4-MeO-PCP
4-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
oraltrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Threshold | 25 mg | 25 mg | low |
| Low | 25–50 mg | 25–50 mg | low |
| Common | 50–100 mg | 50–100 mg | low |
| Strong | 100–150 mg | 100–150 mg | low |
| Heavy | 250+ mg | 250+ mg | low |
| Editorial | Values from existing database records (community consensus origin). No published dose-response data exist for 4-MeO-PCP. Dose ranges (25–250+ mg oral) are unverified against clinical data. The fatality case involved 280 mg gastric contents in a polysubstance context (McIntyre et al. 2015). | ||
ReasoningReasoningValues from existing database records (community consensus origin). No published dose-response data exist for 4-MeO-PCP. Dose ranges (25–250+ mg oral) are unverified against clinical data. The fatality case involved 280 mg gastric contents in a polysubstance context (McIntyre et al. 2015). Evidence basis: community_consensus_small | |||
insufflatedtrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Threshold | 15 mg | 15 mg | low |
| Low | 15–30 mg | 15–30 mg | low |
| Common | 30–70 mg | 30–70 mg | low |
| Strong | 70–100 mg | 70–100 mg | low |
| Heavy | 150+ mg | 150+ mg | low |
| Editorial | Values from existing database records (community consensus origin). No published dose-response data exist for insufflated 4-MeO-PCP. All values are unverified against clinical or pharmacokinetic data. | ||
ReasoningReasoningValues from existing database records (community consensus origin). No published dose-response data exist for insufflated 4-MeO-PCP. All values are unverified against clinical or pharmacokinetic data. Evidence basis: community_consensus_small | |||
Duration
oral
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Peaktrace | 3–5 hours | 3–5 hours | low |
| Editorial | Community consensus. Broad sustained peak inferred from total duration and PCP-class kinetics. | ||
ReasoningReasoningCommunity consensus. Broad sustained peak inferred from total duration and PCP-class kinetics. Evidence basis: community_consensus_small | |||
| Onsettrace | 30–90 minutes | 30–90 minutes | low |
| Editorial | Community consensus. No published PK data. Slow onset consistent with oral arylcyclohexylamine absorption. | ||
ReasoningReasoningCommunity consensus. No published PK data. Slow onset consistent with oral arylcyclohexylamine absorption. Evidence basis: community_consensus_small | |||
| Come uptrace | 60–120 minutes | 60–120 minutes | low |
| Editorial | Community consensus. Gradual build consistent with lipophilic CNS distribution. | ||
ReasoningReasoningCommunity consensus. Gradual build consistent with lipophilic CNS distribution. Evidence basis: community_consensus_small | |||
| Offsettrace | 4–8 hours | 4–8 hours | low |
| Editorial | Community consensus. Prolonged offset consistent with lipophilic redistribution. | ||
ReasoningReasoningCommunity consensus. Prolonged offset consistent with lipophilic redistribution. Evidence basis: community_consensus_small | |||
| Totaltrace | 12–20 hours | 12–20 hours | low |
| Editorial | Existing database values (community consensus origin). Notably longer than most arylcyclohexylamines. Pharmacologically plausible given lipophilicity and CNS accumulation. No clinical verification. | ||
ReasoningReasoningExisting database values (community consensus origin). Notably longer than most arylcyclohexylamines. Pharmacologically plausible given lipophilicity and CNS accumulation. No clinical verification. Evidence basis: community_consensus_small | |||
| After effectstrace | 4–12 hours | 4–12 hours | low |
| Editorial | Community consensus. Residual cognitive impairment and emotional blunting expected after 12-20 hour experience. | ||
ReasoningReasoningCommunity consensus. Residual cognitive impairment and emotional blunting expected after 12-20 hour experience. Evidence basis: community_consensus_small | |||
insufflated
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onsettrace | 5–30 minutes | 5–30 minutes | low |
| Editorial | Community consensus. Faster onset than oral via nasal absorption. | ||
ReasoningReasoningCommunity consensus. Faster onset than oral via nasal absorption. Evidence basis: community_consensus_small | |||
| Come uptrace | 30–60 minutes | 30–60 minutes | low |
| Editorial | Community consensus. | ||
ReasoningReasoningCommunity consensus. Evidence basis: community_consensus_small | |||
| Peaktrace | 3–5 hours | 3–5 hours | low |
| Editorial | Community consensus. Peak duration similar to oral despite faster onset, due to CNS redistribution dynamics. | ||
ReasoningReasoningCommunity consensus. Peak duration similar to oral despite faster onset, due to CNS redistribution dynamics. Evidence basis: community_consensus_small | |||
| Offsettrace | 4–6 hours | 4–6 hours | low |
| Editorial | Community consensus. | ||
ReasoningReasoningCommunity consensus. Evidence basis: community_consensus_small | |||
| Totaltrace | 12–18 hours | 12–18 hours | low |
| Editorial | Existing database values (community consensus origin). Slightly shorter range than oral, consistent with faster onset but similar CNS retention. | ||
ReasoningReasoningExisting database values (community consensus origin). Slightly shorter range than oral, consistent with faster onset but similar CNS retention. Evidence basis: community_consensus_small | |||
| After effectstrace | 4–10 hours | 4–10 hours | low |
| Editorial | Community consensus. | ||
ReasoningReasoningCommunity consensus. Evidence basis: community_consensus_small | |||
Safety
Toxicity Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Acute | moderate | moderate | low |
| Chronic | moderate | moderate | low |
| Organs Affected | cns, cardiovascular, respiratory, musculoskeletal, renal | cns, cardiovascular, respiratory, musculoskeletal, renal | low |
| Editorial | Classified as moderate (downgraded from high): the single fatality and mouse lethality data would suggest high acute toxicity, but the fatality involved polysubstance exposure, and all toxidrome characterization derives from PCP class analogs rather than substance-specific data. Chronic toxicity is moderate by class inference from PCP/ketamine (urological, neurological damage) but no 4-MeO-PCP-specific chronic data exist. | ||
ReasoningReasoningClassified as moderate (downgraded from high): the single fatality and mouse lethality data would suggest high acute toxicity, but the fatality involved polysubstance exposure, and all toxidrome characterization derives from PCP class analogs rather than substance-specific data. Chronic toxicity is moderate by class inference from PCP/ketamine (urological, neurological damage) but no 4-MeO-PCP-specific chronic data exist. Evidence basis: single_case_report | |||
Dependence Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Physical | low | low | low |
| Psychological | moderate | moderate | low |
| Compulsive Redosing | low | low | low |
| Dose Escalation | moderate | moderate | low |
| Editorial | No substance-specific dependence data exist. Profile inferred from PCP (documented SUD, tolerance, compulsive use; Morris and Wallach 2014; Bertron et al. 2018) and ketamine (well-documented dependence). PCP-like drug discrimination confirms abuse liability (Shaw et al. 2024). Physical dependence rated low rather than moderate because PCP physical withdrawal is less severe than for classical depressants. | ||
ReasoningReasoningNo substance-specific dependence data exist. Profile inferred from PCP (documented SUD, tolerance, compulsive use; Morris and Wallach 2014; Bertron et al. 2018) and ketamine (well-documented dependence). PCP-like drug discrimination confirms abuse liability (Shaw et al. 2024). Physical dependence rated low rather than moderate because PCP physical withdrawal is less severe than for classical depressants. Evidence basis: structural_analogy | |||
Withdrawal Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Severity | mild | mild | low |
| Symptoms | dysphoria, anxiety, cravings, cognitive impairment, sleep disturbance | dysphoria, anxiety, cravings, cognitive impairment, sleep disturbance | low |
| Fatal | No | No | low |
| Medical Supervision | Not required | Not required | low |
| Editorial | No withdrawal data specific to 4-MeO-PCP. PCP and ketamine withdrawal is characterized by dysphoria, cravings, and psychological distress rather than life-threatening physical withdrawal. Severity rated mild by class inference. | ||
ReasoningReasoningNo withdrawal data specific to 4-MeO-PCP. PCP and ketamine withdrawal is characterized by dysphoria, cravings, and psychological distress rather than life-threatening physical withdrawal. Severity rated mild by class inference. 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, 3-MeO-PCP, ketamine, methoxetamine, dextromethorphan | PCP, 3-MeO-PCP, ketamine, methoxetamine, dextromethorphan | low |
| Editorial | No substance-specific tolerance data exist. Values carried forward from existing database records (community consensus). Mechanism and cross-tolerance pattern inferred from PCP/ketamine NMDA antagonist pharmacology. The long duration of action may slow tolerance development relative to shorter-acting dissociatives. | ||
ReasoningReasoningNo substance-specific tolerance data exist. Values carried forward from existing database records (community consensus). Mechanism and cross-tolerance pattern inferred from PCP/ketamine NMDA antagonist pharmacology. The long duration of action may slow tolerance development relative to shorter-acting dissociatives. Evidence basis: community_consensus_small | |||
Effects & Profile
Contraindications
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| cardiovascular cardiovascular diseasetrace | relative | relative | low |
| Editorial | Class-level inference from PCP cardiovascular toxicity (Jentsch and Roth 1999). No 4-MeO-PCP-specific cardiovascular data. | ||
ReasoningReasoningClass-level inference from PCP cardiovascular toxicity (Jentsch and Roth 1999). No 4-MeO-PCP-specific cardiovascular data. | |||
| psychiatric psychotic disorderstrace | absolute | absolute | medium |
| Editorial | PCP is the canonical pharmacological model of psychosis (Jentsch and Roth 1999). 4-MeO-PCP confirmed PCP-like in drug discrimination (Shaw et al. 2024). Class-level absolute contraindication. | ||
ReasoningReasoningPCP is the canonical pharmacological model of psychosis (Jentsch and Roth 1999). 4-MeO-PCP confirmed PCP-like in drug discrimination (Shaw et al. 2024). Class-level absolute contraindication. | |||
| psychiatric bipolar disordertrace | relative | relative | low |
| Editorial | 3-MeO-PCP mania reported in clinical literature (Bäckberg et al. 2015). 4-MeO-PCP shares the PCP binding site mechanism. Community reports suggest lower but non-zero mania risk. | ||
ReasoningReasoning3-MeO-PCP mania reported in clinical literature (Bäckberg et al. 2015). 4-MeO-PCP shares the PCP binding site mechanism. Community reports suggest lower but non-zero mania risk. | |||
| neurological epilepsytrace | relative | relative | low |
| Editorial | Class-level inference from PCP neurotoxicity. No 4-MeO-PCP-specific seizure data published. | ||
ReasoningReasoningClass-level inference from PCP neurotoxicity. No 4-MeO-PCP-specific seizure data published. | |||
| hepatic hepatic impairmenttrace | relative | relative | low |
| Editorial | Metabolic pathway inferred from 3-MeO-PCP data (Michely et al. 2017). Hepatic accumulation demonstrated in fatality case (120 mg/kg liver concentration; McIntyre et al. 2015). | ||
ReasoningReasoningMetabolic pathway inferred from 3-MeO-PCP data (Michely et al. 2017). Hepatic accumulation demonstrated in fatality case (120 mg/kg liver concentration; McIntyre et al. 2015). | |||
| renal renal impairmenttrace | relative | relative | low |
| Editorial | Rhabdomyolysis with AKI documented for 3-methyl-PCP (Deutsch et al. 2026). Class-level renal risk inference. | ||
ReasoningReasoningRhabdomyolysis with AKI documented for 3-methyl-PCP (Deutsch et al. 2026). Class-level renal risk inference. | |||
| pregnancy breastfeeding pregnancytrace | absolute | absolute | medium |
| Editorial | NMDA receptors are essential for neurodevelopment. Class-level precautionary contraindication. No substance-specific data. | ||
ReasoningReasoningNMDA receptors are essential for neurodevelopment. Class-level precautionary contraindication. No substance-specific data. | |||
| other concurrent serotonergic medicationstrace | relative | relative | medium |
| Editorial | SERT affinity confirmed (Roth et al. 2013). Fatality case involved SNRI co-exposure (McIntyre et al. 2015). No serotonin syndrome cases specifically documented for 4-MeO-PCP, but pharmacodynamic risk is clear. | ||
ReasoningReasoningSERT affinity confirmed (Roth et al. 2013). Fatality case involved SNRI co-exposure (McIntyre et al. 2015). No serotonin syndrome cases specifically documented for 4-MeO-PCP, but pharmacodynamic risk is clear. | |||
Timeline Phases
insufflated
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Come uptrace | 1800–3600 sec(i=0.35) | 1800–3600 sec(i=0.35) | low |
| Editorial | No controlled data exist. Timings derived from community consensus (12–18 hours total insufflated) with faster onset adjusted for nasal bioavailability. Phase proportions inferred from PCP-class pharmacokinetics. | ||
