4-HO-DPT

# Research Output: 4-HO-DPT

## Chemical Identity

**Verified data (PubChem CID 21854223 [Ref 24], API-confirmed):**

- **Systematic IUPAC name:** 3-[2-(dipropylamino)ethyl]-1H-indol-4-ol
- **Molecular formula:** C₁₆H₂₄N₂O
- **Molecular weight:** 260.37 g/mol
- **InChIKey:** MZLRMPTVOVJXLW-UHFFFAOYSA-N
- **PubChem CID:** 21854223
- **CAS number:** 63065-88-3 (web-retrieved [Ref 25])
- **SMILES:** Not returned by PubChem API call; no discrepancy, brief left SMILES blank
- **Melting point (freebase):** 96–97 °C — first reported by Repke et al. 1977 (Ref 12), confirmed identically by Shulgin 1997 (Ref 23)

**Seed data cross-check:**
- Molecular formula, weight, and IUPAC name all **confirmed** against PubChem.
- PubChem CID was blank in the brief; now established as 21854223.
- SMILES was blank in the brief; not returned by API — generation agent should pull from PubChem directly using CID 21854223.
- Street name "Procin" confirmed in multiple secondary sources (Refs 24, 25).

**⚠ FLAG (chemical identity):** SMILES string not returned by PubChem API. Generation agent should retrieve via PubChem CID 21854223 REST endpoint before publication.

---

## Pharmacology

### Primary Mechanism — 5-HT2A Agonism

4-HO-DPT is a serotonin 5-HT2A receptor agonist, placing it within the classical serotonergic psychedelic class alongside psilocin and DMT. All 4-hydroxy-N,N-dialkyltryptamines tested in the Klein et al. (2021 [Ref 11]) SAR study acted as full or partial agonists at 5-HT2A, 5-HT2B, and 5-HT2C receptor subtypes. 4-HO-DPT is notably more selective for 5-HT2A versus 5-HT2C compared to psilocin: a 129-fold selectivity difference was reported (Ref 25, citing Klein et al. [Ref 11]).

**Key receptor pharmacology from SAR studies:**
- Klein et al. 2021 (Ref 11) tested 17 tryptamines with 4-hydroxy or 4-acetoxy groups. Tryptamines with bulkier N-alkyl substituents (such as N,N-dipropyl, as in 4-HO-DPT) showed lower potency at 5-HT2C receptors and higher efficacy at 5-HT2B. 4-HO-DPT produced head-twitch responses (HTR) in mice, consistent with psychedelic-like activity mediated by 5-HT2A.
- Glatfelter et al. 2022 (Ref 18) confirmed that 4-hydroxy and 4-acetoxy tryptamines show similar pharmacological profiles, with 4-acetoxy analogs acting as prodrugs that deacetylate in vivo. Tertiary amine analogs induce HTR; secondary amines do not.

**⚠ FLAG:** No substance-specific binding affinity (Ki or EC50) values for 4-HO-DPT itself were found in the published literature. The binding data above applies to the 4-hydroxy tryptamine class and close structural analogs tested in Klein et al. 2021. Generation agent should label these as class-inferred where no compound-specific value is cited.

### Parent Compound DPT Pharmacology

The pharmacology of N,N-dipropyltryptamine (DPT, the base compound without the 4-hydroxy group) has been characterized in multiple published studies, providing important context:

- **5-HT2A:** DPT is a full agonist at 5-HT2A. Tyagi et al. 2023 (Ref 1) reported Ki = 152 nM and EC50 = 445 nM (TRUPATH biosensor assay, rank order: 5-HT2A > 5-HT1B > 5-HT1A).
- **5-HT1B:** Ki = 8,081 nM, partial agonist (~85% max response) [Ref 1]
- **5-HT1A:** Ki = 1,640 nM, partial agonist (~52% max response) [Ref 1]
- DPT produces 5-HT2A-mediated head twitch responses in mice; the 5-HT2A antagonist M100907 blocked these effects insurmountably while the 5-HT1A antagonist WAY-100635 produced surmountable antagonism, indicating a modulatory role for 5-HT1A (Fantegrossi et al. 2008 [Ref 2]).
- DPT substitutes in rats trained to discriminate LSD, psilocybin, and MDMA, supporting its psychedelic-class behavioral profile (Fantegrossi et al. 2008 [Ref 2]).
- In the GTPγS assay in rat brain membranes, DPT produced measurable G-protein activation, ranking below 5-MeO-DMT and 5-MeO-DALT in potency but above alpha-methyltryptamine (Nonaka et al. 2007 [Ref 9]).
- DPT acts as a substrate (not a blocker) at the serotonin uptake transporter (SERT): KI for [³H]5-HT uptake inhibition = 0.594 ± 0.12 μM in human platelets. Also a substrate at VMAT2 (KI = 19 ± 2.3 μM). High binding-to-uptake ratios confirm substrate behavior at both transporters (Cozzi et al. 2009 [Ref 4]).

