KETAMINEKETAMINE

Ketamine’s Properties and Ketamine’s Properties and Effect on Brain DevelopmentEffect on Brain Development

OVERVIEWOVERVIEW Pharmacology of ketaminePharmacology of ketamine

Brief history Brief history

Effects of ketamine usageEffects of ketamine usage

Ketamine & neuronal degeneration Ketamine & neuronal degeneration in a rat brainin a rat brain

PHARMACOLOGY/PHARMACOLOGY/HISTORYHISTORY

Structurally related to phencyclidine (PCP)Structurally related to phencyclidine (PCP) Prevents the actions of excitatory amino Prevents the actions of excitatory amino

acids, such as glutamate and aspartate. acids, such as glutamate and aspartate. Dissociative anesthetic first used during Dissociative anesthetic first used during

the Vietnam War the Vietnam War Currently still used for veterinary practices Currently still used for veterinary practices

and with childrenand with children First choice for victims w/unknown medical First choice for victims w/unknown medical

historieshistories In recent years, drug users have In recent years, drug users have

discovered its hallucinogenic properties discovered its hallucinogenic properties Also used by sexual predators to incapacitate Also used by sexual predators to incapacitate

their victimstheir victims

EFFECTS OF KETAMINEEFFECTS OF KETAMINE CardiovascularCardiovascular

RespiratoryRespiratory

VisionVision

GastrointestinalGastrointestinal

Immune systemImmune system

PsychoactivePsychoactive

BRAIN DEGENERATIONBRAIN DEGENERATION Apoptosis (programmed cell death)Apoptosis (programmed cell death)

Origin of control mechanism still undetermined Origin of control mechanism still undetermined but stimulation of NMDA (N-methyl-D-but stimulation of NMDA (N-methyl-D-aspartate) seems vital to the survival of aspartate) seems vital to the survival of developing nerve cellsdeveloping nerve cells

Need right amount of NMDA situation for Need right amount of NMDA situation for sufficient brain developmentsufficient brain development

Negative effects for both over and under-Negative effects for both over and under-stimulation of NMDA receptors:stimulation of NMDA receptors: Over-stimulation of NMDA receptors, known as Over-stimulation of NMDA receptors, known as

excitatory neurotoxicity, is known to excitatory neurotoxicity, is known to exacerbate neuronal damageexacerbate neuronal damage

Not enough NMDA stimulation triggers Not enough NMDA stimulation triggers apoptosis in an immature central nervous apoptosis in an immature central nervous systemsystem

Table 2: The effect of ketamine on weight gain

Table 1: The effect of ketamine on righting reflex

This table shows the effect of a single dose of ketamine on different parts of the brain.

This table shows the effect of multiple ketamine doses on different parts of the brain.

This table shows the effect of MK-801 doses during a 24 hour duration.

Ketamine = Noncompetitive NMDA receptor Ketamine = Noncompetitive NMDA receptor antagonistantagonist

Obvious evidence that it causes neurological Obvious evidence that it causes neurological degeneration after prolonged exposuredegeneration after prolonged exposure

Duration of NMDA receptor blockage appears Duration of NMDA receptor blockage appears crucial factor in triggering neuronal degeneration crucial factor in triggering neuronal degeneration in the developing rat brainin the developing rat brain

However, results might not necessary mirror However, results might not necessary mirror similar effects in humans due to interspecies similar effects in humans due to interspecies variability (i.e. different duration of brain variability (i.e. different duration of brain development)development)

Probable that the capability of the human brain Probable that the capability of the human brain can stand more damage than a rat braincan stand more damage than a rat brain

BRAIN DEGENERATION BRAIN DEGENERATION (con’t)(con’t)

DEGENERATION FROM DEGENERATION FROM KETAMINEKETAMINE

Figure 1Silver-cupric staining of brain slices from P7 rat treated with saline (a) or ketamine (b) Degenerating neurones (dark cells) are abundant in the brain of the rats treated with ketamine.

DISCUSSION/CONCLUSIONDISCUSSION/CONCLUSION

Ketamine has a balance of positive and Ketamine has a balance of positive and negative effectsnegative effects

Excessive neuronal damage from Excessive neuronal damage from apoptosis after 24 hours of prolonged apoptosis after 24 hours of prolonged exposure to ketamineexposure to ketamine

More research is necessary to reveal More research is necessary to reveal ketamine’s full effect on humans.ketamine’s full effect on humans.

REFERENCESREFERENCES

Dikkes P, Hayashi H, Soriano SG. Repeated Dikkes P, Hayashi H, Soriano SG. Repeated administration of ketamine may lead to administration of ketamine may lead to neuronal degeneration in the developing rat neuronal degeneration in the developing rat brain. brain. Paedriatric AnaesthesiaPaedriatric Anaesthesia 2002; 2002; 1212: 770-: 770-774.774.

Copeland J, Dillon P. The health and psycho-Copeland J, Dillon P. The health and psycho-social consequences of ketamine use. social consequences of ketamine use. The The International Journal of Drug PolicyInternational Journal of Drug Policy 2005; 2005; 1616: : 122-131.122-131.