3-MeO-PCP

Multiple fatal cases involved amphetamine co-ingestionsupported

Also diphenhydramine (4.1 mg/L), amphetamine (<0.10 mg/L). Death: combined toxicity. bkw056

3-MeO-PCP is metabolized by CYP2D6, CYP2C19, CYP2B6, and CYP3A4supported

CYP3A4, CYP2D6, CYP2C19 as primary metabolic enzymes. s00204-025-04283-x

Paroxetine and bupropion were co-present in one fatal polysubstance case, though causality cannot be established from a single observation.supported

second for ethanol, bupropion, delorazepam, paroxetine, mitragynine. bkx048

Published postmortem blood concentrations in fatal intoxications span a wide range: approximately 50–3,525 ng/mL (0.05–3.5 mg/L)supported

Fatal 3-MeO-PCP case. Femoral blood: 3525 ng/mL. 20961790.2021.1928821

Copeland et al. reviewed 16 published fatalities as of 2022 and concluded that blood concentrations associated with toxicity and death "remain unclear"supported

First UK fatal case. 15 prior fatal intoxication reports. bkac015

Claim in safety — inconclusiveinconclusiveworking →

In silico estimates from Noga and Jurowski predict rat oral LD₅₀ of approximately 200–630 mg/kg (EPA Category III, moderate acute toxicity) and mouse IV LD₅₀ of approximately 25–59 mg/kgsupported

Rat oral LD50 estimates: ~200-630 mg/kg; mouse IV LD50 ~25-59 mg/kg. Moderate acute oral toxicity (EPA Category III). s00204-025-04242-6

In silico hERG channel inhibition is predicted with IC₅₀ of approximately 4.9–12.3 µM, indicating QT-prolongation risksupported

hERG IC50 ~4.9-12.3 µM (QT-prolongation risk). s00204-025-04242-6

Copeland et al. specifically cautioned against use in exercise or "club drug" settings where elevated heart rate, body temperature, and blood pressure may exacerbate cardiovascular toxicity.supported

Exercise may exacerbate toxicity via elevated HR, body temperature, blood pressure. bkac015

In silico modeling predicts primary organ targets as lung (probability 0.89–0.93), liver (up to 0.91), and blood (up to 0.85), with gastrointestinal involvement also predicted (up to 0.82)partially supported

Organ targets: lungs (0.89-0.93), liver (up to 0.91), blood (up to 0.85). s00204-025-04242-6

Consistent features across published intoxication case reports include coma (Glasgow Coma Scale 3 in severe cases), agitation and delirium during recovery, respiratory acidosis and respiratory depression, hypothermia, mydriasis (including unilateral anisocoria), visual hallucinations and psychosis, and behavioral disinhibition.supported

Glasgow score 3, respiratory acidosis, mydriasis, hypothermia. j.forsciint.2016.12.028

Consistent features across published intoxication case reports include coma (Glasgow Coma Scale 3 in severe cases), agitation and delirium during recovery, respiratory acidosis and respiratory depression, hypothermia, mydriasis (including unilateral anisocoria), visual hallucinations and psychosis, and behavioral disinhibition.supported

Two cases of 3-MeO-PCP intoxication in same patient with literature review. Severe intoxication manifestations characterized. md.0000000000018295

Consistent features across published intoxication case reports include coma (Glasgow Coma Scale 3 in severe cases), agitation and delirium during recovery, respiratory acidosis and respiratory depression, hypothermia, mydriasis (including unilateral anisocoria), visual hallucinations and psychosis, and behavioral disinhibition.supported

Glasgow score 3, respiratory acidosis, mydriasis, hypothermia. j.forsciint.2016.12.028

Consistent features across published intoxication case reports include coma (Glasgow Coma Scale 3 in severe cases), agitation and delirium during recovery, respiratory acidosis and respiratory depression, hypothermia, mydriasis (including unilateral anisocoria), visual hallucinations and psychosis, and behavioral disinhibition.supported

