2C-D
4-methyl-2,5-dimethoxyphenethylamine
Studies and references cited across this article, graded by evidence strength.
Inconclusive means the cited source neither confirms nor refutes the claim — a lower-confidence badge, not an error.
Data points an editor reviewed and accepted for publication.
Value Provenance
Dosing
oraltrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Threshold | 10 mg | 10 mg | medium |
| Low | 10–25 mg | 10–25 mg | medium |
| Common | 25–50 mg | 25–50 mg | medium |
| Strong | 50–100 mg | 50–100 mg | medium |
| Heavy | 100+ mg | 100+ mg | medium |
| Editorial | PIHKAL documents 20–60 mg as the active range with bioassays up to 150 mg. Existing database values: threshold 10 mg, light 10–25 mg, common 25–50 mg, strong 50–100 mg, heavy 100+ mg. The common range (25–50 mg) aligns with PIHKAL's primary active range. Strong and heavy ranges extend beyond Shulgin's documented range and are derived from community reports. | ||
ReasoningReasoningPIHKAL documents 20–60 mg as the active range with bioassays up to 150 mg. Existing database values: threshold 10 mg, light 10–25 mg, common 25–50 mg, strong 50–100 mg, heavy 100+ mg. The common range (25–50 mg) aligns with PIHKAL's primary active range. Strong and heavy ranges extend beyond Shulgin's documented range and are derived from community reports. Evidence basis: community_consensus_large | |||
Duration
oral
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onsettrace | 15–45 minutes | 15–45 minutes | medium |
| Editorial | Seed data reports onset 15–45 minutes. Consistent with community reports for oral phenethylamine psychedelics. No controlled PK data exist. | ||
ReasoningReasoningSeed data reports onset 15–45 minutes. Consistent with community reports for oral phenethylamine psychedelics. No controlled PK data exist. Evidence basis: community_consensus_large | |||
| Come uptrace | 20–40 minutes | 20–40 minutes | medium |
| Editorial | Seed data reports come-up 20–40 minutes. Consistent with oral absorption kinetics for substituted phenethylamines. | ||
ReasoningReasoningSeed data reports come-up 20–40 minutes. Consistent with oral absorption kinetics for substituted phenethylamines. Evidence basis: community_consensus_large | |||
| Peaktrace | 1.5–2.5 hours | 1.5–2.5 hours | medium |
| Editorial | Seed data reports peak duration 1.5–2.5 hours. Consistent with PIHKAL's total duration of 4–6 hours when combined with other phase durations. | ||
ReasoningReasoningSeed data reports peak duration 1.5–2.5 hours. Consistent with PIHKAL's total duration of 4–6 hours when combined with other phase durations. Evidence basis: community_consensus_large | |||
| Offsettrace | 0.5–1.5 hours | 0.5–1.5 hours | medium |
| Editorial | Seed data reports offset 0.5–1.5 hours. Combined with other phases, total subjective duration sums to approximately 4–5.5 hours, concordant with PIHKAL's 4–6 hours. | ||
ReasoningReasoningSeed data reports offset 0.5–1.5 hours. Combined with other phases, total subjective duration sums to approximately 4–5.5 hours, concordant with PIHKAL's 4–6 hours. Evidence basis: community_consensus_large | |||
| After effectstrace | 1–4 hours | 1–4 hours | low |
| Editorial | Seed data reports aftereffects 1–4 hours. No published data confirm this; value is community-derived. | ||
ReasoningReasoningSeed data reports aftereffects 1–4 hours. No published data confirm this; value is community-derived. Evidence basis: community_consensus_large | |||
| Totaltrace | 4–6 hours | 4–6 hours | medium |
| Editorial | PIHKAL (primary bioassay source) documents total duration of 4–6 hours. Seed data lists 3–5 hours but PIHKAL is more authoritative. Proposing 4–6 hours per PIHKAL. | ||
ReasoningReasoningPIHKAL (primary bioassay source) documents total duration of 4–6 hours. Seed data lists 3–5 hours but PIHKAL is more authoritative. Proposing 4–6 hours per PIHKAL. Evidence basis: community_consensus_large | |||
Safety
Toxicity Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Acute | low | low | low |
| Chronic | low | low | low |
| Organs Affected | cardiovascular | cardiovascular | low |
| Editorial | Classified as low (downgraded from moderate): no substance-specific toxicity data exist. Adverse event profile extrapolated from 2C-series class data (Dean et al. 2013), where fatalities involved more potent congeners (2C-E, 2C-I). 2C-D's weak receptor affinity and absence of reported serious adverse events suggest lower acute toxicity than more potent 2C compounds. | ||
ReasoningReasoningClassified as low (downgraded from moderate): no substance-specific toxicity data exist. Adverse event profile extrapolated from 2C-series class data (Dean et al. 2013), where fatalities involved more potent congeners (2C-E, 2C-I). 2C-D's weak receptor affinity and absence of reported serious adverse events suggest lower acute toxicity than more potent 2C compounds. Evidence basis: structural_analogy | |||
Dependence Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Physical | none | none | medium |
| Psychological | negligible | negligible | medium |
| Compulsive Redosing | negligible | negligible | medium |
| Dose Escalation | negligible | negligible | medium |
| Editorial | No abuse potential studies specific to 2C-D exist. Dean et al. (2013) review documents no dependence for any 2C-series drug. Classification based on class-level evidence for serotonergic psychedelics, which consistently demonstrate negligible dependence liability. | ||
ReasoningReasoningNo abuse potential studies specific to 2C-D exist. Dean et al. (2013) review documents no dependence for any 2C-series drug. Classification based on class-level evidence for serotonergic psychedelics, which consistently demonstrate negligible dependence liability. Evidence basis: structural_analogy | |||
Withdrawal Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Severity | none | none | medium |
| Symptoms | — | — | medium |
| Fatal | No | No | medium |
| Medical Supervision | Not required | Not required | medium |
| Editorial | No withdrawal syndrome documented for 2C-D or any 2C-series compound. Consistent with class-level evidence for serotonergic psychedelics. | ||
ReasoningReasoningNo withdrawal syndrome documented for 2C-D or any 2C-series compound. Consistent with class-level evidence for serotonergic psychedelics. Evidence basis: structural_analogy | |||
Tolerance Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Buildup | rapid | rapid | medium |
| Half-life | 3 days | 3 days | medium |
| Full Reset | 7 days | 7 days | medium |
| Cross-tolerances | lsd, psilocybin, mescaline, 2c-b, 2c-e, 2c-i, dom, doi | lsd, psilocybin, mescaline, 2c-b, 2c-e, 2c-i, dom, doi | medium |
| Editorial | Tolerance mechanism confirmed in mouse models (de la Fuente Revenga et al. 2022) via 5-HT2A downregulation. Reset period values (3-day half-life, 7-day full reset) are community-derived class estimates, not 2C-D-specific. Cross-tolerance expected across all classical psychedelics sharing the 5-HT2A mechanism. | ||
ReasoningReasoningTolerance mechanism confirmed in mouse models (de la Fuente Revenga et al. 2022) via 5-HT2A downregulation. Reset period values (3-day half-life, 7-day full reset) are community-derived class estimates, not 2C-D-specific. Cross-tolerance expected across all classical psychedelics sharing the 5-HT2A mechanism. Evidence basis: animal_study | |||
Effects & Profile
Contraindications
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| psychiatric psychotic disorderstrace | absolute | absolute | medium |
| Editorial | Class-level contraindication for all 5-HT2A agonist psychedelics. No 2C-D-specific data but mechanism is shared across the class. | ||
ReasoningReasoningClass-level contraindication for all 5-HT2A agonist psychedelics. No 2C-D-specific data but mechanism is shared across the class. | |||
| psychiatric bipolar disordertrace | relative | relative | low |
| Editorial | Class-level contraindication for serotonergic psychedelics. No 2C-D-specific data. | ||
ReasoningReasoningClass-level contraindication for serotonergic psychedelics. No 2C-D-specific data. | |||
| cardiovascular cardiovascular diseasetrace | relative | relative | low |
| Editorial | Cardiovascular adverse effects documented for 2C-series class (Dean et al. 2013). No 2C-D-specific cardiovascular data, but class mechanism applies. | ||
ReasoningReasoningCardiovascular adverse effects documented for 2C-series class (Dean et al. 2013). No 2C-D-specific cardiovascular data, but class mechanism applies. | |||
| neurological epilepsytrace | relative | relative | low |
| Editorial | Seizures documented in 2C-series class toxicology data. No 2C-D-specific seizure reports but mechanism is shared. | ||
ReasoningReasoningSeizures documented in 2C-series class toxicology data. No 2C-D-specific seizure reports but mechanism is shared. | |||
| other concurrent MAOI usetrace | absolute | absolute | medium |
| Editorial | 2C-D's MAO inhibitory potential documented by Wagmann et al. (2019). MAOI + psychedelic phenethylamine interactions documented for 2C-series class (Rached et al. 2026). | ||
ReasoningReasoning2C-D's MAO inhibitory potential documented by Wagmann et al. (2019). MAOI + psychedelic phenethylamine interactions documented for 2C-series class (Rached et al. 2026). | |||
| other concurrent serotonergic medicationtrace | relative | relative | medium |
| Editorial | Serotonin syndrome case reports documented for 2C-series compounds combined with serotonergic agents (Schifano et al. 2021). Tramadol interaction supported by mechanistic evidence (Baldo 2018, Rached et al. 2026). | ||
ReasoningReasoningSerotonin syndrome case reports documented for 2C-series compounds combined with serotonergic agents (Schifano et al. 2021). Tramadol interaction supported by mechanistic evidence (Baldo 2018, Rached et al. 2026). | |||
| pregnancy breastfeeding pregnancytrace | absolute | absolute | medium |
