1.
Opioid
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Opioids are substances that act on opioid receptors to produce morphine-like effects. Opioids are most often used medically to relieve pain, and by people addicted to opioids, opioids include opiates, an older term that refers to such drugs derived from opium, including morphine itself. Other opioids are semi-synthetic and synthetic drugs such as hydrocodone, oxycodone and fentanyl, antagonist drugs such as naloxone, the terms opiate and narcotic are sometimes encountered as synonyms for opioid. Opiate is properly limited to the alkaloids found in the resin of the opium poppy although some include semi-synthetic derivatives. In some jurisdictions all controlled drugs are classified as narcotics. The term can have pejorative connotations and its use is discouraged where that is the case. Primarily used for relief, including anesthesia they are also used to suppress cough, suppress diarrhea, treat addiction, reverse opioid overdose. Extremely strong opioids are approved only for use such as immobilizing large mammals. Opioids act by binding to receptors, which are found principally in the central and peripheral nervous system. These receptors mediate both the psychoactive and the effects of opioids. The side effects of opioids may include itchiness, sedation, nausea, respiratory depression, constipation, Tolerance and dependence will develop with continuous use, requiring increasing doses and leading to a withdrawal syndrome upon abrupt discontinuation. The euphoria attracts recreational use, and frequent, escalating recreational use of opioids typically results in addiction, accidental overdose or concurrent use with other depressant drugs commonly results in death from respiratory depression. Because of opioid drugs reputation for addiction and fatal overdose, most are controlled substances, illicit production, smuggling, and addiction to opioids prompted treaties, laws and policing which have realized limited success. In 2013 between 28 and 38 million people used opioids illicitly, in 2011 an estimated 4 million people in the United States used opioids recreationally or were dependent on them. Current increased rates of use and addiction are attributed to over-prescription of opioid medications. Conversely, fears about over-prescribing, exaggerated side effects and addiction from opioids are similarly blamed for under-treatment of pain, the term opioid originated in the 1950s. It combines opium + -oid meaning opiate-like, by the late 1960s, research found that opiate effects are mediated by activation of specific molecular receptors in the nervous system, which were termed opioid receptors. The definition of opioid was later refined to refer to substances that have activities that are mediated by the activation of opioid receptors
2.
Scientific method
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The scientific method is a body of techniques for investigating phenomena, acquiring new knowledge, or correcting and integrating previous knowledge. To be termed scientific, a method of inquiry is commonly based on empirical or measurable evidence subject to specific principles of reasoning, experiments need to be designed to test hypotheses. The most important part of the method is the experiment. The scientific method is a process, which usually begins with observations about the natural world. Human beings are naturally inquisitive, so often come up with questions about things they see or hear. The best hypotheses lead to predictions that can be tested in various ways, in general, the strongest tests of hypotheses come from carefully controlled and replicated experiments that gather empirical data. Depending on how well the tests match the predictions, the hypothesis may require refinement. If a particular hypothesis becomes very well supported a theory may be developed. Although procedures vary from one field of inquiry to another, identifiable features are shared in common between them. The overall process of the method involves making conjectures, deriving predictions from them as logical consequences. A hypothesis is a conjecture, based on knowledge obtained while formulating the question, the hypothesis might be very specific or it might be broad. Scientists then test hypotheses by conducting experiments, the purpose of an experiment is to determine whether observations agree with or conflict with the predictions derived from a hypothesis. Experiments can take anywhere from a college lab to CERNs Large Hadron Collider. There are difficulties in a statement of method, however. Though the scientific method is presented as a fixed sequence of steps. Not all steps take place in scientific inquiry, and are not always in the same order. Some philosophers and scientists have argued there is no scientific method, such as Lee Smolin. Nola and Sankey remark that For some, the idea of a theory of scientific method is yester-years debate
3.