Glasgow score 3, respiratory acidosis, mydriasis, hypothermia. j.forsciint.2016.12.028

Consistent features across published intoxication case reports include coma (Glasgow Coma Scale 3 in severe cases), agitation and delirium during recovery, respiratory acidosis and respiratory depression, hypothermia, mydriasis (including unilateral anisocoria), visual hallucinations and psychosis, and behavioral disinhibition.supported

Clinical and laboratory data of two non-fatal 3-MeO-PCP intoxication cases. bkx009

Claim in safety — inconclusiveinconclusiveworking →

Claim in safety — inconclusiveinconclusiveworking →

LC-MS/MS is required for analytical confirmation — standard immunoassays are unreliable.supported

3-MeO-PCP showed 1-143% cross-reactivity in all PCP IAs tested. bkz026

Multiple fatal cases involved amphetamine co-ingestionsupported

Polysubstance: 3-MeO-PCP + amphetamine + alcohol. j.jflm.2019.05.011

Substance-induced psychotic disorder (SIP) with persistent symptoms after cessation has been documented: Pepe et al. described a 29-year-old male who developed psychosis with cognitive impairment after small oral doses over two weeks followed by high-dose ingestionsupported

case of 29-year-old man with substance-induced psychotic disorder after small oral doses over 2 weeks then high-dose ingestion. ph17040452

Psychotic symptoms including paranoia, delusions, and hallucinations are documented across multiple case reports.supported

Severe intoxication manifestations characterized. md.0000000000018295

Psychotic symptoms including paranoia, delusions, and hallucinations are documented across multiple case reports.supported

substance-induced psychotic disorder after small oral doses over 2 weeks then high-dose ingestion. ph17040452

Mania-like presentations — characterized by grandiosity, agitation, pressured behavior, and disinhibition — occur at moderate-to-high dosessupported

Severe intoxication manifestations characterized. md.0000000000018295

Mania-like presentations — characterized by grandiosity, agitation, pressured behavior, and disinhibition — occur at moderate-to-high dosessupported

Literature review of 3-MeO-PCP mechanisms and effects. ph17040452

Amnesia is reported, which complicates self-assessment of dose and behavioral risk during the experience.supported

Severe intoxication manifestations characterized. md.0000000000018295

Alcohol co-ingestion features in multiple fatal and non-fatal intoxication casessupported

Two young men brought to hospital comatose after 3-MeO-PCP + alcohol. j.forsciint.2016.12.028

Alcohol co-ingestion features in multiple fatal and non-fatal intoxication casessupported

Polysubstance: 3-MeO-PCP + amphetamine + alcohol. j.jflm.2019.05.011

Synergistic CNS and respiratory depression is the primary mechanism of harm. Opioids present extreme risk: Castro et al. documented a fatality from combined 3-MeO-PCP and O-desmethyltramadol (the active opioid metabolite of tramadol), with additive respiratory depression as the probable mechanism. Benzodiazepines appeared in one fatal polysubstance case (delorazepam); while benzodiazepines are used therapeutically for 3-MeO-PCP-induced agitation, unsupervised combination carries respiratory depression risk.supported

Male found unresponsive; death attributed to combined 3-MeO-PCP and O-desmethyltramadol (opioid). Illustrates danger of combining dissociatives with opioids. s00414-022-02818-w

Synergistic CNS and respiratory depression is the primary mechanism of harm. Opioids present extreme risk: Castro et al. documented a fatality from combined 3-MeO-PCP and O-desmethyltramadol (the active opioid metabolite of tramadol), with additive respiratory depression as the probable mechanism. Benzodiazepines appeared in one fatal polysubstance case (delorazepam); while benzodiazepines are used therapeutically for 3-MeO-PCP-induced agitation, unsupervised combination carries respiratory depression risk.supported

second for ethanol, bupropion, delorazepam, paroxetine, mitragynine. bkx048

No published case reports document serotonin syndrome from 3-MeO-PCP combinations, but the mechanism is pharmacologically plausible.supported

