Rolicyclidine
Studies and references cited across this article, graded by evidence strength.
Inconclusive means the cited source neither confirms nor refutes the claim — a lower-confidence badge, not an error.
Data points an editor reviewed and accepted for publication.
Value Provenance
Dosing
smoked
Predates provenance tracking — no derivation record for this dataset
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Threshold | 1 mg | no record | |
| Low | 2–4 mg | no record | |
| Common | 4–8 mg | no record | |
| Strong | 8–12 mg | no record | |
| Heavy | — | no record |
insufflatedtrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Threshold | 1 mg | 1 mg | low |
| Low | 1–3 mg | 1–3 mg | low |
| Common | 3–6 mg | 3–6 mg | low |
| Strong | 6–10 mg | 6–10 mg | low |
| Heavy | 12+ mg | 12+ mg | low |
| Editorial | No published human dose data for rolicyclidine via insufflation. Values are existing database entries (community-derived), slightly lower than oral due to faster mucosal absorption and potentially higher bioavailability. Inferred from PCP class pharmacology and relative potency ranking. All values require editorial verification. | ||
ReasoningReasoningNo published human dose data for rolicyclidine via insufflation. Values are existing database entries (community-derived), slightly lower than oral due to faster mucosal absorption and potentially higher bioavailability. Inferred from PCP class pharmacology and relative potency ranking. All values require editorial verification. Evidence basis: community_consensus_small | |||
oraltrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Threshold | 1 mg | 1 mg | low |
| Low | 2–3 mg | 2–3 mg | low |
| Common | 4–8 mg | 4–8 mg | low |
| Strong | 8–12 mg | 8–12 mg | low |
| Heavy | 14+ mg | 14+ mg | low |
| Editorial | No published human dose data for rolicyclidine. Values are existing database entries (community-derived), consistent with PCPy being slightly less potent than PCP in behavioral assays (Brady & Balster 1981). PCP active dose range is approximately 1-10 mg oral; rolicyclidine values are shifted slightly higher, reflecting its lower potency. All values require editorial verification. | ||
ReasoningReasoningNo published human dose data for rolicyclidine. Values are existing database entries (community-derived), consistent with PCPy being slightly less potent than PCP in behavioral assays (Brady & Balster 1981). PCP active dose range is approximately 1-10 mg oral; rolicyclidine values are shifted slightly higher, reflecting its lower potency. All values require editorial verification. Evidence basis: community_consensus_small | |||
Duration
oral
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Peaktrace | 1.5–3 hours | 1.5–3 hours | low |
| Editorial | Inferred from PCP class oral pharmacology and total duration estimate of 6-12 hours. No published data. | ||
ReasoningReasoningInferred from PCP class oral pharmacology and total duration estimate of 6-12 hours. No published data. Evidence basis: structural_analogy | |||
| After effectstrace | 4–12 hours | 4–12 hours | low |
| Editorial | Inferred from PCP class lipophilic accumulation and prolonged CNS effects. No published data. | ||
ReasoningReasoningInferred from PCP class lipophilic accumulation and prolonged CNS effects. No published data. Evidence basis: structural_analogy | |||
| Come uptrace | 30–60 minutes | 30–60 minutes | low |
| Editorial | Inferred from PCP class oral pharmacology. No published rolicyclidine-specific data. | ||
ReasoningReasoningInferred from PCP class oral pharmacology. No published rolicyclidine-specific data. Evidence basis: structural_analogy | |||
| Onsettrace | 20–90 minutes | 20–90 minutes | low |
| Editorial | Community-derived estimate from existing database. Consistent with PCP class oral onset (20-60 min) adjusted for rolicyclidine's potentially different absorption profile. No published human data. | ||
ReasoningReasoningCommunity-derived estimate from existing database. Consistent with PCP class oral onset (20-60 min) adjusted for rolicyclidine's potentially different absorption profile. No published human data. Evidence basis: community_consensus_small | |||
| Offsettrace | 2–4 hours | 2–4 hours | low |
| Editorial | Inferred from PCP class oral pharmacology. No published data. | ||
ReasoningReasoningInferred from PCP class oral pharmacology. No published data. Evidence basis: structural_analogy | |||
| Totaltrace | 6–12 hours | 6–12 hours | low |
| Editorial | Community-derived estimate from existing database. Consistent with PCP class oral duration. No published human pharmacokinetic data for rolicyclidine. | ||
ReasoningReasoningCommunity-derived estimate from existing database. Consistent with PCP class oral duration. No published human pharmacokinetic data for rolicyclidine. Evidence basis: community_consensus_small | |||
smoked
Predates provenance tracking — no derivation record for this dataset
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onset | 2–20 minutes | no record | |
| Come up | 20–40 minutes | no record | |
| Peak | 2–3 hours | no record | |
| Offset | 1–2 hours | no record | |
| After effects | 4–48 hours | no record | |
| Total | 4–6 hours | no record |
insufflated
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Come uptrace | 10–30 minutes | 10–30 minutes | low |
| Editorial | Inferred from PCP class insufflated pharmacology. Compressed relative to oral. No published data. | ||
ReasoningReasoningInferred from PCP class insufflated pharmacology. Compressed relative to oral. No published data. Evidence basis: structural_analogy | |||
| Offsettrace | 1–2 hours | 1–2 hours | low |
| Editorial | Inferred from PCP class insufflated pharmacology. No published data. | ||
ReasoningReasoningInferred from PCP class insufflated pharmacology. No published data. Evidence basis: structural_analogy | |||
| Onsettrace | 3–30 minutes | 3–30 minutes | low |
| Editorial | Community-derived estimate from existing database. Faster absorption via nasal mucosa compared to oral. No published data. | ||
ReasoningReasoningCommunity-derived estimate from existing database. Faster absorption via nasal mucosa compared to oral. No published data. Evidence basis: community_consensus_small | |||
| Peaktrace | 1–1.5 hours | 1–1.5 hours | low |
| Editorial | Inferred from total duration estimate (4-6 hours insufflated) and PCP class pharmacology. No published data. | ||
ReasoningReasoningInferred from total duration estimate (4-6 hours insufflated) and PCP class pharmacology. No published data. Evidence basis: structural_analogy | |||
| Totaltrace | 4–6 hours | 4–6 hours | low |
| Editorial | Community-derived estimate from existing database. Shorter than oral due to different absorption kinetics. No published data. | ||
ReasoningReasoningCommunity-derived estimate from existing database. Shorter than oral due to different absorption kinetics. No published data. Evidence basis: community_consensus_small | |||
| After effectstrace | 2–8 hours | 2–8 hours | low |
| Editorial | Inferred from PCP class pharmacology. Shorter aftereffect window than oral due to shorter total duration. No published data. | ||
ReasoningReasoningInferred from PCP class pharmacology. Shorter aftereffect window than oral due to shorter total duration. No published data. Evidence basis: structural_analogy | |||
Safety
Toxicity Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Acute | low | low | low |
| Chronic | low | low | low |
| Organs Affected | cardiovascular, liver, brain | cardiovascular, liver, brain | low |
| Editorial | Classified as low (downgraded from moderate): all toxicity evidence derives from PCP class pharmacology, not rolicyclidine-specific studies. The 20-case series (Giannini et al. 1985) reported no fatalities, but sample size is insufficient for toxicity characterization. CYP mechanism-based inhibition (Brady et al. 1987) is substance-specific but studied only in rabbit microsomes. | ||
ReasoningReasoningClassified as low (downgraded from moderate): all toxicity evidence derives from PCP class pharmacology, not rolicyclidine-specific studies. The 20-case series (Giannini et al. 1985) reported no fatalities, but sample size is insufficient for toxicity characterization. CYP mechanism-based inhibition (Brady et al. 1987) is substance-specific but studied only in rabbit microsomes. Evidence basis: structural_analogy | |||
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 | All dependence data derived from PCP class primate studies (Perry et al. 2006; Carroll et al. 2009) and rodent self-administration of 4'-F-PCP (Ryu et al. 2020). No rolicyclidine-specific dependence or reinforcement studies have been published. Rated moderate (downgraded from high) due to reliance on class inference rather than substance-specific data. | ||
ReasoningReasoningAll dependence data derived from PCP class primate studies (Perry et al. 2006; Carroll et al. 2009) and rodent self-administration of 4'-F-PCP (Ryu et al. 2020). No rolicyclidine-specific dependence or reinforcement studies have been published. Rated moderate (downgraded from high) due to reliance on class inference rather than substance-specific data. Evidence basis: structural_analogy | |||
Withdrawal Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Severity | moderate | moderate | low |
| Symptoms | dysphoria, anxiety, irritability, decreased appetite, cognitive impairment, sleep disturbance | dysphoria, anxiety, irritability, decreased appetite, cognitive impairment, sleep disturbance | low |
| Fatal | No | No | low |
| Medical Supervision | Not required | Not required | low |
| Editorial | Withdrawal profile inferred from PCP primate data showing reduced operant responding and physiological disruption during withdrawal. No rolicyclidine-specific withdrawal data exist. | ||
ReasoningReasoningWithdrawal profile inferred from PCP primate data showing reduced operant responding and physiological disruption during withdrawal. No rolicyclidine-specific withdrawal data exist. Evidence basis: structural_analogy | |||
Tolerance Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Buildup | moderate | moderate | low |
| Half-life | 5 days | 5 days | low |
| Full Reset | 10 days | 10 days | low |
| Cross-tolerances | phencyclidine, ketamine, eticyclidine, tenocyclidine, 3-MeO-PCP, 3-MeO-PCE, deschloroketamine | phencyclidine, ketamine, eticyclidine, tenocyclidine, 3-MeO-PCP, 3-MeO-PCE, deschloroketamine | low |
| Editorial | No published tolerance data specific to rolicyclidine. Values carried forward from existing database (originally community-derived). Cross-tolerance supported by drug discrimination generalization data (Brady & Balster 1981). NMDA receptor upregulation mechanism inferred from class pharmacology. | ||
ReasoningReasoningNo published tolerance data specific to rolicyclidine. Values carried forward from existing database (originally community-derived). Cross-tolerance supported by drug discrimination generalization data (Brady & Balster 1981). NMDA receptor upregulation mechanism inferred from class pharmacology. Evidence basis: structural_analogy | |||