ReasoningReasoningNo controlled data exist. Timings derived from community consensus (12–18 hours total insufflated) with faster onset adjusted for nasal bioavailability. Phase proportions inferred from PCP-class pharmacokinetics. Evidence basis: community_consensus_small | |||
| Onsettrace | 300–1800 sec(i=0.05) | 300–1800 sec(i=0.05) | low |
| Editorial | No controlled data exist. Timings derived from community consensus (12–18 hours total insufflated) with faster onset adjusted for nasal bioavailability. Phase proportions inferred from PCP-class pharmacokinetics. | ||
ReasoningReasoningNo controlled data exist. Timings derived from community consensus (12–18 hours total insufflated) with faster onset adjusted for nasal bioavailability. Phase proportions inferred from PCP-class pharmacokinetics. Evidence basis: community_consensus_small | |||
| Peaktrace | 10800–16200 sec(i=1.00) | 10800–16200 sec(i=1.00) | low |
| Editorial | No controlled data exist. Timings derived from community consensus (12–18 hours total insufflated) with faster onset adjusted for nasal bioavailability. Phase proportions inferred from PCP-class pharmacokinetics. | ||
ReasoningReasoningNo controlled data exist. Timings derived from community consensus (12–18 hours total insufflated) with faster onset adjusted for nasal bioavailability. Phase proportions inferred from PCP-class pharmacokinetics. Evidence basis: community_consensus_small | |||
| Plateautrace | 7200–14400 sec(i=0.50) | 7200–14400 sec(i=0.50) | low |
| Editorial | No controlled data exist. Timings derived from community consensus (12–18 hours total insufflated) with faster onset adjusted for nasal bioavailability. Phase proportions inferred from PCP-class pharmacokinetics. | ||
ReasoningReasoningNo controlled data exist. Timings derived from community consensus (12–18 hours total insufflated) with faster onset adjusted for nasal bioavailability. Phase proportions inferred from PCP-class pharmacokinetics. Evidence basis: community_consensus_small | |||
| Resolutiontrace | 5400–10800 sec(i=0.20) | 5400–10800 sec(i=0.20) | low |
| Editorial | No controlled data exist. Timings derived from community consensus (12–18 hours total insufflated) with faster onset adjusted for nasal bioavailability. Phase proportions inferred from PCP-class pharmacokinetics. | ||
ReasoningReasoningNo controlled data exist. Timings derived from community consensus (12–18 hours total insufflated) with faster onset adjusted for nasal bioavailability. Phase proportions inferred from PCP-class pharmacokinetics. Evidence basis: community_consensus_small | |||
| Afterglowtrace | 14400–36000 sec(i=0.05) | 14400–36000 sec(i=0.05) | low |
| Editorial | No controlled data exist. Timings derived from community consensus (12–18 hours total insufflated) with faster onset adjusted for nasal bioavailability. Phase proportions inferred from PCP-class pharmacokinetics. | ||
ReasoningReasoningNo controlled data exist. Timings derived from community consensus (12–18 hours total insufflated) with faster onset adjusted for nasal bioavailability. Phase proportions inferred from PCP-class pharmacokinetics. Evidence basis: community_consensus_small | |||
oral
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onsettrace | 1800–5400 sec(i=0.05) | 1800–5400 sec(i=0.05) | low |
| Editorial | No controlled pharmacokinetic or duration data exist. All phase timings are derived from community consensus (12–20 hours total oral) and pharmacological plausibility given PCP-class lipophilicity and CNS accumulation. Phase proportions inferred from PCP and 3-MeO-PCP temporal profiles. | ||
ReasoningReasoningNo controlled pharmacokinetic or duration data exist. All phase timings are derived from community consensus (12–20 hours total oral) and pharmacological plausibility given PCP-class lipophilicity and CNS accumulation. Phase proportions inferred from PCP and 3-MeO-PCP temporal profiles. Evidence basis: community_consensus_small | |||
| Come uptrace | 3600–7200 sec(i=0.30) | 3600–7200 sec(i=0.30) | low |
| Editorial | No controlled pharmacokinetic or duration data exist. All phase timings are derived from community consensus (12–20 hours total oral) and pharmacological plausibility given PCP-class lipophilicity and CNS accumulation. Phase proportions inferred from PCP and 3-MeO-PCP temporal profiles. | ||
ReasoningReasoningNo controlled pharmacokinetic or duration data exist. All phase timings are derived from community consensus (12–20 hours total oral) and pharmacological plausibility given PCP-class lipophilicity and CNS accumulation. Phase proportions inferred from PCP and 3-MeO-PCP temporal profiles. Evidence basis: community_consensus_small | |||
| Peaktrace | 10800–18000 sec(i=1.00) | 10800–18000 sec(i=1.00) | low |
| Editorial | No controlled pharmacokinetic or duration data exist. All phase timings are derived from community consensus (12–20 hours total oral) and pharmacological plausibility given PCP-class lipophilicity and CNS accumulation. Phase proportions inferred from PCP and 3-MeO-PCP temporal profiles. | ||
ReasoningReasoningNo controlled pharmacokinetic or duration data exist. All phase timings are derived from community consensus (12–20 hours total oral) and pharmacological plausibility given PCP-class lipophilicity and CNS accumulation. Phase proportions inferred from PCP and 3-MeO-PCP temporal profiles. Evidence basis: community_consensus_small | |||
| Plateautrace | 10800–18000 sec(i=0.50) | 10800–18000 sec(i=0.50) | low |
| Editorial | No controlled pharmacokinetic or duration data exist. All phase timings are derived from community consensus (12–20 hours total oral) and pharmacological plausibility given PCP-class lipophilicity and CNS accumulation. Phase proportions inferred from PCP and 3-MeO-PCP temporal profiles. | ||
ReasoningReasoningNo controlled pharmacokinetic or duration data exist. All phase timings are derived from community consensus (12–20 hours total oral) and pharmacological plausibility given PCP-class lipophilicity and CNS accumulation. Phase proportions inferred from PCP and 3-MeO-PCP temporal profiles. Evidence basis: community_consensus_small | |||
| Resolutiontrace | 7200–14400 sec(i=0.20) | 7200–14400 sec(i=0.20) | low |
| Editorial | No controlled pharmacokinetic or duration data exist. All phase timings are derived from community consensus (12–20 hours total oral) and pharmacological plausibility given PCP-class lipophilicity and CNS accumulation. Phase proportions inferred from PCP and 3-MeO-PCP temporal profiles. | ||
ReasoningReasoningNo controlled pharmacokinetic or duration data exist. All phase timings are derived from community consensus (12–20 hours total oral) and pharmacological plausibility given PCP-class lipophilicity and CNS accumulation. Phase proportions inferred from PCP and 3-MeO-PCP temporal profiles. Evidence basis: community_consensus_small | |||
| Afterglowtrace | 14400–43200 sec(i=0.05) | 14400–43200 sec(i=0.05) | low |
| Editorial | No controlled pharmacokinetic or duration data exist. All phase timings are derived from community consensus (12–20 hours total oral) and pharmacological plausibility given PCP-class lipophilicity and CNS accumulation. Phase proportions inferred from PCP and 3-MeO-PCP temporal profiles. | ||
ReasoningReasoningNo controlled pharmacokinetic or duration data exist. All phase timings are derived from community consensus (12–20 hours total oral) and pharmacological plausibility given PCP-class lipophilicity and CNS accumulation. Phase proportions inferred from PCP and 3-MeO-PCP temporal profiles. Evidence basis: community_consensus_small | |||
Dose Tier Summaries
At threshold doses, effects are barely perceptible: a mild sense of detachment from surroundings, slight cognitive slowing, and subtle changes in spatial awareness. Some users describe a faint heaviness in the limbs and a vague sense that sensory processing has shifted without being able to identify how. Physically, mild sedation and slight pupil dilation may be noticeable. Functional impairment is minimal, though subtle coordination changes can occur. Given the prolonged duration profile of 4-MeO-PCP, even threshold effects may persist for several hours.
No published dose-response data exist for 4-MeO-PCP. Threshold description inferred from PCP class phenomenology, community reports, and the compound's confirmed PCP-like interoceptive profile (Shaw et al. 2024). All values are community consensus.
ReasoningReasoning
No published dose-response data exist for 4-MeO-PCP. Threshold description inferred from PCP class phenomenology, community reports, and the compound's confirmed PCP-like interoceptive profile (Shaw et al. 2024). All values are community consensus.
Evidence basis: community_consensus_small
Light doses produce a recognizable dissociative state: mild depersonalization, a sense of emotional detachment, and noticeable cognitive slowing. Spatial perception begins to distort — distances may feel altered, and proprioception becomes unreliable. Thought patterns become somewhat disconnected, with reduced verbal fluency. Physically, sedation becomes more pronounced than at threshold. Mild nystagmus may appear. Coordination is impaired, and ambulation feels unsteady. The onset is slow (community reports suggest 1–2 hours oral), and effects may persist for 12 hours or longer, making this a substantial time commitment.
Inferred from PCP class phenomenology and community consensus. No published clinical data characterize light-dose effects of 4-MeO-PCP. The sedating character relative to 3-MeO-PCP is consistent with reduced locomotor stimulation in rodents (Shaw et al. 2024).
ReasoningReasoning
Inferred from PCP class phenomenology and community consensus. No published clinical data characterize light-dose effects of 4-MeO-PCP. The sedating character relative to 3-MeO-PCP is consistent with reduced locomotor stimulation in rodents (Shaw et al. 2024).
Evidence basis: community_consensus_small
At common doses, the full dissociative experience emerges: pronounced depersonalization and derealization, significant distortion of spatial and temporal perception, and a sense of detachment from the body. Visual disturbances include drifting, morphing of surfaces, and suppression of visual acuity. Thought processes become markedly fragmented, with difficulty maintaining linear trains of thought. Physically, sedation is prominent — more so than with 3-MeO-PCP at equivalent subjective intensity. Nystagmus, ataxia, and slurred speech are typical. Nausea may occur during onset. The total experience extends 12–18 hours by community report, precluding normal activities for the full duration and requiring a clear schedule with no obligations.
Community consensus dose ranges and qualitative descriptions. Sedating character inferred from reduced locomotor stimulation vs PCP (Shaw et al. 2024) and community reports distinguishing 4-MeO-PCP from the more stimulant 3-MeO-PCP (Bäckberg et al. 2015).
ReasoningReasoning
Community consensus dose ranges and qualitative descriptions. Sedating character inferred from reduced locomotor stimulation vs PCP (Shaw et al. 2024) and community reports distinguishing 4-MeO-PCP from the more stimulant 3-MeO-PCP (Bäckberg et al. 2015).
Evidence basis: community_consensus_small
Strong doses produce deep dissociation approaching the 'hole' experience: near-complete detachment from sensory input, profound derealization, loss of body awareness, and immersive internal experiences that may include complex hallucinations and distorted time perception so severe that minutes feel like hours. Communication becomes extremely difficult or impossible. Amnesia for portions of the experience is common. Physically, motor function is severely impaired — standing or walking is dangerous. Respiratory depression becomes a concern, particularly in combination with other CNS depressants. Hypothermia is possible based on animal data. The duration at this range may extend to 16–20 hours, with residual cognitive impairment lasting well beyond.
Inferred from PCP class pharmacology, animal toxicology (Shaw et al. 2024), clinical intoxication presentations of 3-MeO-PCP (coma, respiratory acidosis at GCS 3; Bertol et al. 2017), and community consensus. No published clinical data for 4-MeO-PCP at strong doses.
ReasoningReasoning
Inferred from PCP class pharmacology, animal toxicology (Shaw et al. 2024), clinical intoxication presentations of 3-MeO-PCP (coma, respiratory acidosis at GCS 3; Bertol et al. 2017), and community consensus. No published clinical data for 4-MeO-PCP at strong doses.
Evidence basis: community_consensus_small
Heavy doses carry serious medical risk. Complete dissociation from external reality, catatonia or unresponsive states, and psychotic episodes with paranoia and agitation (upon partial recovery) are expected based on PCP class pharmacology. Loss of consciousness progressing to coma is possible, as documented for 3-MeO-PCP at comparable intoxication severity. Respiratory depression requiring medical intervention, rhabdomyolysis, cardiovascular stress (tachycardia, hypertension), and seizures represent the primary acute dangers. The single published 4-MeO-PCP fatality involved massive ingestion (280 mg gastric contents) in a polysubstance context. Duration at these doses is unpredictable and may exceed 20 hours, with psychiatric and cognitive aftereffects potentially lasting days.
