LSZ

# Research Output: LSZ
**Substance:** LSZ (lysergic acid 2,4-dimethylazetidide)
**PSX ID:** PSX-0229
**Research date:** 2026-04-26
**Characterization:** Emerging — NPS, first published 2002, market appearance 2013

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## Chemical Identity

**Verified from PubChem CID 71301249 and HandWiki:**

| Property | Value | Source |
|---|---|---|
| PubChem CID | 71301249 | api_verified [Ref 18] |
| Molecular formula | C₂₁H₂₅N₃O | api_verified [Ref 18] |
| Molecular weight | 335.4 g/mol | api_verified [Ref 18] |
| IUPAC name | [(6aR,9R)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-[(2S,4S)-2,4-dimethylazetidin-1-yl]methanone | api_verified [Ref 18] |
| InChIKey | DUKNIHFTDAXJON-CTQRGLTFSA-N | api_verified [Ref 18] |
| SMILES | `C[C@H]1C[C@@H](N1C(=O)[C@H]2CN([C@@H]3CC4=CNC5=CC=CC(=C45)C3=C2)C)C` | web_retrieved [Ref 18] |
| CAS (freebase) | 470666-31-0 | web_retrieved [Ref 18] |
| CAS (tartrate salt) | 470666-32-1 | web_retrieved [Ref 18] |

**Discrepancies with seed data:** The brief listed no SMILES, molecular formula, molecular weight, or InChIKey, and no PubChem CID. All four are now confirmed. The IUPAC name in the brief matches the PubChem record exactly.

The brief's systematic name — [(6aR,9R)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-[(2S,4S)-2,4-dimethylazetidin-1-yl]methanone — is confirmed correct by PubChem [Ref 18].

**Physical properties:** No melting point or solubility data located in published literature. No stability data found. Sold commercially as both free base (powder) and tartrate salt (blotter); the tartrate form is standard per Brandt et al. 2017 [Ref 2], who document a mixed salt ratio of approximately 1:0.8 (LSZ:tartaric acid) by NMR.

**Stereochemistry:** LSZ is specifically the (2'S,4'S)-trans diastereomer. Three diastereomers were synthesized by Nichols et al. 2002 [Ref 1]: (S,S)-(+), (R,R)-(−), and the cis isomer. Only the (S,S) isomer — LSZ — showed pharmacology closely matching LSD at 5-HT₂A and in behavioral assays [Ref 1]. The (R,R) and cis isomers were significantly less potent in all assays [Ref 1].

**Structural relationship to LSD:** The 2,4-dimethylazetidine ring serves as a conformationally rigid analogue of the diethylamine group of LSD. Its synthesis was specifically designed to map the binding orientation of the diethylamide moiety at the 5-HT₂A receptor [Ref 1].

**Isomers and related compounds:** N-ethyl-N-cyclopropyl lysergamide (ECPLA) is a constitutional isomer of LSZ. ECPLA and LSZ can be differentiated by NMR, GC-sIR, and GC/LC methods; key MS fragmentation differences include m/z 267 and m/z 98 product ions under ESI conditions (LSZ but not ECPLA) [Ref 5]. ECPLA also produces LSD-like HTR in mice [Ref 6].

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## Pharmacology

### Receptor Binding

Ki values for LSZ at monoamine receptors are sourced from Nichols et al. 2002 [Ref 1] and compiled in secondary literature [Ref 18]. No independent published binding affinity table with explicit Ki values for LSZ appears in any peer-reviewed paper other than Nichols 2002, which did not publish a full numeric table in its abstract. The following values are attributed to Nichols 2002 via HandWiki [Ref 18] and should be treated as web_retrieved pending full-text verification:

| Receptor | Ki (nM) | Notes |
|---|---|---|
| 5-HT₁A | 0.45 | Partial agonist by class analogy |
| 5-HT₂A | 0.54–19.2 | Range across studies; primary psychedelic target |
| 5-HT₂B | ~27 | 5-HT₂B agonism linked to cardiac valvulopathy at chronic high doses [Ref 25] |
| 5-HT₂C | ~37 | |
| D3 | 6.0 | |

**FLAG for human review:** These Ki values are sourced indirectly via HandWiki [Ref 18] attributing Nichols 2002 [Ref 1]. The Nichols 2002 abstract does not present a numerical binding table. Full-text verification of these Ki values against the original J. Med. Chem. paper is required before publishing.