**4-OH substitution effects:** The 4-hydroxy group on the indole ring (as in 4-HO-DPT vs. DPT) has several known effects in this compound class:
- Enhanced selectivity for 5-HT2A over 5-HT2C (Klein et al. 2021 [Ref 11])
- The 4-hydroxy group is consistent with psilocin-like pharmacology; psilocin (4-HO-DMT) is the dephosphorylated active form of psilocybin
- Gerasimov et al. 1999 (Ref 22) found that 4-hydroxy tryptamine rigidized analogs had potency at 5-HT2A comparable to DOI in LSD-trained rat discrimination, supporting that the 4-hydroxy group confers LSD/psilocin-like hallucinogenic properties

### Signaling Pathway

5-HT2A-mediated psychedelic effects are mediated through Gq protein coupling (not β-arrestin2 recruitment). Wallach et al. 2023 (Ref 20) demonstrated that 5-HT2A-Gq efficacy predicts psychedelic potential as measured by HTR magnitude in mice, while β-arrestin-biased agonists block psychedelic effects and induce receptor downregulation (tachyphylaxis). This mechanism is consistent with the rapid tolerance observed with 4-HO-DPT and related compounds.

### 5-HT2B Risk

Per Klein et al. 2021 (Ref 11), tryptamines with bulkier N-alkyl groups (like N,N-dipropyl) show higher efficacy at 5-HT2B receptors. Chronic 5-HT2B agonism is associated with cardiac valvulopathy, though no specific cases have been documented for 4-HO-DPT. **⚠ FLAG:** No clinical cardiac safety data exists for 4-HO-DPT.

### Pharmacokinetics

**No published pharmacokinetic studies exist for 4-HO-DPT.** The following is class-inferred or extrapolated from analogues and must be labelled accordingly:

- **Bioavailability:** Unknown. By analogy with psilocin (oral bioavailability ~50%), and given that 4-HO-DPT appears active by both oral and insufflated routes, some oral bioavailability is expected. The 4-acetoxy prodrug analog (4-AcO-DPT, if it exists) would presumably be deacetylated to 4-HO-DPT in vivo per Glatfelter et al. 2022 (Ref 18).
- **Onset difference by ROA:** User reports (PsychonautWiki [Ref 25]) describe slower oral onset (45–60 min) vs. insufflated (15–45 min), consistent with first-pass effects.
- **Metabolism:** Unknown. For the parent compound psilocin, hepatic glucuronidation is a primary pathway. Tryptamines are generally substrates for MAO-A. No CYP enzyme involvement data exists for 4-HO-DPT specifically.
- **Half-life:** Not studied. Tolerance data (see below) suggests functional half-life consistent with other tryptamines.

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## History

### Discovery and Synthesis

4-HO-DPT was first synthesized by **Repke, Ferguson, and Bates** (1977 [Ref 12]) as compound "4b" in a paper titled "Psilocin analogs. 1. Synthesis of 3-[2-(dialkylamino)ethyl] and 3-[2-(cycloalkylamino)ethyl] indol-4-ols," published in the *Journal of Heterocyclic Chemistry* (volume 14, pages 71–74). The paper reported the synthesis of multiple psilocin analogs via a route starting from 6,7-dihydroindol-4(5H)one, with the freebase melting point of 96–97 °C.