| Editorial | No reproductive safety data for 2C-D or any 2C-series compound. Precautionary contraindication. | ||
ReasoningReasoningNo reproductive safety data for 2C-D or any 2C-series compound. Precautionary contraindication. | |||
Timeline Phases
oral
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onsettrace | 900–2700 sec(i=0.05) | 900–2700 sec(i=0.05) | medium |
| Editorial | PIHKAL documents total duration of 4–6 hours. Seed data provides onset 15–45 min, come-up 20–40 min, peak 1.5–2.5 hours, offset 0.5–1.5 hours, aftereffects 1–4 hours. Timeline phases anchor to PIHKAL's total duration as primary source, with phase breakdowns informed by seed data and community reports. No controlled PK data exist to refine timing. | ||
ReasoningReasoningPIHKAL documents total duration of 4–6 hours. Seed data provides onset 15–45 min, come-up 20–40 min, peak 1.5–2.5 hours, offset 0.5–1.5 hours, aftereffects 1–4 hours. Timeline phases anchor to PIHKAL's total duration as primary source, with phase breakdowns informed by seed data and community reports. No controlled PK data exist to refine timing. | |||
| Come uptrace | 1200–2400 sec(i=0.30) | 1200–2400 sec(i=0.30) | medium |
| Editorial | PIHKAL documents total duration of 4–6 hours. Seed data provides onset 15–45 min, come-up 20–40 min, peak 1.5–2.5 hours, offset 0.5–1.5 hours, aftereffects 1–4 hours. Timeline phases anchor to PIHKAL's total duration as primary source, with phase breakdowns informed by seed data and community reports. No controlled PK data exist to refine timing. | ||
ReasoningReasoningPIHKAL documents total duration of 4–6 hours. Seed data provides onset 15–45 min, come-up 20–40 min, peak 1.5–2.5 hours, offset 0.5–1.5 hours, aftereffects 1–4 hours. Timeline phases anchor to PIHKAL's total duration as primary source, with phase breakdowns informed by seed data and community reports. No controlled PK data exist to refine timing. | |||
| Peaktrace | 5400–9000 sec(i=1.00) | 5400–9000 sec(i=1.00) | medium |
| Editorial | PIHKAL documents total duration of 4–6 hours. Seed data provides onset 15–45 min, come-up 20–40 min, peak 1.5–2.5 hours, offset 0.5–1.5 hours, aftereffects 1–4 hours. Timeline phases anchor to PIHKAL's total duration as primary source, with phase breakdowns informed by seed data and community reports. No controlled PK data exist to refine timing. | ||
ReasoningReasoningPIHKAL documents total duration of 4–6 hours. Seed data provides onset 15–45 min, come-up 20–40 min, peak 1.5–2.5 hours, offset 0.5–1.5 hours, aftereffects 1–4 hours. Timeline phases anchor to PIHKAL's total duration as primary source, with phase breakdowns informed by seed data and community reports. No controlled PK data exist to refine timing. | |||
| Resolutiontrace | 1800–5400 sec(i=0.20) | 1800–5400 sec(i=0.20) | medium |
| Editorial | PIHKAL documents total duration of 4–6 hours. Seed data provides onset 15–45 min, come-up 20–40 min, peak 1.5–2.5 hours, offset 0.5–1.5 hours, aftereffects 1–4 hours. Timeline phases anchor to PIHKAL's total duration as primary source, with phase breakdowns informed by seed data and community reports. No controlled PK data exist to refine timing. | ||
ReasoningReasoningPIHKAL documents total duration of 4–6 hours. Seed data provides onset 15–45 min, come-up 20–40 min, peak 1.5–2.5 hours, offset 0.5–1.5 hours, aftereffects 1–4 hours. Timeline phases anchor to PIHKAL's total duration as primary source, with phase breakdowns informed by seed data and community reports. No controlled PK data exist to refine timing. | |||
| Afterglowtrace | 3600–14400 sec(i=0.05) | 3600–14400 sec(i=0.05) | medium |
| Editorial | PIHKAL documents total duration of 4–6 hours. Seed data provides onset 15–45 min, come-up 20–40 min, peak 1.5–2.5 hours, offset 0.5–1.5 hours, aftereffects 1–4 hours. Timeline phases anchor to PIHKAL's total duration as primary source, with phase breakdowns informed by seed data and community reports. No controlled PK data exist to refine timing. | ||
ReasoningReasoningPIHKAL documents total duration of 4–6 hours. Seed data provides onset 15–45 min, come-up 20–40 min, peak 1.5–2.5 hours, offset 0.5–1.5 hours, aftereffects 1–4 hours. Timeline phases anchor to PIHKAL's total duration as primary source, with phase breakdowns informed by seed data and community reports. No controlled PK data exist to refine timing. | |||
Dose Tier Summaries
At common doses (25–50 mg oral), 2C-D produces its characteristic profile: mild sensory enhancement, thought connectivity, emotional warmth, and facilitated communication. Visual effects are subtle — slight color alteration, gentle visual drifting, and enhanced pattern recognition — but do not dominate the experience. The cognitive space is clear and communicative, distinguishing 2C-D from more visually intense 2C-series compounds. Physically, stimulation becomes noticeable: increased energy, mild jaw tension, pupil dilation, and slight cardiovascular elevation (heart rate, blood pressure). Appetite suppression is common. Duration is 4–6 hours, with 1–3 hours of mild residual stimulation.
PIHKAL documents 20–60 mg as the active range with qualitative descriptions matching this profile. The common range (25–50 mg) falls within Shulgin's primary bioassay range. Existing database values corroborate this range.
ReasoningReasoning
PIHKAL documents 20–60 mg as the active range with qualitative descriptions matching this profile. The common range (25–50 mg) falls within Shulgin's primary bioassay range. Existing database values corroborate this range.
Evidence basis: community_consensus_large
At threshold doses (5–10 mg oral), effects are barely perceptible and easily attributed to expectation. A faint mood lift, slight increase in sensory clarity, and mild stimulation may be noticed. No visual distortions or overt cognitive changes occur at this level. Physically, mild pupil dilation is possible but unlikely to be noticeable. Body load is absent. The experience does not interfere with normal functioning, and sleep is unaffected at typical evening hours.
No published threshold data specific to 2C-D. PIHKAL documents the active range beginning at 20 mg; threshold inferred from community consensus placing it at approximately half the lower active dose. Existing database values position threshold at 10 mg.
ReasoningReasoning
No published threshold data specific to 2C-D. PIHKAL documents the active range beginning at 20 mg; threshold inferred from community consensus placing it at approximately half the lower active dose. Existing database values position threshold at 10 mg.
Evidence basis: community_consensus_large
At light doses (10–25 mg oral), 2C-D produces subtle but identifiable effects: mild stimulation, slight color enhancement, enhanced appreciation for music and conversation, and a gentle sense of openness. This range corresponds to the lower end of Shulgin's documented active range and the 'pharmacological tofu' characterization — effects that lightly season the experience without defining it. Physical effects are minimal: slight pupil dilation, mild increase in heart rate and body temperature. Appetite may be mildly suppressed. Duration at this range is approximately 3–5 hours, with negligible aftereffects.
PIHKAL documents 20 mg as the lower bound of the active range, describing effects at this level as subtle and facilitating. Light range aligns with existing database values (10–25 mg) and PIHKAL's lower active range.
ReasoningReasoning
PIHKAL documents 20 mg as the lower bound of the active range, describing effects at this level as subtle and facilitating. Light range aligns with existing database values (10–25 mg) and PIHKAL's lower active range.
Evidence basis: community_consensus_large
At strong doses (50–100 mg oral), 2C-D transitions from its characteristic subtle profile into recognizable psychedelic territory. Visual drifting, color alteration, and geometric patterning become more prominent. Thought acceleration and thought connectivity intensify, with increased introspective depth. Emotional enhancement is marked — both positive and challenging emotional content may surface with greater force. Physical load increases: noticeable stimulation, body temperature fluctuation, jaw clenching, and pupil dilation. Nausea is possible during the come-up. The experience lasts 4–6 hours with 2–4 hours of aftereffects. This range extends beyond Shulgin's primary documented range (20–60 mg) and is less well-characterized.
PIHKAL's primary range extends to 60 mg; doses of 50–100 mg are derived from community reports rather than controlled data. One PIHKAL bioassay at 150 mg reported 2C-B-like intensity, suggesting that strong psychedelic effects do emerge at higher doses. Existing database values place the strong tier at 50–100 mg.
ReasoningReasoning
PIHKAL's primary range extends to 60 mg; doses of 50–100 mg are derived from community reports rather than controlled data. One PIHKAL bioassay at 150 mg reported 2C-B-like intensity, suggesting that strong psychedelic effects do emerge at higher doses. Existing database values place the strong tier at 50–100 mg.
Evidence basis: community_consensus_large
At heavy doses (100+ mg oral), 2C-D produces moderate to strong psychedelic effects approaching the intensity of more potent 2C-series compounds. Shulgin's 150 mg bioassay reported intense color enhancement comparable to 2C-B. Pronounced open-eye visuals, significant thought disruption, time distortion, and deep emotional intensity characterize this range. The experience may become difficult to navigate without preparation. Physical effects are substantial: marked stimulation, tachycardia, hypertension, jaw tension, and potential nausea. Temperature dysregulation and difficulty sleeping for several hours after the experience are expected. This dose range is poorly documented and carries unknown risk — no controlled data exist above 60 mg.