Effects & Profile
Contraindications
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| psychiatric psychotic disorderstrace | absolute | absolute | medium |
| Editorial | PHP psychosis documented in 20-case series (Giannini et al. 1985). PCP class is the pharmacological model of psychosis. Absolute contraindication supported by class-level evidence. | ||
ReasoningReasoningPHP psychosis documented in 20-case series (Giannini et al. 1985). PCP class is the pharmacological model of psychosis. Absolute contraindication supported by class-level evidence. | |||
| psychiatric bipolar disordertrace | relative | relative | low |
| Editorial | Class-level inference from PCP psychotomimetic pharmacology. No rolicyclidine-specific psychiatric comorbidity data exist. | ||
ReasoningReasoningClass-level inference from PCP psychotomimetic pharmacology. No rolicyclidine-specific psychiatric comorbidity data exist. | |||
| cardiovascular cardiovascular diseasetrace | relative | relative | low |
| Editorial | Class-level inference from PCP cardiovascular pharmacology. No rolicyclidine-specific cardiovascular data published. | ||
ReasoningReasoningClass-level inference from PCP cardiovascular pharmacology. No rolicyclidine-specific cardiovascular data published. | |||
| hepatic hepatic impairmenttrace | relative | relative | low |
| Editorial | Hepatic metabolism documented via CYP2B6 (Michely et al. 2017) and CYP inhibition (Brady et al. 1987). Contraindication is mechanistically supported but not clinically studied for rolicyclidine. | ||
ReasoningReasoningHepatic metabolism documented via CYP2B6 (Michely et al. 2017) and CYP inhibition (Brady et al. 1987). Contraindication is mechanistically supported but not clinically studied for rolicyclidine. | |||
| respiratory respiratory compromisetrace | relative | relative | low |
| Editorial | Class-level inference from PCP respiratory pharmacology. No rolicyclidine-specific respiratory data published. | ||
ReasoningReasoningClass-level inference from PCP respiratory pharmacology. No rolicyclidine-specific respiratory data published. | |||
| pregnancy breastfeeding pregnancytrace | absolute | absolute | low |
| Editorial | Class-level inference from PCP/ketamine developmental neurotoxicity animal data. No rolicyclidine-specific reproductive toxicity data exist. | ||
ReasoningReasoningClass-level inference from PCP/ketamine developmental neurotoxicity animal data. No rolicyclidine-specific reproductive toxicity data exist. | |||
| neurological epilepsytrace | relative | relative | low |
| Editorial | Class-level inference. Seizure risk documented for PCP at high doses. No rolicyclidine-specific seizure data. | ||
ReasoningReasoningClass-level inference. Seizure risk documented for PCP at high doses. No rolicyclidine-specific seizure data. | |||
Timeline Phases
oral
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Plateautrace | 3600–7200 sec(i=0.50) | 3600–7200 sec(i=0.50) | low |
| Editorial | No published human duration data exist for rolicyclidine. Timeline is inferred from community-derived oral duration estimates (onset 20-90 min, total 6-12 hours) and PCP class pharmacology. All values are unverified and require editorial review. | ||
ReasoningReasoningNo published human duration data exist for rolicyclidine. Timeline is inferred from community-derived oral duration estimates (onset 20-90 min, total 6-12 hours) and PCP class pharmacology. All values are unverified and require editorial review. | |||
| Come uptrace | 1800–3600 sec(i=0.30) | 1800–3600 sec(i=0.30) | low |
| Editorial | No published human duration data exist for rolicyclidine. Timeline is inferred from community-derived oral duration estimates (onset 20-90 min, total 6-12 hours) and PCP class pharmacology. All values are unverified and require editorial review. | ||
ReasoningReasoningNo published human duration data exist for rolicyclidine. Timeline is inferred from community-derived oral duration estimates (onset 20-90 min, total 6-12 hours) and PCP class pharmacology. All values are unverified and require editorial review. | |||
| Resolutiontrace | 3600–7200 sec(i=0.20) | 3600–7200 sec(i=0.20) | low |
| Editorial | No published human duration data exist for rolicyclidine. Timeline is inferred from community-derived oral duration estimates (onset 20-90 min, total 6-12 hours) and PCP class pharmacology. All values are unverified and require editorial review. | ||
ReasoningReasoningNo published human duration data exist for rolicyclidine. Timeline is inferred from community-derived oral duration estimates (onset 20-90 min, total 6-12 hours) and PCP class pharmacology. All values are unverified and require editorial review. | |||
| Peaktrace | 5400–10800 sec(i=1.00) | 5400–10800 sec(i=1.00) | low |
| Editorial | No published human duration data exist for rolicyclidine. Timeline is inferred from community-derived oral duration estimates (onset 20-90 min, total 6-12 hours) and PCP class pharmacology. All values are unverified and require editorial review. | ||
ReasoningReasoningNo published human duration data exist for rolicyclidine. Timeline is inferred from community-derived oral duration estimates (onset 20-90 min, total 6-12 hours) and PCP class pharmacology. All values are unverified and require editorial review. | |||
| Onsettrace | 1200–5400 sec(i=0.05) | 1200–5400 sec(i=0.05) | low |
| Editorial | No published human duration data exist for rolicyclidine. Timeline is inferred from community-derived oral duration estimates (onset 20-90 min, total 6-12 hours) and PCP class pharmacology. All values are unverified and require editorial review. | ||
ReasoningReasoningNo published human duration data exist for rolicyclidine. Timeline is inferred from community-derived oral duration estimates (onset 20-90 min, total 6-12 hours) and PCP class pharmacology. All values are unverified and require editorial review. | |||
| Afterglowtrace | 14400–43200 sec(i=0.05) | 14400–43200 sec(i=0.05) | low |
| Editorial | No published human duration data exist for rolicyclidine. Timeline is inferred from community-derived oral duration estimates (onset 20-90 min, total 6-12 hours) and PCP class pharmacology. All values are unverified and require editorial review. | ||
ReasoningReasoningNo published human duration data exist for rolicyclidine. Timeline is inferred from community-derived oral duration estimates (onset 20-90 min, total 6-12 hours) and PCP class pharmacology. All values are unverified and require editorial review. | |||
insufflated
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onsettrace | 180–1800 sec(i=0.05) | 180–1800 sec(i=0.05) | low |
| Editorial | No published human duration data exist for rolicyclidine via insufflation. Timeline inferred from community-derived estimates (onset 3-30 min, total 4-6 hours) and PCP class pharmacology for intranasal administration. All values are unverified. | ||
ReasoningReasoningNo published human duration data exist for rolicyclidine via insufflation. Timeline inferred from community-derived estimates (onset 3-30 min, total 4-6 hours) and PCP class pharmacology for intranasal administration. All values are unverified. | |||
| Come uptrace | 600–1800 sec(i=0.35) | 600–1800 sec(i=0.35) | low |
| Editorial | No published human duration data exist for rolicyclidine via insufflation. Timeline inferred from community-derived estimates (onset 3-30 min, total 4-6 hours) and PCP class pharmacology for intranasal administration. All values are unverified. | ||
ReasoningReasoningNo published human duration data exist for rolicyclidine via insufflation. Timeline inferred from community-derived estimates (onset 3-30 min, total 4-6 hours) and PCP class pharmacology for intranasal administration. All values are unverified. | |||
| Peaktrace | 3600–5400 sec(i=1.00) | 3600–5400 sec(i=1.00) | low |
| Editorial | No published human duration data exist for rolicyclidine via insufflation. Timeline inferred from community-derived estimates (onset 3-30 min, total 4-6 hours) and PCP class pharmacology for intranasal administration. All values are unverified. | ||
ReasoningReasoningNo published human duration data exist for rolicyclidine via insufflation. Timeline inferred from community-derived estimates (onset 3-30 min, total 4-6 hours) and PCP class pharmacology for intranasal administration. All values are unverified. | |||
| Plateautrace | 1800–3600 sec(i=0.50) | 1800–3600 sec(i=0.50) | low |
| Editorial | No published human duration data exist for rolicyclidine via insufflation. Timeline inferred from community-derived estimates (onset 3-30 min, total 4-6 hours) and PCP class pharmacology for intranasal administration. All values are unverified. | ||
ReasoningReasoningNo published human duration data exist for rolicyclidine via insufflation. Timeline inferred from community-derived estimates (onset 3-30 min, total 4-6 hours) and PCP class pharmacology for intranasal administration. All values are unverified. | |||
| Resolutiontrace | 1800–3600 sec(i=0.20) | 1800–3600 sec(i=0.20) | low |
| Editorial | No published human duration data exist for rolicyclidine via insufflation. Timeline inferred from community-derived estimates (onset 3-30 min, total 4-6 hours) and PCP class pharmacology for intranasal administration. All values are unverified. | ||
ReasoningReasoningNo published human duration data exist for rolicyclidine via insufflation. Timeline inferred from community-derived estimates (onset 3-30 min, total 4-6 hours) and PCP class pharmacology for intranasal administration. All values are unverified. | |||
| Afterglowtrace | 7200–28800 sec(i=0.05) | 7200–28800 sec(i=0.05) | low |
| Editorial | No published human duration data exist for rolicyclidine via insufflation. Timeline inferred from community-derived estimates (onset 3-30 min, total 4-6 hours) and PCP class pharmacology for intranasal administration. All values are unverified. | ||
ReasoningReasoningNo published human duration data exist for rolicyclidine via insufflation. Timeline inferred from community-derived estimates (onset 3-30 min, total 4-6 hours) and PCP class pharmacology for intranasal administration. All values are unverified. | |||
Dose Tier Summaries
At threshold doses, effects are barely perceptible: a subtle shift in bodily awareness, mild lightness or heaviness in the limbs, and a faint sense of detachment from immediate surroundings. Cognitive changes are minimal — slight slowing of thought or a vague sense that perception has shifted without clear alteration. Physically, mild numbness or tingling may be noticed, particularly in the extremities and face. Coordination is not meaningfully impaired at this level. These doses produce effects that could easily be attributed to placebo or fatigue. No published human data confirm the threshold range for rolicyclidine specifically.