**Alexander Shulgin** independently synthesized 4-HO-DPT and documented it in *TiHKAL: The Continuation* (Shulgin & Shulgin, 1997 [Ref 23]). He reported an identical melting point (96–97 °C), confirming Repke's synthesis. Shulgin self-administered 20 mg orally, reporting "possible threshold, nothing more." He noted that the compound is "difficult to make" and listed both dosage and duration as "unknown." This assessment effectively terminated systematic investigation of 4-HO-DPT for nearly two decades.

**Jochen Gartz** (1990) filed a patent (DD278600A1) for a method of bioaccumulating tryptamine derivatives in mushroom fruiting bodies through growth medium supplementation. The patent potentially encompassed 4-HO-DPT [Ref 25].

**Chapman et al.** (2018 [Ref 16]) reported NMR spectral data for 4-HO-DPT fumarate salt obtained from grey-market vendors, confirming chemical identity and purity. **Sammeta et al.** (2020 [Ref 15]) reported the first single-crystal X-ray diffraction structure of 4-HO-DPT hydrochloride salt (IUCrData).

### Context Within DPT Research

The parent compound, N,N-dipropyltryptamine (DPT), was studied clinically in the early 1970s as a psycholytic therapy adjunct:
- Soskin, Grof, and Richards (1973 [Ref 14]) published "Low doses of dipropyltryptamine in psychotherapy" in *Archives of General Psychiatry*, describing a double-blind study of DPT (15–30 mg IM) in alcoholism treatment at Spring Grove State Hospital.
- Soskin (1975 [Ref 13]) published a further clinical report on DPT in psychotherapy (*Current Psychiatric Therapies*).
- These studies were part of the broader psycholytic therapy movement in the US and Europe from the 1950s–1970s (Passie et al. 2022 [Ref 19]).

4-HO-DPT is the 4-hydroxyl analog of DPT. While DPT has a documented human clinical history, **4-HO-DPT itself has not been used in any published clinical trials or formal human studies.** Available human data consists of Shulgin's single self-experiment and informal user reports.

### Appearance on Research Chemical Markets

4-HO-DPT is characterized as an "emerging" compound in the Psychedex database. Its appearance on grey-market research chemical vendor sites (documented by Chapman 2017 [Ref 16]) occurred substantially later than many other substituted tryptamines, consistent with the synthesis difficulty noted by Shulgin. No specific date of first market appearance could be confirmed from published sources.

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## Subjective Effects

### Published Descriptions

**No controlled human studies exist for 4-HO-DPT.** The only published human data is Shulgin's single self-experiment (20 mg oral = possible threshold) [Ref 23]. All subjective effect descriptions derive from informal user reports.

### Structural and Pharmacological Analog Inference

Based on its pharmacological profile as a 5-HT2A agonist and structural analog of psilocin, 4-HO-DPT is expected to produce psychedelic effects qualitatively similar to psilocin/psilocybin, but with a potentially distinct character due to the N,N-dipropyl vs. N,N-dimethyl substitution:
- Tryptamines with bulkier N-alkyl groups tend to produce more pronounced visual and sensory effects relative to cognitive/introspective effects compared to N,N-dimethyl analogs (user-report-only; no controlled data) [Ref 25].
- The 5-HT1A partial agonist activity of DPT (Ki = 1,640 nM [Ref 1]) may contribute modulatory effects including sedation, muscle relaxation, and anxiolytic or anxiogenic components, consistent with the biphasic dose-effect curve observed in rodent models (Fantegrossi et al. 2008 [Ref 2]).

### Duration Data

From the Psychedex database seed values (community consensus origin), cross-referenced against user report aggregation sites:
- **Oral:** onset 45–60 min, come-up 60–120 min, peak 2–3 hours, offset 1–2 hours, total 5–8 hours
- **Insufflated:** onset 15–45 min, come-up 30–45 min, peak 1–3 hours, offset 1–2 hours, total 4–6 hours

**⚠ FLAG:** These duration values are user-report-based community consensus with no controlled study support. They should be labelled accordingly in the article.

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## Safety & Toxicity

### LD50 and Toxic Dose

**No LD50 data exists for 4-HO-DPT.** The toxic dose in humans is unknown [Ref 25]. No case reports of overdose or fatal toxicity attributable to 4-HO-DPT were found in the published literature.

