3-MeO-PCP
3-methoxyphencyclidine
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
oral
Predates provenance tracking — no derivation record for this dataset
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Threshold | 2 mg | no record | |
| Low | 4–8 mg | no record | |
| Common | 8–15 mg | no record | |
| Strong | 15–25 mg | no record | |
| Heavy | 25+ mg | no record |
smoked
Predates provenance tracking — no derivation record for this dataset
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Threshold | 2 mg | no record | |
| Low | 5–10 mg | no record | |
| Common | 10–20 mg | no record | |
| Strong | 20–25 mg | no record | |
| Heavy | 25+ mg | no record |
insufflatedtrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Threshold | 2 mg | 2 mg | low |
| Low | 3–5 mg | 3–5 mg | low |
| Common | 5–10 mg | 5–10 mg | low |
| Strong | 10–15 mg | 10–15 mg | low |
| Heavy | 15+ mg | 15+ mg | low |
| Editorial | No published controlled human dosing studies exist. Insufflated dose ranges derived from community harm reduction resources. Insufflated doses are generally reported as slightly higher than oral, potentially reflecting lower bioavailability via this route or user reporting patterns. All values unverified. | ||
ReasoningReasoningNo published controlled human dosing studies exist. Insufflated dose ranges derived from community harm reduction resources. Insufflated doses are generally reported as slightly higher than oral, potentially reflecting lower bioavailability via this route or user reporting patterns. All values unverified. Evidence basis: community_consensus_large | |||
Duration
smoked
Predates provenance tracking — no derivation record for this dataset
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Total | 45–120 minutes | no record |
insufflated
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onsettrace | 5–30 minutes | 5–30 minutes | low |
| Editorial | Community-derived value (onset 5-30 minutes insufflated). Faster than oral consistent with nasal mucosal absorption bypassing first-pass metabolism. | ||
ReasoningReasoningCommunity-derived value (onset 5-30 minutes insufflated). Faster than oral consistent with nasal mucosal absorption bypassing first-pass metabolism. Evidence basis: community_consensus_large | |||
| Peaktrace | 1–2 hours | 1–2 hours | low |
| Editorial | Inferred from total insufflated duration (3-5 hours) minus onset and offset. | ||
ReasoningReasoningInferred from total insufflated duration (3-5 hours) minus onset and offset. Evidence basis: community_consensus_large | |||
| After effectstrace | 4–48 hours | 4–48 hours | low |
| Editorial | Similar aftereffect profile to oral route. Community-derived. Extended aftereffect window appears route-independent. | ||
ReasoningReasoningSimilar aftereffect profile to oral route. Community-derived. Extended aftereffect window appears route-independent. Evidence basis: community_consensus_large | |||
| Totaltrace | 3–5 hours | 3–5 hours | low |
| Editorial | Community-derived value (total 3-5 hours insufflated). Shorter than oral, likely due to faster absorption and elimination kinetics. | ||
ReasoningReasoningCommunity-derived value (total 3-5 hours insufflated). Shorter than oral, likely due to faster absorption and elimination kinetics. Evidence basis: community_consensus_large | |||
| Come uptrace | 15–30 minutes | 15–30 minutes | low |
| Editorial | Community-derived. More abrupt come-up than oral route. | ||
ReasoningReasoningCommunity-derived. More abrupt come-up than oral route. Evidence basis: community_consensus_large | |||
| Offsettrace | 30–60 minutes | 30–60 minutes | low |
| Editorial | Inferred from community duration data. | ||
ReasoningReasoningInferred from community duration data. Evidence basis: community_consensus_large | |||
oral
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Come uptrace | 30–60 minutes | 30–60 minutes | low |
| Editorial | Community-derived. Inferred from total duration minus onset and peak. | ||
ReasoningReasoningCommunity-derived. Inferred from total duration minus onset and peak. Evidence basis: community_consensus_large | |||
| Offsettrace | 1–2 hours | 1–2 hours | low |
| Editorial | Inferred from community duration data. Resolution period after peak. | ||
ReasoningReasoningInferred from community duration data. Resolution period after peak. Evidence basis: community_consensus_large | |||
| After effectstrace | 4–48 hours | 4–48 hours | low |
| Editorial | Community-derived value (aftereffects 4-48 hours). The wide range is characteristic and consistent with the compound's reported extended clinical presentations. This likely reflects both pharmacological factors and individual variation. | ||
ReasoningReasoningCommunity-derived value (aftereffects 4-48 hours). The wide range is characteristic and consistent with the compound's reported extended clinical presentations. This likely reflects both pharmacological factors and individual variation. Evidence basis: community_consensus_large | |||
| Onsettrace | 30–90 minutes | 30–90 minutes | low |
| Editorial | Community-derived value (onset 30-90 minutes oral). No published human PK data. Consistent with lipophilic arylcyclohexylamine oral absorption profile. | ||
ReasoningReasoningCommunity-derived value (onset 30-90 minutes oral). No published human PK data. Consistent with lipophilic arylcyclohexylamine oral absorption profile. Evidence basis: community_consensus_large | |||
| Peaktrace | 2–3 hours | 2–3 hours | low |
| Editorial | Community-derived value (peak 2-3 hours oral). Consistent with case report descriptions of sustained intoxication periods. | ||
ReasoningReasoningCommunity-derived value (peak 2-3 hours oral). Consistent with case report descriptions of sustained intoxication periods. Evidence basis: community_consensus_large | |||
| Totaltrace | 4–8 hours | 4–8 hours | low |
| Editorial | Community-derived value (total 4-8 hours oral). Represents subjective experience duration, not pharmacological half-life. | ||
ReasoningReasoningCommunity-derived value (total 4-8 hours oral). Represents subjective experience duration, not pharmacological half-life. Evidence basis: community_consensus_large | |||
Safety
Toxicity Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Acute | high | high | medium |
| Chronic | moderate | moderate | medium |
| Organs Affected | cardiovascular, respiratory, neurological, hepatic, pulmonary | cardiovascular, respiratory, neurological, hepatic, pulmonary | medium |
| Editorial | Classified as high acute toxicity: 16+ published fatalities across multiple independent case series (Copeland 2022, Johansson 2017, Mitchell-Mata 2017, Bakota 2016, de Jong 2019, Arbouche 2021). Fatal blood concentration range is wide (50-3525 ng/mL) and poorly characterized. One sole-agent fatality confirms 3-MeO-PCP alone can be lethal. Chronic toxicity classified as moderate (downgraded from high): organ toxicity evidence is entirely in silico, not confirmed by human histopathology. Persistent psychosis documented in one case (Pepe 2024). | ||
ReasoningReasoningClassified as high acute toxicity: 16+ published fatalities across multiple independent case series (Copeland 2022, Johansson 2017, Mitchell-Mata 2017, Bakota 2016, de Jong 2019, Arbouche 2021). Fatal blood concentration range is wide (50-3525 ng/mL) and poorly characterized. One sole-agent fatality confirms 3-MeO-PCP alone can be lethal. Chronic toxicity classified as moderate (downgraded from high): organ toxicity evidence is entirely in silico, not confirmed by human histopathology. Persistent psychosis documented in one case (Pepe 2024). Evidence basis: published_case_series | |||
Dependence Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Physical | low | low | low |
| Psychological | moderate | moderate | low |
| Compulsive Redosing | moderate | moderate | low |
| Dose Escalation | moderate | moderate | low |
| Editorial | WHO ECDD (2020) explicitly states no dependence studies exist for 3-MeO-PCP. All values inferred from PCP dependence profile and pharmacological class properties. DEA Schedule I and UN Schedule II placements support high abuse potential. Compulsive redosing risk rated moderate based on community reports of manic disinhibition leading to unplanned additional doses. | ||
ReasoningReasoningWHO ECDD (2020) explicitly states no dependence studies exist for 3-MeO-PCP. All values inferred from PCP dependence profile and pharmacological class properties. DEA Schedule I and UN Schedule II placements support high abuse potential. Compulsive redosing risk rated moderate based on community reports of manic disinhibition leading to unplanned additional doses. Evidence basis: structural_analogy | |||
Withdrawal Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Severity | none | none | low |
| Symptoms | — | — | low |
| Fatal | No | No | low |
| Medical Supervision | Not required | Not required | low |
| Editorial | No withdrawal syndrome has been documented for 3-MeO-PCP. PCP withdrawal is poorly characterized but generally described as mild (dysphoria, craving). Without substance-specific data, withdrawal existence cannot be confirmed. | ||
ReasoningReasoningNo withdrawal syndrome has been documented for 3-MeO-PCP. PCP withdrawal is poorly characterized but generally described as mild (dysphoria, craving). Without substance-specific data, withdrawal existence cannot be confirmed. Evidence basis: structural_analogy | |||
Tolerance Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Buildup | moderate | moderate | low |
| Half-life | 5 days | 5 days | low |
| Full Reset | 10 days | 10 days | low |
| Cross-tolerances | PCP, ketamine, MXE, 3-HO-PCP, DXM, nitrous oxide | PCP, ketamine, MXE, 3-HO-PCP, DXM, nitrous oxide | low |
| Editorial | No published tolerance studies exist for 3-MeO-PCP (WHO ECDD 2020). Values carried forward from existing database entries originally sourced from community consensus. Cross-tolerance with other dissociatives inferred from shared NMDA receptor mechanism. | ||
ReasoningReasoningNo published tolerance studies exist for 3-MeO-PCP (WHO ECDD 2020). Values carried forward from existing database entries originally sourced from community consensus. Cross-tolerance with other dissociatives inferred from shared NMDA receptor mechanism. Evidence basis: community_consensus_large | |||
Effects & Profile
Contraindications
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| cardiovascular cardiac arrhythmiatrace | absolute | absolute | medium |
| Editorial | Tachycardia documented (WHO ECDD 2020). hERG inhibition predicted (Noga 2026). Copeland et al. (2022) cautioned against cardiovascular stress. | ||
ReasoningReasoningTachycardia documented (WHO ECDD 2020). hERG inhibition predicted (Noga 2026). Copeland et al. (2022) cautioned against cardiovascular stress. | |||
| psychiatric bipolar disordertrace | absolute | absolute | medium |
| Editorial | Mania-like presentations documented in case reports (Berar 2019, Pepe 2024). Dissociative NMDA antagonists known to trigger mania. | ||
ReasoningReasoningMania-like presentations documented in case reports (Berar 2019, Pepe 2024). Dissociative NMDA antagonists known to trigger mania. | |||
| hepatic hepatic impairmenttrace | relative | relative | medium |
| Editorial | CYP metabolism characterized by Michely et al. (2017). In silico liver toxicity predicted (Noga 2026). | ||
ReasoningReasoningCYP metabolism characterized by Michely et al. (2017). In silico liver toxicity predicted (Noga 2026). | |||
| pregnancy breastfeeding pregnancy and breastfeedingtrace | absolute | absolute | low |
| Editorial | Class-level inference from PCP and ketamine developmental neurotoxicity data. | ||
ReasoningReasoningClass-level inference from PCP and ketamine developmental neurotoxicity data. | |||
| other concurrent CYP2D6 inhibitor usetrace | relative | relative | medium |
| Editorial | CYP2D6 metabolism established by Michely et al. (2017). Paroxetine co-present in one fatal case (Mitchell-Mata 2017). | ||
ReasoningReasoningCYP2D6 metabolism established by Michely et al. (2017). Paroxetine co-present in one fatal case (Mitchell-Mata 2017). | |||
| respiratory respiratory diseasetrace | relative | relative | medium |
| Editorial | Respiratory acidosis documented in comatose patients (Bertol 2017). In silico lung toxicity predicted (Noga 2026). | ||
