PCP and Ketamines By: Brad Boyle, Jason Taylor-

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PCP and Ketamines By: Brad Boyle, Jason Taylor- - Description

Ohmes. , Lacy Flanagan. Background and . History: PCP. PCP or . phencyclindine. Chemical name 1-(1-phenylcyclohexyl) . piperidine. 1950s – first tested as a potential anesthetic agent by Parke, Davis and Company. ID: 676499 Download Presentation

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PCP and Ketamines By: Brad Boyle, Jason Taylor-




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Presentations text content in PCP and Ketamines By: Brad Boyle, Jason Taylor-

Slide1

PCP and KetaminesBy: Brad Boyle, Jason Taylor-Ohmes, Lacy Flanagan

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Background and History: PCPPCP or phencyclindine

Chemical name 1-(1-phenylcyclohexyl) piperidine1950s – first tested as a potential anesthetic agent by Parke, Davis and Companycaused and unusual form of anesthesiashowed no response to painful stimuliexhibited trancelike or catatonic like state with vacant facial expressions, staring eyes, and maintenance of muscle tonedid not produce respiratory depression as other barbituratesome patients began to develop problematic reactionsagitation rather than quieting during induced statesmilds – blurred vision, dizziness, disorientation

severe- hallucinations, severe agitation, violence

1965 – clinical use of PCP terminated

1967 – PCP found its way to the streets

mid 1970s – PCP use and abuse became more widespread throughout the country

street names –

PeaCe

Pill, angel dust, hog

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Background and History: KetamineKetamineSafer alternative to PCPParke, Davis was adamant about finding a less toxic compound in its behavioral effects

CI-581 was developed in 1962Less potent and shorter actiongUsed particularly for surgery in childrenSedative and immobilizing agent for veterinariansLegal as a prescription under the trade names Ketalar, Ketaset, and VetalarDespite low potency, ketamine can still cause adverse emergency reactions similar to PCP

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PCP: Pharmacokinetics

Powder or pill form p.o.Slowest onsetLower addictivenessNot as severe effectsI.M.

Intranasal

I.V.

Fastest onset

Highest addictiveness

Most intense effects

Inhalant

Applied to tobacco and marijuana

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Katamine: PharmacokineticsMarketed as an injectable liquidOccurs most often

I.V. or I.M.Evaporated and sold as a powderOccurs on streetsIntranasal Snort small line or pile called bumpsProduces small highp

.o.

Tolerance

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PCP: EffectsSubanesthetic dose

Psychological effectsDetachment from body, sensations of floatingNumbness, dreamlike stateApathy, loneliness, negativism or euphoriaPhysiological effectsDrowsiness, difficulty maintaining concentration

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Ketamine: EffectsSubanesthetic dose

Similar effects to PCPFloating, dreamlike state, detached from bodyAnesthetic dose1mg/kgLose all mental contact with environmentEyes remain opened and retain muscle toneDissociative anesthesia

“K-Hole”

Spiritually uplifting or terrifying

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Self AdministrationReinforcement in animalsStudies on Rhesus monkeys

Self-administer high doses of PCPTook in high quantities to be intoxicated continuouslyWhile intoxicated sat in awkward position by leverDopamineIncrease of DA cell firing and DA release in monkeysContributes to RFT?

Rats self-administer PCP directly to NA

DA independent

DA and non-DA mechanisms in RFT

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Noncompetitive Antagonists of NMDA ReceptorsPrincipal molecular target for both is NMDA receptorNMDA is an important

ionotropic receptor for glutamateBoth are noncompetitive antagonists They block the receptor at a different site than the site at which NMDA or glutamate bindsNMDA plays a role in glutamate signalingCerebral cortex and hippocampus contain many NMDA receptorsBehavioral and subjective effects are thought to be mediated by NMDA receptor antagonismDextromethorphan is common in OTC cough and cold medications and is another noncompetitive NMDA antagonist with abuse potential

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Drugs of AbuseAbusePrevalence of PCP use is much lower than that of other majorly abused drugs

There are currently no comparable statistics for ketamineWho uses it?People at ravesMedical or veterinary practitionersMarcia Moore and Dr. John LillyTolerance and DependenceKarl Jansen’s Ketamine Research (2001)Research demonstrated dose escalation and compulsive useMany ketamine dependent subjects studied were described as highly intelligentOvercoming ketamine was described as “harder than heroin”

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Getting high on cough syrupDextromethorphanAntitussive

Does not directly stimulate opioid receptors like codeineNon-competitive NMDA receptor antagonistInitially tablets, but then was put into cough syrupLarge amounts of syrup would have to be consumed to get a psychoactive effect—people still abuse it.Typical dose 15-30 mg. Recreational users take 10x this or more.Adverse side effectsSyrup: Nausea and vomiting due to guaifenesin

Coricidin

tablets:

Cholorpheniramine

reactions

So users developed a way to extract the substance and resell it as re-packaged pills or powders

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DextromethorphanDose-related plateausLow Doses (2 oz.)Mild euphoria and intoxication

May experience slight perceptual effectsThe second plateau (4 oz.)The desired high, about 200 mg of dextromethorphanUser becomes ataxicVisual hallucinations when the eyes are closedSignificantly more intoxicatedThird and Fourth plateaus (8+ oz.)400 to 1000 mg dextromethorphanPowerful dissociative effects mirroring those of PCP and ketamineSimilarities to ketamine and PCP

Dextrorphan

PCP-like

discriminitive

stimulus effects in animal studies

Dissociative effects are consistent with a mechanism involving NMDA receptor blockade

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PCP, Ketamine, and schizophreniaWhy these drugs may be helpful:Perceptual, cognitive, and affective responses mirror those of schizophrenia

Administration of either drug to schizophrenic increases their symptomsResearchHealthy participants were given doses of ketamine (IV)Positive symptomsHallucinatory responses, conceptual disorganization, and bizarre thought contentNegative symptomsBlunted affect, emotional withdrawal, and motor retardationPsychotic-like reactions diminished afterwards

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Future ResearchAnimal ModelsLong term PCP administration may provide a model for the severe cognitive deficits in schizophrenic patients

Researchers found 2 weeks of twice daily PCP administrations to monkeys caused deficits in object retrieval detour learning tasks one week after the last drug doseDetour task involves the prefrontal cortexRepeated PCP treatment has lead to a reduction in DA utilization in the prefrontal cortexThe future treatment of schizophreniaAnimal models using chronic PCP administration may help us to understand and treat some of the underlying mechanisms involved in schizophrenia

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SummaryPCP and Ketamine classified as dissociative anestheticsAcute effects – sensory distortions and altered body image, cognitive disorganization, and various affective changesHigh doses of ketamine = state called “k-hole”

K-hole – user feels separated form their bodyBoth are reinforcing to animalsMay be mediated by both dopaminergic and non-dopaminergic mechanismsDirect molecular target is glutamate NMDA receptorUser dose escalation and compulsive use indicates development of high tolerance and dependenceMay help to understand the neurochemical processed underlying schizophrenia


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