DET

# Research Output: DET (N,N-Diethyltryptamine)

**PSX ID:** PSX-0154  
**Research date:** 2026-04-26  
**Generation provenance:** a7b1100e-4e09-4e35-8ba3-d6fd2e152a7b

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## Chemical Identity

**Confirmed via PubChem CID 6090 [Ref 22]:**

| Property | Value |
|---|---|
| PubChem CID | 6090 |
| IUPAC name | N,N-diethyl-2-(1H-indol-3-yl)ethanamine |
| Molecular formula | C₁₄H₂₀N₂ |
| Molecular weight | 216.32 g/mol |
| InChIKey | LSSUMOWDTKZHHT-UHFFFAOYSA-N |
| CAS number | 7558-72-7 [Ref 26] |
| SMILES | CCN(CC)CCc1c[nH]c2ccccc12 ⚠️ *Derived from structure — not returned by PubChem API; flag for editorial verification* |

**Physical properties:**
- Melting point (HCl salt): 169–171°C [Ref 18; Ref 26]
- Melting point (free base): 84–87°C [Ref 18]
- Solubility: Water-soluble as HCl salt (no quantitative data published)
- Stability: No published stability data found

**Discrepancies with seed data:**
- Seed data listed no SMILES, molecular formula, molecular weight, InChIKey, or PubChem CID. All now confirmed via PubChem. CAS 7558-72-7 added.
- SMILES derived from known structure; **flag for editorial verification** before publication.

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## Pharmacology

### Primary Receptor Targets

**5-HT2A receptor (primary target):**  
DET acts as an agonist at the serotonin 5-HT2A receptor and stimulates Gq-mediated phosphoinositide (PI) hydrolysis in a concentration-dependent manner, as demonstrated in PC12 cells stably expressing the rat 5-HT2A receptor (Rabin et al. 2002 [Ref 1]). This PI hydrolysis is consistent with the compound's hallucinogenic profile, though Rabin et al. note that 5-HT2A-mediated PI hydrolysis alone is not the sole determinant of the discriminative hallucinogen stimulus — 6-fluoro-DET also stimulates PI hydrolysis yet lacks hallucinogen-like discriminative effects. Blair et al. (2000 [Ref 2]) tested DET and its fluorinated ring analogues at 5-HT2A, 5-HT2C, and 5-HT1A receptors using radioligand competition assays. Specific Ki values for DET at these receptors are reported in the full paper but were not accessible in the abstract retrieved. The 5-HT2A Gq signaling pathway (not β-arrestin2) predicts psychedelic potential: Wallach et al. (2023 [Ref 4]) demonstrated in mice that 5-HT2A-Gq but not 5-HT2A-β-arrestin2 recruitment efficacy predicts head-twitch response (HTR) magnitude, the primary animal model of hallucinogenic potential.

⚠️ **FLAG:** Specific Ki/EC50 values for DET at 5-HT2A, 5-HT2C, and 5-HT1A are cited in Blair et al. 2000 [Ref 2] but were not retrievable from the abstract. The full paper (PMID 11101361) should be obtained to extract these values. DET's exact binding affinity in nM terms remains unconfirmed in this research pass.

**5-HT2C receptor:**  
DET has documented affinity at 5-HT2C receptors (Blair et al. 2000 [Ref 2]) consistent with its chemical class. DET-specific Ki at 5-HT2C not retrievable from abstract; see Blair 2000 for values.

**5-HT1A receptor:**  
DET has been tested at 5-HT1A in the fluorinated tryptamine series (Blair et al. 2000 [Ref 2]). The role of 5-HT1A in modulating tryptamine psychedelic effects has been characterized at the class level: 5-HT1A agonism dampens 5-HT2A-mediated HTR, as demonstrated for 5-MeO-DMT analogs (Glatfelter et al. 2024 [Ref not found — class-level inference]).

**Sigma-1 receptor:**  
The seed data lists sigma-1 receptor agonism as a pharmacological class for DET. This classification is well-established for DMT (Fontanilla et al. 2009 [Ref 8]; Su & Hayashi 2009 [Ref 24]), where DMT acts as an endogenous sigma-1 agonist and inhibits voltage-gated sodium channels. DET belongs to the same N,N-dialkyltryptamine structural class and is presumed to share sigma-1 activity, but **no published study has specifically measured DET's binding affinity or functional activity at sigma-1 receptors**. ⚠️ **FLAG: This is class-level inference, not substance-specific data.**

**Serotonin transporter (SERT) and VMAT2:**  
N,N-dialkyltryptamines including DMT, DPT, MIPT, and DIPT act as substrates (not blockers) at SERT and VMAT2, with high binding-to-uptake ratios supporting transporter substrate behavior rather than reuptake inhibition (Cozzi et al. 2009 [Ref 9]). DET-specific SERT KI data was not found. Class-level inference strongly suggests DET is also a SERT substrate.