No published human dose data exist for rolicyclidine. Threshold described by structural analogy to PCP class dissociatives and community-derived estimates. Existing database suggests ~1 mg oral threshold.
ReasoningReasoning
No published human dose data exist for rolicyclidine. Threshold described by structural analogy to PCP class dissociatives and community-derived estimates. Existing database suggests ~1 mg oral threshold.
Evidence basis: structural_analogy
Light doses produce a recognizable dissociative state: mild depersonalization, slight derealization, and a sense of distance from the body and environment. Thought becomes somewhat disconnected, with occasional lapses in short-term memory. Mild euphoria and mood elevation are typical. Physical effects include noticeable numbness and analgesia, mild ataxia (unsteady gait), and slight nystagmus. Speech may become mildly slurred. Nausea is possible but uncommon at this range. Functional impairment is present but manageable. The experience is recognizably dissociative without being overwhelming.
Inferred from PCP class pharmacology and community-derived dose ranges. No published rolicyclidine-specific human dosing data. Existing database suggests light range of 2-3 mg oral.
ReasoningReasoning
Inferred from PCP class pharmacology and community-derived dose ranges. No published rolicyclidine-specific human dosing data. Existing database suggests light range of 2-3 mg oral.
Evidence basis: structural_analogy
At common doses, a full dissociative experience emerges: pronounced depersonalization and derealization, distortion of body perception (body parts may feel enlarged, shrunken, or absent), and significant time distortion. Thought disorganization increases, with loose associations and impaired ability to maintain a coherent train of thought. Euphoria may be prominent. Auditory and visual distortions occur — sounds may seem distant or distorted, and visual field may appear flattened or tunnel-like. Physically, marked ataxia and motor impairment are expected. Analgesia is substantial. Nystagmus, tachycardia, and mild hypertension are typical PCP-class effects at this range. Nausea and vomiting are possible. Speech is significantly impaired. The individual is clearly intoxicated and should not attempt activities requiring coordination or judgment.
Inferred from PCP class pharmacology, clinical case reports describing PCP-like psychotomimetic effects (Giannini et al. 1985), and community-derived dose ranges. Existing database suggests common range of 4-8 mg oral.
ReasoningReasoning
Inferred from PCP class pharmacology, clinical case reports describing PCP-like psychotomimetic effects (Giannini et al. 1985), and community-derived dose ranges. Existing database suggests common range of 4-8 mg oral.
Evidence basis: structural_analogy
Strong doses produce profound dissociation approaching the 'dissociative hole' state: near-complete detachment from the body, loss of environmental awareness, intense derealization, and ego dissolution. Internal hallucinations — both visual and auditory — may dominate the experience. Thought becomes severely disorganized, and amnesia for portions of the experience is likely. Motor impairment is severe: ambulation is dangerous or impossible. Analgesia is profound, masking potential injury. Tachycardia, hypertension, and hyperthermia become more pronounced. Risk of nausea and vomiting increases. Psychological distress, paranoia, and agitation are significantly more likely at this range. The psychotomimetic presentation documented in PHP case reports — hallucinations, agitation, disorganized thinking — is consistent with strong-dose PCP-class effects.
Inferred from PCP class pharmacology and clinical case reports of PHP intoxication (Giannini & Castellani 1982; Giannini et al. 1985). Existing database suggests strong range of 8-12 mg oral.
ReasoningReasoning
Inferred from PCP class pharmacology and clinical case reports of PHP intoxication (Giannini & Castellani 1982; Giannini et al. 1985). Existing database suggests strong range of 8-12 mg oral.
Evidence basis: structural_analogy
Heavy doses carry significant medical risk. Complete dissociation from the body and environment is expected, with total loss of motor control and environmental responsiveness. Amnesia is near-total. The experience may involve intense internal hallucinations or complete loss of conscious awareness. Cardiovascular stress (severe hypertension, tachycardia), respiratory depression, hyperthermia, and risk of seizures represent the primary acute dangers at this range. Rhabdomyolysis from sustained muscular rigidity is possible. The psychotomimetic state may persist for hours and can present as an acute psychiatric emergency indistinguishable from PCP overdose. Medical monitoring is strongly advisable. Risk of serious adverse outcome increases sharply above the strong dose range.
Inferred from PCP class toxicology and the absence of published rolicyclidine-specific lethal dose data. Existing database suggests heavy threshold at ~14 mg oral. All values are unverified community estimates.
ReasoningReasoning
Inferred from PCP class toxicology and the absence of published rolicyclidine-specific lethal dose data. Existing database suggests heavy threshold at ~14 mg oral. All values are unverified community estimates.
Evidence basis: structural_analogy
History
backfill Jun 4, 2026
Historical versions do not record which reviewer approved them; editorial accountability is recorded per value in the database and in the publication ledger going forward.
Sources
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- [2]weakRolicyclidine - NCATS Inxight DrugsNational Center for Advancing Translational Sciences · 2023linkno claims checked
- [3]weakPHP, a new drug of abuse.Budd RD · 1980 · The New England Journal of Medicinepubmed 74022312 claims checked2 inconclusive
- [4]moderateMechanism-based inhibition of cytochrome P-450 by heterocyclic analogues of phencyclidine.Brady JF, Dokko J, Di Stefano EW, Cho AK · 1987 · Drug Metabolism and Dispositionpubmed 28914819 claims checked6 verified2 partial1 inconclusive
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- [6]weakA case of phenylcyclohexylpyrrolidine (PHP) intoxication treated with physostigmine.Giannini AJ, Castellani S · 1982 · Journal of Toxicology. Clinical Toxicologypubmed 71759967 claims checked7 verified
- [7]weakTreatment of phenylcyclohexylpyrrolidine (PHP) psychosis with haloperidol.Giannini AJ, Price WA, Loiselle RH, Malone DW · 1985 · Journal of Toxicology. Clinical Toxicologypubmed 40573127 claims checked5 verified2 inconclusive
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- [19]moderateQualitative confirmation of 30 phencyclidine analogs in human blood and urine using GC-HRMS and a self-built library searchSong Z, Guo Z, Tang Y, Zhang M, Xiang P, Liu W, Yan H · 2025 · Journal of Chromatography B
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- [21]moderateThe Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4'-F-PCP) in RodentsRyu IS, Kim OH, Lee YE, et al. · 2020 · International Journal of Molecular Sciences
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 claims6verified1partial1inconclusive
partialIn behavioral pharmacology, rolicyclidine occupies an intermediate position among PCP analogues — more potent than ketamine and the morpholine analogue (PCM) but less potent than PCP and eticyclidine (PCE) in both discriminative stimulus and operant suppression assays[1]model confidence 82%
The discriminative stimulus potency ranking (TCP > PCP = PCE > PHP > PCM > ketamine) directly confirms rolicyclidine's intermediate position. However, the abstract only reports drug-lever responding data; 'operant suppression assays' is a second specific assertion not present in the abstract.
Relative potency for drug-lever responding: TCP > PCP = PCE > PHP > PCM > ketamine.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveSynthesized in 1958 by Parke-Davis chemists, rolicyclidine was never developed for medical use and appeared briefly on US illicit markets in the late 1970s as a PCP substitute[3]model confidence 50%
Abstract not available for this case report.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedIts current significance is limited to structure-activity relationship studies of the arylcyclohexylamine series and its documented role as a substrate in cytochrome P450 mechanism-based inhibition research.[4]model confidence 85%
The abstract directly confirms mechanism-based CYP inhibition for PCPY (rolicyclidine) and PCP analogues, establishing its documented role in CYP inhibition research.
PCPY and PCP analogues cause mechanism-based CYP inhibition.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedAs an arylcyclohexylamine, rolicyclidine is presumed to act through use-dependent blockade of the NMDA receptor ion channel pore, with secondary activity at sigma receptors and the dopamine transporter inferred from class pharmacology[5]model confidence 78%
The abstract confirms sigma binding sites have affinity for PCP analogues and that NMDA receptor blockade is the physiologically significant effect for the PCP receptor. The dopamine transporter is inferred from class pharmacology as the claim states.
PCP receptor has preferential affinity for PCP analogues and non-competitive NMDA antagonists. Physiological significance associated with blockade of NMDA receptor.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedClinical case reports describe a psychotomimetic syndrome indistinguishable from PCP intoxication — hallucinations, agitation, disorganized thinking, and motor impairment — with presentation and treatment response closely paralleling PCP psychosis[6]model confidence 80%
The abstract confirms neurological and psychic symptoms following PHP ingestion in a clinical case, documenting treatment response. The claim about similarity to PCP is supported further by the parallel treatment response.
A case is presented of a 31-year-old male who showed neurological and psychic symptoms following ingestion of phenylcyclohexylpyrrolidine (PHP).
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedClinical case reports describe a psychotomimetic syndrome indistinguishable from PCP intoxication — hallucinations, agitation, disorganized thinking, and motor impairment — with presentation and treatment response closely paralleling PCP psychosis[7]model confidence 90%
The abstract explicitly states that results of haloperidol treatment of PHP psychosis 'were similar to previously published reports with phencyclidine (PCP) psychosis,' directly confirming parallel clinical presentation and treatment response.
Results of haloperidol treatment of PHP psychosis were similar to previously published reports with phencyclidine (PCP) psychosis.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedNo controlled toxicity data exist for rolicyclidine — no LD₅₀, therapeutic index, or human lethal dose has been published. The compound is a documented mechanism-based inhibitor of hepatic cytochrome P450 enzymes, creating pharmacokinetic drug-drug interaction risk atypical among recreational dissociatives[4]model confidence 85%
The abstract confirms PCPY (rolicyclidine) is a mechanism-based CYP inhibitor, supporting the drug-drug interaction risk claim. Absence of toxicity data is consistent with the paper's narrow focus on CYP inhibition.
