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ketamine, PCP, DXM +5 moreketamine, PCP, DXM, MXE, 3-HO-PCP, 3-MeO-PCE, O-PCE, nitrous oxide show less
3-HO-PCE
3-hydroxyeticyclidine
3-HO-PCE (3-hydroxyeticyclidine) is a synthetic dissociative of the arylcyclohexylamine class. It is closely related to ketamine but carries an opioid-active modification that ketamine lacks. It blocks glutamate signaling and simultaneously activates opioid receptors, producing dissociative detachment layered with warmth and analgesia.[1][2]
3-HO-PCE (3-hydroxyeticyclidine) is a synthetic dissociative of the arylcyclohexylamine class. It is the 3-hydroxy structural analog of eticyclidine (PCE) and the N-ethyl counterpart of 3-HO-PCP. 3-HO-PCE is a presumed NMDA receptor antagonist with additional μ-opioid agonism, producing its effects through cortical disconnection and opioid-mediated analgesia.[1][2]
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ketamine, PCP, DXM +5 moreketamine, PCP, DXM, MXE, 3-HO-PCP, 3-MeO-PCE, O-PCE, nitrous oxide show less
3-HO-PCE was never synthesized for medical use — it appeared on research chemical markets during the 2010s, assembled from two known pharmacologically active structural features. The first scientific study directly addressing the compound was published in 2023, characterizing its metabolism.[3] It remains unscheduled by name in most countries and circulates through online research chemical vendors.
Subjective effects include dissociation, pain suppression, euphoria, bodily warmth, sedation, and cognitive disconnection. The experience is warmer and more euphoric than ketamine — the opioid layer adds a physical glow absent from most dissociatives. Compulsive redosing, amnesia, and manic disinhibition are characteristic unsought effects.[4]
3-HO-PCE carries meaningful physical dependence risk, and the toxic dose is completely unknown.safety citation needed The opioid component means combining it with other depressants can suppress breathing through two mechanisms at once — and standard drug tests will not identify it in an emergency.[5] Almost nothing has been formally studied — current understanding rests entirely on analogy to related compounds and user reports.
History[edit]
Discovery
The arylcyclohexylamine class began with phencyclidine (PCP), synthesized in 1956. Eticyclidine (PCE), the direct parent of 3-HO-PCE, was developed in the 1970s as an anesthetic candidate but set aside after ketamine proved more practical.[6] In 1978, researchers added a hydroxyl group to PCP's phenyl ring, creating 3-HO-PCP and discovering that this change added opioid activity — the property 3-HO-PCE inherits.[2]
Research chemical emergence
3-HO-PCE appeared on research chemical markets in the 2010s, combining the N-ethyl group of PCE with the opioid-conferring 3-hydroxyphenyl group of 3-HO-PCP. Larabi et al. published the first and only scientific study in 2023 — a metabolic characterization — noting that little was known about its pharmacology, metabolism, or toxicity.[3] No clinical trials have been registered.
Regulatory context
PCE is Schedule I under both US law and the UN 1971 Convention on Psychotropic Substances. In March 2026, the closely related 3-MeO-PCP was added to DEA Schedule I,[7] continuing a pattern of regulatory attention to ring-substituted arylcyclohexylamine analogs.
The name "3-HO-PCE" follows systematic research chemical nomenclature: "3-HO" marks the hydroxyl position on the phenyl ring, "PCE" abbreviates the parent compound eticyclidine. The compound has no street names or cultural identity outside research chemical communities, where it is discussed mainly in comparison to 3-HO-PCP.
Chemistry[edit]
Structural class
3-HO-PCE belongs to the arylcyclohexylamine family — the same class as PCP and ketamine. It is derived from eticyclidine (PCE) by a single addition: a hydroxyl group at the 3-position of the phenyl ring. This modification is pharmacologically significant — it adds opioid receptor activity that the unsubstituted parent lacks.[2]
Molecular identity
| Molecular formula | C₁₄H₂₁NO |
| Molecular weight | 219.32 g/mol |
Its closest structural relatives are 3-HO-PCP (same hydroxyl position, different amine group) and 3-MeO-PCE (methoxy instead of hydroxy at the same position). Physical properties — melting point, solubility, stability — have not been reported in the scientific literature.citation needed
Pharmacology[edit]
Mechanism of action
3-HO-PCE blocks glutamate receptors in the brain — the NMDA mechanism shared by ketamine and PCP.[1] The hydroxyl group on its ring additionally activates opioid receptors, a property established for its closest structural analog 3-HO-PCP.[2] No receptor binding data have been published for 3-HO-PCE itself — the entire pharmacological profile is inferred from structural analogy.
PCP-type compounds also interact with sigma receptors,[8] which regulate ion channels and neurotransmitter release.[9] The contribution of sigma activity to the overall experience has not been characterized for 3-HO-PCE.
Pharmacokinetics
A 2023 study identified 15 putative metabolites using human liver microsomes.[3] The likely metabolizing enzymes are CYP3A4 and CYP2B6, by analogy to ketamine.[10] CYP2B6 inhibitors produced a 2.4-fold increase in oral ketamine exposure in a controlled study[11] — similar interactions may affect 3-HO-PCE.
Neuroscience[edit]
Where it acts
NMDA blockade disrupts inhibitory interneurons in the cortex and limbic system,[1] paradoxically exciting other neurons while breaking down coherent thought. Brain mapping of 3-HO-PCP — the closest characterized structural analog — shows binding concentrated in the hippocampus, cortex, and striatum.[12] The opioid component simultaneously reaches brainstem respiratory centers.[2]
Dual-mechanism reinforcement
Both mechanisms reinforce use. The dissociative component may trigger rapid synaptogenesis — the same brain-rewiring linked to ketamine's antidepressant effect.[13] Direct opioid reward adds a second driver, likely explaining the compulsive redosing reported in community sources.[4]
High doses of NMDA antagonists produce paranoia, hallucinations, and delusional thinking in humans and neurotoxicity in animal models.[14] Whether 3-HO-PCE causes the same, and whether the opioid component changes that risk, is unknown.
