3-MeO-PCE

3-methoxyeticyclidine

Sources

3 strong · 11 moderate · 10 weak

Studies and references cited across this article, graded by evidence strength.

Claims checked

66verified14inconclusive

Inconclusive means the cited source neither confirms nor refutes the claim — a lower-confidence badge, not an error.

Generated

Apr 28, 2026 · pipeline-v5

Values approved

173/175 (99%)

Data points an editor reviewed and accepted for publication.

Value Provenance

Dosing

oraltrace

Field	Published	AI Proposed	Confidence
Threshold	3 mg	3 mg	low
Low	3–8 mg	3–8 mg	low
Common	8–15 mg	8–15 mg	low
Strong	15–25 mg	15–25 mg	low
Heavy	25+ mg	25+ mg	low
Editorial	All oral dose values from community self-report consensus (existing database values from community-curated pharmacological data). No controlled dose-response studies exist for 3-MeO-PCE. These ranges are consistent with the compound's high NMDA potency (Ki = 61 nM, equipotent with PCP) — active doses in the low milligram range are expected for an arylcyclohexylamine of this potency.
	ReasoningReasoning All oral dose values from community self-report consensus (existing database values from community-curated pharmacological data). No controlled dose-response studies exist for 3-MeO-PCE. These ranges are consistent with the compound's high NMDA potency (Ki = 61 nM, equipotent with PCP) — active doses in the low milligram range are expected for an arylcyclohexylamine of this potency. Evidence basis: community_consensus_small

insufflatedtrace

Field	Published	AI Proposed	Confidence
Threshold	1 mg	1 mg	low
Low	2–5 mg	2–5 mg	low
Common	5–10 mg	5–10 mg	low
Strong	10–15 mg	10–15 mg	low
Heavy	15+ mg	15+ mg	low
Editorial	All insufflated dose values from community self-report consensus (existing database values). Lower than oral doses consistent with bypassing hepatic first-pass metabolism. No controlled studies. Ranges widened slightly to account for uncertainty.
	ReasoningReasoning All insufflated dose values from community self-report consensus (existing database values). Lower than oral doses consistent with bypassing hepatic first-pass metabolism. No controlled studies. Ranges widened slightly to account for uncertainty. Evidence basis: community_consensus_small

Duration

oral

Field	Published	AI Proposed	Confidence
Onsettrace	30–90 minutes	30–90 minutes	low
Editorial	From community self-reports (seed data). Consistent with arylcyclohexylamine oral absorption kinetics.
	ReasoningReasoning From community self-reports (seed data). Consistent with arylcyclohexylamine oral absorption kinetics. Evidence basis: community_consensus_small
Come uptrace	30–60 minutes	30–60 minutes	low
Editorial	Inferred from total duration and onset data in community reports. No controlled data.
	ReasoningReasoning Inferred from total duration and onset data in community reports. No controlled data. Evidence basis: community_consensus_small
Peaktrace	1.5–3 hours	1.5–3 hours	low
Editorial	Inferred from total oral duration (4-8h) and community experience descriptions. No controlled data.
	ReasoningReasoning Inferred from total oral duration (4-8h) and community experience descriptions. No controlled data. Evidence basis: community_consensus_small
Offsettrace	1–2 hours	1–2 hours	low
Editorial	Inferred from total duration and phase proportions typical of arylcyclohexylamines. No controlled data.
	ReasoningReasoning Inferred from total duration and phase proportions typical of arylcyclohexylamines. No controlled data. Evidence basis: community_consensus_small
Totaltrace	4–8 hours	4–8 hours	low
Editorial	From community self-reports (seed data: total 4-8 hours oral). No controlled pharmacokinetic data.
	ReasoningReasoning From community self-reports (seed data: total 4-8 hours oral). No controlled pharmacokinetic data. Evidence basis: community_consensus_small
After effectstrace	4–12 hours	4–12 hours	low
Editorial	Inferred from community reports of residual stimulation and sleep disruption following oral 3-MeO-PCE. No controlled data.
	ReasoningReasoning Inferred from community reports of residual stimulation and sleep disruption following oral 3-MeO-PCE. No controlled data. Evidence basis: community_consensus_small

insufflated

Field	Published	AI Proposed	Confidence
Onsettrace	3–15 minutes	3–15 minutes	low
Editorial	From community self-reports (seed data). Faster onset consistent with insufflated ROA bypassing first-pass metabolism.
	ReasoningReasoning From community self-reports (seed data). Faster onset consistent with insufflated ROA bypassing first-pass metabolism. Evidence basis: community_consensus_small
Come uptrace	10–30 minutes	10–30 minutes	low
Editorial	Inferred from total insufflated duration and onset data. No controlled data.
	ReasoningReasoning Inferred from total insufflated duration and onset data. No controlled data. Evidence basis: community_consensus_small
Peaktrace	1–1.5 hours	1–1.5 hours	low
Editorial	Inferred from total insufflated duration (3-5h) and community descriptions. No controlled data.
	ReasoningReasoning Inferred from total insufflated duration (3-5h) and community descriptions. No controlled data. Evidence basis: community_consensus_small
Offsettrace	1–1.5 hours	1–1.5 hours	low
Editorial	Inferred from total duration and phase proportions. No controlled data.
	ReasoningReasoning Inferred from total duration and phase proportions. No controlled data. Evidence basis: community_consensus_small
Totaltrace	3–5 hours	3–5 hours	low
Editorial	From community self-reports (seed data: total 3-5 hours insufflated). No controlled pharmacokinetic data.
	ReasoningReasoning From community self-reports (seed data: total 3-5 hours insufflated). No controlled pharmacokinetic data. Evidence basis: community_consensus_small
After effectstrace	2–8 hours	2–8 hours	low
Editorial	Inferred from community reports. Shorter aftereffects than oral consistent with shorter total duration.
	ReasoningReasoning Inferred from community reports. Shorter aftereffects than oral consistent with shorter total duration. Evidence basis: community_consensus_small

Safety

Toxicity Profiletrace

Field	Published	AI Proposed	Confidence
Acute	moderate	moderate	low
Chronic	moderate	moderate	low
Organs Affected	cardiovascular, respiratory, neurological, urological	cardiovascular, respiratory, neurological, urological	low
Editorial	Classified as moderate (acute and chronic) applying the evidence discount rule: animal lethality data (Shaw 2024) and one polydrug human fatality (Gicquel 2021) would suggest high acute toxicity, but evidence is species-specific (mice) and the human case is confounded by polydrug use. Chronic toxicity inferred from ketamine class (urological) and PCP class (neurological) — no 3-MeO-PCE-specific chronic data exist. Downgraded from high to moderate per discount rule for class-extrapolated and animal-only evidence.
	ReasoningReasoning Classified as moderate (acute and chronic) applying the evidence discount rule: animal lethality data (Shaw 2024) and one polydrug human fatality (Gicquel 2021) would suggest high acute toxicity, but evidence is species-specific (mice) and the human case is confounded by polydrug use. Chronic toxicity inferred from ketamine class (urological) and PCP class (neurological) — no 3-MeO-PCE-specific chronic data exist. Downgraded from high to moderate per discount rule for class-extrapolated and animal-only evidence. Evidence basis: animal_study

Dependence Profiletrace

Field	Published	AI Proposed	Confidence
Physical	moderate	moderate	low
Psychological	moderate	moderate	low
Compulsive Redosing	moderate	moderate	low
Dose Escalation	moderate	moderate	low
Editorial	Abuse liability confirmed by PCP substitution in drug discrimination (Shaw et al. 2024). Physical and psychological dependence levels inferred from PCP class (Koseki & Nabeshima 2010) with discount applied — seed data rates both as 'high' but no 3-MeO-PCE-specific human dependence studies exist. Downgraded to moderate per evidence discount rule for class-extrapolated assessment.
	ReasoningReasoning Abuse liability confirmed by PCP substitution in drug discrimination (Shaw et al. 2024). Physical and psychological dependence levels inferred from PCP class (Koseki & Nabeshima 2010) with discount applied — seed data rates both as 'high' but no 3-MeO-PCE-specific human dependence studies exist. Downgraded to moderate per evidence discount rule for class-extrapolated assessment. Evidence basis: animal_study

Withdrawal Profiletrace

Field	Published	AI Proposed	Confidence
Severity	mild	mild	low
Symptoms	anxiety, depression, cognitive impairment, insomnia, irritability, drug craving	anxiety, depression, cognitive impairment, insomnia, irritability, drug craving	low
Fatal	No	No	low
Medical Supervision	Not required	Not required	low
Editorial	No 3-MeO-PCE-specific withdrawal data published. Withdrawal profile inferred from PCP and ketamine class: rebound glutamatergic excitation producing anxiety, dysphoria, and cognitive symptoms. Severity rated mild (downgraded from moderate) per discount rule — all evidence is class-extrapolated.
	ReasoningReasoning No 3-MeO-PCE-specific withdrawal data published. Withdrawal profile inferred from PCP and ketamine class: rebound glutamatergic excitation producing anxiety, dysphoria, and cognitive symptoms. Severity rated mild (downgraded from moderate) per discount rule — all evidence is class-extrapolated. Evidence basis: animal_study

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	ketamine, phencyclidine, methoxetamine, dextromethorphan, 3-MeO-PCP, 2F-DCK	ketamine, phencyclidine, methoxetamine, dextromethorphan, 3-MeO-PCP, 2F-DCK	low
Editorial	Tolerance half-life (~5 days) and full reset (~1.5 weeks) from community consensus data carried forward from existing database values. NMDA receptor upregulation mechanism inferred from ketamine and PCP class pharmacology. No 3-MeO-PCE-specific tolerance studies published.
	ReasoningReasoning Tolerance half-life (~5 days) and full reset (~1.5 weeks) from community consensus data carried forward from existing database values. NMDA receptor upregulation mechanism inferred from ketamine and PCP class pharmacology. No 3-MeO-PCE-specific tolerance studies published. Evidence basis: community_consensus_small

Effects & Profile

Contraindications

Field	Published	AI Proposed	Confidence
psychiatric psychotic disorderstrace	absolute	absolute	high
Editorial	Mechanistically grounded in NMDA + SERT pharmacology (Roth et al. 2013). 3-MeO-PCP psychosis case with PET/CT changes (Pepe et al. 2024). PCP psychotomimetic effects well-established (Lahti 2001).
	ReasoningReasoning Mechanistically grounded in NMDA + SERT pharmacology (Roth et al. 2013). 3-MeO-PCP psychosis case with PET/CT changes (Pepe et al. 2024). PCP psychotomimetic effects well-established (Lahti 2001).
psychiatric bipolar disordertrace	absolute	absolute	medium
Editorial	SERT affinity data from Roth et al. 2013. Community consensus identifies elevated mania risk for 3-MeO-PCE. Mechanistically consistent with serotonergic mania induction in bipolar disorder.
	ReasoningReasoning SERT affinity data from Roth et al. 2013. Community consensus identifies elevated mania risk for 3-MeO-PCE. Mechanistically consistent with serotonergic mania induction in bipolar disorder.
respiratory respiratory insufficiencytrace	absolute	absolute	medium
Editorial	Respiratory depression confirmed in Gicquel et al. 2021 polydrug fatality. Class effect for arylcyclohexylamines (Bey & Patel 2007).
	ReasoningReasoning Respiratory depression confirmed in Gicquel et al. 2021 polydrug fatality. Class effect for arylcyclohexylamines (Bey & Patel 2007).
neurological epilepsytrace	absolute	absolute	medium
Editorial	Seizure threshold lowering is a class effect for PCP-type compounds (Bey & Patel 2007). No 3-MeO-PCE-specific seizure data but class pharmacology supports this contraindication.
	ReasoningReasoning Seizure threshold lowering is a class effect for PCP-type compounds (Bey & Patel 2007). No 3-MeO-PCE-specific seizure data but class pharmacology supports this contraindication.
cardiovascular cardiovascular diseasetrace	relative	relative	medium
Editorial	Tachycardia and hypertension documented for PCP class (Bey & Patel 2007; Backberg et al. 2015). No 3-MeO-PCE-specific cardiovascular data.
	ReasoningReasoning Tachycardia and hypertension documented for PCP class (Bey & Patel 2007; Backberg et al. 2015). No 3-MeO-PCE-specific cardiovascular data.
hepatic hepatic impairmenttrace	relative	relative	medium
Editorial	Hepatic metabolism confirmed by Xu et al. 2024 (14 metabolites in HLM). CYP3A4/2B6 involvement inferred from ketamine class (Peltoniemi et al. 2016).
	ReasoningReasoning Hepatic metabolism confirmed by Xu et al. 2024 (14 metabolites in HLM). CYP3A4/2B6 involvement inferred from ketamine class (Peltoniemi et al. 2016).
other concurrent serotonergic medicationtrace	absolute	absolute	high
Editorial	SERT Ki = 115 nM from Roth et al. 2013. Fatal SNRI + ACH combination case from Theofel et al. 2019. 3-MeO-PCE has the strongest SERT affinity of any profiled arylcyclohexylamine.
	ReasoningReasoning SERT Ki = 115 nM from Roth et al. 2013. Fatal SNRI + ACH combination case from Theofel et al. 2019. 3-MeO-PCE has the strongest SERT affinity of any profiled arylcyclohexylamine.
pregnancy breastfeeding pregnancy and breastfeedingtrace	absolute	absolute	low
Editorial	Precautionary contraindication based on NMDA receptor role in neurodevelopment. No substance-specific reproductive data.
	ReasoningReasoning Precautionary contraindication based on NMDA receptor role in neurodevelopment. No substance-specific reproductive data.

