LSD, LSD toxicity data is the relevant reference:

**LSD toxicity:** LSD has an extremely low toxicity relative to its effective dose. No deaths from LSD's direct pharmacological action alone have been documented in published peer-reviewed literature under controlled conditions. LSD is considered physiologically safe and non-addictive (Nichols 2016 [Ref 26]). The lethal dose in animals is orders of magnitude above the effective psychoactive dose, giving LSD one of the highest therapeutic indices of any known psychoactive substance. Omidian & Omidian (2025 [Ref 29]) review safety considerations including cardiovascular risks.

**Cardiovascular effects:** LSD produces modest dose-dependent tachycardia and mild blood pressure elevation. These are clinically significant primarily in individuals with pre-existing cardiovascular disease. At 100 µg LSD, autonomic effects were moderate and comparable to psilocybin (Ley et al. 2023 [Ref 13]).

**Psychological safety:** Acute anxiety and panic reactions ("bad trips") can occur, particularly at higher doses, in predisposed individuals, or in challenging set/setting conditions. At 200 µg LSD, anxiety and ratings of ego dissolution were significantly higher than at 100 µg (Holze et al. 2022 [Ref 14]).

**Chronic toxicity:** No published chronic toxicity data specific to 1P-LSD. Given rapid and complete conversion to LSD, LSD chronic data applies: no evidence of organ toxicity at psychotherapeutic doses.

### HPPD

Hallucinogen Persisting Perception Disorder (HPPD) is a recognized but uncommon disorder associated primarily with LSD use. It is characterized by recurrence of perceptual disturbances after use has ceased. Halpern & Pope (2003 [Ref 18]) reviewed 50 years of evidence and concluded HPPD is genuine but uncommon, with no randomized controlled trials for treatment. HPPD appears to involve disinhibition of low-level visual processing and GABAergic mechanisms (Litjens et al. 2014 [Ref 34]).

**FLAG — safety-critical:** No HPPD incidence data specific to 1P-LSD. Risk assumed similar to LSD given identical active metabolite.

### Psychological Risks

Vulnerability to psychosis: LSD can precipitate or exacerbate psychotic episodes in predisposed individuals. Contraindicated in personal or family history of psychosis, schizophrenia, or bipolar disorder. Drug-induced psychosis and schizophrenia-related symptoms are documented in the literature (De Gregorio et al. 2016 [Ref 15]).

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## Harm Reduction

**Set and setting:** Non-pharmacological factors (mindset, setting, intention) are significant predictors of subjective response and adverse experience (Vizeli et al. 2024 [Ref 39]; Haijen et al. 2018 [Ref in context]).

**Dose titration:** Starting with lower doses (25–50 µg LSD-equivalent) and having experience with the substance before attempting higher doses significantly reduces risk of overwhelming experiences.

**Sitter/supervision:** A trusted, sober companion reduces risk of harm-to-self in disorientation.

**Testing:** Reagent testing (Ehrlich reagent — turns purple with indoles; Hofmann reagent) is recommended to confirm ergoline identity and screen for fentanyl or NBOMe adulterants. LSD-class substances should be tested as 1P-LSD blotters may be mislabeled.

**Emergency reversal:** The 5-HT₂A antagonist ketanserin almost fully reverses acute LSD effects even when administered after onset (Becker et al. 2023 [Ref 40]); benzodiazepines are the current standard for managing acute adverse reactions in clinical settings.

**Contraindicated conditions:** Personal/family history of psychosis or schizophrenia; bipolar disorder; cardiovascular disease (uncontrolled hypertension, arrhythmias); pregnancy/lactation (no safety data); hepatic impairment (metabolic processing); concurrent use of lithium (seizure risk reports, see Interactions).

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## Tolerance & Dependence

### Tolerance

Tolerance to LSD's subjective effects develops very rapidly — essentially beginning after the first dose — and is linked to 5-HT₂A receptor downregulation in the frontal cortex (de la Fuente Revenga et al. 2022 [Ref 8]). Cross-tolerance between LSD and DOI (and other psychedelics) is confirmed; this class-level tolerance is mediated by 5-HT₂A receptor activation and is beta-arrestin-2 independent (de la Fuente Revenga et al. 2022 [Ref 8]).

**Seed data values (from DB):** Buildup "almost immediately after ingestion"; half-life 6 days; full reset 14 days; cross-tolerances: psychedelic class. These values are consistent with the published mechanism (receptor downregulation resolving over ~2 weeks) but the specific time values (6-day half-life, 14-day reset) are not directly verified against a specific published source for LSD or 1P-LSD. They represent commonly cited community estimates consistent with mechanism. **FLAG for editorial review.**

### Dependence

LSD (and by extension 1P-LSD) is considered physiologically non-addictive: no physical dependence, no withdrawal syndrome, and psychological dependence is uncommon given the tolerance profile (rapid tolerance development makes compulsive use self-limiting) (Nichols 2016 [Ref 26]; Das et al. 2016 [Ref 25]). LSD does not activate the mesolimbic dopamine reward pathway in the manner of addictive drugs. The brief's characterization of "non-addictive with low abuse potential" is consistent with the published literature.

