Excerpt from Toxicity, Phencyclidine

Synonyms, Key Words, and Related Terms: angel dust, dust, crystal, crystal joint, hog, CJ, KJ, peace, peace weed, super grass, super weed, rocket fuel, elephant tranquilizer, tranks, sheets, surfer, snorts, scuffle, Cadillac, cyclones, soma, mist, goon, TIC, TAC, PCP, illicit drug use, drug abuse, Sernylan, animal tranquilizer, controlled substance, street drug, dissociative anesthetic.

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Background: Phencyclidine, 1-(1-phenylcyclohexyl) piperidine (PCP), is a dissociative anesthetic that was originally synthesized for intravenous use in 1957 and was marketed under the trade name Sernylan. Because of its postoperative emergence reactions (ie, hallucinations, prolonged abnormal level of consciousness, agitation), it fell out of favor; its use as an anesthetic in humans was discontinued in 1963. Subsequently, it was used primarily as an animal tranquilizer and was distributed for veterinary use until 1978, when the US government added the drug to its list of controlled substances. Today, several of its congeners (eg, ketamine) are used in anesthesia or are under investigation for use as anesthetics.

PCP emerged as an oral drug of abuse, known as the PeaCe Pill on the streets of San Francisco in 1967. However, its reputation for bad trips (ie, unexpected and unpleasant reactions), coupled with its unpredictable effects, quickly filtered through the drug community and caused the drug to wane in popularity. In the early 1970s, smoking of PCP was recognized as an effective method of use because its mind-altering effects could be titrated.

Pathophysiology: PCP is a commonly abused street drug sold under many different names and in many different forms. It may be sold on the street in tablet or capsule form, as a powder, or as a solution. The PCP content in each form differs widely, commonly containing only 10-30% PCP. Angel dust, the powdered form of PCP, generally has a higher PCP content, occasionally reaching 100%. Angel dust may be sniffed, smoked, ingested, or injected intravenously. Percutaneous absorption has also been reported to occur in individuals handling PCP (eg, law enforcement officers). Smoking remains the desired method of use; the substance is commonly sprinkled onto dried leaf material (eg, marijuana, tobacco, oregano, mint) and then smoked.

PCP is easy to synthesize, and a number of its analogs or byproducts of synthesis may be found on the streets. These include phenylcyclohexylethylamine (PCE), thienylcyclohexylpiperidine (TCP), and phenylcyclohexylpyrrolidine (PHP), which have similar pharmacologic activity to PCP but may be more toxic. One byproduct, piperidinocyclohexane carbonitrile (PCC), can cause cyanide poisoning.

Pharmacokinetics

PCP is a dissociative anesthetic because it renders the patient motionless (ie, rigid muscles, flat facies, staring gaze) while maintaining a wakeful, although amnestic, state. The anesthetic effect results from PCP's ability to block selected sensory stimuli, such as pain. It produces profound analgesia and anesthesia while preserving spontaneous respiration and without major effects on the cardiovascular system.

PCP is an arylcyclohexylamine compound, and, like other arylcyclohexylamines, it interacts with most neurotransmitter systems, resulting in a combination of CNS stimulant and depressant effects. For example, it blocks the N-methyl-D-aspartic acid (NMDA)–type glutamate receptors located in both the cortex and limbic regions of the brain, it inhibits GABA, and it increases dopamine synthesis and release while inhibiting its presynaptic reuptake. PCP also blocks acetylcholine receptors, thus resulting in anticholinergic activity; however, PCP may also inhibit acetylcholinesterase, resulting in cholinergic activity. Additionally, PCP has some interaction with the sigma opiate receptors in the hippocampus and competitively inhibits norepinephrine and serotonin. While the predominant effect is sympathomimetic, a number of other effects may be observed to varying degrees in individuals who are intoxicated with PCP.

PCP is a weak base (pKa 8.6-9.4) that is absorbed well orally, nasally, and percutaneously, especially when in liquid form. When ingested, PCP has an oral bioavailability of approximately 50-90%, and it is absorbed best from the alkaline environment of .....