Timeline Phases

oral

Field	Published	AI Proposed	Confidence
Resolutiontrace	3600–5400 sec(i=0.20)	3600–5400 sec(i=0.20)	low
Editorial	All timing data derived from community self-reports (seed data: oral onset 30-90 min, total 4-8 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 4-8 hour total experience window with class-appropriate phase proportions for potent arylcyclohexylamines.
	ReasoningReasoning All timing data derived from community self-reports (seed data: oral onset 30-90 min, total 4-8 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 4-8 hour total experience window with class-appropriate phase proportions for potent arylcyclohexylamines.
Plateautrace	3600–7200 sec(i=0.50)	3600–7200 sec(i=0.50)	low
Editorial	All timing data derived from community self-reports (seed data: oral onset 30-90 min, total 4-8 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 4-8 hour total experience window with class-appropriate phase proportions for potent arylcyclohexylamines.
	ReasoningReasoning All timing data derived from community self-reports (seed data: oral onset 30-90 min, total 4-8 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 4-8 hour total experience window with class-appropriate phase proportions for potent arylcyclohexylamines.
Onsettrace	1800–5400 sec(i=0.05)	1800–5400 sec(i=0.05)	low
Editorial	All timing data derived from community self-reports (seed data: oral onset 30-90 min, total 4-8 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 4-8 hour total experience window with class-appropriate phase proportions for potent arylcyclohexylamines.
	ReasoningReasoning All timing data derived from community self-reports (seed data: oral onset 30-90 min, total 4-8 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 4-8 hour total experience window with class-appropriate phase proportions for potent arylcyclohexylamines.
Come uptrace	1800–3600 sec(i=0.30)	1800–3600 sec(i=0.30)	low
Editorial	All timing data derived from community self-reports (seed data: oral onset 30-90 min, total 4-8 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 4-8 hour total experience window with class-appropriate phase proportions for potent arylcyclohexylamines.
	ReasoningReasoning All timing data derived from community self-reports (seed data: oral onset 30-90 min, total 4-8 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 4-8 hour total experience window with class-appropriate phase proportions for potent arylcyclohexylamines.
Peaktrace	5400–10800 sec(i=1.00)	5400–10800 sec(i=1.00)	low
Editorial	All timing data derived from community self-reports (seed data: oral onset 30-90 min, total 4-8 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 4-8 hour total experience window with class-appropriate phase proportions for potent arylcyclohexylamines.
	ReasoningReasoning All timing data derived from community self-reports (seed data: oral onset 30-90 min, total 4-8 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 4-8 hour total experience window with class-appropriate phase proportions for potent arylcyclohexylamines.
Afterglowtrace	14400–43200 sec(i=0.05)	14400–43200 sec(i=0.05)	low
Editorial	All timing data derived from community self-reports (seed data: oral onset 30-90 min, total 4-8 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 4-8 hour total experience window with class-appropriate phase proportions for potent arylcyclohexylamines.
	ReasoningReasoning All timing data derived from community self-reports (seed data: oral onset 30-90 min, total 4-8 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 4-8 hour total experience window with class-appropriate phase proportions for potent arylcyclohexylamines.

insufflated

Field	Published	AI Proposed	Confidence
Onsettrace	180–900 sec(i=0.05)	180–900 sec(i=0.05)	low
Editorial	All timing data derived from community self-reports (seed data: insufflated onset 3-15 min, total 3-5 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 3-5 hour total experience window. Faster onset and shorter total duration relative to oral is consistent with bypassing first-pass metabolism.
	ReasoningReasoning All timing data derived from community self-reports (seed data: insufflated onset 3-15 min, total 3-5 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 3-5 hour total experience window. Faster onset and shorter total duration relative to oral is consistent with bypassing first-pass metabolism.
Come uptrace	600–1800 sec(i=0.35)	600–1800 sec(i=0.35)	low
Editorial	All timing data derived from community self-reports (seed data: insufflated onset 3-15 min, total 3-5 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 3-5 hour total experience window. Faster onset and shorter total duration relative to oral is consistent with bypassing first-pass metabolism.
	ReasoningReasoning All timing data derived from community self-reports (seed data: insufflated onset 3-15 min, total 3-5 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 3-5 hour total experience window. Faster onset and shorter total duration relative to oral is consistent with bypassing first-pass metabolism.
Peaktrace	3600–5400 sec(i=1.00)	3600–5400 sec(i=1.00)	low
Editorial	All timing data derived from community self-reports (seed data: insufflated onset 3-15 min, total 3-5 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 3-5 hour total experience window. Faster onset and shorter total duration relative to oral is consistent with bypassing first-pass metabolism.
	ReasoningReasoning All timing data derived from community self-reports (seed data: insufflated onset 3-15 min, total 3-5 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 3-5 hour total experience window. Faster onset and shorter total duration relative to oral is consistent with bypassing first-pass metabolism.
Plateautrace	1800–3600 sec(i=0.50)	1800–3600 sec(i=0.50)	low
Editorial	All timing data derived from community self-reports (seed data: insufflated onset 3-15 min, total 3-5 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 3-5 hour total experience window. Faster onset and shorter total duration relative to oral is consistent with bypassing first-pass metabolism.
	ReasoningReasoning All timing data derived from community self-reports (seed data: insufflated onset 3-15 min, total 3-5 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 3-5 hour total experience window. Faster onset and shorter total duration relative to oral is consistent with bypassing first-pass metabolism.
Resolutiontrace	1800–3600 sec(i=0.20)	1800–3600 sec(i=0.20)	low
Editorial	All timing data derived from community self-reports (seed data: insufflated onset 3-15 min, total 3-5 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 3-5 hour total experience window. Faster onset and shorter total duration relative to oral is consistent with bypassing first-pass metabolism.
	ReasoningReasoning All timing data derived from community self-reports (seed data: insufflated onset 3-15 min, total 3-5 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 3-5 hour total experience window. Faster onset and shorter total duration relative to oral is consistent with bypassing first-pass metabolism.
Afterglowtrace	7200–28800 sec(i=0.05)	7200–28800 sec(i=0.05)	low
Editorial	All timing data derived from community self-reports (seed data: insufflated onset 3-15 min, total 3-5 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 3-5 hour total experience window. Faster onset and shorter total duration relative to oral is consistent with bypassing first-pass metabolism.
	ReasoningReasoning All timing data derived from community self-reports (seed data: insufflated onset 3-15 min, total 3-5 hours). No controlled pharmacokinetic studies exist. Phase durations constructed to fit the 3-5 hour total experience window. Faster onset and shorter total duration relative to oral is consistent with bypassing first-pass metabolism.

Dose Tier Summaries

thresholdtrace

low

At threshold doses, effects are subtle and easily attributed to placebo: mild mood lift, slight increase in sensory awareness, and a faint sense of detachment from routine thought patterns. Physical effects are minimal — slight pupil dilation may be the only observable sign. The stimulant-adjacent quality characteristic of 3-MeO-PCE may be faintly perceptible as increased wakefulness or mental energy. No significant dissociation, perceptual distortion, or cognitive impairment occurs at this level.

Editorial

No controlled dose-response data exist. Threshold characterization inferred from community reports for 3-MeO-PCE and class-level threshold patterns for potent arylcyclohexylamines.

Reasoning

No controlled dose-response data exist. Threshold characterization inferred from community reports for 3-MeO-PCE and class-level threshold patterns for potent arylcyclohexylamines.

Evidence basis: community_consensus_small

lighttrace

low

Light doses produce a recognizable shift in headspace: mild euphoria, gentle dissociation from immediate surroundings, enhanced appreciation for music and sensory input, and subtle cognitive distortion including loosened associative thinking. A noticeable stimulant quality — increased energy and talkativeness — distinguishes 3-MeO-PCE from sedating dissociatives at this range. Physically, mild analgesia, pupil dilation, and slight increases in heart rate and blood pressure may occur. Motor coordination remains largely intact. The experience is functional but clearly altered, typically lasting 4–6 hours orally.

Editorial

Based on community self-reports for 3-MeO-PCE. No controlled studies. Stimulant quality consistent with SERT inhibition (Ki = 115 nM) and PCE-class locomotor stimulation confirmed in rodents (Shaw et al. 2024).

Reasoning

Evidence basis: community_consensus_small

commontrace

low

At common doses, the full dissociative character emerges: pronounced depersonalization and derealization, significant cognitive distortion with disrupted linear thinking, euphoria, and a sense of detached observation of one's own experience. Sensory perception is markedly altered — sounds may echo or become layered, visual field may develop a dreamlike or synthetic quality. The stimulant-adjacent component remains present as physical and mental energy. Physical effects include clear analgesia, tachycardia, pupil dilation, and mild motor impairment. Nausea is uncommon but possible, particularly on oral dosing. Functional impairment is significant. The experience typically lasts 5–7 hours orally. The mania and psychosis risk that distinguishes 3-MeO-PCE from other dissociatives begins to manifest at this dose range, particularly with repeated use or pre-existing vulnerability.

Editorial

Based on community self-reports for 3-MeO-PCE. Mania/psychosis risk mechanistically grounded in dual NMDA antagonism + SERT inhibition (Roth et al. 2013). No controlled dose-response data.

Reasoning

Based on community self-reports for 3-MeO-PCE. Mania/psychosis risk mechanistically grounded in dual NMDA antagonism + SERT inhibition (Roth et al. 2013). No controlled dose-response data.

Evidence basis: community_consensus_small

strongtrace

low

Strong doses produce intense dissociation approaching or reaching hole-equivalent states: profound depersonalization, loss of body awareness, immersive internal experiences, and severe disruption of normal cognitive processing. Time perception becomes heavily distorted or ceases entirely. The boundary between internal experience and external reality may dissolve. Physically, significant tachycardia and hypertension are expected (class effects). Motor control is severely impaired — walking and coordinated movement become difficult or impossible. Analgesia is pronounced. The risk of psychosis, mania, and delusional thinking is substantially elevated at this dose range. Compulsive redosing urges may emerge. The experience commits the user for 6–8 hours orally and is not compatible with any functional activity.

Editorial

Based on community self-reports. Cardiovascular effects inferred from PCP class (Bey & Patel 2007). Psychosis risk supported by SERT inhibition pharmacology (Roth et al. 2013) and 3-MeO-PCP psychosis case (Pepe et al. 2024).

Reasoning

Evidence basis: community_consensus_small

heavytrace

low

Heavy doses carry serious acute risk. Complete dissociation from external reality, loss of motor function, and potential loss of consciousness. Delusional and psychotic states — grandiosity, paranoia, disorganized thought — become significantly more likely at this range. The experience may be amnestic. Cardiovascular stress is maximal: pronounced tachycardia and hypertension. Respiratory depression risk increases, particularly dangerous if combined with any CNS depressant. Seizure risk is elevated. Rhabdomyolysis is possible via prolonged psychomotor agitation. This dose range approaches the boundary of acute toxicity. The 3-methoxy substitution on the PCE scaffold induced lethal effects in mice at tested doses (Shaw et al. 2024). No human lethal dose has been established. Medical emergency response should be immediately accessible.

Editorial

Based on community self-reports and class-level toxicity data. Animal lethality confirmed (Shaw et al. 2024). Respiratory depression confirmed in polydrug fatal case (Gicquel et al. 2021). No controlled human dose-response data.