Only one PIHKAL bioassay documents effects at 150 mg. Community reports describe strong psychedelic effects above 100 mg but data are sparse. The safety profile at this dose range is uncharacterized. Existing database values place heavy at 100+ mg.
ReasoningReasoning
Only one PIHKAL bioassay documents effects at 150 mg. Community reports describe strong psychedelic effects above 100 mg but data are sparse. The safety profile at this dose range is uncharacterized. Existing database values place heavy at 100+ mg.
Evidence basis: community_consensus_small
History
backfill Jun 4, 2026
Historical versions do not record which reviewer approved them; editorial accountability is recorded per value in the database and in the publication ledger going forward.
Sources
- [1]weak
- [2]weakSynthetic Drug Abuse Prevention Act of 2012 (within FDASIA, P.L. 112-144)United States Congress · 2012linkno claims checked
- [3]weak
- [4]moderateSerotonin, via 5-HT2A receptors, increases EPSCs in layer V pyramidal cells of prefrontal cortex by an asynchronous mode of glutamate releaseAghajanian GK, Marek GJ · 1999 · Brain Researchpubmed 102161833 claims checked3 verified
- [5]moderateSerotonin and hallucinogensAghajanian GK, Marek GJ · 1999 · Neuropsychopharmacologypubmed 104324843 claims checked3 verified
- [6]moderateBehavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and functionEshleman AJ, Forster MJ, Wolfrum KM, Johnson RA, Janowsky A, Gatch MB · 2014 · Psychopharmacologydoi.org/10.1007/s00213-013-3303-6pubmed 241422034 claims checked2 verified1 inconclusive1 not supported
- [7]strong2C or Not 2C: Phenethylamine Designer Drug ReviewDean BV, Stellpflug SJ, Burnett A, Engebretsen KM · 2013 · Journal of Medical Toxicology
- [8]moderateTolerance and Cross-Tolerance among Psychedelic and Nonpsychedelic 5-HT2A Receptor Agonists in Micede la Fuente Revenga M, Jaster AM, McGinn J, Silva G, Saha S, Gonzalez-Maeso J · 2022 · ACS Chemical Neurosciencedoi.org/10.1021/acschemneuro.2c00170pubmed 359008763 claims checked1 verified1 partial1 inconclusive
- [9]moderateInteractions of phenethylamine-derived psychoactive substances of the 2C-series with human monoamine oxidasesWagmann L, Brandt SD, Stratford A, Maurer HH, Meyer MR · 2019 · Drug Testing and Analysis
- [10]weak
- [11]moderate1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI): From an Obscure to Pivotal Member of the DOX Family of Serotonergic Psychedelic Agents - A Review.Glennon RA, Dukat M · 2024 · ACS Pharmacology & Translational Science
- [12]strongChemistry and Structure-Activity Relationships of Psychedelics.Nichols DE · 2018 · Current Topics in Behavioral Neurosciences
- [13]moderateHallucinogens as discriminative stimuli in animals: LSD, phenethylamines, and tryptamines.Winter JC · 2009 · Psychopharmacology
- [14]moderateAnalysis of 2,5-dimethoxy-amphetamines and 2,5-dimethoxy-phenethylamines aiming their determination in biological matrices: a review.Nieddu M, Baralla E, Sodano F, Boatto G · 2023 · Forensic Toxicology
- [15]moderateSynthesis and pharmacological characterization of a series of geometrically constrained 5-HT(2A/2C) receptor ligandsChambers JJ, Parrish JC, Jensen NH, Kurrasch-Orbaugh DM, Marona-Lewicka D, Nichols DE · 2003 · Journal of Medicinal Chemistrypubmed 128775911 claim checked1 inconclusive
- [16]moderateOpioid analgesic drugs and serotonin toxicity (syndrome): mechanisms, animal models, and links to clinical effectsBaldo BA · 2018 · Archives of Toxicology
- [17]strongSafety and Efficacy of Monoamine Oxidase Inhibitors in Patients Who Use Psychoactive SubstancesRached G, Campana A, Fiani D, et al. · 2026 · CNS Drugs
- [18]strongNew psychoactive substances (NPS) and serotonin syndrome onset: A systematic review.Schifano F, Chiappini S, Miuli A, Corkery JM, Scherbaum N, Napoletano F, Arillotta D, Zangani C, Catalani V, Vento A, Pettorruso M, Martinotti G, Massimo DG, Guirguis A · 2021 · Experimental neurology
- [19]strongThe 4-alkyl chain length of 2,5-dimethoxyamphetamines differentially affects in vitro serotonin receptor actions versus in vivo psychedelic-like effectsLuethi D et al. · 2026 · Molecular Psychiatry
Claim Verification
Citation-bearing claims in this article were checked by an AI model against the abstract of the source they cite — every safety-critical claim, plus a sample of the rest. Verdicts below are model-issued, not human-issued; when an editor overrides a verdict, the override is recorded alongside it. Claims whose source does not support them are flagged for editorial review.
summary7 claims3verified2partial1inconclusive1not supported
verified2C-D acts as an agonist at 5-HT₂A and 5-HT₂C receptors, with psychedelic effects mediated through the canonical 5-HT₂A pathway in cortical layer V pyramidal neurons[4]model confidence 88%
Abstract directly establishes 5-HT₂A activation induces asynchronous glutamate release in layer V pyramidal cells of PFC; DOI (a phenethylamine 5-HT₂A agonist) replicated effects. Core mechanism claim is directly supported.
5-HT2A receptor activation induces asynchronous glutamate release in layer V pyramidal cells of prefrontal cortex; DOI (5-HT2A agonist) replicated these effects.
checked by claude-sonnet-4-6 · Apr 26, 2026
verified2C-D acts as an agonist at 5-HT₂A and 5-HT₂C receptors, with psychedelic effects mediated through the canonical 5-HT₂A pathway in cortical layer V pyramidal neurons[5]model confidence 90%
Abstract explicitly states phenethylamines are partial agonists at 5-HT₂A receptors and proposes 5-HT₂A-mediated enhancement of glutamatergic EPSPs in cortical layer V pyramidal cells as mechanism for perceptual distortions.
Convergent evidence that tryptamines and phenethylamines are partial agonists at 5-HT2A receptors. 5-HT2A-mediated enhancement of glutamatergic EPSPs in cortical layer V pyramidal cells proposed as mechanism for perceptual distortions.
checked by claude-sonnet-4-6 · Apr 26, 2026
not supportedSpecific binding affinity values (Ki, EC₅₀) for 2C-D have not been published in accessible form[6]model confidence 95%
cited source's abstract does not support this claim — flagged for editorial review
Abstract actively contradicts the claim: it explicitly states in vitro receptor binding and function data for 2C-D were published in this paper.
In vitro receptor binding and function data for 2C-C, 2C-D, 2C-E, 2C-I, 2C-T-2, and DOC.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedNo LD₅₀ or toxic dose data have been published for 2C-D, and no fatalities attributable to 2C-D alone appear in the clinical literature[7]model confidence 85%
Abstract confirms no specific 2C-D deaths documented. As a clinical toxicology review covering pharmacokinetics and adverse effects, absence of LD₅₀ mention is consistent with claim. Does not contradict.
No specific 2C-D deaths documented.
checked by claude-sonnet-4-6 · Apr 26, 2026
partialTolerance develops rapidly via 5-HT₂A receptor downregulation in the frontal cortex, a class-wide mechanism confirmed in mouse models. 2C-D demonstrates MAO inhibitory potential, elevating the risk of serotonin toxicity in combination with serotonergic agents[8]model confidence 85%
Tolerance via 5-HT₂A receptor downregulation in frontal cortex in mouse models is directly supported. The second sentence about 2C-D's MAO inhibitory potential is not addressed by this abstract at all.
Tolerance develops after single and repeated DOI administration via 5-HT2AR downregulation in frontal cortex. Cross-tolerance between DOI and LSD confirmed. Mechanism independent of beta-arrestin-2.
checked by claude-sonnet-4-6 · Apr 26, 2026
partialTolerance develops rapidly via 5-HT₂A receptor downregulation in the frontal cortex, a class-wide mechanism confirmed in mouse models. 2C-D demonstrates MAO inhibitory potential, elevating the risk of serotonin toxicity in combination with serotonergic agents[9]model confidence 85%
MAO inhibitory potential of 2C-D is directly supported. The first sentence about tolerance via 5-HT₂A receptor downregulation in mouse models is not addressed by this abstract.
17 drugs tested including 2C-D. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveNo dependence or withdrawal syndromes have been documented for any 2C-series compound[7]model confidence 65%
Abstract covers clinical adverse effects of 2C intoxication but does not specifically address dependence or withdrawal syndromes. Full text may discuss this topic.
Reviews pharmacology, pharmacokinetics, clinical effects, and treatment of 2C drug intoxication.
checked by claude-sonnet-4-6 · Apr 26, 2026
chemistry2 claims2verified
verifiedThe "2C" designation refers to the two carbon atoms in the ethylamine side chain, distinguishing this series from their α-methylated amphetamine analogs (the DOx series). 2C-D bears a 4-methyl group, making it the structural phenethylamine counterpart of dom (2,5-dimethoxy-4-methylamphetamine)[11]model confidence 90%
Abstract explicitly discusses the relationship between DOM and 2C-D via shared 4-methyl substitution and the DOx family context, directly supporting the structural counterpart claim.
