DiPT

# Research Output: DiPT (N,N-Diisopropyltryptamine)

**PSX ID:** PSX-0165 | **Slug:** dipt | **Generation Provenance:** aa957ff6-c78f-4184-86fc-37d614eca6ad
**Research completed:** 2026-04-26 | **Substance readiness:** sparse (< 0.3) — DiPT is a minimally studied research chemical with no controlled human trials

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## Chemical Identity

**Verified via PubChem CID 26903** (api_verified):

| Field | Value |
|---|---|
| Molecular formula | C16H24N2 |
| Molecular weight | 244.37 g/mol |
| IUPAC name | N-[2-(1H-indol-3-yl)ethyl]-N-propan-2-ylpropan-2-amine |
| InChIKey | ZRVAAGAZUWXRIP-UHFFFAOYSA-N |
| CAS number | 14780-24-6 |
| PubChem CID | 26903 |
| Free base melting point | 72–74 °C |
| HCl salt melting point | 192–193 °C |
| Distillation range | 170–185 °C at 0.05 mmHg |

The systematic IUPAC name and molecular formula in the brief's seed data match PubChem exactly. The brief's CID, SMILES, and InChIKey fields were blank — these are now verified and provided above. CAS number 14780-24-6 confirmed via multiple reagent supplier records (Cayman Chemical, Bertin Bioreagent).

DiPT is a **substituted tryptamine**: an indole ring bearing a 2-aminoethyl sidechain, with both hydrogen atoms on the terminal amine replaced by isopropyl groups. It is an isomeric positional variant of DPT (N,N-dipropyltryptamine, which carries n-propyl rather than i-propyl groups).

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## Pharmacology

### Receptor Profile

The most specific published pharmacological data for DiPT comes from Blough et al. (2014 [Ref 12]), which tested DiPT (listed as compound 22) in functional assays at serotonin receptors and in transporter binding assays. Key findings:

| Target | Value | Assay |
|---|---|---|
| 5-HT2A (functional, IP1 mobilization) | EC50 = **33.5 ± 1.5 nM** | Full agonist (110% intrinsic efficacy vs. 5-HT) |
| 5-HT1A | **Inactive at 10 µM** | IP1 mobilization |
| 5-HT2A β-arrestin recruitment | **>10,000 nM** (no recruitment) | BRET assay |
| SERT (serotonin transporter) | IC50 = **288 ± 2.3 nM** | Uptake inhibition |
| DAT (dopamine transporter) | IC50 = **4,788 ± 416 nM** | Release assay |
| NET (norepinephrine transporter) | **>10,000 nM** | Inactive |

**⚠️ FLAG — 5-HT1A classification error in seed data:** The brief lists "Serotonin 1A receptor agonist" as a pharmacological class for DiPT. Blough et al. (2014 [Ref 12]) found DiPT inactive at 5-HT1A at concentrations up to 10 µM. This contradicts the seed data classification. The 5-HT1A agonist classification should be removed from the pharmacological class. (Note: 5-MeO-DiPT, the 5-methoxy analogue, *does* have 5-HT1A activity — the 5-methoxy substitution is required for that activity, as reviewed in Reckweg et al. 2022.)

**5-HT2A full agonism and biased signaling:** DiPT acts as a full agonist at 5-HT2A (110% efficacy, exceeding the reference agonist 5-HT), yet shows no β-arrestin2 recruitment at this receptor at concentrations up to 10 µM (Blough et al. 2014 [Ref 12]). This G-protein-biased agonist profile at 5-HT2A is pharmacologically notable and shares characteristics with other tryptamine hallucinogens at this receptor.

**SERT inhibition:** DiPT inhibits the serotonin transporter (IC50 288 nM), which may contribute to serotonergic activity beyond direct receptor agonism. This weak-to-moderate SERT inhibition is consistent with Blough et al. (2014 [Ref 12]) noting that multiple neurochemical mechanisms beyond 5-HT2A agonism operate across the tryptamine class.