Key unknowns: whether the N-ethyl group shifts the balance between NMDA and opioid activity compared to 3-HO-PCP; whether the opioid component causes naloxone-reversible breathing suppression at moderate dissociative doses; and whether separating the two enantiomers could yield a dissociative without respiratory depression risk.
Subjective Effects[edit]
3-HO-PCE disconnects the mind from its environment the way most dissociatives do — but adds something most lack. Opioid activity produces a genuine physical warmth and bodily euphoria beneath the detachment. Lower doses lean stimulating; higher doses bring heavy sedation and deep cognitive disconnection.
Compared to ketamine, 3-HO-PCE is longer-lasting, warmer, and more euphoric — the opioid layer is the defining difference. Compared to 3-HO-PCP, it is less potent and reportedly shorter-acting, with a similar but less overwhelming character.
3-HO-PCE has no precedent in academic literature prior to its appearance on research chemical markets during the 2010s. The first published study directly addressing the compound — a 2023 metabolic characterization — noted that "little is known about its pharmacological properties, metabolism, and toxicity".[3] No receptor binding data or clinical trials have been published for 3-HO-PCE specifically.
Subjective effects include dissociation, analgesia, euphoria, cognitive disconnection, sedation, and warmth. The experience is defined by an opioid-tinged warmth layered over dissociative detachment — warmer and more euphoric than ketamine, less overwhelming than 3-HO-PCP. Compulsive redosing, mania, and amnesia are characteristic unsought effects.[4]
The toxic dose is completely unknown, and the dual opioid–NMDA mechanism introduces respiratory depression risk absent from most dissociatives.[5][6] The opioid component may confer higher physical dependence liability than pure NMDA antagonists, but this has not been characterized. No substance-specific safety data exist — the current understanding rests entirely on structural analogy and community reports.
History[edit]
Discovery
The arylcyclohexylamine class began with the synthesis of phencyclidine (PCP) by Parke-Davis in 1956. Eticyclidine (PCE), the direct parent compound of 3-HO-PCE, was developed in the 1970s as an anesthetic candidate but abandoned after ketamine proved clinically superior.[7] The 3-hydroxy structural motif was first explored in 1978 with the synthesis of 3-HO-PCP, which revealed that a hydroxyl group at the phenyl 3-position confers μ-opioid activity[2] — the pharmacological principle 3-HO-PCE inherits.
Research chemical emergence
3-HO-PCE appeared on research chemical markets during the 2010s as part of a wave of novel arylcyclohexylamine analogs combining known pharmacologically active motifs — the N-ethyl group of PCE with the 3-hydroxyphenyl moiety of 3-HO-PCP. The first published scientific study appeared in 2023, when Larabi et al. characterized its metabolism using human liver microsomes.[3] No clinical trials have been registered.
Regulatory context
Eticyclidine (PCE) is Schedule I under both US and UN conventions. The closely related 3-MeO-PCP was placed in DEA Schedule I in March 2026,[8] demonstrating ongoing regulatory attention to phenyl-substituted arylcyclohexylamine analogs.
The name "3-HO-PCE" follows systematic research chemical nomenclature: "3-HO" denotes the 3-hydroxy phenyl substitution, "PCE" abbreviates the parent compound eticyclidine. The compound has no established street names or cultural identity beyond research chemical communities, where it is discussed primarily in comparison to its more potent relative 3-HO-PCP.
Chemistry[edit]
Structural class
3-HO-PCE belongs to the arylcyclohexylamine family — compounds defined by a cyclohexane ring bearing an aryl group and an amine at the same carbon. It is distinguished from its parent compound eticyclidine (PCE) by a single modification: a hydroxyl group at the 3-position of the phenyl ring. This substitution is pharmacologically consequential — it confers μ-opioid affinity absent in the unsubstituted parent.[2]
Within the broader structure-activity landscape, 3-HO-PCE sits at the intersection of two modification axes: the N-alkyl series (PCP → PCE, differing in amine substitution) and the phenyl-hydroxy series (PCE → 3-HO-PCE, differing in ring substitution). Its closest structural relatives are 3-HO-PCP (the N-piperidyl version) and 3-MeO-PCE (bearing a methoxy rather than hydroxy group).
Molecular identity
| Molecular formula | C₁₄H₂₁NO |
| Molecular weight | 219.32 g/mol |
The molecule comprises a cyclohexane ring with two substituents at C1: a secondary amine bearing an ethyl group and a phenyl ring hydroxylated at the meta position. The phenolic –OH functions as both hydrogen bond donor and acceptor, influencing receptor binding and metabolic conjugation.
Stereochemistry
The C1 carbon bearing both the amine and aryl group constitutes a stereocenter. Like PCP and PCE, 3-HO-PCE exists as a racemic mixture of (R)- and (S)-enantiomers. Whether research chemical material is racemic, and whether the enantiomers differ in pharmacological activity (as documented for ketamine), has not been investigated.
Physical properties
No published characterization of the free base or salt forms exists. Melting point, solubility, and stability data have not been reported in the peer-reviewed literature.citation needed
Pharmacology[edit]
Mechanism of action
3-HO-PCE has no published receptor binding data. Its pharmacological profile is entirely inferred from structural analogy to characterized compounds and from class membership within the arylcyclohexylamine family.