### Mechanism of Action

DET's hallucinogenic effects are mediated primarily through 5-HT2A receptor activation with Gq-coupled signaling. Wallach et al. (2023 [Ref 4]) demonstrated that a threshold level of Gq activation at 5-HT2A is required to produce psychedelic-like effects; β-arrestin2 recruitment plays no predictive role. Repeated 5-HT2A activation induces receptor downregulation and tolerance, consistent with the cross-tolerance observed across classical psychedelics (de la Fuente Revenga et al. 2022 [Ref 10]).

DET is notably **orally active without MAOI co-administration**, distinguishing it from DMT. The accepted mechanism is that the two N-ethyl groups create greater steric bulk than DMT's N-methyl groups, reducing the rate of MAO-A-mediated deamination in the gut and liver sufficiently to allow CNS absorption at meaningful concentrations [Ref 26]. This is a pharmacokinetic distinction, not a receptor-level difference.

### Pharmacokinetics

**Oral bioavailability:** Demonstrated (Szára 1957 and later studies [Ref 17]); does not require MAOI co-administration unlike DMT.  
**Onset (oral):** 30–90 minutes [Ref 18, Ref 22]  
**Peak (oral):** 2–4 hours [Ref 18]  
**After-effects:** 2–8 hours [Ref 18]

**Metabolism:**  
No published human pharmacokinetic study specifically characterizing DET metabolism was found. Based on class-level data:
- Primary metabolic route for N,N-dialkyltryptamines is MAO-A-mediated oxidative deamination (class-level; Callaway 2005 [Ref not found])
- CYP2D6 mediates oxygenated metabolite formation for DMT in vitro (Eckernäs et al. 2023 [Ref 23]); this may apply to DET but no published data exist
- Szára's early research identified **6-hydroxy-DET** as a metabolite with minor psychoactive activity; 6-hydroxy-DMT was inactive (TIHKAL [Ref 18])
- The indole ring hydroxylation pattern suggests P450 involvement, but DET-specific CYP enzyme mapping has not been published

⚠️ **FLAG: No published human PK study exists for DET. All pharmacokinetic parameters are derived from historical clinical observation or structural analogy to DMT.**

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## History

DET was first synthesized by Hungarian chemist and psychiatrist **Stephen (István) Szára** in **1956**. Szára, working in Budapest, had synthesized a series of tryptamine derivatives and was the first to systematically investigate their hallucinogenic properties in humans [Ref 26; Ref 17]. His initial human self-experiment involved **intramuscular administration of 60 mg** of DET in 1956 [Ref 26; Ref 17].

The first published systematic clinical study of DET was by **Böszörményi, Dér, and Nagy (1959)** [Ref 16], "Observations on the Psychotogenic Effect of N,N-Diethyltryptamine, a New Tryptamine Derivative," published in the *Journal of Mental Science* (Vol. 105, Issue 438, January 1959). This study employed institutionalized psychiatric patients under conditions that Shulgin later characterized as oppressive, producing predominantly negative/anxiety-dominated reports.

Szára published a comprehensive review of DMT and its homologues, including DET's psychological effects and metabolism, in **1961** [Ref 17]. These early studies established that DET's effects were broadly similar to but milder than LSD, and included visual phenomena and altered perception of time and space.

DET's early clinical use occurred within the broader mid-20th century era of psycholytic therapy, during which numerous tryptamine and lysergamide compounds were explored in European psychiatric settings (Passie et al. 2022 [Ref 20]).

DET was placed on **Schedule I of the 1971 Convention on Psychotropic Substances**, making it one of only five tryptamines under international control at that time (alongside DMT, etryptamine, psilocin, and psilocybin) [Ref 19].

Alexander Shulgin independently documented DET in **TiHKAL (1997)** [Ref 18] as entry #3, providing synthesis routes, dosing, duration, and personal/collected experience narratives.

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## Subjective Effects

Primary published sources: Böszörményi et al. 1959 [Ref 16] (early clinical); Szára 1961 [Ref 17]; TIHKAL [Ref 18] (collected reports).