Based on the published 4-MeO-PCP fatality case (McIntyre et al. 2015), 3-MeO-PCP intoxication case reports (Bertol et al. 2017; Johansson et al. 2017), PCP class toxidrome literature, and community consensus. All heavy-dose characterization is class inference or analog extrapolation.
ReasoningReasoning
Based on the published 4-MeO-PCP fatality case (McIntyre et al. 2015), 3-MeO-PCP intoxication case reports (Bertol et al. 2017; Johansson et al. 2017), PCP class toxidrome literature, and community consensus. All heavy-dose characterization is class inference or analog extrapolation.
Evidence basis: structural_analogy
History
backfill Jun 4, 2026
Historical versions do not record which reviewer approved them; editorial accountability is recorded per value in the database and in the publication ledger going forward.
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- [18]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
- [19]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
- [20]moderate1-cyclohexyl-x-methoxybenzene derivatives, novel psychoactive substances seized on the internet market: Synthesis and in vivo pharmacological studies in miceFantinati A, Ossato A, Bianco S, Canazza I, De-Giorgio F, et al. · 2017 · Human Psychopharmacology Clinical and Experimental
- [21]weakRhabdomyolysis and Acute Kidney Injury after Use of 3-Methyl-PCP: A Case ReportDeutsch AB, Ebeling-Koning NE, Krotulski AJ, Walton SE, Katz KD · 2026 · Journal of Medical Toxicology
- [22]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
- [23]moderateWhen good times go bad: managing 'legal high' complications in the emergency departmentCaffrey C, Lank PM · 2017 · Open Access Emergency 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.
summary7 claims4verified3partial
verifiedPCP-like drug discrimination confirms dissociative interoceptive effects[5]model confidence 97%
The abstract explicitly states all novel ACXs substituted at least partially for PCP in drug discrimination, directly confirming PCP-like interoceptive effects.
All novel ACXs substituted at least partially for PCP (drug discrimination).
checked by claude-sonnet-4-6 · Apr 28, 2026
partial4-MeO-PCP was first synthesized in 1965 by Victor Maddox at Parke-Davis and holds the distinction of being the first dissociative research chemical sold online, introduced to the market in late 2008[1]model confidence 85%
The abstract confirms 4-MeO-PCP was the first dissociative research chemical and appeared on the market in 2008, but contains no information about the 1965 synthesis, Victor Maddox, or Parke-Davis — those specific historical details cannot be verified from this abstract.
4-MeO-PCP identified as the first dissociative research chemical, appearing on the market in 2008.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThis event pioneered the online dissociative novel psychoactive substance (NPS) market that subsequently produced over a dozen additional compounds[1]model confidence 88%
The abstract documents a historical account of non-medical use of over 30 dissociative compounds, which supports that the market pioneered by 4-MeO-PCP went on to produce well over a dozen additional compounds.
Historical account of non-medical use of over 30 dissociative compounds.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe compound acts as a high-affinity ligand at the phencyclidine binding site on the NMDA glutamate receptor, with additional affinity for sigma receptors and the serotonin transporter[3]model confidence 95%
The paper title explicitly states 3- and 4-methoxy analogues of phencyclidine (including 4-MeO-PCP) are high-affinity NMDA receptor ligands; the abstract confirms PCP analogues have high sigma receptor affinities and appreciable serotonin transporter affinities.
PCP analogues exhibited high affinities for sigma receptors. Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter.
checked by claude-sonnet-4-6 · Apr 28, 2026
partialStructure-activity data from the morpholine analog series indicate that para-methoxy substitution reduces NMDAR affinity relative to the meta-isomer, and rodent studies confirm reduced locomotor stimulation compared to PCP[4]model confidence 80%
The abstract clearly supports the morpholine SAR finding (4-MeO-PCMo has lowest NMDAR affinity, below 3-MeO-PCMo). However, the rodent locomotor reduction claim is not addressed by this citation — that data comes from a separate study (Shaw et al. 2024).
NMDAR affinity rank: 3-Me > 3-MeO > PCMo > 3,4-MD > 2-MeO > 4-MeO-PCMo.
checked by claude-sonnet-4-6 · Apr 28, 2026
partialStructure-activity data from the morpholine analog series indicate that para-methoxy substitution reduces NMDAR affinity relative to the meta-isomer, and rodent studies confirm reduced locomotor stimulation compared to PCP[5]model confidence 80%
The abstract directly supports the rodent locomotor reduction (addition of -OMe at 4-position reduces locomotor effectiveness vs PCP), but says nothing about the morpholine analog series SAR data, which comes from a separate citation.
Addition of -OMe at 4-position reduces locomotor effectiveness vs parent PCP.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedOne confirmed fatality involved 4-MeO-PCP as the principal cause of death in a polysubstance context (peripheral blood 8.2 mg/L), though this single case does not establish a lethal threshold[6]model confidence 98%
The abstract directly confirms 4-MeO-PCP as principal cause of death, peripheral blood 8.2 mg/L, and lists co-medications (polysubstance context).
Postmortem toxicology case: 4-MeO-PCP principal cause of death. Peripheral blood 8.2 mg/L.
checked by claude-sonnet-4-6 · Apr 28, 2026
history7 claims3verified4inconclusive
inconclusive2015: The first confirmed fatality attributed principally to 4-MeO-PCP was published.[6]model confidence 70%
The abstract confirms this is a fatality case attributed principally to 4-MeO-PCP, but provides no publication date. The year 2015 cannot be verified from the abstract text.
Postmortem toxicology case: 4-MeO-PCP principal cause of death.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveThe synthesis of 4-MeO-PCP was first reported in 1965 by Victor Maddox, a medicinal chemist at Parke-Davis — the same pharmaceutical company that had originated phencyclidine in 1956[1]model confidence 65%
The abstract addresses 4-MeO-PCP's market appearance in 2008 but contains no information about its 1965 synthesis, Victor Maddox, or Parke-Davis. These synthesis history details cannot be verified from this abstract.
4-MeO-PCP identified as the first dissociative research chemical, appearing on the market in 2008.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusivePCP itself was withdrawn from human clinical use in 1965 due to severe psychotomimetic side effects — the same year 4-MeO-PCP was synthesized.[8]model confidence 62%
The abstract covers PCP history broadly but does not specifically confirm the 1965 clinical withdrawal date. This detail would likely be in the full review but cannot be confirmed from the brief abstract.
PCP history, synthesis, pharmacology, drug metabolism, and folklore.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedPCP's mechanism of action — NMDA receptor hypofunction — later became foundational to the glutamate hypothesis of schizophrenia[9]model confidence 97%
The abstract explicitly names the NMDA receptor hypofunction hypothesis as its core subject and links it to PCP's pharmacology, directly supporting this claim.
Review of PCP neuropsychopharmacology; NMDA receptor hypofunction hypothesis.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveAt least 14 PCP derivatives circulated for non-medical use from the late 1960s through the 1990s before the internet-enabled research chemical market emerged.[1]model confidence 60%
The abstract covers a historical account of non-medical use of over 30 dissociative compounds, which is consistent with the broad claim, but the specific number 14 and the pre-internet time period (late 1960s–1990s) cannot be verified from the abstract alone.
Historical account of non-medical use of over 30 dissociative compounds.
checked by claude-sonnet-4-6 · Apr 28, 2026
verified4-MeO-PCP holds the distinction of being the first dissociative research chemical sold online[1]model confidence 99%
The abstract directly identifies 4-MeO-PCP as the first dissociative research chemical, appearing on the market in 2008.
4-MeO-PCP identified as the first dissociative research chemical, appearing on the market in 2008.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThis event pioneered the online dissociative NPS market that subsequently produced at least 12 additional compounds including methoxetamine, 3-meo-pcp, and others.[1]model confidence 88%
The abstract documents a historical account of over 30 dissociative compounds. A market that ultimately covered 30+ compounds would have included at least 12 additional compounds after 4-MeO-PCP, supporting the claim.
Historical account of non-medical use of over 30 dissociative compounds.
checked by claude-sonnet-4-6 · Apr 28, 2026
chemistry2 claims2verified
verifiedThree positional isomers exist — 2-MeO-PCP, 3-MeO-PCP, and 4-MeO-PCP — each with distinct pharmacological profiles and analytically distinguishable by GC-MS retention time and mass spectral fragmentation.[11]model confidence 85%
The abstract demonstrates full GC-MS and LC-MS/MS analytical characterization of MeO-PCP analogues, establishing their analytical distinguishability. The paper characterizes 3-MeO and 4-MeO variants and includes GC degradation data specific to 4-MeO-PCP, supporting the broader claim about isomer distinguishability.
Synthesis and full analytical characterization of 3-MeO-, 4-MeO- and 3-Me-PCP and PCPy analogues. GC-MS, LC-MS/MS, IR, NMR data.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThree positional isomers exist — 2-MeO-PCP, 3-MeO-PCP, and 4-MeO-PCP — each with distinct pharmacological profiles and analytically distinguishable by GC-MS retention time and mass spectral fragmentation.[12]model confidence 83%
The abstract confirms GC-MS method development and validation for 3-MeO-PCP and 4-MeO-PCP as analytically distinct compounds, supporting the claim about analytical distinguishability of the isomers.
GC-MS method development and validation for 3-MeO-PCP/4-MeO-PCP.
checked by claude-sonnet-4-6 · Apr 28, 2026
pharmacology10 claims7verified1partial2inconclusive
verified4-MeO-PCP acts as a high-affinity ligand at the phencyclidine binding site on the NMDA glutamate receptor, the primary molecular target responsible for the dissociative and anesthetic effects of the arylcyclohexylamine class[3]model confidence 96%
The paper title and abstract confirm 4-methoxy analogues of phencyclidine are high-affinity ligands for the glutamate NMDA receptor via NIMH PDSP screening.
3-MeO-PCE confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe compound was characterized as part of the NIMH Psychoactive Drug Screening Program (PDSP) alongside methoxetamine and the 3-methoxy PCP isomer[3]model confidence 97%
The abstract explicitly states pharmacological profiles were obtained via NIMH PDSP; the title names methoxetamine and 3- and 4-methoxy analogues of phencyclidine as the study compounds.
Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveNMDA receptor blockade occurs at the open channel state, producing use-dependent inhibition of glutamatergic neurotransmission — the same mechanism responsible for PCP's anesthetic, psychotomimetic, and neuroprotective properties.[9]model confidence 65%
The abstract confirms this is a review of PCP neuropsychopharmacology and the NMDA receptor hypofunction hypothesis, which would encompass open-channel blockade mechanisms. However, the abstract is too brief to confirm the specific mechanistic details claimed (open channel state, use-dependence), requiring the full paper.
Review of PCP neuropsychopharmacology; NMDA receptor hypofunction hypothesis.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedExact Ki values (in nM) for 4-MeO-PCP at the NMDA receptor, sigma receptors, and serotonin transporter were reported by Roth et al. (2013) but could not be extracted from the available abstract.[3]model confidence 90%
The abstract confirms pharmacological profiling at NMDA, sigma, and serotonin transporter targets via NIMH PDSP, establishing that Ki values were measured. The claim accurately acknowledges the values are not extractable from the abstract, which is consistent with the abstract's level of detail.
Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP. PCP analogues exhibited high affinities for sigma receptors.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedBeyond the NMDA receptor, 4-MeO-PCP exhibits appreciable affinity for sigma receptors and the serotonin transporter (SERT)[3]model confidence 97%
The abstract directly states that PCP analogues showed high affinities for sigma receptors and appreciable affinities for the serotonin transporter.
Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter; PCP analogues exhibited high affinities for sigma receptors.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveDopamine reuptake inhibition is plausible as a class-level inference — PCP inhibits DAT, contributing to its stimulant and psychotomimetic properties — but no published study has specifically quantified DAT affinity for 4-MeO-PCP. The para-isomer of 1-cyclohexyl-methoxybenzene (structurally analogous) was inactive at mu, kappa, and delta opioid receptors in vitro.[9]model confidence 60%
The abstract only mentions 'PCP neuropsychopharmacology' and 'NMDA receptor hypofunction hypothesis' without specifics on DAT or opioid receptors. The opioid inactivity data comes from a different citation. The DAT claim is plausible within the scope of the review but not confirmable from the abstract alone.
Review of PCP neuropsychopharmacology; NMDA receptor hypofunction hypothesis.
checked by claude-sonnet-4-6 · Apr 28, 2026
partialDopamine reuptake inhibition is plausible as a class-level inference — PCP inhibits DAT, contributing to its stimulant and psychotomimetic properties — but no published study has specifically quantified DAT affinity for 4-MeO-PCP. The para-isomer of 1-cyclohexyl-methoxybenzene (structurally analogous) was inactive at mu, kappa, and delta opioid receptors in vitro.[15]model confidence 82%
The abstract directly confirms that the 1-cyclohexyl-x-methoxybenzene series (including para isomer) was inactive at mu/kappa/delta opioid receptors in vitro, supporting that portion of the claim. However, the DAT/PCP inhibition component is not addressed in this abstract.