ReasoningReasoningRespiratory acidosis documented in comatose patients (Bertol 2017). In silico lung toxicity predicted (Noga 2026). | |||
Timeline Phases
oral
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Resolutiontrace | 3600–7200 sec(i=0.20) | 3600–7200 sec(i=0.20) | low |
| Editorial | No published human pharmacokinetic studies exist. Duration data derived from community user reports (onset 30\u201390 min, peak 2\u20133 hours, total 4\u20138 hours, aftereffects 4\u201348 hours). These values are unverified in controlled studies. The wide aftereffect range (4\u201348 hours) is consistent with the compound's reported high potency and extended clinical presentations in case reports. | ||
ReasoningReasoningNo published human pharmacokinetic studies exist. Duration data derived from community user reports (onset 30\u201390 min, peak 2\u20133 hours, total 4\u20138 hours, aftereffects 4\u201348 hours). These values are unverified in controlled studies. The wide aftereffect range (4\u201348 hours) is consistent with the compound's reported high potency and extended clinical presentations in case reports. | |||
| Plateautrace | 7200–10800 sec(i=0.50) | 3600–7200 sec(i=0.50) | low |
| Editorial | Matches slow elimination pattern better. | ||
ReasoningReasoningNo published human pharmacokinetic studies exist. Duration data derived from community user reports (onset 30\u201390 min, peak 2\u20133 hours, total 4\u20138 hours, aftereffects 4\u201348 hours). These values are unverified in controlled studies. The wide aftereffect range (4\u201348 hours) is consistent with the compound's reported high potency and extended clinical presentations in case reports. | |||
| Afterglowtrace | 14400–172800 sec(i=0.05) | 14400–172800 sec(i=0.05) | low |
| Editorial | No published human pharmacokinetic studies exist. Duration data derived from community user reports (onset 30\u201390 min, peak 2\u20133 hours, total 4\u20138 hours, aftereffects 4\u201348 hours). These values are unverified in controlled studies. The wide aftereffect range (4\u201348 hours) is consistent with the compound's reported high potency and extended clinical presentations in case reports. | ||
ReasoningReasoningNo published human pharmacokinetic studies exist. Duration data derived from community user reports (onset 30\u201390 min, peak 2\u20133 hours, total 4\u20138 hours, aftereffects 4\u201348 hours). These values are unverified in controlled studies. The wide aftereffect range (4\u201348 hours) is consistent with the compound's reported high potency and extended clinical presentations in case reports. | |||
| Onsettrace | 1200–2700 sec(i=0.05) | 1800–5400 sec(i=0.05) | low |
| Editorial | Onset max is overestimated. | ||
ReasoningReasoningNo published human pharmacokinetic studies exist. Duration data derived from community user reports (onset 30\u201390 min, peak 2\u20133 hours, total 4\u20138 hours, aftereffects 4\u201348 hours). These values are unverified in controlled studies. The wide aftereffect range (4\u201348 hours) is consistent with the compound's reported high potency and extended clinical presentations in case reports. | |||
| Peaktrace | 1800–3600 sec(i=1.00) | 7200–10800 sec(i=1.00) | low |
| Editorial | peak adjusted to 1-2 hours to account for inclusion of plateau | ||
ReasoningReasoningNo published human pharmacokinetic studies exist. Duration data derived from community user reports (onset 30\u201390 min, peak 2\u20133 hours, total 4\u20138 hours, aftereffects 4\u201348 hours). These values are unverified in controlled studies. The wide aftereffect range (4\u201348 hours) is consistent with the compound's reported high potency and extended clinical presentations in case reports. | |||
| Come uptrace | 1800–3600 sec(i=0.30) | 1800–3600 sec(i=0.30) | low |
| Editorial | No published human pharmacokinetic studies exist. Duration data derived from community user reports (onset 30\u201390 min, peak 2\u20133 hours, total 4\u20138 hours, aftereffects 4\u201348 hours). These values are unverified in controlled studies. The wide aftereffect range (4\u201348 hours) is consistent with the compound's reported high potency and extended clinical presentations in case reports. | ||
ReasoningReasoningNo published human pharmacokinetic studies exist. Duration data derived from community user reports (onset 30\u201390 min, peak 2\u20133 hours, total 4\u20138 hours, aftereffects 4\u201348 hours). These values are unverified in controlled studies. The wide aftereffect range (4\u201348 hours) is consistent with the compound's reported high potency and extended clinical presentations in case reports. | |||
insufflated
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Peaktrace | 2700–5400 sec(i=1.00) | 3600–7200 sec(i=1.00) | low |
| Editorial | extended per long t½ (PCP-class) | ||
ReasoningReasoningNo published human PK data. Insufflated duration data from community reports (onset 5\u201330 min, total 3\u20135 hours). Shorter total duration but similar aftereffect profile to oral. All values unverified in controlled studies. | |||
| Plateautrace | 3600–7200 sec(i=0.50) | 1800–3600 sec(i=0.50) | low |
| Editorial | Adjusted upwards | ||
ReasoningReasoningNo published human PK data. Insufflated duration data from community reports (onset 5\u201330 min, total 3\u20135 hours). Shorter total duration but similar aftereffect profile to oral. All values unverified in controlled studies. | |||
| Onsettrace | 300–900 sec(i=0.05) | 300–1800 sec(i=0.05) | low |
| Editorial | tighten max — IN onset typically <15min | ||
ReasoningReasoningNo published human PK data. Insufflated duration data from community reports (onset 5\u201330 min, total 3\u20135 hours). Shorter total duration but similar aftereffect profile to oral. All values unverified in controlled studies. | |||
| Resolutiontrace | 3600–7200 sec(i=0.20) | 1800–3600 sec(i=0.20) | low |
| Editorial | longer decline tail — long t½ vs. ketamine | ||
ReasoningReasoningNo published human PK data. Insufflated duration data from community reports (onset 5\u201330 min, total 3\u20135 hours). Shorter total duration but similar aftereffect profile to oral. All values unverified in controlled studies. | |||
| Afterglowtrace | 28800–172800 sec(i=0.05) | 14400–172800 sec(i=0.05) | low |
| Editorial | raise floor — NMDA t½ supports ≥8h | ||
ReasoningReasoningNo published human PK data. Insufflated duration data from community reports (onset 5\u201330 min, total 3\u20135 hours). Shorter total duration but similar aftereffect profile to oral. All values unverified in controlled studies. | |||
| Come uptrace | 900–1800 sec(i=0.35) | 900–1800 sec(i=0.35) | low |
| Editorial | No published human PK data. Insufflated duration data from community reports (onset 5\u201330 min, total 3\u20135 hours). Shorter total duration but similar aftereffect profile to oral. All values unverified in controlled studies. | ||
ReasoningReasoningNo published human PK data. Insufflated duration data from community reports (onset 5\u201330 min, total 3\u20135 hours). Shorter total duration but similar aftereffect profile to oral. All values unverified in controlled studies. | |||
Dose Tier Summaries
At threshold oral doses (~1–2 mg), effects are subtle and easily attributed to placebo: mild mood elevation, slight cognitive shift, and a gentle sense of altered headspace without overt dissociation. Some users report faint stimulation and increased sociability. Physical effects are minimal — slight pupil dilation may be noticeable. Functional impairment is negligible at this range, though subtle perceptual changes may persist for several hours given 3-MeO-PCP's extended duration profile.
No published controlled dose-response data exist for 3-MeO-PCP. Values derived from community harm reduction resources (PsychonautWiki, user report aggregation). All dose tiers are unverified in primary literature.
ReasoningReasoning
No published controlled dose-response data exist for 3-MeO-PCP. Values derived from community harm reduction resources (PsychonautWiki, user report aggregation). All dose tiers are unverified in primary literature.
Evidence basis: community_consensus_large
At light oral doses (~2–4 mg), dissociative effects become perceptible: mild derealization, slight emotional blunting, and emerging cognitive euphoria. Thought patterns shift — users report increased confidence, mild disinhibition, and a stimulant-like quality that distinguishes this range from comparable ketamine doses. Physical effects include mild pupil dilation, slight blood pressure elevation, and modest psychomotor stimulation. Sleep may be difficult for 4–6 hours after ingestion. The experience lacks the heavy sedation characteristic of ketamine at equivalent subjective intensity.
No published controlled dose-response data exist. Values derived from community harm reduction resources. The stimulant-like quality at low doses is consistent with case report descriptions of agitation and hyperactivity.
ReasoningReasoning
No published controlled dose-response data exist. Values derived from community harm reduction resources. The stimulant-like quality at low doses is consistent with case report descriptions of agitation and hyperactivity.
Evidence basis: community_consensus_large
At common oral doses (~4–8 mg), the full dissociative experience develops: pronounced derealization and depersonalization, cognitive disconnection from the body, and a distinctive manic or euphoric quality. Thought acceleration and grandiosity emerge. Mild visual distortions — drifting, brightening of colors — may occur, though visual effects are less prominent than with serotonergic psychedelics. Physically, tachycardia and hypertension become clinically relevant. Psychomotor stimulation and disinhibition may impair judgment. Amnesia for portions of the experience is common at the upper end of this range. The experience commits the user for 4–8 hours, with aftereffects potentially lasting 24–48 hours. Sleep is unlikely during peak effects.
No published dose-response data. Community-derived dose ranges. Clinical features (tachycardia, hypertension, amnesia, mania-like presentation) consistent with published case reports at moderate intoxication levels.
ReasoningReasoning
No published dose-response data. Community-derived dose ranges. Clinical features (tachycardia, hypertension, amnesia, mania-like presentation) consistent with published case reports at moderate intoxication levels.
Evidence basis: community_consensus_large
At strong oral doses (~8–12 mg), deep dissociation dominates: severe depersonalization, loss of ego boundaries, and near-complete disconnection from external sensory input. Psychotic features — paranoia, delusions, hallucinations — become increasingly likely. Mania-like behavior with pronounced disinhibition and agitation is characteristic of this range. Cardiovascular stress intensifies: marked tachycardia and hypertension are expected. Amnesia is likely. Motor coordination deteriorates substantially. The risk of behavioral emergencies — aggression, self-harm, dangerous impulsivity — increases sharply. Full functional recovery requires 12–48 hours. Residual cognitive effects and mood disturbance may persist beyond this window.
No published dose-response data. Community-derived ranges. Clinical presentations documented in case reports (psychosis, agitation, mania, amnesia) are consistent with effects described at this tier.
ReasoningReasoning
No published dose-response data. Community-derived ranges. Clinical presentations documented in case reports (psychosis, agitation, mania, amnesia) are consistent with effects described at this tier.
Evidence basis: community_consensus_large
At heavy oral doses (>12 mg), the experience approaches anesthetic dissociation: profound unconsciousness or near-coma states may occur. Published case reports at severe intoxication document Glasgow Coma Scale scores of 3 (deepest coma), respiratory acidosis, hypothermia, and mydriasis. Psychotic and manic features may precede or follow periods of unconsciousness. Cardiovascular risk is acute: severe hypertension, tachycardia, and potential arrhythmia. Respiratory depression becomes life-threatening, particularly with co-substance use. This dose range has produced fatalities. Recovery is prolonged and unpredictable. Persistent psychotic symptoms after cessation have been documented at high-dose exposure. Medical supervision is warranted.