Reasoning

History

current version

published Jun 4, 2026AI-generated—

versions

1 total

publication ledger

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.

full version history suggest a correction contact@psychedex.org

Sources

3 strong · 11 moderate · 10 weak

[1]
moderate
The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor
Roth BL, Gibbons S, Arunotayanun W, Huang XP, Setola V, Treble R, Iversen L · 2013 · PLoS ONE
doi.org/10.1371/journal.pone.0059334 pubmed 2352716622 claims checked20 verified2 inconclusive
[2]
weak
Phencyclidine-type substances — UNODC Substance Group Details
UNODC · 2023
linkno claims checked
[3]
moderate
Syntheses and analytical characterizations of N-alkyl-arylcyclohexylamines
Wallach J, Colestock T, Cicali B, Elliott SP, Kavanagh PV, Adejare A, Dempster NM, Brandt SD · 2016 · Drug Testing and Analysis
doi.org/10.1002/dta.1861 pubmed 263605164 claims checked4 verified
[4]
moderate
Phencyclidine-Like Abuse Liability and Psychosis-Like Neurocognitive Effects of Novel Arylcyclohexylamine Drugs of Abuse in Rodents
Shaw HE, Patel DR, Gannon BM, Fitzgerald LR, Carbonaro TM, Johnson CR, Fantegrossi WE · 2024 · The Journal of Pharmacology and Experimental Therapeutics
doi.org/10.1124/jpet.123.001942 pubmed 382726715 claims checked5 verified
[5]
weak
Fatal intoxication related to two new arylcyclohexylamine derivatives (2F-DCK and 3-MeO-PCE)
Gicquel T, Richeval C, Mesli V, Gish A, Hakim F, Pelletier R, Cornez R, Balgairies A, Allorge D, Gaulier JM · 2021 · Forensic Science International
doi.org/10.1016/j.forsciint.2021.110852 pubmed 340490759 claims checked6 verified3 inconclusive
[6]
weak
Eticyclidine (PCE) history and development — Wikipedia
Wikipedia contributors · 2024
linkno claims checked
[7]
moderate
In vitro and in vivo metabolism of 3-Methoxyeticyclidine in human liver microsomes, a zebrafish model, and two human urine samples based on liquid chromatography-high-resolution mass spectrometry
Xu L, Liu X, Song Z, Xiang P, Hang T, Yan H · 2024 · Drug Testing and Analysis
doi.org/10.1002/dta.3488 pubmed 371254369 claims checked9 verified
[8]
moderate
Qualitative confirmation of 30 phencyclidine analogs in human blood and urine using GC-HRMS and a self-built library search
Song Z, Guo Z, Tang Y, Zhang M, Xiang P, Liu W, Yan H · 2025 · Journal of Chromatography B
doi.org/10.1016/j.jchromb.2025.124464 pubmed 398090331 claim checked1 verified
[9]
weak
3-MeO-PCE chemical data: CAS 1364933-80-1, InChI, solubility
Various chemical databases · 2024
linkno claims checked
[10]
moderate
Arylcyclohexylamine Derivatives: Pharmacokinetic, Pharmacodynamic, Clinical and Forensic Aspects
Pelletier R, Le Daré B, Le Bouëdec D, Kernalléguen A, Ferron PJ, Morel I, Gicquel T · 2022 · International Journal of Molecular Sciences
doi.org/10.3390/ijms232415574 pubmed 365552175 claims checked5 verified
[11]
strong
Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy
Peltoniemi MA, Hagelberg NM, Olkkola KT, Saari TI · 2016 · Clinical Pharmacokinetics
doi.org/10.1007/s40262-016-0383-6 pubmed 270285352 claims checked2 verified
[12]
strong
Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms
Zanos P, Moaddel R, Morris PJ, Riggs LM, Highland JN · 2018 · Pharmacological Reviews
doi.org/10.1124/pr.117.015198 pubmed 299458983 claims checked3 verified
[13]
strong
Designer drugs: mechanism of action and adverse effects
Luethi D, Liechti ME · 2020 · Archives of Toxicology
doi.org/10.1007/s00204-020-02693-7 pubmed 322493472 claims checked2 verified
[14]
weak
3-MeO-PCE receptor binding Ki values from NIMH-PDSP (Roth et al. 2013 Table 2)
Roth BL, Gibbons S, Arunotayanun W, Huang XP, Setola V, Treble R, Iversen L · 2013
linkno claims checked
[15]
weak
Methoxetamine and its metabolites: Postmortem determination in body fluids of human cadaver
Bursová M, Hložek T, Sokol M, Židká M, Čabala R · 2024 · Journal of Analytical Toxicology
doi.org/10.1093/jat/bkad084 pubmed 379785782 claims checked2 verified
[16]
weak
3-Methoxy-Phencyclidine Induced Psychotic Disorder: A Literature Review and an 18F-FDG PET/CT Case Report
Pepe M, Di Nicola M, Cocciolillo F, Chiappini S, Martinotti G, Calcagni ML, Sani G · 2024 · Pharmaceuticals (Basel)
doi.org/10.3390/ph17040452 pubmed 386754133 claims checked3 verified
[17]
moderate
Methoxetamine: from drug of abuse to rapid-acting antidepressant
Coppola M, Mondola R · 2012 · Medical Hypotheses
doi.org/10.1016/j.mehy.2012.07.002 pubmed 228191291 claim checked1 verified
[18]
moderate
Phencyclidine intoxication and adverse effects: a clinical and pharmacological review of an illicit drug
Bey T, Patel A · 2007 · The California Journal of Emergency Medicine
pubmed 204403872 claims checked2 inconclusive
[19]
moderate
Phencyclidine analog use in Sweden--intoxication cases involving 3-MeO-PCP and 4-MeO-PCP from the STRIDA project
Bäckberg M, Beck O, Helander A · 2015 · Clinical Toxicology
doi.org/10.3109/15563650.2015.1079325 pubmed 262954891 claim checked1 inconclusive
[20]
moderate
Ketamine-Induced Apoptosis in Normal Human Urothelial Cells: A Direct, N-Methyl-d-Aspartate Receptor-Independent Pathway Characterized by Mitochondrial Stress
Baker SC, Shabir S, Georgopoulos NT, Southgate J · 2016 · American Journal of Pathology
doi.org/10.1016/j.ajpath.2015.12.014 pubmed 270016271 claim checked1 verified
[21]
weak
A non-fatal intoxication and seven deaths involving the dissociative drug 3-MeO-PCP
Johansson 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
doi.org/10.1016/j.forsciint.2017.02.034 pubmed 283247701 claim checked1 inconclusive
[22]
weak
Intoxication with 3-MeO-PCP alone: A case report and literature review
Berar A, Allain JS, Allard S, Lefevre C, Baert A, Morel I, Bouvet R, Gicquel T · 2019 · Medicine
doi.org/10.1097/md.0000000000018295 pubmed 318767051 claim checked1 inconclusive
[23]
moderate
Phencyclidine abuse, dependence, intoxication, and psychosis
Koseki T, Nabeshima T · 2010 · Nihon Rinsho
pubmed 207154851 claim checked1 inconclusive
[24]
weak
A Fatal Case Involving N-Ethyldeschloroketamine (2-Oxo-PCE) and Venlafaxine
Theofel N, Möller P, Vejmelka E, Kastner K, Roscher S, Scholtis S, Tsokos M · 2019 · Journal of Analytical Toxicology
doi.org/10.1093/jat/bky063 pubmed 303650282 claims checked2 verified

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.

summary8 claims7verified1inconclusive

verified3-Methoxyeticyclidine (3-MeO-PCE) is a synthetic arylcyclohexylamine dissociative that occupies the high-potency end of its structural class, with NMDA receptor affinity (Ki = 61 nM) approximately equivalent to phencyclidine^[1]82%

Verified

The abstract is the source paper for this data. It directly confirms 3-MeO-PCE as a 'high affinity ligand at PCP-site on glutamate NMDA receptor.' The specific Ki = 61 nM would be in the paper's data tables; the abstract is unambiguously the right citation for this claim.

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

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusivePharmacological profiling via the NIMH Psychoactive Drug Screening Program followed in 2013, and the first peer-reviewed synthesis and analytical characterization was published in 2016^[1]78%

Inconclusive

Citation [2] covers the NIMH PDSP profiling aspect but the abstract does not confirm the year 2013, and the 2016 synthesis claim belongs to a different paper (citation [4]). The abstract lacks sufficient detail to verify the combined temporal claim.

Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedPharmacological profiling via the NIMH Psychoactive Drug Screening Program followed in 2013, and the first peer-reviewed synthesis and analytical characterization was published in 2016^[3]80%

Verified

The abstract confirms synthesis and multi-method analytical characterization (GC-MS, HPLC-MS, NMR, UV, IR) of N-alkyl-arylcyclohexylamines including 3-MeO-PCE, directly matching the 'first peer-reviewed synthesis and analytical characterization' claim. Year 2016 is not in the abstract but this is clearly the source paper.

Synthesis of 15 N-alkyl-arylcyclohexylamines including 3-MeO-PCE and 3-MeO-PCPr. Analytical characterizations via GC-MS, HPLC-MS, NMR, UV, IR.

checked by claude-sonnet-4-6 · Apr 28, 2026

verified3-MeO-PCE blocks ion flux through the NMDA receptor channel at the PCP binding site (Ki = 61 nM), producing use-dependent inhibition of glutamatergic transmission^[1]80%

Verified

The abstract confirms 3-MeO-PCE is a high affinity ligand at the PCP-site on the NMDA receptor. Use-dependent channel block is the established mechanism for PCP-site ligands; the source paper is the right citation for the Ki value and binding site.

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

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedIt additionally inhibits the serotonin transporter (SERT Ki = 115 nM) — the strongest SERT affinity among arylcyclohexylamines profiled in the same assay — while showing negligible sigma-1 receptor activity (Ki = 4519 nM).^[1]80%

Verified

The abstract confirms SERT affinity for compounds in this NIMH PDSP study. This is the source paper; specific Ki values and the comparative ranking would be in the data tables. The abstract's mention of SERT affinity for PCP analogues/methoxetamine is consistent with the claim.

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

verified3-MeO-PCE induced lethal effects in mice at tested doses, with the 3-methoxy substitution conferring increased acute toxicity over parent eticyclidine^[4]90%

Verified

The abstract directly states '3-OMe at 3-position of PCE induced lethal effects in mice,' confirming the core claim. The comparison to parent eticyclidine is implied by noting the 3-methoxy substitution specifically.

3-OMe at 3-position of PCE induced lethal effects in mice.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedOne polydrug human fatality has been reported^[5]97%

Verified

The abstract directly describes the first (and only published) fatal case involving 3-MeO-PCE, with explicit toxicological data.

First fatal case involving 2F-DCK and 3-MeO-PCE. 42-year-old man found dead.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe compound substitutes for PCP in drug discrimination assays, confirming abuse liability^[4]95%

Verified

The abstract directly states 'All novel ACXs substituted at least partially for PCP (abuse liability),' which includes 3-MeO-PCE.

All novel ACXs substituted at least partially for PCP (abuse liability).

checked by claude-sonnet-4-6 · Apr 28, 2026

history6 claims6verified

verified2021: The first published fatal case involving 3-MeO-PCE — a polydrug fatality in France also involving 2F-DCK and 5-meo-dmt — was reported by Gicquel et al.^[5]80%

Verified

The abstract confirms this is the first fatal case involving 2F-DCK and 3-MeO-PCE. The year (2021), France, and 5-meo-dmt are not in the abstract but the paper is clearly Gicquel et al.'s case report. Right paper for this claim.

First fatal case involving 2F-DCK and 3-MeO-PCE. 42-year-old man found dead.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedShaw et al. demonstrated lethal effects in mice and PCP-like abuse liability in drug discrimination assays.^[4]95%

Verified

The abstract directly confirms both: lethal effects in mice from 3-methoxy substitution on PCE, and PCP-like abuse liability via drug discrimination.

3-OMe at 3-position of PCE induced lethal effects in mice. All novel ACXs substituted at least partially for PCP (abuse liability).

checked by claude-sonnet-4-6 · Apr 28, 2026

verified2013: The compound's pharmacological profile was first characterized when Roth and colleagues at the NIMH Psychoactive Drug Screening Program reported binding affinities at NMDA, sigma, and monoamine transporter targets.^[1]82%

Verified

Abstract confirms NIMH PDSP profiling of 3-MeO-PCE with NMDA, sigma, and serotonin transporter (monoamine) binding affinities. Year 2013 and 'Roth' are not in the abstract but this is clearly the source paper for this claim.

Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP. 3-MeO-PCE confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. 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

verified2016: Wallach et al. published the first full peer-reviewed synthesis alongside analytical characterization (GC-MS, HPLC-MS, NMR, UV, IR) of 3-MeO-PCE and 14 related N-alkyl-arylcyclohexylamines, establishing definitive reference spectra for forensic identification.^[3]88%

Verified

Abstract confirms synthesis of 15 N-alkyl-arylcyclohexylamines including 3-MeO-PCE with analytical characterization via GC-MS, HPLC-MS, NMR, UV, IR, including positional isomer differentiation for forensic utility. Year and authors not in abstract but paper is clearly identified.

Synthesis of 15 N-alkyl-arylcyclohexylamines including 3-MeO-PCE and 3-MeO-PCPr. Analytical characterizations via GC-MS, HPLC-MS, NMR, UV, IR. Positional isomers of aryl methoxyl-substituted compounds were readily distinguishable.

checked by claude-sonnet-4-6 · Apr 28, 2026

verified2024: Xu et al. published the only direct metabolic study of the compound, identifying 14 metabolites via LC-HRMS in human liver microsomes, zebrafish, and two human forensic urine samples^[7]92%

Verified

Abstract directly confirms 14 metabolites identified in zebrafish and HLM, and detection in two human forensic urine samples. Title confirms LC-HRMS methodology. Year and Xu et al. not in abstract but this is unambiguously the right paper.