In vitro: 1-cyclohexyl-x-methoxybenzene (ortho, meta, para) inactive at mu/kappa/delta opioid receptors.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedIn the morpholine-ring analog series (PCMo), the rank order of NMDAR affinity follows: 3-Me > 3-MeO > PCMo > 3,4-MD > 2-MeO > 4-MeO-PCMo (lowest)[4]model confidence 99%
The abstract provides the exact rank order verbatim: 3-Me > 3-MeO > PCMo > 3,4-MD > 2-MeO > 4-MeO-PCMo.
NMDAR affinity rank: 3-Me > 3-MeO > PCMo > 3,4-MD > 2-MeO > 4-MeO-PCMo.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe metabolic fate of the closest characterized analog, 3-meo-pcp, was elucidated in rat urine and pooled human liver microsomes by Michely et al. (2017):[14]model confidence 98%
The abstract directly confirms that the metabolic fate of 3-MeO-PCP was elucidated using rat urine and pooled human liver microsomes.
Metabolic fate of 3-MeO-PCP and 3-MeO-PCPy elucidated in rat urine and pooled human liver microsomes.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedPoor metabolizers at CYP2D6 may show elevated parent drug exposure, though clinical confirmation is lacking.[14]model confidence 87%
The abstract confirms CYP2D6 is responsible for O-demethylation. The inference that poor metabolizers at CYP2D6 would show elevated parent drug exposure is a well-established pharmacogenomic principle, reasonable from this data.
CYP2C19 and CYP2D6 for O-demethylation.
checked by claude-sonnet-4-6 · Apr 28, 2026
receptor pharmacology6 claims5verified1inconclusive
verifiedSerotonin syndrome has not been reported for 4-MeO-PCP specifically, but the single published fatality involved co-ingestion with venlafaxine (an SNRI).[6]model confidence 95%
The abstract confirms venlafaxine was among the co-medications detected. The absence of a serotonin syndrome report is consistent with a postmortem case report that describes cause of death without specifically mentioning serotonin syndrome.
Co-medications: venlafaxine, olanzapine, lorazepam, hydroxyzine at therapeutic levels.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedRoth et al. (2013) confirmed 4-MeO-PCP as a high-affinity ligand for the PCP binding site within the NMDA receptor ion channel using the NIMH PDSP radioligand displacement assay[3]model confidence 97%
The title directly states 4-methoxy analogues of phencyclidine are high-affinity NMDA receptor ligands; the abstract confirms this was done via NIMH PDSP.
Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe rank order 3-Me > 3-MeO > parent > 3,4-MD > 2-MeO > 4-MeO indicates that the 4-MeO position is the least favourable for NMDAR binding in this series.[4]model confidence 99%
The abstract provides the exact rank order confirming 4-MeO-PCMo has the lowest NMDAR affinity among all isomers tested.
NMDAR affinity rank: 3-Me > 3-MeO > PCMo > 3,4-MD > 2-MeO > 4-MeO-PCMo.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedPCP and its methoxy analogues — including 4-MeO-PCP — exhibit high affinities for sigma receptors[3]model confidence 97%
The abstract directly states that PCP analogues exhibited high affinities for sigma receptors.
PCP analogues exhibited high affinities for sigma receptors.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusivePCP inhibits DAT, contributing to stimulant and psychotomimetic properties[9]model confidence 58%
The abstract mentions PCP neuropsychopharmacology and the dopamine hypothesis in the paper title, but the abstract itself only references the NMDA hypofunction hypothesis. DAT inhibition as a specific mechanism is not confirmed in the available abstract text.
Review of PCP neuropsychopharmacology; NMDA receptor hypofunction hypothesis.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe para-methoxy isomer of 1-cyclohexyl-methoxybenzene (structurally analogous to 4-MeO-PCP) was inactive at mu, kappa, and delta opioid receptors in vitro[15]model confidence 99%
The abstract directly confirms that the full series of 1-cyclohexyl-x-methoxybenzene compounds (ortho, meta, para) were inactive at mu, kappa, and delta opioid receptors in vitro.
In vitro: 1-cyclohexyl-x-methoxybenzene (ortho, meta, para) inactive at mu/kappa/delta opioid receptors.
checked by claude-sonnet-4-6 · Apr 28, 2026
neuroscience6 claims6verified
verifiedPCP and ketamine block NMDA receptors on GABAergic interneurons in the prefrontal cortex, paradoxically disinhibiting glutamatergic pyramidal neurons and producing a downstream surge in cortical glutamate release[9]model confidence 87%
This is a review specifically of PCP neuropsychopharmacology centered on the NMDA receptor hypofunction hypothesis. GABAergic interneuron disinhibition leading to glutamate surge is the canonical cellular mechanism underlying the NMDA hypofunction hypothesis, placing it squarely within this review's stated scope.
Review of PCP neuropsychopharmacology; NMDA receptor hypofunction hypothesis.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe resulting disruption of normal prefrontal cortical function underlies the cognitive fragmentation, depersonalization, and reality distortion characteristic of dissociative states. 4-MeO-PCP, acting through the same PCP binding site, is expected to produce qualitatively similar cortical disruption.[3]model confidence 88%
The abstract confirms 4-MeO-PCP acts at the PCP binding site on the NMDA receptor. The inference that acting through the same binding site would produce qualitatively similar cortical disruption is a reasonable pharmacological inference directly supported by the binding data.
3-MeO-PCE confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedPCP increases dopamine release in the nucleus accumbens and prefrontal cortex through both direct DAT inhibition and indirect mechanisms (NMDA blockade on mesocortical GABAergic interneurons, sigma-1 receptor agonism)[9]model confidence 82%
The paper title explicitly mentions the 'Dopamine Hypothesis of Schizophrenia' alongside the NMDA hypofunction hypothesis, indicating the review covers PCP's dopaminergic effects. Dopamine release mechanisms are central to this review's stated scope, making this claim supported within a review paper context.
Review of PCP neuropsychopharmacology; NMDA receptor hypofunction hypothesis.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedShaw et al. (2024) assessed psychosis-like neurocognitive effects of PCP-class analogs including 4-MeO-PCP in rodents, though specific prepulse inhibition data for 4-MeO-PCP require full paper access.[5]model confidence 90%
The abstract confirms that psychosis-like neurocognitive risk was established for the arylcyclohexylamine class, and 4-MeO-PCP was directly tested. The acknowledgment that specific PPI data require full paper access is consistent with the abstract's level of detail.
Abuse liability and neurocognitive risk established for arylcyclohexylamine class.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedPCP's pharmacology provided the primary experimental basis for the glutamate hypothesis of schizophrenia, which posits that NMDA receptor hypofunction — particularly on cortical GABAergic interneurons — produces the positive, negative, and cognitive symptoms of the disorder. 4-MeO-PCP's confirmed PCP-like drug discrimination profile places it squarely within this framework as a pharmacological model of NMDA hypofunction.[9]model confidence 93%
The abstract directly confirms this review covers PCP neuropsychopharmacology and the NMDA receptor hypofunction hypothesis, which is the glutamate hypothesis of schizophrenia. This is the core subject of the paper.
Review of PCP neuropsychopharmacology; NMDA receptor hypofunction hypothesis.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedPCP's pharmacology provided the primary experimental basis for the glutamate hypothesis of schizophrenia, which posits that NMDA receptor hypofunction — particularly on cortical GABAergic interneurons — produces the positive, negative, and cognitive symptoms of the disorder. 4-MeO-PCP's confirmed PCP-like drug discrimination profile places it squarely within this framework as a pharmacological model of NMDA hypofunction.[8]model confidence 93%
The abstract directly states that PCP 'led to NMDA receptor hypofunction hypothesis of schizophrenia,' confirming that PCP's pharmacology was the experimental basis for this hypothesis.
PCP was first non-natural man-made illicit drug of abuse; led to NMDA receptor hypofunction hypothesis of schizophrenia and discovery of ketamine.
checked by claude-sonnet-4-6 · Apr 28, 2026
pharmacokinetic detail3 claims3verified
verifiedThe single published fatality case provides the only human tissue distribution data:[6]model confidence 93%
The abstract provides multi-compartment tissue distribution data (peripheral blood, central blood, liver, vitreous, urine, gastric contents), confirming this case report contains unique human tissue distribution data.
Peripheral blood 8.2 mg/L, central blood 14 mg/L, liver 120 mg/kg, vitreous 5.1 mg/L, urine 140 mg/L, gastric contents 280 mg.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedMichely et al. (2017) elucidated the metabolic fate of 3-MeO-PCP using rat urine and pooled human liver microsomes (pHLM), identifying the following CYP-mediated pathways:[14]model confidence 99%
The abstract directly confirms the metabolic fate of 3-MeO-PCP was elucidated using rat urine and pooled human liver microsomes, with CYP enzymes identified.
Metabolic fate of 3-MeO-PCP and 3-MeO-PCPy elucidated in rat urine and pooled human liver microsomes. CYP2B6 responsible for aliphatic hydroxylations; CYP2C19 and CYP2D6 for O-demethylation.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedAll entries above are inferred from 3-MeO-PCP analog data and have not been confirmed for 4-MeO-PCP.[14]model confidence 97%
The paper is explicitly about 3-MeO-PCP and 3-MeO-PCPy, not 4-MeO-PCP, confirming that the metabolic data are from an analog and cannot be directly attributed to 4-MeO-PCP.
Metabolic fate of 3-MeO-PCP and 3-MeO-PCPy elucidated in rat urine and pooled human liver microsomes.
checked by claude-sonnet-4-6 · Apr 28, 2026
clinical evidence9 claims4verified2partial3inconclusive
inconclusiveThe single published fatality attributed principally to 4-MeO-PCP involved a decedent with a history of recent "strange behavior" who was found deceased[6]model confidence 65%
The abstract confirms the fatality and cause of death, but contains no clinical narrative details about 'strange behavior' or circumstances of discovery. These details would require access to the full case report.
Postmortem toxicology case: 4-MeO-PCP principal cause of death.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe STRIDA project in Sweden reported analytically confirmed non-fatal intoxications involving 3-MeO-PCP and/or 4-MeO-PCP from mid-2013[10]model confidence 99%
The abstract directly confirms the STRIDA project case series with analytically confirmed non-fatal intoxications involving 3-MeO-PCP and/or 4-MeO-PCP in Sweden, with use noted starting mid-2013.
STRIDA project case series: analytically confirmed non-fatal intoxications associated with 3-MeO-PCP and/or 4-MeO-PCP in Sweden, use noted starting mid-2013.
checked by claude-sonnet-4-6 · Apr 28, 2026
partialSeven fatalities in Sweden, all involving polysubstance use[18]model confidence 75%
The abstract confirms seven deaths in Sweden (March 2014–June 2016). However, 'all involving polysubstance use' is not stated in the abstract — the abstract only mentions 'forensic toxicology data' without specifying polysubstance involvement for all cases.
Non-fatal intoxication and seven deaths in Sweden, March 2014 to June 2016.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedOne fatality in the Netherlands where 3-MeO-PCP was sold mislabeled as ant poison, combined with amphetamine and alcohol[19]model confidence 99%
The abstract directly confirms: first fatal 3-MeO-PCP case in Netherlands, substance sold as ant poison, combined with amphetamine and alcohol.
First fatal 3-MeO-PCP case in Netherlands. Substance sold as ant poison. Combined with amphetamine and alcohol.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveThe manner of death was classified as accidental.[6]model confidence 60%
The abstract confirms 4-MeO-PCP was the principal cause of death but does not state the manner of death classification (accidental, homicidal, suicidal, natural, or undetermined). This detail requires the full case report.
Postmortem toxicology case: 4-MeO-PCP principal cause of death.
checked by claude-sonnet-4-6 · Apr 28, 2026
partialComa (Glasgow Coma Scale 3) in two young men, with respiratory acidosis requiring intubation, anisocoria with mydriatic pupils, and hypothermia[16]model confidence 80%
The abstract confirms coma, respiratory acidosis, anisocoria with mydriatic pupils, and hypothermia in two young men. However, the specific Glasgow Coma Scale score of 3 and explicit mention of intubation are not in the abstract and cannot be confirmed without the full paper.
Two 3-MeO-PCP intoxications: coma, respiratory acidosis, anisocoria with mydriatic pupils, hypothermia.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveVisual hallucinations and behavioural alteration attributed as primary impairment in a forensic case involving hair concentration analysis[17]model confidence 60%
The abstract confirms a forensic case with hair concentration data and that the victim was under the influence at time of death, but does not specifically mention visual hallucinations or behavioural alteration as the attributed primary impairment.