Hallucinogen
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A hallucinogen is a psychoactive agent which can cause hallucinations, perceptual anomalies, and other substantial subjective changes in thoughts, emotion, and consciousness. The common types of hallucinogens are psychedelics, dissociatives and deliriants, although hallucinations are a common symptom of amphetamine psychosis, amphetamines are not considered hallucinogens, as they are not a primary effect of the drugs themselves. While hallucinations can occur when abusing stimulants, the nature of stimulant psychosis is not unlike delirium, a debate persists on criteria which would easily differentiate a substance which is psychedelic from one hallucinogenic. Sir Thomas Browne in 1646 coined the term hallucination from the Latin word alucinari meaning to wander in the mind, the term psychedelic is derived from the Ancient Greek words psychē and dēloun, or mind-revealing. A hallucinogen and a psychedelic may refer correctly to the same substance, hallucinations and psychedelia may both refer to the same aspects of subjective experience in a given instance. A hallucinogen in this sense refers to any substance which causes changes in perception or hallucinations. In contrast to Hollisters original criteria, adverse effects may predominate with some hallucinogens with this application of the term, the word psychedelic was coined to express the idea of a drug that makes manifest a hidden but real aspect of the mind. One explanatory model for the experiences provoked by psychedelics is the reducing valve concept, in this view, the drugs disable the brains filtering ability to selectively prevent certain perceptions, emotions, memories and thoughts from ever reaching the conscious mind. This effect has been described as mind expanding, or consciousness expanding, many designer drugs and research chemicals are hallucinogenic in nature, such as those in the 2C and NBOMe families. Dissociatives produce analgesia, amnesia and catalepsy at anesthetic doses, dissociative symptoms include the disruption or compartmentalization of. the usually integrated functions of consciousness, memory, identity or perception. p. 523 Dissociation of sensory input can cause derealization, the perception of the world as being dream-like or unreal. The primary dissociatives achieve their effect through blocking the signals received by the NMDA receptor set and include ketamine, methoxetamine, phencyclidine, dextromethorphan, however, dissociation is also remarkably administered by salvinorin As potent κ-opioid receptor agonism. Some dissociatives can have CNS depressant effects, thereby carrying similar risks as opioids, DXM in higher doses can increase heart rate and blood pressure and still depress respiration. Inversely, PCP can have unpredictable effects and has often been classified as a stimulant. While many have reported that they feel no pain while under the effects of PCP, DXM and Ketamine, this does not fall under the usual classification of anesthetics in recreational doses. Rather, true to their name, they process pain as a kind of far away sensation, pain, although present, becomes a disembodied experience, as for probably the most common dissociative, nitrous oxide, the principal risk seems to be due to oxygen deprivation. Injury from falling is also a danger, as nitrous oxide may cause loss of consciousness. Because of the level of physical activity and relative imperviousness to pain induced by PCP
4.
Guinea pig
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The guinea pig, cavy or domestic guinea pig, or cuy for livestock breeds, is a species of rodent belonging to the family Caviidae and the genus Cavia. Despite their common name, these animals are not in the pig family Suidae, recent studies applying molecular markers, in addition to studying the skull and skeletal morphology of current and mummified animals, revealed that the ancestor is most likely Cavia tschudii. Since the 1960s, efforts have made to increase consumption of the animal outside South America. In Western societies, the guinea pig has enjoyed widespread popularity as a household pet since its introduction by European traders in the 16th century. Their docile nature, friendly, even affectionate responsiveness to handling and feeding, biological experimentation on guinea pigs has been carried out since the 17th century. They are still used in research, primarily as models for medical conditions such as juvenile diabetes, tuberculosis, scurvy. The guinea pig was first domesticated as early as 5000 BC for food by tribes in the Andean region of South America, statues dating from circa 500 BC to 500 AD that depict guinea pigs have been unearthed in archaeological digs in Peru and Ecuador. The Moche people of ancient Peru worshipped animals and often depicted the guinea pig in their art, from about 1200 AD to the Spanish conquest in 1532, selective breeding resulted in many varieties of domestic guinea pigs, which form the basis for some of the modern domestic breeds. They continue to be a source in the region, many households in the Andean highlands raise the animal. Folklore traditions involving guinea pigs are numerous, they are exchanged as gifts, used in social and religious ceremonies. They also play a role in healing rituals by folk doctors, or curanderos, who use the animals to diagnose diseases such as jaundice, rheumatism, arthritis. They are rubbed against the bodies of the sick, and are seen as a supernatural medium, black guinea pigs are considered especially useful for diagnoses. The animal also may be cut open and its entrails examined to determine whether the cure was effective and these methods are widely accepted in many parts of the Andes, where Western medicine is either unavailable or distrusted. Spanish, Dutch, and English traders brought guinea pigs to Europe, the guinea pig was first described in the West in 1554 by the Swiss naturalist Conrad Gessner. Its binomial scientific name was first used by Erxleben in 1777, it is an amalgam of Pallas generic designation, the scientific name of the common species is Cavia porcellus, with porcellus being Latin for little pig. Cavia is New Latin, it is derived from cabiai, the name in the language of the Galibi tribes once native to French Guiana. Cabiai may be an adaptation of the Portuguese çavia, which is derived from the Tupi word saujá. Guinea pigs are called quwi or jaca in Quechua and cuy or cuyo in the Spanish of Ecuador, Peru, and Bolivia
5.