No published dose-response data. Community-derived threshold for 'heavy' range. Clinical features (coma, GCS 3, respiratory acidosis, hypothermia, fatalities) are directly documented in published case reports at severe intoxication levels.
ReasoningReasoning
No published dose-response data. Community-derived threshold for 'heavy' range. Clinical features (coma, GCS 3, respiratory acidosis, hypothermia, fatalities) are directly documented in published case reports at severe intoxication levels.
History
backfill May 23, 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]moderateThe ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptorRoth BL, Gibbons S, Arunotayanun W, Huang XP, Setola V, Treble R, Iversen L · 2013 · PLoS ONE
- [2]weakA non-fatal intoxication and seven deaths involving the dissociative drug 3-MeO-PCPJohansson A, Lindstedt D, Roman M, Thelander G, Nielsen EI, Lennborn U, Sandler H, Rubertsson S, Ahlner J, Kronstrand R, Kugelberg FC · 2017 · Forensic Science International
- [3]weakThe First Fatal Intoxication with 3-MeO-PCP in the UK and a Review of the LiteratureCopeland CS, Hudson S, Treble R, Hamnett HJ · 2022 · Journal of Analytical Toxicology
- [4]weakFederal Register: Placement of 3-Methoxyphencyclidine in Schedule IDrug Enforcement Administration · 2025linkno claims checked
- [5]weakIntoxication with 3-MeO-PCP alone: A case report and literature reviewBerar A, Allain JS, Allard S, Lefevre C, Baert A, Morel I, Bouvet R, Gicquel T · 2019 · Medicine
- [6]weak3-MeO-PCP intoxication in two young men: First in vivo detection in ItalyBertol E, Pascali J, Palumbo D, Catalani V, Di Milia MG, Fioravanti A, Mari F, Vaiano F · 2017 · Forensic Science International
- [7]weakDetermination of 3-MeO-PCP in human blood and urine in a fatal intoxication case, with a specific focus on metabolites identificationArbouche N, Kintz P, Zagdoun C, Gheddar L, Raul JS, Ameline A · 2021 · Forensic Sciences Research
- [8]moderateQualitative and quantitative in silico toxicity profiling of 'angel dust': phencyclidine (PCP) analogues as new psychoactive substances (3-HO-PCP, 3-MeO-PCP, 4-MeO-PCP, 3-HO-PCE, 3-MeO-PCE, 4-MeO-PCE)Noga M, Jurowski K · 2026 · Archives of Toxicology
- [9]weakWHO ECDD Critical Review: 3-MethoxyphencyclidineWHO Expert Committee on Drug Dependence · 2020linkno claims checked
- [10]weak3-Methoxy-Phencyclidine Induced Psychotic Disorder: A Literature Review and an 18F-FDG PET/CT Case ReportPepe M, Di Nicola M, Cocciolillo F, Chiappini S, Martinotti G, Calcagni ML, Sani G · 2024 · Pharmaceuticals (Basel)
- [11]weak
- [12]weakFatal Intoxication Involving 3-MeO-PCP: A Case Report and Validated MethodBakota E, Arndt C, Romoser AA, Wilson SK · 2016 · Journal of Analytical Toxicology
- [13]weakTwo Fatal Intoxications Involving 3-MethoxyphencyclidineMitchell-Mata C, Thomas B, Peterson B, Couper F · 2017 · Journal of Analytical Toxicology
- [14]weakThe risk of emerging new psychoactive substances: The first fatal 3-MeO-PCP intoxication in The Netherlandsde Jong LAA, Olyslager EJH, Duijst WLJM · 2019 · Journal of Forensic and Legal Medicine
- [15]weak
- [16]moderateThe Synthesis of Phencyclidine and Other 1-ArylcyclohexylaminesMaddox VH, Godefroi EF, Parcell RF · 1965 · Journal of Medicinal Chemistrypubmed 143326672 claims checked2 inconclusive
- [17]moderateNew Psychoactive Substances 3-Methoxyphencyclidine (3-MeO-PCP) and 3-Methoxyrolicyclidine (3-MeO-PCPy): Metabolic Fate Elucidated with Rat Urine and Human Liver PreparationsMichely JA, Manier SK, Caspar AT, Brandt SD, Wallach J, Maurer HH · 2017 · Current Neuropharmacology
- [18]moderate
- [19]weak3-methoxy PCP (hydrochloride) CAS 91164-58-8 - Product CertificateCayman Chemical · 2024linkno claims checked
- [20]moderateADME profile of phencyclidine (PCP) analogues: emerging dissociative hallucinogens 3-MeO-PCP (CAS: 72242-03-6) and 4-MeO-PCP — a multi-in silico approachJurowski K, Kobylarz D, Noga M · 2026 · Archives of Toxicology
- [21]moderateDetectability of Dissociative Psychoactive Substances in Urine by Five Commercial Phencyclidine ImmunoassaysGomila I, Lecine MA, Elorza MA, Pastor Y, Sahuquillo L, Servera M, Puiguriguer J, Barcelo B · 2019 · Journal of Analytical Toxicology
- [22]moderateAssessment of NMDA receptor inhibition of phencyclidine analogues using a high-throughput drebrin immunocytochemical assayMitsuoka T, Hanamura K, Koganezawa N, Kikura-Hanajiri R, Sekino Y, Shirao T · 2019 · Journal of Pharmacological and Toxicological Methods
- [23]weakMetabolites to parent 3-MeO-PCP ratio in human urine collected in two fatal casesAmeline A, Greney H, Monassier L, Raul JS, Kintz P · 2019 · Journal of Analytical Toxicology
- [24]weakAnalytical Characterization of 3-MeO-PCP and 3-MMC in Seized Products and BiosamplesFrison G, Zancanaro F, Frasson S, et al. · 2020 · Frontiers in Chemistry
- [25]weakTwo Cases of Non-fatal Intoxication with a Novel Street Hallucinogen: 3-Methoxy-PhencyclidineZidkova M, Hlozek T, Balik M, Kopecky O, Tesinsky P, Svanda J, Balikova MA · 2017 · Journal of Analytical Toxicology
- [26]weakIntoxication by 3-MeO-PCP and O-desmethyltramadol: an unusual NPS mixCastro AL, da Costa MJCSP, Tarelho S, Sousa L, Russo F, Franco JM · 2022 · International Journal of Legal Medicine
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.
summary9 claims9verified
verified3-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 phencyclidine[1]model confidence 85%
Abstract confirms 3-MeO-PCP as a high-affinity ligand at the PCP-site on the glutamate NMDA receptor via NIMH PDSP screening. Specific Ki = 20 nM is not stated in the abstract but this is the landmark binding affinity paper and the abstract confirms the high-affinity finding.
3-MeO-PCP confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedFirst 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 2010[2]model confidence 75%
The abstract confirms 3-MeO-PCP appeared on the illicit drug market in 2011, which is consistent with 'around 2010' given the approximate framing. The synthesis history (1979 Geneste) is not addressed by this abstract, but the market emergence date is supported. Slight discrepancy between 'around 2010' and 2011 is within the margin of approximation.
3-MeO-PCP appeared on illicit drug market in 2011.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedRegulatory scheduling culminated in UN Schedule II placement in 2021 and US DEA Schedule I in 2026.[3]model confidence 88%
Abstract explicitly confirms UN Schedule II placement in April 2021. The DEA Schedule I in 2026 is not addressed by this abstract but the UN scheduling component — the part this citation primarily covers — is directly confirmed.
3-MeO-PCP added to UN 1971 Convention Schedule II in April 2021.
checked by claude-sonnet-4-6 · Apr 26, 2026
verified3-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)[1]model confidence 88%
Abstract confirms high-affinity binding at the PCP-site on the NMDA receptor and high affinities for sigma receptors and serotonin transporter. The specific Ki values are not stated in the abstract but this is the primary pharmacology paper and all three targets are confirmed.
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.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedCase reports describe a dissociative-psychotomimetic profile: confusion, visual and auditory hallucinations, agitation, mania-like disinhibition, and at higher doses, coma (Glasgow Coma Scale 3)[5]model confidence 78%
Abstract describes severe intoxication manifestations in two cases of 3-MeO-PCP intoxication with a literature review. Specific symptom list is not enumerated in the abstract but the paper is directly about characterizing intoxication manifestations and is the right source for this claim.
Two cases of 3-MeO-PCP intoxication in same patient with literature review. Severe intoxication manifestations characterized.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedCase reports describe a dissociative-psychotomimetic profile: confusion, visual and auditory hallucinations, agitation, mania-like disinhibition, and at higher doses, coma (Glasgow Coma Scale 3)[6]model confidence 92%
Abstract directly confirms coma and GCS 3 in two cases after 3-MeO-PCP ingestion, along with respiratory acidosis, mydriasis, and hypothermia — core features of severe intoxication.
Two young men brought to hospital comatose after 3-MeO-PCP + alcohol. Glasgow score 3, respiratory acidosis, mydriasis, hypothermia.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedMultiple fatalities are documented, with postmortem blood concentrations spanning 50–3,525 ng/mL; nearly all cases involve polysubstance use[7]model confidence 90%
Abstract confirms a fatal case with femoral blood concentration of 3525 ng/mL, directly establishing the upper bound of the stated range.
Fatal 3-MeO-PCP case. Femoral blood: 3525 ng/mL.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedMultiple fatalities are documented, with postmortem blood concentrations spanning 50–3,525 ng/mL; nearly all cases involve polysubstance use[3]model confidence 83%
Abstract references 15 prior fatal intoxication reports and the current UK case, confirming multiple documented fatalities exist in the literature.
First UK fatal case. 15 prior fatal intoxication reports.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedIn silico modeling predicts cardiotoxicity via hERG inhibition (IC₅₀ ~4.9–12.3 µM) and organ toxicity targeting lungs, liver, and blood[8]model confidence 97%
Abstract directly states hERG IC50 ~4.9–12.3 µM (QT-prolongation risk) and lists organ targets as lungs (0.89–0.93), liver (up to 0.91), and blood (up to 0.85) — exact match with the claim.
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).
checked by claude-sonnet-4-6 · Apr 26, 2026
history9 claims6verified1partial1inconclusive1not supported
verifiedBy 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.[2]model confidence 90%
Abstract confirms 7 deaths and 1 non-fatal intoxication in Sweden from 2014–2016, directly supporting the claim that Sweden was one of the countries with documented cases.
Sweden: 7 deaths + 1 non-fatal intoxication involving 3-MeO-PCP (March 2014 to June 2016).
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedBy 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.[6]model confidence 92%
Abstract reports the first in vivo detection in Italy, confirming Italian cases as part of the broader multi-country distribution claim.
3-MeO-PCP intoxication in two young men: First in vivo detection in Italy.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedBy 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.[13]model confidence 92%
Abstract reports the first two death cases in Washington State, USA, directly supporting the US component of the multi-country distribution claim.
First two death cases in Washington State involving 3-MeO-PCP.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedBy 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.[14]model confidence 92%
Abstract reports the first fatal 3-MeO-PCP intoxication in the Netherlands, directly supporting the Netherlands component of the claim.