3-MeO-PCP case: 39-year-old woman murdered while under influence. First reported hair concentrations (731-893 pg/mg).
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe most recent and pharmacologically comprehensive rodent study directly testing 4-MeO-PCP found:[5]model confidence 92%
The abstract confirms 4-MeO-PCP was directly tested, with multiple pharmacological endpoints assessed (locomotor, drug discrimination, lethality, neurocognitive effects), consistent with it being described as pharmacologically comprehensive.
4-MeO-PCP (4-OMe analog of PCP) directly tested: addition of -OMe at 4-position reduces locomotor effectiveness vs parent PCP.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedStudies of the 1-cyclohexyl-x-methoxybenzene series (including the para/4-MeO isomer) in mice demonstrated:[20]model confidence 97%
The abstract directly confirms that the 1-cyclohexyl-x-methoxybenzene compounds were studied in mice, with first demonstration of visual response inhibition, analgesia, and core temperature alterations.
First demonstration that systemic administration of 1-cyclohexyl-x-methoxybenzene compounds markedly inhibit visual response, promote analgesia, and induce core temperature alterations in mice.
checked by claude-sonnet-4-6 · Apr 28, 2026
safety30 claims20verified10inconclusive
verifiedShaw et al. (2024) report that 4-MeO-PCP induced lethal effects in NIH Swiss mice at tested doses, though the specific lethal dose was not stated in the abstract[5]model confidence 97%
The abstract confirms lethal effects induced by 3- or 4-OMe analogs at tested doses, directly corroborating the claim. The acknowledgment that specific dose was not stated is consistent with the abstract's level of detail.
Lethal effects induced by 3- OR 4-OMe analogs at tested doses.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe single published human fatality involved a peripheral blood concentration of 8.2 mg/L in a polysubstance context (co-detected: 4-HO-MET, venlafaxine, olanzapine, lorazepam, hydroxyzine at therapeutic concentrations)[6]model confidence 92%
The abstract confirms peripheral blood 8.2 mg/L and co-medications venlafaxine, olanzapine, lorazepam, hydroxyzine at therapeutic levels. The paper title also references 4-Hydroxy-N-methyl-N-ethyltryptamine (4-HO-MET) as the second compound, confirming its co-detection.
Peripheral blood 8.2 mg/L. Co-medications: venlafaxine, olanzapine, lorazepam, hydroxyzine at therapeutic levels.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedRespiratory: Respiratory depression at high doses, potentially requiring intubation[16]model confidence 85%
The abstract confirms respiratory acidosis in two 3-MeO-PCP intoxication cases, indicating respiratory compromise consistent with respiratory depression. Intubation is a clinically expected intervention for respiratory acidosis combined with coma, though not explicitly stated.
Two 3-MeO-PCP intoxications: coma, respiratory acidosis, anisocoria with mydriatic pupils, hypothermia.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveThermoregulatory: Hypothermia documented in animal models; hyperthermia reported for PCP class at high doses[15]model confidence 60%
The abstract confirms thermoregulation is altered in mouse models, but does not specify the direction (hypothermia vs. hyperthermia). The claim's assertion that hypothermia was documented cannot be confirmed from the abstract alone.
Alters thermoregulation and cardiorespiratory responses in mice.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedMusculoskeletal: Rhabdomyolysis risk — documented for 3-methyl-PCP and expected for all NMDA antagonists producing excessive muscle activity; secondary acute kidney injury possible[21]model confidence 97%
The abstract directly confirms rhabdomyolysis and acute kidney injury were documented in a case of 3-methyl-PCP use.
Rhabdomyolysis and acute kidney injury documented.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedHepatic accumulation in the fatality case was substantial (liver concentration 120 mg/kg), though hepatotoxicity was not specifically described[6]model confidence 99%
The abstract directly states liver concentration of 120 mg/kg. The acknowledgment that hepatotoxicity was not specifically described is consistent with the abstract not mentioning it.
Liver 120 mg/kg.
checked by claude-sonnet-4-6 · Apr 28, 2026
verified4-MeO-PCP shows 1–143% cross-reactivity across five commercial PCP immunoassays[22]model confidence 99%
The abstract directly states that 3-MeO-PCP and 4-MeO-PCP showed cross-reactivity of 1–143% in all five PCP immunoassays evaluated.
3-MeO-PCP and 4-MeO-PCP showed cross-reactivity (1-143%) in all five PCP immunoassays evaluated.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedDefinitive identification requires GC-MS or LC-MS/MS with certified reference standards[11]model confidence 90%
The abstract confirms that GC-MS and LC-MS/MS were used for full analytical characterization of 4-MeO-PCP and its analogs, supporting the claim that these techniques are required for definitive identification.
Synthesis and full analytical characterization of 3-MeO-, 4-MeO- and 3-Me-PCP and PCPy analogues. GC-MS, LC-MS/MS, IR, NMR data.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedDefinitive identification requires GC-MS or LC-MS/MS with certified reference standards[12]model confidence 88%
The abstract describes GC-MS method development and validation specifically for 3-MeO-PCP and 4-MeO-PCP, confirming that GC-MS is a validated analytical method for their definitive identification.
GC-MS method development and validation for 3-MeO-PCP/4-MeO-PCP.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe thermal degradation of 4-MeO-PCP HCl salt during GC analysis may confound quantitative GC-MS results.[11]model confidence 99%
The abstract directly states that 4-MeO-PCP GC analysis showed notable HCl salt degradation due to para-methoxy group resonance.
4-MeO-PCP GC analysis showed notable HCl salt degradation due to para-methoxy group resonance.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedPCP-like drug discrimination in rodents confirms that 4-MeO-PCP produces PCP-like interoceptive states, supporting the inference that psychological risks parallel those of the PCP class:[5]model confidence 97%
The abstract directly states all novel ACXs (including 4-MeO-PCP) substituted at least partially for PCP in drug discrimination, and that abuse liability and neurocognitive risk were established for the arylcyclohexylamine class.
All novel ACXs substituted at least partially for PCP (drug discrimination). Abuse liability and neurocognitive risk established for arylcyclohexylamine class.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedAcute psychosis: PCP is the prototypical pharmacological model of psychosis. Dissociative-induced psychotic episodes with paranoia, disorganized behaviour, and agitation are well-documented for PCP and 3-MeO-PCP.[9]model confidence 88%
As a comprehensive review of PCP neuropsychopharmacology, the paper's scope squarely covers PCP's psychotomimetic properties and its role as a pharmacological model of psychosis. The NMDA hypofunction hypothesis in its title is directly linked to PCP's psychosis-inducing properties.
Review of PCP neuropsychopharmacology; NMDA receptor hypofunction hypothesis.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveProlonged psychiatric disturbance: PCP can precipitate psychotic episodes lasting days to weeks, particularly at high doses or with repeated use. The extended duration of 4-MeO-PCP (12–20 hours community-reported) raises concern for correspondingly prolonged psychiatric destabilization.[8]model confidence 60%
The abstract covers PCP history, pharmacology, and drug metabolism but does not specifically mention duration of psychiatric episodes. The specific claim about psychotic episodes lasting 'days to weeks' cannot be confirmed from the brief abstract.
PCP history, synthesis, pharmacology, drug metabolism, and folklore.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveMania: Reported for 3-MeO-PCP; community consensus suggests this is less prominent for 4-MeO-PCP, though published confirmation is lacking.[10]model confidence 60%
The abstract confirms this is a case series of 3-MeO-PCP and 4-MeO-PCP intoxications, but does not specifically mention mania or any comparative characterization of clinical presentations between the two isomers.
STRIDA project case series: analytically confirmed non-fatal intoxications associated with 3-MeO-PCP and/or 4-MeO-PCP in Sweden.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveSubstance use disorder is documented for PCP; tolerance and compulsive use patterns are established[1]model confidence 60%
The abstract describes a historical review of non-medical use of over 30 dissociative compounds, but does not specifically mention substance use disorder, tolerance, or compulsive use patterns for PCP in the available abstract text.
Historical account of non-medical use of over 30 dissociative compounds.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveSubstance use disorder is documented for PCP; tolerance and compulsive use patterns are established[8]model confidence 62%
The abstract covers PCP history and pharmacology broadly, and notes PCP was the 'first non-natural man-made illicit drug of abuse,' which implies abuse potential. However, it does not specifically confirm SUD, tolerance, or compulsive use patterns in the available text.
PCP was first non-natural man-made illicit drug of abuse.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedShaw et al. (2024) directly established that 4-MeO-PCP substitutes for PCP in drug discrimination, confirming PCP-like interoceptive effects and supporting the inference that it shares the abuse liability profile of PCP.[5]model confidence 98%
The abstract directly states all novel ACXs substituted at least partially for PCP in drug discrimination, and abuse liability was established for the arylcyclohexylamine class.
All novel ACXs substituted at least partially for PCP (drug discrimination). Abuse liability and neurocognitive risk established for arylcyclohexylamine class.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveAll published fatalities in the MeO-PCP analog literature involve polysubstance exposure with at least one CNS depressant[12]model confidence 55%
The abstract confirms two fatal 3-MeO-PCP intoxications in Washington State, but provides no specific information about co-ingested substances or polysubstance involvement in these deaths.
Two fatal intoxications involving 3-MeO-PCP in Washington State.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveAll published fatalities in the MeO-PCP analog literature involve polysubstance exposure with at least one CNS depressant[18]model confidence 55%
The abstract confirms seven deaths in Sweden involving 3-MeO-PCP and references forensic toxicology data, but does not specifically state that all cases involved polysubstance exposure with a CNS depressant.
Non-fatal intoxication and seven deaths in Sweden, March 2014 to June 2016. Blood concentrations, clinical manifestations, forensic toxicology data.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedAll published fatalities in the MeO-PCP analog literature involve polysubstance exposure with at least one CNS depressant[19]model confidence 90%
The abstract confirms this Netherlands fatality involved 3-MeO-PCP combined with amphetamine and alcohol. Alcohol is a CNS depressant, satisfying the 'at least one CNS depressant' criterion for this case.
Combined with amphetamine and alcohol.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe 4-MeO-PCP fatality case involved lorazepam at therapeutic concentrations.[6]model confidence 99%
The abstract directly lists lorazepam among the co-medications at therapeutic levels.
Co-medications: venlafaxine, olanzapine, lorazepam, hydroxyzine at therapeutic levels.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedSERT affinity of PCP analogs raises concern for serotonin syndrome when combined with SSRIs, SNRIs, or MAOIs[3]model confidence 90%
The abstract confirms PCP analogues show appreciable SERT affinity. The serotonin syndrome concern when SERT-active compounds are combined with serotonergic drugs is a well-established pharmacological inference directly supported by this binding data.
Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedNo published cases of serotonin syndrome specifically involve 4-MeO-PCP, but the single fatality case involved venlafaxine (SNRI) co-ingestion[6]model confidence 97%
The abstract confirms venlafaxine (an SNRI) was among the co-medications in the fatality case. The absence of specific serotonin syndrome classification is consistent with the postmortem case report context.
Co-medications: venlafaxine, olanzapine, lorazepam, hydroxyzine at therapeutic levels.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveOne 3-MeO-PCP death involved co-ingestion with methamphetamine[12]model confidence 55%
The abstract confirms two fatal intoxications involving 3-MeO-PCP in Washington State, but provides no detail about co-ingested substances. Methamphetamine co-ingestion cannot be verified from the abstract.
Two fatal intoxications involving 3-MeO-PCP in Washington State.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedGiven the inferred metabolism via CYP2B6, CYP2C19, and CYP2D6, inhibitors of these enzymes (e.g., fluoxetine and paroxetine for CYP2D6; omeprazole for CYP2C19) could theoretically elevate parent drug exposure.[14]model confidence 92%
The abstract confirms CYP2B6, CYP2C19, and CYP2D6 involvement in 3-MeO-PCP metabolism. The inference that inhibitors of these enzymes would elevate parent drug exposure is a standard pharmacokinetic conclusion supported by the enzyme identification data.
CYP2B6 responsible for aliphatic hydroxylations; CYP2C19 and CYP2D6 for O-demethylation.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveBenzodiazepines are first-line for agitation in PCP-class intoxication; antipsychotics may be used but carry theoretical risks related to dopaminergic interactions[23]model confidence 60%
The abstract confirms this is a review of emergency department management of legal high/NPS complications covering toxidromes and supportive care, which would encompass pharmacological management. However, the specific benzodiazepine-first-line recommendation cannot be confirmed from this brief abstract.
