Historical Overview

Phencyclidine (PCP) is a synthetic drug that possesses attractive physiological properties. It was originally synthesized in the early 1980s as a possible surgical anesthetic. PCP allowed the patient to enter a surreal state in which the awareness of pain could be separated from the sensation of pain, a state that has been termed “Dissociative anesthesia”. In this state, the patient can experience profound insensitivity to pain, but may be conscious with his eyes open. The dissociative properties and other side effects of PCP mimic the symptoms of schizophrenia. Researchers explored and continue to explore the possibility of using PCP as a model drug to induce a schizophrenia-like state in experimental subjects, although the validity of this approach remains a topic of debate. When the drug was administered to volunteers, many symptoms were produced that are also commonly seen in schizophrenia, including social removal, depersonalization, impaired abstract thinking, and thought disorder. Schizophrenic patients given PCP are more sensitive than normal patients to its effects, and often suffer relapse.

PCP also possesses unwanted properties that make its use intolerable as a sedative. A significant percentage of people who undergo anesthesia with PCP experience a phenomenon called emergence delirium, in which the patient may exhibit agitation, disorientation, restlessness, and uncontrollable crying. Patients may persist to experience unpleasant dreams up to 24 h after the drug has been given.

The current story of PCP started at Parke-Davis and Comparer in the early 1960s. An active area of chemical research at that time was the study of the addition of Grignard reagents to compounds containing numerous bonds. Dr. Victor Maddox at Parke-Davis was studying compounds formed by the addition of Grignard reagents to nitrites. In 1966, he began to studs 1-1-pheny-clohexyl, later to be called phencyclidine, and then PCP. The compound was sent for animal testing, and Dr. Graham Chen found that the compound possessed anesthetic properties and induced an unusual cataleptic state. This cataleptic state was thought to have potential and the compound was marketed as a large animal tranquilizer under the name Sernyl. Toxicity studies indicated that PCP had a therapeutic index about 5 times greater than existing anesthetics.

Dr. F. E. Greifenstein, in 1957 started human clinical studies on PCP based on the positive anesthetic results seen by Chen in animals. These human studies showed that PCP had a similar anesthetic effect and therefore potential as a surgical anesthetic. The US Army administered PCP to volunteers in the 1950s to study its potential as a chemical warfare agent. In further studies investigating neurotic patients, PGP use led to the patients experiencing repressed memories.

Psychiatrists in England took advantage of this property in therapeutic situations in the early 1960s. However, the continuing problems with emergence delirium resulted in PCP being relegated to use as a large animal tranquilizer.

Phencyclidine initially appeared as a “street drug” in California in the 1960s. Members of the drug-using public found that PCP could be used as a hallucinogen. The drug was diverted from legitimate sources to the illegal market, and clandestine labs began to produce the drug. Originally, the drug was sold illegally in capsules for oral ingestion. Phencyclidine was rather popular for several years and was responsible for a large number of visits to emergency rooms to treat the unwanted effects. As word of these ‘Bad trips’ spread, its popularity declined. Users of these oral preparations reported that the effects were unpleasant, unpredictable, and sometimes severe.

In l970, The Controlled Substances Act was signed into law, and PCP was placed m Schedule m as a drug with some potential for abuse and the potential for low-to-moderate physical dependence or high psychological dependence Street exploration of the effects of PCP continued in the 1970s, and it was discovered that remolding the drug could ease the unpleasant reactions experienced with oral ingestion. PGP Yeas placed on vegetable material, usually parsley or marijuana, and the vapors were inhaled. This technique allowed the drug user to control, or titrate, the amount of drug getting into the system. Also, since PGP is easily synthesized, it remained relatively inexpensive compared to other drugs.

In an attempt to fight the increase in PCP use, the Drug Enforcement Administration (DEA) moved the drug into Schedule I, a classification reserved for drugs with high potential for abuse and the use of which may lead to severe physical or psychological dependence. The illicit manufacture of the drug was addressed by making the precursor chemicals more difficult to obtain. In 1978, PCP was withdrawn from veterinary use and is now available in the United States only through illicit manufacturing. Despite all attempts by the DEA to halt the use of PCP, PCP continues to be a major drug of abuse in many large cities and in the rural areas of central California.

Phencyclidine has been illegally marketed under many diverse names, more than any other street drug except perhaps marijuana Some common names include animal tranquilizer, angel dust, cannabinol, CJ, crystal, elephant tranquilizer, embalming fluid, horse tranquilizer, juice, lovely, mint weed, peace pill, rocket fuel, sherm, Sherman, super grass, super weed, THC, frank, water, and wack. A group called Dance Safe has reported that PCP has appeared combined with methamphetamine or ephedrine in pills sold as Ecstasy at raves in Ohio and Michigan in the year 2000. A new street drug called “illy” appeared in Connecticut in 2005. Of 59 patients treated for silly intoxication, 92% tested positive for phencyclidine, suggesting that the active ingredient in illy is primarily Phencyclidine.

Phencyclidine use in the United States in the 1990s remained relatively constant. The Monitoring the Future study shows that the number of high school seniors reporting PCP use has varied from 1.4 to 2.6%, with the data from 2000 showing 2.3%. Phencyclidine is apparently not a common drug of abuse in other countries. The international Narcotics Control Strategy Reports produced by the US State Department from 1997 to 2008 mention PCP and its analogs by stating that a small number of labs in the Balkan states have been seized in the past 10 years.

Other compounds, such as dextromethorphan, have been subject to abuse apparently because of weak PCP-like behavioral properties. Dextromethorphan, and its metabolite, dextromethorphan interact with receptors in a manner similar to PCP, and abuse by youth is a growmg phenomenon. In addition, dizocilpine a very potent drug also known as MK-801—interacts in the brain in a manner similar to PCP. One death due to MK 801 overdose has been observed at the Harris County Medical Examiner’s office.

The synthetic procedures used for the manufacture of PCP have been adapted to illegally manufacture several compounds related to PCP, including 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP), N-ethyl-l-phenylcyclohexylamine (PCE), 1-(1-phenylcyclohexyl)pyrrolidine (PHP or PCP), 1 -piperidinocyclohexane carbonitrile (PCC) , and 1 -phenylcyclohexylamine. New designer analogs of PCP like N-(1-phenylcyclohexyl)-3-ethoxypropanamine (PCEPA) and 2-hydroxy-1-(1-phenyltetralyl)piperidine have been produced in an attempt to capitalize on the analgesic effects of the drug while avoiding the abuse potential and undesirable side effects.