PCP is most commonly used in the United States.[14] While usage peaked in the US in the 1970s,[15] between 2005 and 2011 an increase in visits to emergency departments as a result of the drug occurred.[10] As of 2017 in the United States, about 1% of people in
12th grade reported using PCP in the prior year while 2.9% of those over the age of 25 reported using it at some point in their lives.[16]
Recreational uses
Phencyclidine is used for its ability to induce a dissociative state.[17]
Effects
Behavioral effects can vary by dosage. Low doses produce a numbness in the extremities and intoxication, characterized by staggering, unsteady gait, slurred speech, bloodshot eyes, and loss of balance. Moderate doses (5–10 mg intranasal, or 0.01–0.02 mg/kg intramuscular or intravenous) will produce
analgesia and anesthesia. High doses may lead to
convulsions.[18] The drug is often illegally produced under poorly controlled conditions; this means that users may be unaware of the actual dose they are taking.[19]
Psychological effects include severe changes in
body image,
loss of ego boundaries,
paranoia, and
depersonalization. Psychosis, agitation and dysphoria, hallucinations, blurred vision,
euphoria, and
suicidal impulses are also reported, as well as occasional aggressive behavior.[20][21]: 48–49 [18] Like many other drugs, PCP has been known to alter mood states in an unpredictable fashion, causing some individuals to become detached, and others to become animated. PCP may induce feelings of strength, power, and invulnerability as well as a numbing effect on the mind.[8]
Studies by the
Drug Abuse Warning Network in the 1970s show that media reports of PCP-induced violence are greatly exaggerated and that incidents of violence are unusual and often limited to individuals with reputations for aggression regardless of drug use.[21]: 48 Although uncommon, events of PCP-intoxicated individuals acting in an unpredictable fashion, possibly driven by their delusions or hallucinations, have been publicized.[22] Other commonly cited types of incidents include inflicting property damage and self-mutilation of various types, such as pulling one's own teeth.[21]: 48 [22] These effects were not noted in its medicinal use in the 1950s and 1960s, however, and reports of physical violence on PCP have often been shown to be unfounded.[23][24]
Recreational doses of the drug also occasionally appear to
induce a psychotic state, with emotional and cognitive impairment that resembles a
schizophrenic episode.[25][26] Users generally report feeling detached from reality.[27]
Symptoms are summarized by the
mnemonic device RED DANES: rage,
erythema (redness of skin), dilated pupils, delusions,
amnesia,
nystagmus (oscillation of the eyeball when moving laterally), excitation, and skin dryness.[28]
A 2019 review found that the transition rate from a diagnosis of
hallucinogen-induced psychosis (which included PCP) to that of schizophrenia was 26%. This was lower than cannabis-induced psychosis (34%) but higher than amphetamine (22%), opioid (12%), alcohol (10%), and sedative (9%) induced psychoses. In comparison, the transition rate to schizophrenia for "brief, atypical and not otherwise specified" psychosis was found to be 36%.[31]
Methods of administration
"Sherm stick" redirects here. For the song by Jayo Felony, see
Take a Ride.
PCP is easily accessible because of the various routes of administration available. Most commonly, the powder form of the drug is snorted. PCP can also be orally ingested, injected subcutaneously or intravenously, or smoked laced with marijuana or cigarettes.[32]
PCP can be ingested through smoking. "Fry" and "sherm" are street terms for marijuana or tobacco cigarettes that are dipped in PCP and then dried.[33]
PCP hydrochloride can be insufflated (snorted), depending upon the purity. This is most often referred to as "angel dust".[32]
An oral pill can also be compressed from the co-compounded powder form of the drug. This is usually referred to as "peace pill".[32]
The
free base is hydrophobic and may be absorbed through skin and mucus membranes (often inadvertently). This form of the drug is commonly called "wack".[32]
Management of intoxication
Management of PCP intoxication mostly consists of supportive care – controlling breathing, circulation, and body temperature – and, in the early stages, treating psychiatric symptoms.[34][35][36]Benzodiazepines, such as
lorazepam, are the
drugs of choice to control agitation and seizures (when present).