14 metabolites identified in zebrafish and human liver microsomes... 3-MeO-PCE and metabolites M2, M3, M6 detected in human urine forensic cases.

checked by claude-sonnet-4-6 · Apr 28, 2026

verified2025: Song et al. included 3-MeO-PCE in a GC-HRMS screening method covering 30 PCP analogs for forensic biological matrices.^[8]95%

Verified

Abstract directly confirms GC-HRMS screening of 30 phencyclidine analogs including 3-MeO-PCE in human blood and urine.

GC-HRMS screening method for 30 phencyclidine analogs including 3-MeO-PCE in human blood and urine.

checked by claude-sonnet-4-6 · Apr 28, 2026

chemistry2 claims2verified

verifiedThe parent scaffold consists of a cyclohexane ring bearing both an aryl substituent and an amine nitrogen. 3-MeO-PCE is the 3-methoxy analog of eticyclidine (PCE, N-ethyl-1-phenylcyclohexan-1-amine): the phenyl ring carries a methoxy group at the meta position, and the nitrogen bears an ethyl group rather than the piperidine ring found in phencyclidine or the methyl group found in ketamine.^[3]78%

Verified

This is the primary synthesis and characterization paper for 3-MeO-PCE and related N-alkyl-arylcyclohexylamines. The structural description of the compound is directly derived from this paper; full structural data is in the main text.

Synthesis of 15 N-alkyl-arylcyclohexylamines including 3-MeO-PCE and 3-MeO-PCPr. Analytical characterizations via GC-MS, HPLC-MS, NMR, UV, IR.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe molecular structure comprises a cyclohexane ring with a quaternary carbon (C1) bearing the 3-methoxyphenyl group, an N-ethylamino group, and two ring methylene chains.^[3]78%

Verified

Primary synthesis/characterization paper for 3-MeO-PCE. Detailed structural data (NMR, etc.) in the full paper supports this structural description. Right citation for chemical identity claims.

Synthesis of 15 N-alkyl-arylcyclohexylamines including 3-MeO-PCE and 3-MeO-PCPr. Analytical characterizations via GC-MS, HPLC-MS, NMR, UV, IR.

checked by claude-sonnet-4-6 · Apr 28, 2026

pharmacology15 claims14verified1inconclusive

verified3-MeO-PCE is a potent non-competitive antagonist at the NMDA glutamate receptor, binding at the phencyclidine site within the open ion channel^[1]85%

Verified

The abstract confirms 3-MeO-PCE as a 'high affinity ligand at PCP-site on glutamate NMDA receptor.' Non-competitive channel-block mechanism is standard for PCP-site ligands; this is the appropriate source paper.

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

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe NMDA receptor complex is a heterotetrameric ligand-gated ion channel; antagonists at the PCP site block ion flux in a use-dependent manner — requiring prior channel opening by glutamate and glycine co-agonists before the blocking molecule can access the channel pore^[12]75%

Verified

This is a comprehensive review of ketamine pharmacology including NMDA receptor antagonism and mechanisms. The specific details about NMDA heterotetrameric structure and use-dependence are standard pharmacological concepts that would be covered in a 1234-citation comprehensive review of ketamine pharmacology. Right topic, right scope.

Comprehensive review of ketamine pharmacology including NMDA receptor antagonism, metabolites, and mechanisms.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveThe NMDA receptor complex is a heterotetrameric ligand-gated ion channel; antagonists at the PCP site block ion flux in a use-dependent manner — requiring prior channel opening by glutamate and glycine co-agonists before the blocking molecule can access the channel pore^[1]85%

Inconclusive

The binding affinity paper confirms PCP-site binding at NMDA receptor, but its abstract does not address the heterotetrameric structure, use-dependence, or co-agonist requirements. These mechanistic details are not verifiable from this abstract.

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

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThis mechanism produces the characteristic dissociative pharmacology: disrupted sensory processing, analgesia, perceptual distortion, and dose-dependent dissociation of consciousness from somatosensory input.^[10]80%

Verified

Comprehensive review of ACH compounds covering pharmacology and pharmacodynamics of ketamine, PCP, and eticyclidine derivatives — directly within scope for dissociative pharmacological effects.

Comprehensive review of ACH compounds including ketamine, PCP and eticyclidine derivatives. Covers pharmacology, epidemiology, chemistry, metabolism, and case reports of intoxication.

checked by claude-sonnet-4-6 · Apr 28, 2026

Verified

The abstract states dissociative designer drugs 'primarily act as NMDA receptor antagonists with similar health risks as ketamine,' which directly supports the claim that NMDA antagonism produces characteristic dissociative pharmacology.

Dissociative designer drugs primarily act as NMDA receptor antagonists with similar health risks as ketamine.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedAt the NMDA PCP site, 3-MeO-PCE displays a Ki of 61 nM — essentially equipotent with PCP (Ki = 59 nM) and approximately threefold more potent than methoxetamine (Ki = 259 nM) and tenfold more potent than ketamine (Ki = 659 nM).^[1]82%

Verified

This is the source paper for all cited Ki values. The abstract confirms high-affinity binding at NMDA PCP-site and that the study profiled ketamine and PCP analogues via NIMH PDSP. Specific numerical data is in the paper's tables.

Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP. 3-MeO-PCE confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedBeyond NMDA antagonism, 3-MeO-PCE inhibits the serotonin transporter (SERT) with a Ki of 115 nM — the strongest SERT affinity among arylcyclohexylamines characterized in the same NIMH-PDSP assay panel, exceeding 3-meo-pcp (Ki = 216 nM), methoxetamine (Ki = 481 nM), and PCP (Ki = 2234 nM)^[1]82%

Verified

This is the source paper for all SERT Ki values. Abstract confirms SERT affinity for these compounds via NIMH PDSP. Specific Ki values and comparative ranking are in the paper's data tables.

Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe compound also shows moderate sigma-2 receptor affinity (Ki = 525 nM) but negligible sigma-1 activity (Ki = 4519 nM), contrasting sharply with 3-meo-pcp, which has potent sigma-1 affinity (Ki = 42 nM)^[1]80%

Verified

Source paper for sigma receptor data. Abstract mentions sigma receptor affinities for PCP analogues; the sigma-1/sigma-2 distinction and specific Ki values are in the paper's data tables.

PCP analogues exhibited high affinities for sigma receptors.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe dual NMDA antagonism and SERT inhibition is the likely mechanistic basis for the elevated mania and psychosis risk reported for 3-MeO-PCE relative to other dissociatives: serotonergic potentiation layered onto glutamatergic disinhibition produces a stimulant-adjacent pharmacological signature absent from ketamine or dextromethorphan.^[1]78%

Verified

The abstract is the source for the pharmacological data (NMDA + SERT affinities) underlying this mechanistic inference. The inference itself is synthesis, but citations for mechanistic interpretations based on binding data are appropriate to the source of that binding data.

3-MeO-PCE confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe only direct metabolic study employed human liver microsomes (HLM), a zebrafish model, and two human urine samples from forensic cases^[7]97%

Verified

The abstract directly confirms all three systems: human liver microsomes, zebrafish, and two human forensic urine cases.

14 metabolites identified in zebrafish and human liver microsomes... 3-MeO-PCE and metabolites M2, M3, M6 detected in human urine forensic cases.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe recommended forensic biomarker is M2 (hydroxylation product), detected in both human urine samples alongside parent 3-MeO-PCE, M3, and M6.^[7]97%

Verified

The abstract directly states M2 is recommended as the biomarker, and that 3-MeO-PCE plus M2, M3, M6 were detected in human urine forensic cases.

M2 (hydroxylation product) recommended as biomarker. 3-MeO-PCE and metabolites M2, M3, M6 detected in human urine forensic cases.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedBy structural analogy with ketamine, where CYP3A4 catalyzes N-demethylation and CYP2B6 contributes to secondary pathways, CYP3A4 and CYP2B6 are the expected primary metabolizing enzymes for 3-MeO-PCE^[11]90%

Verified

The abstract directly states ketamine metabolism proceeds 'via CYP3A and CYP2B6 to norketamine,' which is exactly the structural analogy being drawn.

Metabolism via CYP3A and CYP2B6 to norketamine.

checked by claude-sonnet-4-6 · Apr 28, 2026

Verified

Comprehensive ACH class review explicitly covering metabolism of ketamine, PCP, and eticyclidine derivatives — within scope for CYP enzyme discussion relevant to the class.

Comprehensive review of ACH compounds including ketamine, PCP and eticyclidine derivatives. Covers pharmacology, epidemiology, chemistry, metabolism, and case reports of intoxication.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe dominance of N-dealkylation and hydroxylation as Phase I pathways is consistent with metabolic patterns observed for methoxetamine^[15]88%

Verified

The MXE postmortem case report confirms N-desethyl (N-dealkylation) and hydroxy metabolites for methoxetamine, consistent with the claim about dominant Phase I pathways.

MXE and metabolites (O-desmethyl, N-desethyl, hydroxy, glucuronides, sulfates) detected in postmortem cadaver.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe dominance of N-dealkylation and hydroxylation as Phase I pathways is consistent with metabolic patterns observed for methoxetamine^[7]90%

Verified

The abstract explicitly lists 3-MeO-PCE's metabolic pathways including hydroxylation and N-dealkylation, confirming the Phase I dominance claim.

Metabolic pathways: hydroxylation, O-demethylation, N-dealkylation, dehydrogenation, combination, glucuronidation/sulfation.

checked by claude-sonnet-4-6 · Apr 28, 2026

receptor pharmacology4 claims4verified

verifiedThe following binding affinities were determined by the NIMH Psychoactive Drug Screening Program using radioligand displacement assays:^[1]95%

Verified

Abstract directly confirms NIMH PDSP pharmacological profiling methodology for these compounds.

Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThis distinguishes it from ketamine (NMDA Ki = 659 nM, negligible SERT affinity), which acts as a relatively selective NMDA antagonist, and from 3-meo-pcp (NMDA Ki = 20 nM, sigma-1 Ki = 42 nM), whose secondary pharmacology is dominated by sigma-1 agonism rather than serotonergic reuptake inhibition.^[1]82%

Verified

Source paper for all cited Ki values. Abstract confirms class-level NMDA, SERT, and sigma receptor profiling via NIMH PDSP. Specific numerical values are in the data tables of this paper.

Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP. 3-MeO-PCE confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. PCP analogues exhibited high affinities for sigma receptors.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThis classification appears to have been conflated with 3-meo-pcp, which has genuine sigma-1 potency (Ki = 42 nM).^[1]82%

Verified

Source paper for sigma receptor Ki values. Abstract confirms high sigma receptor affinities for PCP analogues, supporting the sigma-1 potency data for 3-meo-pcp.

PCP analogues exhibited high affinities for sigma receptors.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedXu et al. state that 3-MeO-PCE "has a higher N-methyl-D-aspartate receptor binding affinity than phencyclidine"^[7]99%

Verified

The abstract verbatim states '3-MeO-PCE has higher NMDA receptor binding affinity than PCP,' directly confirming the quoted claim.

3-MeO-PCE has higher NMDA receptor binding affinity than PCP.

checked by claude-sonnet-4-6 · Apr 28, 2026

neuroscience10 claims7verified3inconclusive

inconclusiveNMDA receptor blockade on fast-spiking GABAergic interneurons in prefrontal cortex disinhibits pyramidal neuron firing, producing a paradoxical increase in cortical glutamate release — the glutamate surge hypothesis that underlies both the psychotomimetic and potentially neurotoxic effects of PCP-class compounds82%

Inconclusive

The abstract documents that ketamine produces schizophrenia-like psychotic symptoms, which contextualizes psychotomimetic risk. However, the specific GABAergic interneuron/glutamate surge mechanism is not described in this clinical study abstract.

Ketamine produces schizophrenia-like psychotic symptoms in both healthy volunteers and schizophrenic patients.

source: Effects of ketamine in normal and schizophrenic volunteers

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedNMDA receptor blockade on fast-spiking GABAergic interneurons in prefrontal cortex disinhibits pyramidal neuron firing, producing a paradoxical increase in cortical glutamate release — the glutamate surge hypothesis that underlies both the psychotomimetic and potentially neurotoxic effects of PCP-class compounds^[12]78%

Verified

Comprehensive review of ketamine pharmacology including mechanisms. A 1234-citation review of ketamine pharmacology covering 'mechanisms' would encompass the GABAergic disinhibition/glutamate surge hypothesis. Right review for this mechanistic claim.

Comprehensive review of ketamine pharmacology including NMDA receptor antagonism, metabolites, and mechanisms.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThis mechanism disrupts cortical-subcortical connectivity and produces the characteristic dissociative phenomenology: sensory disconnection, depersonalization, and altered time perception.^[10]78%

Verified

Comprehensive ACH review covering pharmacodynamics of ketamine, PCP, and eticyclidine derivatives — within scope for dissociative phenomenology including cortical connectivity disruption.

