AL-LAD

# Research Output: AL-LAD

**Substance:** AL-LAD (N6-allyl-6-norlysergic acid diethylamide)
**PSX ID:** PSX-0092
**Research Date:** 2026-04-24
**Provenance ID:** be2617be-804a-4f00-a803-c82821c18e0f

---

## Chemical Identity

**Verified via PubChem CID 15227511:**

| Property | Verified Value | Brief Seed Data |
|---|---|---|
| Molecular Formula | C22H27N3O | Missing |
| Molecular Weight | 349.5 g/mol | Missing |
| InChIKey | JCQLEPDZFXGHHQ-OXQOHEQNSA-N | Missing |
| PubChem CID | 15227511 | Missing |
| CAS | 65527-61-9 | Missing |
| SMILES | Not returned by API (see note) | Missing |
| IUPAC Name | (6aR,9R)-N,N-diethyl-7-prop-2-enyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide | Missing |

**Systematic name from brief:** N6-allyl-6-norlysergic acid diethylamide — consistent with PubChem IUPAC and confirmed correct.

**SMILES note:** PubChem CID 15227511 was successfully retrieved but the API did not return a SMILES string in this query. Cayman Chemical product 30442 (CAS 65527-61-9) confirms compound identity but did not provide SMILES in the fetched content. SMILES should be retrieved directly from PubChem compound page or ChEMBL for population. ⚠️ FLAG for generation agent.

**Stereochemistry:** The IUPAC name specifies absolute configuration (6aR,9R), identical to the configuration of natural d-lysergic acid derivatives and consistent with LSD's active (5R,8R) ergoline numbering convention. AL-LAD is described and sold as a single stereoisomer. No data on inactive enantiomers found.

**Physical properties:** Melting point, aqueous solubility, and stability data not found in the searched primary literature for AL-LAD specifically. As an ergoline compound it is expected to be light-sensitive (class-level inference). ⚠️ FLAG: physical property data absent from literature.

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## Pharmacology

### Receptor Pharmacology

**Primary mechanism:** AL-LAD is a serotonin 5-HT2A receptor agonist. This has been confirmed experimentally via the head-twitch response (HTR) assay — a validated 5-HT2A-mediated behavioral proxy for hallucinogenic activity in rodents — which was blocked by pretreatment with the selective 5-HT2A antagonist M100907 in the broader lysergamide series (Brandt et al. 2015 [Ref 9]).

**In vivo potency:** Brandt et al. (2017 [Ref 1]) characterized AL-LAD using the HTR assay in male C57BL/6J mice. AL-LAD produced an inverted U-shaped dose-response function with maximal response at 200 µg/kg. The ED50 was **174.9 nmol/kg** (AL-LAD), compared to **132.8 nmol/kg** for LSD, making AL-LAD approximately 75% as potent as LSD in this assay. LSZ was approximately equipotent to LSD (ED50 = 114.2 nmol/kg) in the same study.

**Receptor binding constants (Ki/EC50):** ⚠️ FLAG — No published AL-LAD-specific binding affinity data (Ki or EC50) at individual receptors (5-HT2A, D2, 5-HT1A, etc.) was identified in the searched literature. All receptor pharmacology for AL-LAD is inferred from: (a) the HTR/5-HT2A assay result above; (b) class-level ergoline pharmacology; and (c) data from closely related lysergamides in the Brandt/Halberstadt series. This is an important data gap for the pharmacology section.

**Mechanistic pathway:** Wallach et al. (2023 [Ref 25]) demonstrated that 5-HT2A-Gq/11 signaling (not β-arrestin2 recruitment) predicts psychedelic potential in mice, with a threshold level of Gq activation required to produce hallucinogen-like effects. This pathway is presumed to mediate AL-LAD's psychedelic effects by class analogy, though this has not been directly confirmed for AL-LAD.

**EL2 lid mechanism:** Wacker et al. (2017 [Ref 18]) solved the crystal structure of LSD bound to 5-HT2B, revealing that extracellular loop 2 (EL2) forms a "lid" over the binding pocket that restricts dissociation kinetics and explains LSD's characteristically prolonged receptor occupancy. This mechanism is structurally relevant to AL-LAD, which shares the core ergoline scaffold, though specific residence time data for AL-LAD has not been published.