NMDA receptor antagonism is the class-defining mechanism. All arylcyclohexylamines block the ion channel of the NMDA, preventing glutamate from driving excitatory signaling.[1] The closely related 3-MeO-PCE was confirmed as a high-affinity NMDA ligand via standardized binding assays,[9] and 3-HO-PCP binds the NMDA channel with approximately 8-fold higher affinity than PCP itself.[10]
Mu-opioid receptor agonism is specifically conferred by the 3-hydroxy phenyl substitution. Research on 3-HO-PCP demonstrated dose-dependent, naloxone-reversible opioid activity and high affinity for opioid binding sites.[2] This dual mechanism — dissociative disconnection plus opioid warmth — distinguishes 3-HO-PCE from ketamine and PCP.
Sigma-1 receptor activity is expected based on class membership. PCP-type compounds display appreciable sigma receptor affinity,[9] and the sigma-1 receptor modulates ion channel activity and neurotransmitter release.[11]
Pharmacokinetics
No human pharmacokinetic studies exist. Half-life, bioavailability, and distribution parameters are uncharacterized.
The sole metabolic data comes from Larabi et al. (2023), who identified 15 putative metabolites using human liver microsomes.[3] Primary pathways include N-dealkylation, deamination, hydroxylation, and O-glucuronidation. The metabolic profile closely resembles that of O-PCE (deschloroketamine), suggesting analogous enzymatic processing.[3]
By analogy to ketamine, CYP3A4 and CYP2B6 are likely the primary metabolizing enzymes.[12] CYP2B6 inhibitors produced a 2.4-fold increase in oral ketamine exposure in a controlled study,[13] suggesting that analogous interactions may affect 3-HO-PCE.
Neuroscience[edit]
Where it acts
NMDA blockade preferentially affects GABAergic interneurons in cortical and limbic structures,[1] disinhibiting glutamatergic neurons and paradoxically increasing cortical excitability while disrupting coherent information processing. Autoradiographic mapping of the closest structural analog (3-HO-PCP) showed binding concentrated in hippocampus, cortex, and striatum.[10] The μ-opioid component simultaneously engages descending pain modulation pathways, mesolimbic reward circuitry, and — critically — respiratory centers in the brainstem.[2]
Dual-mechanism reinforcement
The combination of NMDA antagonism (which may drive rapid synaptogenesis via AMPA-mediated BDNF release, as demonstrated for ketamine[14]) and direct mu-opioid agonism creates a dual reinforcement mechanism. Both neuroplasticity-mediated mood elevation and direct opioid reward contribute to behavioral reinforcement — likely explaining the compulsive redosing tendency noted in community reports.[4]
NMDA antagonists including PCP and ketamine produce dose-dependent neurotoxicity in animal models and a schizophrenia-like psychosis in humans.[15] Whether 3-HO-PCE produces equivalent neurotoxicity, and whether the opioid component modifies this risk, is unknown.
Key unknowns include whether the N-ethyl group alters NMDA vs. opioid receptor selectivity relative to 3-HO-PCP, whether the opioid component is sufficient to produce naloxone-reversible respiratory depression at moderate dissociative doses, and whether enantiomeric separation could yield a dissociative without respiratory depression risk.
Subjective Effects[edit]
The experiential character of 3-HO-PCE is shaped by its dual mechanism: NMDA blockade produces dissociative detachment from environment and self, while μ-opioid agonism contributes a warmth, analgesia, and bodily euphoria atypical of most dissociatives. Users consistently report a stimulating body feel at lower doses transitioning to heavy sedation at higher doses, with set and setting strongly modulating whether the experience presents as introspective or manic.
Relative to ketamine, 3-HO-PCE is longer-acting, less anesthetic, and more euphoric — the opioid warmth distinguishes it from ketamine's colder dissociation. Compared to 3-HO-PCP, it is less potent per milligram and reportedly shorter in duration, with a similar but less overwhelming opioid character.
Effect Grid
A clear dissociative state with the signature dual character of 3-HO-PCE: NMDA-mediated cognitive disconnection layered with opioid-derived bodily euphoria and warmth. Time alteration, spatial disorientation, and visual drifting become pronounced. Internal hallucinations may emerge in closed-eye states. Thought deceleration and thought disorganization reduce analytical capacity.
Physically, motor control impairment is significant — walking becomes unsteady. Pain suppression is marked. Dizziness and vestibular distortion are common. The stimulating quality of lower doses gives way to a neutral or mildly sedating body load. Appetite is suppressed; dehydration sensation may occur.
Full 4–6 hour duration commitment. Driving and complex tasks are impossible. Compulsive redosing urge is notable — the opioid reinforcement makes additional doses feel appealing before the previous dose has peaked.
Modeled from the effect's dose-dependence curve — not per-substance measurements.