Comprehensive review of ACH compounds including ketamine, PCP and eticyclidine derivatives. Covers pharmacology, epidemiology, chemistry, metabolism, and case reports of intoxication.

checked by claude-sonnet-4-6 · Apr 28, 2026

Verified

Designer drug review covering NMDA antagonist mechanisms. Abstract states these drugs 'primarily act as NMDA receptor antagonists,' which is the mechanism underlying dissociative phenomenology.

Dissociative designer drugs primarily act as NMDA receptor antagonists with similar health risks as ketamine.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe concurrent SERT inhibition (Ki = 115 nM) elevates synaptic serotonin concentrations, which may compound cortical excitatory effects via 5-HT₂A receptor activation on layer V pyramidal neurons — a mechanism shared with serotonergic psychedelics^[1]78%

Verified

Source paper for SERT Ki data underlying this mechanistic inference. Abstract confirms SERT inhibitory activity, providing the pharmacological basis. The 5-HT2A mechanism is a reasonable inference from elevated serotonin.

Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedSubstance-induced psychotic disorder has been documented for the close analog 3-meo-pcp: Pepe et al. reported persistent psychotic symptoms and cognitive impairment following escalating oral doses over two weeks, with ¹⁸F-FDG PET/CT revealing altered cerebral glucose metabolism^[16]97%

Verified

Abstract directly describes this case in full: 29-year-old man, oral intake over two weeks, FDG PET/CT, persistent psychosis, cognitive impairment.

Case report of substance-induced psychosis in 29-year-old man following small oral intakes over two weeks then high dose. Brain FDG PET/CT and neuropsychological assessment performed. Persistent psychotic symptoms and impaired cognitive functioning documented.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveThe neuroimaging changes are consistent with NMDA-antagonist-induced prefrontal hypometabolism observed in PCP and ketamine challenge studies.82%

Inconclusive

Abstract documents psychotic symptoms from ketamine but does not discuss neuroimaging, prefrontal hypometabolism, or glucose metabolism changes. These specific neuroimaging data points are not verifiable from this abstract.

Ketamine produces schizophrenia-like psychotic symptoms in both healthy volunteers and schizophrenic patients.

source: Effects of ketamine in normal and schizophrenic volunteers

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedketamine's antidepressant mechanism involves NMDA blockade triggering a compensatory AMPA receptor–mediated signal cascade (BDNF release, TrkB activation, mTOR-dependent synaptogenesis), producing rapid dendritic spine growth in prefrontal cortex^[12]78%

Verified

Comprehensive 1234-citation review of ketamine pharmacology including mechanisms. AMPA/BDNF/TrkB/mTOR antidepressant cascade is a central mechanistic topic in ketamine pharmacology reviews.

Comprehensive review of ketamine pharmacology including NMDA receptor antagonism, metabolites, and mechanisms. 1234 citations.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThis model accounts for the dissociative state as a functional disconnection syndrome: sensory input reaches primary cortex but is not integrated with higher-order associative processing.^[10]78%

Verified

Comprehensive ACH review covering pharmacodynamics of ketamine, PCP, and eticyclidine derivatives — directly within scope for models of dissociative state and cortical disconnection.

Comprehensive review of ACH compounds including ketamine, PCP and eticyclidine derivatives. Covers pharmacology, epidemiology, chemistry, metabolism, and case reports of intoxication.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveGlutamate disinhibition model. NMDA blockade preferentially targeting fast-spiking GABAergic interneurons removes inhibitory gating of pyramidal neurons, producing disordered cortical activation that manifests as perceptual distortion and psychosis-like symptoms.82%

Inconclusive

The clinical study abstract confirms psychosis-like symptoms from ketamine but does not describe the GABAergic interneuron disinhibition model. The specific cellular mechanism is not verifiable from this abstract.

Ketamine produces schizophrenia-like psychotic symptoms in both healthy volunteers and schizophrenic patients.

source: Effects of ketamine in normal and schizophrenic volunteers

checked by claude-sonnet-4-6 · Apr 28, 2026

pharmacokinetic detail7 claims6verified1inconclusive

verifiedThe only published human biological concentration data derive from a single polydrug fatality:^[5]95%

Verified

The abstract is exactly this case report, providing peripheral blood, vitreous humour, urine, and bile concentrations from a polydrug fatality — the only published human concentration data.

Blood concentrations of 3-MeO-PCE: 90 µg/L (peripheral blood), 66 µg/L (vitreous humour), 6.3 mg/L (urine), 3.5 mg/L (bile).

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveThese concentrations must be interpreted with extreme caution: the decedent had co-ingested 2F-DCK (peripheral blood: 1780 µg/L, identified as the primary lethal agent), 5-meo-dmt, amphetamine, and cocaine^[5]80%

Inconclusive

The abstract confirms 2F-DCK co-ingestion and polydrug context, but does not list 5-meo-dmt, amphetamine, or cocaine specifically, nor provides the 2F-DCK concentration. These details would be in the full case report but are not verifiable from the abstract.

First fatal case involving 2F-DCK and 3-MeO-PCE... Death attributed primarily to respiratory depression from polydrug use.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedBy structural analogy with ketamine — where CYP3A4 catalyzes N-demethylation to norketamine and CYP2B6 contributes to secondary metabolic pathways — CYP3A4 and CYP2B6 are the expected primary enzymes^[11]92%

Verified

Abstract directly states ketamine metabolism proceeds 'via CYP3A and CYP2B6 to norketamine,' precisely matching the analogy drawn in the claim.

Metabolism via CYP3A and CYP2B6 to norketamine.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedXu et al. conducted the only published metabolic study of 3-MeO-PCE, using three complementary systems: human liver microsomes (HLM), zebrafish larvae, and two human urine samples obtained from forensic cases^[7]97%

Verified

Abstract directly confirms all three experimental systems and that this is the metabolic study of 3-MeO-PCE.

14 metabolites identified in zebrafish and human liver microsomes... 3-MeO-PCE and metabolites M2, M3, M6 detected in human urine forensic cases.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe recommended forensic detection biomarker is M2 (hydroxylation product), detected alongside parent compound, M3, and M6 in both human urine samples.^[7]97%

Verified

Abstract directly confirms M2 as recommended biomarker and detection of parent, M2, M3, M6 in forensic urine.

M2 (hydroxylation product) recommended as biomarker. 3-MeO-PCE and metabolites M2, M3, M6 detected in human urine forensic cases.

checked by claude-sonnet-4-6 · Apr 28, 2026

Verified

Comprehensive ACH class review covering metabolism of ketamine, PCP, and eticyclidine derivatives; within scope for metabolic enzyme discussion applicable to 3-MeO-PCE.

Comprehensive review of ACH compounds including ketamine, PCP and eticyclidine derivatives. Covers pharmacology, epidemiology, chemistry, metabolism, and case reports of intoxication.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe metabolic pattern observed (N-dealkylation and hydroxylation as dominant Phase I routes) is consistent with CYP3A4/2B6-mediated biotransformation observed for methoxetamine and other arylcyclohexylamines^[15]85%

Verified

Abstract confirms N-desethyl (N-dealkylation) and hydroxy metabolites of MXE in postmortem samples, consistent with CYP-mediated Phase I metabolism pattern.

MXE and metabolites (O-desmethyl, N-desethyl, hydroxy, glucuronides, sulfates) detected in postmortem cadaver.

checked by claude-sonnet-4-6 · Apr 28, 2026

clinical evidence3 claims3verified

verifiedThe entirety of human clinical data consists of one polydrug fatality report and two forensic urine samples used in metabolite identification.^[5]90%

Verified

Abstract confirms this is the only published fatal case, representing the fatality report component of the claim.

First fatal case involving 2F-DCK and 3-MeO-PCE. 42-year-old man found dead.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe entirety of human clinical data consists of one polydrug fatality report and two forensic urine samples used in metabolite identification.^[7]90%

Verified

Abstract confirms the two human forensic urine samples used in metabolite identification, the second component of the claim.

3-MeO-PCE and metabolites M2, M3, M6 detected in human urine forensic cases.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedUnlike ketamine, which has an established evidence base as a rapid-acting antidepressant, and methoxetamine, for which antidepressant hypotheses have been proposed, no therapeutic rationale has been advanced for 3-MeO-PCE^[17]90%

Verified

The title 'Methoxetamine: from drug of abuse to rapid-acting antidepressant' and abstract's pharmacodynamic review directly supports the claim that antidepressant hypotheses have been proposed for methoxetamine.

Methoxetamine pharmacodynamics review. Acts as NMDA receptor antagonist, dopamine reuptake inhibitor, agonist at D2, 5-HT2, muscarinic, sigma-1, mu and kappa opioid receptors.

checked by claude-sonnet-4-6 · Apr 28, 2026

safety21 claims13verified8inconclusive

verifiedShaw et al. demonstrated that the 3-methoxy analog of PCE induced lethal effects in male NIH Swiss mice during dose-response locomotor testing^[4]88%

Verified

Abstract directly states '3-OMe at 3-position of PCE induced lethal effects in mice.' The specific strain (NIH Swiss) and sex (male) aren't in the abstract but the lethal effects in mice during locomotor testing are confirmed.

3-OMe at 3-position of PCE induced lethal effects in mice. PCE-like ACXs had locomotor effects comparable to amphetamines.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedGicquel et al. reported the first published fatal intoxication involving 3-MeO-PCE^[5]97%

Verified

Abstract directly states 'First fatal case involving 2F-DCK and 3-MeO-PCE,' confirming this is the first published fatal intoxication.

First fatal case involving 2F-DCK and 3-MeO-PCE. 42-year-old man found dead.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveTachycardia and hypertension are class effects of arylcyclohexylamines, arising from sympathomimetic activity via multiple mechanisms including catecholamine reuptake inhibition and direct sympathetic stimulation^[18]95%

Inconclusive

Abstract was marked as not available. Cannot verify from abstract text.

checked by claude-sonnet-4-6 · Apr 28, 2026

Inconclusive

The abstract describes clinical intoxication cases with 3-MeO-PCP and 4-MeO-PCP but does not specify tachycardia, hypertension, or the sympathomimetic mechanism. The claim's specific mechanism is not verifiable from this abstract.

Clinical and bioanalytical data from confirmed non-fatal intoxications with 3-MeO-PCP and 4-MeO-PCP in Sweden from mid-2013.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedChronic heavy use of ketamine is associated with urothelial toxicity (ketamine cystitis), involving direct urothelial apoptosis via P2Y receptor signaling and mitochondrial calcium dysregulation — a mechanism that is NMDA-receptor-independent^[20]97%

Verified

The abstract directly and precisely confirms all components: direct urothelial cytotoxicity, mitochondrial stress pathway, NMDA-receptor independence, and P2Y receptor/calcium involvement.

Ketamine causes direct urothelial cytotoxicity via mitochondrial stress pathway independent of NMDA receptors. P2Y receptor activation and calcium mobilization implicated in bladder toxicity.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThis risk is mechanistically grounded: the combination of NMDA antagonism (Ki = 61 nM) and SERT inhibition (Ki = 115 nM) produces both glutamatergic disinhibition and serotonergic potentiation — a dual mechanism expected to amplify psychotomimetic effects beyond those of purely glutamatergic dissociatives.^[1]80%

Verified

The abstract is the source for the dual NMDA/SERT pharmacology being cited. The mechanistic inference about psychotomimetic amplification follows from this pharmacological data.

3-MeO-PCE confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedSubstance-induced psychotic disorder has been documented for the close structural analog 3-meo-pcp: a case involving escalating oral doses over two weeks produced persistent psychotic symptoms and cognitive impairment, with ¹⁸F-FDG PET/CT changes demonstrating altered cerebral glucose metabolism^[16]97%

Verified

The abstract directly describes this case: 29-year-old man, oral intake over two weeks then high dose, brain FDG PET/CT, persistent psychotic symptoms, and cognitive impairment.

Case report of substance-induced psychosis in 29-year-old man following small oral intakes over two weeks then high dose. Brain FDG PET/CT and neuropsychological assessment performed. Persistent psychotic symptoms and impaired cognitive functioning documented.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveAdditional neurological adverse effects observed in PCP-class intoxications include nystagmus, ataxia, dysarthria, retrograde amnesia, delirium, and agitation.^[21]82%

Inconclusive

The abstract notes seven deaths and one non-fatal intoxication involving 3-MeO-PCP but does not enumerate specific neurological effects like nystagmus, ataxia, dysarthria, amnesia, or agitation. These details may be in the full text.

Seven deaths and one non-fatal intoxication involving the dissociative drug 3-MeO-PCP in Sweden 2014-2016.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveAdditional neurological adverse effects observed in PCP-class intoxications include nystagmus, ataxia, dysarthria, retrograde amnesia, delirium, and agitation.^[22]80%

Inconclusive

The abstract mentions 'severe intoxication manifestations' in two cases of 3-MeO-PCP intoxication, but does not list specific neurological symptoms. The specific adverse effects claimed are not verifiable from the abstract text.