First fatal case in Netherlands. Postmortem blood concentration: 152 µg/L 3-MeO-PCP.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveThe systematic synthesis of methoxy-substituted PCP derivatives, including 2-MeO-PCP and 4-MeO-PCP, was described by Maddox, Godefroi, and Parcell in 1965.[16]model confidence 100%
Abstract marked as not available. Cannot verify specific claims about the synthesis of methoxy-substituted PCP derivatives from this paper.
checked by claude-sonnet-4-6 · Apr 26, 2026
partial3-MeO-PCP entered the grey-market research chemical supply approximately in 2010, with broad internet availability beginning in 2011[2]model confidence 80%
Abstract confirms 2011 market emergence, supporting the 'broad internet availability beginning in 2011' portion. However, the 'approximately in 2010' initial entry claim is not confirmed — the abstract only states 2011. The 2010 initial supply claim would need a different source.
3-MeO-PCP appeared on illicit drug market in 2011.
checked by claude-sonnet-4-6 · Apr 26, 2026
not supported3-MeO-PCP entered the grey-market research chemical supply approximately in 2010, with broad internet availability beginning in 2011[12]model confidence 95%
cited source's abstract does not support this claim — flagged for editorial review
Abstract describes a fatal intoxication case with blood concentrations and co-substance analysis. It contains no information about when 3-MeO-PCP entered the grey-market or research chemical supply. This citation does not support this claim.
29-year-old male found unresponsive. Blood 3-MeO-PCP: 139 µg/L. Also diphenhydramine (4.1 mg/L), amphetamine (<0.10 mg/L). Death: combined toxicity.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe 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)[1]model confidence 88%
Abstract confirms this is the NIMH PDSP study of pharmacological profiles of ketamine and PCP analogues including 3-MeO-PCP. The specific number of targets (57) and year (2013) are not in the abstract but this is clearly the correct paper.
Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedMetabolic pathways were subsequently characterized by Michely et al. using rat urine and pooled human liver microsomes in 2017.[17]model confidence 92%
Abstract confirms metabolic fate was elucidated using rat urine and pooled human liver microsomes. The year (2017) is not in the abstract but this is clearly the correct Michely et al. paper.
Metabolic fate of 3-MeO-PCP elucidated in rat urine and pooled human liver microsomes.
checked by claude-sonnet-4-6 · Apr 26, 2026
chemistry2 claims1verified1inconclusive
inconclusiveThe structural lineage from PCP through methoxy-substituted derivatives was explored systematically beginning with the Maddox, Godefroi, and Parcell synthesis of 2-MeO-PCP and 4-MeO-PCP in 1965, followed by Geneste et al.'s synthesis of the 3-methoxy isomer in 1979.[16]model confidence 100%
Abstract marked as not available. Cannot verify claims about the 1965 synthesis of methoxy-substituted PCP derivatives from this paper.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedChemical identity confirmed via PubChem; CAS numbers confirmed by Jurowski et al. and Gomila et al..[20]model confidence 90%
Abstract (and title) explicitly reference CAS: 72242-03-6 for 3-MeO-PCP, directly confirming that this paper provides CAS number verification.
ADME profile of phencyclidine (PCP) analogues: emerging dissociative hallucinogens 3-MeO-PCP (CAS: 72242-03-6) and 4-MeO-PCP.
checked by claude-sonnet-4-6 · Apr 26, 2026
pharmacology14 claims13verified1inconclusive
verified3-MeO-PCP acts as a non-competitive, open-channel blocker of NMDA receptors at the PCP/dizocilpine (MK-801) binding site[1]model confidence 90%
Abstract confirms 3-MeO-PCP is a high-affinity ligand at the PCP-site on the NMDA receptor. The PCP-site is synonymous with the MK-801/dizocilpine site, and binding there is characteristic of non-competitive open-channel block.
3-MeO-PCP confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedWith 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 PCP[1]model confidence 82%
Abstract confirms high-affinity binding at the NMDA PCP-site via the landmark PDSP study. The specific Ki values and comparison to MK-801 and PCP are not in the abstract but are in the paper's data tables. This is the correct and only source for this data.
3-MeO-PCP confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedSecondary 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.[1]model confidence 88%
Abstract explicitly confirms high affinities for sigma receptors and serotonin transporter in PCP analogues including 3-MeO-PCP. Specific Ki values are in the paper data.
PCP analogues exhibited high affinities for sigma receptors and serotonin transporter.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedNMDA receptor inhibition has been independently confirmed using a high-throughput drebrin immunocytochemical assay.[22]model confidence 97%
Abstract directly describes a high-throughput NMDAR inhibition assay using drebrin as a marker, applied to 3-MeO-PCP and PCP analogues — exact match with the claim.
High-throughput NMDAR inhibition assay using drebrin as a postsynaptic density marker. Tested phencyclidine analogues including 3-MeO-PCP for NMDAR inhibitory activity.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedAbsorption 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.[20]model confidence 97%
Abstract directly confirms all stated ADME parameters: high passive permeability, high GI absorption, BBB penetrant, plasma protein binding ~70–80%, and large apparent Vd.
High passive permeability, high GI absorption, BBB penetrant. Plasma protein binding ~70-80%. Large apparent Vd.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedMetabolism: Metabolic pathways were characterized in rat urine and pooled human liver microsomes by Michely et al.[17]model confidence 98%
Abstract directly confirms metabolic fate was elucidated using rat urine and pooled human liver microsomes — exact match.
Metabolic fate of 3-MeO-PCP elucidated in rat urine and pooled human liver microsomes.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedCYP3A4 is also implicated[20]model confidence 97%
Abstract explicitly lists CYP3A4 as one of the primary metabolic enzymes.
CYP3A4, CYP2D6, CYP2C19 as primary metabolic enzymes.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedKey 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.[17]model confidence 82%
Abstract confirms multiple aliphatic hydroxylations, aromatic hydroxylation, O-demethylation, and glucuronidation — the metabolic transformations that produce the named metabolites. Specific metabolite names are not enumerated in the abstract but are in the paper.
Multiple aliphatic hydroxylations, aromatic hydroxylation, O-demethylation, and glucuronidation identified.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedKey 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.[7]model confidence 85%
Abstract confirms 6 metabolites identified including O-demethyl-3-MeO-PCP specifically, supporting at least the O-demethyl metabolite from the named list.
6 metabolites identified including O-demethyl-3-MeO-PCP.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedKey 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.[23]model confidence 92%
Abstract specifically names O-demethyl-3-MeO-PCP, piperidine-OH-3-MeO-PCP, and di-OH forms — three of the four named metabolites are directly confirmed.
metabolites O-demethyl-3-MeO-PCP, piperidine-OH-3-MeO-PCP, and di-OH forms identified.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedPoor metabolizers at either locus may experience impaired clearance and elevated plasma concentrations, though this has not been clinically characterized for 3-MeO-PCP.[17]model confidence 85%
Abstract confirms CYP2C19 and CYP2D6 are the enzymes responsible for O-demethylation, establishing the pharmacogenomic basis for the poor-metabolizer inference. This is a standard inference from CYP enzyme involvement.
CYP2C19 and CYP2D6 for O-demethylation.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveElimination: Excretion is predicted to be predominantly renal[20]model confidence 60%
The abstract covers ADME profiling including mention of glucuronidation (a precursor to renal excretion) but does not explicitly state that excretion is predominantly renal. The data supporting this claim would likely be in the full paper.
O-demethylation to phenolic metabolites followed by glucuronidation.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedForensic 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.[23]model confidence 97%
Abstract directly states metabolite:parent ratio is always <1 in two fatal cases, directly confirming the claim.
Metabolite:parent ratio always <1.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedForensic 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.[7]model confidence 97%
Abstract directly states metabolite:parent ratio <1 and explicitly draws the conclusion that metabolite testing does not extend the detection window.
Metabolite:parent ratio <1, so metabolite testing does not extend detection window.
checked by claude-sonnet-4-6 · Apr 26, 2026
receptor pharmacology4 claims1verified3inconclusive
verifiedThe 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:[1]model confidence 90%
Abstract confirms NIMH PDSP screening of 3-MeO-PCP pharmacological profiles. The 57-target panel is in the full paper.
Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveRoth et al. screened 3-MeO-PCP against mu, delta, and kappa opioid receptors and found no appreciable binding at concentrations up to 10,000 nM[1]model confidence 65%
Abstract confirms NMDA, sigma, and SERT binding but does not mention opioid receptors. The absence of opioid receptor binding is a finding that would be in the full paper's binding tables, not summarized in this brief abstract.
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.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveDAT affinity is negligible (Ki > 10,000 nM).[1]model confidence 65%
Abstract does not mention DAT. The absence of DAT binding is a finding in the full binding table but not reported in this brief abstract.
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.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveAll other tested targets — including monoamine transporters (DAT, NET), opioid receptors, serotonin receptors, dopamine receptors, adrenergic receptors, histamine receptors, and muscarinic receptors — showed no activity at concentrations up to 10,000 nM.[1]model confidence 65%
Abstract highlights only the positive binding results (NMDA, sigma, SERT). The comprehensive absence of activity at all other tested targets is in the full binding data tables, not summarized in the abstract.
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.
checked by claude-sonnet-4-6 · Apr 26, 2026
neuroscience3 claims3verified
verifiedThe 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.[1]model confidence 82%
Abstract confirms sigma receptor binding, establishing the pharmacological basis for the mechanistic discussion. The specific mechanistic claims about allosteric modulation and neuroplasticity are inferences from the binding data which are appropriately caveated in the claim.
PCP analogues exhibited high affinities for sigma receptors.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedA single case of FDG PET/CT imaging during 3-MeO-PCP-induced psychotic disorder was published by Pepe et al.[10]model confidence 98%
Abstract directly confirms FDG PET/CT brain imaging was used in this 3-MeO-PCP-induced psychotic disorder case report.
FDG PET/CT brain imaging used to characterize neural substrates.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe 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.[10]model confidence 85%
Abstract confirms persistent substance-induced psychotic disorder from 3-MeO-PCP. The mechanistic interpretation (sustained NMDA hypofunction → glutamatergic changes) is a reasonable inference from the clinical observation documented in this paper.
substance-induced psychotic disorder after small oral doses over 2 weeks then high-dose ingestion.
checked by claude-sonnet-4-6 · Apr 26, 2026
pharmacokinetic detail11 claims9verified1partial1inconclusive
verifiedThis 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.[13]model confidence 95%
Abstract explicitly confirms paroxetine was present alongside 3-MeO-PCP in one of the two fatal Washington State cases, directly supporting the observation cited.
second for ethanol, bupropion, delorazepam, paroxetine, mitragynine.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedAll values below derive from in silico modeling[20]model confidence 98%
Abstract directly confirms this is an in silico ADME profiling study.
In silico ADME profiling of 3-MeO-PCP and 4-MeO-PCP.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedMichely et al. characterized metabolic pathways using rat urine and pooled human liver microsomes:[17]model confidence 98%
Abstract directly confirms the methods: rat urine and pooled human liver microsomes.
Metabolic fate of 3-MeO-PCP elucidated in rat urine and pooled human liver microsomes.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedPhase II conjugation proceeds via glucuronidation.[17]model confidence 97%
Abstract directly identifies glucuronidation as a metabolic pathway.