**Secondary receptor targets (class-level):**
- **Dopamine receptors (D2/D1):** Watts et al. (1995 [Ref 33]) showed LSD and structural analogs bind D2-like receptors in rat striatum with affinity comparable to their 5-HT2 binding (~2-3 fold lower affinity at D1). The brief's classification of AL-LAD as a "Dopamine receptor agonist" is supported by class-level ergoline pharmacology.
- **5-HT1A (partial agonism):** Ergoline class pharmacology; the related compound LSM-775 was shown to have functional 5-HT1A agonism that masked its 5-HT2A effects (Brandt et al. 2018 [Ref 23]). 5-HT1A partial agonism is consistent with the brief's classification.
- **5-HT2B:** Ergoline class consideration; LSD's 5-HT2B agonism is associated with potential cardiac valvulopathy concerns at high chronic doses (Lewis et al. 2023 [Ref noted in OpenAlex]; no specific AL-LAD 5-HT2B data found).

### Pharmacokinetics

**No published human PK data exists for AL-LAD.** The following is from the LSD comparator for contextual reference:

- **LSD (microdoses 5–20 µg):** Tmax = 1.1 h, elimination half-life = 2.7 h, Cmax dose-proportional from 151–500 pg/mL (Holze et al. 2021 [Ref 22]).
- AL-LAD's shorter reported duration relative to LSD (see Duration section) is consistent with possible faster clearance or altered receptor kinetics, but no pharmacokinetic data from human studies has been published.

**Metabolism:** Wagmann et al. (2019 [Ref 4]) investigated AL-LAD's metabolic fate using pooled human liver S9 fractions. Key findings:
- Primary metabolizing enzymes: **CYP1A2** and **CYP3A4**
- Primary reactions: hydroxylation of the ergoline ring structure and N-dealkylation
- Parent compound was **not detectable in rat urine** at expected recreational doses using standard screening procedures, indicating extensive first-pass metabolism

Additional metabolic detail was obtained from the 1P-AL-LAD study (Brandt et al. 2022 [Ref 2]) which confirmed AL-LAD as the **most abundant metabolite** when 1P-AL-LAD is incubated with pooled human liver microsomes (pHLM). Fourteen total metabolites of the parent/metabolite system were detected: hydroxylation of core ring structure and N6-allyl group, dihydrodiol formation, N-dealkylation, N1-deacylation, dehydrogenation, and combinations thereof. This provides indirect evidence of AL-LAD's own metabolic fate.

---

## History

**First synthesis (1976):** AL-LAD appears to have been first synthesized by Japanese chemists **Tetsukichi Niwaguchi, Yuji Nakahara, and Hisashi Ishii** during studies on LSD and related compounds, specifically focusing on synthesis of various amide derivatives of norlysergic acid (Niwaguchi et al. 1976 [Ref 17]). This was part of investigations into microbial transformation products of LSD.

**First pharmacological characterization (1985):** **Andrew J. Hoffman and David E. Nichols** first described LSD-like discriminative stimulus properties of AL-LAD as part of a systematic structure-activity relationship (SAR) study of N6-alkyl norlysergic acid diethylamide derivatives (Hoffman & Nichols 1985 [Ref 16]). This study, published in the *Journal of Medicinal Chemistry*, established AL-LAD alongside ETH-LAD (N6-ethyl) and PRO-LAD (N6-propyl) as pharmacologically active LSD analogs.

**TIHKAL documentation (1997):** Alexander Shulgin documented AL-LAD in *TiHKAL: Tryptamines I Have Known and Loved* (Shulgin & Shulgin 1997 [Ref 27]).

**NPS market appearance (2013):** AL-LAD appeared on the "research chemicals"/new psychoactive substances (NPS) market in 2013 in both powdered and blotter form, as documented by Brandt et al. (2017 [Ref 1]). It was sold as a tartrate salt on blotter paper for recreational use.

**Ongoing NPS relevance:** As of 2023, AL-LAD continues to appear as an impurity or component in blotters sold online for recreational use, including as a detected impurity in 1cP-AL-LAD samples (Kavanagh et al. 2023 [Ref 3]), confirming ongoing market presence.

**No clinical/institutional research program exists for AL-LAD.** Unlike LSD, psilocybin, or MDMA, AL-LAD has never been the subject of a registered clinical trial or institutional human study.

---

## Subjective Effects

**No controlled human administration studies have been published for AL-LAD.** Available evidence derives from: (1) the mouse HTR assay confirming 5-HT2A-mediated activity, (2) one survey of self-reported user experiences.