PCP analogues exhibited high affinities for sigma receptors and serotonin transporter. journal.pone.0059334

3-MeO-PCP is metabolized by CYP2D6, CYP2C19, CYP2B6, and CYP3A4partially supported

CYP2B6 responsible for aliphatic hydroxylations; CYP2C19 and CYP2D6 for O-demethylation. 1570159x14666161018151716

Copeland et al. cautioned that physical activity may exacerbate 3-MeO-PCP cardiovascular toxicity through elevated heart rate, body temperature, and blood pressure.supported

Exercise may exacerbate toxicity via elevated HR, body temperature, blood pressure. bkac015

In silico hERG inhibition predicts QT-prolongation risksupported

hERG IC50 ~4.9-12.3 µM (QT-prolongation risk). s00204-025-04242-6

Psychotic disorders and bipolar disorder: 3-MeO-PCP reliably produces psychotomimetic effects and has triggered persistent substance-induced psychotic disordersupported

case of 29-year-old man with substance-induced psychotic disorder after small oral doses over 2 weeks then high-dose ingestion. ph17040452

Hepatic impairment: Hepatic metabolism via CYP2D6, CYP2C19, and CYP2B6 is the primary elimination pathwaysupported

CYP2B6 responsible for aliphatic hydroxylations; CYP2C19 and CYP2D6 for O-demethylation. 1570159x14666161018151716

3-MeO-PCP acts as a non-competitive, open-channel blocker of NMDA receptors at the PCP/dizocilpine (MK-801) binding sitesupported

3-MeO-PCP confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. journal.pone.0059334

With a Ki of 20 nM, it ranks among the most potent NMDA antagonists characterized, exceeded only by dizocilpine (MK-801, Ki = 4.8 nM) and surpassing the parent compound PCPsupported

3-MeO-PCP confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. journal.pone.0059334

Secondary pharmacological activity includes sigma-1 receptor agonism (Ki = 42 nM), which may contribute to psychotomimetic, analgesic, and stimulant-like properties, and moderate serotonin transporter (SERT) inhibition (Ki = 216 nM), which introduces serotonergic activity relevant to both subjective effects and drug interaction risk.supported

PCP analogues exhibited high affinities for sigma receptors and serotonin transporter. journal.pone.0059334

NMDA receptor inhibition has been independently confirmed using a high-throughput drebrin immunocytochemical assay.supported

High-throughput NMDAR inhibition assay using drebrin as a postsynaptic density marker. Tested phencyclidine analogues including 3-MeO-PCP for NMDAR inhibitory activity. j.vascn.2019.106583

Absorption and distribution: In silico ADME modeling predicts high passive permeability, high gastrointestinal absorption, ready blood-brain barrier penetration, approximately 70–80% plasma protein binding, and a large volume of distribution consistent with extensive tissue partitioning.supported

High passive permeability, high GI absorption, BBB penetrant. Plasma protein binding ~70-80%. Large apparent Vd. s00204-025-04283-x

Metabolism: Metabolic pathways were characterized in rat urine and pooled human liver microsomes by Michely et al.supported

Metabolic fate of 3-MeO-PCP elucidated in rat urine and pooled human liver microsomes. 1570159x14666161018151716

CYP3A4 is also implicatedsupported

CYP3A4, CYP2D6, CYP2C19 as primary metabolic enzymes. s00204-025-04283-x

Key metabolites identified include O-demethyl-3-MeO-PCP, piperidine-OH-3-MeO-PCP, O-demethyl-piperidine-di-OH-3-MeO-PCP, and piperidine-di-OH-3-MeO-PCP.supported

Multiple aliphatic hydroxylations, aromatic hydroxylation, O-demethylation, and glucuronidation identified. 1570159x14666161018151716

Key metabolites identified include O-demethyl-3-MeO-PCP, piperidine-OH-3-MeO-PCP, O-demethyl-piperidine-di-OH-3-MeO-PCP, and piperidine-di-OH-3-MeO-PCP.supported