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## Interactions

### Tramadol — DANGEROUS

**Mechanism:** Tramadol potently inhibits the human serotonin transporter (SERT) at clinical plasma concentrations (IC50 ~1.0 µM; inhibition ~97% at initial plasma concentrations) (Barann et al. 2006 [Ref 21]). Combined with serotonergic psychedelics such as LSD (the active metabolite of 1P-LSD), this creates risk of serotonin toxicity (serotonin syndrome). Baldo (2018 [Ref 20]) reviews the class-level risk of serotonin toxicity with opioid SERT inhibitors and confirms tramadol as the most commonly implicated opioid in serotonin toxicity cases.

**Assessment:** The seed data classification of tramadol as "dangerous" is confirmed by published mechanism. Serotonin syndrome may present with hyperthermia, autonomic instability, neuromuscular abnormalities, and is potentially life-threatening. This interaction warrants a **DANGEROUS** classification.

**FLAG:** The specific severity rating "dangerous" for tramadol is supported by mechanistic evidence (SERT inhibition + 5-HT₂A agonism). However, no published case reports of serotonin syndrome specifically from tramadol + 1P-LSD were located — the evidence is mechanistic/class-based.

### Cannabis — UNKNOWN

No published controlled data on cannabis + 1P-LSD or cannabis + LSD interactions was found in the literature search. The seed data "unknown" classification is accurate. By extrapolation from user reports and general principles, cannabis may potentiate psychedelic effects and increase anxiety/paranoia, particularly at higher cannabis doses. This remains unquantified. **FLAG for safety-critical data point with no verified source.**

### SSRIs/SNRIs

Chronic SSRI use may attenuate psychedelic effects (pharmacodynamic tolerance via 5-HT₂A downregulation or receptor desensitization). Malcolm & Thomas (2022 [Ref 19]) assess serotonin toxicity risk between psychedelics and SSRIs; the risk appears lower than for MAOIs but is not zero, particularly at high doses of both agents. Paroxetine (CYP2D6 inhibitor) raised LSD Cmax 1.4× and AUC 1.5× but did not change pleasant effects and reduced anxiety/nausea, suggesting add-on LSD treatment with CYP2D6-inhibiting SSRIs is tolerable (Becker et al. 2025 [Ref 22]).

### MAOIs

Not listed in seed data interactions but mechanistically significant: MAO inhibitors impair catabolism of serotonin; combined with serotonergic psychedelics they increase serotonin syndrome risk. Malcolm & Thomas (2022 [Ref 19]) identify this as a relevant concern. **FLAG: Should be added to contraindications.**

### Lithium

Not listed in seed data interactions. User reports and harm reduction literature describe an association between LSD + lithium and seizure risk. No peer-reviewed primary source was identified in this search specifically documenting lithium + LSD seizures. **FLAG: Safety-critical claim not verified against primary published source — requires editorial sourcing.**

### MDMA

MDMA co-administration did not change the quality of acute LSD subjective effects but prolonged effect duration and increased LSD plasma Cmax/AUC (via CYP inhibition). More pronounced cardiovascular effects with the combination (Straumann et al. 2023 [Ref 12]).

---

## Legal Status

| Jurisdiction | Status | Notes |
|---|---|---|
| United States | Unscheduled | Subject to Federal Analogue Act (21 U.S.C. § 813) if intended for human consumption; LSD is Schedule I. Legal gray area. |
| United Kingdom | Illegal | Covered by Psychoactive Substances Act 2016; possession/supply prohibited |
| Germany | Controlled | Added to NpSG (Neue-psychoaktive-Stoffe-Gesetz) July 2019 |
| Canada | Unscheduled | Analog considerations may apply; legal gray area |
| Australia | Controlled | Prohibited substance |
| Sweden | Likely controlled | Listed as hazardous substance (web source; requires verification) |

**Source note:** Legal status data is from web sources [Ref 23]. Peer-reviewed legal analysis of 1P-LSD scheduling was not found. All legal claims should be treated as web-retrieved only (not api_verified) and verified against primary regulatory databases before publication.

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## Clinical Trials

**1P-LSD specific:** No registered clinical trials were found on ClinicalTrials.gov for 1P-LSD. None are anticipated in the near term given its legal status in most research-active jurisdictions.

**LSD clinical context (relevant as active metabolite):** Multiple completed and active trials exist for LSD, including:
- NCT04558294 — Ketanserin after LSD (completed, University Hospital Basel)
- NCT03019822 — Role of dopamine/serotonin/5-HT2A in emotion processing (completed, University Hospital Basel)
- NCT04421105 — Very low dose LSD in 55–75 year olds (completed, Eleusis Therapeutics)
- NCT05964647 — Ketanserin, olanzapine, lorazepam after LSD (completed, University Hospital Basel)
- NCT07189299 — Microdosing LSD in women with premenstrual disorders (not yet recruiting)

The meta-analysis by Hojlund et al. (2025 [Ref 35]) found psilocybin/ayahuasca/LSD significantly reduced depressive symptoms in MDD (SMD = −0.62, GRADE: very low) and anxiety (SMD = −0.88, GRADE: very low).