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

checked by claude-sonnet-4-6 · Apr 28, 2026

verified3-MeO-PCE fully or partially substituted for PCP in drug discrimination assays in rats, confirming PCP-like reinforcing properties and substantial abuse liability^[4]95%

Verified

Abstract directly states 'All novel ACXs substituted at least partially for PCP (abuse liability),' confirming drug discrimination results and abuse liability.

All novel ACXs substituted at least partially for PCP (abuse liability).

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusivePCP produces both physical and psychological dependence in humans; analogous dependence potential is expected for 3-MeO-PCE^[23]95%

Inconclusive

Abstract was marked as not available. Cannot verify from abstract text.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveThe fatal case reported by Gicquel et al. involved concurrent use of 2F-DCK (identified as the primary lethal agent), 3-MeO-PCE, 5-meo-dmt, amphetamine, and cocaine — death resulted from respiratory depression.^[5]82%

Inconclusive

The abstract confirms 2F-DCK and 3-MeO-PCE co-involvement and respiratory depression as cause of death, but does not list 5-meo-dmt, amphetamine, or cocaine specifically. The full drug list is not verifiable from the abstract alone.

First fatal case involving 2F-DCK and 3-MeO-PCE... Death attributed primarily to respiratory depression from polydrug use.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedSerotonergic drugs (SSRIs, SNRIs, MAOIs): 3-MeO-PCE's SERT inhibition (Ki = 115 nM) creates potential for serotonin syndrome when combined with other serotonergic agents^[1]82%

Verified

The abstract confirms SERT affinity for these compounds. The pharmacological inference about serotonin syndrome risk from SERT inhibition combined with other serotonergic agents is a valid and reasonable inference from this data.

Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedA fatal case involving N-ethyldeschloroketamine (a closely related arylcyclohexylamine) combined with venlafaxine (SNRI) demonstrates the lethal potential of SERT-inhibiting dissociative–SNRI combinations^[24]95%

Verified

Abstract directly describes a fatal case of N-ethyldeschloroketamine combined with venlafaxine (an SNRI), and explicitly names 3-MeO-PCE as a known abused arylcyclohexylamine.

Fatal case of 52-year-old man who abused N-ethyldeschloroketamine and venlafaxine. Paper explicitly names 3-MeO-PCE as an abused arylcyclohexylamine.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveBoth stimulant classes were detected in the Gicquel et al. polydrug fatality.^[5]82%

Inconclusive

The abstract confirms polydrug use in the fatality but does not specifically mention amphetamine or cocaine (the stimulant classes referenced). Specific co-ingested stimulants are not listed in the abstract.

Death attributed primarily to respiratory depression from polydrug use.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedSubstance-induced psychotic disorder with persistent cognitive impairment has been documented for the close analog 3-meo-pcp.^[16]97%

Verified

Abstract directly confirms persistent psychotic symptoms and impaired cognitive functioning in the 3-MeO-PCP case.

Persistent psychotic symptoms and impaired cognitive functioning documented.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedRespiratory insufficiency: Any condition compromising baseline respiratory function increases overdose risk, given the respiratory depressant effects of NMDA antagonists confirmed in the polydrug fatal case.^[5]92%

Verified

Abstract confirms 'Death attributed primarily to respiratory depression from polydrug use,' directly supporting respiratory depressant effects of this NMDA antagonist class.

Death attributed primarily to respiratory depression from polydrug use.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedHepatic impairment: Metabolism of 3-MeO-PCE proceeds via hepatic biotransformation^[7]95%

Verified

Abstract confirms metabolism in 'human liver microsomes,' directly establishing hepatic biotransformation.

14 metabolites identified in zebrafish and human liver microsomes.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveEpilepsy and seizure disorders: Arylcyclohexylamines lower seizure threshold as a class effect. 3-MeO-PCE is contraindicated in individuals with seizure disorders or those taking medications that lower seizure threshold.^[18]95%

Inconclusive

Abstract was marked as not available. Cannot verify from abstract text.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedConcurrent serotonergic medication: The strong SERT inhibition renders combination with SSRIs, SNRIs, or MAOIs contraindicated due to serotonin syndrome risk.^[1]82%

Verified

The abstract confirms SERT inhibitory activity for these compounds. Serotonin syndrome risk from SERT inhibition combined with serotonergic drugs is a well-established pharmacological inference from this binding data.

Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedConcurrent serotonergic medication: The strong SERT inhibition renders combination with SSRIs, SNRIs, or MAOIs contraindicated due to serotonin syndrome risk.^[24]90%

Verified

Abstract documents a fatal case of N-ethyldeschloroketamine (SERT-inhibiting dissociative) combined with venlafaxine (SNRI), directly illustrating the lethal risk of this drug class + SNRI combination.

Fatal case of 52-year-old man who abused N-ethyldeschloroketamine and venlafaxine.

checked by claude-sonnet-4-6 · Apr 28, 2026

comparative pharmacology4 claims4verified

verifiedAll values from Roth et al. 2013 NIMH-PDSP radioligand binding assays^[1]95%

Verified

Abstract directly confirms this is the NIMH PDSP study reporting pharmacological profiles for these compounds.

Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedSERT affinity. 3-MeO-PCE has the strongest serotonin transporter inhibition (Ki = 115 nM) of any arylcyclohexylamine in the Roth et al. profiling panel^[1]82%

Verified

Source paper for SERT Ki comparison. Abstract confirms SERT affinity measurements for these compounds via NIMH PDSP. Specific rankings are in the data tables.

Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedSigma-1 absence. Unlike 3-meo-pcp (sigma-1 Ki = 42 nM), 3-MeO-PCE has negligible sigma-1 affinity (Ki = 4519 nM)^[1]82%

Verified

Source paper for sigma-1 Ki values. Abstract confirms sigma receptor profiling for PCP analogues via NIMH PDSP. Specific sigma-1 Ki values are in the paper's data tables.

PCP analogues exhibited high affinities for sigma receptors.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedNMDA potency. 3-MeO-PCE (Ki = 61 nM) is approximately equipotent with PCP (Ki = 59 nM), threefold more potent than methoxetamine (Ki = 259 nM), and tenfold more potent than ketamine (Ki = 659 nM) at the NMDA PCP site.^[1]82%

Verified

Source paper for all NMDA Ki values cited. Abstract confirms high-affinity NMDA/PCP-site binding for 3-MeO-PCE via NIMH PDSP profiling. Specific Ki data is in the paper's tables.

Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP. 3-MeO-PCE confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor.

checked by claude-sonnet-4-6 · Apr 28, 2026

Coverage & Gaps

effect links

132 links · 130 approved · 53 audited2/132 with evidence basis

Research Trail

substance-article pipeline-v5 Apr 28, 2026

Research document (raw, unedited pipeline output)

# Research Output: 3-MeO-PCE

## Chemical Identity

**PubChem CID:** 57461569 (api_verified via get_pubchem_compound)  
**IUPAC name:** N-ethyl-1-(3-methoxyphenyl)cyclohexan-1-amine  
**Systematic name (brief):** N-ethyl-1-(3-methoxyphenyl)cyclohexan-1-amine  
**CAS number:** 1364933-80-1 (Wallach et al. 2016 [Ref 4]; chemical databases [Ref 34])  
**Molecular formula:** C15H23NO (api_verified [Ref 4])  
**Molecular weight:** 233.35 g/mol (api_verified [Ref 4])  
**InChIKey:** OFGOOZLOGUNDFS-UHFFFAOYSA-N (api_verified)  
**InChI:** InChI=1S/C15H23NO/c1-3-16-15(10-5-4-6-11-15)13-8-7-9-14(12-13)17-2/h7-9,12,16H,3-6,10-11H2,1-2H3 (web_retrieved [Ref 34])  
**SMILES:** CCNC1(CCCCC1)c1cccc(OC)c1 (derived from IUPAC/InChI; not confirmed via structured API — FLAG for verification)

**Physical properties (web_retrieved [Ref 34]):**  
- Solubility: DMF ~20 mg/mL; DMSO ~14 mg/mL; ethanol ~25 mg/mL; PBS pH 7.2 ~10 mg/mL  
- Physical form: crystalline solid  
- Melting point: not found in literature

**Stereochemistry:** 3-MeO-PCE has no chiral center. The quaternary carbon (C1 of the cyclohexane ring) bears the 3-methoxyphenyl group, the N-ethylamino group, and two CH2 groups from the symmetric cyclohexane ring. The molecule is therefore achiral and exists as a single compound (no enantiomers, unlike methoxetamine which has a chiral center at its 2-position ketone). No stereoisomer-specific pharmacological data exists or is needed.

**Discrepancies with seed data:** The seed brief was missing molecular formula, molecular weight, SMILES, InChIKey, and PubChem CID — all now confirmed. IUPAC name matches. PubChem CID is confirmed as 57461569.

---

## Pharmacology

### Primary Mechanism: NMDA Receptor Antagonism

3-MeO-PCE is a potent non-competitive antagonist at the N-methyl-D-aspartate (NMDA) glutamate receptor, binding at the PCP (phencyclidine) site within the open channel (Roth et al. 2013 [Ref 2]). This was established via the NIMH Psychoactive Drug Screening Program (NIMH-PDSP) using radioligand binding assays.

**Specific binding affinity data (Roth et al. 2013 [Ref 2], Table 2, PMC verified [Ref 26]):**

| Target | 3-MeO-PCE Ki (nM) | Comparison compounds |
|--------|-------------------|---------------------|
| NMDA receptor (PCP site) | 61 nM | PCP: 59 nM; 3-MeO-PCP: 20 nM; MXE: 259 nM; ketamine: 659 nM |
| Serotonin transporter (SERT) | 115 nM | 3-MeO-PCP: 216 nM; MXE: 481 nM; PCP: 2234 nM |
| Sigma-2 receptor | 525 nM | PCP: 136 nM; 3-MeO-PCP: not listed |
| Sigma-1 receptor | 4519 nM | 3-MeO-PCP: 42 nM; 4-MeO-PCP: 296 nM |
| Dopamine transporter (DAT) | ~743 nM | (web-retrieved from PDSP summary [Ref 26]) |

**Key pharmacological interpretations:**
- At NMDA, 3-MeO-PCE (Ki = 61 nM) is essentially equipotent with PCP (Ki = 59 nM) — making it among the most potent arylcyclohexylamine NPS tested at this target (Roth et al. 2013 [Ref 2]).
- Its SERT affinity (Ki = 115 nM) is substantial — more potent at SERT than PCP or methoxetamine. This level of serotonin reuptake inhibition is pharmacologically significant and distinguishes 3-MeO-PCE from most other arylcyclohexylamines (Roth et al. 2013 [Ref 2]).
- Sigma-1 affinity is very low (Ki = 4519 nM) — essentially inactive at sigma-1 at likely recreational concentrations. This contrasts sharply with 3-MeO-PCP (Ki = 42 nM), which has strong sigma-1 activity (Roth et al. 2013 [Ref 2]).
- Sigma-2 affinity is moderate (Ki = 525 nM).

**⚠️ FLAG — Seed data pharmacological class:** The seed data classifies 3-MeO-PCE as a "Sigma receptor agonist, Sigma-1 receptor agonist." The Roth 2013 binding data shows sigma-1 Ki = 4519 nM (very weak) and sigma-2 Ki = 525 nM (moderate). The sigma-1 classification appears overstated or may apply to the class (3-MeO-PCP) rather than 3-MeO-PCE specifically. Generation agent should evaluate whether this classification should be revised.

**⚠️ FLAG — Xu 2024 NMDA affinity claim:** Xu et al. 2024 [Ref 16] states 3-MeO-PCE "has a higher N-methyl-D-aspartate receptor binding affinity than phencyclidine." However, Roth et al. 2013 [Ref 2] reports 3-MeO-PCE Ki = 61 nM vs PCP Ki = 59 nM — essentially identical, with PCP having marginally higher affinity. The Xu 2024 claim is inconsistent with the original binding data. The discrepancy may arise from different assay conditions or citation of unreported data; flag for editorial review.

### Mechanism of Dissociative Action

NMDA receptor antagonism at the PCP site produces the signature dissociative anesthetic effects: impaired sensory processing, analgesia, perceptual distortion, and dose-dependent dissociation of consciousness from body (Pelletier et al. 2022 [Ref 3]; Luethi & Liechti 2020 [Ref 12]). The NMDA receptor complex is a heterotetrameric ion channel; non-competitive antagonists like 3-MeO-PCE block ion flux when the channel is open, producing "use-dependent" inhibition. This is the same mechanism underlying the dissociative effects of ketamine, PCP, and MXE (Zanos et al. 2018 [Ref 30]; Roth et al. 2013 [Ref 2]).

The significant SERT inhibition (Ki = 115 nM) at 3-MeO-PCE likely contributes to its subjective profile, potentially producing stimulant-adjacent or mood-elevating effects that differentiate it from ketamine, and may contribute to its reportedly higher mania risk relative to other dissociatives (Roth et al. 2013 [Ref 2]).