For comparison, the parent compound DPT produced proconvulsant effects at doses >20 mg/kg in mice (Tyagi et al. 2023 [Ref 1]), suggesting a dose-dependent pro-convulsant risk — but this involves the unsubstituted DPT in animal models and cannot be directly extrapolated to human 4-HO-DPT doses.

### Cardiovascular Risk

5-HT2B agonism is associated with cardiac valvulopathy at chronic doses. Klein et al. 2021 (Ref 11) found that tryptamines with bulkier N-alkyl substituents (such as N,N-dipropyl) show increased 5-HT2B efficacy relative to psilocin. This represents a theoretical concern for repeated high-dose use; no clinical cardiac data for 4-HO-DPT exists.

### Serotonin Syndrome

As a 5-HT2A agonist and (via its parent compound class) SERT substrate, 4-HO-DPT carries theoretical risk of serotonin toxicity when combined with:
- MAO inhibitors (MAOIs) — would prevent oxidative degradation of tryptamines, dramatically increasing plasma levels
- SERT inhibitors (SSRIs, SNRIs)
- Other serotonergic agents

Baldo 2018 (Ref 17) reviews the tramadol–serotonin toxicity mechanism: tramadol inhibits human SERT in HEK293 cells and, combined with serotonergic drugs, can cause serotonin syndrome. This mechanistically supports the "dangerous" interaction label for tramadol in the seed data.

### Acute Psychological Risks

Consistent with the class of serotonergic psychedelics: anxiety, paranoia, panic, and dysphoric reactions are possible — especially at high doses, in unsupported settings, or in individuals with personal or family history of psychotic disorders. No substance-specific case reports were identified.

### General Tryptamine Toxicology

Malaca et al. 2020 (Ref 7) note that tryptamine morbidity is "considerable and underestimated." Tittarelli et al. 2015 (Ref 8) reviewed NPS tryptamine cases including fatalities, predominantly associated with poly-drug use, cardiovascular events, and hyperthermia. None were specific to 4-HO-DPT.

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## Harm Reduction

### Key Principles

- **Synthesis difficulty** means grey-market 4-HO-DPT may be misrepresented or impure. Reagent testing (e.g., Ehrlich, Hofmann) is strongly recommended. Chapman 2017 (Ref 16) documented that grey-market tryptamine products can be correctly identified via NMR, but field reagent limitations should be noted.
- **Start low:** Given the extreme paucity of human data, the dose-response curve in humans is poorly characterized. Shulgin found 20 mg oral to be threshold only.
- **Set and setting:** Class-standard psychedelic harm reduction; no 4-HO-DPT-specific protocols exist.
- **Avoid drug combinations** (see Interactions section below).

### Contraindications

The following are class-based contraindications with no 4-HO-DPT-specific data:
- **MAO inhibitors (MAOIs):** Potentially fatal. MAOI + serotonergic tryptamine dramatically elevates synaptic serotonin and tryptamine levels; risk of serotonin syndrome.
- **Personal or family history of psychosis or schizophrenia:** 5-HT2A agonists can exacerbate or precipitate psychotic episodes.
- **Lithium:** Combination with psychedelics has been reported to increase seizure risk (class-based, from literature on psilocybin/LSD; no 4-HO-DPT-specific data).
- **Tramadol:** Dangerous (see Interactions; mechanistic basis in Baldo 2018 [Ref 17]).
- **Cardiovascular disease:** Theoretical 5-HT2B risk; no 4-HO-DPT-specific data.

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## Tolerance & Dependence

### Tolerance

**Mechanism:** 5-HT2A receptor downregulation via β-arrestin2-mediated internalization following Gq activation (Wallach et al. 2023 [Ref 20]). Tolerance develops essentially immediately after administration.

**Cross-tolerance:** 4-HO-DPT is expected to show full cross-tolerance to other classical serotonergic psychedelics (LSD, psilocin, mescaline) via shared 5-HT2A receptor downregulation. This is consistent with the "psychedelic" cross-tolerance listed in the seed data.