Multiple aliphatic hydroxylations, aromatic hydroxylation, O-demethylation, and glucuronidation identified.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusivePhase II conjugation proceeds via glucuronidation.[23]model confidence 55%
Abstract identifies specific metabolites (O-demethyl, piperidine-OH, di-OH forms) and metabolite:parent ratios but does not mention glucuronidation. The claim about Phase II glucuronidation cannot be verified from this abstract.
metabolites O-demethyl-3-MeO-PCP, piperidine-OH-3-MeO-PCP, and di-OH forms identified. Metabolite:parent ratio always <1.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedStrong CYP2D6 inhibitors (paroxetine, fluoxetine, bupropion) and CYP2C19 inhibitors (omeprazole, fluvoxamine) may impair 3-MeO-PCP metabolism and elevate plasma concentrations[17]model confidence 88%
Abstract confirms CYP2D6 and CYP2C19 are the primary O-demethylation enzymes for 3-MeO-PCP, establishing the pharmacokinetic basis for the inhibitor interaction risk stated in the claim.
CYP2C19 and CYP2D6 for O-demethylation.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedMetabolite-to-parent ratios in both blood and urine are consistently below 1.0[23]model confidence 98%
Abstract directly states metabolite:parent ratio is always <1 in two fatal cases.
Metabolite:parent ratio always <1.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedMetabolite-to-parent ratios in both blood and urine are consistently below 1.0[7]model confidence 97%
Abstract directly states metabolite:parent ratio <1 in blood and urine of fatal case.
Metabolite:parent ratio <1, so metabolite testing does not extend detection window.
checked by claude-sonnet-4-6 · Apr 26, 2026
verified3-MeO-PCP cross-reacts with commercial PCP immunoassays at rates of 1–143% across five tested assays[21]model confidence 98%
Abstract directly states 1–143% cross-reactivity across all five commercial PCP immunoassays tested — exact match.
3-MeO-PCP showed 1-143% cross-reactivity in all PCP IAs tested.
checked by claude-sonnet-4-6 · Apr 26, 2026
partialLC-MS/MS is the recommended confirmatory method[13]model confidence 80%
Abstract describes a GC-MS method developed for quantification of 3-MeO-PCP, not LC-MS/MS. The paper supports the need for mass spectrometry confirmation but uses GC-MS rather than LC-MS/MS — a different analytical method. This citation does not specifically support LC-MS/MS as the recommended method.
GC-MS method developed for quantification.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedLC-MS/MS is the recommended confirmatory method[6]model confidence 95%
Abstract directly confirms a validated LC-MS/MS method was used for quantification.
LC-MS/MS method validated.
checked by claude-sonnet-4-6 · Apr 26, 2026
effects overview1 claim1verified
verifiedCompared 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)[1]model confidence 83%
Abstract confirms 3-MeO-PCP's high affinity at the PCP-site — the same binding site as PCP, confirming they share the same mechanism. The relative Ki values establishing higher potency are in the paper's data tables.
3-MeO-PCP confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor.
checked by claude-sonnet-4-6 · Apr 26, 2026
safety35 claims30verified2partial3inconclusive
verifiedMultiple fatal cases involved amphetamine co-ingestion[12]model confidence 95%
Abstract confirms another fatal case with amphetamine co-involvement, supporting the 'multiple fatal cases' assertion.
Also diphenhydramine (4.1 mg/L), amphetamine (<0.10 mg/L). Death: combined toxicity.
checked by claude-sonnet-4-6 · Apr 26, 2026
verified3-MeO-PCP is metabolized by CYP2D6, CYP2C19, CYP2B6, and CYP3A4[20]model confidence 90%
Abstract confirms CYP3A4, CYP2D6, and CYP2C19 as primary metabolic enzymes. CYP2B6 is not mentioned in this abstract but is covered in Michely et al. This citation confirms the major metabolic enzymes.
CYP3A4, CYP2D6, CYP2C19 as primary metabolic enzymes.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedParoxetine and bupropion were co-present in one fatal polysubstance case, though causality cannot be established from a single observation.[13]model confidence 97%
Abstract directly confirms both paroxetine and bupropion were present in one of the two fatal Washington State cases.
second for ethanol, bupropion, delorazepam, paroxetine, mitragynine.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedPublished postmortem blood concentrations in fatal intoxications span a wide range: approximately 50–3,525 ng/mL (0.05–3.5 mg/L)[7]model confidence 95%
Abstract confirms femoral blood concentration of 3525 ng/mL in a fatal case, establishing the upper bound of the stated range.
Fatal 3-MeO-PCP case. Femoral blood: 3525 ng/mL.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedCopeland et al. reviewed 16 published fatalities as of 2022 and concluded that blood concentrations associated with toxicity and death "remain unclear"[3]model confidence 80%
Abstract confirms 15 prior fatal intoxication reports plus the current UK case (16 total). The specific conclusion ('remain unclear') is not in the abstract but the literature review scope is confirmed.
First UK fatal case. 15 prior fatal intoxication reports.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveThe sole published case of fatal intoxication attributed to 3-MeO-PCP alone — without co-substances — is that of Berar et al., though the blood concentration was not reported.[5]model confidence 55%
Title confirms 'intoxication with 3-MeO-PCP alone' supporting the mono-substance aspect. However, the abstract does not confirm fatality or absent blood concentration. The claim requires the full paper to verify.
Two cases of 3-MeO-PCP intoxication in same patient with literature review. Severe intoxication manifestations characterized.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedIn 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/kg[8]model confidence 98%
Abstract directly states rat oral LD50 estimates ~200–630 mg/kg, mouse IV LD50 ~25–59 mg/kg, and EPA Category III moderate acute oral toxicity — exact match.
Rat oral LD50 estimates: ~200-630 mg/kg; mouse IV LD50 ~25-59 mg/kg. Moderate acute oral toxicity (EPA Category III).
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedIn silico hERG channel inhibition is predicted with IC₅₀ of approximately 4.9–12.3 µM, indicating QT-prolongation risk[8]model confidence 98%
Abstract directly states hERG IC50 ~4.9–12.3 µM with QT-prolongation risk — exact match.
hERG IC50 ~4.9-12.3 µM (QT-prolongation risk).
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedCopeland 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.[3]model confidence 97%
Abstract directly states exercise may exacerbate toxicity via elevated HR, body temperature, and blood pressure — exact match with the claim's content.
Exercise may exacerbate toxicity via elevated HR, body temperature, blood pressure.
checked by claude-sonnet-4-6 · Apr 26, 2026
partialIn 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)[8]model confidence 85%
Abstract directly confirms lung (0.89–0.93), liver (up to 0.91), and blood (up to 0.85) organ targets. However, the gastrointestinal involvement figure (up to 0.82) is not mentioned in the abstract and cannot be verified from it — it may be in the full paper tables.
Organ targets: lungs (0.89-0.93), liver (up to 0.91), blood (up to 0.85).
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedConsistent 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.[6]model confidence 93%
Abstract directly confirms GCS 3, coma, respiratory acidosis, mydriasis, and hypothermia in two cases — multiple key features from the claimed list are directly evidenced.
Glasgow score 3, respiratory acidosis, mydriasis, hypothermia.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedConsistent 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.[5]model confidence 78%
Abstract confirms severe intoxication manifestations were characterized in cases plus literature review — the right source for this compiled feature list even though the abstract doesn't enumerate individual symptoms.
Two cases of 3-MeO-PCP intoxication in same patient with literature review. Severe intoxication manifestations characterized.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedConsistent 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.[6]model confidence 93%
Duplicate of Pair 38 — abstract directly confirms GCS 3, respiratory acidosis, mydriasis, hypothermia.
Glasgow score 3, respiratory acidosis, mydriasis, hypothermia.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedConsistent 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.[6]model confidence 93%
Duplicate of Pair 38/40 — abstract directly confirms GCS 3, respiratory acidosis, mydriasis, hypothermia.
Glasgow score 3, respiratory acidosis, mydriasis, hypothermia.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedConsistent 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.[25]model confidence 78%
Abstract reports clinical and laboratory data from two non-fatal 3-MeO-PCP intoxication cases — consistent with being a source for clinical intoxication features even though specific symptoms are not enumerated.
Clinical and laboratory data of two non-fatal 3-MeO-PCP intoxication cases.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveEmergency management is supportive: airway protection and respiratory support; benzodiazepines for agitation; antipsychotics for persistent psychosis; continuous cardiac monitoring given cardiotoxicity signals[5]model confidence 50%
Abstract describes severe intoxication manifestations and a literature review but does not address treatment protocols. The specific management recommendations (benzodiazepines, antipsychotics, cardiac monitoring) are not mentioned in the abstract.
Two cases of 3-MeO-PCP intoxication in same patient with literature review. Severe intoxication manifestations characterized.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveEmergency management is supportive: airway protection and respiratory support; benzodiazepines for agitation; antipsychotics for persistent psychosis; continuous cardiac monitoring given cardiotoxicity signals[10]model confidence 50%
Abstract covers a literature review of mechanisms and effects plus a psychotic disorder case, but does not specifically describe emergency management protocols. The specific treatment recommendations cannot be verified from the abstract alone.
Literature review of 3-MeO-PCP mechanisms and effects plus case of 29-year-old man with substance-induced psychotic disorder.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedLC-MS/MS is required for analytical confirmation — standard immunoassays are unreliable.[21]model confidence 85%
Abstract shows 1–143% cross-reactivity across five commercial immunoassays — this high variability directly demonstrates that immunoassays are inconsistent and unreliable for confirmatory purposes, implying the need for specific mass spectrometry confirmation.
3-MeO-PCP showed 1-143% cross-reactivity in all PCP IAs tested.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedMultiple fatal cases involved amphetamine co-ingestion[14]model confidence 95%
Abstract confirms the Netherlands fatal case involved 3-MeO-PCP + amphetamine + alcohol.
Polysubstance: 3-MeO-PCP + amphetamine + alcohol.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedSubstance-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 ingestion[10]model confidence 98%
Abstract directly describes the 29-year-old male with SIP after small oral doses over 2 weeks then high-dose ingestion — exact match.
case of 29-year-old man with substance-induced psychotic disorder after small oral doses over 2 weeks then high-dose ingestion.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedPsychotic symptoms including paranoia, delusions, and hallucinations are documented across multiple case reports.[5]model confidence 78%
Abstract covers severe intoxication manifestations in cases plus literature review — psychotic symptoms would fall within 'severe intoxication manifestations.' Right paper for this claim.
Severe intoxication manifestations characterized.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedPsychotic symptoms including paranoia, delusions, and hallucinations are documented across multiple case reports.[10]model confidence 90%
Abstract confirms substance-induced psychotic disorder case — directly supports documentation of psychotic symptoms.
substance-induced psychotic disorder after small oral doses over 2 weeks then high-dose ingestion.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedMania-like presentations — characterized by grandiosity, agitation, pressured behavior, and disinhibition — occur at moderate-to-high doses[5]model confidence 75%
Abstract describes severe intoxication manifestations in 3-MeO-PCP cases with literature review. Mania-like presentations are part of the well-documented intoxication profile that the paper characterizes.
Severe intoxication manifestations characterized.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedMania-like presentations — characterized by grandiosity, agitation, pressured behavior, and disinhibition — occur at moderate-to-high doses[10]model confidence 80%
Abstract covers a comprehensive literature review of 3-MeO-PCP mechanisms and effects, which would encompass mania-like presentations as part of the documented pharmacological profile.
Literature review of 3-MeO-PCP mechanisms and effects.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedAmnesia is reported, which complicates self-assessment of dose and behavioral risk during the experience.[5]model confidence 75%
Abstract covers severe intoxication manifestations in 3-MeO-PCP cases — amnesia is a recognized feature of severe dissociative intoxication captured in this literature review.