LSD and its close structural analogs also bind D1 (Ki ~25–50 nM) and D2 dopamine receptors with agonist-type profiles (Watts et al. 1995 [Ref 7]). The D2 affinity of lysergamides is comparable to their 5-HT₂A affinity; D1 affinity is 2–3-fold lower [Ref 7]. By structural analogy, LSZ likely shares this dopaminergic profile.

The polypharmacology study by Jain et al. 2025 [Ref 8] profiled 41 classical psychedelics (including multiple lysergamides) against 318 human GPCRs and found potent actions at nearly every serotonin, dopamine, and adrenergic receptor. Multiple 5-HT₂A transducers correlate with psychedelic drug-like actions in vivo [Ref 8].

### Mechanism of Action

LSZ's primary psychedelic mechanism is agonism at the serotonin 5-HT₂A receptor [Ref 1, Ref 2]. This is confirmed by:
1. Head-twitch response (HTR) in mice blocked by selective 5-HT₂A antagonist M100907 [Ref 2]
2. The (S,S) diastereomer's HTR potency correlating with 5-HT₂A affinity [Ref 1]
3. Class-level evidence: ketanserin (5-HT₂A antagonist) almost fully blocks LSD's acute psychedelic effects in humans [Ref 29, Ref 30]

LSD (and by class inference, LSZ) also engages dopamine D2-like receptors in a temporally delayed second phase of action [Marona-Lewicka et al. 2005, Ref 19]. This D2 phase may contribute to late-phase effects distinct from the initial serotonergic phase.

The TrkB receptor (BDNF receptor) has been identified as a high-affinity binding target for LSD, with 1000-fold higher affinity than classical antidepressants (Moliner et al. 2023 [Ref 34]). Effects on neuroplasticity and antidepressant-like behavior depend on TrkB binding independent of 5-HT₂A activation. Whether LSZ similarly binds TrkB has not been directly investigated.

### Behavioral Potency

Mouse head-twitch response (HTR) dose-response study by Brandt et al. 2017 [Ref 2]:
- **LSZ ED₅₀ = 114.2 nmol/kg** (95% CI: 82.0–159.1 nmol/kg)
- LSD ED₅₀ = 132.8 nmol/kg (comparison)
- AL-LAD ED₅₀ = 174.9 nmol/kg (comparison)
- Maximal HTR at 200 µg/kg; inverted-U dose-response curve

**Conclusion:** LSZ is equipotent to LSD in mice in the HTR paradigm [Ref 2]. Halberstadt et al. 2020 [Ref 11] demonstrated a strong positive correlation (r = 0.9448) between mouse HTR potency and reported hallucinogenic potency in humans across 36 compounds. This validates cautious extrapolation: LSZ is likely equipotent to LSD in humans, though direct human study data are absent.

**Rat drug discrimination:** In a two-lever drug discrimination paradigm in rats trained on LSD, the (S,S)-(+) LSZ isomer had ED₅₀ ≈ 25 nmol/kg, making it slightly more potent than LSD in this assay [Nichols 2002, Ref 1, as reported in PMC5411264]. This makes LSZ approximately 1.8-fold more potent than LSD in the rat drug discrimination model.

**FLAG for human review:** The drug discrimination ED₅₀ of 25 nmol/kg for LSZ is cited from the PMC full text of Brandt et al. 2017 [Ref 2] which references Nichols 2002 [Ref 1]. This figure was attributed to Nichols 2002 but not independently verifiable from the abstract. Full-text Nichols 2002 verification is required.