PCPY and PCP analogues cause mechanism-based CYP inhibition. NADPH-dependent; requires substituted nitrogen in heterocyclic ring.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedDependence liability is inferred from PCP-class primate studies demonstrating physical dependence and reinforcing properties[9]model confidence 82%
The abstract confirms PCP physical dependence in primates through measurable withdrawal. Reinforcing properties are inferred from class pharmacology as the claim states.
Males show greater PCP withdrawal severity than females in primates.
checked by claude-sonnet-4-6 · Apr 26, 2026
history4 claims1verified3inconclusive
inconclusiveThe compound belongs to the 1-arylcyclohexylamine series whose general synthesis was formally reported by Maddox, Godefroi, and Parcell in 1965model confidence 50%
Abstract not available for this landmark synthesis paper.
source: The Synthesis of Phencyclidine and Other 1-Arylcyclohexylamines
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveThe synthetic route proceeds from cyclohexanone precursors via Mannich-type reactions with pyrrolidine as the secondary amine; phenylmagnesium bromide introduces the aryl group via Grignard additionmodel confidence 50%
Abstract not available for this landmark synthesis paper.
source: The Synthesis of Phencyclidine and Other 1-Arylcyclohexylamines
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveBudd published the first identification of PHP (phenylcyclohexylpyrrolidine) as a new drug of abuse in the New England Journal of Medicine in 1980[3]model confidence 50%
Abstract not available for this case report.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedClinical case reports from Giannini and colleagues subsequently documented the drug's psychotomimetic effects and treatment responses: a single case of PHP intoxication treated with physostigmine was reported in 1982, followed by a series of 20 PHP psychosis cases treated with haloperidol in 1985[6]model confidence 82%
The abstract directly confirms this is a case report of a single PHP intoxication treated with physostigmine, supporting the physostigmine-case portion of the claim. The 1982 date is not confirmed in the abstract.
A case is presented of a 31-year-old male who showed neurological and psychic symptoms following ingestion of phenylcyclohexylpyrrolidine (PHP)... Treatment with physostigmine (IM) produced a rapid and sustained reversal.
checked by claude-sonnet-4-6 · Apr 26, 2026
chemistry1 claim1inconclusive
inconclusiveIn rolicyclidine, the amine is incorporated into a five-membered pyrrolidine ring, distinguishing it from PCP (six-membered piperidine) and PCM (six-membered morpholine)model confidence 50%
Abstract not available for this landmark synthesis paper.
source: The Synthesis of Phencyclidine and Other 1-Arylcyclohexylamines
checked by claude-sonnet-4-6 · Apr 26, 2026
pharmacology10 claims6verified2partial2inconclusive
verifiedRolicyclidine is a non-competitive NMDA receptor antagonist that binds at the phencyclidine site within the ion channel pore of the NMDA receptor complex[13]model confidence 78%
The abstract confirms PCP-like drugs inhibit NMDA-stimulated neurotransmitter release via the PCP-sigma receptor and establishes an allosteric link with the NMDA receptor, consistent with non-competitive NMDA antagonism at the PCP site.
PCP-like drugs inhibit NMDA-stimulated ACh and DA release via PCP-sigma receptor. Allosteric link between PCP-sigma receptor and NMDA receptor suggested.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveBlockade is use-dependent: the channel must be in the open (activated) state for the drug to access the binding site, meaning glutamate and glycine co-agonism at the NMDA receptor potentiates channel opening and thereby enhances access to the PCP site[13]model confidence 60%
The abstract mentions NMDA-stimulated inhibition consistent with activity-dependence, but the specific open-channel blocking mechanism and requirement for glutamate/glycine co-agonism are not described. This mechanistic detail is not confirmable from the abstract.
PCP-like drugs inhibit NMDA-stimulated ACh and DA release via PCP-sigma receptor.
checked by claude-sonnet-4-6 · Apr 26, 2026
partialRolicyclidine is also classified as a sigma receptor agonist and dopamine reuptake inhibitor, consistent with the pharmacological profile of arylcyclohexylamines as a class[5]model confidence 72%
The abstract confirms sigma receptor activity for PCP analogues. However, dopamine reuptake inhibition is not mentioned anywhere in the abstract; this is a specific pharmacological classification not verified by this source.
Sigma binding sites have preferential affinity for benzomorphan opiates. PCP receptor has preferential affinity for PCP analogues and non-competitive NMDA antagonists.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedAmong PCP analogues studied, rolicyclidine generates the largest proportion of PCA relative to PCP and other ring-size variants.[14]model confidence 95%
The abstract directly states the pyrrolidine analogue (rolicyclidine) generated the largest proportion of PCA among the analogues studied.
Pyrrolidine analogue generated largest proportion of PCA.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedMetabolic pathway data from the closely related compound 3-methoxyrolicyclidine (3-MeO-PCPy) identify multiple aliphatic hydroxylations at the cyclohexyl and pyrrolidine rings, a single aromatic hydroxylation, carboxylation following ring opening, and glucuronidation of hydroxylated metabolites[15]model confidence 97%
The abstract directly confirms all listed metabolic pathways: multiple aliphatic hydroxylations at cyclohexyl and pyrrolidine rings, aromatic hydroxylation, carboxylation after ring opening, and glucuronidation.
multiple aliphatic hydroxylations at cyclohexyl and pyrrolidine rings, aromatic hydroxylation, carboxylation after ring opening, O-demethylation, glucuronidation.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedCYP2B6 catalyzes aliphatic hydroxylations, while CYP2C9 and CYP2D6 catalyze O-demethylation in the methoxylated analogue[15]model confidence 97%
The abstract directly confirms CYP2B6 for aliphatic hydroxylations and CYP2C9 and CYP2D6 for O-demethylation.
CYP2B6 for aliphatic hydroxylations; CYP2C9 and CYP2D6 for O-demethylation.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedCYP2B6 is likely the primary enzyme for aliphatic hydroxylation; CYP3A4 involvement is inferred from human liver microsome studies of the parent compound PCP.[16]model confidence 90%
The abstract confirms CYP3A plays a major role in PCP metabolism in human liver microsomes, directly supporting the inference about CYP3A4 from PCP metabolism studies.
CYP3A major role in PCP metabolism in human liver microsomes.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedRolicyclidine causes mechanism-based (irreversible) inhibition of cytochrome P450 enzymes[4]model confidence 97%
The abstract directly confirms PCPY (rolicyclidine) causes mechanism-based CYP inhibition.
PCPY and PCP analogues cause mechanism-based CYP inhibition.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveIn phenobarbital-induced rabbit liver microsomes, preincubation with rolicyclidine reduced CYP-dependent N-demethylation activity in a process that was NADPH-dependent, associated with reduced CO binding to microsomes, and followed pseudo-first-order kinetics[4]model confidence 65%
The abstract confirms NADPH-dependence for the mechanism-based CYP inhibition, but the specific details about phenobarbital-induced rabbit liver microsomes, N-demethylation activity, CO binding reduction, and pseudo-first-order kinetics are not present in the abstract and may only be in the full text.
PCPY and PCP analogues cause mechanism-based CYP inhibition. NADPH-dependent; requires substituted nitrogen in heterocyclic ring.
checked by claude-sonnet-4-6 · Apr 26, 2026
partialThe mechanism requires a substituted nitrogen within a heterocyclic ring; the cyclic carbinolamine intermediate formed during alpha-carbon oxidation is implicated as the species responsible for enzyme inactivation.[4]model confidence 75%
The abstract directly confirms the structural requirement for a substituted nitrogen in a heterocyclic ring. However, the cyclic carbinolamine intermediate as the responsible species is not mentioned in the abstract and cannot be verified from it.
requires substituted nitrogen in heterocyclic ring.
checked by claude-sonnet-4-6 · Apr 26, 2026
neuroscience5 claims2verified3inconclusive
inconclusiveNMDA receptor hypofunction — whether induced pharmacologically by arylcyclohexylamines or occurring endogenously in disease states — produces a symptom constellation closely resembling schizophrenia, including positive symptoms (hallucinations, delusions), negative symptoms (withdrawal, flat affect), and cognitive deficits[17]model confidence 50%
The abstract is a general NPS review covering dissociatives and their effects. The specific claim about NMDA hypofunction producing schizophrenia-like symptoms including positive, negative, and cognitive symptom clusters is not mentioned in the abstract.
Review of novel psychoactive substances (NPS) including dissociatives similar to ketamine and PCP. Covers pharmacodynamics, subjective/physical effects, harmfulness, and dependency risk for each class.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveNMDA receptor antagonism in the PCP class disrupts corticocortical and thalamocortical signaling, producing the characteristic dissociative state — a functional disconnection between sensory processing and higher-order cortical integration[8]model confidence 50%
The review abstract covers mechanisms of dissociative NMDA antagonists but does not specifically describe corticocortical and thalamocortical signaling disruption. This circuit-level mechanistic detail is not confirmable from the abstract.
Comprehensive review of designer drug mechanisms including dissociative NMDA receptor antagonists.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveDopamine reuptake inhibition, documented for PCP-class arylcyclohexylamines, contributes to mesolimbic reward pathway activation (ventral tegmental area to nucleus accumbens)[5]model confidence 50%
The abstract focuses on sigma binding sites and the PCP receptor as NMDA antagonists. There is no mention of dopamine reuptake or mesolimbic pathways. As a review about sigma receptors, this specific dopaminergic mechanism claim is outside the abstract's stated scope.
Sigma binding sites in the brain; an emerging concept for multiple sites and their relevance for psychiatric disorders.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe structural analogue 4'-F-PCP demonstrates robust self-administration behavior in rodents through dopaminergic mechanisms in the nucleus accumbens, supporting a dopaminergic component to the reinforcing and euphorigenic properties of the arylcyclohexylamine class.[21]model confidence 95%
The abstract directly confirms 4'-F-PCP has high abuse potential via dopaminergic mechanisms in the nucleus accumbens with altered DAT and D1 receptor expression.