Depth perception distortion · Touch suppression · Visual haze / noise · Visual acuity suppression · Perspective distortion · Auditory distortion · Auditory misinterpretation · Color alteration · Ganzfeld effect · Light sensitivity · Sensory deprivation · Sound sensitivity · Touch enhancement · Visual drifting · Music enhancement · Visual morphing · After-images · Auditory enhancement · Auditory suppression · Brightness alteration · Color enhancement · Color suppression · Dreaming enhancement · Dreaming suppression · Environmental patterning · Peripheral misidentification · Peripheral vision distortion · Tinnitus · Tracers · Visual magnification · Holotropic state · Geometry · Synesthesia · Visual breathing · Visual melting · Visual processing suppression · Internal hallucinations · Auditory hallucinations · Environmental orbism / cubism · External hallucinations · Object transformations · Perspective hallucinations · Visual scenery slicing · Visual recursion · Object activation · Shadow people · Olfactory hallucination
Perspective distortion · Auditory distortion · Auditory misinterpretation · Color alteration · Ganzfeld effect · Light sensitivity · Sensory deprivation · Sound sensitivity · Touch enhancement · Visual drifting · Music enhancement · Visual morphing · After-images · Auditory enhancement · Auditory suppression · Brightness alteration · Color enhancement · Color suppression · Dreaming enhancement · Dreaming suppression · Environmental patterning · Peripheral misidentification · Peripheral vision distortion · Tinnitus · Tracers · Visual magnification · Holotropic state · Geometry · Synesthesia · Visual breathing · Visual melting · Visual processing suppression · Internal hallucinations · Auditory hallucinations · Environmental orbism / cubism · External hallucinations · Object transformations · Perspective hallucinations · Visual scenery slicing · Visual recursion · Object activation · Shadow people · Olfactory hallucination
Dizziness · Body high · Body schema distortion · Body scan awareness · Physical fatigue · Bodily heaviness · Muscle relaxation · Pupil constriction · Dehydration sensation · Nausea · Breathing alteration · Constipation · Dry mouth · Headache · Heart rate perception changes · Laughter fits · Spontaneous body sensations · Tactile euphoria · Yawning · Bodily pressures · Insomnia · Involuntary body movements · Sexual arousal suppression · Tingling / electric sensations · Vasoconstriction · Vibrations / buzzing · Vomiting · Excessive sweating · Appetite suppression · Bodily lightness · Muscle tension · Restlessness · Salivation · Trembling · Watery eyes · Stimulation · Abnormal heartbeat · Respiratory depression · Increased urination · Bodily dissociation · Seizure threshold reduction · Phantom limb sensations · Tactile hallucination
Body scan awareness · Physical fatigue · Bodily heaviness · Muscle relaxation · Pupil constriction · Dehydration sensation · Nausea · Breathing alteration · Constipation · Dry mouth · Headache · Heart rate perception changes · Laughter fits · Spontaneous body sensations · Tactile euphoria · Yawning · Bodily pressures · Insomnia · Involuntary body movements · Sexual arousal suppression · Tingling / electric sensations · Vibrations / buzzing · Vomiting · Excessive sweating · Appetite suppression · Bodily lightness · Muscle tension · Restlessness · Salivation · Trembling · Watery eyes · Stimulation · Abnormal heartbeat · Respiratory depression · Increased urination · Bodily dissociation · Seizure threshold reduction · Phantom limb sensations · Tactile hallucination
Information processing suppression · Memory suppression · Memory fragmentation · Thought loops · Cognitive euphoria · Thought deceleration · Thought disorganization · Analysis suppression · Cognitive fatigue · Delusions of sobriety · Language suppression · Motivation suppression · Compulsive redosing urge · Immersion enhancement · Pattern recognition suppression · Humor enhancement · Aesthetic enhancement · Cognitive dysphoria · Cognitive flexibility · Creativity suppression · Introspection enhancement · Novelty enhancement · Openness enhancement · Conceptual thinking · Creativity enhancement · Memory replays · Multiple thought streams · Thought connectivity · Amnesia · Delusions · Delirium
Thought loops · Cognitive euphoria · Thought deceleration · Thought disorganization · Analysis suppression · Cognitive fatigue · Language suppression · Motivation suppression · Compulsive redosing urge · Immersion enhancement · Pattern recognition suppression · Humor enhancement · Aesthetic enhancement · Cognitive dysphoria · Cognitive flexibility · Creativity suppression · Introspection enhancement · Novelty enhancement · Openness enhancement · Conceptual thinking · Creativity enhancement · Memory replays · Multiple thought streams · Thought connectivity · Amnesia · Delusions · Delirium
Anxiety · Emotional lability · Empathy suppression · Simultaneous emotions · Anhedonia · Catharsis · Dysphoria · Emotional enhancement · Empathy enhancement · Irritability · Mania
Simultaneous emotions · Anhedonia · Catharsis · Dysphoria · Emotional enhancement · Empathy enhancement · Irritability
Social disconnection · Automaticity · Craving · Sociability suppression · Disinhibition · Emotional susceptibility · Compulsive behavior reduction · Ego inflation · Flow state · Sociability enhancement · Cognitive disconnection · Identity alteration · Boundary dissolution · Ego dissolution
Disinhibition · Emotional susceptibility · Compulsive behavior reduction · Ego inflation · Flow state · Sociability enhancement · Cognitive disconnection · Identity alteration · Boundary dissolution · Ego dissolution
Time cessation
Near-death experience · Noetic insight · Non-dual awareness · Transpersonal feelings · Transpersonal visions · Voidness
Transpersonal visions · Voidness
Timeline
Initial awareness of altered state emerges as subtle body warmth and a faint dissociative edge. Cognition remains largely intact but a perceptual softening begins.
Dissociation and opioid warmth build progressively. Motor coordination begins to decline. Spatial awareness shifts.
Full dissociative state with opioid euphoria, cognitive disconnection, time alteration, and perceptual distortion. Pain suppression and bodily warmth are maximal. Motor impairment is significant.
Gradual return of environmental connection and cognitive function. Residual warmth and mild dissociation persist. Motor coordination slowly recovers but remains impaired.
Mild residual dissociation, possible afterglow warmth or cognitive fog. Some users report mood elevation; others note fatigue.
⚠ Do not drive or operate machinery for at least 8 hours after ingestion — residual dissociation and motor impairment may persist beyond subjective return to baseline.
Safety[edit]
- Acute toxicity
- Moderate
- Chronic toxicity
- Moderate
- Withdrawal
- Mild
- Tolerance buildup
- moderate
- Tolerance reset
- 10.5 days
- Physical
- Moderate
- Psychological
- Moderate
- Compulsive redosing
- High
- Dose escalation
- Moderate
- Cross-tol.