### Pharmacokinetics

**LSZ-specific human PK data: NONE PUBLISHED.** The following is class-level reference data from LSD studies:

Human LSD pharmacokinetics (Holze et al. 2021 [Ref 23]; Dolder et al. 2015 [Ref 21]; Dolder et al. 2017 [Ref 22]):
- **Tmax:** ~1–2 hours (oral)
- **Elimination half-life:** 2.7 h (range 1.5–6.2 h) at microdoses [Ref 23]; longer estimates at full doses (~3–5 h per Dolder 2017 [Ref 22])
- **Pharmacokinetics:** Dose-proportional, first-order elimination [Ref 23, Ref 41]
- **Duration of subjective effects:** 6.7–11 h dose-dependently at 25–200 µg LSD [Ref 29]

**LSZ metabolism:** Wagmann et al. 2019 [Ref 3] studied LSZ metabolism in pooled human liver S9 fractions. Primary metabolic pathways are **N-dealkylation and hydroxylation**, catalyzed principally by **CYP1A2 and CYP3A4**. Importantly, the parent compound was not detectable in rat urine at expected recreational doses by standard urinalysis screening procedures [Ref 3]. This has forensic implications: urinalysis at clinical doses may miss LSZ exposure; targeted metabolite methods are needed.

**FLAG for human review:** No published human bioavailability, Cmax, Tmax, or half-life data exist for LSZ specifically. All PK figures applicable to LSZ are extrapolated from LSD studies. Individual variation in CYP1A2 and CYP3A4 activity may alter LSZ's effective half-life substantially.

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## History

### Discovery and Synthesis

LSZ was first synthesized and pharmacologically characterized by **David E. Nichols, Sangita Frescas, Danuta Marona-Lewicka, and Dawn M. Kurrasch-Orbaugh** at **Purdue University** and published in 2002 in the *Journal of Medicinal Chemistry* [Ref 1]. The work was part of a systematic SAR study to determine how the diethylamide moiety of LSD binds to the 5-HT₂A receptor.

The rationale: the 2,4-dimethylazetidine ring was used as a conformationally restricted analogue of diethylamine, effectively "locking" the amide group into defined geometric orientations. By comparing the pharmacology of the three diastereomers, Nichols et al. determined that the (S,S)-(+) isomer (LSZ) had a binding geometry most similar to LSD's optimal conformation — distinct from what X-ray crystallography of LSD in the solid state had predicted [Ref 1].

### Pre-Publication History (Unconfirmed)

According to journalist Hamilton Morris's interview with Krystle Cole, the clandestine LSD manufacturers **William Leonard Pickard and Gordon Todd Skinner** may have synthesized and distributed a psychedelic compound called **"diazedine"** around the year 2000 — prior to the Nichols 2002 publication [Ref 18]. This compound may have been LSZ or a related lysergamide. This claim is unconfirmed from any published primary source and should be treated as anecdotal. The street names "Diazedine" and "λ" (Lambda) for LSZ may derive from this history.

### NPS Market Emergence

LSZ **first definitely appeared as a novel designer drug in Europe in December 2013**, distributed in both powdered and blotter form [Ref 2]. It was sold as a "research chemical" by vendors including **Lizard Labs** (Lizart Trading B.V. / Synex Synthetics B.V., Maastricht, Netherlands), which operated from 2012 to December 31, 2024 [Ref 18]. Commercial blotters were labeled at 150 µg; measured content was approximately 112–131 µg per blotter (recovery ~93.3%) [Ref 2, via PMC].

In 2023, LSZ was identified in sheet products in Japan alongside other LSD analogs, demonstrating continued global distribution [Ref 4].

### Regulatory History

- **UK:** Added to Schedule 1 of the Misuse of Drugs Act as a Class A substance in January 2015 (sources cite January 6, 7, or 15 — see Gaps). [Ref 17, Ref 18]
- **Denmark:** Controlled as of May 2015 [Ref 18]
- **Switzerland:** Illegal as of December 2015 [Ref 18]
- **Sweden:** Classified as a controlled narcotic as of January 26, 2016 [Ref 17, Ref 18]
- **France:** Listed as narcotic (date not confirmed) [Ref 18]
- **Germany:** Covered under NpSG (Neue-psychoaktive-Stoffe-Gesetz) [Ref 18]

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## Subjective Effects

**No published controlled human studies exist for LSZ specifically.** All subjective effect descriptions are inferred from:
1. Class-level LSD studies (Holze et al. 2021 [Ref 29], Holze et al. 2022 [Ref 40])
2. The HTR behavioral equivalence to LSD [Ref 2, Ref 11]
3. Self-report data from NPS community sources (seed data, PsychonautWiki)

### Effects Documented from LSD Controlled Studies (Class Reference)

Holze et al. 2021 [Ref 29] (16 healthy subjects, LSD 25–200 µg, DB-RCT) documented the following acute effects:

**Perceptual:** Visual alterations, hallucinations, and perceptual distortions increase dose-dependently. No specific breakdown of visual subtypes is provided but effects are consistent with the taxonomy in the brief (tracers, drifting, color enhancement, pattern recognition, internal hallucinations).

