3-HO-PCE
3-hydroxyeticyclidine
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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]
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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.
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
No 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.
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] ^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]
- [5]
- [6]