- ketamine · PCP · DXM
Toxicity
No lethal dose data exist for 3-HO-PCE in any species. The toxic dose is completely unknown.safety citation needed
Dual NMDA–opioid risk
Analog fatality data
Every published fatality involving closely related compounds occurred in polydrug settings. A fatal 3-HO-PCP case involved a blood concentration of 524 ng/mL alongside multiple co-ingestants including methadone.[15] A 3-MeO-PCE death involved concurrent 2F-DCK use, with breathing failure as the cause.[5]
From 25 confirmed O-PCE (eticyclidine family) acute poisoning cases, clinical presentation included impaired consciousness (84%), high blood pressure (80%), confusion (60%), rapid heart rate (40%), and seizures (16%).[16] Muscle breakdown and acute kidney injury have also been documented with arylcyclohexylamine compounds.[17]
Psychological risks
High doses of NMDA antagonists produce paranoia, hallucinations, and delusional thinking in humans — a state that typically resolves when the drug clears.[14]
Specific psychological risks include:
- Psychosis precipitation: NMDA antagonism may trigger persistent psychotic episodes in vulnerable individuals[4]
- Compulsive redosing: The opioid component drives behavioral reinforcement beyond what pure dissociatives produce — cumulative effects are reported as dangerous[4]
- Mania: Dose-dependent disinhibition
- Amnesia: Memory blackouts that may lead to unintended redosing
- Depersonalization: Core dissociative effects that may persist beyond the acute experience in susceptible individuals
Tolerance and dependence
No published tolerance or dependence data exist. Community-estimated values — tolerance building with regular use, a half-life of around 5.5 days, full reset around 1.5 weeks, and cross-tolerance with other dissociatives[4] — have no pharmacokinetic validation.
The opioid component introduces a dependence pathway not shared by ketamine or PCP. Dextromethorphan — which shares NMDA antagonism but lacks direct opioid agonism — has been documented to produce dependence, psychosis, and physical withdrawal,[18] suggesting the dissociative mechanism alone can drive compulsive use.
Drug Interactions
No published interaction data exist for 3-HO-PCE. All assessments below are class-level inferences.
CNS depressants (highest risk)
Combining with opioids, benzodiazepines, alcohol, or GHB is the highest-risk category. Every published fatality involving 3-HO-PCP or 3-MeO-PCE occurred in polydrug settings.[15][5] The opioid component makes this more dangerous than equivalent ketamine combinations — breathing suppression comes through two mechanisms at once.
Other opioid agonists
Combining with fentanyl, heroin, methadone, or codeine stacks opioid receptor activation. The fatal 3-HO-PCP case involved co-ingested methadone.[15]
Other NMDA antagonists
Combining with ketamine, 2F-DCK, MXE, DXM, or nitrous oxide deepens dissociation and CNS depression. The 3-MeO-PCE fatality involved concurrent 2F-DCK.[5]
CYP enzyme interactions
CYP2B6 inhibitors — including ticlopidine and clopidogrel — may substantially increase 3-HO-PCE exposure. A 2.4-fold increase in oral ketamine was documented with ticlopidine.[11] CYP3A4 inhibitors (azole antifungals, macrolide antibiotics, grapefruit juice) may also increase exposure.[10]
Contraindications
9 knownNo substance-specific contraindication data exist. The following are inferred from the expected pharmacological profile:
- Respiratory compromise (absolute): The opioid component adds breathing suppression risk. Obstructive sleep apnea, COPD, or other breathing conditions increase the risk of fatal respiratory failure.
- Concurrent opioid use (absolute): Additive breathing suppression through shared receptor engagement.
- History of psychosis (absolute): NMDA antagonism can replicate and may trigger persistent psychotic episodes.[14]
- Liver impairment (relative): Impaired clearance could prolong exposure and increase toxicity.
- Heart conditions (relative): High blood pressure and rapid heart rate were documented in 80% and 40% of O-PCE poisoning cases respectively.[16]
- Pregnancy (absolute): NMDA receptor antagonism disrupts neurodevelopment.
- Seizure disorders (relative): Seizures were documented in 16% of O-PCE acute poisoning cases.[16]
Harm Reduction[edit]
Forms & Identification
3-HO-PCE circulates exclusively as a research chemical powder with no regulated supply chain. Purity varies between batches and vendors. Reagent kits can rule out common substitutions but cannot confirm identity or purity. Quantitative analysis — FTIR or GC-MS through a drug checking service — is the only reliable way to confirm a sample is not a more potent structural analog like 3-HO-PCP.
Given the narrow active dose range (5–25 mg), even small purity variations can shift a dose from moderate to heavy.
Guidelines
- Use a milligram-accurate scale (±1 mg) for every dose — eyeballing is unacceptable at this potency
- Start at the low end of the dose range (5–8 mg oral) to assess individual sensitivity
- Pre-measure any planned doses and remove remaining material from reach before onset to prevent compulsive redosing
- Do not redose within the first 90 minutes — onset may be slow and cumulative effects are reported as dangerous[4]
- Use only one substance — polydrug combinations, especially with depressants or opioids, account for all known fatalities in this class[15]
- Have a sober companion present who knows what was taken and the expected duration
- Do not use alone, especially at higher doses where respiratory depression risk increases
- Inform any companion about naloxone and its potential applicability
Set & Setting
The dual opioid–dissociative mechanism produces unpredictable dose-response transitions. Lower doses may feel stimulating; higher doses produce deep sedation and disconnection. A calm, familiar, private environment with a sober companion significantly reduces risk — particularly given the compulsive redosing tendency and dose-dependent amnesia.
Aftercare & integration. Allow 24–48 hours before making important decisions or operating vehicles. Some people report residual cognitive fog or emotional flatness for 1–2 days after moderate-to-heavy doses.
If depersonalization or feelings of unreality persist beyond 48 hours, physical exercise, structured routine, and sensory engagement are first-line responses. Symptoms persisting beyond one week warrant professional support. The opioid component may produce a mild withdrawal-like dysphoria in the days following use, particularly after repeated sessions.
Recovery & Support
The combination of dissociative escapism and opioid reward creates a reinforcement pattern that can develop into compulsive use. Signs of problematic use include escalating frequency, using alone, dose escalation to overcome tolerance, and continued use despite negative consequences.