4'-F-PCP has high abuse potential via dopaminergic mechanisms in NAc. DAT and D1 receptor expression altered.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe reversal of PHP psychosis by physostigmine in one case report implicates cholinergic neurotransmission in the expression of PCP-class psychotomimesis, though the mechanism remains unclear and the observation has not been replicated.[6]model confidence 88%
The abstract confirms physostigmine IM produced rapid and sustained reversal of PHP symptoms in one case. The cholinergic implication is a direct pharmacological inference from physostigmine's mechanism (cholinesterase inhibition).
Treatment with physostigmine (IM) produced a rapid and sustained reversal of these symptoms.
checked by claude-sonnet-4-6 · Apr 26, 2026
receptor pharmacology4 claims3verified1not supported
verifiedThe only quantitative potency data derive from drug discrimination studies in squirrel monkeys:[1]model confidence 78%
The abstract is from a squirrel monkey drug discrimination study that provides quantitative potency ranking data, correctly identifying this study as a source of quantitative data for rolicyclidine's potency.
Squirrel monkeys trained to discriminate PCP from saline. PHP and four other analogues generalized to PCP with dose-dependent responding.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedTCP > PCP = PCE > PHP (rolicyclidine) > PCM > ketamine[1]model confidence 98%
The abstract exactly matches this ranking for drug-lever responding.
Relative potency for drug-lever responding: TCP > PCP = PCE > PHP > PCM > ketamine.
checked by claude-sonnet-4-6 · Apr 26, 2026
not supportedPCP = TCP > PHP > PCE > PCM > ketamine[1]model confidence 97%
cited source's abstract does not support this claim — flagged for editorial review
The abstract's ranking (TCP > PCP = PCE > PHP > PCM > ketamine) materially contradicts the claim. In the abstract, PCE equals PCP and is more potent than PHP — the claim incorrectly places PCE below PHP. Additionally, the claim equates PCP and TCP whereas the abstract shows TCP > PCP.
Relative potency for drug-lever responding: TCP > PCP = PCE > PHP > PCM > ketamine.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedRolicyclidine is thus intermediate in potency among the arylcyclohexylamine series — more potent than ketamine and the morpholine analogue (PCM), less potent than PCP and eticyclidine (PCE)[1]model confidence 97%
The abstract's ranking (TCP > PCP = PCE > PHP > PCM > ketamine) directly confirms rolicyclidine is more potent than ketamine and PCM, and less potent than PCP and PCE.
Relative potency for drug-lever responding: TCP > PCP = PCE > PHP > PCM > ketamine.
checked by claude-sonnet-4-6 · Apr 26, 2026
pharmacokinetic detail6 claims5verified1inconclusive
verifiedPrimary metabolism proceeds through CYP2B6-catalyzed aliphatic hydroxylation, based on data from the closely related 3-methoxyrolicyclidine[15]model confidence 95%
The abstract directly confirms CYP2B6 catalyzes aliphatic hydroxylations in 3-MeO-PCPy (3-methoxyrolicyclidine).
CYP2B6 for aliphatic hydroxylations.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedCYP3A4 involvement is inferred from PCP metabolism in human liver microsomes[16]model confidence 95%
The abstract directly confirms CYP3A plays a major role in PCP metabolism in human liver microsomes.
CYP3A major role in PCP metabolism in human liver microsomes.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedRolicyclidine is itself a mechanism-based CYP inhibitor, which may prolong its own elimination and that of co-administered drugs in a dose-dependent manner.[4]model confidence 87%
The abstract directly confirms mechanism-based CYP inhibition for PCPY. The self-inhibition and prolonged elimination consequences are standard pharmacological inferences from mechanism-based CYP inhibition.
PCPY and PCP analogues cause mechanism-based CYP inhibition. NADPH-dependent.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe mechanism-based (irreversible) CYP inhibition documented for rolicyclidine creates a pharmacokinetic interaction risk atypical of most recreational dissociatives[4]model confidence 85%
The abstract directly documents mechanism-based (irreversible) CYP inhibition for rolicyclidine. The claim about this being atypical among recreational dissociatives is a reasonable inference not contradicted by the abstract.
PCPY and PCP analogues cause mechanism-based CYP inhibition.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveRolicyclidine is not detected by standard immunoassay PCP screens, which target PCP itself[19]model confidence 55%
The abstract describes a specialized GC-HRMS method for detecting PCP analogues, implying standard methods are insufficient, but never explicitly states that rolicyclidine is missed by immunoassay PCP screens.
Novel GC-HRMS method for identification of 30 PCP analogues in blood and urine.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedConfirmatory identification requires GC-HRMS or targeted LC-MS/MS methods[19]model confidence 85%
The abstract describes the development of a GC-HRMS method specifically for identifying 30 PCP analogues, directly supporting the need for this type of confirmatory methodology.
Novel GC-HRMS method for identification of 30 PCP analogues in blood and urine.
checked by claude-sonnet-4-6 · Apr 26, 2026
effects overview4 claims4verified
verifiedThe experiential profile is reconstructed entirely from clinical case reports of illicit intoxication and behavioral pharmacology in non-human primates[6]model confidence 88%
This abstract is a clinical case report of illicit PHP intoxication, directly representing one of the two cited data source types (clinical case reports).
A case is presented of a 31-year-old male who showed neurological and psychic symptoms following ingestion of phenylcyclohexylpyrrolidine (PHP).
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe experiential profile is reconstructed entirely from clinical case reports of illicit intoxication and behavioral pharmacology in non-human primates[7]model confidence 88%
This abstract represents a clinical case series of illicit PHP intoxication, one of the two cited data source types.
Twenty white males who presented with psychosis were later found to have ingested PHP.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe experiential profile is reconstructed entirely from clinical case reports of illicit intoxication and behavioral pharmacology in non-human primates[1]model confidence 92%
This abstract is behavioral pharmacology in non-human primates (squirrel monkeys), directly representing the second cited data source type.
Squirrel monkeys trained to discriminate PCP from saline. PHP and four other analogues generalized to PCP with dose-dependent responding.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedRolicyclidine's experiential character is expected to fall between ketamine and PCP in intensity at equipotent doses, consistent with its intermediate behavioral potency in the arylcyclohexylamine series[1]model confidence 88%
The potency ranking (PCP = PCE > PHP > ketamine) directly supports the inference that rolicyclidine's effects fall between those of PCP and ketamine at comparable doses.
Relative potency for drug-lever responding: TCP > PCP = PCE > PHP > PCM > ketamine.
checked by claude-sonnet-4-6 · Apr 26, 2026
safety14 claims11verified1partial1inconclusive1not supported
verifiedPCP-class drugs carry established risks of psychosis, cardiovascular stimulation, and respiratory depression at high doses; rolicyclidine-specific incidence data are absent[8]model confidence 75%
The abstract is a comprehensive review covering adverse effects and health risks of dissociative NMDA receptor antagonists, the right class for this claim.
Comprehensive review of designer drug mechanisms including dissociative NMDA receptor antagonists. Covers adverse effects and health risks.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedNo LD₅₀ or human lethal dose data have been published for rolicyclidine. Acute toxicity is inferred from PCP class pharmacology: cardiovascular stimulation (hypertension, tachycardia), respiratory depression at high doses, hyperthermia, and rhabdomyolysis are documented for PCP and are plausibly applicable to rolicyclidine.[8]model confidence 75%
This comprehensive designer drug review covers mechanisms and adverse effects of dissociative NMDA antagonists. The class-level toxicity claim (cardiovascular, respiratory, etc.) falls squarely within the review's stated scope.
Comprehensive review of designer drug mechanisms including dissociative NMDA receptor antagonists. Covers adverse effects and health risks.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveThe published case series of 20 PHP intoxications reported no fatalities[7]model confidence 55%
The abstract describes successful treatment of 20 cases but does not explicitly state that no fatalities occurred. The claim requires more detail than is available in the abstract.
Twenty white males who presented with psychosis were later found to have ingested PHP. Treatment with haloperidol 5 mg IM caused significant improvement.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedIn a single case, physostigmine produced rapid symptom reversal, suggesting anticholinergic-like features in the acute toxidrome.[6]model confidence 90%
The abstract directly confirms physostigmine IM produced rapid and sustained reversal. The inference about anticholinergic-like features is a standard clinical interpretation of physostigmine efficacy.
Treatment with physostigmine (IM) produced a rapid and sustained reversal of these symptoms.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedRolicyclidine's mechanism-based inhibition of hepatic CYP enzymes introduces a toxicity dimension not shared by most recreational dissociatives[4]model confidence 82%
The abstract directly confirms mechanism-based CYP inhibition by rolicyclidine. The claim that this is atypical among recreational dissociatives is a reasonable inference not contradicted by the abstract.
PCPY and PCP analogues cause mechanism-based CYP inhibition.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedPCP-class dissociatives are established precipitants of acute psychosis, characterized by hallucinations, paranoid ideation, agitation, and disorganized behavior[7]model confidence 88%
The abstract confirms 20 cases of psychosis following PHP (PCP-class) ingestion and successful antipsychotic treatment, establishing PHP as a precipitant of acute psychosis.
Twenty white males who presented with psychosis were later found to have ingested PHP.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedPCP-class dissociatives are established precipitants of acute psychosis, characterized by hallucinations, paranoid ideation, agitation, and disorganized behavior[17]model confidence 75%
The review covers pharmacodynamics and subjective/physical effects of PCP-like dissociatives, which includes psychotomimetic effects. Right topic for this general claim.
Review of novel psychoactive substances (NPS) including dissociatives similar to ketamine and PCP. Covers pharmacodynamics, subjective/physical effects, harmfulness, and dependency risk for each class.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedPHP-induced psychosis is clinically indistinguishable from PCP psychosis in presentation[7]model confidence 88%
The abstract explicitly states that haloperidol treatment results for PHP psychosis 'were similar to previously published reports with phencyclidine (PCP) psychosis,' directly supporting clinical indistinguishability.