6 metabolites identified including O-demethyl-3-MeO-PCP. 20961790.2021.1928821

Key metabolites identified include O-demethyl-3-MeO-PCP, piperidine-OH-3-MeO-PCP, O-demethyl-piperidine-di-OH-3-MeO-PCP, and piperidine-di-OH-3-MeO-PCP.supported

metabolites O-demethyl-3-MeO-PCP, piperidine-OH-3-MeO-PCP, and di-OH forms identified. bky097

Poor metabolizers at either locus may experience impaired clearance and elevated plasma concentrations, though this has not been clinically characterized for 3-MeO-PCP.supported

CYP2C19 and CYP2D6 for O-demethylation. 1570159x14666161018151716

Claim in pharmacology — inconclusiveinconclusiveworking →

Forensic detection: Metabolite-to-parent ratios in both blood and urine are consistently below 1.0, meaning metabolite testing does not meaningfully extend the detection window beyond the parent compound.supported

Metabolite:parent ratio always <1. bky097

Forensic detection: Metabolite-to-parent ratios in both blood and urine are consistently below 1.0, meaning metabolite testing does not meaningfully extend the detection window beyond the parent compound.supported

Metabolite:parent ratio <1, so metabolite testing does not extend detection window. 20961790.2021.1928821

This interaction has not been studied clinically but is supported by the observation that paroxetine (a potent CYP2D6 inhibitor) was co-present in one fatal polysubstance case.supported

second for ethanol, bupropion, delorazepam, paroxetine, mitragynine. bkx048

All values below derive from in silico modelingsupported

In silico ADME profiling of 3-MeO-PCP and 4-MeO-PCP. s00204-025-04283-x

Michely et al. characterized metabolic pathways using rat urine and pooled human liver microsomes:supported

Metabolic fate of 3-MeO-PCP elucidated in rat urine and pooled human liver microsomes. 1570159x14666161018151716

Phase II conjugation proceeds via glucuronidation.supported

Multiple aliphatic hydroxylations, aromatic hydroxylation, O-demethylation, and glucuronidation identified. 1570159x14666161018151716

Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

Strong CYP2D6 inhibitors (paroxetine, fluoxetine, bupropion) and CYP2C19 inhibitors (omeprazole, fluvoxamine) may impair 3-MeO-PCP metabolism and elevate plasma concentrationssupported

CYP2C19 and CYP2D6 for O-demethylation. 1570159x14666161018151716

Metabolite-to-parent ratios in both blood and urine are consistently below 1.0supported

Metabolite:parent ratio always <1. bky097

Metabolite-to-parent ratios in both blood and urine are consistently below 1.0supported

Metabolite:parent ratio <1, so metabolite testing does not extend detection window. 20961790.2021.1928821

3-MeO-PCP cross-reacts with commercial PCP immunoassays at rates of 1–143% across five tested assayssupported

3-MeO-PCP showed 1-143% cross-reactivity in all PCP IAs tested. bkz026

LC-MS/MS is the recommended confirmatory methodpartially supported

GC-MS method developed for quantification. bkx048

LC-MS/MS is the recommended confirmatory methodsupported

LC-MS/MS method validated. j.forsciint.2016.12.028

By mid-decade, 3-MeO-PCP had become one of the most widely distributed novel dissociative substances, with fatal and non-fatal intoxication cases reported across Sweden, Italy, France, the Netherlands, the United Kingdom, and the United States.supported

Sweden: 7 deaths + 1 non-fatal intoxication involving 3-MeO-PCP (March 2014 to June 2016). j.forsciint.2017.02.034

By mid-decade, 3-MeO-PCP had become one of the most widely distributed novel dissociative substances, with fatal and non-fatal intoxication cases reported across Sweden, Italy, France, the Netherlands, the United Kingdom, and the United States.supported

3-MeO-PCP intoxication in two young men: First in vivo detection in Italy. j.forsciint.2016.12.028

By mid-decade, 3-MeO-PCP had become one of the most widely distributed novel dissociative substances, with fatal and non-fatal intoxication cases reported across Sweden, Italy, France, the Netherlands, the United Kingdom, and the United States.supported