If physical dependence has developed, tapering with professional guidance is safer than abrupt cessation. No specific treatment protocols exist for arylcyclohexylamine dependence — addiction medicine specialists and harm reduction organizations can provide individualized support. SMART Recovery, peer support, and addiction counseling are appropriate starting points.
Recovery resources, crisis lines, and support pathways → View all
Emergency Response
Recognizing an emergency:
- Breathing becomes slow, shallow, or stops
- Lips or fingertips turn blue or grey
- Person is unresponsive to loud voice and sternal rub
- Seizure activity
- Body temperature feels extremely high through clothing
These signs distinguish a medical emergency from uncomfortable-but-safe dissociative intensity (confusion, inability to communicate, apparent unresponsiveness that resolves with loud stimulation).
Immediate steps:
- Call emergency services immediately
- If breathing is slow or absent and naloxone is available, administer it — the opioid component of 3-HO-PCE is naloxone-reversible[2]
- Place the person in the recovery position (on their side) if unconscious but breathing
- Do not leave them alone
- Do not induce vomiting
- Monitor breathing continuously until help arrives
What to tell the dispatcher:
Name the substance (3-HO-PCE, a dissociative with opioid properties), approximate amount taken, time of ingestion, and current symptoms. Note that standard opioid drug screens will not detect this compound.[5] Good Samaritan laws in many jurisdictions protect people who call for help during drug emergencies.
Reversal agents:
Naloxone may partially reverse respiratory depression from the opioid component. It will not reverse NMDA-mediated dissociation or sedation. Multiple doses may be required. Naloxone availability is recommended whenever 3-HO-PCE is used.
Legal Status[edit]
3-HO-PCE is not specifically listed in controlled substance schedules of most jurisdictions as of 2026. Its parent compound eticyclidine (PCE) is internationally controlled under Schedule I of the UN 1971 Convention, creating variable legal exposure depending on how national law handles structural analog or derivative provisions. The legal landscape for arylcyclohexylamine analogs is actively evolving.[7]
| Jurisdiction | Classification | Key provisions |
|---|---|---|
| United States | Not specifically scheduled; Federal Analogue Act applies | PCE is Schedule I. Under 21 U.S.C. § 813, substances substantially similar in structure or pharmacology to Schedule I compounds are treated as Schedule I when intended for human consumption. Prosecution as a controlled substance analogue is plausible.[6] |
| United Kingdom | Prohibited under Psychoactive Substances Act 2016 | Blanket prohibition on supply, production, and import/export. Not specifically listed under the Misuse of Drugs Act 1971. Possession for personal use is not an offence under PSA 2016. |
| Canada | Uncertain | PCP is Schedule I under CDSA. PCE is not specifically identified. Canada lacks a structural analogue provision equivalent to the US Federal Analogue Act. |
| Australia | Uncertain; PCP is Schedule 9 | PCP is a Schedule 9 prohibited substance. 3-HO-PCE is not specifically listed. Coverage depends on state/territory NPS legislation. |
| European Union | No EU-wide scheduling identified | Individual member states may schedule under national NPS legislation. No EMCDDA/EUDA alert specific to 3-HO-PCE has been issued. |
| International (UN) | Not specifically scheduled | PCE is Schedule I of the 1971 Convention. Coverage of 3-HO-PCE as a derivative depends on national implementation. |
Analog and derivative considerations
The DEA's March 2026 placement of 3-MeO-PCP in Schedule I[7] establishes regulatory precedent for ring-substituted arylcyclohexylamine analogs. 3-HO-PCE shares greater structural similarity to PCP/PCE than 3-MeO-PCP does, suggesting vulnerability to future scheduling or current prosecution under the Federal Analogue Act.
Safety[edit]
- Acute toxicity
- Moderate
- Chronic toxicity
- Moderate
- Withdrawal
- Mild
- Tolerance buildup
- moderate
- Tolerance reset
- 10.5 days
- Physical
- Moderate
- Psychological
- Moderate
- Compulsive redosing
- High
- Dose escalation
- Moderate
- Cross-tol.
- ketamine · PCP · DXM
Toxicity
No lethal dose data exist for 3-HO-PCE in any species. No human fatalities attributed solely to 3-HO-PCE have been reported. The toxic dose is completely unknown.safety citation needed
Dual NMDA–opioid risk
Analog fatality data
Every published fatality involving closely related compounds occurred in polydrug contexts. A fatal 3-HO-PCP case involved a blood concentration of 524 ng/mL alongside multiple co-ingestants including methadone.[5] A 3-MeO-PCE fatality involved concurrent 2F-DCK use, with death attributed primarily to respiratory depression.[6]
From 25 confirmed O-PCE (eticyclidine family) acute poisoning cases, clinical presentation included impaired consciousness (84%), confusion (60%), high blood pressure (80%), rapid heart rate (40%), and convulsions (16%).[16] Muscle breakdown and acute kidney injury have been documented with arylcyclohexylamine derivatives.[17]
Psychological risks
NMDA receptor antagonists produce a psychosis in humans — characterized by hallucinations, delusions, withdrawal, and cognitive disorganization — that is dose-dependent and typically self-limiting upon drug clearance.[15]
Specific psychological risks include:
- Psychosis precipitation: NMDA antagonism in vulnerable individuals may trigger persistent psychotic episodes[4]
- Compulsive redosing: The opioid reinforcement component adds behavioral drive beyond pure NMDA antagonists. Community sources warn that "redosing may result in dangerous cumulative effects"[4]
- Mania: Dose-dependent, associated with disinhibition
- Amnesia: Dose-dependent memory blackouts may lead to unintended redosing
- Depersonalization: Core dissociative effects that may persist beyond acute intoxication in susceptible individuals
Tolerance and dependence
No published tolerance or dependence data exist for 3-HO-PCE. Community-derived estimates — tolerance buildup with prolonged use, half-life approximately 5.5 days, full reset approximately 1.5 weeks, cross-tolerance with other dissociatives[4] — lack pharmacokinetic validation.