**Importantly:** Smith et al. 2014 (Ref 3) found that daily DPT administration in mice did *not* produce tolerance to the head-twitch response (unlike the phenethylamine hallucinogens DOI and 2C-T-7). This is a significant finding suggesting that *tryptamine-derived hallucinogens may develop tolerance more slowly than phenethylamines*, and that the acute self-tolerance after a single use may not persist as robustly into the next day. However, cross-tolerance from DOI to DPT was still observed (insurmountable), consistent with shared 5-HT2A downregulation.

**Seed data tolerance values** (threshold 3-day half-life, full reset 7 days) are community consensus estimates consistent with class-level data; no controlled pharmacokinetic study supports these specific numbers for 4-HO-DPT.

### Dependence

Serotonergic psychedelics are not considered habit-forming by FDA, DEA, or the clinical research consensus. No physical dependence syndrome or withdrawal has been documented for this class. DPT does not produce compulsive redosing in the controlled study context (Soskin et al. 1973 [Ref 14]). The seed data characterization of "not habit-forming" is consistent with published class pharmacology.

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## Interactions

### Tramadol — Dangerous

**Mechanistic basis confirmed:** Tramadol inhibits human SERT (Baldo 2018 [Ref 17]). Combined with a serotonergic tryptamine that acts as a SERT substrate (as DPT does, per Cozzi et al. 2009 [Ref 4]), this could substantially increase synaptic serotonin concentrations, raising serotonin syndrome risk. The tramadol + serotonergic drug combination is recognized by the FDA (2016 Drug Safety Communication) as carrying serotonin toxicity risk. Additionally, tramadol lowers seizure threshold, and at high DPT doses, proconvulsant effects have been observed in mice (Tyagi et al. 2023 [Ref 1]).

**Assessment:** The "dangerous" interaction rating in the seed data is pharmacologically supported.

### Cannabis — Unknown

THC and cannabinoids interact with 5-HT2A signaling via CB1 receptor mechanisms. Cheer et al. 1999 (Ref not indexed) showed oleamide and HU210 potentiated DOI-elicited back muscle contractions in rats via CB1. The clinical implication is that cannabis may potentiate or modify the subjective effects of 4-HO-DPT, potentially increasing anxiety or intensity. However, no controlled data exists for this specific combination. The "unknown" rating in the seed data is accurate.

### MAO Inhibitors (Not Listed in Seed Data)

**⚠ FLAG for editorial review:** MAOIs are not listed in the seed data interactions but represent a potentially life-threatening combination with serotonergic tryptamines. For comparison, DMT and other tryptamines are routinely noted as dangerous with MAOIs. Given that DPT is a SERT substrate (Cozzi et al. 2009 [Ref 4]) and MAO-A is a primary catabolic enzyme for tryptamines, MAOI co-administration could dramatically elevate effective tryptamine plasma levels. Generation agent should flag this as a critical omission from the interactions table for editorial review.

### Lithium (Not Listed in Seed Data)

**⚠ FLAG for editorial review:** Lithium combined with serotonergic psychedelics is associated with increased seizure risk in published case reports and is a widely recognized contraindication. Not listed in the seed data. Should be added as a "dangerous" or "caution" interaction.

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## Legal Status

All legal status data is web-retrieved and should be independently verified before publication.

| Jurisdiction | Status | Basis | Notes |
|---|---|---|---|
| United States | Unscheduled | Not explicitly listed in CSA Schedule I–V | Federal Analogue Act (21 U.S.C. § 813) may apply if intended for human consumption; substantially similar to psilocin (Schedule I). No formal scheduling action taken. DEA proposed scheduling of 4-OH-DiPT (not 4-HO-DPT) and later withdrew it [Ref 24]. |
| United Kingdom | Class A | Tryptamine catch-all clause under Misuse of Drugs Act 1971 | Possession and supply are criminal offenses. UK Psychoactive Substances Act 2016 also applies. |
| Germany | Controlled | Neue-psychoaktive-Stoffe-Gesetz (NpSG), as of July 2019 | NpSG covers broad NPS categories. |
| Canada | Unscheduled | Not listed in Controlled Drugs and Substances Act Schedules | Status as of 2025; subject to change. |
| Switzerland | Possibly legal | Not controlled under Buchstaben A–D | Uncertain; subject to change. |
| Australia | Status unclear | Not confirmed from published sources | Several tryptamines are Schedule 9 Prohibited Substances in Australia; 4-HO-DPT status not confirmed. **⚠ FLAG:** Needs independent verification. |

---

## Clinical Trials

**No clinical trials have been registered for 4-HO-DPT** on ClinicalTrials.gov (search conducted May 2026). No clinical trials involving 4-HO-DPT were found in any registry.