Discusses relationship between 4-methyl (DOM/2C-D) and 4-iodo (DOI/2C-I) substitution.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe 4-methyl substituent is the smallest commonly encountered in the 2C-x family, a structural feature directly responsible for 2C-D's relatively low potency.[12]model confidence 88%
Abstract directly discusses the importance of 4-substituent size/lipophilicity on potency for the 2C series, supporting the claim that the small 4-methyl group explains 2C-D's lower potency.
Discusses 2C series and the importance of 4-substituent size/lipophilicity on potency.
checked by claude-sonnet-4-6 · Apr 26, 2026
pharmacology10 claims5verified5inconclusive
verified2C-D exerts its psychedelic effects primarily through agonism at serotonin 5-HT₂A receptors, the principal molecular target for classical hallucinogenic phenethylamines and tryptamines. 5-HT₂A activation on layer V pyramidal neurons in the prefrontal cortex induces enhanced asynchronous glutamatergic excitatory postsynaptic currents (EPSCs), a mechanism proposed to underlie the perceptual distortions and cognitive alterations characteristic of psychedelic states. 2C-D also acts as an agonist at 5-HT₂C receptors, though the relative contribution of 5-HT₂C activation to its subjective effects has not been delineated.[12]model confidence 82%
Abstract establishes 5-HT₂A as principal target and discusses 2C series SAR. Supports the primary mechanism and 2C-series pharmacology claims, though layer V specifics are not detailed in the abstract.
5-HT2A as principal target. Discusses 2C series and the importance of 4-substituent size/lipophilicity on potency.
checked by claude-sonnet-4-6 · Apr 26, 2026
verified2C-D exerts its psychedelic effects primarily through agonism at serotonin 5-HT₂A receptors, the principal molecular target for classical hallucinogenic phenethylamines and tryptamines. 5-HT₂A activation on layer V pyramidal neurons in the prefrontal cortex induces enhanced asynchronous glutamatergic excitatory postsynaptic currents (EPSCs), a mechanism proposed to underlie the perceptual distortions and cognitive alterations characteristic of psychedelic states. 2C-D also acts as an agonist at 5-HT₂C receptors, though the relative contribution of 5-HT₂C activation to its subjective effects has not been delineated.[5]model confidence 92%
Abstract directly supports 5-HT₂A agonism in phenethylamines and tryptamines, layer V pyramidal cell glutamatergic EPSP mechanism for perceptual distortions.
Convergent evidence that tryptamines and phenethylamines are partial agonists at 5-HT2A receptors. 5-HT2A-mediated enhancement of glutamatergic EPSPs in cortical layer V pyramidal cells proposed as mechanism for perceptual distortions.
checked by claude-sonnet-4-6 · Apr 26, 2026
verified2C-D exerts its psychedelic effects primarily through agonism at serotonin 5-HT₂A receptors, the principal molecular target for classical hallucinogenic phenethylamines and tryptamines. 5-HT₂A activation on layer V pyramidal neurons in the prefrontal cortex induces enhanced asynchronous glutamatergic excitatory postsynaptic currents (EPSCs), a mechanism proposed to underlie the perceptual distortions and cognitive alterations characteristic of psychedelic states. 2C-D also acts as an agonist at 5-HT₂C receptors, though the relative contribution of 5-HT₂C activation to its subjective effects has not been delineated.[4]model confidence 92%
Abstract directly demonstrates 5-HT₂A-mediated asynchronous glutamate release in layer V pyramidal cells of PFC; DOI (structural phenethylamine cousin of 2C-D) confirmed these effects.
5-HT2A receptor activation induces asynchronous glutamate release in layer V pyramidal cells of prefrontal cortex; DOI (5-HT2A agonist) replicated these effects.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveDrug discrimination studies in rats trained to discriminate lsd have demonstrated generalization to 2C-D, confirming a shared 5-HT₂A-mediated mechanism across the hallucinogenic class.[6]model confidence 70%
Abstract confirms rat drug discrimination data for 2C-D exists in this paper, but does not specify LSD as the trained discriminative stimulus. The specific LSD-trained claim requires the full text.
Includes transporter binding, mouse locomotion, and rat drug discrimination data.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveDrug discrimination studies in rats trained to discriminate lsd have demonstrated generalization to 2C-D, confirming a shared 5-HT₂A-mediated mechanism across the hallucinogenic class.[13]model confidence 65%
Review covers drug discrimination paradigm for hallucinogens including phenethylamines, but the abstract does not confirm LSD-trained generalization to 2C-D specifically.
Review of drug discrimination paradigm for hallucinogens including phenethylamines across structural classes.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedWagmann et al. evaluated 17 psychoactive 2C-series drugs including 2C-D for inhibition of human monoamine oxidase A (MAO-A) and MAO-B[9]model confidence 98%
Abstract directly confirms: 17 drugs tested including 2C-D, with both MAO-A and MAO-B inhibition measured.
17 drugs tested including 2C-D. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedCompound-specific IC₅₀ values for 2C-D were reported in the full paper's tables but are not available from the published abstract[9]model confidence 88%
Abstract provides only class-wide IC₅₀ ranges (10–125 μM MAO-A; 1.7–180 μM MAO-B), not 2C-D-specific values. This is consistent with the claim that compound-specific values are in the full paper tables, not the abstract.
IC50 values ranged from 10–125 μM for MAO-A and 1.7–180 μM for MAO-B.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveThe MAO inhibition potential is pharmacologically relevant: elevated monoamine levels from MAO inhibition have been associated with agitation, nausea, tachycardia, hypertension, and seizures.[9]model confidence 70%
Abstract establishes MAO inhibition by 2C-D compounds, but does not discuss the clinical consequences (agitation, nausea, tachycardia, hypertension, seizures) asserted in the claim.
17 drugs tested including 2C-D. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveFor the 2C-series generally, metabolism is believed to proceed via O-demethylation at positions 2 and 5 of the aromatic ring, with MAO-A as a primary metabolic enzyme[7]model confidence 60%
Abstract mentions pharmacokinetics in scope but does not describe O-demethylation or MAO-A as a primary metabolic enzyme. This level of metabolic detail is likely in the full text.
Reviews pharmacology, pharmacokinetics, clinical effects, and treatment of 2C drug intoxication.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveSome CYP involvement (CYP2D6 has been implicated for other 2C analogs) may occur, but no specific CYP enzyme identification studies for 2C-D have been published.[14]model confidence 60%
Abstract covers analytical methods for detection in biological matrices, not CYP enzyme involvement. CYP2D6 and absence of CYP studies for 2C-D are not addressed.
Review of analytical methods for quantification of DOx and 2C-x series drugs in biological matrices including blood and urine.
checked by claude-sonnet-4-6 · Apr 26, 2026
receptor pharmacology4 claims3verified1inconclusive
verifiedEshleman et al. conducted in vitro receptor binding and functional studies on six substituted phenethylamines including 2C-D, measuring binding affinities at multiple receptor targets and monoamine transporters (DAT, NET, SERT) alongside behavioral data in rodent models[6]model confidence 97%
Abstract directly confirms: six compounds including 2C-D, in vitro receptor binding and function, transporter binding, mouse locomotion, and rat drug discrimination data.
In vitro receptor binding and function data for 2C-C, 2C-D, 2C-E, 2C-I, 2C-T-2, and DOC. Includes transporter binding, mouse locomotion, and rat drug discrimination data.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe Eshleman et al. paper appears to include transporter binding data for 2C-D, but values were not accessible from the abstract[6]model confidence 90%
Abstract confirms transporter binding data is included in the paper, but no specific values are listed in the abstract text — consistent with the claim.
Includes transporter binding, mouse locomotion, and rat drug discrimination data.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe 4-methyl group of 2C-D is the smallest common substituent, resulting in lower receptor affinity than 2c-b (4-bromo), 2c-i (4-iodo), or 2c-e (4-ethyl)[12]model confidence 85%
Abstract establishes that 4-substituent size/lipophilicity governs potency in the 2C series. The specific ranking placing 4-methyl below 4-bromo/4-iodo/4-ethyl follows directly from this SAR principle.
Discusses 2C series and the importance of 4-substituent size/lipophilicity on potency.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveConformationally constrained analogs of the 2,5-dimethoxyphenethylamine scaffold have been used to probe 5-HT₂A and 5-HT₂C receptor geometry requirements, establishing that the unsubstituted ethylamine chain of 2C-D adopts a preferred anti-periplanar conformation for receptor binding.[15]model confidence 65%
Abstract confirms conformationally constrained phenethylamine analogs were tested at 5-HT₂A and 5-HT₂C receptors. The specific claim about 2C-D's anti-periplanar ethylamine chain conformation is not mentioned in the abstract.
Conformationally constrained phenethylamine analogs tested at 5-HT2A and 5-HT2C receptors. Most potent compound: Ki 2.6 nM (5-HT2A) and 1.1 nM (5-HT2C).
checked by claude-sonnet-4-6 · Apr 26, 2026
neuroscience2 claims2verified
verifiedAs a 5-HT₂A receptor agonist, 2C-D is expected to engage the same cortical circuits characterized for other serotonergic psychedelics. 5-HT₂A receptors are densely expressed on layer V pyramidal neurons in the prefrontal cortex, where agonist binding increases glutamatergic transmission through an asynchronous release mechanism[4]model confidence 95%
Abstract directly demonstrates 5-HT₂A-mediated asynchronous glutamate release in layer V pyramidal cells of PFC; DOI confirmed these effects. Core mechanism claim fully supported.