**N,N-diisopropyl substituent effects on binding affinity:** McKenna et al. (1990 [Ref 3]) evaluated binding affinities of 21 indolealkylamine derivatives at 5-HT1A and 5-HT2A, finding that "the size of the N,N-dialkyl substituent was a secondary determinant of affinity, with groups larger than N,N-diisopropyl resulting in a marked reduction in affinity at both the 5-HT2A and 5-HT1A recognition sites." This means DiPT (N,N-diisopropyl) represents the boundary case: substituents of this size already reduce receptor affinity compared to smaller groups (N,N-dimethyl, N,N-diethyl), consistent with Gatch et al. (2021 [Ref 9]) finding that "N,N-diisopropyl compounds were less potent than the dimethyl, diethyl, N-methyl-N-ethyl, and N-methyl-N-isopropyl compounds" in a DOM discrimination model.

**Discriminative stimulus pharmacology:** Carbonaro et al. (2013 [Ref 2]) conducted the only published animal pharmacology study directly evaluating DiPT, using a DOM (2,5-dimethoxy-4-methylamphetamine) drug discrimination model in rats. DiPT was confirmed to produce hallucinogen-like discriminative stimulus effects. The abstract notes the compound "is known for its production of auditory distortions," distinguishing it from 5-HT2A agonists like LSD and DMT that produce primarily visual effects.

### Mechanism of Auditory Selectivity

Hurst and Bajo (2026 [Ref 1]) published the first mechanistic hypothesis for DiPT's distinctive frequency-selective pitch distortion ("diptogenia"). The paper proposes neural mechanisms by which 5-HT2A receptor agonism in auditory cortical circuits, combined with DiPT's particular binding profile, preferentially disrupts tonotopic processing in ways that shift pitch perception downward. The paper also discusses potential therapeutic application for tinnitus — representing a novel proposed use case in the emerging psychedelic therapeutics landscape.

### Oral Bioavailability

DiPT is notably orally active without co-administration of an MAOI, unlike simpler tryptamines such as DMT. The standard explanation at the class level (Yu 2008 [Ref 7]) is that bulky N-substituents provide steric protection against first-pass deamination by monoamine oxidase (MAO), particularly MAO-A. The N,N-diisopropyl groups in DiPT are large enough to significantly reduce MAO substrate activity. This is consistent with Shulgin and Carter (1980 [Ref 23]) explicitly describing DiPT as an "orally active" tryptamine analog, contrasting it implicitly with DMT.

### CYP450 Metabolism

No DiPT-specific metabolism studies have been published. Class-level data from Yu (2008 [Ref 7]) indicates that indolealkylamine drugs of abuse are substrates for CYP2D6, with CYP2D6 polymorphism representing a risk factor for variable pharmacokinetics and drug-drug interactions. For structurally related 5-methoxy-N,N-dialkyl tryptamines (e.g., 5-MeO-2-Me-DIPT), Caspar et al. (2018) identified CYP1A2, CYP2C19, CYP2D6, and CYP3A4 involvement in hydroxylation, with CYP2C19 and CYP2D6 responsible for N-dealkylation — metabolism profiles that likely generalize to DiPT. No published human PK parameters (Tmax, t½, bioavailability) exist for DiPT specifically.

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## History

### First Synthesis

DiPT was first prepared in the scientific literature by R.B. Barlow and colleagues approximately 1959. This represents the earliest chemical documentation of the compound, though no psychoactive properties were characterized in that work.

### First Human Pharmacology

Alexander Shulgin conducted the first human trials of DiPT beginning in 1975. The findings were co-published with Michael F. Carter in 1980 as: **Shulgin AT, Carter MF (1980). "N,N-Diisopropyltryptamine (DIPT) and 5-Methoxy-N,N-Diisopropyltryptamine (5-MEO-DIPT). Two Orally Active Tryptamine Analogs with CNS Activity." *Communications in Psychopharmacology*, 4(5):363–369.** [PMID 6949674, Ref 23]. This paper constitutes the primary published human pharmacology report for DiPT. The abstract is not available in the PubMed record; the full text is referenced at the Purdue University Archives (Shulgin Archive).

