Index
Also known as PCP, angel dust, among other names, is a drug used for its mind-altering effects.
Phencyclidine can cause hallucinations , distorted perceptions of sounds, and violent behavior.
As a recreational drug, it is usually smoked, but can be taken by mouth, snorted, or injected. It can also be mixed with cannabis or tobacco.
Adverse effects can include seizures, coma, addiction, and an increased risk of suicide. Flashbacks can occur despite stopping use.
Chemically, phencyclidine is a member of the arylcyclohexylamine class, and pharmacologically, it is a dissociative anesthetic. Phencyclidine functions primarily as an N-methyl-D-aspartate receptor antagonist.
Phencyclidine is used most often in the United States. While use peaked in the 1970s, between 2005 and 2011 there was an increase in visits to emergency departments as a result of the drug.
As of 2017 in the United States, approximately 1% of people in grade twelve reported using phencyclidine in the previous year, while 2.9% of people age 25 and older reported using it at some point of their life.
Phencyclidine was first created in 1926 and marketed as an anesthetic drug in the 1950s. Its use in humans was not allowed in the United States in 1965 due to high rates of side effects, while its use in other animals is not allowed in 1978.
Furthermore, ketamine was discovered and better tolerated as an anesthetic. Phencyclidine is currently illegal in the United States, where it is classified as a Schedule II drug. Various phencyclidine derivatives have been sold for recreational and non-medical use.
Recreational uses
Effects edit
Behavioral effects can vary by dose. Low doses produce numbness in the extremities and intoxication, characterized by a shaky and unsteady gait, slurred speech, red eyes (bloodshot eyes), and loss of balance.
Moderate doses (5-10 mg intranasal, or 0.01-0.02 mg / kg intramuscularly or intravenously) will produce analgesia and anesthesia. High doses can cause seizures.
The drug is often produced illegally under conditions of inadequate control; this means that users may be unaware of the actual dose they are taking.
The psychological effects include severe changes in body image, loss of ego boundaries, paranoia, and depersonalization. Hallucinations, euphoria, and suicidal urges are also reported, as well as occasional aggressive behavior.
Like many other drugs, phencyclidine is known to alter moods in unpredictable ways, causing some people to take off and others to perk up.
Phencyclidine can induce feelings of strength, power, and invulnerability, as well as a numbing effect on the mind.
Studies conducted by the Drug Abuse Warning Network in the 1970s show that media reports of phencyclidine-induced violence are greatly exaggerated and incidents of violence are rare and often limited to individuals with reputations for aggression. regardless of drug use.
Although rare, the events of individuals intoxicated with phencyclidine acting in unpredictable ways, possibly prompted by their delusions or hallucinations, have been reported.
An example is the case of Big Lurch , a former rapper with a history of violent crime, who was convicted of murdering and killing his roommate under the influence of phencyclidine.
Other types of incidents commonly cited include inflicting property damage and self-mutilation of various kinds, such as pulling one’s own teeth.
However, these effects were not seen in its medicinal use in the 1950s and 1960s, and reports of physical violence against phencyclidine have often proven unfounded.
Recreational doses of the drug also occasionally appear to induce a psychotic state resembling a schizophrenic episode, sometimes lasting for months. Users generally report that they feel detached from reality.
The symptoms are : fury, erythema (reddening of the skin), dilated pupils, delusions, amnesia , nystagmus (oscillation of the eyeball when it moves laterally), excitement and dryness of the skin.
Addiction
Phencyclidine is self-administered and induces the expression of ΔFosB (Delta FosB) in D1-type medium spiny neurons of the nucleus accumbens, and consequently, excessive use of phencyclidine is known to cause addiction.
Delta FosB or ΔFosB is a truncated splice variant of FosB. ΔFosB has been implicated as a critical factor in the development of virtually all forms of drug addiction and behaviors.
In the brain’s reward system, it is linked to changes in various other gene products. In the body, ΔFosB regulates the commitment of mesenchymal precursor cells to the adipocyte or osteoblast lineage.
The reward and reinforcing effects of phencyclidine are mediated, at least in part, by N-methyl-D-aspartate receptors on glutamatergic inputs to D1-type spiny neurons in the nucleus accumbens.
Phencyclidine has been shown to produce conditioned place aversion and conditioned place preference in animal studies.
Administration methods
Phencyclidine comes in liquid and powdered form (phencyclidine base is most often dissolved in ether), but is usually sprayed onto a leaf material such as cannabis, peppermint, oregano, tobacco, parsley, or ginger, and then smoked .