The parent compound DPT was used in human clinical studies at Spring Grove State Hospital in the early 1970s (Soskin et al. 1973 [Ref 14]; Soskin 1975 [Ref 13]), but these were for DPT, not 4-HO-DPT, and predate modern clinical trial registration.

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## Community Feedback Analysis

No community feedback was submitted (Part A2 of the brief is empty). No community feedback items require investigation or reporting.

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## Gaps & Flags

### Critical Data Gaps

1. **No human pharmacology studies:** No controlled or observational studies have been published on 4-HO-DPT in humans. All dose, duration, and effect data is community consensus (user reports) or inferred from structural analogs.

2. **No pharmacokinetic data:** Metabolism, bioavailability, half-life, CYP enzyme involvement, and plasma pharmacokinetics are completely unstudied. This is a critical gap for any safety claim.

3. **No toxicological data:** LD50 unknown, toxic dose unknown, no case reports of overdose.

4. **No substance-specific receptor binding data (Ki/EC50):** Binding affinity values in this report are for the class or for structural analogs (Klein et al. 2021 [Ref 11] studied multiple 4-OH tryptamines but 4-HO-DPT-specific Ki values are not available in the literature).

5. **SMILES string missing:** Not returned by PubChem API; should be retrieved separately from PubChem CID 21854223.

### Safety-Critical Flags for Editorial Review

6. **⚠ Tramadol interaction rated "dangerous" — confirmed:** The mechanistic basis is solid (Baldo 2018 [Ref 17] + Cozzi 2009 [Ref 4]).

7. **⚠ MAOI interaction not in seed data — critical omission:** MAOIs + serotonergic tryptamines is a widely recognized potentially fatal combination. Should be added as "dangerous" to interactions table immediately.

8. **⚠ Lithium interaction not in seed data:** Lithium + psychedelics is associated with increased seizure risk per published case reports and standard psychedelic harm reduction guidelines. Should be added to interactions table.

9. **⚠ Cardiovascular risk not characterized:** 5-HT2B agonism at higher efficacy for N,N-dipropyl substituted tryptamines (Klein et al. 2021 [Ref 11]) represents a theoretical chronic cardiotoxicity risk. No clinical data exists; label as theoretical.

10. **⚠ Australia legal status unconfirmed:** Could not confirm from published sources whether 4-HO-DPT falls under Australian Schedules. Needs independent verification.

11. **⚠ Dose/duration data is community consensus only:** The dose ranges in the DB (20 mg threshold through 130+ mg heavy, oral) align with user report aggregation sites (PsychonautWiki [Ref 25]) and Shulgin's observation (20 mg = threshold [Ref 23]). However, Shulgin — the only person who has published a self-experiment — found 20 mg to be only a possible threshold. This is consistent with the starting dose of the DB range but should be flagged: the compound may require higher doses than other 4-hydroxy tryptamines, and the full dose range has essentially no controlled human data to support it.

12. **⚠ Synthesis difficulty caveat:** Shulgin explicitly noted synthesis difficulty for 4-HO-DPT. Grey-market samples should be tested for purity and identity. Chapman 2017 (Ref 16) documented correct identity of fumarate salt samples from vendors, providing some assurance, but adulteration risk exists.

13. **⚠ Proconvulsant risk at high doses:** DPT parent compound caused convulsions at ≥20 mg/kg in mice (Tyagi et al. 2023 [Ref 1]). This cannot be directly extrapolated to 4-HO-DPT in humans, but represents a notable safety signal for the compound class at high doses.

### Contradictions Between Seed Data and Sources

- **No contradictions identified** between the seed data and primary sources. The chemical identity, dose range, duration, and characterization as "emerging" are all consistent with the available evidence.
- The "primary ROA: insufflated" designation in the seed data is somewhat unusual — most sources and user reports list oral as primary, with insufflated as secondary. This may merit review by an editor, as the insufflated bioavailability data for 4-HO-DPT is not published.