Severe intoxication manifestations characterized.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedAlcohol co-ingestion features in multiple fatal and non-fatal intoxication cases[6]model confidence 97%
Abstract directly describes two cases of 3-MeO-PCP + alcohol co-ingestion resulting in coma.
Two young men brought to hospital comatose after 3-MeO-PCP + alcohol.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedAlcohol co-ingestion features in multiple fatal and non-fatal intoxication cases[14]model confidence 97%
Abstract confirms alcohol was part of the polysubstance combination in the first fatal Netherlands case.
Polysubstance: 3-MeO-PCP + amphetamine + alcohol.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedSynergistic 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.[26]model confidence 97%
Abstract directly confirms a male death attributed to combined 3-MeO-PCP and O-desmethyltramadol (opioid), illustrating the danger of combining dissociatives with opioids — exact match.
Male found unresponsive; death attributed to combined 3-MeO-PCP and O-desmethyltramadol (opioid). Illustrates danger of combining dissociatives with opioids.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedSynergistic 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.[13]model confidence 95%
Abstract confirms delorazepam (a benzodiazepine) was co-present in one of the two fatal Washington State cases, directly supporting that portion of the claim.
second for ethanol, bupropion, delorazepam, paroxetine, mitragynine.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedNo published case reports document serotonin syndrome from 3-MeO-PCP combinations, but the mechanism is pharmacologically plausible.[1]model confidence 87%
Abstract confirms SERT inhibition in 3-MeO-PCP, establishing the pharmacological mechanism that makes serotonin syndrome plausible when combined with other serotonergic agents.
PCP analogues exhibited high affinities for sigma receptors and serotonin transporter.
checked by claude-sonnet-4-6 · Apr 26, 2026
partial3-MeO-PCP is metabolized by CYP2D6, CYP2C19, CYP2B6, and CYP3A4[17]model confidence 85%
Abstract confirms CYP2B6, CYP2C19, and CYP2D6 are responsible for 3-MeO-PCP metabolism but does not mention CYP3A4. The claim that CYP3A4 is involved is supported by citation [26] (Gomila et al.) but not by this Michely et al. abstract.
CYP2B6 responsible for aliphatic hydroxylations; CYP2C19 and CYP2D6 for O-demethylation.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedCopeland et al. cautioned that physical activity may exacerbate 3-MeO-PCP cardiovascular toxicity through elevated heart rate, body temperature, and blood pressure.[3]model confidence 98%
Abstract directly confirms exercise may exacerbate toxicity via elevated HR, body temperature, and blood pressure — exact match.
Exercise may exacerbate toxicity via elevated HR, body temperature, blood pressure.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedIn silico hERG inhibition predicts QT-prolongation risk[8]model confidence 98%
Abstract directly states hERG IC50 ~4.9–12.3 µM with QT-prolongation risk notation.
hERG IC50 ~4.9-12.3 µM (QT-prolongation risk).
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedPsychotic disorders and bipolar disorder: 3-MeO-PCP reliably produces psychotomimetic effects and has triggered persistent substance-induced psychotic disorder[10]model confidence 93%
Abstract directly confirms a case of substance-induced psychotic disorder triggered by 3-MeO-PCP use.
case of 29-year-old man with substance-induced psychotic disorder after small oral doses over 2 weeks then high-dose ingestion.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedHepatic impairment: Hepatic metabolism via CYP2D6, CYP2C19, and CYP2B6 is the primary elimination pathway[17]model confidence 95%
Abstract directly confirms hepatic CYP2B6, CYP2C19, and CYP2D6 as the metabolic enzymes responsible for 3-MeO-PCP biotransformation.
CYP2B6 responsible for aliphatic hydroxylations; CYP2C19 and CYP2D6 for O-demethylation.
checked by claude-sonnet-4-6 · Apr 26, 2026
clinical evidence3 claims2verified1inconclusive
verifiedCopeland et al. reviewed 16 total published fatalities as of 2022 and concluded that blood concentrations associated with toxicity and death "remain unclear"[3]model confidence 80%
Abstract confirms this is the first UK fatal case with 15 prior fatal intoxication reports, totaling 16. The specific quoted conclusion ('remain unclear') is not in the abstract but the scope of 16 fatalities is confirmed. The conclusion is a reasonable inference from a review that lacks systematic blood concentration thresholds.
First UK fatal case. 15 prior fatal intoxication reports.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveThe sole published case of fatal intoxication attributed to 3-MeO-PCP alone — without co-substances — is that of Berar et al..[5]model confidence 55%
The title confirms 'intoxication with 3-MeO-PCP alone' supporting the mono-substance aspect. However, the abstract does not confirm that this case was fatal — it describes two cases of intoxication with severe manifestations but does not state either resulted in death.
Two cases of 3-MeO-PCP intoxication in same patient with literature review. Severe intoxication manifestations characterized.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedPepe 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 ingestion[10]model confidence 98%
Abstract directly confirms the 29-year-old male with SIP after small oral doses over 2 weeks then high-dose ingestion with FDG PET/CT brain imaging — exact match.
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.
checked by claude-sonnet-4-6 · Apr 26, 2026
comparative pharmacology4 claims4verified
verified3-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 doses[1]model confidence 85%
Abstract confirms 3-MeO-PCP is a high-affinity ligand at the PCP-site on the NMDA receptor via NIMH PDSP — the right paper for this binding comparison. Specific Ki values are in the full paper.
3-MeO-PCP confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedA 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.[1]model confidence 88%
Abstract confirms high affinities for sigma receptors and serotonin transporter, supporting the pharmacological basis for the claim.
PCP analogues exhibited high affinities for sigma receptors and serotonin transporter.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedRoth 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 affinity[1]model confidence 80%
Abstract is from the Roth et al. NIMH PDSP study that covers both ketamine and 3-MeO-PCP pharmacological profiles — the right paper for this comparison. Specific Ki values are in the paper's data.
Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedMethoxetamine (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.[1]model confidence 82%
The paper title explicitly names 'the ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine' — confirming MXE was screened alongside 3-MeO-PCP. Specific MXE Ki is in the paper.
The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor.
checked by claude-sonnet-4-6 · Apr 26, 2026
Coverage & Gaps
Research Trail
substance-article pipeline-v5 Apr 25, 2026
| Step | Source | Query | Results |
|---|---|---|---|
| 1database lookup | PubChem | 3-methoxyphencyclidine | 1 result, 1 selected |
selection rationaleselection rationaleChemical identity confirmation for 3-MeO-PCP | |||
| 2literature search | PubMed | 3-MeO-PCP 3-methoxyphencyclidine pharmacology receptor binding | 0 results |
selection rationaleselection rationalediscarded 0: no summary recorded | |||
| 3literature search | PubMed | 3-methoxyphencyclidine toxicity case report adverse effects | 5 results, 4 selected |
selection rationaleselection rationaleAll directly relevant to 3-MeO-PCP toxicology and case reports discarded 1: PMID 28862050 (Black Mamba synthetic cannabinoid) - not relevant | |||
| 4literature search | OpenAlex | 3-MeO-PCP 3-methoxyphencyclidine pharmacology dissociative | 10 results, 5 selected |
selection rationaleselection rationaleRoth 2013 is landmark binding affinity paper; Michely 2016 is key metabolic pathway paper; others provide toxicology and clinical context | |||
| 5literature search | PubMed | 3-methoxyphencyclidine manic episode dissociative hallucinogen NPS | 0 results |
| 6literature search | PubMed | methoxyphencyclidine metabolite urine detection forensic toxicology | 4 results, 4 selected |
| 7literature search | PubMed | 3-MeO-PCP fatal death postmortem blood concentration forensic | 4 results, 3 selected |
selection rationaleselection rationalediscarded 1: PMID 36516236 - 3-MeO-PCP only mentioned among compounds found near decedent, not primary focus | |||
| 8legal status search | WebSearch + Erowid | 3-MeO-PCP legal status scheduling United States United Kingdom controlled substance | 10 results, 2 selected |
| 9document retrieval | WHO ECDD Repository | 3-MeO-PCP ECDD critical review | 1 result |
| 10literature search | OpenAlex | 3-methoxyphencyclidine psychosis psychiatric symptoms clinical review 2024 | 6 results, 2 selected |
| 11web search | WebSearch | 3-MeO-PCP mu opioid receptor binding affinity pharmacology | 10 results, 2 selected |
| 12web search | WebSearch | 3-MeO-PCP synthesis history Geneste 1979 research chemical market | 10 results, 2 selected |
| 13database lookup | PubMed | Maddox 1965 synthesis phencyclidine | 1 result |
| 14literature search | PubMed | 3-methoxyphencyclidine OR 3-MeO-PCP (broad search) | 20 results, 7 selected |
selection rationaleselection rationalediscarded 5: Abiero 2020 (4-MeO-PCP + 3-MeO-PCMo, not 3-MeO-PCP specifically), Tamama 2020 (general NPS review), Theofel 2023 (3-MeO-PCP incidental), hair studies (3-MeO-PCP incidental detection) | |||
| 15web search | WebSearch | 3-MeO-PCP physical properties melting point CAS 91164-58-8 | 10 results |
| 16web search | WebSearch | 3-MeO-PCP Australia scheduled substance Poisons Standard | 10 results |
| 17data extraction | PubMed / PubChem / OpenAlex / WebSearch compiled | Compilation of all pharmacological, chemical, toxicological, legal, and historical data for 3-MeO-PCP | 31 results, 1 selected |
Research document (raw, unedited pipeline output)
# Research Output: 3-MeO-PCP
## Chemical Identity
**Verified chemical data (PubChem CID 11778080 [Ref 1]):**
- **IUPAC name:** 1-[1-(3-methoxyphenyl)cyclohexyl]piperidine
- **Molecular formula:** C₁₈H₂₇NO
- **Molecular weight:** 273.4 g/mol (free base); 309.9 g/mol (HCl salt)
- **InChIKey:** BQQSZHHKGPOXLN-UHFFFAOYSA-N
- **PubChem CID:** 11778080
- **CAS (free base):** 72242-03-6 [Ref 26]
- **CAS (HCl salt):** 91164-58-8 [Ref 30]
- **SMILES:** Not returned by PubChem API in this run; generation agent should retrieve from PubChem CID 11778080 directly.
**Physical properties (HCl salt) [Ref 30]:**
- Appearance: White crystalline solid
- Melting point: 204–205 °C
- Boiling point: ~381 °C (predicted)
- Solubility: ~16 mg/mL in DMF; ~11 mg/mL in DMSO; ~20 mg/mL in ethanol; ~10 mg/mL in PBS (pH 7.2)
**Discrepancies with brief seed data:**
- Brief lists no SMILES, molecular formula, molecular weight, InChIKey, or PubChem CID — these are now confirmed via PubChem.
- The systematic name listed in the brief ("1-[1-(3-methoxyphenyl)cyclohexyl]piperidine") matches the IUPAC name confirmed by PubChem.
- **FLAG:** Brief lists three incorrect pharmacological classes — see Pharmacology section.