Phencyclidine can be ingested when smoking. “Fry” or “Fry” is a street term for marijuana or tobacco cigarettes that are dipped in phencyclidine and then dried.
Phencyclidine Hydrochloride can be insufflated (inhaled), depending on purity.
The free base is quite hydrophobic and can be absorbed through the skin and mucous membranes (often inadvertently).
Management of poisoning
The management of phencyclidine poisoning consists mainly of supportive care, which controls breathing, circulation and body temperature, and, in the early stages, in the treatment of psychiatric symptoms.
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 they can produce many undesirable side effects, such as dystonia, so their use is no longer preferred.
Phenothiazines are particularly risky as they can lower the seizure threshold, worsen hyperthermia, and increase the anticholinergic effects of phencyclidine. If an antipsychotic is administered, intramuscular haloperidol is recommended.
Forced acid diuresis (with ammonium chloride or, more likely, ascorbic acid) can increase the clearance of phencyclidine from the body, and has been somewhat controversially recommended as a decontamination measure in the past.
However, it is now known that only about 10% of a dose of phencyclidine is excreted by the kidneys, which would increase minor urinary clearance.
Additionally, urinary acidification is dangerous as it can induce acidosis and worsen rhabdomyolysis (muscle breakdown), which is not an unusual manifestation of phencyclidine toxicity.
Pharmacology
Pharmacodinámica
Phencyclidine is well known for its primary action on the N-methyl-D-aspartate receptor, an ionotropic glutamate receptor, in rats and rat brain homogenate.
As such, phencyclidine is an N-methyl-D-aspartate receptor antagonist. The role of N-methyl-D-aspartate receptor antagonism on the effect of phencyclidine, ketamine, and related dissociative agents was first published in the early 1980s by David Lodge and colleagues.
Other N-methyl-D-aspartate receptor antagonists include ketamine, tiletamine, dextromethorphan, nitrous oxide, and dizocilpine (MK-801).
Research also indicates that phencyclidine inhibits nicotinic acetylcholine receptors (nAChRs) among other mechanisms.
Phencyclidine analogs exhibit variable potency at nicotinic acetylcholine receptors and N-methyl-D-aspartate receptors.
The results demonstrate that presynaptic nicotinic acetylcholine receptors and N-methyl-D-aspartate receptor interactions influence postsynaptic maturation of glutamatergic synapses and consequently affect synaptic development and plasticity in the brain.
These effects can lead to inhibition of the excitatory activity of glutamate in certain regions of the brain, such as the hippocampus and cerebellum, which can lead to memory loss as one of the effects of long-term use.
Acute effects on the cerebellum manifest as changes in blood pressure, respiratory rate, pulse rate, and loss of muscle coordination during intoxication.
Phencyclidine, like ketamine, also acts as a potent partial agonist of the dopamine D2High receptor in rat brain homogenate and has affinity for the cloned human D2High receptor.
This activity may be associated with some of the other more psychotic features of phencyclidine poisoning, which is evidenced by the successful use of D2 receptor antagonists (such as haloperidol) in the treatment of phencyclidine psychosis.
In addition to its well-explored interactions with N-methyl-D-aspartate receptors, phencyclidine has also been shown to inhibit dopamine reuptake and thus increase extracellular dopamine levels and thus increase the dopaminergic neurotransmission.
However, phencyclidine has low affinity for human monoamine transporters, including the dopamine transporter (DAT).
Instead, their inhibition of monoamine reuptake may be mediated by interactions with allosteric sites on monoamine transporters.
Phencyclidine is notably a high affinity ligand for the phencyclidine site 2 (Ki = 154 nM), a poorly characterized site associated with inhibition of monoamine reuptake.
Studies in rats indicate that phencyclidine indirectly interacts with opioid receptors (endorphin and enkephalin) to produce analgesia.
A binding study evaluated phencyclidine at 56 sites, including neurotransmitter receptors and transporters, and found that phencyclidine had Ki values of> 10,000 nM at all sites except the dizocylpine (MK-801) site of the N-methyl-receptor. D-aspartate (Ki = 59 nM), the σ2 receptor (PC12) (Ki = 136 nM) and the serotonin transporter (Ki = 2234 nM).
The study found Ki values of> 10,000 nM for the D2 receptor, opioid receptors, σ1 receptor, and dopamine and norepinephrine transporters.