Results of haloperidol treatment of PHP psychosis were similar to previously published reports with phencyclidine (PCP) psychosis.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedViolence and self-injury during PCP-class intoxication are recognized risks, driven by the combination of psychotomimesis, motor disinhibition, and analgesia[8]model confidence 73%
The comprehensive designer drug review covers adverse effects and health risks of dissociative NMDA antagonists, which includes behavioral risks during intoxication.
Comprehensive review of designer drug mechanisms including dissociative NMDA receptor antagonists. Covers adverse effects and health risks.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedOral PCP self-administration in rhesus monkeys produces physical dependence with measurable withdrawal, and males show greater withdrawal severity than females[9]model confidence 95%
The abstract directly confirms both that PCP causes physical dependence with withdrawal in primates and that males show greater withdrawal severity than females.
Males show greater PCP withdrawal severity than females in primates. PCP intake equal when weight normalized.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedPCP withdrawal reduces operant responding maintained by food reinforcement, indicating physiological disruption beyond psychological craving[20]model confidence 95%
The abstract directly confirms withdrawal of PCP reduces operant responding maintained by food, demonstrating dependence.
Withdrawal of PCP reduces operant responding maintained by food, demonstrating dependence.
checked by claude-sonnet-4-6 · Apr 26, 2026
not supportedHigh-affinity NMDA antagonists including PCP function as reinforcers in intravenous self-administration paradigms.[16]model confidence 95%
cited source's abstract does not support this claim — flagged for editorial review
The abstract is entirely about CYP3A-mediated PCP metabolism in human liver microsomes. It contains no information about self-administration, reinforcing properties, or IV drug paradigms — an entirely different topic.
CYP3A major role in PCP metabolism in human liver microsomes. Multiple metabolites with significant inter-individual variation.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedCross-tolerance among PCP-class dissociatives is supported by full generalization in drug discrimination paradigms — consistent with shared NMDA open-channel blockade as the common mechanism driving both tolerance and cross-tolerance[1]model confidence 85%
The abstract confirms full generalization of PHP and four other analogues to PCP in drug discrimination, directly supporting cross-tolerance. The NMDA open-channel blockade mechanism is stated as consistent inference.
PHP and four other analogues generalized to PCP with dose-dependent responding.
checked by claude-sonnet-4-6 · Apr 26, 2026
partialRolicyclidine's mechanism-based CYP inhibition creates the most pharmacologically distinctive interaction risk among PCP analogues[4]model confidence 70%
The abstract confirms mechanism-based CYP inhibition for rolicyclidine but also shows that PCP has equal or greater inactivation rates (PCP >= PCPY). The claim that rolicyclidine creates 'the most' distinctive CYP interaction risk is not supported — PCP is at least equally potent as a mechanism-based inhibitor.
Relative rates of inactivation: PCP >= PCPY > PCHMI.
checked by claude-sonnet-4-6 · Apr 26, 2026
clinical evidence4 claims3verified1inconclusive
inconclusiveNo fatalities were reported in the published series.[7]model confidence 55%
The abstract describes 20 cases with significant improvement from haloperidol treatment, implying survival, but never explicitly states that no fatalities occurred. The absence of fatalities claim requires data not present in the abstract.
Twenty white males who presented with psychosis were later found to have ingested PHP. Treatment with haloperidol 5 mg IM caused significant improvement.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedGiannini and Castellani (1982) reported a single case of PHP intoxication presenting with psychosis and motor impairment[6]model confidence 88%
The abstract confirms a single case of PHP intoxication with neurological (motor impairment) and psychic (psychosis) symptoms. The 1982 date is not confirmed in the abstract itself.
A case is presented of a 31-year-old male who showed neurological and psychic symptoms following ingestion of phenylcyclohexylpyrrolidine (PHP).
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedPhysostigmine administered intramuscularly produced rapid and sustained reversal of symptoms, suggesting anticholinergic-like features in the toxidrome[6]model confidence 93%
The abstract directly confirms physostigmine IM produced a rapid and sustained reversal of symptoms. The anticholinergic-like inference is standard from physostigmine's mechanism of action.
Treatment with physostigmine (IM) produced a rapid and sustained reversal of these symptoms.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedGiannini et al. (1985) published a series of 20 cases of PHP-induced psychosis[7]model confidence 93%
The abstract directly confirms 20 males who presented with psychosis after PHP ingestion, matching the described case series.
Twenty white males who presented with psychosis were later found to have ingested PHP.
checked by claude-sonnet-4-6 · Apr 26, 2026
comparative pharmacology4 claims3verified1inconclusive
verifiedThe following table summarizes the relative potency ranking from drug discrimination studies in squirrel monkeys:[1]model confidence 97%
The abstract provides the relative potency ranking from squirrel monkey drug discrimination studies, directly confirming this as the source of the tabulated data.
Squirrel monkeys trained to discriminate PCP from saline. Relative potency for drug-lever responding: TCP > PCP = PCE > PHP > PCM > ketamine.
checked by claude-sonnet-4-6 · Apr 26, 2026
inconclusiveThe dose required to suppress operant behavior was 3–5 times higher than the discrimination ED₅₀ across all analogues, indicating a consistent dissociation between subjective-like effects and motor impairment throughout the series.[1]model confidence 55%
The abstract only reports drug-lever responding (discriminative stimulus) data with a potency ranking. There is no mention of operant suppression doses or a 3–5× ratio in the abstract; this detail would need to be in the full paper.
Squirrel monkeys trained to discriminate PCP from saline. PHP and four other analogues generalized to PCP with dose-dependent responding.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedThe morpholine analogue 3-MeO-PCMo shows NMDA affinity approximately 12-fold lower than PCP[18]model confidence 97%
The abstract directly states 3-MeO-PCMo has moderate NMDA affinity approximately 12-fold lower than PCP.
3-MeO-PCMo has moderate NMDA affinity comparable to ketamine, ~12-fold lower than PCP.
checked by claude-sonnet-4-6 · Apr 26, 2026
verifiedRolicyclidine is distinguished from other PCP analogues by generating the largest proportion of phenylcyclohexylamine (PCA) during alpha-carbon oxidation — a metabolic consequence of the pyrrolidine ring's susceptibility to sequential alpha-hydroxylation[14]model confidence 93%
The abstract directly confirms the pyrrolidine analogue generated the largest proportion of PCA, and that alpha-hydroxylation is the dominant pathway with all congeners forming PCA via second alpha-hydroxylation.
Alpha-hydroxylation is dominant pathway; all congeners form phenylcyclohexylamine (PCA) via second alpha-hydroxylation. Pyrrolidine analogue generated largest proportion of PCA.
checked by claude-sonnet-4-6 · Apr 26, 2026
Coverage & Gaps
Research Trail
substance-article pipeline-v5 Apr 26, 2026
| Step | Source | Query | Results |
|---|---|---|---|
| 1database lookup | PubChem | rolicyclidine | 1 result, 1 selected |
selection rationaleselection rationaleConfirmed chemical identity, molecular formula, weight, InChIKey. SMILES not returned by API. | |||
| 2literature search | PubMed | rolicyclidine PCPy pharmacology | 5 results, 5 selected |
selection rationaleselection rationaleAll directly relevant to rolicyclidine pharmacology, clinical toxicology, and behavioral effects | |||
| 3literature search | OpenAlex | rolicyclidine PCPy 1-phenylcyclohexyl pyrrolidine | 4 results, 2 selected |
selection rationaleselection rationale3-MeO-PCPy metabolism paper directly relevant to rolicyclidine analog. Legal highs review provides context. | |||
| 4clinical trial search | ClinicalTrials.gov | rolicyclidine PCPy dissociative | 0 results |
selection rationaleselection rationaleNo trials to report | |||
| 5literature search | PubMed | phencyclidine analogue NMDA receptor binding affinity arylcyclohexylamine | 2 results, 2 selected |
selection rationaleselection rationaleProvides SAR context and receptor binding data for PCP analogue class | |||
| 6literature search | PubMed | phencyclidine metabolism cytochrome P450 CYP enzyme | 7 results, 3 selected |
selection rationaleselection rationalePCP/PCPy alpha-oxidation paper directly reports on pyrrolidine analogue metabolism | |||
| 7web search | WebSearch | rolicyclidine PCPy legal status Schedule I DEA controlled substance US UK | 10 results, 3 selected |
selection rationaleselection rationaleLegal status data for major jurisdictions | |||
| 8document retrieval | NCATS Inxight Drugs | — | 1 result, 3 selected |
selection rationaleselection rationaleVerified SMILES and CAS number from authoritative federal database | |||
| 9document retrieval | UNODC | — | 1 result, 1 selected |
selection rationaleselection rationaleOfficial UN international scheduling status | |||
| 10web search | WebSearch | rolicyclidine PHP synthesis history Maddox 1965 | 10 results, 2 selected |
selection rationaleselection rationaleHistorical synthesis record | |||
| 11literature search | PubMed | PCP analogue self-administration reinforcing behavioral drug dependence | 2 results, 1 selected |
selection rationaleselection rationaleDocuments PCP analogue reinforcing properties and abuse potential mechanism via DAT/dopamine pathways | |||
| 12literature search | PubMed | phencyclidine PCP self-administration reinforcing dependence monkey primate | 10 results, 2 selected |
selection rationaleselection rationalePCP dependence and withdrawal data applicable to PCPy by pharmacological class | |||
| 13web search | WebSearch | rolicyclidine melting point solubility physical properties chemical | 10 results, 4 selected |
selection rationaleselection rationalePhysical property data for rolicyclidine not available in academic literature; commercial databases are the only source | |||
| 14literature search | PubMed | phenylcyclohexylpyrrolidine PCPy PHP sigma NMDA binding radioligand displacement | 0 results |
selection rationaleselection rationaleConfirmed absence of specific binding affinity data for rolicyclidine - key gap documented discarded 0: no summary recorded | |||
| 15cross reference | Multiple sources | Rolicyclidine data cross-reference | 23 results |
selection rationaleselection rationaleFinal cross-reference confirms data integrity; key gap is absence of quantitative binding affinity data (Ki/EC50) for rolicyclidine specifically | |||
Research document (raw, unedited pipeline output)
# Research Output: Rolicyclidine
## Chemical Identity
**Verified from PubChem (CID 62436) [Ref 12] and NCATS Inxight Drugs [Ref 12]:**
| Property | Value |
|---|---|
| PubChem CID | 62436 |
| CAS Number | 2201-39-0 |
| DEA Number | 7458 |
| IUPAC Name | 1-(1-phenylcyclohexyl)pyrrolidine |
| Molecular Formula | C₁₆H₂₃N |
| Molecular Weight | 229.36 g/mol |
| SMILES | C1CCN(C1)C2(CCCCC2)C3=CC=CC=C3 |
| InChIKey | FYOWWXMGDATDQY-UHFFFAOYSA-N |
**Seed data discrepancies:**
- The brief lacked a SMILES string and PubChem CID. Both are now verified: CID 62436, SMILES C1CCN(C1)C2(CCCCC2)C3=CC=CC=C3.