Shulgin documented DiPT in further detail in his 1997 book *TiHKAL: Tryptamines I Have Known and Loved* (co-authored with Ann Shulgin) as Entry #4 [Ref 16]. The TiHKAL entry describes two synthesis routes, detailed chemical characterization, dosage titration from personal experimentation, and first-person accounts of the auditory effects.

### Research Chemical Market

DiPT appeared in research chemical markets in the late 1990s and early 2000s, associated with the broader emergence of unscheduled tryptamine analogues. Unlike its 5-methoxy analogue (5-MeO-DiPT, "Foxy Methoxy"), which received significant law enforcement attention, DiPT remained a lower-profile compound and was not specifically scheduled in most jurisdictions at that time.

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## Subjective Effects

Published descriptions come from two primary sources: Shulgin's self-experimentation documented in TiHKAL [Ref 16, 23] (human, n=small group) and the Erowid experience vault [Ref 19] (user reports). Animal pharmacology from Carbonaro et al. (2013 [Ref 2]) confirms the compound produces hallucinogen-like discriminative stimulus effects in rats. Hurst and Bajo (2026 [Ref 1]) contextualize the effects within a mechanistic framework.

**Auditory effects (primary and distinctive):**
- Downward pitch shift affecting all heard sounds — voices, music, and environmental noise sound lower in pitch than normal ("the auditory world of the subject sounds lower in pitch than in a sober state of consciousness" — Hurst & Bajo 2026 [Ref 1])
- Musical disharmony: chords and melodies sound discordant because the shift is not uniform across frequencies, distorting harmonic relationships
- Single pure tones may be perceived relatively normally, while complex sounds (speech, music) are markedly distorted
- Auditory hallucinations (at higher doses) — consistent with effects taxonomy in brief
- Auditory enhancement at lower doses before distortion onset

**Visual and other perceptual effects:**
- Visual effects are notably minimal at typical doses — this distinguishes DiPT from most other psychedelic tryptamines
- At higher doses, mild geometric patterns and visual drifting have been reported (consistent with brief taxonomy)
- Some reports of synesthesia (consistent with serotonergic mechanism — Brogaard 2013 [Ref 20])

**Somatic effects:**
- Nausea (commonly reported, especially oral administration)
- Stimulation and wakefulness
- Spontaneous body sensations
- Pupil dilation (consistent with serotonergic effects)
- Some reports of abnormal heartbeat/tachycardia
- Yawning
- Stomach bloating and gastrointestinal discomfort

**Cognitive effects:**
- Thought acceleration and analysis enhancement reported at mild doses
- Ego dissolution at high doses
- Confusion documented

**Duration data (source comparison):**
- **TiHKAL [Ref 16] (primary human source, Shulgin):** Duration 6–8 hours (oral), onset not specified but implied ~30-60 min
- **Seed brief:** Total 3–6 hours (oral), onset 30–60 min, aftereffects 2–4 hours
- **Community consensus (web sources):** Onset 30–60 minutes; 3–6 hours commonly reported; some report up to 8 hours
- **Animal model (Carbonaro 2013 [Ref 2], IP rodent):** Onset within 5 min, effects resolved within 4 hours — *note: IP rodent pharmacokinetics differ significantly from oral human administration; these data cannot be directly translated*
- ⚠️ **FLAG — Duration discrepancy:** TiHKAL (primary source) specifies 6–8 hours, while the seed brief states 3–6 hours. Community reports span both ranges. The discrepancy may reflect dose-dependency (higher doses approaching 100 mg lasting 6–8h; lower doses lasting 3–5h). Recommend editorial review; the generation agent should present a dose-dependent range and flag TiHKAL as primary source.

**Smoked ROA:**
- Onset: 5–15 minutes
- Duration: 15–60 minutes total
- TiHKAL reports 8 mg as an active smoked dose [Ref 16]
- Effects are similar in character but shorter duration and faster onset vs. oral

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## Safety & Toxicity

### Lethal Dose / LD50
No published LD50 or lethal dose data for DiPT in any species. The toxic dose in humans is unknown. This is consistent with the brief's "toxic dose is unknown" notation and is a safety-critical gap.