These results suggest that phencyclidine is a highly selective ligand for the N-methyl-D-aspartate receptor and for the σ2 receptor. However, phencyclidine can also interact with allosteric sites on monoamine transporters to produce inhibition of monoamine reuptake.
Neurotoxicidad
Some studies found that, like other N-methyl-D-aspartate receptor antagonists, phencyclidine can cause a type of brain damage called Olney’s lesions in rats.
Studies in rats showed that high doses of the N-methyl-D-aspartate receptor antagonist dizocilpine caused the formation of reversible vacuoles in certain regions of rat brains.
All studies of Olney’s lesions have only been conducted in non-human animals and may not apply to humans.
An unpublished study by Frank Sharp reportedly showed no harm from the N-methyl-D-aspartate antagonist ketamine, a similar drug, well beyond recreational doses, but because the study was never published , its validity is controversial.
Phencyclidine has also been shown to cause schizophrenia-like changes in the levels of N-acetylaspartate and N-acetylaspartyl glutamate in rat brain, which are detectable both in live rats and on necropsy examination of brain tissue.
It also induces symptoms in humans that mimic schizophrenia. Not only did phencyclidine produce schizophrenia-like symptoms, but it also produced EEG changes in the thalamocortical pathway (increased delta decreased alpha) and in the hippocampus (increased theta bursts) that were similar to those of schizophrenia.
The phencyclidine-induced increase in dopamine release may link N-methyl-D-aspartate and the DA hypothesis of schizophrenia.
Pharmacokinetics
Phencyclidine is metabolized to 1- (1-phenylcyclohexyl) -4-hydroxypiperidine (PCHP), 4-phenyl-4- (1-piperidinyl) cyclohexanol, also known as PPC and PCAA (for its acronym in English), or 5- [N- (1-phenylcyclohexyl)] -aminopentanoic acid.
When smoked, part of the compound is decomposed by heat into 1-phenylcyclohexene (PC) and piperidine.
Chemistry
Phencyclidine is an arylcyclohexylamine .
Analogues
Less than 30 different phencyclidine analogs were reported to have been used on the street during the 1970s and 1980s, primarily in the United States.
The best known of these are rolicyclidine (PCPy or 1- (1-phenylcyclohexyl) pyrrolidine); ethyclidine (PCE or N-ethyl-1-phenylcyclohexylamine); and tenocyclidine (TCP or 1- (1- (2-thienyl) cyclohexyl) piperidine). Only some of these compounds were widely used.
The generalized structural motif required for phencyclidine-like activity is derived from structure-activity relationship studies of phencyclidine derivatives, and is summarized in the illustration (right).
It is likely that all of these derivatives share some of their psychoactive effects with phencyclidine itself, although a range of varying potencies and 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 phencyclidine-like controlled substances and are therefore illegal drugs if sold for human consumption, although many of them have never been made or tried.
Other Phencyclidine analogs include 3-Hydroxyphencyclidine (3-HO-PCP), 3-MeO-PCMo, and 3-Methoxyphencyclidine (3-MeO-PCP).
Use
Phencyclidine began to emerge as a recreational drug in major cities in the United States in the 1960s. In 1978, People magazine and Mike Wallace of 60 Minutes named Phencyclidine the “number one” drug problem in the country.
Although recreational use of the drug had always been relatively low, it began to decline significantly in the 1980s. In surveys, the number of high school students who admitted to having tried phencyclidine at least once decreased from 13% in 1979 to less than 3% in 1990.
History
It is commonly wrongly reported that phencyclidine was first synthesized in 1926. This early synthesis, in fact, refers to the intermediate phencyclidine Piperidinocyclohexanecarbonitrile.
Phencyclidine was discovered by Victor Maddox , a chemist at Parke-Davis in Michigan, while researching synthetic analgesic agents. Although unexpected, phencyclidine was identified as potentially interesting, and as such underwent pharmacological testing.
The promising results of these pharmacological investigations led to the rapid development of phencyclidine.
It was approved for use as an investigational drug under the brand names Sernyl and Sernylan in the 1950s as an anesthetic, but due to its long terminal half-life and adverse side effects, such as hallucinations, mania, delirium, and disorientation, it was withdrawn from the market. in 1965 and limited to veterinary use.
Regulation
Phencyclidine is a Schedule II substance in the United States and its Administrative Controlled Substances Code Number (ACSCN) is 7471. Its manufacturing quota for 2014 was 19 grams.
It is a Schedule I drug by the Drugs and Controlled Substances Act in Canada, a Schedule I drug by the Opium Act in the Netherlands, and a Class A substance in the UK.