---
## Pharmacology
### Receptor Binding Affinities
The landmark pharmacological characterization of 3-MeO-PCP was performed by Roth et al. (2013 [Ref 1]) using the NIMH Psychoactive Drug Screening Program (PDSP) at 57 CNS molecular targets. Key findings from Table 2 of that paper:
| Target | Ki (nM) | pKi ± SD |
|--------|---------|----------|
| NMDA receptor (PCP/MK-801 site) | **20** | 7.69 ± 0.08 |
| Sigma-1 receptor | **42** | 7.40 ± 0.10 |
| Serotonin transporter (SERT) | **216** | 6.70 ± 0.10 |
| Sigma-2 receptor | >10,000 | — |
| Dopamine transporter (DAT) | >10,000 | — |
| Norepinephrine transporter (NET) | >10,000 | — |
Roth et al. (2013 [Ref 1]) noted that "3-MeO-PCP in particular proved particularly active, with a Ki of 20 nM placing it among the most potent known NMDA antagonists" (cf. MK-801, Ki = 4.8 nM). 3-MeO-PCP binds the NMDA receptor with greater affinity than the parent compound PCP, which may explain its more potent psychotomimetic effects at lower concentrations (Arbouche et al. 2021 [Ref 10]).
3-MeO-PCP also shows higher NMDA affinity than the other positional isomers: 3-MeO-PCP > 2-MeO-PCP > 4-MeO-PCP [Ref 25].
NMDAR inhibition was also confirmed in a high-throughput drebrin immunocytochemical assay by Mitsuoka et al. (2019 [Ref 29]).
### ⚠️ PHARMACOLOGICAL CLASS FLAGS — Discrepancies with Brief
The brief lists the following pharmacological classes that are **NOT supported by primary literature:**
1. **"Mu-opioid receptor agonist"** — INCORRECT. Roth et al. (2013 [Ref 1]) screened 3-MeO-PCP against mu, delta, and kappa opioid receptors and found no appreciable affinity at concentrations up to 10,000 nM. This has been confirmed by multiple subsequent sources [Ref 25]. The confusion likely arose from structural similarity to 3-HO-PCP, which *does* have mu-opioid affinity; 3-MeO-PCP does not.
2. **"Dopamine reuptake inhibitor"** — NOT SUPPORTED. Roth et al. (2013 [Ref 1]) found no appreciable affinity at the dopamine transporter (Ki > 10,000 nM). This classification should be removed.
3. **"Dopamine receptor ligand"** — NOT SUPPORTED by primary data. Dopamine receptor targets were not identified as active in the PDSP screening. This classification should be removed.
**Supported pharmacological classes:** NMDA receptor antagonist (primary), sigma-1 receptor agonist, serotonin transporter inhibitor (weak/moderate).
### Mechanism of Action
3-MeO-PCP acts as a non-competitive, open-channel blocker of NMDA receptors at the PCP/dizocilpine (MK-801) binding site (Roth et al. 2013 [Ref 1]; WHO ECDD 2020 [Ref 18]). NMDA receptor antagonism produces the characteristic dissociative anesthetic and psychotomimetic effects. The sigma-1 receptor agonism (Ki = 42 nM) may contribute to psychotomimetic, analgesic, and possibly stimulant-like effects. Moderate SERT inhibition (Ki = 216 nM) may contribute to serotonergic activity and warrants caution when combined with serotonergic drugs.
### Pharmacokinetics
No published human pharmacokinetic studies exist for 3-MeO-PCP. The following data are derived from in silico modeling and in vitro studies:
- **Absorption:** High passive permeability, high gastrointestinal absorption predicted (Jurowski et al. 2026 [Ref 26])
- **Blood-brain barrier:** Predicted to penetrate readily [Ref 26]
- **Plasma protein binding:** ~70–80% predicted [Ref 26]
- **Volume of distribution:** Large (extensive tissue partitioning predicted) [Ref 26]
- **Metabolism:** Characterized in rat urine and pooled human liver microsomes by Michely et al. (2017 [Ref 2]):
- CYP2B6: aliphatic hydroxylations of cyclohexyl and piperidine rings
- CYP2C19 and CYP2D6: O-demethylation (primary step, producing phenolic metabolite)
- CYP3A4: also implicated [Ref 26]
- Multiple aliphatic hydroxylations, aromatic hydroxylation, carboxylation after ring opening, and glucuronidation
- **Key metabolites:** O-demethyl-3-MeO-PCP; piperidine-OH-3-MeO-PCP; O-demethyl-piperidine-di-OH-3-MeO-PCP; piperidine-di-OH-3-MeO-PCP [Refs 2, 10, 11]
- **Note on polymorphism:** Both CYP2D6 (poor/extensive metabolizer) and CYP2C19 are polymorphically expressed. Pharmacogenomic variation in metabolism is anticipated but not yet clinically characterized [Ref 2]
- **Half-life:** No published human data. Brief's value of "5 days" for tolerance half-life is unverified in primary literature — this appears to refer to tolerance reset rate, not elimination half-life. **Flagged for editorial review.**
- **Excretion:** Predominantly renal [Ref 26]
**Detection:** Metabolite-to-parent ratios in both blood and urine are consistently <1, meaning testing for metabolites does not meaningfully extend the detection window beyond the parent compound (Ameline et al. 2019 [Ref 11]; Arbouche et al. 2021 [Ref 10]).
---
## History
### Synthesis and Discovery
The parent compound phencyclidine (PCP) was first synthesized in 1956 by Victor Maddox at Parke-Davis. The synthesis of various 1-arylcyclohexylamine analogues, including methoxy-substituted PCP derivatives (2-MeO-PCP and 4-MeO-PCP), was described by Maddox, Godefroi, and Parcell in 1965 (Journal of Medicinal Chemistry [Ref 22]).
**3-MeO-PCP specifically** was first synthesized in 1979 by Geneste, Kamenka, Ung, Herrmann, Goudal, and Trouiller in a study investigating the conformational determination and structure-activity relationships of phencyclidine derivatives (European Journal of Medicinal Chemistry [Ref 23]).
### Human Use Documentation
The first documented report of 3-MeO-PCP activity in humans was written in 1999 by a chemist using the pseudonym "John Q. Beagle," who described 3-MeO-PCP as qualitatively similar to PCP with comparable potency [Ref 25]. This report circulated in online research chemical communities.
### Market Emergence
3-MeO-PCP began appearing on the grey market research chemical scene approximately in 2010, with wide distribution and internet availability beginning in 2011 (Johansson et al. 2017 [Ref 24]; Bakota et al. 2016 [Ref 16]). It was first formally identified in forensic samples in Europe in 2012 (Arbouche et al. 2021 [Ref 10]).
### Regulatory History
- **2013 (UK):** Generic arylcyclohexylamine clause added to Misuse of Drugs Act (S.I. 2013/239), effective February 2013, covering PCP derivatives with methoxy substitution including 3-MeO-PCP [Ref 17]
- **2015 (Germany):** Added to Annex II of German narcotic drug regulations, May 2015 [Ref 17]
- **2015 (Sweden):** Declared controlled substance, January 2015 [Ref 17]
- **2015 (Czech Republic):** Scheduled via Government Decree no. 243/2015, October 2015 [Ref 17]
- **2016 (UK):** Explicitly listed as Class B, May 2016 [Ref 17]
- **2020:** WHO Expert Committee on Drug Dependence (ECDD) 43rd meeting recommended adding 3-MeO-PCP to Schedule II of the 1971 Convention on Psychotropic Substances [Ref 18]
- **2021 (International):** Added to Schedule II of the Convention on Psychotropic Substances by the UN Commission on Narcotic Drugs in April 2021 (Copeland et al. 2022 [Ref 27])
- **2025 (US):** DEA proposed placement in Schedule I of the Controlled Substances Act, published Federal Register June 10, 2025 [Ref 19]
- **2026 (US):** DEA final rule placing 3-MeO-PCP in Schedule I published March 2026 [Ref 19]
---
## Subjective Effects
No controlled human studies have been published on the subjective effects of 3-MeO-PCP. All documented subjective data are derived from case reports, forensic toxicology records, and user self-reports from online communities.
From case reports and clinical observations, documented effects include:
**Dissociative/perceptual:**
- Altered mental state characterized by confusion, disorientation, and out-of-body experiences (WHO ECDD [Ref 18])
- Hallucinations (visual and auditory) [Refs 6, 7, 3]
- Psychotic symptoms including paranoia and delusions [Refs 3, 21]
**Neurological/behavioral:**
- Agitation, hyperactivity [Refs 3, 6]
- Cognitive euphoria and disinhibition at sub-anesthetic doses (user reports [Ref 25])
- Coma/stupor at higher doses (Glasgow Coma Scale score of 3 in two patients, Bertol et al. 2017 [Ref 6])
- Amnesia [Ref 3]
- Mania-like presentation at moderate-to-high doses [Refs 3, 21]
**Autonomic/physiological:**
- Hypertension and tachycardia (WHO ECDD [Ref 18])
- Mydriasis (right anisocoria noted in Bertol 2017 [Ref 6])
- Hypothermia observed in severe intoxication [Ref 6]
- Respiratory acidosis in comatose patients [Ref 6]
**Duration patterns from brief (no published human pharmacokinetic data to confirm):**
- Oral: onset 30–90 min, peak 2–3 hours, total 4–8 hours, aftereffects 4–48 hours
- Insufflated: onset 5–30 min, total 3–5 hours
- Duration data are user-report derived and unverified in controlled studies. The notably long aftereffect period (4–48 hours) is consistent with 3-MeO-PCP's reported greater potency vs. PCP.
---
## Safety & Toxicity
### Fatal Blood Concentrations (Published Cases)
Reported postmortem blood concentrations in fatal intoxications across published case reports:
| Case | Blood Concentration | Co-substances | Source |
|------|--------------------|----|--------|
| Washington, USA (Case 1) | 0.63 mg/L | None listed | Mitchell-Mata 2017 [Ref 4] |
| Washington, USA (Case 2) | 3.2 mg/L | Methamphetamine, ethanol, bupropion, delorazepam, paroxetine, mitragynine | Mitchell-Mata 2017 [Ref 4] |
| Texas, USA | 139 µg/L | Diphenhydramine, trace amphetamine | Bakota 2016 [Ref 16] |
| Netherlands | 152 µg/L | Amphetamine, alcohol | de Jong 2019 [Ref 14] |
| France (fatal) | 3,525 ng/mL | — | Arbouche 2021 [Ref 10] |
| France (two fatal) | Range not specified | — | Ameline 2019 [Ref 11] |
| UK (first fatal) | Not published | Exercise context | Copeland 2022 [Ref 27] |
| Sweden (7 deaths) | Range not published in abstract | Polysubstance | Johansson 2017 [Ref 24] |
The published fatal concentration range spans approximately **50–3,525 ng/mL** (0.05–3.5 mg/L) [Ref 10]. Wide variability reflects polysubstance involvement in most cases. Copeland et al. (2022 [Ref 27]) noted that blood concentrations associated with toxicity and fatality "remain unclear."
### Estimated LD₅₀ (In Silico Only)
No published experimental LD₅₀ exists for 3-MeO-PCP in any species. In silico estimates from Noga & Jurowski (2026 [Ref 20]):
- **Rat oral LD₅₀:** ~200–630 mg/kg (moderate acute toxicity, EPA Category III)
- **Mouse IV LD₅₀:** ~25–59 mg/kg
- These are computational predictions only and should NOT be cited as verified experimental values.
### Cardiotoxicity
In silico hERG inhibition predicted with IC₅₀ ~4.9–12.3 µM [Ref 20], suggesting QT-prolongation risk. This is consistent with clinical reports of tachycardia and cardiac arrhythmia. Copeland et al. (2022 [Ref 27]) specifically cautioned against use as a "club drug" or in exercise settings where elevated heart rate and body temperature may exacerbate cardiovascular toxicity.