First two death cases in Washington State involving 3-MeO-PCP. bkx048

By mid-decade, 3-MeO-PCP had become one of the most widely distributed novel dissociative substances, with fatal and non-fatal intoxication cases reported across Sweden, Italy, France, the Netherlands, the United Kingdom, and the United States.supported

First fatal case in Netherlands. Postmortem blood concentration: 152 µg/L 3-MeO-PCP. j.jflm.2019.05.011

Claim in history — inconclusiveinconclusiveworking →

3-MeO-PCP entered the grey-market research chemical supply approximately in 2010, with broad internet availability beginning in 2011partially supported

3-MeO-PCP appeared on illicit drug market in 2011. j.forsciint.2017.02.034

Claim in history — not_supportednot supportedworking →

The landmark — and to date only comprehensive — receptor binding study was published in 2013 by Roth and colleagues, who screened 3-MeO-PCP against 57 CNS molecular targets through the NIMH Psychoactive Drug Screening Program (PDSP)supported

Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP. journal.pone.0059334

Metabolic pathways were subsequently characterized by Michely et al. using rat urine and pooled human liver microsomes in 2017.supported

Metabolic fate of 3-MeO-PCP elucidated in rat urine and pooled human liver microsomes. 1570159x14666161018151716

3-Methoxyphencyclidine (3-MeO-PCP) is a synthetic dissociative of the arylcyclohexylamine class, distinguished by exceptional potency at the NMDA receptor (Ki = 20 nM) — placing it among the most potent NMDA antagonists characterized to date and exceeding the parent compound phencyclidinesupported

3-MeO-PCP confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. journal.pone.0059334

First synthesized in 1979 by Geneste and colleagues during a structure-activity study of phencyclidine derivatives, 3-MeO-PCP remained an obscure research compound for three decades before appearing on the grey-market research chemical scene around 2010supported

3-MeO-PCP appeared on illicit drug market in 2011. j.forsciint.2017.02.034

Regulatory scheduling culminated in UN Schedule II placement in 2021 and US DEA Schedule I in 2026.supported

3-MeO-PCP added to UN 1971 Convention Schedule II in April 2021. bkac015

3-MeO-PCP acts as a non-competitive, open-channel blocker at the PCP/dizocilpine site of the NMDA receptor (Ki = 20 nM), with secondary sigma-1 receptor agonism (Ki = 42 nM) and moderate serotonin transporter inhibition (Ki = 216 nM)supported

3-MeO-PCP confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. PCP analogues exhibited high affinities for sigma receptors and serotonin transporter. journal.pone.0059334

Case reports describe a dissociative-psychotomimetic profile: confusion, visual and auditory hallucinations, agitation, mania-like disinhibition, and at higher doses, coma (Glasgow Coma Scale 3)supported

Two cases of 3-MeO-PCP intoxication in same patient with literature review. Severe intoxication manifestations characterized. md.0000000000018295

Case reports describe a dissociative-psychotomimetic profile: confusion, visual and auditory hallucinations, agitation, mania-like disinhibition, and at higher doses, coma (Glasgow Coma Scale 3)supported

Two young men brought to hospital comatose after 3-MeO-PCP + alcohol. Glasgow score 3, respiratory acidosis, mydriasis, hypothermia. j.forsciint.2016.12.028

Multiple fatalities are documented, with postmortem blood concentrations spanning 50–3,525 ng/mL; nearly all cases involve polysubstance usesupported

Fatal 3-MeO-PCP case. Femoral blood: 3525 ng/mL. 20961790.2021.1928821

Multiple fatalities are documented, with postmortem blood concentrations spanning 50–3,525 ng/mL; nearly all cases involve polysubstance usesupported