Typical antipsychotics such as
phenothiazines and
haloperidol have been used to control psychotic symptoms, but may produce many undesirable side effects – such as
dystonia – and their use is therefore no longer preferred; phenothiazines are particularly risky, as they may lower the
seizure threshold, worsen
hyperthermia, and boost the
anticholinergic effects of PCP.[34][35] If an antipsychotic is given,
intramuscular haloperidol has been recommended.[36][37][38]
Forced acid diuresis (with
ammonium chloride or, more safely,
ascorbic acid) may increase clearance of PCP from the body, and was somewhat controversially recommended in the past as a
decontamination measure.[34][35][36] However, it is now known that only around 10% of a dose of PCP is removed by the kidneys, which would make increased urinary clearance of little consequence; furthermore, urinary
acidification is dangerous, as it may induce
acidosis and worsen
rhabdomyolysis (muscle breakdown), a not-unusual manifestation of PCP toxicity.[34][35]
Research also indicates that PCP inhibits
nicotinic acetylcholine receptors (nAChRs) among other mechanisms. Analogues of PCP exhibit varying potency at nACh receptors[55] and NMDA receptors.[56] Findings demonstrate that presynaptic nAChRs and NMDA receptor interactions influence postsynaptic maturation of glutamatergic synapses and consequently impact synaptic development and plasticity in the brain.[57] These effects can lead to inhibition of excitatory glutamate activity in certain brain regions such as the
hippocampus[58] and
cerebellum[59] thus potentially leading to memory loss as one of the effects of prolonged use. Acute effects on the
cerebellum manifest as changes in blood pressure, breathing rate, pulse rate, and loss of muscular coordination during intoxication.[11]
PCP, like ketamine, also acts as a potent
dopamineD2High receptorpartial agonist in rat brain homogenate[46] and has affinity for the human cloned D2High receptor.[60] This activity may be associated with some of the other more psychotic features of PCP intoxication, which is evidenced by the successful use of D2 receptor antagonists (such as
haloperidol) in the treatment of PCP psychosis.[61]
A binding study assessed PCP at 56 sites including
neurotransmitter receptors and
transporters and found that PCP had Ki values of >10,000 nM at all sites except the
dizocilpine (MK-801) site of the NMDA receptor (Ki = 59 nM), the
σ2 receptor (
PC12) (Ki = 136 nM), and the
serotonin transporter (Ki = 2,234 nM).[41] The study notably found Ki values of >10,000 nM for the
D2 receptor, the
opioid receptors, the
σ1 receptor, and the
dopamine and
norepinephrine transporters.[41] These results suggest that PCP is a highly selective ligand of the NMDAR and σ2 receptor.[41] However, PCP may also interact with allosteric sites on the monoamine transporters to produce inhibition of monoamine reuptake.[41]
Mechanism of action
Phencyclidine is a noncompetitive NMDA receptor antagonist that blocks the activity of the NMDA receptor to cause anaesthesia and analgesia without causing cardiorespiratory depression.[64][20] NMDA is an excitatory receptor in the brain, when activated normally the receptor acts as an ion channel and there is an influx of positive ions through the channel to cause nerve cell depolarisation. Phencyclidine inhibits the NMDA receptor by binding to the specific PCP binding site located within the ion channel.[65] The PCP binding site is within close proximity to the magnesium blocking site, which may explain the similar inhibitory effects.[66] Binding at the PCP site is mediated by two non-covalent interactions within the receptor: hydrogen bonding and hydrophobic interaction.[67] Binding is also controlled by the gating mechanism of the ion channel. Because the PCP site is located within the ion channel, a coagonist such as glycine must bind and open the channel in order for PCP to enter, bind to the PCP site, and block the channel.[68]
Neurotoxicity
Some studies found that, like other NMDA receptor antagonists, PCP can cause a kind of
brain damage called
Olney's lesions in rats.[69][70] Studies conducted on rats showed that high doses of the NMDA receptor antagonist
dizocilpine caused reversible
vacuoles to form in certain regions of the rats' brains. All studies of Olney's lesions have only been performed on non-human animals and may not apply to humans. One unpublished study by Frank Sharp reportedly showed no damage by the NDMA antagonist ketamine, a structurally similar drug, far beyond recreational doses,[71] but due to the study never having been published, its validity is controversial.
PCP has also been shown to cause schizophrenia-like changes in N-acetylaspartate and N-acetylaspartylglutamate levels in the rat brain, which are detectable both in living rats and upon necropsy examination of brain tissue.[72] It also induces symptoms in humans that mimic schizophrenia.[73] PCP not only produced symptoms similar to schizophrenia, it also yielded
electroencephalogram changes in the thalamocortical pathway (increased delta decreased alpha) and in the hippocampus (increase theta bursts) that were similar to those in schizophrenia.[74] PCP-induced augmentation of dopamine release may link the NMDA and
dopamine hypotheses of schizophrenia.[75]
The time taken before the effects of PCP manifest is dependent on the route of administration. The onset of action for inhalation occurs in 2–5 minutes, whereas the effects may take 15 to 60 minutes when ingested orally.[20]
The generalized structural motif required for PCP-like activity is derived from structure-activity relationship studies of PCP derivatives. All of these derivatives are likely to share some of their psychoactive effects with PCP itself, although a range of potencies and varying mixtures of anesthetic, dissociative, and stimulant effects are known, depending on the particular drug and its substituents. In some countries such as the United States, Australia, and New Zealand, all of these compounds would be considered controlled substance analogs of PCP under the
Federal Analog Act and are hence illegal drugs if sold for human consumption.[76][77]
History
Phencyclidine was initially discovered in 1926 by
Arthur Kötz [
de] and his student Paul Merkel as a product of a
Grignard reaction of 1-piperidinocyclohexancarbonitrile.[78]
It was again made in 1956 and brought to market as an
anesthetic medication.[74][13][79][78][80] Its use in humans was disallowed in the United States in 1965 due to the high rates of side effects, while its use in animals was disallowed in 1978.[1][13][81] Moreover,
ketamine was discovered and was better tolerated as an anesthetic.[81]
PCP is classified as a
schedule II drug in the United States.[1] A number of derivatives of PCP have been sold for recreational and non-medical use.[51]
Society and culture
Regulation
PCP is a
Schedule II substance in the United States and its
ACSCN is 7471.[82] Its manufacturing quota for 2014 was 19 grams.[83]
It is a Schedule I drug by the Controlled Drugs and Substances act in Canada, a List I drug of the
Opium Law in the
Netherlands, and a
Class A substance in the United Kingdom.[84]
Frequency of use
PCP began to emerge as a
recreational drug in major cities in the United States in the 1960s.[10] In 1978, People magazine and
Mike Wallace of 60 Minutes called PCP the country's "number one" drug problem. Although recreational use of the drug had always been relatively low, it began declining significantly in the 1980s. In surveys, the number of
high school students admitting to trying PCP at least once fell from 13% in 1979 to less than 3% in 1990.[21]: 46–49
In
Vivienne Medrano's adult animated musical comedy television series
Hazbin Hotel, Angel Dust is an adult film star in Hell and one of the main protagonists.[86] He is known to struggle with addiction to phencyclidine, currently and during his time on earth. Additionally his canon cause of death is overdose by phencyclidine, naming himself after the drug.[87]
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