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## Community Feedback Analysis

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

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## Gaps & Flags

### Chemical/Physical

1. **SMILES:** Not confirmed from PubChem API in this session. PubChem CID 119025985 should be queried for SMILES via the full PubChem REST API. The generation agent should use the IUPAC name and InChIKey (confirmed) for chemical identity display.

2. **Melting point, aqueous solubility, photostability:** No published data specific to 1P-LSD was located. These are standard physical properties missing from the literature.

### Pharmacology

3. **Direct receptor binding Ki for 1P-LSD:** No peer-reviewed binding affinity data (Ki values) specific to 1P-LSD at individual receptors was located. Halberstadt et al. (2020 [Ref 2]) confirmed 1P-LSD has reduced 5-HT₂A affinity (1–2 orders below LSD) but specific numerical Ki values were not extractable from the abstract alone. This is a data gap.

4. **CYP2D6 involvement in 1P-LSD deacylation specifically:** CYP2D6 involvement was established for LSD metabolism (Becker et al. 2025 [Ref 22]) but not specifically for the deacylation step of 1P-LSD. Wagmann et al. (2019 [Ref 3]) identified CYP1A2 and CYP3A4 for the S9 fraction studies.

### Pharmacokinetics

5. **t1/2 discrepancy:** The Grumann 2020 study (n=2) found LSD t1/2 ~6.4h from oral 1P-LSD, which is longer than values from direct LSD studies (~2.7–3.5h). This discrepancy likely reflects ongoing prodrug conversion acting as a "depot" rather than a true difference in LSD elimination. **FLAG for generation agent:** Onset and duration data from the DB may be based on LSD data rather than 1P-LSD-specific data.

6. **Onset timing:** The seed data says onset 20–60 minutes. No specific 1P-LSD onset data was published. Given prodrug conversion time, onset may be slightly delayed vs direct LSD (where Tmax ~1.1–1.5h). This is consistent with the stated range but not directly verified.

### Dose Data

7. **Dose values in the DB are based on LSD equivalency:** The seed dose data (threshold 15 µg, light 25–75 µg, common 75–150 µg, etc.) is LSD-equivalent dosing. Given that Grumann 2020 confirms ~100% LSD bioavailability from oral 1P-LSD, this dose equivalency appears justified. However, 1P-LSD has MW 379.5 vs LSD 323.4 g/mol, meaning by mass 1P-LSD is slightly less potent per µg (ratio ~1.17). **FLAG for editorial review:** The DB dose values may or may not have already accounted for molecular weight difference. The Psychedelic community consensus typically treats 1P-LSD as approximately dose-equivalent to LSD by microgram (i.e., 100 µg 1P-LSD ≈ 100 µg LSD effect) — this appears consistent with Grumann 2020 (n=2 at 100 µg, effects "comparable to LSD in other studies").

### Safety

8. **LD50 data:** No published LD50 for 1P-LSD. Historical preclinical data for LSD gives very high therapeutic index but specific values were not confirmed against a current primary source.

9. **HPPD incidence:** No substance-specific HPPD incidence data for 1P-LSD. Risk assumed similar to LSD.

10. **Pregnancy/lactation:** No published safety data for 1P-LSD or LSD in pregnancy.

### Interactions

11. **Tramadol "dangerous" rating:** Supported by mechanistic evidence (SERT inhibition) but no published case report specifically involving 1P-LSD + tramadol was found. The rating is well-supported by class-level pharmacology.

12. **Cannabis "unknown" rating:** Confirmed as unknown — no controlled data found.

13. **Lithium seizure risk:** Not listed in seed data interactions but widely reported in harm reduction communities as dangerous. No primary published source was identified. **FLAG: Safety-critical — requires addition to contraindications if confirmed.**

14. **MAOI interaction:** Not listed in seed data but is a known dangerous interaction for LSD-class substances. Should be added.

### Tolerance/Dependence

15. **Tolerance time values (6-day half-life, 14-day full reset):** Community consensus values consistent with receptor downregulation mechanism but not directly verified against a peer-reviewed source citing these specific numbers for LSD or 1P-LSD.

### Legal Status

16. **All legal status data is web-retrieved** and should be independently verified against primary regulatory databases before publication.

### Human Evidence Base

17. **Only n=2 human study:** The Grumann 2020 study is the only published controlled human study of 1P-LSD. The n=2 self-experiment design is a significant limitation. All dose/duration/effect characterization relies heavily on LSD extrapolation from larger, well-controlled studies. The generation agent should be transparent about this when writing the article.