The NMDA component is expected to produce tolerance through receptor adaptation. Cross-tolerance with other dissociatives (ketamine, PCP, DXM) is expected given the shared binding site.
The mu-opioid component introduces an additional dependence mechanism not shared by ketamine or PCP. Physical dependence through receptor desensitization is theoretically possible with chronic use but has not been documented. Dextromethorphan — which shares NMDA antagonism and sigma-1 receptor agonism without direct opioid agonism — has been documented to produce dependence, psychosis, and physical withdrawal.[18]
Drug Interactions
No published interaction data exist for 3-HO-PCE. All assessments below are class-level inferences.
CNS depressants (highest risk)
Combination with opioids, benzodiazepines, alcohol, or GHB represents the highest-risk category. Every published fatality involving 3-HO-PCP or 3-MeO-PCE occurred in polydrug contexts.[5][6] The opioid component makes this interaction qualitatively more dangerous than equivalent combinations with ketamine — additive respiratory depression occurs through both NMDA-mediated sedation and direct opioid receptor suppression.
Other opioid agonists
Co-administration with fentanyl, heroin, methadone, or codeine creates additive mu-opioid engagement. The fatal 3-HO-PCP case involved co-ingested methadone.[5]
Other NMDA antagonists
Combination with ketamine, 2F-DCK, MXE, DXM, or nitrous oxide produces additive dissociation and CNS depression. The 3-MeO-PCE fatality involved concurrent 2F-DCK.[6]
CYP enzyme interactions
CYP2B6 inhibitors (ticlopidine, clopidogrel) may significantly increase 3-HO-PCE exposure — a 2.4-fold increase in oral ketamine was documented with ticlopidine.[13] CYP3A4 inhibitors (azole antifungals, macrolide antibiotics, grapefruit juice) may also increase exposure.[12]
Contraindications
9 knownNo substance-specific contraindication data exist. The following are inferred from the expected pharmacological profile:
- Respiratory compromise (absolute): The opioid component adds respiratory depression risk. Obstructive sleep apnea, COPD, or other breathing conditions elevate risk of fatal respiratory failure.
- Concurrent opioid use (absolute): Additive respiratory depression through shared receptor engagement.
- History of psychosis (absolute): NMDA antagonism replicates and may precipitate psychotic episodes.[15]
- Liver impairment (relative): Impaired clearance could prolong exposure and increase toxicity.
- Heart conditions (relative): Rapid heart rate and high blood pressure documented in class-level data (40% and 80% respectively in O-PCE cases).[16]
- Pregnancy (absolute): NMDA receptor antagonism disrupts neurodevelopment.
- Seizure disorders (relative): Convulsions documented in 16% of O-PCE acute poisoning cases.[16]
Harm Reduction[edit]
Forms & Identification
3-HO-PCE circulates exclusively as a research chemical powder with no regulated supply chain. The absence of pharmaceutical-grade production means purity varies between batches and vendors. Testing matters more than usual here: reagent kits can exclude common substitutions (cathinones, other dissociatives) but cannot confirm identity or purity with certainty. Quantitative analysis (e.g. FTIR or GC-MS through drug checking services) is the only way to confirm that a sample is 3-HO-PCE rather than a more potent structural analog like 3-HO-PCP. Given the narrow active dose range (5–25 mg), even small purity variations can shift a dose from moderate to heavy.
Guidelines
- Use a milligram-accurate scale (±1 mg) for every dose — eyeballing is unacceptable at this potency
- Start at the low end of the dose range (5–8 mg oral) to assess individual sensitivity
- Pre-measure any planned doses and remove remaining material from reach before onset to prevent compulsive redosing
- Do not redose within the first 90 minutes — onset may be slow and cumulative effects are reported as dangerous[4]
- Use only one substance — polydrug combinations (especially with other depressants or opioids) account for all known fatalities in this class[5]
- Have a sober companion present who knows the substance was taken and its expected duration
- Do not use alone, especially at higher doses where respiratory depression risk increases
- Inform your companion about naloxone and its potential applicability
Set & Setting
The dual opioid–dissociative mechanism produces unpredictable dose-response transitions. Lower doses may feel stimulating and social; higher doses produce deep sedation and disconnection. A calm, familiar, private environment with a sober companion significantly reduces risk — particularly given the compound's association with compulsive redosing and dose-dependent amnesia. Avoid situations requiring coordination, driving, or decision-making.
Aftercare & integration. Dissociative experiences can produce lasting shifts in perception of self and environment. After 3-HO-PCE use, allow 24–48 hours before making important decisions or operating vehicles. Some users report residual cognitive fog or emotional flatness for 1–2 days following moderate-to-heavy doses.
If depersonalization or feelings of unreality persist beyond 48 hours, grounding techniques (physical exercise, structured routine, sensory engagement) are first-line responses. Persistent symptoms beyond one week warrant professional support. The opioid component may produce a mild withdrawal-like dysphoria in the days following use, particularly after repeated sessions.
Recovery & Support
The combination of dissociative escapism and opioid reward creates a reinforcement pattern that can develop into compulsive use. Signs of problematic use include escalating frequency, using alone, dose escalation to overcome tolerance, and continued use despite negative consequences.
If physical dependence has developed (evidenced by withdrawal symptoms between doses), tapering with professional guidance is safer than abrupt cessation. No specific treatment protocols exist for arylcyclohexylamine dependence; addiction medicine specialists and harm reduction organizations can provide individualized support. SMART Recovery, community-based peer support, and addiction counseling services are appropriate starting points.