### User Survey Data

Coney et al. (2017 [Ref 8]) conducted a comparative survey of LSD analogue users (AL-LAD, 1P-LSD, ETH-LAD) and LSD users via the Global Drug Survey. Key findings:
- LSD analogues (including AL-LAD) were reported as **similar in time to peak and duration as LSD** but **weaker in strength, pleasurable high, and comedown**
- User profiles of LSD analogue users overlapped substantially with LSD users
- Authors note these are self-reported data without chemical confirmation of dose or substance identity ⚠️ (user-report limitation)

### Effects Taxonomy Cross-Reference

The seed database taxonomy (perception, body, thinking, transpersonal, time, feeling, awareness effects) is consistent with what is known of 5-HT2A-mediated serotonergic psychedelic effects and ergoline class pharmacology. No published controlled study has verified specific individual effects listed in the taxonomy as specifically attributable to AL-LAD rather than the ergoline class in general.

### Duration Data

The seed database duration values (onset 20–60 min, come-up 30–60 min, peak 2.5–5 h, offset 2–3 h, aftereffects 2–18 h, total 7–10 h) are consistent with the Coney survey finding of "similar duration to LSD" and are plausible given AL-LAD's slightly lower potency. LSD's typical duration at recreational doses is 8–12 hours; AL-LAD's slightly shorter reported duration may reflect receptor kinetics or dose differences. These values derive from user self-report and are not verified by controlled study. ⚠️ FLAG: duration data is user-report only.

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## Safety & Toxicity

### Acute Toxicity

**No LD50 data has been published for AL-LAD.** No fatal overdose case reports were identified in the searched literature. The seed database characterization of "negligible" acute and chronic toxicity and "unknown toxic dose" is consistent with the class-level profile described by Nichols (2004 [Ref 19]): hallucinogens are considered "physiologically safe" with no known lethal dose in humans at recreational quantities.

### Adverse Event Profile

The primary risks of AL-LAD are psychological, consistent with the broader serotonergic psychedelic class:

- **Acute psychological distress:** Anxiety, panic attacks, paranoia, and persecutory ideation during intoxication. Kopra et al. (2022 [Ref 24]) found that recreational LSD use requiring emergency treatment was predominantly associated with acute psychological adverse events rather than physiological toxicity.
- **Psychosis triggering:** Serotonergic psychedelics can precipitate or exacerbate psychotic episodes in predisposed individuals. This is a class-level risk documented across LSD and psilocybin literature (Goldberg et al. 2020 [Ref 31]).
- **HPPD:** Hallucinogen persisting perception disorder (HPPD) is a rare but documented adverse outcome of serotonergic psychedelic use. Two types are recognized: Type 1 (brief flashbacks) and Type 2 (chronic, waxing/waning perceptual disturbances). Associated risk factors include pre-existing anxiety disorders, tinnitus, and prior perceptual abnormalities (Halpern et al. 2018 [Ref 13]). Leistenschneider et al. (2024 [Ref 32]) found neuropsychological evidence of impaired visual memory and executive function in some HPPD patients. No AL-LAD-specific HPPD cases were identified.
- **Seizure threshold reduction:** Listed in the seed effects taxonomy; consistent with the pharmacological class (5-HT2A agonism can increase cortical excitability). No AL-LAD-specific data found. ⚠️ FLAG — safety-critical value without AL-LAD-specific published evidence.

### Cardiovascular

Class-level data suggests mild transient sympathomimetic effects (increased heart rate and blood pressure) during acute serotonergic psychedelic intoxication, primarily mediated via 5-HT2A and adrenergic receptor activation. No AL-LAD-specific cardiovascular data was found. The "abnormal heartbeat" effect listed in the taxonomy aligns with the ergoline class profile.

### Chronic Toxicity

The seed database states "negligible" chronic toxicity, which is consistent with class-level evidence but not specifically studied for AL-LAD.

---

## Harm Reduction

### Testing

AL-LAD can be tentatively identified using the **Ehrlich reagent** (dimethylaminobenzaldehyde), which reacts with the indole ring system of ergolines and tryptamines to produce a purple/violet color. A positive Ehrlich reaction indicates the presence of an indole compound, consistent with AL-LAD or LSD, but does not distinguish between them. Mass spectrometry (HPLC-ESI-MS/MS, GC-MS) is required for definitive identification, as characterized by Brandt et al. (2017 [Ref 1]).

Drug checking services using point-of-care Raman spectroscopy and advanced HPLC-MS have been developed for NPS identification (Mullin et al. 2023 [Ref in drug checking literature]; Hirschfeld et al. 2021 [Ref noted in OpenAlex]), though detecting lysergamides at blotter concentrations remains analytically challenging.

