PCP and Ketamine: Effects, Pharmacology, and Risks PDF

## Phencyclidine (PCP) and Ketamine ### Introduction Phencyclidine, also known as PCP, is a synthetic drug developed and marketed in 1963 by the Parke-Davis Company as an analgesic and anesthetic. PCP was withdrawn from the pharmaceutical market because patients reported that, while recovering fro...

## Phencyclidine (PCP) and Ketamine ### Introduction Phencyclidine, also known as PCP, is a synthetic drug developed and marketed in 1963 by the Parke-Davis Company as an analgesic and anesthetic. PCP was withdrawn from the pharmaceutical market because patients reported that, while recovering from the drug, they experienced a state of delirium, disorientation, and agitation. Ketamine was first synthesized in 1962 and marketed in 1969 as a safer alternative to PCP. ### Routes of Administration and Pharmacokinetics - PCP comes in the form of a liquid, tablet, capsule, or a white or colored crystalline powder that readily dissolves in water or alcohol. - PCP can be consumed orally, injected, snorted, or smoked. - The most common method of recreational PCP use involves saturating plant material with PCP and rolling it into a cigarette. - The effects of a typical (5-10 mg) dose of PCP are felt within 2-5 minutes after smoking or within 30-60 minutes after oral administration. - Peak effects usually occur within 10-90 minutes of drug use, and overall effects typically last for 4-8 hours. - Ketamine is available in the form of a colorless, tasteless liquid that may be injected, dripped onto a cigarette and smoked, or mixed into a drink and consumed orally. - After oral administration, ketamine is slowly absorbed from the gastrointestinal tract and highly susceptible to degradation by first-pass metabolism. ### Neuropharmacology - Dissociative anesthetics alter the functioning of many neurotransmitter systems, including norepinephrine, epinephrine, dopamine, serotonin, opioid, adenosine, and acetylcholine. - Their principal effects appear to be mediated by their noncompetitive antagonist actions at glutamate NMDA receptors. - PCP and ketamine bind to a site embedded deep within the ion channel of the NMDA receptor. - When the binding site is occupied by PCP or ketamine, the NMDA receptor ion channel is blocked, rendering glutamate ineffective. - This mechanism of action is thought to be similar to that of the alcohol molecule. - When dissociative anesthetics inhibit the functioning of NMDA receptors, especially in the frontal cortex, negative symptoms of psychosis appear. - The reinforcing effects of dissociative anesthetics are likely the result of their influence on glutamate activity, and thereby dopamine release, in the mesolimbic and mesocortical pathways. ### Effects of Dissociative Anesthetics on Behavior #### Memory & Cognition - Dissociative anesthetics are known to cause amnesia for events that occur while intoxicated. - PCP has been found to produce a greater disruption of memory than that caused by LSD, THC, opioids, and many other psychoactive drugs. - Prolonged ketamine use leads to the emergence of cognitive deficits, including impairments in the encoding of episodic memory, deficits in semantic memory and procedural learning, and problems in the manipulation (but not maintenance) of working memory. - PCP and ketamine are also capable of inducing symptoms of disordered thought like those exhibited in schizophrenia. #### Other Effects - PCP and ketamine are not hallucinogenic. - At usual doses, the dissociative anesthetics cause relaxation, sedation, immobility, warmth, a tingling feeling, a sense of numbness, analgesia, and euphoria. - At low doses or when emerging from anesthesia, there are distortions in body image and a feeling of floating in space. - When these effects wear off, they are sometimes followed by a mild depression that may last from 24 hours to 1 week. - At higher doses, symptoms of psychosis may emerge, including catatonic excitation, marked by frenzied motor activity, or catatonic stupor, in which the person remains immobile for prolonged periods of time. #### Stimulus Properties - Dissociative anesthetics appear to have unique stimulus properties. - Animals trained to discriminate PCP and ketamine from saline do not generalize responding to any other class of drugs, including stimulants, depressants, or hallucinogens, and no drug has been found to antagonize their stimulus properties. - Animals generalize responding only to other drugs also known to block NMDA receptors, such as dextromethorphan. #### Tolerance - PCP is typically used sporadically. - Tolerance develops when the drug is used daily. - When users first try the drug, they need only a few puffs of a PCP-laced cigarette to get high, but within 2-6 weeks, they may require two full joints to achieve the same effect. - Tolerance also seems to develop to the analgesic effects of the dissociative anesthetics. #### Withdrawal - Animal research suggests there may be some withdrawal after repeated use of PCP. - The symptoms include vocalizations, grinding of the teeth, diarrhea, difficulty staying awake, anxiety, tremors, memory impairment, and depressive-like symptoms. - Reports of withdrawal symptoms in humans following the prolonged use of ketamine or PCP are inconsistent. ### Harmful Effects - PCP and ketamine have an unfounded reputation for causing violence and uncontrollable behavior. - The psychotic state induced by large doses of dissociative anesthetics is marked by disorientation, agitation, and hyperactivity. This can lead to injury, either to the individual using the drug or to others nearby. - Long-lasting psychotic behavior has been reported following PCP use, even in individuals without prior psychotic tendencies. - Acute behavioral effects of PCP and ketamine can sometimes be responsible for injury and death. - Chronic ketamine use is associated with long-term neurological changes. ### Genetic Damage and Reproduction - In pregnant women, the use of PCP has been found to slow the growth of the fetus, precipitate labor, and cause fetal distress. - Children born to mothers who use PCP often show muscle stiffness, tremor, irritability, and impaired attention and behavior control that may last for several years. - The use of PCP and ketamine has been linked to widespread cell death in the developing rat brain. ### Lethal Effects - A lethal dose of ketamine taken intranasally is estimated to be about 2700 mg, nearly 40 times greater than the usual effective dose. - High doses of PCP and ketamine can cause respiratory arrest, convulsions, and coma. - Kidney failure and brain hemorrhage have also been reported. - The lethal effects of PCP and ketamine are potentiated by the co-presence of other CNS-depressant drugs, such as alcohol and barbiturates, in the body.