Recovery resources, crisis lines, and support pathways → View all
Emergency Response
Recognizing an emergency:
- Breathing becomes slow, shallow, or stops
- Lips or fingertips turn blue or grey
- Person is unresponsive to loud voice and sternal rub
- Seizure activity
- Body temperature feels extremely high through clothing
These signs distinguish a medical emergency from uncomfortable-but-safe dissociative intensity (confusion, inability to communicate, apparent unresponsiveness that resolves with loud stimulation).
Immediate steps:
- Call emergency services immediately
- If breathing is slow or absent and naloxone is available, administer it — the opioid component of 3-HO-PCE is naloxone-reversible[2]
- Place the person in the recovery position (on their side) if unconscious but breathing
- Do not leave them alone
- Do not induce vomiting
- Monitor breathing continuously until help arrives
What to tell the dispatcher:
Name the substance (3-HO-PCE, a dissociative with opioid properties), approximate amount taken, time of ingestion, and current symptoms. Note that standard opioid drug screens will not detect this compound.[6] Good Samaritan laws in many jurisdictions protect people who call for help during drug emergencies.
Reversal agents:
Naloxone may partially reverse respiratory depression from the opioid component. It will not reverse NMDA-mediated dissociation or sedation. Multiple doses may be required. Naloxone availability is recommended whenever 3-HO-PCE is used.
Legal Status[edit]
3-HO-PCE is not specifically listed in controlled substance schedules of most jurisdictions as of 2026. Its parent compound eticyclidine (PCE) is internationally controlled under Schedule I of the UN 1971 Convention on Psychotropic Substances, creating variable legal exposure depending on how national legislation handles derivative or structural analog provisions. The legal landscape for phenyl-substituted arylcyclohexylamine analogs is actively evolving.[8]
| Jurisdiction | Classification | Key provisions |
|---|---|---|
| United States | Not specifically scheduled; Federal Analogue Act applies | PCE is Schedule I. Under 21 U.S.C. § 813, substances substantially similar in structure or pharmacology to Schedule I compounds are treated as Schedule I when intended for human consumption. Prosecution as a controlled substance analogue is plausible.[7] |
| United Kingdom | Prohibited under Psychoactive Substances Act 2016 | Blanket prohibition on supply, production, and import/export. Not specifically listed under the Misuse of Drugs Act 1971. Possession for personal use is not an offence under PSA 2016. |
| Canada | Uncertain | PCP is Schedule I under CDSA. PCE is not specifically identified. Canada lacks a structural analogue provision equivalent to the US Federal Analogue Act. |
| Australia | Uncertain; PCP is Schedule 9 | PCP is a Schedule 9 prohibited substance. 3-HO-PCE is not specifically listed. Coverage depends on state/territory NPS legislation. |
| European Union | No EU-wide scheduling identified | Individual member states may schedule under national NPS legislation. No EMCDDA/EUDA alert specific to 3-HO-PCE has been issued. |
| International (UN) | Not specifically scheduled | PCE is Schedule I of the 1971 Convention. Coverage of 3-HO-PCE as a derivative depends on national implementation. |
Analog and derivative considerations
The DEA's March 2026 placement of 3-MeO-PCP in Schedule I[8] establishes regulatory precedent for scheduling ring-substituted arylcyclohexylamine analogs. 3-HO-PCE shares greater structural similarity to PCP/PCE (both Schedule I) than 3-MeO-PCP does, suggesting vulnerability to future scheduling or current prosecution under the Federal Analogue Act.
Frequently asked questions
How long does 3-HO-PCE last?
Total duration by route of administration — Oral: 4 – 6 hours. Ranges vary with dose and individual factors; see the duration table for onset, peak, and after-effect phases.
Where can I find dosage information for 3-HO-PCE?
Psychedex publishes a dosage table for 3-HO-PCE on this page covering these routes of administration: oral. Dose values are presented only in that table, always alongside their route of administration.
What are dangerous combinations with 3-HO-PCE?
The highest-severity documented interactions for 3-HO-PCE: Benzodiazepines, Barbiturates (Lethal), GHB, Baclofen (Lethal), GHB, GBL (Lethal), Local anesthetics (Lethal), Alpha-2 adrenergic receptor antagonist (Dangerous). See the interactions section for the full list with mechanisms and severity levels.
Is 3-HO-PCE addictive?
Psychedex records tolerance and dependence data rather than a yes/no rating. Recorded tolerance indicators for 3-HO-PCE: tolerance builds moderate; full reset takes 10.5 days; cross-tolerance develops with ketamine, PCP, DXM, MXE, 3-HO-PCP, 3-MeO-PCE, O-PCE, nitrous oxide. See the article's dependence and safety sections for recorded dependence data.
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First-person accounts of subjective effects, timing, and outcomes — submitted for harm reduction.
references
- [1] ^abcMartin D, Lodge D (1988) Phencyclidine receptors and N-methyl-D-aspartate antagonism: electrophysiologic data correlates with known behaviours — Pharmacology, Biochemistry and Behavior PMID:2854262
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- [3] ^abcLarabi IA, Joseph D, Lesueur C, Alvarez JC (2023) Characterization of 3-Hydroxyeticyclidine (3-HO-PCE) Metabolism in Human Liver Microsomes and Biological Samples Using High-Resolution Mass Spectrometry — Metabolites doi:10.3390/metabo13030432
- [4]
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references
- [1] ^abcMartin D, Lodge D (1988) Phencyclidine receptors and N-methyl-D-aspartate antagonism: electrophysiologic data correlates with known behaviours — Pharmacology, Biochemistry and Behavior PMID:2854262
- [2]
- [3] ^abcdLarabi IA, Joseph D, Lesueur C, Alvarez JC (2023) Characterization of 3-Hydroxyeticyclidine (3-HO-PCE) Metabolism in Human Liver Microsomes and Biological Samples Using High-Resolution Mass Spectrometry — Metabolites doi:10.3390/metabo13030432
- [4]
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- [6]