**Visual effects:**
- Visual patterns (greens and oranges noted); drifting, color alteration, after-images, and internal closed-eye imagery [Ref 16, Ref 18]
- Less visually intense than DMT at equivalent doses (class-level comparisons in TIHKAL [Ref 18])
- Visual acuity enhancement, depth perception distortion, and object transformations reported [Ref 18]

**Cognitive effects:**
- Novelty enhancement, pattern recognition enhancement, conceptual thinking
- Memory suppression and cognitive euphoria reported [Ref 18]
- Thought loops and delusions documented, particularly in early clinical studies with institutionalized patients [Ref 16]
- Personal insight and philosophical/mystical thinking in more positive set/setting contexts [Ref 18]

**Perceptual/temporal:**
- Time distortion — time appears to slow dramatically [Ref 16, Ref 18]
- Enhanced appreciation for music ("profound, enriching" musical experience) [Ref 18]
- Mystical and unity experiences reported in willing subjects under supportive conditions [Ref 18]

**Physical/somatic:**
- Tremors, tachycardia, sweating, vertigo documented in early clinical literature [Ref 16, Ref 17]
- Pupil dilation consistent with serotonergic stimulation
- Nausea reported in some accounts [Ref 18]
- Stimulation (energizing quality) distinct from sedating compounds

**Affective:**
- Emotional enhancement; euphoria when set/setting is positive [Ref 18]
- Anxiety, particularly in early studies with coercive clinical contexts [Ref 16]
- Unity and interconnectedness in some accounts [Ref 18]

**Route differences (from TIHKAL [Ref 18]):**
- *Oral:* Gradual onset (30–90 min), softer experience, longer duration
- *Smoking:* Rapid onset (~5 minutes), euphoric, empathogenic qualities, shorter duration
- *IM/IV:* More rapid and intense onset; visual patterns, enhanced music perception

**Duration data:**
- Oral onset: 30–90 minutes
- Oral peak: 2–4 hours
- Oral aftereffects: 2–8 hours
These values are consistent between TIHKAL [Ref 18] and PsychonautWiki [Ref 22], and are supported by Szára's historical clinical observations [Ref 17].

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## Safety & Toxicity

**LD50:** Not published. The toxic dose in humans is unknown. No LD50 data in any species was found in the indexed literature. ⚠️ **FLAG: Safety-critical value absent from published sources — confirmed consistent with seed data "toxic dose unknown."**

**Human case reports:** No published case reports of DET-specific overdose, adverse event, or fatality were found in PubMed or general web searches. This may reflect DET's relatively uncommon use rather than confirmed safety.

**Tryptamine class toxicity context:** Alpha-methyltryptamine (AMT), a structurally related tryptamine, caused at least one documented fatality in the US in 2003, with postmortem blood levels of 2.0 mg/L (Boland et al. 2005 [Ref 25]). This demonstrates serious toxicity potential within the tryptamine class at high doses, though AMT has distinct pharmacology (MAO inhibitor activity) that DET lacks.

**Documented adverse effects from clinical and self-report data:**
- Tachycardia and elevated heart rate — documented in early clinical studies [Ref 16, Ref 17]
- Tremors — documented clinically [Ref 16]
- Sweating, vertigo [Ref 17, Ref 18]
- Anxiety, paranoia, thought loops — especially without appropriate set/setting [Ref 16, Ref 18]
- Psychological risk in predisposed individuals (latent psychosis risk): class-level concern for all serotonergic psychedelics

**Cardiovascular:** Sympathomimetic effects (tachycardia, elevated blood pressure) are documented for the tryptamine class but DET-specific cardiovascular data is from historical clinical reports only [Ref 16, Ref 17].

**Psychological risks:**
- Acute psychosis-like states documented in early institutionalized patient studies [Ref 16] — these likely reflect adverse set/setting conditions
- Persistent perceptual disturbances (HPPD) not specifically reported for DET but documented as a class-level risk

---

## Harm Reduction

**Testing:** DET produces a positive Ehrlich reaction (purple color) consistent with indole-containing compounds, confirming the presence of an indole ring. This is a class-level identification marker for tryptamines and does not distinguish DET from other indoles (DMT, psilocin, psilocybin). ⚠️ No published analytical methodology specific to DET field testing was found.