- The brief listed no molecular formula or weight. Both verified from PubChem: C₁₆H₂₃N, 229.36 g/mol.
- The brief listed no InChIKey. Verified: FYOWWXMGDATDQY-UHFFFAOYSA-N.
- The compound is achiral with no defined stereocenters [Ref 12].
**Physical Properties** (from commercial chemical databases [Ref 21] — not from peer-reviewed sources; ⚑ FLAG):
- Melting point (free base): 44–45°C
- Boiling point: 114–123°C at 0.14 Torr (reduced pressure)
- Water solubility: ~55 mg/L at 25°C (estimated by computation)
- pKa: ~9.86 (moderately strong organic base; predominantly protonated at physiological pH 7.4)
## Pharmacology
### Mechanism of Action
Rolicyclidine (PCPy) is a non-competitive (open-channel) NMDA receptor antagonist, acting at the phencyclidine binding site within the ion channel pore of the NMDA receptor complex [Ref 4, Ref 19]. This site is activated only when the channel is open (use-dependent blockade), blocking calcium and cation influx in a voltage-sensitive manner. The PCP receptor site is allosterically linked to the NMDA recognition site, with glutamate and glycine co-agonism potentiating channel opening and thus enhancing access to the PCP site [Ref 19].
Rolicyclidine is also described as a sigma receptor agonist and dopamine reuptake inhibitor, consistent with the pharmacological class of arylcyclohexylamines [Ref 22]. These secondary activities are inferred from class pharmacology; no published binding studies specifically measuring rolicyclidine's affinity at sigma-1, sigma-2, or DAT have been identified (see Gaps & Flags).
### Receptor Binding Affinity
**⚑ FLAG — No published Ki/EC50 values for rolicyclidine at any receptor have been identified in the peer-reviewed literature.** All potency estimates must be inferred from behavioral pharmacology and structural analogy.
Relative potency data from drug discrimination studies in squirrel monkeys (Brady & Balster 1981 [Ref 4]):
- For PCP-like discriminative stimulus: **TCP > PCP = PCE > PHP (rolicyclidine) > PCM > ketamine**
- For suppression of operant responding: **PCP = TCP > PHP > PCE > PCM > ketamine**
- PHP is thus intermediate in NMDA antagonist potency — more potent than ketamine and PCM, but less potent than PCP and PCE.
For comparison, arylcyclohexylmorpholine analogues have been quantitatively measured in vitro: 3-MeO-PCMo shows NMDA affinity ~12-fold lower than PCP (Colestock et al. 2018 [Ref 9]); the morpholine ring is less active at the PCP site than the piperidine ring. The pyrrolidine ring (in rolicyclidine) falls behaviorally between piperidine (PCP) and morpholine (PCM) — consistent with ring size-dependent steric effects at the PCP site.
### CYP Inhibition
Rolicyclidine causes mechanism-based inhibition of cytochrome P450 (Brady et al. 1987 [Ref 5]). Preincubation of phenobarbital-induced rabbit liver microsomes with PCPy (rolicyclidine) reduced CYP-dependent N-demethylation activity in a process that was:
- NADPH-dependent
- Associated with reduced CO binding to microsomes
- Following pseudo-first-order kinetics
Relative rates of CYP inactivation: **PCP ≥ PCPy > PCHMI** (the 7-membered ring analogue). The mechanism requires a substituted nitrogen within a heterocyclic ring — the cyclic carbinolamine intermediate is implicated as the inactivating species [Ref 5].
### Metabolism
**Alpha-carbon oxidation** is a primary metabolic pathway for PCPy. Stefek et al. (1990 [Ref 7]) demonstrated that the pyrrolidine analogue generates the largest proportion of phenylcyclohexylamine (PCA) — the product of two sequential alpha-hydroxylations — compared to PCP and other analogues. PCA formation involves: (1) alpha-hydroxylation adjacent to nitrogen → ring-opened carbinolamine → secondary amine; then (2) further oxidation to PCA.
For the closely related compound 3-methoxyrolicyclidine (3-MeO-PCPy), Michely et al. (2017 [Ref 6]) elucidated the following metabolic pathways in rat urine and pooled human liver microsomes:
- Multiple aliphatic hydroxylations at the cyclohexyl ring and pyrrolidine ring
- Single aromatic hydroxylation
- Carboxylation following ring opening
- O-demethylation (not applicable to unsubstituted PCPy)
- Glucuronidation of hydroxylated metabolites
- **CYP2B6** catalyzes aliphatic hydroxylations; **CYP2C9** and **CYP2D6** catalyze O-demethylation
For unsubstituted rolicyclidine, only the hydroxylation and ring-opening pathways apply (no O-methyl group). CYP2B6 is likely the primary enzyme for aliphatic hydroxylation; CYP3A4 also plays a role in the broader PCP class (Laurenzana & Owens 1997 [Ref 10]).
**⚑ FLAG:** No human pharmacokinetic studies for rolicyclidine have been published. Half-life, bioavailability, Tmax, and protein binding data are not available from published literature.
### Pharmacokinetic Data
No published human pharmacokinetic studies for rolicyclidine identified. The database entry (half-life 5 days, tolerance reset 1.5 weeks) is consistent with the extended lipophilic nature of arylcyclohexylamines and their known CNS accumulation, but these values are not confirmed by published literature for rolicyclidine specifically. **⚑ FLAG for editorial review.**
## History
Rolicyclidine was synthesized in **1958** by Parke-Davis chemists, documented in a British patent [Ref 12]. It belongs to the same arylcyclohexylamine class as phencyclidine (PCP), whose synthesis — along with other 1-arylcyclohexylamines — was formally reported by Maddox, Godefroi, and Parcell in the *Journal of Medicinal Chemistry* in 1965 [Ref 11]. The Maddox 1965 paper describes the general synthetic route: 1-arylcyclohexylamines are prepared from cycloalkanone precursors using Mannich-type reactions with the appropriate secondary amine; phenylmagnesium bromide is then used to introduce the aryl group [Ref 11].
Rolicyclidine was **never developed for medical use**. It appeared on illicit drug markets in the United States in the **late 1970s**, typically sold as a PCP substitute. Budd (1980 [Ref 1]) published the first case report in the *New England Journal of Medicine* identifying PHP (phenylcyclohexylpyrrolidine) as a new drug of abuse. Clinical case reports from Giannini and colleagues documented the drug's psychotomimetic effects and treatment approaches in the early 1980s (Giannini & Castellani 1982 [Ref 2]; Giannini et al. 1985 [Ref 3]).
Due to its pharmacological similarity to PCP, rolicyclidine was placed into **Schedule I** in the United States in the early-to-mid 1970s, ahead of its widespread appearance on street markets. It never achieved significant abuse prevalence and is now rarely encountered [Ref 12].
## Subjective Effects
No controlled human studies of rolicyclidine's subjective effects have been published. Clinical descriptions are drawn from case reports and drug discrimination data.
**From clinical case reports** (Giannini & Castellani 1982 [Ref 2]; Giannini et al. 1985 [Ref 3]):
- Psychosis resembling that of PCP: hallucinations, agitation, disorganized thinking
- Neurological symptoms: motor impairment, ataxia
- PHP psychosis closely resembled PCP psychosis in presentation and response to treatment
- Physostigmine produced rapid and sustained reversal of symptoms in one case, suggesting cholinergic involvement [Ref 2]
**From behavioral pharmacology** (Brady & Balster 1981 [Ref 4]):
- PHP fully generalizes to PCP in drug discrimination paradigms in squirrel monkeys
- All PCP-class analogues produced dose-dependent PCP-appropriate responding
- Dose needed to suppress operant behavior was 3–5× higher than the discrimination ED₅₀ dose across all analogues — consistent with a dissociation between subjective-like effects and motor impairment
**Published effect domain inference** (Luethi & Liechti 2020 [Ref 15]; Baumeister et al. 2015 [Ref 8]):
Dissociative PCP-class drugs produce: analgesia, amnesia, ego dissolution, derealization/depersonalization, hallucinations (visual and auditory), thought disorganization, motor impairment, nausea, and tachycardia. These are class-level descriptions — none are specific to rolicyclidine.
**Duration data note:** The dose/duration data in the brief (oral onset 20–90 min, total 6–12 hours; insufflated onset 3–30 min, total 4–6 hours) are not confirmed by any published source and appear to be community-derived or extrapolated from PCP class data. **⚑ FLAG for editorial review.**
## Safety & Toxicity
### LD₅₀ / Lethal Dose
No published LD₅₀ data for rolicyclidine have been identified. **⚑ FLAG: This is safety-critical data absent from published literature.** Class-level inference from PCP suggests acute toxicity risk at high doses, particularly via cardiovascular and respiratory depression.