**Cognitive:** Impairments in control and cognition at 200 µg. Thought alterations consistent with the effect categories in the brief (thought acceleration, creativity enhancement, thought loops, pattern recognition).

**Affective:** "Good drug effects" plateau at 100 µg; anxiety and ego dissolution increase markedly at 200 µg [Ref 29]. Emotional enhancement documented.

**Transpersonal:** Ego dissolution dose-dependently increases; at 200 µg significantly higher than at 100 µg [Ref 29, Ref 40].

**Physical:** Blood pressure and heart rate moderately increased. Pupil dilation expected by class mechanism (adrenergic activation). Wakefulness consistent with class data.

**Duration:** At LSD 25–200 µg, average duration of subjective effects was **6.7–11 hours** dose-dependently [Ref 29]. LSZ duration in seed data is listed as 6–10 hours total, consistent with LSD at lower doses. Duration appears shorter than LSD at equivalent potency doses — this is consistent with user reports but unconfirmed by controlled data.

### Dose Ranges

Seed data dose ranges (threshold 50 µg, light 100–150 µg, common 150–300 µg, strong 300–400 µg, heavy 400+ µg) appear reasonable relative to LSZ's equipotency with LSD in animals [Ref 2, Ref 11]. The HandWiki summary [Ref 18] lists a typical oral dose of 150–200 µg and a range of 100–300 µg, broadly consistent with seed data. Note that labeled blotter doses are inaccurate (112–131 µg when labeled 150 µg) [Ref 2], adding practical dose uncertainty.

**FLAG for human review:** Dose ranges for LSZ are entirely based on structural analog inference from LSD data, animal potency data (HTR, drug discrimination), and uncontrolled user reports. No clinical study has established safe or effective dose ranges for LSZ in humans.

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## Safety & Toxicity

### Acute Toxicity

**No LD₅₀ or toxic dose data have been published for LSZ.** The brief correctly notes "toxic dose is unknown."

The closest available class reference is Klock et al. 1974 [Ref 33]: eight cases of massive intranasal LSD overdose (pure LSD tartrate powder, self-administered). Toxidrome included:
- Emesis and collapse
- Sympathetic overactivity
- Hyperthermia
- Coma and respiratory arrest
- Mild generalized bleeding with platelet dysfunction
- Serum LSD concentrations: 2.1–26 ng/mL; gastric concentrations 1,000–7,000 µg/100 mL

All eight patients survived with supportive care [Ref 33]. Only two deaths attributable to direct LSD toxicity are reported in the historical literature; most LSD-associated fatalities involve accidents during intoxication rather than pharmacological toxicity per se.

### Cardiovascular Effects

At clinical doses of LSD (100–200 µg), Holze et al. 2021 [Ref 29] document **moderate blood pressure and heart rate increases**. LSD increases heart rate more than psilocybin at comparable doses; psilocybin increases blood pressure more [Ref 40]. These sympathomimetic effects are class-level; likely applicable to LSZ.

**5-HT₂B and cardiac valvulopathy:** LSD (unlike 2-Br-LSD) has documented agonist activity at 5-HT₂B receptors [Ref 25]. Chronic 5-HT₂B agonism is associated with cardiac valvulopathy (as seen with ergot derivatives such as fenfluramine and pergolide). LSZ has a Ki of approximately 27 nM at 5-HT₂B [Ref 18]. At typical psychedelic dose frequencies (infrequent use), this risk is considered theoretical; with heavy chronic use, monitoring is warranted.

### Psychological Risks

**Anxiety and ego dissolution:** At LSD 200 µg, anxiety and ego dissolution increase significantly beyond what is seen at 100 µg [Ref 29, Ref 40]. Given LSZ's equipotency with LSD, similar dose-dependent increases in psychological distress are expected at higher doses.