**General psychedelic harm reduction principles applicable to DET:**
- Start with threshold doses (10 mg oral) when unfamiliar with personal response
- Ensure trusted sitter/guide present, particularly for common-to-strong doses
- Avoid in personal/historical context of psychosis, schizophrenia, or bipolar disorder with psychotic features (class-level contraindication)

**Drug interactions (serotonin syndrome risk):**
Malcolm and Thomas (2022 [Ref 21]) evaluated serotonin toxicity risk between serotonergic psychedelics and SSRIs/MAOIs at the class level. For tryptamines specifically:
- **MAOIs:** Co-administration is a serious risk. DET is not typically MAOI-dependent for oral activity (unlike DMT), but irreversible MAOIs (phenelzine, tranylcypromine) combined with serotonergic tryptamines create serotonin toxicity risk. Reversible MAOIs (moclobemide, harmaline) also carry risk.
- **SSRIs:** Serotonin toxicity risk at the class level; SSRIs may also blunt or paradoxically alter psychedelic effects
- **Lithium:** Class-level contraindication for psychedelics — case reports of seizures and cardiac arrhythmia (not DET-specific; applies to all classic psychedelics)
- **Tricyclics:** Additive serotonergic risk

⚠️ **FLAG: No DET-specific drug interaction studies published. All interaction data is class-level for serotonergic psychedelics.**

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## Tolerance & Dependence

**Tolerance development mechanism:**
Tolerance to serotonergic psychedelics develops rapidly (essentially after a single use) through 5-HT2A receptor downregulation in the frontal cortex (de la Fuente Revenga et al. 2022 [Ref 10]). This is a β-arrestin2-independent mechanism — it persists in β-arrestin2 knockout mice, indicating it is driven by G-protein-coupled receptor desensitization/internalization rather than arrestin-mediated mechanisms.

**Cross-tolerance:**
Cross-tolerance is established between serotonergic psychedelics (de la Fuente Revenga et al. 2022 [Ref 10]; DOI ↔ LSD cross-tolerance confirmed in mice). DET would be expected to show complete cross-tolerance with all classic psychedelics sharing the 5-HT2A Gq mechanism (LSD, psilocybin, DMT, mescaline, DOx compounds). ⚠️ **FLAG: Cross-tolerance is class-level inference for DET; no DET-specific cross-tolerance studies published.**

**Tolerance timeline (seed data — unverified against primary sources):**
- Buildup: Almost immediately after ingestion
- Half-life: 3 days (consistent with receptor resensitization timeline in class-level animal data)
- Full reset: 7 days
These values are consistent with the class-level human self-report literature and the mechanistic data from de la Fuente Revenga et al. [Ref 10], but are not confirmed by published DET-specific studies. ⚠️ **FLAG: Tolerance timeline is class-level inference and community-derived data.**

**Dependence liability:**
Classical psychedelics (including DET by class) do not produce physical dependence or withdrawal syndromes. This is consistent with the non-habit-forming characterization in the seed data. Drug discrimination and self-administration studies in rodents have consistently failed to demonstrate reinforcement with classical 5-HT2A agonist psychedelics (Gatch et al. 2011 [Ref 12]).

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## Interactions

| Interaction | Risk Level | Mechanism | Data Quality |
|---|---|---|---|
| Irreversible MAOIs (phenelzine, tranylcypromine) | ⚠️ Serious | Serotonin syndrome; elevated tryptamine levels | Class-level [Ref 21] |
| Reversible MAOIs (moclobemide, harmaline) | ⚠️ Moderate | Increased tryptamine duration/intensity; serotonin toxicity risk | Class-level [Ref 21] |
| SSRIs | Moderate | Serotonin toxicity; blunted/paradoxical effect | Class-level [Ref 21] |
| Lithium | ⚠️ Serious | Seizure and cardiac risk with psychedelics | Class-level, anecdotal |
| Tricyclic antidepressants | Moderate | Additive serotonergic load | Class-level |
| Other serotonergic psychedelics | Low-moderate | Additive effect + cross-tolerance | Class-level [Ref 10] |
| Stimulants (amphetamines, cocaine) | Moderate | Cardiovascular strain, anxiety potentiation | Class-level |
| Cannabis | Variable | Potentiation of perceptual effects, anxiety risk | Class-level |
| Alcohol | Moderate | CNS depressant interaction, judgment impairment | Class-level |

⚠️ **FLAG: No DET-specific interaction studies exist. All interaction data is class-level inference from general psychedelic research.**

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## Legal Status

DET is one of only **five tryptamines under international control**, explicitly listed in **Schedule I of the 1971 Convention on Psychotropic Substances** [Ref 19]. The others are DMT, etryptamine, psilocin, and psilocybin.

| Jurisdiction | Status | Notes |
|---|---|---|
| International (UN 1971) | Schedule I | One of 5 controlled tryptamines [Ref 19] |
| United Kingdom | Class A | Controlled since Misuse of Drugs Act 1971 [Ref 26] |
| Germany | Anlage I (BtMG) | Controlled since January 24, 1974 [Ref 26] |
| Canada | Schedule III, CDSA | Explicitly named in Controlled Drugs and Substances Act [Ref 26] |
| Australia | Schedule 9 | Poisons Standard (substances of abuse/misuse, prohibited except research) [Ref 26] |
| United States | Not explicitly listed (CSA) | Not in CSA Schedule I by name; Federal Analogue Act may apply if intended for human consumption, given structural similarity to scheduled tryptamines [Ref 26] |
| Netherlands | Unknown | Not confirmed in searches |