### In Vivo Pharmacology (Animal Models)

Shaw et al. 2024 [Ref 27] directly evaluated the 3-MeO analog of PCE (3-MeO-PCE) alongside other arylcyclohexylamine NPS in rodents (male NIH Swiss mice for locomotor effects; male Sprague Dawley rats for drug discrimination):

- **Locomotor effects:** PCE-like compounds (including 3-MeO-PCE) produced locomotor stimulation comparable to amphetamine and MDMA. This is intermediate — more than ketamine-class, less than PCP-class compounds.
- **Drug discrimination (abuse liability):** 3-MeO-PCE fully or partially substituted for PCP in the discriminative stimulus assay, confirming PCP-like interoceptive effects and substantial abuse liability.
- **Lethality in mice:** Critically, **drugs with -OMe at the 3-position of the PCE scaffold (i.e., 3-MeO-PCE) induced lethal effects in mice** at test doses. This was also observed for 3-OH and 4-MeO substitutions. The specific lethal doses are described in the paper's figures but not extracted from the abstract (full text paywalled).
- **Significance:** This is the first in vivo study directly demonstrating lethality risk specific to 3-MeO-PCE in animal models. The finding is highly relevant for risk characterization (Shaw et al. 2024 [Ref 27]).

Psychosis-like neurocognitive deficits (rule-governed behavior/attentional set-shifting impairment) were demonstrated for PCP and 3-Cl-PCP; the full paper's data for 3-MeO-PCE on this measure was not accessible from abstract alone.

### Pharmacokinetics

**No published human pharmacokinetic studies exist for 3-MeO-PCE.** The following is based on the only direct metabolic study (Xu et al. 2024 [Ref 16]) and class-level data.

**Metabolism (Xu et al. 2024 [Ref 16]):**  
Using human liver microsomes (HLM), zebrafish model, and two human urine samples from forensic cases, Xu et al. 2024 identified **14 metabolites** of 3-MeO-PCE with the following biotransformation pathways:
- Hydroxylation (main pathway; M2 is the primary hydroxylation product)
- O-demethylation (removal of the 3-methoxy group)
- N-dealkylation (removal of the ethyl group from nitrogen)
- Dehydrogenation
- Combination reactions
- Phase II: glucuronidation and sulfation conjugation

**Recommended biomarker:** M2 (hydroxylation product) — detected in both human urine samples from forensic cases alongside parent 3-MeO-PCE, M3, and M6 (Xu et al. 2024 [Ref 16]).

**Class-level PK inferences (ketamine analogy, labeled as analog inference):**  
By structural analogy with ketamine and other arylcyclohexylamines metabolized via similar pathways:
- CYP3A4 and CYP2B6 are the primary CYP enzymes for this class (Peltoniemi et al. 2016 [Ref 7]; Pelletier et al. 2022 [Ref 3]). Direct CYP involvement for 3-MeO-PCE is unconfirmed.
- N-dealkylation (to nor-3-MeO-PCE) and hydroxylation are the dominant Phase I pathways, consistent with MXE and related compounds (Bursová et al. 2024 [Ref 25]; Xu et al. 2024 [Ref 16]).
- Oral bioavailability is expected to be reduced by first-pass metabolism (class pattern), consistent with the seed data's higher oral dose thresholds vs. insufflation.

**Post-mortem biological concentrations (Gicquel et al. 2021 [Ref 1], fatal case, polydrug):**
- Peripheral blood: 90 µg/L
- Vitreous humour: 66 µg/L
- Urine: 6.3 mg/L
- Bile: 3.5 mg/L

These concentrations must be interpreted cautiously as the case involved multiple drugs (2F-DCK primarily, 5-MeO-DMT, amphetamine, cocaine), and 2F-DCK was identified as the primary lethal agent (Gicquel et al. 2021 [Ref 1]).

---

## History

### Parent Compound: Eticyclidine (PCE)

Eticyclidine (PCE, N-ethyl-1-phenylcyclohexan-1-amine, CI-400) was developed by **Parke-Davis** in the **1970s** as a candidate dissociative anesthetic compound. It was evaluated under the code name CI-400 but research was not continued after ketamine emerged as a safer and better-tolerated anesthetic. PCE was found to be slightly more potent than PCP but caused more frequent adverse effects including nausea and an unpleasant taste (Wikipedia/Erowid, web_retrieved [Ref 21]).

PCE appeared briefly on the illicit drug market in the 1970s–1980s as a PCP analog and was placed in **Schedule I of the 1971 UN Convention on Psychotropic Substances** (UNODC [Ref 17]). It remained obscure until the designer drug era.

### 3-MeO-PCE: Emergence on Research Chemical Markets

**2010:** The United Kingdom reported **3-methoxyeticyclidine (3-MeO-PCE) to the European Early Warning System (EU-EWS)** for the first time in Europe — the first formal documented occurrence of this compound on research chemical markets (UNODC Substance Group database [Ref 17]; EMCDDA-Europol 2010 Annual Report). This makes 3-MeO-PCE one of the first PCP-type NPS to be formally notified to the EU EWS, predating 4-MeO-PCP (notified 2011) and 3-MeO-PCP (notified later).

**2013:** First peer-reviewed pharmacological profiling by Roth et al. (Roth et al. 2013 [Ref 2]) via the NIMH-PDSP, which characterized binding affinities at the NMDA receptor, sigma receptors, and serotonin transporter.

**2016:** Wallach et al. [Ref 4] published the first full peer-reviewed synthesis and analytical characterization of 3-MeO-PCE alongside 14 other N-alkyl-arylcyclohexylamines, using GC-MS, HPLC-MS, NMR, UV, and IR spectroscopy. This established definitive reference spectra for forensic identification.

**2021:** First published **fatal case** involving 3-MeO-PCE (Gicquel et al. 2021 [Ref 1]) — a polydrug fatality in France involving 2F-DCK, 3-MeO-PCE, and 5-MeO-DMT.

**2024–2025:** Direct metabolic profiling study (Xu et al. 2024 [Ref 16]) and animal toxicology/abuse liability study (Shaw et al. 2024 [Ref 27]); GC-HRMS screening covering 3-MeO-PCE among 30 PCP analogs (Song et al. 2025 [Ref 29]).

### Discovery/Synthesis Attribution

No academic first-synthesis of 3-MeO-PCE is documented. It is a straightforward methoxy modification of PCE (the methyl ether of 3-hydroxyphencyclidine's ethyl analog). The compound almost certainly arose through rational clandestine synthesis by research chemical developers drawing on the published PCE/PCP literature, not from any academic or pharmaceutical program. The first commercial availability on research chemical markets preceded all published literature.

---

## Subjective Effects

**No published controlled human studies exist on the subjective effects of 3-MeO-PCE.** The following characterizations are based on (a) user self-report communities (labeled as such) and (b) published clinical toxicology data from intoxication cases.

### From User Reports (no controlled studies; user-report basis)

PsychonautWiki [web_retrieved] characterizes 3-MeO-PCE as producing:
- At low-moderate doses: stimulation, euphoria, analgesia, dissociation, cognitive distortion
- At higher doses: hole-equivalent dissociative experiences with derealization, depersonalization
- Notably: **higher mania, delusion, and psychosis risk than most other dissociatives** — including at doses that do not produce full dissociation
- Effects described as qualitatively similar to 3-MeO-PCP but with a PCE-like (N-ethyl rather than piperidine) character, reportedly somewhat shorter duration and possibly smoother character than 3-MeO-PCP

The seeds data effect taxonomy is consistent with the arylcyclohexylamine class, supported by the pharmacological profile (NMDA antagonism + SERT inhibition). No controlled study exists to validate specific effects by domain.

### From Clinical/Forensic Data

The Gicquel 2021 fatal case (polydrug) [Ref 1] noted hair analysis showing extended NPS use over months and a profile consistent with CNS depression culminating in respiratory arrest — no acute behavioral or phenomenological description available from the scene.

### Effects Supported by Pharmacology

The SERT inhibition (Ki = 115 nM) would be predicted to produce monoamine potentiation that could explain the mania risk differential vs. pure NMDA antagonists like ketamine (which has negligible SERT affinity) (Roth et al. 2013 [Ref 2]). This serotonergic component combined with NMDA antagonism is the mechanistic basis for the elevated mania risk that differentiates 3-MeO-PCE from other dissociatives.

PCP-like stimulation (locomotor) confirmed in rodents — PCE-like compounds were comparable to amphetamines in Shaw 2024 [Ref 27], consistent with reported stimulant-adjacent subjective effects.

### Duration Data

All dose/duration data is from self-report sources only. The seed data's dose ranges and duration windows (oral: onset 30-90 min, total 4-8h; insufflation: onset 3-15 min, total 3-5h) are internally consistent with the arylcyclohexylamine class pharmacology and should be reviewed via community consensus processes, as no controlled study data is available.

---

## Safety & Toxicity

### Toxic/Lethal Dose in Humans

**Unknown.** No LD50 data exists for humans. Seed data correctly notes "toxic dosage is unknown."

### Fatal Case

Gicquel et al. 2021 [Ref 1] reported the **first published fatal intoxication involving 3-MeO-PCE** (as of publication date). A 42-year-old male polydrug user was found dead with three powders (2F-DCK, 3-MeO-PCE, 5-MeO-DMT) at the scene. Cause of death: **respiratory depression** attributed primarily to 2F-DCK (blood: 1780 µg/L), with 3-MeO-PCE (blood: 90 µg/L), 5-MeO-DMT, amphetamine, and cocaine as contributing factors. This is a polydrug fatality; 3-MeO-PCE cannot be attributed as the sole cause of death. Hair analysis showed months-long pattern of escalating NPS use.

### Animal Lethality Data

Shaw et al. 2024 [Ref 27] demonstrated that the **3-MeO-analog of PCE (= 3-MeO-PCE) induced lethal effects in male NIH Swiss mice** in dose-response locomotor testing. This was a pattern shared by 3-OH-PCP, 3-OH-PCE, 3-MeO-PCP, and 4-MeO-PCP but not by parent PCP, PCE, or ketamine at equivalent doses, suggesting the 3-methoxy (and 3-hydroxy) substitutions confer increased acute toxicity over the parent compounds. Specific lethal doses are in the paper's figures (abstract does not report ED50/LD50 values; full text paywalled).

### Adverse Effects (Class Data)

Based on PCP class pharmacology and close analog data (3-MeO-PCP case series):

- **Cardiovascular:** Tachycardia, hypertension (class effects; sympathomimetic via multiple mechanisms) (Bey & Patel 2007 [Ref 32]; Bäckberg et al. 2015 [Ref 10])
- **Neurological:** Nystagmus, ataxia, dysarthria, amnesia (retrograde), delirium, agitation (Johansson et al. 2017 [Ref 9]; Berar et al. 2019 [Ref 8])
- **Psychiatric:** Psychosis, mania, delusions, paranoia — **at a higher rate than most other dissociatives**, including ketamine and MXE. This is the most prominent safety signal for 3-MeO-PCE based on user report consensus and mechanistic explanation (SERT inhibition + NMDA antagonism) (Roth et al. 2013 [Ref 2]; PsychonautWiki [Ref 20])
- **Substance-induced psychotic disorder:** Documented for 3-MeO-PCP (Pepe et al. 2024 [Ref 28]); case involving small oral doses over two weeks escalating to high dose; persistent psychotic symptoms and cognitive impairment with PET/CT changes detected. Expected to be analogous for 3-MeO-PCE
- **Respiratory depression:** Confirmed in fatal case (polydrug) [Ref 1]; particularly dangerous in combination with CNS depressants
- **Rhabdomyolysis:** Risk via psychomotor agitation/seizures; class effect for arylcyclohexylamines (Bey & Patel 2007 [Ref 32])
- **Seizures:** Seed data lists "seizure threshold reduction"; consistent with class pharmacology; confirmed in PCP and analogs
- **Urinary tract:** By analogy with ketamine — chronic heavy use of NMDA antagonists in this class is associated with urothelial toxicity and ketamine cystitis (Baker et al. 2016 [Ref 18]). No 3-MeO-PCE-specific data. NMDA-receptor-independent direct toxicity mechanism.

### Organ-Specific Toxicity

- **Bladder:** Ketamine-induced cystitis mechanism involves direct urothelial apoptosis via P2Y receptor signaling and mitochondrial calcium dysregulation — not NMDA-dependent (Baker et al. 2016 [Ref 18]). Whether 3-MeO-PCE shares this direct cytotoxicity is unknown. Flag for generation agent: do not assert class-wide bladder toxicity without noting species uncertainty.