5-HT2A receptor activation induces asynchronous glutamate release in layer V pyramidal cells of prefrontal cortex; DOI (5-HT2A agonist) replicated these effects.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedAs a 5-HT₂A receptor agonist, 2C-D is expected to engage the same cortical circuits characterized for other serotonergic psychedelics. 5-HT₂A receptors are densely expressed on layer V pyramidal neurons in the prefrontal cortex, where agonist binding increases glutamatergic transmission through an asynchronous release mechanism[5]model confidence 92%
Abstract establishes phenethylamines as 5-HT₂A partial agonists and proposes 5-HT₂A-mediated glutamatergic EPSP enhancement in cortical layer V pyramidal cells as the perceptual distortion mechanism.
Convergent evidence that tryptamines and phenethylamines are partial agonists at 5-HT2A receptors. 5-HT2A-mediated enhancement of glutamatergic EPSPs in cortical layer V pyramidal cells proposed as mechanism for perceptual distortions.
checked by claude-sonnet-4-6 · Apr 26, 2026
pharmacokinetic detail4 claims4inconclusive
inconclusiveFor the 2C-series generally, hepatic metabolism proceeds via O-demethylation at the 2- and 5-positions of the aromatic ring and oxidative deamination by MAO-A[7]model confidence 60%
Abstract mentions pharmacokinetics in scope but does not describe O-demethylation at positions 2/5 or MAO-A as primary metabolic enzyme. Metabolic pathway detail is likely in the full text.
Reviews pharmacology, pharmacokinetics, clinical effects, and treatment of 2C drug intoxication.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveFor the 2C-series generally, hepatic metabolism proceeds via O-demethylation at the 2- and 5-positions of the aromatic ring and oxidative deamination by MAO-A[9]model confidence 60%
Abstract addresses MAO inhibition by 2C-D, not MAO-A as a metabolic enzyme for 2C compounds. O-demethylation is not discussed. The MAO inhibition and MAO-mediated metabolism are separate concepts not conflatable from the abstract.
17 drugs tested including 2C-D. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveCYP2D6 has been implicated in the metabolism of certain 2C analogs, but no specific CYP enzyme identification studies for 2C-D have been published[14]model confidence 60%
Abstract covers analytical detection methods for 2C-x compounds in biological matrices. CYP2D6 involvement or absence of CYP studies is not addressed in the abstract.
Review of analytical methods for quantification of DOx and 2C-x series drugs in biological matrices including blood and urine.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveDefinitive identification in biological matrices requires gas chromatography–mass spectrometry (GC-MS) or liquid chromatography–tandem mass spectrometry (LC-MS/MS).[14]model confidence 65%
Abstract confirms the paper reviews analytical methods for quantifying 2C-x drugs in biological matrices (blood and urine), which is exactly the right topic. However, GC-MS and LC-MS/MS are not named in the abstract text provided.
Review of analytical methods for quantification of DOx and 2C-x series drugs in biological matrices including blood and urine.
checked by claude-sonnet-4-6 · Apr 26, 2026
safety17 claims13verified1partial3inconclusive
verifiedNo human toxic dose has been established[7]model confidence 82%
Clinical toxicology review provides a dose range (20–60 mg) but does not establish a toxic dose. As a comprehensive clinical review, absence of toxic dose data is consistent with the claim.
2C-D dose range 20-60mg, duration 4-6h.
checked by claude-sonnet-4-6 · Apr 26, 2026
partialThe Dean et al. clinical toxicology review documented at least five deaths in the 2C drug literature overall, but these involved other 2C compounds — primarily 2c-e and 2c-i — and no 2C-D-specific fatalities were reported.[7]model confidence 82%
Abstract confirms at least 5 deaths and no specific 2C-D deaths, but does not name which compounds (2C-E, 2C-I) were involved. The specific attribution is a factual claim not verifiable from the abstract.
At least 5 deaths reported; excited delirium common. No specific 2C-D deaths documented.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedFor the 2C-series class, acute adverse presentations include:[7]model confidence 92%
Abstract explicitly documents sympathomimetic and serotonin toxicity presentations for the 2C class, directly supporting the existence of documented acute adverse presentations.
Sympathomimetic and serotonin toxicity presentations.
checked by claude-sonnet-4-6 · Apr 26, 2026
verified2C-D's demonstrated MAO inhibitory potential represents an additional toxicological mechanism: MAO inhibition elevates synaptic monoamine concentrations, which can contribute to cardiovascular stress, agitation, and serotonin toxicity, particularly when 2C-D is combined with other serotonergic or sympathomimetic substances.[9]model confidence 85%
Abstract directly establishes 2C-D's MAO inhibitory potential. Clinical implications (cardiovascular stress, serotonin toxicity risk) are pharmacologically established consequences of MAO inhibition that this paper provides the mechanistic basis for.
17 drugs tested including 2C-D. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition. IC50 values ranged from 10–125 μM for MAO-A and 1.7–180 μM for MAO-B.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveDe la Fuente Revenga et al. demonstrated in mice that tolerance to the DOI-induced head-twitch response develops within 24 hours of a single administration, with progressive tolerance emerging over 4 days of repeated dosing[8]model confidence 72%
Abstract confirms tolerance develops after single and repeated DOI administration, but specific timing (24 hours, 4 days) is not mentioned. Full text required to verify temporal claims.
Tolerance develops after single and repeated DOI administration via 5-HT2AR downregulation in frontal cortex.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThis tolerance is mediated by 5-HT₂A receptor downregulation in the frontal cortex and is independent of β-arrestin-2[8]model confidence 98%
Abstract directly and explicitly states both that the mechanism is 5-HT₂AR downregulation in frontal cortex and that it is independent of beta-arrestin-2.
Tolerance develops after single and repeated DOI administration via 5-HT2AR downregulation in frontal cortex. Mechanism independent of beta-arrestin-2.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveNo published evidence of physical dependence, withdrawal syndrome, or compulsive redosing exists for 2C-D or any 2C-series compound.[7]model confidence 65%
Abstract covers clinical adverse effects of 2C intoxication but does not specifically address dependence, withdrawal, or compulsive redosing. Full text may contain relevant discussion.
Reviews pharmacology, pharmacokinetics, clinical effects, and treatment of 2C drug intoxication.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe combination of 2C-D with other serotonergic substances carries risk of serotonin toxicity. 2C-D contributes to this risk through two mechanisms: direct 5-HT₂A agonism and MAO inhibition[9]model confidence 85%
Abstract establishes 2C-D's MAO inhibitory potential, supporting the MAO inhibition mechanism of serotonergic risk. The 5-HT₂A agonism component is separately documented elsewhere.
17 drugs tested including 2C-D. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedTramadol inhibits the serotonin transporter (SERT), elevating synaptic serotonin[16]model confidence 97%
Abstract explicitly states tramadol is implicated in serotonin toxicity via SERT inhibition.
Reviews serotonin toxicity from opioids, particularly tramadol via SERT inhibition. Tramadol implicated in serotonin toxicity through multiple mechanisms.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedCombined with 2C-D's 5-HT₂A agonism and MAO inhibitory potential, this creates convergent serotonergic stimulation[9]model confidence 85%
Abstract directly establishes 2C-D's MAO inhibitory potential, which is the cited mechanism for one component of convergent serotonergic stimulation.
17 drugs tested including 2C-D. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedTramadol fatalities in combination with MAOIs are documented[17]model confidence 97%
Abstract explicitly states tramadol + MAOI fatalities are documented.
tramadol + MAOI fatalities documented.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedClassical MAOIs combined with 2C-D would produce dual MAO inhibition (exogenous MAOI plus 2C-D's own MAO inhibitory activity) alongside direct 5-HT₂A agonism — a high-risk combination for serotonin toxicity.[9]model confidence 85%
Abstract confirms 2C-D's MAO inhibitory activity, directly supporting the dual MAO inhibition concept. The risk inference is mechanistically sound given the established data.
17 drugs tested including 2C-D. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedClassical MAOIs combined with 2C-D would produce dual MAO inhibition (exogenous MAOI plus 2C-D's own MAO inhibitory activity) alongside direct 5-HT₂A agonism — a high-risk combination for serotonin toxicity.[17]model confidence 82%
Abstract notes 2C-B (analogous phenethylamine psychedelic) with agitation in MAOI combinations and documents MAOI-related fatalities, supporting the high-risk characterization of this combination.
2C-B noted with agitation adverse events in MAOI combinations; MAOIs generally manageable with some classic hallucinogens with monitoring.
checked by claude-sonnet-4-6 · Apr 26, 2026
verified2C-series drugs including 2C-I have been specifically documented in serotonin syndrome case reports when combined with other serotonergic agents. 2C-D carries the same mechanistic risk.[18]model confidence 90%
Abstract explicitly implicates 2C-I (psychedelic phenethylamine) in serotonin toxicity from NPS. Extension to 2C-D as sharing mechanistic risk is reasonable given shared 5-HT₂A pharmacology.
Systematic review of serotonin toxicity from NPS. Psychedelic phenethylamines (2C-I, 25I-NBOMe) implicated.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedCardiovascular disease — sympathomimetic effects (hypertension, tachycardia) documented for the 2C-series class may be clinically significant in patients with pre-existing cardiovascular conditions[7]model confidence 88%
Abstract explicitly documents sympathomimetic presentations for the 2C class, supporting hypertension and tachycardia risk claims.
Sympathomimetic and serotonin toxicity presentations.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedConcurrent MAOI use — dual MAO inhibition plus 5-HT₂A agonism creates high risk for serotonin toxicity[9]model confidence 85%
Abstract establishes 2C-D's MAO inhibitory potential, directly supporting the dual MAO inhibition component of this interaction risk claim.
17 drugs tested including 2C-D. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveEpilepsy or seizure disorders — seizures are documented among 2C-series adverse events[7]model confidence 60%
Abstract mentions adverse presentations (excited delirium, sympathomimetic effects) but does not specifically document seizures. Full text required to confirm seizure data.
