Phencyclidine
Phencyclidine or phenylcyclohexyl piperidine, also known in its use as a street drug as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hallucinations, distorted perceptions of sounds, and psychotic behavior. As a recreational drug, it is typically smoked, but may be taken by mouth, snorted, or injected. It may also be mixed with cannabis or tobacco.
Adverse effects may include paranoia, addiction, and an increased risk of suicide, as well as seizures and coma in cases of overdose. Flashbacks may occur despite stopping usage. Chemically, PCP is a member of the arylcyclohexylamine class. PCP works primarily as an NMDA receptor antagonist.
PCP is most commonly used in the US. While usage peaked in the US in the 1970s, between 2005 and 2011, an increase in visits to emergency departments as a result of the drug occurred. As of 2022, in the US, about 0.7% of 12th-grade students reported using PCP in the prior year, while 1.7% of people in the US over age 25 reported using it at some point in their lives.
Recreational uses
Phencyclidine is used for its ability to induce a dissociative state.Effects
Behavioral effects can vary by dosage. Low doses produce numbness in the extremities and intoxication, characterized by staggering, unsteady gait, slurred speech, bloodshot eyes, and loss of balance. Moderate doses will produce analgesia and anesthesia. High doses may lead to convulsions. The drug is often illegally produced under poorly controlled conditions; this means that users may be unaware of the actual dose they are taking.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. PCP may induce feelings of strength, power, and invulnerability as well as a numbing effect on the mind.
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. Although uncommon, events of PCP-intoxicated individuals acting in an unpredictable fashion, possibly driven by their delusions or hallucinations, have been publicized. Other commonly cited types of incidents include inflicting property damage and self-mutilation of various types, such as pulling out one's teeth. These effects were not noted in its medicinal use in the 1950s and 1960s, however, reports of physical violence on PCP have often been shown to be unfounded.
Recreational doses of the drug also occasionally appear to induce a psychotic state, with emotional and cognitive impairment that resembles a schizophrenic episode. Users generally report feeling detached from reality.
Symptoms are summarized by the mnemonic device RED DANES: rage, erythema, dilated pupils, delusions, amnesia, nystagmus, excitation, and skin dryness.
Addiction
PCP is self-administered and induces ΔFosB expression in the D1-type medium spiny neurons of the nucleus accumbens, and accordingly, excessive PCP use is known to cause addiction. PCP's rewarding and reinforcing effects are at least partly mediated by blocking the NMDA receptors in the glutamatergic inputs to D1-type medium spiny neurons in the nucleus accumbens. PCP has been shown to produce conditioned place aversion and conditioned place preference in animal studies.Schizophrenia
A 2019 review found that the transition rate from a diagnosis of hallucinogen-induced psychosis to that of schizophrenia was 26%. This was lower than cannabis-induced psychosis but higher than amphetamine-, opioid-, alcohol-, and sedative-induced psychoses. In comparison, the transition rate to schizophrenia for "brief, atypical and not otherwise specified" psychosis was found to be 36%.Methods of administration
PCP has multiple routes of administration. 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.- 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.
- PCP hydrochloride can be insufflated, depending upon the purity. This is most often referred to as "angel dust".
- An oral pill can also be compressed from the co-compounded powder form of the drug. This is usually referred to as "peace pill".
- The free base is hydrophobic and may be absorbed through skin and mucous membranes. This form of the drug is commonly called "wack".
Management of intoxication
Forced acid diuresis may increase the clearance of PCP from the body, and was somewhat controversially recommended in the past as a decontamination measure. 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, a not-unusual manifestation of PCP toxicity.
Pharmacology
Pharmacodynamics
PCP is well known for its primary action on the NMDA receptor, an ionotropic glutamate receptor. As such, PCP is a non-competitive NMDA receptor antagonist. The role of NMDAR antagonism in the effect of PCP, ketamine, and related dissociative agents was first published in the early 1980s by David Lodge and colleagues. Other NMDA receptor antagonists include ketamine, tiletamine, dextromethorphan, nitrous oxide, and dizocilpine.Research also indicates that PCP inhibits nicotinic acetylcholine receptors among other mechanisms. Analogues of PCP exhibit varying potency at nACh receptors and NMDA receptors. Findings demonstrate that presynaptic nAChRs and NMDA receptor interactions influence the postsynaptic maturation of glutamatergic synapses and consequently impact synaptic development and plasticity in the brain. These effects can lead to inhibition of excitatory glutamate activity in certain brain regions such as the hippocampus and cerebellum 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.
PCP, like ketamine, also acts as a potent dopamine D2High receptor partial agonist in rat brain homogenate and has affinity for the human cloned D2High receptor. 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 in the treatment of PCP psychosis.
In addition to its well-explored interactions with NMDA receptors, PCP has also been shown to inhibit dopamine reuptake, and thereby leads to increased extracellular levels of dopamine and hence increased dopaminergic neurotransmission. However, PCP has little affinity for the human monoamine transporters, including the dopamine transporter. Instead, its inhibition of monoamine reuptake may be mediated by interactions with allosteric sites on the monoamine transporters. PCP is notably a high-affinity ligand of the PCP site 2, a not-well-characterized site associated with monoamine reuptake inhibition.
Studies on rats indicate that PCP interacts indirectly with opioid receptors to produce analgesia.
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 site of the NMDA receptor, the σ2 receptor , and the serotonin transporter. 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. These results suggest that PCP is a highly selective ligand of the NMDAR and σ2 receptor. However, PCP may also interact with allosteric sites on the monoamine transporters to produce inhibition of monoamine reuptake.