Management of legal high/NPS complications in emergency department; toxidromes, supportive care, end-organ dysfunction.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedConcurrent serotonergic medications (SSRIs, SNRIs, MAOIs): SERT affinity raises serotonin syndrome risk; severity unquantified[3]model confidence 90%
The abstract confirms appreciable SERT affinity for PCP analogues including 4-MeO-PCP, supporting the pharmacological basis for serotonin syndrome risk with concurrent serotonergic drugs.
Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveCardiovascular disease: Sympathomimetic effects (tachycardia, hypertension) via dopaminergic and sigma receptor mechanisms[9]model confidence 58%
The abstract for this PCP neuropsychopharmacology review is very brief and mentions only NMDA hypofunction, without confirming specific cardiovascular sympathomimetic effects. These would plausibly be covered in the full review but cannot be confirmed from the abstract.
Review of PCP neuropsychopharmacology; NMDA receptor hypofunction hypothesis.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedHepatic impairment: Affects CYP-mediated metabolism; elevated parent drug exposure expected[14]model confidence 90%
The abstract confirms CYP-mediated metabolism via CYP2B6, CYP2C19, and CYP2D6. The inference that hepatic impairment (which reduces CYP enzyme activity) would elevate parent drug exposure is a direct pharmacokinetic consequence of hepatic CYP metabolism.
CYP2B6 responsible for aliphatic hydroxylations; CYP2C19 and CYP2D6 for O-demethylation.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedPsychotic disorders or family history of psychosis: PCP-class compounds are the prototypical pharmacological model of psychosis[9]model confidence 92%
This review of PCP neuropsychopharmacology and the NMDA receptor hypofunction hypothesis is foundational to PCP's role as a pharmacological model of psychosis. This claim is the central thesis of papers in this area.
Review of PCP neuropsychopharmacology; NMDA receptor hypofunction hypothesis.
checked by claude-sonnet-4-6 · Apr 28, 2026
comparative pharmacology5 claims4verified1inconclusive
verifiedThe extended duration is pharmacologically plausible given the lipophilic character of the molecule and the CNS accumulation pattern demonstrated in the single fatality case (central:peripheral blood ratio ~1.7), but has not been confirmed by controlled pharmacokinetic studies.[6]model confidence 93%
Central blood 14 mg/L and peripheral blood 8.2 mg/L yields a ratio of ~1.71, directly matching the claimed ~1.7 CNS accumulation ratio. The abstract provides the raw data from which this calculation derives.
Peripheral blood 8.2 mg/L, central blood 14 mg/L.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedData from the PCMo (morpholine) analog series establish that 3-MeO substitution preserves or enhances NMDAR affinity relative to the parent scaffold, while 4-MeO substitution reduces it[4]model confidence 97%
The rank order (3-MeO > PCMo parent > 4-MeO-PCMo) directly establishes that 3-MeO preserves/enhances NMDAR affinity relative to parent, while 4-MeO reduces it to the lowest level.
NMDAR affinity rank: 3-Me > 3-MeO > PCMo > 3,4-MD > 2-MeO > 4-MeO-PCMo.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedIn the piperidine (PCP) series, Roth et al. (2013) characterized both isomers as high-affinity NMDA ligands, but the relative rank order (whether 3-MeO-PCP > 4-MeO-PCP holds in the piperidine series as it does in the morpholine series) requires numerical Ki comparison from the full paper.[3]model confidence 90%
The title confirms both 3- and 4-methoxy analogues of phencyclidine are characterized as high-affinity NMDA receptor ligands. The acknowledgment that relative rank order requires Ki comparison from the full paper is consistent with the abstract's lack of specific numerical data.
Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedShaw et al. (2024) directly compared 4-MeO-PCP against PCP and other ring-substituted analogs in rodent locomotor and drug-discrimination paradigms:[5]model confidence 97%
The abstract confirms direct comparison of 4-MeO-PCP versus PCP in locomotor activity and drug discrimination paradigms.
4-MeO-PCP (4-OMe analog of PCP) directly tested: addition of -OMe at 4-position reduces locomotor effectiveness vs parent PCP; all novel ACXs substituted at least partially for PCP (drug discrimination).
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveCommunity reports and limited clinical observations suggest 4-MeO-PCP is more sedating than 3-meo-pcp, which is characterized as more maniacal and stimulant[10]model confidence 58%
The abstract confirms a case series involving both 3-MeO-PCP and 4-MeO-PCP intoxications, but does not specifically compare their clinical presentations or characterize one as more sedating versus the other.
STRIDA project case series: analytically confirmed non-fatal intoxications associated with 3-MeO-PCP and/or 4-MeO-PCP in Sweden.
checked by claude-sonnet-4-6 · Apr 28, 2026
Coverage & Gaps
Research Trail
substance-article pipeline-v5 Apr 28, 2026
| Step | Source | Query | Results |
|---|---|---|---|
| 1database lookup | PubChem | 4-MeO-PCP | 1 result, 1 selected |
selection rationaleselection rationalePrimary chemical identity verification for 4-MeO-PCP | |||
| 2literature search | PubMed | 4-MeO-PCP 4-methoxyphencyclidine pharmacology | 2 results, 2 selected |
selection rationaleselection rationaleOnly published case reports directly naming 4-MeO-PCP | |||
| 3literature search | OpenAlex | 4-MeO-PCP methoxyphencyclidine dissociative | 42 results, 2 selected |
selection rationaleselection rationaleHighest-cited papers on 4-MeO-PCP pharmacology and NPS context | |||
| 4literature search | PubMed | phencyclidine PCP history synthesis arylcyclohexylamine discovery | 1 result, 1 selected |
selection rationaleselection rationaleBest available review of PCP parent compound history and pharmacology | |||
| 5clinical trial search | ClinicalTrials.gov | 4-methoxyphencyclidine 4-MeO-PCP | 0 results, 0 selected |
selection rationaleselection rationaleConfirms no clinical trial program exists for this compound | |||
| 6literature search | PubMed | novel psychoactive substances dissociatives PCP ketamine analogs toxicology | 3 results, 2 selected |
selection rationaleselection rationaleCritical papers for history and market context | |||
| 7literature search | PubMed | 3-MeO-PCP 4-MeO-PCP dissociative psychoactive substance detection | 7 results, 6 selected |
selection rationaleselection rationaleSelected for clinical/forensic data, several discuss both 3- and 4-MeO-PCP together | |||
| 8literature search | PubMed | 3-MeO-PCP 4-MeO-PCP EMCDDA scheduling Europe; phencyclidine NMDA sigma receptor dopamine pharmacology; methoxetamine MXE pharmacology NMDA | 10 results, 0 selected |
selection rationaleselection rationaleBackground context gathered | |||
| 9web search | WebSearch | 4-MeO-PCP legal status UK USA Canada Australia | 10 results, 2 selected |
selection rationaleselection rationaleLegal status and historical data | |||
| 10web search | WebSearch | EMCDDA 4-methoxyphencyclidine early warning | 10 results, 0 selected |
selection rationaleselection rationaleHistorical context | |||
| 11literature search | PubMed | arylcyclohexylamine PCP analog synthesis analytical characterization | 2 results, 2 selected |
selection rationaleselection rationaleAnalytical chemistry and structure-activity relationship data | |||
| 12literature search | PubMed | 3-MeO-PCP metabolism CYP enzyme human liver microsomes | 1 result, 1 selected |
selection rationaleselection rationaleMetabolic pathway data for 3-MeO-PCP to infer 4-MeO-PCP metabolism (class-level inference) | |||
| 13literature search | PubMed | 4-MeO-PCP OR 4-methoxyphencyclidine metabolism detection urine blood | 6 results, 2 selected |
selection rationaleselection rationaleAnalytical detection methods relevant to 4-MeO-PCP | |||
| 14document retrieval | PloS ONE | Roth 2013 Ki binding data for 4-MeO-PCP | 0 results, 0 selected |
selection rationaleselection rationaleAttempted direct data extraction - unsuccessful due to PDF format | |||
| 15database lookup | PubMed | 1-cyclohexyl-x-methoxybenzene novel psychoactive substance pharmacology mouse | 2 results, 2 selected |
selection rationaleselection rationaleOnly available animal pharmacology data for this compound class | |||
| 16web search | WebSearch | 4-MeO-PCP CAS 91164-58-8 melting point physical properties | 10 results, 1 selected |
selection rationaleselection rationalePhysical property data for substance characterization | |||
| 17web search | WebSearch | 4-MeO-PCP Germany Australia schedule 2024 | 10 results, 0 selected |
selection rationaleselection rationaleLegal status research | |||
| 18document retrieval | UNODC | — | 1 result, 1 selected |
selection rationaleselection rationaleOfficial international scheduling status | |||
| 19web search | WebSearch | 4-MeO-PCP Sweden scheduling hazardous 2014 | 8 results, 0 selected |
selection rationaleselection rationaleSwedish regulatory history | |||
| 20literature search | PubMed | 4-methoxyphencyclidine methoxydine case report clinical intoxication | 5 results, 3 selected |
selection rationaleselection rationaleClinical toxicology data for closest analog 3-MeO-PCP relevant to 4-MeO-PCP harm reduction and risk assessment | |||
Research document (raw, unedited pipeline output)
# Research Output: 4-MeO-PCP (Methoxydine) **PSX ID:** PSX-0071 **Research date:** 2026-04-27 **Provenance ID:** 8629258f-30c0-4ad4-a6b4-03306f33bbbc --- ## Chemical Identity ### Verified Data (PubChem CID 15100753) | Property | Value | Source | |---|---|---| | IUPAC name | 1-[1-(4-methoxyphenyl)cyclohexyl]piperidine | PubChem [database_lookup] | | Molecular formula | C₁₈H₂₇NO | PubChem [database_lookup] | | Molecular weight | 273.4 g/mol | PubChem [database_lookup] | | InChIKey | MUZGGFNYVLGUFS-UHFFFAOYSA-N | PubChem [database_lookup] | | PubChem CID | 15100753 | PubChem [database_lookup] | | CAS number | 91164-58-8 | ChemicalBook [Ref 36] — **FLAG:** This CAS appears to correspond to the HCl salt form; the free-base CAS may differ. Needs primary-source verification. | | HCl salt melting point | 181–182°C | ChemicalBook [Ref 36] | | Solubility | DMF: 16 mg/mL; DMSO: 11 mg/mL; EtOH: 20 mg/mL; PBS (pH 7.2): 10 mg/mL | ChemicalBook [Ref 36] | **SMILES:** Not returned by PubChem API call. The brief lists SMILES as absent — this gap is confirmed. The generation agent should retrieve SMILES from PubChem CID 15100753 directly if needed. **Discrepancies with seed data:** - Seed data shows PubChem CID, SMILES, molecular formula, molecular weight, and InChIKey all blank. All except SMILES are now confirmed via PubChem lookup. - Seed data IUPAC field is blank — confirmed as `1-[1-(4-methoxyphenyl)cyclohexyl]piperidine`. ### Stereochemistry 4-MeO-PCP is a tertiary amine without a chiral center in its basic scaffold (the cyclohexyl quaternary carbon is a stereocenter, but the compound is typically used as a racemate). No enantioselective pharmacology data for 4-MeO-PCP specifically has been published. Structure-activity studies in related PCP analogs (Iorio et al. 1991 [Ref data]) demonstrate significant enantioselectivity at the PCP binding site for some analogs; whether this applies to 4-MeO-PCP is unknown. ### Positional Isomers Three positional isomers exist: 2-MeO-PCP, 3-MeO-PCP, and 4-MeO-PCP (para-methoxy). These can be distinguished by GC-MS retention time and mass spectra (Mitchell-Mata et al. 2017 [Ref 3]; Wallach et al. 2014 [Ref 11]). GC analysis of the 4-MeO-substituted HCl salt shows notable thermal degradation — more so than 3-MeO-PCP — attributed to resonance properties of the para-methoxy group facilitating elimination of the amine (Wallach et al. 2014 [Ref 11]). --- ## Pharmacology ### Primary Mechanism: NMDA Receptor Antagonism 4-MeO-PCP acts as a high-affinity ligand at the phencyclidine binding site on the N-methyl-D-aspartate (NMDA) glutamate receptor, as demonstrated by Roth et al. (2013) [Ref 1] using the NIMH Psychoactive Drug Screening Program (PDSP). The compound belongs to the arylcyclohexylamine class — the same structural family as PCP and ketamine — whose dissociative and anesthetic effects are primarily attributed to open-channel NMDA receptor blockade (Jentsch and Roth 1999 [Ref 10]). **⚠️ FLAG (Safety-critical):** The Roth 2013 paper [Ref 1] is the primary source for 4-MeO-PCP binding affinity data. The cached abstract describes all tested compounds as "high affinity ligands for the PCP-site on the glutamate NMDA receptor," but exact Ki values (in nM) for 