Reviews pharmacology, pharmacokinetics, clinical effects, and treatment of 2C drug intoxication. At least 5 deaths reported; excited delirium common.
checked by claude-sonnet-4-6 · Apr 26, 2026
comparative pharmacology2 claims2verified
verifiedThe 4-methyl substituent produces lower 5-HT₂A affinity than the 4-bromo (2c-b), 4-iodo (2c-i), or 4-ethyl (2c-e) analogs[12]model confidence 85%
Abstract establishes that 4-substituent size/lipophilicity governs 5-HT₂A potency in the 2C series. The SCOPE confirms the paper demonstrates 2C-D is less potent than 2C-B and 2C-I due to smaller 4-methyl group.
Discusses 2C series and the importance of 4-substituent size/lipophilicity on potency.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedLuethi et al. demonstrated that DOM was the most efficacious compound in the head-twitch response (HTR) assay among the 4-alkyl 2,5-dimethoxyamphetamine series, with in vitro 5-HT₂A activities across the series ranging from 2–56 nM[19]model confidence 97%
Abstract directly confirms DOM was most efficacious in the HTR assay, and in vitro 5-HT₂A activities ranged from 2–56 nM across the alkyl chain length series.
DOM (4-methyl 2,5-dimethoxyamphetamine; closest known amphetamine analog of 2C-D) was most efficacious in head-twitch response assay. 5-HT2 subtypes primary targets; in vitro 5-HT2A activities 2-56 nM across alkyl chain length series.
checked by claude-sonnet-4-6 · Apr 26, 2026
Coverage & Gaps
Research Trail
substance-article pipeline-v5 Apr 26, 2026
| Step | Source | Query | Results |
|---|---|---|---|
| 1database lookup | PubChem | 2C-D | 1 result, 1 selected |
selection rationaleselection rationaleOnly match; confirms seed data chemical identity | |||
| 2literature search | PubMed | 2C-D 2,5-dimethoxy-4-methylphenethylamine pharmacology | 1 result, 1 selected |
selection rationaleselection rationaleDirect study on 2C-D pharmacology; receptor binding and drug discrimination data | |||
| 3literature search | OpenAlex | 2C-D psychedelic phenethylamine receptor binding | 342 results, 1 selected |
selection rationaleselection rationaleOnly MAO inhibition paper directly relevant to 2C-D discarded 9: General psychedelic papers not specific to 2C-D | |||
| 4literature search | PubMed | 2C-D serotonin receptor 5-HT2A binding affinity 2,5-dimethoxy-4-methylphenethylamine | 1 result, 0 selected |
selection rationaleselection rationaleNo new papers found | |||
| 5literature search | PubMed | 2C phenethylamine series 5-HT2A receptor binding Ki hallucinogen discrimination | 1 result, 1 selected |
selection rationaleselection rationaleRelevant SAR context for 2C series | |||
| 6literature search | OpenAlex | 2C-D 2,5-dimethoxy-4-methylphenethylamine Shulgin | 13 results, 3 selected |
selection rationaleselection rationaleAll directly relevant to 2C series pharmacology context | |||
| 7clinical trial search | ClinicalTrials.gov | 2C-D phenethylamine psychedelic | 0 results, 0 selected |
selection rationaleselection rationaleNo relevant results | |||
| 8document retrieval | PMC | 2C-D specific dosage pharmacokinetics | 1 result, 3 selected |
selection rationaleselection rationaleDirect article text with 2C-D specific data | |||
| 9web search | Web Search | 2C-D PIHKAL Shulgin 1991 synthesis first described history | 10 results, 3 selected |
selection rationaleselection rationaleKey historical provenance data | |||
| 10document retrieval | Erowid | 2C-D PIHKAL entry dosage effects history | 1 result, 5 selected |
selection rationaleselection rationalePrimary source for 2C-D human bioassay and synthesis history | |||
| 11legal status search | Web Search | 2C-D legal status scheduling DEA US controlled substance | 10 results, 3 selected |
selection rationaleselection rationaleKey legal status data by jurisdiction | |||
| 12database lookup | Cayman Chemical | 2C-D chemical identifiers | 1 result, 1 selected |
selection rationaleselection rationaleConfirms CAS registry number | |||
| 13literature search | PubMed | 4-alkyl chain 2,5-dimethoxyamphetamine serotonin receptor psychedelic Molecular Psychiatry | 1 result, 1 selected |
selection rationaleselection rationaleDOM is the amphetamine analog of 2C-D; provides closest published in vitro data for the 4-methyl 2,5-dimethoxy scaffold | |||
| 14literature search | PubMed | psychedelic cross-tolerance serotonin 5-HT2A receptor downregulation LSD | 1 result, 1 selected |
selection rationaleselection rationaleDirectly supports tolerance mechanism section | |||
| 15literature search | PubMed | 2,5-dimethoxy-amphetamine phenethylamine biological matrices forensic toxicology | 1 result, 1 selected |
selection rationaleselection rationaleRelevant to analytical detection and metabolic pathways for 2C-x series | |||
| 16legal status search | Web Search | 2C-D UK Misuse of Drugs Act Class A schedule legal status Europe Australia | 10 results, 3 selected |
selection rationaleselection rationaleLegal status by jurisdiction | |||
| 17cross reference | Multiple | Comparing seed data duration vs PIHKAL data | 2 results, 2 selected |
selection rationaleselection rationaleIdentified discrepancy requiring editorial flag | |||
Research document (raw, unedited pipeline output)
# Research Output: 2C-D
## Chemical Identity
**Verified data (PubChem CID 135740 [Ref N/A — database lookup]):**
| Field | Value | Source |
|---|---|---|
| Systematic IUPAC name | 2-(2,5-dimethoxy-4-methylphenyl)ethanamine | PubChem CID 135740 |
| Molecular formula | C₁₁H₁₇NO₂ | PubChem CID 135740 |
| Molecular weight | 195.26 g/mol | PubChem CID 135740 |
| InChIKey | UNQQFDCVEMVQHM-UHFFFAOYSA-N | PubChem CID 135740 |
| PubChem CID | 135740 | PubChem |
| CAS number (HCl salt) | 25505-65-1 | Cayman Chemical product 11888 [Ref 14] |
| CAS number (free base) | 24333-19-5 | Wikidoc [Ref 20]; **unverified via API** |
| SMILES | COc1cc(CCN)c(OC)cc1C | Derived from IUPAC; Wikidoc gives equivalent Kekulé form NCCC1=C(OC)C=C(C)C(OC)=C1 [Ref 20] |
| Melting point (HCl salt) | 213–214°C | Wikidoc [Ref 20]; **not confirmed by primary source** |
| Also known as | LE-25 | PIHKAL [Ref 12]; Wikidoc [Ref 20] |
**Seed data comparison:** The brief did not include SMILES, molecular formula, molecular weight, or PubChem CID. All are now confirmed from PubChem. The systematic name "2-(2,5-dimethoxy-4-methylphenyl)ethanamine" in the brief matches PubChem exactly. No discrepancies in chemical identity.
**⚠️ FLAG:** Two CAS numbers appear in sources. CAS 25505-65-1 is confirmed by Cayman Chemical as the **hydrochloride salt**. CAS 24333-19-5 from Wikidoc may refer to the free base but could not be verified via API lookup. Generation agent should confirm which CAS belongs to which form and which to use as primary.
---
## Pharmacology
### Receptor Binding Mechanism
2C-D is a serotonin 5-HT₂A and 5-HT₂C receptor agonist. The psychedelic effects of 2C-D are mediated primarily through agonism at the 5-HT₂A receptor, the principal target for hallucinogenic phenethylamines and tryptamines (Nichols DE 2018 [Ref 22]; Aghajanian & Marek 1999 [Ref 19]). 5-HT₂A activation in layer V pyramidal cells of the prefrontal cortex induces enhanced asynchronous glutamatergic excitatory postsynaptic currents — a proposed mechanism for the perceptual distortions characteristic of classical psychedelics (Aghajanian & Marek 1999 [Ref 11]).
Cayman Chemical's research chemical catalog describes 2C-D as a **weak serotonin receptor agonist** at 5-HT₂A and 5-HT₂C receptors [Ref 14], distinguishing it from more potent 2C-series compounds (e.g., 2C-B, 2C-I, 2C-E) that bear larger, more lipophilic 4-position substituents.
### In Vitro Receptor Binding Data
Eshleman et al. (2014 [Ref 1]) conducted in vitro receptor binding and functional studies on six substituted phenethylamines including 2C-D. The study included:
- **Receptor binding:** Binding affinities at multiple targets using radioligand displacement assays
- **Transporter binding:** Monoamine transporter interaction data (DAT, NET, SERT)
- **Functional assays:** Receptor activation potency
- **Behavioral data (rodents):** Mouse locomotion and rat drug discrimination studies
**⚠️ FLAG — Critical data gap:** The published abstract of Eshleman et al. (2014 [Ref 1]) does not disclose specific Ki or EC₅₀ values for 2C-D. The full paper contains these values (reported in tables), but they were not accessible via the API tools used in this research. The generation agent should note that quantitative binding data exist for 2C-D but were not directly extracted here, and should retrieve the full paper if values are needed for structured data.
### Structure-Activity Relationships
Within the 2C-series, 5-HT₂A affinity correlates with the size and lipophilicity of the 4-position substituent on the phenethylamine ring. 2C-D's 4-methyl group is the smallest common substituent in the 2C-x family, resulting in lower receptor affinity than 2C-B (4-bromo), 2C-I (4-iodo), or 2C-E (4-ethyl) (Nichols DE 2018 [Ref 22]). This structural analysis explains 2C-D's relatively high dose requirements and moderate potency.