### Human Adverse Events
No published case reports of adverse events or overdoses specifically attributable to DiPT were found in PubMed, Malaca et al. (2020 [Ref 6]) tryptamine toxicology review, or Tittarelli et al. (2015 [Ref 5]) recreational tryptamine review. This likely reflects the compound's low prevalence of use rather than an absence of adverse potential. No deaths attributed to DiPT have been reported in the published literature.

⚠️ **FLAG:** Absence of adverse event data should not be interpreted as safety confirmation. All safety data is class-level inference.

### Analogue Adverse Events (for class context)
- 5-MeO-DiPT (5-methoxy analogue) has caused rhabdomyolysis and transient acute renal failure following ingestion in a 23-year-old male (Alatrash et al. 2006 [Ref not yet in registry — PMID 16610577]). This represents a serious adverse event in the N,N-diisopropyltryptamine class.
- Tryptamine class adverse effects include tachycardia, hypertension, hyperthermia, rhabdomyolysis, and serotonin syndrome (Malaca et al. 2020 [Ref 6]).
- The morbidity accompanying tryptamine intake is described as "considerable" (Malaca et al. 2020 [Ref 6]).

### Physiological Safety at Typical Doses
Nichols (2016 [Ref 14]) states that serotonergic psychedelics are "generally considered physiologically safe and do not lead to dependence or addiction" at typical doses. This class-level statement applies with the caveat that DiPT lacks its own safety data.

### Psychological Risks
- Risk of anxiety, panic, and dysphoria inherent to 5-HT2A-mediated psychedelic states [Nichols 2016, Ref 14]
- The unusual auditory distortion profile may be psychologically disturbing, particularly in unfamiliar settings
- No published HPPD (Hallucinogen Persisting Perception Disorder) cases specifically attributed to DiPT

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## Harm Reduction

### MAOI Contraindication
DiPT is a serotonergic compound with SERT inhibition (288 nM) and 5-HT2A full agonism. Co-administration with monoamine oxidase inhibitors (MAOIs), including irreversible MAOIs (e.g., phenelzine, tranylcypromine), reversible MAOIs (e.g., moclobemide), and naturally occurring MAOIs (e.g., harmaline in ayahuasca) creates elevated serotonin syndrome risk. Yu (2008 [Ref 7]) and Malcolm & Thomas (2022 [Ref 8]) both emphasize that DDIs with indolealkylamine drugs of abuse can "occur additively at the pharmacokinetic and pharmacodynamic levels, leading to severe or even fatal serotonin toxicity."

**Note on MAO resistance:** Although DiPT itself is orally active (unlike DMT, which requires MAO inhibition), the N,N-diisopropyl groups reduce but do not eliminate MAO substrate activity. Combining DiPT with an MAOI could still amplify serotonergic load through MAOI's effect on endogenous serotonin metabolism and potential blockade of residual DiPT deamination.

### SSRI/Serotonergic Drug Interactions
Psychedelic use with concurrent SSRIs/SNRIs presents both pharmacodynamic interactions (additive serotonergic load) and pharmacokinetic interactions via shared CYP2D6 metabolism (Yu 2008 [Ref 7]; Malcolm & Thomas 2022 [Ref 8]).

### Testing
DiPT will produce a **positive Ehrlich test** (purple/violet) confirming indole structure. Hofmann reagent provides a green-blue color for tryptamines. These reagents do not distinguish DiPT from other tryptamines but confirm the presence of an indole ring. Mass spectrometry (LC-MS/MS) is required for definitive identification.

### Contraindications
No published DiPT-specific contraindications. Class-level contraindications from serotonergic psychedelic literature include:
- Personal or family history of schizophrenia or other psychotic disorders
- Lithium use (reported seizure risk with psychedelic tryptamines in case reports)
- MAOI co-administration (serotonin syndrome risk)
- Cardiovascular disease (tachycardia, hypertension risk)
- Pregnancy (unknown teratogenic risk; no published data)

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## Tolerance & Dependence

### Tolerance Mechanism
No DiPT-specific tolerance studies have been published. Class-level mechanism established by Buckholtz et al. (1990 [Ref 24]) and de la Fuente Revenga et al. (2022 [Ref 15]): repeated serotonergic psychedelic administration causes downregulation of 5-HT2A receptors in the frontal cortex, reducing subsequent response. This mechanism is 5-HT2A activation-dependent and independent of β-arrestin-2. Notably, DiPT shows no β-arrestin recruitment at 5-HT2A (Blough et al. 2014 [Ref 12]) — whether this affects tolerance development is unknown.