### Contraindications

Based on class-level evidence:
- Personal or family history of psychotic disorders (schizophrenia, schizotypal disorder)
- Cardiovascular conditions (class-level sympathomimetic effects)
- Lithium carbonate coadministration (class-level seizure risk; no AL-LAD-specific data) ⚠️ FLAG
- Tramadol coadministration (serotonin syndrome risk — see Interactions)

### Set and Setting

Standard harm reduction guidance for serotonergic psychedelics applies: preparation, experienced presence, safe physical environment, no mixing with other substances, availability of benzodiazepine antidote (for psychological distress management). No AL-LAD-specific harm reduction protocols are published.

---

## Tolerance & Dependence

### Tolerance

The seed database states: tolerance builds almost immediately after ingestion, half-life 6 days, full reset at 14 days. This is consistent with the established mechanism:

de la Fuente Revenga et al. (2022 [Ref 15]) demonstrated in mice that:
- Repeated administration of the 5-HT2A agonist DOI produced progressive HTR tolerance
- Cross-tolerance was demonstrated between DOI and LSD
- Tolerance developed via **5-HT2A receptor downregulation** in frontal cortex
- The mechanism is independent of β-arrestin-2 signaling
- Non-psychedelic 5-HT2A agonists did NOT induce tolerance, suggesting tolerance is specific to the psychedelic signaling pathway

These findings support the seed database's tolerance characterization as class-level evidence applicable to AL-LAD. The specific 6-day half-life and 14-day reset values are widely cited in user communities but lack a published controlled study basis. ⚠️ FLAG — tolerance timeline values are community-derived, not from published controlled research.

Cross-tolerance within the psychedelic class (LSD, psilocybin, mescaline, AL-LAD) is expected based on shared 5-HT2A receptor downregulation mechanism.

### Dependence

Nichols (2004 [Ref 19]) reviewed that hallucinogens "do not produce dependence or addiction" and are considered physiologically safe. This is supported by the lack of dopaminergic reward pathway involvement as a primary mechanism (unlike addictive substances). The seed database characterization of AL-LAD as "not habit-forming" is consistent with class-level evidence.

No AL-LAD-specific dependence liability studies were found.

---

## Interactions

### Tramadol — DANGEROUS ⚠️

The seed database classifies the tramadol/AL-LAD combination as **dangerous**. This is supported by mechanism:

Tramadol is a weak mu-opioid receptor agonist that also inhibits serotonin and norepinephrine reuptake. Park et al. (2014 [Ref 20]) reviewed the risk of serotonin syndrome when tramadol is combined with serotonergic drugs, including antidepressants. When combined with a serotonergic agonist like AL-LAD, tramadol's SNRI properties could produce additive serotonergic excess, increasing risk of serotonin syndrome. Additionally, tramadol lowers seizure threshold, which may compound AL-LAD's class-level seizure threshold reduction. This interaction mechanism is supported at the pharmacological level; no AL-LAD+tramadol-specific case reports were found in the searched literature.

**Assessment:** The "dangerous" classification is pharmacologically well-supported at the class level. Confirmed as appropriate.

### Cannabis — UNKNOWN ⚠️

The seed database classifies the cannabis/AL-LAD combination as **unknown**. Kuc et al. (2022 [Ref 21]) conducted a prospective online survey (n=321) and found cannabis modulated psychedelic experience in a dose-dependent manner. Design limitations (self-report, no chemical confirmation) prevented causal inference. No controlled study of cannabis+AL-LAD specifically has been published.

**Assessment:** "Unknown" classification is appropriate. Some modulating interaction is plausible; direction and magnitude are unclear.

### Other Interactions (class-level inference — NOT AL-LAD-specific data):

- **MAOIs:** Potential for serotonin syndrome; class-level concern
- **SSRIs/SNRIs:** May reduce psychedelic effects (antagonism at 5-HT2A) and carry serotonin syndrome risk
- **Lithium:** Class-level seizure risk reported for LSD+lithium; no specific data for AL-LAD
- **Antipsychotics:** 5-HT2A/D2 antagonists would block or reduce AL-LAD effects