First UK fatal case. 15 prior fatal intoxication reports. bkac015

In silico modeling predicts cardiotoxicity via hERG inhibition (IC₅₀ ~4.9–12.3 µM) and organ toxicity targeting lungs, liver, and bloodsupported

hERG IC50 ~4.9-12.3 µM (QT-prolongation risk). Organ targets: lungs (0.89-0.93), liver (up to 0.91), blood (up to 0.85). s00204-025-04242-6

3-MeO-PCP and its parent compound PCP share the arylcyclohexylamine scaffold and the same primary mechanism — non-competitive NMDA receptor antagonism at the PCP/MK-801 binding site. 3-MeO-PCP displays higher NMDA receptor affinity (Ki = 20 nM) compared to PCP (Ki ≈ 60 nM), consistent with user reports describing 3-MeO-PCP as active at lower dosessupported

3-MeO-PCP confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. journal.pone.0059334

A key pharmacological difference is 3-MeO-PCP's sigma-1 receptor agonism (Ki = 42 nM) and moderate SERT inhibition (Ki = 216 nM), which may account for its reportedly more stimulant-like and serotonergically modulated subjective profile compared to PCP.supported

PCP analogues exhibited high affinities for sigma receptors and serotonin transporter. journal.pone.0059334

Roth et al. reported ketamine NMDA Ki values in the range of approximately 500–3,000 nM depending on preparation, compared to 20 nM for 3-MeO-PCP — an approximately 25–150-fold difference in binding affinitysupported

Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP. journal.pone.0059334

Methoxetamine (MXE), another arylcyclohexylamine screened alongside 3-MeO-PCP by Roth et al., showed NMDA Ki of approximately 260 nM — roughly 13-fold less potent than 3-MeO-PCP at the NMDA receptor.supported

The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor. journal.pone.0059334

The definitive receptor binding characterization was performed by Roth et al. using the NIMH Psychoactive Drug Screening Program (PDSP), screening 3-MeO-PCP against 57 CNS molecular targets:supported

Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP. journal.pone.0059334

Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

Copeland et al. reviewed 16 total published fatalities as of 2022 and concluded that blood concentrations associated with toxicity and death "remain unclear"supported

First UK fatal case. 15 prior fatal intoxication reports. bkac015

Claim in clinical-evidence — inconclusiveinconclusiveworking →

Pepe et al. reported FDG PET/CT imaging of a 29-year-old male who developed substance-induced psychotic disorder after repeated oral 3-MeO-PCP administration over two weeks, followed by a high-dose ingestionsupported

case of 29-year-old man with substance-induced psychotic disorder after small oral doses over 2 weeks then high-dose ingestion. FDG PET/CT brain imaging used to characterize neural substrates. ph17040452

The sigma-1 receptor agonism (Ki = 42 nM) may modulate NMDA receptor function allosterically and contribute to neuroplasticity and neuroprotective signaling, though the behavioral significance of sigma-1 activation at this occupancy level — independent of NMDA antagonism — is uncertain.supported

PCP analogues exhibited high affinities for sigma receptors. journal.pone.0059334

A single case of FDG PET/CT imaging during 3-MeO-PCP-induced psychotic disorder was published by Pepe et al.supported

FDG PET/CT brain imaging used to characterize neural substrates. ph17040452

The observation that 3-MeO-PCP can produce persistent psychotic symptoms after cessation supports the view that sustained NMDA hypofunction may trigger lasting changes in glutamatergic circuit function.supported

substance-induced psychotic disorder after small oral doses over 2 weeks then high-dose ingestion. ph17040452

Claim in chemistry — inconclusiveinconclusiveworking →

Chemical identity confirmed via PubChem; CAS numbers confirmed by Jurowski et al. and Gomila et al..supported

ADME profile of phencyclidine (PCP) analogues: emerging dissociative hallucinogens 3-MeO-PCP (CAS: 72242-03-6) and 4-MeO-PCP. s00204-025-04283-x

Compared to PCP, the subjective effects are qualitatively similar but achieved at lower doses owing to 3-MeO-PCP's higher NMDA receptor affinity (Ki = 20 nM vs. ~60 nM)supported

3-MeO-PCP confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. journal.pone.0059334