**Seed data (not independently verified for DiPT specifically):**
- Buildup: almost immediately after ingestion
- Half-life of tolerance: ~3 days
- Full reset: ~7 days
- These values are consistent with cross-psychedelic class data but are not confirmed by a published DiPT-specific study.

### Cross-Tolerance
Serotonergic psychedelics share cross-tolerance mediated by shared 5-HT2A downregulation (Nichols 2016 [Ref 14]; de la Fuente Revenga et al. 2022 [Ref 15]). Cross-tolerance between DiPT and LSD, psilocybin, DMT, and other 5-HT2A agonists is expected.

### Dependence Liability
Nichols (2016 [Ref 14]) classifies serotonergic psychedelics as generally not dependence-forming. The rapid tolerance development itself limits compulsive use patterns. No published case reports of DiPT dependence or withdrawal syndrome.

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## Interactions

### Published Drug Interaction Data
No DiPT-specific drug interaction studies exist in the published literature. The following are class-level inferences:

**MAOI — HIGH RISK:** Serotonin syndrome risk from combined 5-HT2A agonism, SERT inhibition, and MAOI-mediated serotonin accumulation. May be fatal (Yu 2008 [Ref 7]).

**Lithium — ELEVATED RISK:** Case reports associate lithium + classical psychedelic combinations with seizures and increased psychological disturbance. Mechanism not fully elucidated.

**SSRIs/SNRIs — INTERACTION:** Pharmacodynamic blunting of psychedelic effects (5-HT2A downregulation from chronic SSRI use), combined with additive serotonergic load risk at pharmacodynamic level. CYP2D6 competition possible at pharmacokinetic level (Yu 2008 [Ref 7]).

**Tricyclic antidepressants (TCAs):** Serotonergic DDI risk (Malcolm & Thomas 2022 [Ref 8]).

**Other serotonergic psychedelics:** Cross-tolerance but also potential for additive serotonergic effects.

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## Legal Status

### United States
DiPT is **not federally scheduled** as of April 2026. The DEA published a proposed rule (87 FR 2376, January 14, 2022 [Ref 11]) to place DiPT in Schedule I of the Controlled Substances Act alongside 4-OH-DiPT, 5-MeO-AMT, 5-MeO-MiPT, and 5-MeO-DET. The DEA subsequently **withdrew this proposed rule on July 27, 2022** (87 FR 45290 [Ref 10]), citing the need for new HHS scientific and medical evaluation and scheduling recommendation. The public hearing scheduled for August 22, 2022 was cancelled. DiPT remains potentially subject to the **Federal Analog Act** (21 U.S.C. § 813) if sold or possessed for human consumption with substantially similar pharmacological effects to a Schedule I or II substance.

**⚠️ FLAG for editorial review:** Legal status may change. The HHS review process initiated following the 2022 withdrawal could result in a new scheduling recommendation at any time.

### United Kingdom
DiPT is a **Class A controlled substance** under the Misuse of Drugs Act 1971 under the tryptamine generic catch-all clause. The generic definition covers any compound structurally derived from tryptamine with N,N-dialkyl substitution; DiPT (N,N-diisopropyltryptamine) is explicitly cited as an example compound in the legislative reference materials [Ref 18].

### Australia
DiPT is a **Schedule 9 (Prohibited Substance)** under Australia's Poisons Standard (Standard for the Uniform Scheduling of Medicines and Poisons). Possession and supply are prohibited without a government-issued licence; research use requires special authorization.