---

## Legal Status

| Jurisdiction | Status | Details |
|---|---|---|
| United Kingdom | Class A (illegal) | Named specifically in Misuse of Drugs Act, effective **January 7, 2015** |
| United States | Unscheduled | Federal Analog Act (FAA) may apply; no specific scheduling |
| Canada | Uncontrolled | Not listed as controlled substance (as of 2025) |
| Sweden | Schedule I | Narcotics Control Act, effective **January 26, 2016** |
| France | Illegal | Controlled substance |
| Denmark | Illegal | Controlled substance |
| Switzerland | Illegal | Controlled substance |
| Latvia | Possibly illegal | May be covered by LSD structural analog provisions (June 2015) |
| Australia | Restricted | Prohibited under import/export provisions; state-level restrictions likely |
| International (UN) | Not scheduled | Not listed under UN Convention on Psychotropic Substances |

Source: Web search corroborating multiple jurisdiction databases [Ref 28].

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## Clinical Trials

**No clinical trials found** on ClinicalTrials.gov for AL-LAD. Search conducted April 2026 using query "AL-LAD lysergamide." AL-LAD has not been investigated in any registered clinical trial as of this research date.

No compassionate use, expanded access, or investigational new drug (IND) applications for AL-LAD were identified.

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## Community Feedback Analysis

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

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## Gaps & Flags

The following items require attention by the generation agent and human editors:

### ⚠️ Safety-Critical Flags

1. **Seizure threshold reduction (effect listed):** No AL-LAD-specific published evidence. This effect appears in the taxonomy but is class-level inference from 5-HT2A pharmacology. Do not present as confirmed AL-LAD-specific finding.

2. **Tramadol/AL-LAD interaction:** Classified as "dangerous" in seed data. Mechanism is well-supported pharmacologically (tramadol SNRI + serotonergic agonist = serotonin syndrome risk); no AL-LAD-specific case report found to confirm, but mechanism is clear. The classification is appropriate.

3. **Dose range data:** All dose ranges in the seed database (threshold 20 µg through heavy 350+ µg) derive from user self-report and are NOT verified by any published controlled human study. No conversion calculation from mouse ED50 to human dose has been published. ⚠️ Flag all dose values as user-report-derived.

4. **Duration data:** All duration values in seed database are user-report-derived. No controlled pharmacokinetic study exists for AL-LAD in humans.

5. **Tolerance timeline (6-day half-life, 14-day reset):** These values are community-consensus estimates, not from published controlled research. Cross-tolerance and rapid development are confirmed at class level; specific timeline figures require editorial review.

### Data Gaps

6. **No published Ki/EC50 binding affinity data** for AL-LAD at any receptor. All receptor classifications are based on: (a) HTR assay confirming 5-HT2A activity; (b) class-level ergoline pharmacology. Generation agent should note absence of binding constant data explicitly.

7. **SMILES string:** Not returned by PubChem API in this query. Should be populated from PubChem compound page (CID 15227511) directly before article generation.

8. **No published human pharmacokinetic study** for AL-LAD. LSD PK data is cited as comparator only; AL-LAD PK may differ.

9. **Physical properties (melting point, solubility, stability):** Not found in searched primary literature. Cannot be provided by this research phase.

10. **No LD50 data** published for AL-LAD. "Toxic dose unknown" from seed data is correct but cannot be further specified.

11. **No case reports** of AL-LAD-specific overdose, adverse events, or fatalities in the searched literature. Adverse event characterization relies on LSD class-level evidence.

12. **Original synthesis SMILES/procedure:** The Hoffman & Nichols 1985 paper [Ref 16] is the primary SAR reference but full text was not retrieved. The Niwaguchi 1976 paper [Ref 17] has minimal abstract data. Full synthesis details are in these pre-digital papers.

13. **5-HT2B agonism:** LSD is a 5-HT2B agonist associated with cardiac valvulopathy concerns. Whether AL-LAD shares this profile has not been published. This may be relevant for cardiovascular safety characterization.

### Editorial Attention Needed

14. **Duration data (seed DB):** The "aftereffects" range of "2–18 hours" is extremely wide. This likely reflects high individual variability in subjective afterglow. Worth noting this range in the article.

15. **"Characterization: emerging"** in seed data is appropriate — AL-LAD has limited but growing peer-reviewed literature (primarily from the Brandt/Halberstadt/Nichols group).

16. **Historical note:** The Niwaguchi 1976 synthesis paper predates Nichols' 1985 pharmacological characterization. The question of whether the 1976 synthesis specifically targeted the N6-allyl compound versus a series of N-substituted analogs requires full text review of that paper. ⚠️ Flag for editorial review of history section.