**Challenging experiences:** Schlag et al. 2022 [Ref 14] (systematic review of psychedelic adverse effects) documents anxiety, panic, paranoia, and psychosis as documented psychological adverse effects of classical psychedelics. Individuals with personal or family history of psychosis or schizophrenia-spectrum disorders are at elevated risk.

**HPPD:** Hallucinogen Persisting Perception Disorder (HPPD) is a documented rare adverse effect of hallucinogen use [Ref 13]. Type 1 consists of brief "flashbacks"; Type 2 is chronic and involves persistent visual phenomena, waxing and waning over months to years. Vulnerability factors include: pre-existing anxiety, tinnitus, eye floaters, and concentration difficulties [Ref 13]. No LSZ-specific HPPD cases have been published.

### No Published Case Reports

No published adverse event, overdose, or case report data specific to LSZ was identified. Safety data is entirely by class analogy with LSD and other lysergamides.

**FLAG for human review:** The absence of case reports does not mean LSZ is safer than LSD — it may simply reflect lower prevalence of use and limited forensic detection. All safety statements for LSZ are structural analog inferences.

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## Harm Reduction

### Testing and Identification

The **Ehrlich reagent** reacts with indole-containing compounds including LSZ, producing a purple color [Ref 18]. This confirms the presence of an indole moiety but cannot distinguish LSZ from LSD, psilocin, or other tryptamines. For definitive identification, NMR or LC-MS is required [Ref 2, Ref 5].

Blotter content verification: Brandt et al. 2017 [Ref 2] found that commercial blotters labeled at 150 µg contained 112–131 µg of LSZ (93.3% recovery by HPLC). Users should assume labeled doses may be inaccurate.

### General Psychedelic Harm Reduction

The following principles apply to LSZ as a potent 5-HT₂A agonist with LSD-equivalent potency:
- Start with threshold doses (50 µg); titrate incrementally
- Set and setting are critical to outcome [class data]
- Do not combine with lithium or tramadol (see Interactions)
- Avoid use in personal or family history of psychosis, mania, or schizophrenia
- Have a sober trip sitter for first experiences or higher doses
- Do not operate heavy machinery or drive during the experience (6–10+ h duration)

### Emergency Response

If 5-HT₂A antagonism is needed in an acute emergency, ketanserin administration after LSD was shown to effectively reverse acute subjective effects in a controlled study [Ref 30]. Benzodiazepines are commonly used clinically for agitation management (class data). No LSZ-specific emergency protocols exist.

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## Tolerance & Dependence

### Tolerance Development

Tolerance to serotonergic psychedelics develops rapidly via **5-HT₂A receptor downregulation in the frontal cortex** [de la Fuente Revenga et al. 2022, Ref 12; Smith et al. 1999, Ref 35]. The mechanism is 5-HT₂A receptor-dependent but **independent of β-arrestin-2** [Ref 12]. Tolerance begins almost immediately after ingestion and continues to develop with repeated administration.

Seed data values (buildup: almost immediately; half-life: 3 days; full reset: 7 days) are consistent with published class data for LSD-type psychedelics and have not been contradicted by any published source.

### Cross-Tolerance

**Full cross-tolerance exists** between LSZ and other serotonergic psychedelics (LSD, psilocybin, mescaline, DMT) via shared 5-HT₂A downregulation [Ref 12]. Cross-tolerance was demonstrated between DOI and LSD in mice [Ref 12]; no cross-tolerance was found with non-psychedelic 5-HT₂A agonist lisuride, confirming the mechanism is psychedelic-specific.

### Dependence Liability

LSZ has low dependence liability by class data. Classical psychedelics are not considered habit-forming and do not produce physical withdrawal syndromes [Ref 14, Ref 9]. No reinforcing behavior has been demonstrated in animal models for LSD-class compounds. Seed data states "not habit-forming" — consistent with published class data.

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## Interactions

### Tramadol — DANGEROUS

**Classification in seed data: dangerous.** Mechanism confirmed: tramadol inhibits the serotonin transporter (SERT) and has partial 5-HT₂A agonist activity [Ref 15]. When combined with a serotonergic psychedelic like LSZ (itself a potent 5-HT₂A agonist), the risk of **serotonin syndrome** (hyperthermia, clonus, altered mental status) is real and documented for the opioid+serotonergic class [Ref 15, Ref 16]. The FDA issued a Drug Safety Communication in 2016 warning about serotonin toxicity with the entire class of opioid pain medicines in combination with serotonergic agents [Ref 15].