The amphetamine analog of 2C-D is **DOM** (2,5-dimethoxy-4-methylamphetamine). Luethi et al. (2026 [Ref 15]) demonstrated that DOM (the 4-methyl 2,5-dimethoxyamphetamine) was the **most efficacious compound** in the head-twitch response (HTR) assay among the 4-alkyl 2,5-dimethoxyamphetamine series. In vitro 5-HT₂A activities across the series ranged from 2–56 nM. This finding suggests the 4-methyl substitution does not diminish functional efficacy despite its lower affinity, though data from the amphetamine series cannot be directly extrapolated to the phenethylamine (2C-D) analog without caution.
Drug discrimination studies in rats trained to discriminate LSD generalized to 2C-D (Eshleman et al. 2014 [Ref 1]; Winter 2009 [Ref 3]), consistent with shared 5-HT₂A agonist mechanism across the hallucinogenic class.
### MAO Inhibition
Wagmann et al. (2019 [Ref 2]) evaluated 17 psychoactive 2C-series drugs including 2C-D for inhibition of human monoamine oxidase A (MAO-A) and MAO-B using an in vitro assay. Among the 12 classic 2Cs tested, 13 showed MAO-A inhibition potential and 11 showed MAO-B inhibition. IC₅₀ values for MAO-A ranged from 10–125 μM, and for MAO-B from 1.7–180 μM across the tested drugs.
**⚠️ FLAG:** The abstract of Wagmann et al. (2019 [Ref 2]) does not provide compound-specific IC₅₀ values for 2C-D individually. The generation agent should note that MAO inhibition for 2C-D cannot be excluded, and specific values require access to the full paper's tables.
The MAO inhibition potential is pharmacologically relevant: elevated monoamine levels from MAO inhibition have been associated with adverse events including agitation, nausea, tachycardia, hypertension, and seizures (Wagmann et al. 2019 [Ref 2]).
### Adrenergic and Dopaminergic Activity
No specific adrenergic or dopaminergic binding data for 2C-D were found in the searched literature. The Eshleman et al. (2014 [Ref 1]) paper appears to include transporter binding data, but values were not accessible from the abstract. Based on structural class (primary amine, no alpha-methyl), 2C-D is not expected to be a substrate/releaser at monoamine transporters in the same manner as the amphetamine class.
### Pharmacokinetics
**No published pharmacokinetic data specific to 2C-D were found.** This is a critical gap. No human studies on bioavailability, plasma half-life, volume of distribution, or time to peak concentration have been published for 2C-D. The Dean et al. (2013 [Ref 6]) review notes that for the 2C-series generally, metabolism likely proceeds via O-demethylation at positions 2 and 5 of the ring, with MAO-A as a primary metabolic enzyme. Some CYP involvement (CYP2D6 has been implicated for other 2C analogs) may occur but is not confirmed for 2C-D.
**Data gap:** No specific CYP enzyme identification studies for 2C-D are published (Nieddu et al. 2023 [Ref 17]).
---
## History
### Discovery and First Documentation
2C-D was first described in the **scientific literature by Beng T. Ho and colleagues at the Texas Research Institute of Mental Sciences in 1970** [Ref 13]. The original paper documented its synthesis and initial pharmacological evaluation.
Alexander Shulgin reportedly tested 2C-D at sub-threshold doses as early as **1964–1965**, and at active doses in **1974–1975**, observing its psychoactive properties in self-experiments [Ref 13]. The human psychopharmacology of 2C-D was described by **Alexander Shulgin and Michael Carter in 1975** [Ref 13].
2C-D was also investigated under the designation **LE-25** by **Hanscarl Leuner**, a German psychiatrist and pioneer of psycholytic psychotherapy. Leuner reportedly explored 2C-D as a tool for extending the effects of other psychoactive substances used in therapeutic contexts in Germany [Ref 12, Ref 20].
### PiHKAL Documentation
2C-D appears as **entry #23** in Alexander Shulgin and Ann Shulgin's 1991 book *PiHKAL: Phenethylamines I Have Known and Loved* (Transform Press) [Ref 12]. The entry provides:
- Synthesis route (via Vilsmeier formylation of methylated toluhydroquinone, condensation with nitromethane, reduction with LiAlH₄)
- Dose range: 20–60 mg (with bioassay reports up to 150 mg)
- Duration: 4–6 hours
- Subjective description: "pharmacological tofu" — potentiates effects of co-administered substances without producing strongly defined psychoactive effects at typical doses; at higher doses, described as mildly psychedelic
### Regulatory History (United States)
2C-D remained largely unscheduled in the US until 2012. The compound was **explicitly named** in the **Synthetic Drug Abuse Prevention Act of 2012**, which was enacted as part of the **Food and Drug Administration Safety and Innovation Act (FDASIA, P.L. 112-144)**, signed into law on **July 9, 2012** [Ref 23]. This placed 2C-D permanently in **Schedule I** of the Controlled Substances Act.
---
## Subjective Effects
Published subjective descriptions of 2C-D derive primarily from Shulgin's PIHKAL bioassays [Ref 12] and the "2C or Not 2C" clinical toxicology review [Ref 6]:
- At **lower/moderate doses (20–40 mg):** Described as "pharmacological tofu" — subtle, somewhat stimulating, facilitates communication and openness; effects do not strongly define the experience. May enhance sensory perception without producing overt hallucinations.
- At **higher doses (60–150 mg):** Mildly to moderately psychedelic; one bioassay at 150 mg compared favorably to 2C-B with "intense colors" [Ref 12].
- Shulgin's characterization suggests 2C-D's primary utility in early psycholytic research was as an **adjunct or "potentiator"** — extending and facilitating the effects of other substances rather than as a standalone psychedelic.
The effects taxonomy in the seed data (visual drifting, color alteration, tracers, thought connectivity, introspection, emotional enhancement, stimulation, etc.) is consistent with class-based expectations for a 5-HT₂A partial agonist at the dose levels listed, but these specific effects have not been documented in controlled clinical research specific to 2C-D. They represent a combination of Shulgin's bioassays and class-level inference.
**⚠️ FLAG:** No controlled, double-blind clinical studies on 2C-D subjective effects exist. All subjective effect data for 2C-D are from: (1) Shulgin's self-experiments (PIHKAL [Ref 12]), (2) class-level inference from other 2C compounds, and (3) anecdotal reports. The generation agent should label effects accordingly.
### Duration
- **PIHKAL (primary source [Ref 12]):** 4–6 hours total
- **Seed data:** total 3–5 hours; onset 15–45 min; come-up 20–40 min; peak 1.5–2.5 hours; offset 0.5–1.5 hours; aftereffects 1–4 hours
**⚠️ DISCREPANCY FLAG:** PIHKAL states a total duration of **4–6 hours**. The seed data lists **3–5 hours** total. The PIHKAL value (primary source from direct bioassay) is likely more authoritative. However, the seed data's component breakdown (onset + come-up + peak + offset) does sum to approximately 4–5.5 hours if aftereffects are included, which may reconcile these figures. The generation agent should consider proposing 4–6 hours as the total duration range, or flagging this discrepancy for editorial review. The dose range in PIHKAL (20–60 mg) partially aligns with the seed data Common dose (25–50 mg), but PIHKAL lacks the granular threshold/light/strong/heavy breakdown.
---
## Safety & Toxicity
### LD₅₀ / Toxic Dose
**No LD₅₀ or human toxic dose data have been published for 2C-D.** The seed data notes "toxic dose is unknown," which is confirmed by this research. This is consistent with the general sparse toxicological literature for 2C-D specifically (Dean et al. 2013 [Ref 6]).
### Adverse Events and Deaths
No deaths or serious adverse events specifically attributed to **2C-D** alone were identified in the searched literature. The Dean et al. (2013 [Ref 6]) review documented at least five deaths in the 2C drug literature overall, but these involved other 2C compounds (e.g., 2C-E, 2C-I). No 2C-D specific fatalities were reported in that review.
For the 2C-series class, common adverse presentations include [Ref 6]:
- Hallucinations, agitation, aggression, violence, dysphoria
- Hypertension, tachycardia
- Seizures
- Hyperthermia
- Excited delirium (particularly in fatalities)
- Serotonin toxicity syndrome presentation
### Psychological Risks
No controlled clinical data on psychological risk for 2C-D are available. Class-level risks for serotonergic psychedelics include challenging or adverse psychological reactions ("bad trips"), anxiety, panic, and psychological decompensation in vulnerable individuals. These are inferred from the broader psychedelic literature.
### MAO Inhibition as Toxicity Risk
2C-D's demonstrated MAO inhibition potential (Wagmann et al. 2019 [Ref 2]) represents a pharmacological mechanism that could contribute to adverse effects, particularly when combined with other serotonergic or sympathomimetic substances.
---
## Harm Reduction
### Treatment of Intoxication
Treatment of 2C drug intoxication is primarily **supportive**, per Dean et al. (2013 [Ref 6]):
- Immediate intervention for excited delirium, hyperthermia, and seizures
- Benzodiazepines for agitation and seizure control
- Active cooling for hyperthermia
- Monitoring for rhabdomyolysis and renal complications
Serotonin syndrome presentation should be managed per standard protocols; cyproheptadine (5-HT₂A antagonist) may be appropriate in serotonin toxicity cases (Schifano et al. 2021 [Ref 18]).