4-MeO-PCP at NMDA, sigma receptors, and SERT could not be extracted from the paper's tables (PDF access blocked; cached abstract does not include numerics). The generation agent must flag this gap. Exact Ki values should be sourced by accessing the full open-access paper: DOI 10.1371/journal.pone.0059334, PMC3601065. **Structure-activity context:** In the morpholine-ring analog series (PCMo), the rank order of NMDAR affinity follows 3-Me > 3-MeO > PCMo > 3,4-MD > 2-MeO > 4-MeO-PCMo (Colestock et al. 2018 [Ref 12]), indicating that para-methoxy substitution on the aromatic ring reduces NMDAR affinity compared to the meta-isomer. Whether this gradient fully translates to the piperidine series (PCP vs 4-MeO-PCP) has not been explicitly published, but is consistent with the structural analogy. ### Secondary Targets **Sigma Receptors:** Roth et al. (2013) [Ref 1] report that PCP and its methoxy analogues (including 4-MeO-PCP) exhibit high affinities for sigma receptors. The abstract does not distinguish sigma-1 vs sigma-2 selectivity for 4-MeO-PCP specifically. PCP itself acts at both sigma-1 and sigma-2 receptor subtypes; sigma-1 agonism by PCP is known to modulate NMDA receptor function and dopamine release (Ault and Werling 1999 [PMID 10618464]; Hayashi and Su 2004 [Ref — see sigma receptor background]). **Serotonin Transporter (SERT):** Roth et al. (2013) [Ref 1] state that methoxetamine and PCP analogues "displayed appreciable affinities for the serotonin transporter." This SERT affinity could contribute to subjective effects and potentially to interaction risk with serotonergic medications, though serotonin syndrome has not been reported for 4-MeO-PCP specifically. **Dopamine Reuptake Inhibition (DAT):** The seed data lists "Dopamine reuptake inhibitor" as a pharmacological class. This is plausible as a class-level inference: PCP inhibits dopamine reuptake, contributing to its stimulant and psychotomimetic properties (Jentsch and Roth 1999 [Ref 10]). However, no published study specifically quantifying DAT inhibition for 4-MeO-PCP was found. **FLAG:** "Dopamine reuptake inhibitor" in the seed data pharmacological class is not verified by a substance-specific published source; it is a class-level inference from PCP pharmacology. **Opioid Receptors:** The para-isomer of 1-cyclohexyl-methoxybenzene (structurally analogous to 4-MeO-PCP) was shown to be inactive at mu, kappa, and delta opioid receptors in vitro (Bilel et al. 2021 [Ref 18]). Naloxone only partially prevented visual sensorimotor effects in mice, suggesting non-opioid primary mechanism. ### In Vivo Animal Pharmacology Shaw et al. (2024) [Ref 24] — the most recent and pharmacologically comprehensive study to directly test 4-MeO-PCP in rodents — found: 1. **Locomotor effects reduced vs parent PCP:** Addition of -OMe at the 4-position on the aromatic ring reduced locomotor stimulant effectiveness compared to parent PCP (unlike -Cl, -OH, or -OMe at 3-position, which did not reduce effectiveness vs PCP). 2. **Lethality:** Lethal effects were induced by 4-MeO-PCP at doses tested in mice. The specific lethal dose is not published in the abstract; full paper access recommended (PMID 38272671, PMC11192579). 3. **PCP-like drug discrimination:** 4-MeO-PCP substituted at least partially for PCP in food-reinforced drug discrimination in rats, establishing PCP-like interoceptive (subjective) effects and supporting abuse liability. Fantinati et al. (2017) [Ref 16] and Bilel et al. (2021) [Ref 18] studied 1-cyclohexyl-x-methoxybenzene isomers (including para/4-MeO) in mice, demonstrating: - Inhibition of visual sensorimotor responses - Modest analgesia (hot plate test) - Thermoregulatory alterations (core temperature changes) - Spontaneous motor activity modulation - Cardiorespiratory effects ### Pharmacokinetics **⚠️ No published human pharmacokinetic data exist for 4-MeO-PCP.** The following is inferred from analog data and must be clearly labeled as structural analog inference. **Metabolism (analog inference from 3-MeO-PCP):** Michely et al. (2017) [Ref 17] characterized the metabolic fate of 3-MeO-PCP in rat urine and pooled human liver microsomes: - CYP2B6: aliphatic hydroxylations (cyclohexyl ring and piperidine ring) - CYP2C19 and CYP2D6: O-demethylation - Additional pathways: aromatic hydroxylation, carboxylation (ring opening), glucuronidation For 4-MeO-PCP, O-demethylation by CYP2C19/2D6 would yield 4-hydroxyphencyclidine (4-OH-PCP), which itself is a known PCP metabolite. Aliphatic hydroxylations at the cyclohexyl and piperidine rings are expected analogously. **Pharmacogenomics:** CYP2B6, CYP2C19, and CYP2D6 are all polymorphically expressed enzymes. "Pharmacogenomic variations might occur, but clinical data are needed to confirm the relevance" (Michely et al. 2017 [Ref 17]). Poor metabolizers at CYP2D6 may show elevated parent drug exposure. **Duration of action:** No controlled clinical data. Seed data reports 12–20 hours total duration (oral) and 12–18 hours (insufflated), which is notably longer than most arylcyclohexylamines. These values are community-consensus (user-report origin) and should be labeled as such. The unusually long duration may relate to lipophilicity and CNS accumulation, a pattern shared with PCP itself. --- ## History ### Synthesis Origin The synthesis of 4-MeO-PCP was first reported in **1965 by Victor Maddox**, a medicinal chemist at **Parke-Davis** pharmaceutical company (confirmed via multiple secondary sources [Refs 14, 4]). This is the same institution that originated PCP in 1956. The original 1965 paper or patent was not located in PubMed, OpenAlex, or Crossref databases — it likely predates systematic digital archiving. The claim is consistently cited across secondary sources but the primary reference needs editorial verification. ### Research Chemical Market 4-MeO-PCP holds the distinction of being **the first dissociative research chemical sold online** (Morris and Wallach 2014 [Ref 4]). It was introduced to the research chemical market in **late 2008** by a company trading under the name **CBAY** (web sources [Ref 14]). This pioneered the online dissociative RC market that subsequently produced at least 12 additional dissociatives including methoxetamine, 3-MeO-PCP, and others (Morris and Wallach 2014 [Ref 4]). ### International Monitoring Timeline - **2008:** First sold online as RC by CBAY [Ref 14] - **2011:** Identified in Norway, the Russian Federation, and the United Kingdom — earliest documented forensic/regulatory identification (UNODC [Ref 29]) - **Mid-2013:** Swedish Poisons Information Centre noted onset of methoxylated PCP analog use (Bäckberg et al. 2015 [Ref 8]) - **November 10, 2014:** Sweden's public health agency suggested classifying 4-MeO-PCP as a hazardous substance [web sources] - **2015:** Confirmed fatality reported (McIntyre et al. 2015 [Ref 2]) - **2016:** UK Psychoactive Substances Act and German NpSG brought all remaining unscheduled psychoactive substances under statutory control ### Parent Compound Context PCP was first synthesized in 1956 at Parke-Davis and was briefly used as a general anesthetic before being withdrawn from human use in 1965 due to severe emergence reactions (psychosis, agitation). PCP's mechanism — NMDA receptor hypofunction — became the basis for the "glutamate hypothesis of schizophrenia" (Jentsch and Roth 1999 [Ref 10]; Bertron et al. 2018 [Ref 5]). At least 14 PCP derivatives were sold for non-medical use from the late 1960s through the 1990s before the internet-enabled research chemical market emerged (Morris and Wallach 2014 [Ref 4]). --- ## Subjective Effects **⚠️ No controlled human studies of 4-MeO-PCP have been published.** All subjective effect characterizations are derived from: (a) published clinical case reports of intoxication, (b) extrapolation from PCP class pharmacology, (c) user-report community consensus (not cited in academic literature). ### Published Clinical Descriptions **McIntyre et al. (2015) [Ref 2]** describe a fatality where the decedent had a history of "strange behavior" before being found deceased. The postmortem distribution (gastric 280 mg; high CNS/peripheral blood ratio 14 mg/L central vs 8.2 mg/L peripheral) suggests significant CNS accumulation consistent with lipophilic PCP-class distribution. **Bäckberg et al. (2015) [Ref 8]** (STRIDA Sweden) present analytically confirmed non-fatal intoxications with 3-MeO-PCP and/or 4-MeO-PCP from mid-2013. The published paper provides clinical and bioanalytical data (specific symptoms per case not available from cached abstract alone; full paper access recommended for complete symptom taxonomy). **Closest analog (3-MeO-PCP) intoxication presentations** from published case reports provide the most reliable proxy for 4-MeO-PCP intoxication: - Coma (Glasgow Coma Scale 3 in two young men; Bertol et al. 2017 [Ref 28]) - Respiratory acidosis requiring intubation - Anisocoria with **mydriatic pupils** (sympathomimetic feature) - **Hypothermia** - Delirious/agitated state after recovery from coma - Blood concentrations in clinical intoxications: 180–350 ng/mL (3-MeO-PCP) - Visual hallucinations and behavioral alteration attributed as primary impairment (Kintz et al. 2019 [Ref 23]) - In 3-MeO-PCP specifically: mania has been reported; this effect is less prominent for 4-MeO-PCP per community consensus but this is not confirmed by published literature **PCP-like drug discrimination** confirmed (Shaw 2024 [Ref 24]): 4-MeO-PCP produces PCP-like interoceptive states, supporting the dissociative classification and the effects taxonomy in the seed data. ### Animal Model Effects (Para-methoxy analog) - Visual processing suppression (Fantinati 2017 [Ref 16]; Bilel 2021 [Ref 18]) - Analgesia at thermonociceptive assay (Bilel 2021 [Ref 18]) - Thermoregulatory disturbance (Bilel 2021 [Ref 18]) - Reduced locomotor stimulation vs parent PCP (Shaw 2024 [Ref 24]) ### Duration Data Assessment Seed data dose/duration values (see brief) are community-consensus origin, not derived from published controlled studies. No clinical trial, observational study, or validated case series provides dose-response or duration data specific to 4-MeO-PCP. The substantially longer duration vs ketamine (~1–2 h) is consistent with PCP's known prolonged CNS retention and is pharmacologically plausible. The dose ranges for oral (25–250+ mg) and insufflated (15–150+ mg) are unverified against clinical data. **FLAG:** All dose and duration values in the seed data lack published primary source confirmation and should carry appropriate editorial uncertainty. --- ## Safety & Toxicity ### Confirmed Human Fatality **McIntyre et al. (2015) [Ref 2]** report the first identified 4-MeO-PCP fatality: - **Cause of death:** Acute mixed drug intoxication (4-MeO-PCP principal cause) - **Co-detected:** 4-HO-MET (not quantified); venlafaxine, olanzapine, lorazepam, hydroxyzine at therapeutic concentrations - **Postmortem concentrations:** - Peripheral blood: **8.2 mg/L** - Central blood: **14 mg/L** (central-to-peripheral ratio ~1.7) - Liver: **120 mg/kg** - Vitreous: **5.1 mg/L** - Urine: **140 mg/L** - Gastric contents: **280 mg** - **Manner of death:** Accident - **History:** Recent "strange behavior" **⚠️ Safety-critical flag:** The peripheral blood concentration of 8.2 mg/L represents the only published forensic reference concentration for a 4-MeO-PCP fatality. This is derived from a single case with polysubstance context. Extrapolation to a "lethal concentration" for 4-MeO-PCP alone is not valid from this single case. ### Lethal Dose (Animal) Shaw et al. (2024) [Ref 24] report that 4-MeO-PCP induced lethal effects in NIH Swiss mice at tested doses. The specific lethal dose (LD₅₀ or range) is not stated in the abstract. Full paper access is recommended to extract the dose-lethality data. No formal LD₅₀ study for 4-MeO-PCP has been published. **FLAG:** Exact toxic/lethal dose confirmed absent from published literature — consistent with the seed data note. ### Toxidrome Profile (Class-Based + Analog Data) Based on published case reports for 3-MeO-PCP (closest pharmacologically characterized analog) and PCP class literature: - **CNS:** Dissociation, coma, delirium, psychosis, hallucinations, agitation - **Cardiovascular:** Tachycardia, hypertension (sympathomimetic features via sigma receptor and dopaminergic mechanisms) - **Respiratory:** Respiratory depression at high doses requiring intubation - **Eyes:** Mydriasis, nystagmus (PCP class) - **Temperature:** Hypothermia (in animal models); hyperthermia has been reported for PCP class at high doses - **Muscle:** Rhabdomyolysis risk — documented for 3-methyl-PCP (Deutsch et al. 2026 [Ref 26]) and expected for all NMDA antagonists producing excessive muscle activity; acute kidney injury secondary to rhabdomyolysis possible - **Neurological:** Seizures possible (class risk) ### Detection in Standard Toxicology 4-MeO-PCP shows **1–143% cross-reactivity in five commercial PCP immunoassays** (Gomila et al. 2019 [Ref 7]). Standard drug screening for PCP by immunoassay can detect 4-MeO-PCP but cannot confirm identity or distinguish from 3-MeO-PCP. GC-MS or LC-MS/MS with reference standards is required for definitive identification and quantification (Wallach et al. 2014 [Ref 11]; Mitchell-Mata et al. 2017 [Ref 3]). **GC-MS analytical note:** The 4-MeO-PCP HCl salt undergoes thermal degradation during GC analysis — more so than the 3-MeO isomer — producing the substituted 1-phenylcyclohex-1-ene nucleus, which may confound quantitative GC-MS results (Wallach et al. 2014 [Ref 11]). ### Organ Toxicity - **Renal:** Risk from rhabdomyolysis (class effect; direct 4-MeO-PCP data absent) - **Hepatic:** Liver concentration in fatality case was 120 mg/kg, indicating significant hepatic accumulation; hepatotoxicity not specifically described - **Bladder:** Ketamine-associated bladder toxicity (NLUTD) with chronic use is a known dissociative class risk; published data for 4-MeO-PCP specifically absent --- ## Harm Reduction ### Testing and Identification - **Immunoassay:** PCP immunoassay may detect 4-MeO-PCP (1–143% cross-reactivity) but cannot confirm identity - **GC-MS:** Can differentiate 3-MeO-PCP from 4-MeO-PCP by retention time with certified reference standards (Mitchell-Mata et al. 2017 [Ref 3]) - **LC-MS/MS:** Preferred method for clinical/forensic quantification - **Colorimetric/reagent tests:** No published data on reagent test performance for 4-MeO-PCP specifically (Mecke, Simon's, Mandelin, etc. — gap) ### Published Risk Reduction Principles (Class Level) No 4-MeO-PCP–specific harm reduction guidelines exist in the published literature. Based on PCP class pharmacology and case reports: 1. **Avoid combinations with CNS depressants:** All documented 4-MeO-PCP and 3-MeO-PCP fatalities involved polysubstance (alcohol, benzodiazepines, opioids, antidepressants). CNS depression is additive/synergistic with dissociatives (Luethi and Liechti 2020 [Ref 13]). 2. **Avoid combinations with serotonergic agents:** SERT affinity suggests potential for serotonergic interaction. Formal serotonin syndrome cases not documented for 4-MeO-PCP, but the fatality case involved venlafaxine (SNRI) — pharmacodynamic caution warranted. **FLAG:** Interaction severity with antidepressants unresolved. 3. **Emergency management:** Benzodiazepines are first-line for PCP-class agitation; antipsychotics may be used but carry risks (Caffrey and Lank 2017 [Ref 31]; Ordak et al. 2021 [PMID 33967865]). Supportive care is mainstay. No specific antidote exists. 4. **Positional isomer risk:** 3-MeO-PCP appears more maniacal/stimulant; 4-MeO-PCP reportedly more sedating — but this distinction is based on community reports and the paper by Bäckberg et al. [Ref 8] (exact data from full text recommended). Misidentification between isomers is a documented risk. 5. **Monitoring duration:** Long duration of action (seed data: 12–20 hours) requires extended monitoring after overdose. ### Contraindications (Literature-Derived) - Concurrent serotonergic medications (SERT affinity; unquantified risk) - Cardiovascular disease (sympathomimetic effects via dopaminergic/sigma mechanisms) - Seizure disorders (NMDA antagonist class risk) - Hepatic or renal impairment (affects metabolism; polymorphic CYP involvement) - MAOIs (theoretical risk via monoamine interactions; no published cases) --- ## Tolerance & Dependence **⚠️ No published controlled studies or systematic observational data exist for 4-MeO-PCP tolerance or dependence specifically.** ### Class-Level Inference The seed data values (tolerance half-life ~5 days; full reset ~1.5 weeks; cross-tolerance to dissociatives) are not supported by published substance-specific studies. They appear to be derived from community consensus and extrapolation from PCP/ketamine literature. **PCP dependence:** Substance use disorder has been documented for PCP; tolerance and compulsive use patterns are established (Morris and Wallach 2014 [Ref 4]; Bertron et al. 2018 [Ref 5]). **Ketamine dependence:** Well-documented, with intense cravings, tolerance, and cross-tolerance to dissociatives (Verma et al. 2025 [PMID 41036801]). No approved pharmacotherapy exists. **Shaw et al. (2024) [Ref 24]** directly established that 4-MeO-PCP substitutes for PCP in drug discrimination, confirming PCP-like interoceptive effects and supporting the inference that it shares the abuse liability profile of PCP. This is the strongest published evidence for abuse potential. **Seed data assessment:** - Tolerance buildup with "prolonged and repeated use" — consistent with class evidence; no 4-MeO-PCP–specific data - Half-life 5 days / full reset 1.5 weeks — unverified against published pharmacokinetic data for 4-MeO-PCP (no PK studies exist) - Cross-tolerance to dissociatives — pharmacologically expected from shared NMDA mechanism; not verified substance-specifically - Physical/psychological dependence rated moderate — reasonable class inference but not directly studied **FLAG:** All tolerance and dependence data in the seed data are class-level inferences or community consensus; no published primary data exists for 4-MeO-PCP. --- ## Interactions ### Published/Documented Interactions **McIntyre et al. (2015) [Ref 2] fatality case:** - 4-MeO-PCP + 4-HO-MET + venlafaxine (SNRI) + olanzapine (antipsychotic) + lorazepam (benzodiazepine) + hydroxyzine (antihistamine) - Death ruled acute mixed drug intoxication; 4-MeO-PCP was principal cause. The specific interaction contributions of co-medications are not quantified. **General class interactions (PCP/NMDA antagonist class):** - **CNS depressants (alcohol, benzodiazepines, opioids):** Additive CNS depression; all fatal cases in the analog literature involve polysubstance with at least one CNS depressant [Refs 3, 33, 34] - **Stimulants:** Pharmacodynamic antagonism of sedative effects; Mitchell-Mata 2017 [Ref 3] notes one death combined 3-MeO-PCP with methamphetamine - **Serotonergic agents (SSRIs, SNRIs, MAOIs):** SERT affinity of PCP analogs raises serotonin syndrome concern; no published cases specifically for 4-MeO-PCP. The fatality case involved venlafaxine at therapeutic levels — insufficient to establish causality for an interaction but warrants flagging - **Antipsychotics:** Theoretical interaction via dopaminergic effects; clinical management use is documented for agitation in PCP intoxication ### Interaction Gaps - No CYP enzyme inhibition/induction studies for 4-MeO-PCP - No serotonin syndrome risk quantification for 4-MeO-PCP + serotonergics - Alcohol + 4-MeO-PCP: expected additive CNS depression; no direct data **FLAG:** All drug interaction data is class-level inference or extrapolated from case reports of related compounds (3-MeO-PCP, PCP). No controlled interaction studies exist. --- ## Legal Status ### International Control 4-MeO-PCP is **not under international control** as of 2024 (UNODC [Ref 29]). Unlike PCP itself, and the analogs PCE, PHP, and TCP — which are scheduled under Schedule I of the 1971 Convention on Psychotropic Substances — and methoxetamine (Schedule II), 4-MeO-PCP has no UN-level scheduling. 4-MeO-PCP was identified as "the most common PCP-type substance" reported by UN member states (UNODC [Ref 29]). ### Jurisdiction-by-Jurisdiction | Jurisdiction | Status | Notes | |---|---|---| | United States (Federal) | **Unscheduled** | Not a controlled substance. Federal Analogue Act (21 USC §813) may apply as a structural/pharmacological analog of PCP (Schedule II); DEA spokesperson reportedly stated purchasing constitutes a felony. Not formally adjudicated. [Ref 25] | | Virginia (US state) | Temporary Schedule I | June 26, 2019 – December 25, 2020 [Ref 25] | | United Kingdom | **Controlled** | Covered under the Psychoactive Substances Act 2016 (effective May 26, 2016), which bans all psychoactive substances not otherwise exempt. Not named in Misuse of Drugs Act schedules. | | Germany | **Controlled** | Covered under Neue-psychoaktive-Stoffe-Gesetz (NpSG) effective November 26, 2016; generic legislation covering all NPS. | | Sweden | **Hazardous substance** | Public health agency classified 4-MeO-PCP as a hazardous substance November 10, 2014; 3-MeO-PCP formally scheduled January 2015. | | Canada | **Effectively controlled** | Canada's Controlled Drugs and Substances Act (CDSA) Schedule 1 covers PCP and its analogs/derivatives broadly, encompassing 4-MeO-PCP. | | Australia | **Status unconfirmed from primary sources** | Expected to be controlled under the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP) Schedule 9 via PCP analogue provisions, but not confirmed from primary source review. **FLAG: requires editorial verification.** | | EU (general) | **Varies by country** | No EU-level scheduling specific to 4-MeO-PCP; individual member states have generic NPS legislation. | --- ## Clinical Trials **No clinical trials for 4-MeO-PCP were found** in ClinicalTrials.gov (searched: "4-methoxyphencyclidine," "4-MeO-PCP"). This is expected given the compound's recreational-use-only history, lack of therapeutic development, and controlled/hazardous substance status in major jurisdictions. --- ## Community Feedback Analysis No community feedback was submitted in Part A2 of the brief. --- ## Gaps & Flags ### Data Absent from Published Literature 1. **⚠️ Exact Ki values for 4-MeO-PCP** — Roth et al. 2013 [Ref 1] is the primary pharmacology paper and confirms high NMDA affinity, sigma receptor affinity, and SERT affinity, but exact numerical Ki (nM) values could not be extracted from the cached abstract or open-access PDF (access blocked). Generation agent must access the full paper (DOI 10.1371/journal.pone.0059334) to cite precise binding values. 2. **No published human pharmacokinetic data** — bioavailability, Tmax, plasma half-life, Vd for 4-MeO-PCP are unknown. All PK inference is from 3-MeO-PCP analog (Michely et al. 2017 [Ref 17]) and must be labeled as analog inference. 3. **No published metabolic studies for 4-MeO-PCP** — only class-level inference from CYP2B6/2C19/2D6 data for 3-MeO-PCP. 4. **No LD₅₀ data** — "exact toxic dosage is unknown" (seed data) confirmed. Lethality demonstrated in mice (Shaw 2024 [Ref 24]) but dose not specified in abstract. 5. **No controlled human dosing studies** — all dose and duration data in the seed data are community-consensus (user-report) origin and lack clinical verification. 6. **No published tolerance or dependence studies** for 4-MeO-PCP specifically. 7. **No CYP inhibition/induction data** for drug interaction risk assessment. 8. **Maddox 1965 original synthesis paper** not located in academic databases; confirmed only from secondary sources. 9. **Stereochemistry/enantioselective pharmacology** for 4-MeO-PCP not studied. 10. **Reagent/colorimetric test performance** for harm reduction drug checking not published. 11. **Australia legal status** not confirmed from primary government source. ### Contradictions/Discrepancies 12. **CAS number ambiguity:** CAS 91164-58-8 returned for 4-MeO-PCP in chemical supplier databases, but Cayman Chemical assigns CAS 91164-58-8 to 3-methoxy PCP (hydrochloride). This is a potential isomer CAS mix-up and requires editorial verification. 13. **Dopamine reuptake inhibitor:** Listed as a pharmacological class in seed data. No 4-MeO-PCP–specific DAT binding data found in literature. Flag as unverified class inference. 14. **Duration of action** (12–20 hours oral) is unusually long for an arylcyclohexylamine. While pharmacologically plausible given lipophilicity, no published PK data supports this value. Flag as community-report data pending verification. ### Safety-Critical Values Requiring Editorial Review 15. **⚠️** All dose ranges (oral and insufflated) in seed data are **unverified** against published clinical sources. 16. **⚠️** Tolerance half-life (5 days) and reset values (1.5 weeks) are **unverified** against published sources. 17. **⚠️** The peripheral blood concentration in the single 4-MeO-PCP fatality (8.2 mg/L) should NOT be presented as a defined lethal threshold — it reflects a polysubstance case. 18. **⚠️** Serotonin syndrome risk with SSRIs/SNRIs: plausible given SERT affinity, but no published cases confirm severity. The fatality case included venlafaxine — however the primary cause was attributed to 4-MeO-PCP, and interaction specifics were not characterized.