No case report of LSZ+tramadol serotonin syndrome exists specifically, but the mechanism strongly supports the dangerous classification in the brief.

### Lithium — DANGEROUS (not listed in brief, flag for addition)

Nayak et al. 2021 [Ref 31] analyzed 62 online reports of lithium co-administration with classic psychedelics: **47% involved seizures**, and 39% required medical attention. Lamotrigine (n=34) showed no such effect. Edwards et al. 2024 [Ref 32] report a case of three generalized seizures in a 15-year-old within 30 minutes of LSD use while on low-dose lithium therapy; no prior seizure history; prior LSD use without seizures before lithium initiation. Seizures occurred even at subtherapeutic lithium levels.

**FLAG for human review:** Lithium is not listed in the brief's interactions data. Given the strength of evidence (47% seizure rate, a case report), this should be added as a dangerous interaction.

### Cannabis — VARIABLE (listed as "unknown")

Dose-dependent modulation of psychedelic experience by cannabis is documented in prospective survey data [Ref 42]:
- **Low-dose cannabis:** May reduce anxiety/fear subscales (lower scores on "fear" and "insanity" relative to no cannabis)
- **High-dose cannabis:** Significantly intensifies mystical-type experiences, ego dissolution, and visual alterations; also increases risk of challenging experiences
- The interaction is dose-dependent, not uniformly dangerous or uniformly beneficial

The "unknown" classification in the brief should be updated to reflect this dose-dependent pattern. The interaction is not dangerous per se but unpredictable, with high-dose cannabis substantially amplifying psychedelic effects.

### SSRIs/SNRIs — REDUCES EFFECTS

Bonson et al. 1996 [Ref 37]: 88% of subjects on chronic SSRIs (fluoxetine, paroxetine, sertraline, trazodone, >3 weeks) reported decreased or eliminated LSD response. Mechanism: chronic SSRI use downregulates 5-HT₂A receptors, the primary target of lysergamides. Effects may be substantially blunted. Halman et al. 2024 [Ref 38] systematic review confirms this as the dominant interaction pattern, with a minority of users reporting unchanged or enhanced effects.

**Serotonin syndrome risk:** Malcolm & Thomas 2022 [Ref 39] assessed serotonin toxicity risk with psychedelics+SSRIs; 10 studies showed no signs of serotonin syndrome. The primary interaction is blunting, not toxicity, for SSRIs.

### MAOIs — HIGH CAUTION

No specific LSZ+MAOI studies exist. Class-level concern: MAOIs raise extracellular serotonin by blocking metabolic degradation; this, combined with 5-HT₂A agonism from LSZ, could theoretically contribute to serotonin syndrome. Halman et al. 2024 [Ref 38] notes this as a potential interaction but no controlled human data specific to lysergamides+MAOIs exists. In practice, ayahuasca (DMT+MAOI) is widely used without consistent serotonin toxicity, suggesting the risk may be lower than theorized.

### Antipsychotics — BLOCKS EFFECTS

5-HT₂A and D2 receptor antagonists (antipsychotics such as haloperidol, olanzapine, risperidone, quetiapine) are expected to block LSZ's effects by competitive receptor antagonism [Ref 38, Ref 19]. Haloperidol and olanzapine transiently reverse chronic LSD-induced behavioral changes in rats [Ref 19].

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## Legal Status

| Jurisdiction | Status | Date | Notes |
|---|---|---|---|
| United Kingdom | Class A, Schedule 1 | January 2015 | Specifically named in Misuse of Drugs Act; date inconsistent across sources (Jan 6, 7, or 15) [Ref 17, Ref 18] |
| United States | Unscheduled | — | Federal Analogue Act may apply if sold for human consumption as LSD analogue [Ref 17] |
| Germany | NpSG (controlled) | — | Industrial and scientific use only [Ref 18] |
| Denmark | Controlled | May 2015 | [Ref 18] |
| France | Illegal (narcotic) | — | Date not confirmed [Ref 18] |
| Sweden | Controlled narcotic | January 26, 2016 | Manufacturing, trade, or possession prohibited [Ref 17, Ref 18] |
| Switzerland | Illegal | December 2015 | [Ref 18] |
| Canada | Not specifically controlled | — | Analogue clause risk; not explicitly scheduled [web_retrieved] |
| Australia | Likely prohibited | — | TGA captures lysergamide analogues broadly; not confirmed for LSZ specifically [web_retrieved] |
| International | Not controlled | — | Not in UN 1971 or 1961 Conventions; no lysergamide placed under international control since 2015 [Ref 36] |