### Canada
DiPT is **not explicitly listed** under Canada's Controlled Drugs and Substances Act (CDSA). Its status may be subject to interpretation as a tryptamine analogue in enforcement contexts, though no explicit scheduling has been confirmed.

### New Zealand
DiPT is a **Class C controlled drug** as a tryptamine analogue of DMT under New Zealand's Misuse of Drugs Act.

### European Union
No EU-wide scheduling; legal status varies by member state. DiPT is not among the substances specifically scheduled by the EMCDDA early warning system based on available records.

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## Clinical Trials

No clinical trials involving DiPT itself are registered on ClinicalTrials.gov or in the published literature.

**Related compound — 4-OH-DiPT (via RE104 prodrug):**
- RE104 (glutarate ester prodrug of 4-hydroxy-N,N-diisopropyltryptamine) has entered clinical development as a potential therapeutic for depressive disorders.
- Bryson et al. (2024 [Ref 22]) published preclinical characterization. Ludbrook et al. (2025 [Ref 21]) published Phase 1 SAD human data. 4-OH-DiPT via RE104 shows a 2–3 hour psychedelic duration and preclinical antidepressant activity.
- These data are not directly applicable to DiPT but demonstrate that the N,N-diisopropyltryptamine pharmacophore is of active clinical interest.

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## Community Feedback Analysis

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

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## Gaps & Flags

### Safety-Critical Values Not Confirmed by Published Sources
1. **Lethal/toxic dose:** Unknown for DiPT in any species. The brief's note "toxic dose is unknown" is confirmed. ⚠️ SAFETY FLAG.
2. **Duration (oral):** TiHKAL (primary source, Shulgin 1980/1997) states **6–8 hours**; seed brief states **3–6 hours**. This discrepancy is unresolved. The 3–6 hour figure appears in community-sourced references; the 6–8 hour figure is from the originator's documented human trials. Recommend presenting dose-dependent range with TiHKAL as primary source. ⚠️ EDITORIAL FLAG.

### Contradictions Between Seed Data and Published Sources
3. **5-HT1A pharmacological class:** Seed data lists "Serotonin 1A receptor agonist" as a pharmacological class for DiPT. Blough et al. (2014 [Ref 12]) reports DiPT INACTIVE at 5-HT1A at concentrations up to 10 µM. This is a direct contradiction. The 5-HT1A classification likely originated from its analogy with 5-MeO-DiPT (which does have 5-HT1A activity) and should be removed. ⚠️ DATA CORRECTION FLAG.

### Missing Chemical Identity Fields
4. **SMILES, InChIKey, PubChem CID, molecular formula, molecular weight** were not populated in the brief. All are now verified: CID 26903; Formula C16H24N2; MW 244.37; InChIKey ZRVAAGAZUWXRIP-UHFFFAOYSA-N. SMILES can be retrieved from PubChem CID 26903.

### Areas Relying on Structural Analogy or Class Inference
5. **Metabolism/CYP enzymes:** No DiPT-specific metabolism data published. All metabolic pathway inferences are class-level (indolealkylamine class; CYP2D6 likely involved per Yu 2008).
6. **Tolerance buildup rate (3-day half-life, 7-day reset):** Seed data not confirmed by DiPT-specific studies. These values are consistent with class-level 5-HT2A downregulation data but are not substance-verified.
7. **MAOI interactions:** Class-level inference only; no DiPT-specific interaction study exists.
8. **Contraindications:** No DiPT-specific contraindication data; all from class-level psychedelic literature.
9. **Pharmocokinetics (Tmax, t½, bioavailability):** No published human PK data for DiPT exists. The 4-OH-DiPT analogue (RE104) has a 40 min half-life after SC administration in rats (Bryson 2024 [Ref 22]) but this cannot be directly applied to oral DiPT in humans.

### Absence of Published Evidence (Substance-Specific)
10. No published case reports of adverse events or overdose attributable to DiPT.
11. No registered or completed clinical trials for DiPT.
12. No neuroimaging or EEG studies in humans.
13. No controlled human dose-response studies.
14. No published studies on DiPT and long-term effects, HPPD, or psychological harm.
15. Legal status in EU member states not individually confirmed.