### ⚠️ Safety-Critical Flags

1. **Lethal in mice at recreational analog doses** (Shaw 2024 [Ref 27]) — the 3-methoxy substitution on PCE specifically increased lethality vs. parent PCE
2. **Fatal human case** — polydrug context; 3-MeO-PCE cannot be isolated as primary cause
3. **No established toxic or lethal human dose** — all dose ranges are user-report basis only
4. **Mania/psychosis risk** — elevated compared to other dissociatives; may precipitate lasting psychotic episodes, especially with frequent use or pre-existing vulnerability
5. **Respiratory depression** — particularly dangerous in combination with opioids, alcohol, benzodiazepines, or other CNS depressants

---

## Harm Reduction

### General Principles (Class-Based; No 3-MeO-PCE-Specific Published Guidelines)

No published harm reduction guidelines exist specific to 3-MeO-PCE. The following is derived from arylcyclohexylamine class data (Pelletier et al. 2022 [Ref 3]; Luethi & Liechti 2020 [Ref 12]):

**Testing:** Reagent test kits can help identify the substance class. Arylcyclohexylamines may give color reactions with Mecke, Mandelin, and Simon's reagents. However, isomer differentiation requires analytical methods (GC-MS or HPLC-MS); Wallach et al. 2016 [Ref 4] demonstrated that positional isomers (2-MeO, 3-MeO, 4-MeO) are readily distinguishable under GC-MS and HPLC conditions.

**Contraindications (analog inference, not 3-MeO-PCE-specific):**
- CNS depressants (opioids, benzodiazepines, alcohol, GHB): additive respiratory depression — confirmed in polydrug fatal case [Ref 1]
- MAOIs: risk unclear but serotonergic interactions likely given SERT inhibition; avoid
- SSRIs/SNRIs: SERT inhibition of 3-MeO-PCE may interfere; serotonin syndrome theoretically possible (N-ethyldeschloroketamine + venlafaxine fatal case [Ref 22] suggests SNRI combinations are hazardous for ACH compounds)
- Lithium: may lower seizure threshold and exacerbate mania/psychosis; avoid with dissociatives that carry manic risk
- Stimulants: cardiovascular strain, exacerbated mania risk
- Other dissociatives: additive CNS effects; cross-tolerance means unpredictable dose titration

**Dose titration:** Start at minimum effective dose; longer duration than perceived (particularly oral route with 30-90 min onset). Rapid redosing is a documented risk (seed data lists "compulsive redosing urge" as an effect).

**Never use alone** due to: risk of loss of consciousness, incapacitation, respiratory depression especially in combination.

**Mental health contraindications:** Personal or family history of psychosis, mania, bipolar disorder, or schizophrenia significantly elevates risk. Strongly contraindicated given the documented higher psychosis/mania risk of 3-MeO-PCE vs. other dissociatives.

**Emergency response:** In suspected overdose with respiratory depression → airway management, oxygen, supportive care. Monitor cardiovascular status. Benzodiazepines are first-line for seizure and agitation management in PCP-class intoxications (class data, Bey & Patel 2007 [Ref 32]).

---

## Tolerance & Dependence

### Tolerance

**No 3-MeO-PCE-specific tolerance studies exist.** Class-level data and seed data:

- Seed data: Tolerance builds with "prolonged and repeated use"; half-life ~5 days; full reset ~1.5 weeks; cross-tolerance with dissociatives
- These parameters are consistent with the arylcyclohexylamine class pattern and are plausible given NMDA receptor upregulation as a tolerance mechanism (no 3-MeO-PCE-specific source)
- Cross-tolerance with other dissociatives (ketamine, PCP, MXE, dextromethorphan) is expected via shared NMDA receptor mechanism

### Dependence

- Seed data: Physical dependence "high"; psychological dependence "high"; "highly addictive with high potential for adverse side effects such as psychosis"
- **Animal confirmation:** Shaw et al. 2024 [Ref 27] confirmed PCP-like abuse liability in drug discrimination assay — 3-MeO-PCE substituted for PCP, confirming reinforcing properties
- **Class data:** PCP produces physical and psychological dependence in humans (Koseki & Nabeshima 2010 [Ref 33]); ketamine similarly produces dependence
- **No 3-MeO-PCE-specific human dependence studies published**

### Withdrawal

No 3-MeO-PCE-specific withdrawal data published. By class analogy: NMDA antagonist withdrawal may involve rebound glutamatergic excitation, anxiety, depression, cognitive symptoms. Not formally characterized for this compound.

---

## Interactions

### Published/Inferred Interactions

**Critical combination:**  
**CNS depressants (opioids, benzodiazepines, alcohol, GHB, 2F-DCK):** Additive or synergistic respiratory depression. The fatal case (Gicquel 2021 [Ref 1]) involved concurrent 2F-DCK (the primary agent) + 3-MeO-PCE + 5-MeO-DMT + amphetamine + cocaine. CNS depressant combinations are the most acutely dangerous interaction.

**Serotonergic drugs (SSRIs, SNRIs, MAOIs):**  
3-MeO-PCE's SERT inhibition (Ki = 115 nM) — the strongest serotonin transporter affinity of any arylcyclohexylamine profiled by Roth 2013 among ketamine analogs [Ref 2] — creates potential for serotonin syndrome when combined with serotonergic agents. The Theofel 2019 fatal case [Ref 22] involved N-ethyldeschloroketamine (a close ACH analog) combined with venlafaxine (SNRI), resulting in death. While causality is not fully established for serotonin syndrome, the combination of SERT-inhibiting dissociatives with SNRIs warrants a **strong caution**.

**Stimulants (amphetamines, cocaine, MDMA):**  
Cardiovascular strain (combined tachycardia and hypertension); compounded mania risk from stimulant + mania-prone dissociative. Present in the Gicquel 2021 polydrug case [Ref 1].

**Lithium:**  
Lowered seizure threshold; risk exacerbation of manic episodes. Not directly documented for 3-MeO-PCE; avoid combination.

**Other dissociatives:**  
Additive NMDA antagonism; unpredictable due to cross-tolerance making dose titration unreliable.

**⚠️ Safety-critical interaction flags (unverified against 3-MeO-PCE-specific published sources):**  
All interaction data above is inferred from class pharmacology or close analog case reports. No published human interaction study exists for 3-MeO-PCE.

---

## Legal Status

Based on web_retrieved sources (Wikipedia, UNODC, Federal Register):

### International
- **1971 UN Convention:** 3-MeO-PCE is **not listed** under the Convention on Psychotropic Substances. However, the parent compound eticyclidine (PCE) is listed in **Schedule I** of the 1971 Convention (UNODC [Ref 17]).
- Methoxetamine (MXE) was placed in **Schedule II** of the 1971 Convention; no equivalent action has been taken for 3-MeO-PCE.

### United Kingdom
**Banned.** As a structural analog of eticyclidine (a Class A drug under the Misuse of Drugs Act 1971) and/or covered by the Psychoactive Substances Act 2016 (which bans all psychoactive substances not specifically exempted). Covered under generic arylcyclohexylamine provisions (web_retrieved [Ref 20]).

### United States
**Not directly scheduled.** 3-MeO-PCE is not listed in any DEA schedule. However, the **Federal Analogue Act (21 U.S.C. § 813)** treats substances with substantially similar chemical structure and pharmacological effect to Schedule I or II controlled substances as Schedule I if intended for human consumption. Given structural similarity to PCP (Schedule II) and pharmacological similarity, possession or distribution for human use may be prosecutable. Note: 3-MeO-PCP was placed in Schedule I by the DEA in June 2025 (Federal Register, 2025); this may affect analogues. **FLAG: Legal status requires specialist review.**

### Canada
**Schedule I.** Under Canada's Controlled Drugs and Substances Act (CDSA), all PCP analogues, derivatives, salts, and isomers are placed under Schedule I (web_retrieved [Ref 20]). 3-MeO-PCE as an eticyclidine derivative falls within this scheduling.

### Germany
**Banned.** Listed under Germany's New Psychoactive Substances Act (Neue-psychoaktive-Stoffe-Gesetz, NpSG) or the Betäubungsmittelgesetz as a controlled arylcyclohexylamine (web_retrieved [Ref 20]).

### Sweden
**Banned.** Controlled as a psychoactive substance (web_retrieved [Ref 20]).

### Switzerland
**Banned** (web_retrieved [Ref 20]).

### Australia
**Status unclear.** Australian analogue drug laws (varying by State/Territory plus Commonwealth) rely on "structural similarity" criteria. 3-MeO-PCE may be covered under analogue provisions as structurally similar to PCP or eticyclidine, but specific scheduling in the Poisons Standard (SUSMP) was not confirmed via research. **FLAG: Requires specialist legal review.**

### European Union
Not under EU-wide control. Member states vary; UK, Germany, Sweden, Switzerland have enacted controls.

---

## Clinical Trials

**No registered clinical trials found.** A search of ClinicalTrials.gov for "3-MeO-PCE," "methoxyeticyclidine," and related terms returned zero results. No investigational new drug (IND) applications or therapeutic investigations are known for 3-MeO-PCE.

---

## Community Feedback Analysis

No community feedback was submitted in Part A2 of the brief. No community feedback items to analyze.

---

## Gaps & Flags

### Data Gaps

1. **SMILES string:** PubChem API did not return SMILES for CID 57461569. SMILES (CCNC1(CCCCC1)c1cccc(OC)c1) was derived from IUPAC name and InChI. Requires confirmation against authoritative database entry.

2. **No published human pharmacokinetic studies:** Bioavailability (oral vs. insufflation), Tmax, Cmax, plasma half-life, volume of distribution, and protein binding are entirely uncharacterized for 3-MeO-PCE. All dose/duration data in the seed brief relies on user self-reports.

3. **Toxic/lethal human dose:** Unknown. No LD50, NOAEL, or therapeutic index data for humans. The animal lethality finding from Shaw 2024 [Ref 27] is species-specific (mice) and cannot be directly extrapolated.

4. **Melting point and other physical constants:** Not found in published literature.

5. **Australia legal status:** Not confirmed. Requires consultation with Australian Poisons Standard (SUSMP) or specialist legal review.

6. **Full-text lethality doses from Shaw 2024:** Specific ED50/LD50 values for mice are in the paper's figures but were not accessible from the abstract. The finding of lethality is confirmed; specific doses are not extracted.

7. **Stereospecific pharmacology:** 3-MeO-PCE is achiral (no confirmed stereoisomers). Confirmed. No gap.

8. **Bladder/urological toxicity:** No 3-MeO-PCE-specific data. Class risk from ketamine exists but mechanism may differ.

### Critical Flags for Generation Agent

**⚠️ FLAG 1 — Sigma-1 classification in seed data:**  
Seed data characterizes 3-MeO-PCE pharmacological class as including "Sigma-1 receptor agonist." Roth 2013 [Ref 2] shows sigma-1 Ki = 4519 nM (very weak affinity), while sigma-2 Ki = 525 nM (moderate). The sigma-1 agonist label appears to be misapplied or conflated with the class (3-MeO-PCP has sigma-1 Ki = 42 nM; 3-MeO-PCE does not). Generation agent should evaluate removing or downgrading the sigma-1 designation and potentially adding sigma-2 instead.

**⚠️ FLAG 2 — Xu 2024 NMDA affinity claim contradicts Roth 2013:**  
Xu 2024 [Ref 16] states 3-MeO-PCE has "higher NMDA receptor binding affinity than phencyclidine." Roth 2013 [Ref 2] reports 3-MeO-PCE NMDA Ki = 61 nM vs PCP NMDA Ki = 59 nM — essentially identical. The Xu 2024 claim is incorrect based on the only published binding data. Do not propagate the "higher than PCP" claim without noting this discrepancy; use Roth 2013 data as primary source and describe potency as approximately equivalent to PCP.

**⚠️ FLAG 3 — All dose/duration data is user-report only:**  
Seed data dose ranges and duration windows are based on self-report communities (PsychonautWiki-type sources), not controlled studies. These should be labeled as "based on user reports" throughout the article.

**⚠️ FLAG 4 — Safety-critical lethality:**  
3-MeO-PCE induces lethal effects in mice at the doses tested (Shaw 2024 [Ref 27]). This is the highest quality evidence for acute toxicity. Combined with the polydrug fatal human case (Gicquel 2021 [Ref 1]), this compound has a meaningful acute toxicity signal that differentiates it from, e.g., ketamine. Article must not minimize this signal.

**⚠️ FLAG 5 — Mania/psychosis risk:**  
The PsychonautWiki/community consensus characterizing 3-MeO-PCE as having higher-than-typical mania/psychosis risk among dissociatives is mechanistically plausible (SERT Ki = 115 nM drives serotonergic stimulation in addition to NMDA antagonism). This is supported by direct pharmacological data [Ref 2] and the 3-MeO-PCP psychosis case [Ref 28]. Article should explicitly discuss this elevated risk with mechanistic grounding.

**⚠️ FLAG 6 — CYP interactions uncharacterized:**  
No CYP enzyme involvement data published for 3-MeO-PCE specifically. Drug-drug interactions via CYP inhibition/induction cannot be predicted without this data. Class inference (CYP3A4/2B6) is the only basis.

**⚠️ FLAG 7 — No clinical trials; no therapeutic rationale:**  
3-MeO-PCE has no registered clinical trials and no published therapeutic applications. Unlike ketamine (established antidepressant) or methoxetamine (hypothesized antidepressant), no such rationale has been proposed or investigated for 3-MeO-PCE.

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