⚠️ **FLAG: US legal status is uncertain and complex. DET is not in the DEA Schedule I list by name, but the Federal Analog Act (21 USC 813) could apply. Generation agent should recommend editorial/legal review before definitive statements.**

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## Clinical Trials

**Search of ClinicalTrials.gov for "diethyltryptamine DET psychedelic":** One result found (NCT02033707, "Effects of Hallucinogens and Other Drugs on Mood and Performance," Johns Hopkins University, Phase 1, COMPLETED), but this is a general hallucinogen study and does not list DET as a specific study drug.

**Conclusion:** No DET-specific clinical trials are registered on ClinicalTrials.gov as of the search date (2026-04-26). No peer-reviewed controlled clinical trial of DET in humans has been published in the modern era.

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## Community Feedback Analysis

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

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## Gaps & Flags

### Safety-Critical Values (require editorial attention)

1. ⚠️ **LD50 unknown:** No published toxic dose data for any species. Confirmed absent from literature. The seed data note "toxic dose unknown" is accurate. Do not fabricate an LD50.

2. ⚠️ **SMILES string:** PubChem API did not return SMILES for CID 6090. The SMILES `CCN(CC)CCc1c[nH]c2ccccc12` is structurally derived and very likely correct, but must be verified against PubChem's canonical SMILES before publication.

3. ⚠️ **US legal status:** DET is not explicitly listed in the DEA's Schedule I but may fall under the Federal Analogue Act. Do not state DET is "unscheduled" in the US without legal review.

### Data Gaps (substance-specific data not found)

4. **Specific Ki/EC50 binding values:** Ki values for DET at 5-HT2A, 5-HT2C, 5-HT1A are reported in Blair et al. 2000 [Ref 2] (PMID 11101361) but not accessible from the abstract. The full paper should be retrieved to extract the nM binding values.

5. **Sigma-1 receptor data:** No published study has measured DET's binding affinity at sigma-1 receptors. The "sigma-1 receptor agonist" pharmacological class in the seed data is class-level inference from DMT sigma-1 data [Ref 8]. Flag in article prose as "presumed class-level activity."

6. **Human pharmacokinetics:** No published PK study for DET exists. Half-life, bioavailability, Tmax, and clearance are unknown. Dose/duration data is from historical clinical observation and community reports.

7. **DET-specific metabolism:** The 6-hydroxy-DET metabolite is noted in Szára's research (via TIHKAL [Ref 18]) but no published peer-reviewed metabolism study for DET exists. CYP enzyme involvement is unmapped.

8. **Szára 1956/1957 primary papers:** The original Szára synthesis and first human study papers are pre-digital and could not be retrieved via API. The 1959 Böszörményi et al. paper in the Journal of Mental Science is accessible via Cambridge Core but paywalled. Both are cited as [Ref 16, Ref 17] with "unverifiable" status.

9. **DET at SERT:** No DET-specific SERT substrate/inhibitor data was found. Class-level inference from Cozzi et al. 2009 [Ref 9] (tested DMT, DPT, MIPT, DIPT, but not DET).

10. **Case reports/overdose:** No published adverse event or overdose case reports specific to DET were found. This likely reflects low prevalence rather than safety.

11. **Physical properties:** Melting point of HCl salt (169–171°C) and free base (84–87°C) confirmed via TIHKAL [Ref 18] and ChemEurope. Boiling point, density, and aqueous solubility are not published in accessible sources.

12. **Stereochemistry:** DET has no chiral centers (unlike some tryptamine analogs). Single achiral compound. Confirmed by structure.

13. **Dose/duration seed data:** The seed data dose ranges (threshold 10mg, light 20–40mg, common 40–70mg, strong 70–100mg, heavy 100+mg oral) are consistent with TIHKAL's active range (50–100mg oral) and PsychonautWiki. The granular breakdown at lower doses (10–40mg) reflects community reporting not explicitly documented in TIHKAL. No controlled study has validated these thresholds. Propose retaining seed data values — they are well-supported by community evidence and structurally consistent with TIHKAL's active range.

14. **Tolerance timeline (3-day half-life, 7-day reset):** These values are community-derived; they are mechanistically consistent with 5-HT2A receptor resensitization timelines documented in rodent data but not validated specifically for DET in humans. Propose retaining as reasonable estimates derived from cross-tryptamine class data [Ref 10].