### Drug Testing
2C-D may not be detected by standard immunoassay drug screens, which are calibrated for common controlled substances. Definitive identification requires GC-MS or LC-MS/MS (Nieddu et al. 2023 [Ref 17]). Users should be made aware that standard drug tests will not detect 2C-D.
Reagent testing (e.g., Marquis, Mecke, Simon's) can provide provisional identification, though cross-reactivity with other compounds exists.
### Setting and Dose
Given the characterization as "pharmacological tofu" and the dose-dependent nature of effects, starting at the threshold/low end of the range (10–20 mg) with an experienced sitter in a safe setting is prudent. The high-dose range (100+ mg) is poorly documented and should be considered experimental.
---
## Tolerance & Dependence
### Tolerance Mechanism
Psychedelic tolerance develops rapidly following 5-HT₂A receptor agonism. De la Fuente Revenga et al. (2022 [Ref 16]) demonstrated in mice that:
- Tolerance to DOI-induced head-twitch response develops **within 24 hours** of a single administration
- Progressive tolerance emerges with repeated administration over 4 days
- Tolerance is mediated by **5-HT₂A receptor downregulation** in the frontal cortex
- Mechanism is **independent of β-arrestin-2**
These findings are consistent with the seed data's statement that tolerance begins "almost immediately after ingestion."
### Cross-Tolerance
De la Fuente Revenga et al. (2022 [Ref 16]) confirmed **cross-tolerance between DOI and LSD** in mice, supporting the seed data's claim of cross-tolerance among psychedelics. This is a class property expected for all 5-HT₂A agonist psychedelics, including 2C-D.
### Reset Period
The seed data states tolerance half-life of 3 days with full reset at 7 days. This is consistent with general psychedelic tolerance literature and is plausible for a 5-HT₂A-mediated mechanism, though **no 2C-D-specific tolerance data exist in the published literature**. This value should be flagged as class-level inference.
### Dependence
2C-D is characterized as "not habit-forming" in the seed data. No published evidence of physical dependence or withdrawal syndrome for 2C-D or the 2C-series was identified. No abuse potential studies specific to 2C-D are published. The Dean et al. (2013 [Ref 6]) review does not document dependence for any 2C drug.
---
## Interactions
### Tramadol: Dangerous
The seed data flags tramadol as a **dangerous interaction**. This is pharmacologically well-supported:
1. **Tramadol inhibits the serotonin transporter (SERT)**, elevating synaptic serotonin (Baldo 2018 [Ref 9])
2. **2C-D is a 5-HT₂A agonist** and has MAO inhibitory potential (Wagmann et al. 2019 [Ref 2])
3. Combined serotonergic stimulation from tramadol (SERT inhibition) + 5-HT₂A agonism + potential MAO inhibition creates conditions for **serotonin toxicity**
Tramadol fatalities in combination with MAOIs are documented (Rached et al. 2026 [Ref 10]). The combination of tramadol with psychedelic phenethylamines represents a high-risk interaction, though no 2C-D + tramadol specific case reports were found.
**⚠️ FLAG:** The severity classification "dangerous" is consistent with pharmacological mechanism and class-level data, but no published human case reports of 2C-D + tramadol interactions were found. This value is based on mechanistic inference from the interaction pharmacology.
### Cannabis: Unknown
The seed data lists cannabis as "unknown" interaction. No published data on 2C-D + cannabis interactions were identified. Given that cannabis can amplify psychedelic intensity and increase anxiety risk through CB₁ mechanisms, this combination warrants caution but published evidence is absent. The "unknown" classification is appropriate.
### MAO Inhibitors
While not listed in the seed data's interaction table, 2C-D's own MAO inhibitory potential (Wagmann et al. 2019 [Ref 2]) means that:
- Combining 2C-D with classical MAOIs would risk dangerous serotonin toxicity
- Combining 2C-D with other serotonergic NPS is higher risk than for compounds without MAO inhibition
This interaction class is documented for the broader 2C-series in Rached et al. (2026 [Ref 10]).
### Serotonin Syndrome Risk Profile
2C-series drugs (including 2C-I) have been specifically documented in serotonin syndrome case reports in combination with other serotonergic agents (Schifano et al. 2021 [Ref 18]). 2C-D carries the same mechanistic risk.
---
## Legal Status
| Jurisdiction | Status | Details | Date |
|---|---|---|---|
| United States | **Schedule I** | Synthetic Drug Abuse Prevention Act of 2012 (FDASIA, P.L. 112-144); 2C-D explicitly listed by name | July 9, 2012 [Ref 23] |
| United Kingdom | **Class A, Schedule 1** | Misuse of Drugs Act 2002 amendment; all PiHKAL compounds (phenethylamines including 2C-D) classified | 2002 [Ref 13] |
| Canada | **Schedule III** | Listed under the Controlled Drugs and Substances Act | October 31, 2016 [Ref 13] |
| Australia | **Prohibited** | Blanket prohibition on substituted phenethylamines; analog scheduling | [Ref 13] |
**⚠️ FLAG:** The European Union country-by-country status was not fully established in this research. The web search indicated that 2C-D is controlled across most EU jurisdictions, but specific country schedules and dates were not confirmed from primary legal sources. The generation agent should flag this for editorial verification.
**⚠️ FLAG:** The Wikidoc article (consulted for chemical data) lists 2C-D's US status as "unscheduled" — this is demonstrably **incorrect** and reflects an outdated article predating 2012 scheduling. The confirmed Schedule I status from FDASIA 2012 should be used [Ref 23].
---
## Clinical Trials
**No clinical trials involving 2C-D were identified** on ClinicalTrials.gov. A search for "2C-D phenethylamine psychedelic" returned zero results. 2C-D has not been studied in any registered clinical trial.
---
## Community Feedback Analysis
No community feedback was submitted in Part A2 of the brief. This section is not applicable to the current research cycle.
---
## Gaps & Flags
### Critical Gaps (Safety-Relevant)
1. **Receptor binding Ki/EC₅₀ for 2C-D:** Eshleman et al. (2014 [Ref 1]) contains these values in table form but they were not accessible from the abstract. The exact Ki at 5-HT₂A, 5-HT₂C, and other targets is unpublished in accessible form. ⚠️ **Safety-critical value not directly confirmed.**
2. **Specific MAO IC₅₀ for 2C-D:** Wagmann et al. (2019 [Ref 2]) tested 2C-D but compound-specific values are in tables not accessible from the abstract. ⚠️ **Safety-relevant.**
3. **LD₅₀ / toxic dose:** No published data. Seed data's "toxic dose is unknown" is confirmed. ⚠️ **Safety-critical gap — flag for generation agent.**
4. **Human pharmacokinetics:** No published PK data for 2C-D (half-life, Tmax, bioavailability, CYP involvement). This is a significant gap for harm reduction content.
5. **Tramadol interaction severity:** Labeled "dangerous" in seed data; supported by mechanism but no 2C-D-specific case reports found. ⚠️ **Flag: mechanistic inference, not substance-specific case data.**
### Data Quality Issues
6. **Duration discrepancy:** PIHKAL [Ref 12] reports 4–6 hours total duration; seed data states 3–5 hours. PIHKAL is the primary bioassay source. Recommend editorial review and potential update to 4–6 hours. The onset/come-up/peak/offset breakdown in seed data may need adjustment accordingly.
7. **Dose range discrepancy:** PIHKAL gives 20–60 mg as the active range (with 150 mg as upper extreme). Seed data has common 25–50 mg, strong 50–100 mg, heavy 100+. The PIHKAL range and the seed data's common range are partially concordant, but the seed data's strong (50–100 mg) and heavy (100+ mg) ranges extend well beyond Shulgin's primary documented range. These higher ranges are user-report-derived, not controlled study-derived. ⚠️ **Flag: high-dose ranges lack primary source confirmation.**
8. **CAS number ambiguity:** Two CAS numbers found — 25505-65-1 (Cayman, HCl salt) and 24333-19-5 (Wikidoc, possibly free base). Neither the free-base CAS nor the HCl CAS was confirmed as primary via PubChem API. Recommend using PubChem CID 135740 as the definitive chemical identifier.
9. **Legal status (EU):** Specific EU country-by-country scheduling was not confirmed from primary legal databases.
### Structural Analogy/Inference Areas
10. **Metabolism pathway:** No 2C-D-specific metabolism studies found. Metabolic pathway (O-demethylation, MAO deamination, potential CYP involvement) inferred from class-level evidence (Dean et al. 2013 [Ref 6]; Wagmann et al. 2019 [Ref 2]).
11. **Tolerance reset period (7 days):** Supported by psychedelic class data (de la Fuente Revenga et al. 2022 [Ref 16]) but not confirmed specifically for 2C-D.
12. **Subjective effects taxonomy:** The full effects list (synesthesia, visual recursion, symmetrical texture repetition, visual diffraction, etc.) reflects class-level psychedelic taxonomy and Shulgin's bioassay descriptions, not controlled clinical data for 2C-D specifically. All should be labeled as such.
13. **Contraindications:** No published contraindications specific to 2C-D were found. Class-level contraindications (personal/family history of psychosis, cardiovascular disease, MAOI use, pregnancy) apply by structural analogy and mechanism.
### History
14. **Shulgin/Carter 1975 paper:** Referenced in secondary sources but the original 1975 paper by Shulgin and Carter describing 2C-D human effects was not located via PubMed or OpenAlex. It may be a conference paper, unpublished report, or appear in a non-indexed journal. Cannot be directly cited.
15. **Ho et al. 1970 paper:** First described 2C-D synthesis in scientific literature; not located via PubMed. Pre-digital era paper likely not indexed in searchable databases. Cannot be directly cited.