### Acute Toxicity (Case Data)
The case reported by Giannini & Castellani (1982 [Ref 2]) documents:
- Neurological symptoms: motor impairment, likely ataxia
- Psychic symptoms: psychosis-like state
- Urine-confirmed PHP ingestion
- Physostigmine IM produced "rapid and sustained reversal" — suggesting anticholinergic-like toxidrome features
The Giannini et al. (1985 [Ref 3]) series of 20 cases documented:
- PHP-induced psychosis presenting similarly to PCP psychosis
- Haloperidol 5 mg IM produced significant improvement over placebo
- No fatalities reported in the published series
### Mechanism-Based CYP Inhibition Risk
Rolicyclidine inhibits hepatic CYP enzymes by a mechanism-based (irreversible) process [Ref 5]. This creates potential for drug-drug interactions: co-administration of rolicyclidine with drugs metabolized by CYP2B6, CYP2D6, or CYP3A4 may result in elevated plasma levels of those drugs. This is a pharmacokinetic safety concern not typically seen with other recreational dissociatives.
### Psychological Risks
PCP-class drugs are documented to cause psychosis, particularly with high doses or prolonged use [Ref 3, Ref 8]. These effects are not benign and can persist beyond the acute drug period. From the design drugs review (Luethi & Liechti 2020 [Ref 15]), dissociative NMDA antagonists pose risks of: psychosis, agitation, violence, cardiovascular stimulation, and (in overdose) respiratory depression.
### Toxicity Seed Data Note
The brief states toxicity as "moderate" acute and chronic, noting "Inferred from pharmacological class — not sourced from literature." This is accurate — **⚑ FLAG: toxicity values require editorial review; they are class inferences, not rolicyclidine-specific published data.**
## Harm Reduction
No published harm reduction guidelines specific to rolicyclidine have been identified.
**Treatment of acute intoxication** (from case reports):
- **Haloperidol** 5 mg IM was effective in treating PHP-induced psychosis in 20 cases (Giannini et al. 1985 [Ref 3]); this mirrors PCP psychosis treatment protocols
- **Physostigmine** IM produced rapid reversal in one case (Giannini & Castellani 1982 [Ref 2]); however, physostigmine is no longer recommended as a routine antidote in contemporary clinical practice
- General supportive care for dissociative intoxication (calm environment, benzodiazepines for agitation, vital sign monitoring) follows PCP class protocols
**CYP inhibition warning:** Rolicyclidine's mechanism-based CYP inhibition [Ref 5] means that combining it with other substances metabolized by CYP2B6, CYP2D6, or CYP3A4 may produce unpredictably elevated drug levels. This is a pharmacokinetic risk for poly-drug users not documented for most other dissociatives.
**Drug testing:** Rolicyclidine is not detected by standard immunoassay PCP screens (which target PCP itself) [Ref 20]. GC-HRMS or targeted LC-MS/MS methods are required for confirmation (Song et al. 2025 [Ref 20]).
**Contraindications:** No published contraindications specific to rolicyclidine. Class-level contraindications (from PCP analogue literature) include: cardiac arrhythmia history, psychotic disorders, respiratory compromise, concurrent use of CNS depressants.
## Tolerance & Dependence
### Tolerance
No published tolerance data specific to rolicyclidine. The brief states "5-day half-life tolerance buildup with prolonged/repeated use; full reset 1.5 weeks." These figures are not confirmed by published sources for rolicyclidine specifically and appear extrapolated from PCP class data. **⚑ FLAG.**
Cross-tolerance with other dissociatives is supported by PCP class pharmacology: all PCP-class drugs generalize to each other in drug discrimination models (Brady & Balster 1981 [Ref 4]), consistent with a shared mechanism (NMDA open-channel blockade) driving cross-tolerance.
### Dependence Liability
PCP class drugs demonstrate significant dependence potential in preclinical models:
- Physical dependence demonstrated in primates with oral PCP self-administration (Perry et al. 2006 [Ref 18]; Carroll et al. 2009 [Ref 17])
- PCP withdrawal reduced operant responding maintained by food, indicating physiological withdrawal [Ref 17]
- Males showed greater withdrawal severity than females [Ref 18]
- PCP and high-affinity NMDA antagonists are classified as reinforcers in IV self-administration paradigms (Klein et al. 1999 [Ref 10])
- 4'-F-PCP (structural analogue) demonstrated robust self-administration with dopaminergic mechanism in nucleus accumbens (Ryu et al. 2020 [Ref 16])
**The brief's characterization of "high physical and psychological dependence" and "highly addictive with high potential for adverse side effects such as psychosis"** is broadly consistent with published PCP class literature but has not been directly studied for rolicyclidine itself. **⚑ FLAG: This characterization is class-level inference, not substance-specific published data.**
## Interactions
### Published Drug Interaction Data
No interaction studies specific to rolicyclidine have been published.
### Mechanistic Interaction Risks
**CNS Depressants (Alcohol, GHB/GBL, opioids, benzodiazepines):**
Additive CNS and respiratory depression. The brief lists GHB and GBL as "lethal" combinations and alcohol as "dangerous." These severity ratings are consistent with PCP class pharmacology but are not sourced from rolicyclidine-specific published data. **⚑ FLAG: interaction severity ratings require published source confirmation.**
**CYP-Mediated Interactions (mechanism-based inhibitor risk):**
Rolicyclidine is a mechanism-based CYP inhibitor [Ref 5]. This means it may irreversibly inactivate CYP enzymes — particularly CYP2B6, CYP2D6, and CYP3A4 — leading to elevated plasma concentrations of co-administered drugs. Drugs that are narrow therapeutic index CYP substrates (e.g., warfarin, certain antiarrhythmics, opioids metabolized by CYP3A4/CYP2D6) could reach toxic levels.
**Stimulants (Cocaine, MDMA, αMT, Tramadol):**
The brief lists cocaine as "dangerous," MDMA as "dangerous," αMT and tramadol as "lethal." The tramadol + PCP class interaction is pharmacologically plausible via serotonin syndrome (tramadol has serotonergic activity) combined with CNS effects. MDMA is plausibly dangerous via combined cardiovascular effects and possible serotonergic/dopaminergic overload. **⚑ FLAG: all interaction severity ratings are class-level inferences; none confirmed by published rolicyclidine-specific literature.**
### Serotonin Syndrome Risk
Rolicyclidine as an NMDA antagonist is not classified as a serotonergic drug, but dopamine reuptake inhibition (class-level) combined with serotonergic drugs (MDMA, αMT, tramadol) could contribute to monoaminergic excess. Data are extrapolative — no rolicyclidine-specific interaction studies exist.
## Legal Status
| Jurisdiction | Status | Classification | Notes |
|---|---|---|---|
| United States | Controlled | Schedule I (DEA #7458) | Added in 1970s; never approved for medical use [Ref 12] |
| United Kingdom | Controlled | Class A | Added under Misuse of Drugs Act 1971 (Modification) Order 1984 [Ref 14] |
| International | Controlled | Schedule I (1971 UN Convention on Psychotropic Substances) | Listed alongside PCE (eticyclidine) and TCP (tenocyclidine) [Ref 13] |
| Australia | Unknown | Not confirmed from identified sources | Likely covered under Controlled Drug Analogues legislation; **⚑ FLAG** |
| Canada | Unknown | Not confirmed from identified sources | Likely covered under CDSA; **⚑ FLAG** |
| European Union | Varies by member state | Most EU countries controlled via UN Convention obligations | **⚑ FLAG: specific member state confirmation not researched** |
## Clinical Trials
No clinical trials for rolicyclidine found on ClinicalTrials.gov. The substance has no history of medical development and no active or completed trials.
## Community Feedback Analysis
No community feedback submitted in Part A2 of the brief. No community feedback items to evaluate.
## Gaps & Flags
### Critical Gaps (Safety-Relevant)
1. **⚑ No published Ki/EC50 binding affinity values for rolicyclidine at any receptor.** The pharmacological class (NMDA antagonist, sigma agonist, DAT inhibitor) is established, but quantitative binding data do not exist in the published literature for this specific compound. The potency ranking is behavioral (Brady & Balster 1981 [Ref 4]) rather than receptor-level.
2. **⚑ No human pharmacokinetic studies.** Half-life, oral bioavailability, Tmax, protein binding, and volume of distribution are unknown for rolicyclidine in humans. The brief's tolerance half-life value (5 days) is not sourced from published data.
3. **⚑ No LD₅₀ or human lethal dose data published.** Acute lethality parameters are unknown. Toxicity is currently described as "moderate" based on class inference only.
4. **⚑ All drug interaction severity ratings (lethal/dangerous) in the brief are not confirmed by rolicyclidine-specific published sources.** They are plausible class-level extrapolations from PCP pharmacology but have not been independently validated.
5. **⚑ Dose/duration data in the brief are not verified from any published source.** These values appear community-derived or extrapolated from PCP class data. The brief's dose data (threshold 1 mg, common 4–8 mg across ROAs) is internally consistent with PCPy being slightly less potent than PCP but has no published confirmation.
### Data Relying Primarily on Structural Analogy or Class Inference
- **Sigma receptor agonism:** Class inference only; no published binding data for rolicyclidine at sigma-1 or sigma-2
- **Dopamine reuptake inhibition:** Class inference only; no published DAT binding/inhibition data for rolicyclidine
- **Dependence liability ("high physical and psychological dependence"):** Supported by PCP class animal data [Ref 17, Ref 18] but not directly studied in rolicyclidine
- **Psychosis risk:** Documented for PCP class [Ref 3, Ref 8] but rolicyclidine-specific incidence unknown
- **CYP3A4 involvement in metabolism:** Extrapolated from PCP human liver data [Ref 10]; rolicyclidine's specific CYP profile not published
### Data Gaps — Unresolved
- **Australia and Canada scheduling:** Not confirmed from identified primary sources. Likely controlled under domestic law per UN Convention obligations.
- **Physical properties (melting point, solubility, pKa):** Retrieved from commercial chemical databases [Ref 21], not peer-reviewed sources
- **Stereochemistry:** Compound is achiral (no stereocenters); confirmed [Ref 12]. No active isomer consideration required.
- **EU member state-specific scheduling:** Not researched; inferred from UN Convention obligations
- **First British patent reference:** The 1958 Parke-Davis patent is noted in secondary sources but the patent number/text was not retrieved and cannot be cited as a primary source