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## Clinical Trials

**No clinical trials found.** ClinicalTrials.gov search returned zero results for "LSZ lysergamide." No ongoing, completed, or recruiting trials involving LSZ were identified.

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## Community Feedback Analysis

No community feedback submitted (Part A2 of brief was empty).

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## Gaps & Flags

### Safety-Critical Values Not Confirmed by Published Sources

1. **⚠️ LD₅₀ / toxic dose:** Unknown. No published data for LSZ. Brief correctly states this. Safety-critical gap.
2. **⚠️ Dose ranges:** All dose ranges (threshold–heavy) are based on structural analog inference from LSD data and uncontrolled user reports. No clinical dose-finding study exists for LSZ.
3. **⚠️ Ki values:** The receptor binding values (5-HT₁A 0.45 nM, 5-HT₂A 0.54–19.2 nM, etc.) are attributed to Nichols 2002 via HandWiki [Ref 18]. Full-text verification of the original paper is required before these are presented as verified data.
4. **⚠️ Drug discrimination ED₅₀ = 25 nmol/kg:** Cited from PMC full text of Brandt 2017 referencing Nichols 2002. Indirect attribution; requires primary source verification.

### Contradictions Between Seed Data and Published Sources

5. **UK scheduling date:** Seed data does not specify a date. Published sources are inconsistent: Erowid says January 15, 2015 [Ref 17]; HandWiki says January 6, 2015; other sources say January 7, 2015. The exact date should be verified against the UK Misuse of Drugs (Amendments) Order.
6. **Lithium interaction missing from brief:** The brief lists "Tramadol: dangerous" and "Cannabis: unknown" but does not list lithium. Given the 47% seizure rate in combined use reports [Ref 31] and a published case report [Ref 32], lithium should be added as a dangerous interaction.
7. **Cannabis interaction listed as "unknown":** Survey evidence [Ref 42] indicates a dose-dependent interaction pattern — not uniformly dangerous but not fully unknown. "Caution, dose-dependent intensification" would be more accurate.

### Data Absence Flags

8. **No human pharmacokinetics data for LSZ:** All PK parameters (onset, half-life, duration) are extrapolated from LSD studies. Significant uncertainty applies.
9. **No human subjective effects data for LSZ:** No controlled study has been conducted with LSZ in humans. All effect descriptions are class inferences from LSD research.
10. **No case reports:** No published adverse events, overdoses, or case reports specific to LSZ.
11. **No HPPD cases for LSZ:** HPPD risk is documented for the hallucinogen class [Ref 13] but no LSZ-specific cases appear in published literature.
12. **Physical properties gap:** No melting point, aqueous solubility, or stability data found in published or verified literature.
13. **Australia and Canada legal status:** Not confirmed from primary regulatory sources. Listed as likely/probable based on general regulatory frameworks.
14. **"Diazedine" pre-2002 history:** Unconfirmed. Anecdotal via interview with Krystle Cole as reported by Hamilton Morris. Cannot be cited as established fact.
15. **Efficacy data:** LSZ is described as having 56–85% efficacy at 5-HT₂A relative to LSD in the HandWiki source [Ref 18]. This partial efficacy claim should be flagged for verification against Nichols 2002 full text, as full agonism vs. partial agonism at 5-HT₂A is pharmacologically significant.

### Structural Analog Inference Dependency

The following sections rely primarily on LSD class data rather than LSZ-specific data and should be clearly labeled in generated article prose:
- All subjective effects descriptions
- Duration data (except HTR onset timing from mouse studies)
- All human PK parameters
- Cardiovascular effects
- Psychological risk characterization
- Dependence and withdrawal characterization
- HPPD risk
- Most interaction severity assessments (except tramadol/lithium where mechanism is class-confirmed)