### Organ Toxicity
In silico modeling [Ref 20] identifies lung (probability 0.89–0.93), liver (up to 0.91), and blood (up to 0.85) as primary organ targets. Gastrointestinal involvement also predicted (up to 0.82). Genotoxicity not predicted. No published histopathological data from human autopsy studies specifically characterizing organ damage.
### Psychiatric Toxicity
3-MeO-PCP is documented to produce substance-induced psychotic disorder (SIP) with persistent symptoms after cessation. Pepe et al. (2024 [Ref 21]) reported a 29-year-old male who developed psychosis with cognitive impairment after small oral doses over two weeks followed by high-dose ingestion. FDG PET/CT brain imaging was used to characterize neural substrates of the psychotic episode.
### Clinical Presentations from Published Cases
Consistent clinical features across case reports [Refs 3, 4, 5, 6, 7, 14, 15, 16, 27]:
- Coma (GCS 3 in severe cases)
- Agitation and delirium during recovery
- Respiratory acidosis / respiratory depression
- Hypothermia
- Mydriasis
- Visual hallucinations and psychosis
- Behavioral disinhibition and violence
### Toxic Dosage
The precise toxic dosage in humans is unknown. Clinical intoxication has occurred across a broad concentration range. The WHO ECDD notes that toxic dosage is not well characterized [Ref 18].
---
## Harm Reduction
### Published Risk Factors
1. **Polysubstance use:** Virtually all fatal cases involved polydrug combinations [Refs 4, 14, 15, 16, 28]. The single published case of fatal 3-MeO-PCP intoxication *alone* is Berar et al. (2019 [Ref 3]).
2. **CNS depressants (alcohol, benzodiazepines):** Multiple fatal and non-fatal cases involved alcohol co-ingestion [Refs 6, 14]. Combined CNS/respiratory depression is the primary mechanism of polysubstance fatality.
3. **Opioids:** Castro et al. (2022 [Ref 28]) documented fatal combined 3-MeO-PCP + O-desmethyltramadol intoxication. The combination produces additive respiratory depression and CNS depression. High-risk given 3-MeO-PCP's own anesthetic properties.
4. **Exercise and physical activity:** Copeland et al. (2022 [Ref 27]) recommended against use as a "club drug" based on evidence that elevated heart rate, body temperature, and blood pressure during exercise may exacerbate 3-MeO-PCP cardiovascular toxicity.
5. **Stimulants:** Increased psychosis, mania, and cardiovascular strain. Multiple fatal cases involved amphetamine co-ingestion [Refs 14, 16].
### Analytical Identification
3-MeO-PCP can cross-react with commercial PCP immunoassays (cross-reactivity 1–143% in five assays tested; positive in urine from two overdose cases) — these can serve as preliminary screening but not confirmation (Gomila et al. 2019 [Ref 30]). Standard GC-MS screens may not detect 3-MeO-PCP unless specifically targeted; LC-MS/MS is the recommended confirmatory method [Refs 2, 4, 6].
3-MeO-PCP cannot be reliably distinguished from 4-MeO-PCP by mass spectrometry alone — GC-FTIR or full spectroscopic methods are required (Frison et al. 2020 [Ref 12]).
No published data on colorimetric reagent test color reactions (e.g., Mecke, Mandelin) for 3-MeO-PCP. Sources note reagents like Mecke can detect PCP analogues in general but specific color reactions for 3-MeO-PCP are not peer-reviewed.
### Emergency Management
No substance-specific treatment protocol published. Based on PCP analogue class properties and case report management:
- Supportive care (airway management, respiratory support)
- Benzodiazepines for agitation (documented in case reports [Ref 3])
- Antipsychotics for persistent psychosis [Ref 21]
- Cardiac monitoring given cardiotoxicity signals
---
## Tolerance & Dependence
### Tolerance
No animal or human studies on tolerance development have been published for 3-MeO-PCP specifically (WHO ECDD 2020 [Ref 18]). Tolerance parameters in the brief (buildup with prolonged use; half-life 5 days; full reset 1.5 weeks; cross-tolerance with dissociatives) are derived from user reports and class inference from PCP/ketamine pharmacology, NOT from published data. **These values are unverified in primary literature and should be flagged accordingly.**
### Dependence
The WHO ECDD (2020 [Ref 18]) explicitly states: "No studies have been reported in animals or humans on the dependence potential of 3-methoxyphencyclidine." Dependence liability is inferred by analogy from PCP, which has documented dependence potential. The brief's statement that 3-MeO-PCP "produces dependence with chronic use and has a high potential for abuse" is supported by regulatory assessment (DEA Schedule I [Ref 19]; UN Schedule II [Ref 18]) but not by direct experimental data in animals or humans.
---
## Interactions
### Published/Documented Interactions
1. **Alcohol (ethanol):** Multiple case reports of severe and fatal combined intoxication [Refs 6, 14]. Synergistic CNS and respiratory depression. ⚠️ HIGH RISK.
2. **Opioids:** Castro et al. (2022 [Ref 28]) documented death from combined 3-MeO-PCP + O-desmethyltramadol (active opioid metabolite). Additive respiratory depression. ⚠️ HIGH RISK.
3. **Stimulants (amphetamines):** Multiple fatal cases with amphetamine co-ingestion [Refs 14, 16]. Cardiovascular strain, increased psychosis risk. ⚠️ HIGH RISK.
4. **Benzodiazepines:** One fatal case involved delorazepam [Ref 4]. CNS depression, respiratory depression risk. ⚠️ HIGH RISK.
5. **Antidepressants (paroxetine, bupropion):** Present in one fatal polysubstance case [Ref 4]. Paroxetine is a CYP2D6 inhibitor, which may impair O-demethylation metabolism of 3-MeO-PCP. Bupropion also inhibits CYP2D6. **Potential for elevated 3-MeO-PCP blood levels via CYP2D6 inhibition.** ⚠️ FLAG.
6. **Serotonergic agents (SSRIs, MAOIs, serotonergic psychedelics):** 3-MeO-PCP has moderate SERT affinity (Ki = 216 nM). Combined with serotonergic drugs, theoretical serotonin syndrome risk exists. No published case reports documenting serotonin syndrome from 3-MeO-PCP + serotonergic drug combination, but mechanistically plausible. **Caution warranted.** ⚠️ FLAG.
7. **Diphenhydramine:** Co-present in one fatal case [Ref 16]. Potential additive CNS depression and anticholinergic interaction.
8. **Exercise/hyperthermia:** Copeland et al. (2022 [Ref 27]) specifically cautioned that physical exertion may exacerbate 3-MeO-PCP cardiovascular toxicity.
### CYP Interaction Notes
3-MeO-PCP is metabolized by CYP2D6, CYP2C19, and CYP2B6 (Michely et al. 2017 [Ref 2]; Jurowski et al. 2026 [Ref 26]). Strong inhibitors of CYP2D6 (e.g., paroxetine, fluoxetine, bupropion) or CYP2C19 (e.g., omeprazole, fluvoxamine) may impair metabolism and elevate 3-MeO-PCP plasma levels. This is a theoretical interaction not yet documented in clinical studies.
---
## Legal Status
| Jurisdiction | Status | Date | Instrument |
|---|---|---|---|
| International (UN) | Schedule II, 1971 Convention on Psychotropic Substances | April 2021 | UN Commission on Narcotic Drugs [Ref 27, Ref 18] |
| United States | Schedule I, Controlled Substances Act | March 2026 (final rule) | DEA Federal Register [Ref 19] |
| United Kingdom | Class B | 2013 (generic clause); May 2016 (specific) | Misuse of Drugs Act S.I. 2013/239 [Ref 17] |
| Germany | Annex II (controlled) | May 2015 | German narcotic regulations [Ref 17] |
| Sweden | Controlled | January 2015 | Swedish public health regulation [Ref 17] |
| Czech Republic | Scheduled | October 2015 | Government Decree 243/2015 [Ref 17] |
| Canada | Schedule I (analogue) | Pre-existing | Controlled Drugs and Substances Act (PCP analogues) [Ref 25] |
| Australia | Unconfirmed | — | Specific scheduling not verified in this research |
| Netherlands | Unconfirmed | — | First fatal case reported 2019; specific scheduling not confirmed |
---
## Clinical Trials
A search of ClinicalTrials.gov for "3-methoxyphencyclidine" and "dissociative" returned zero results. No clinical trials involving 3-MeO-PCP have been registered.
---
## Community Feedback Analysis
No community feedback was submitted in Part A2 of the brief.
---
## Gaps & Flags
### ⚠️ CRITICAL FLAGS — Pharmacological Class Errors in Seed Data
1. **"Mu-opioid receptor agonist"** classification is INCORRECT. Primary literature (Roth et al. 2013 [Ref 1]) shows no opioid receptor affinity at concentrations up to 10,000 nM. This classification should be removed from the database.
2. **"Dopamine reuptake inhibitor"** classification is NOT SUPPORTED. DAT affinity is negligible (Ki > 10,000 nM). This classification should be removed.
3. **"Dopamine receptor ligand"** classification is NOT SUPPORTED by published receptor binding data. Should be removed.
### ⚠️ DATA FLAGS — Unverified Values
4. **Tolerance half-life of "5 days" (brief):** Unverified in primary literature. No published tolerance studies exist for 3-MeO-PCP. The WHO ECDD explicitly states no dependence studies have been performed. This value derives from user reports (class inference). Flag for editorial review.
5. **Fatal concentration range:** Published cases show a wide range (50–3,525 ng/mL). The lower bound cases almost all involve polysubstance use; it is not clear that 3-MeO-PCP alone is fatal at 50 ng/mL. The single case of sole 3-MeO-PCP fatality (Berar 2019 [Ref 3]) does not report blood concentration. Range should be interpreted with caution.
6. **Dose ranges in brief:** No published controlled human dosing studies exist. All dose ranges are derived from user reports and community harm reduction resources. These are unverified and should be flagged in the article.
### Data Gaps
7. **SMILES string:** Not returned by PubChem API in this session. Generation agent should look up from PubChem CID 11778080.
8. **Human pharmacokinetics:** No published human PK studies. Bioavailability, Tmax, half-life (elimination), and protein binding are unknown from clinical data. In silico estimates exist only.
9. **Physical half-life:** PCP's elimination half-life is ~7–46 hours depending on urinary pH; 3-MeO-PCP's elimination half-life is not published.
10. **Australia-specific scheduling:** Not confirmed. Australia's Poisons Standard information could not be confirmed for 3-MeO-PCP.
11. **Stereochemistry:** No published data on stereoisomers of 3-MeO-PCP or differential activity of enantiomers. PCP itself is used as a racemate; the same likely applies to 3-MeO-PCP, but this has not been studied.
12. **Organ toxicity histopathology:** In silico predictions (lungs, liver, blood) not confirmed by published autopsy/histopathology studies.
13. **Reagent test reactions:** No peer-reviewed data on colorimetric reagent test results for 3-MeO-PCP.
14. **Serotonin syndrome risk:** Mechanistically plausible given SERT Ki = 216 nM, but no published case reports.
15. **CYP2D6/CYP2C19 drug interaction clinical significance:** Theoretically important (paroxetine co-ingestion in one fatal case [Ref 4]) but not clinically characterized.