Brain
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The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. The brain is located in the head, usually close to the organs for senses such as vision. The brain is the most complex organ in a vertebrates body, in a human, the cerebral cortex contains approximately 15–33 billion neurons, each connected by synapses to several thousand other neurons. Physiologically, the function of the brain is to exert centralized control over the other organs of the body, the brain acts on the rest of the body both by generating patterns of muscle activity and by driving the secretion of chemicals called hormones. This centralized control allows rapid and coordinated responses to changes in the environment, the operations of individual brain cells are now understood in considerable detail but the way they cooperate in ensembles of millions is yet to be solved. This article compares the properties of brains across the range of animal species. It deals with the human brain insofar as it shares the properties of other brains, the ways in which the human brain differs from other brains are covered in the human brain article. Several topics that might be covered here are instead covered there because more can be said about them in a human context. The most important is brain disease and the effects of brain damage, the shape and size of the brain varies greatly between species, and identifying common features is often difficult. Nevertheless, there are a number of principles of architecture that apply across a wide range of species. Some aspects of structure are common to almost the entire range of animal species, others distinguish advanced brains from more primitive ones. The simplest way to gain information about brain anatomy is by visual inspection, Brain tissue in its natural state is too soft to work with, but it can be hardened by immersion in alcohol or other fixatives, and then sliced apart for examination of the interior. Visually, the interior of the consists of areas of so-called grey matter, with a dark color, separated by areas of white matter. Further information can be gained by staining slices of tissue with a variety of chemicals that bring out areas where specific types of molecules are present in high concentrations. It is also possible to examine the microstructure of brain tissue using a microscope, the brains of all species are composed primarily of two broad classes of cells, neurons and glial cells. Glial cells come in types, and perform a number of critical functions, including structural support, metabolic support, insulation. Neurons, however, are considered the most important cells in the brain. The property that makes neurons unique is their ability to send signals to target cells over long distances
6.
Mouse
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A mouse is a small rodent characteristically having a pointed snout, small rounded ears, a body-length scaly tail and a high breeding rate. The best known species is the common house mouse. It is also a popular pet, in some places, certain kinds of field mice are locally common. They are known to invade homes for food and shelter, domestic mice sold as pets often differ substantially in size from the common house mouse. This is attributable both to breeding and to different conditions in the wild, the most well known strain, the white lab mouse, has more uniform traits that are appropriate to its use in research. The American white-footed mouse and the mouse, as well as other common species of mouse-like rodents around the world. These, however, are in other genera, cats, wild dogs, foxes, birds of prey, snakes and even certain kinds of arthropods have been known to prey heavily upon mice. Nevertheless, because of its adaptability to almost any environment. Mice, in contexts, can be considered vermin which are a major source of crop damage, causing structural damage. In North America, breathing dust that has come in contact with mouse excrement has been linked to hantavirus, primarily nocturnal animals, mice compensate for their poor eyesight with a keen sense of hearing, and rely especially on their sense of smell to locate food and avoid predators. Mice build intricate burrows in the wild and these burrows typically have long entrances and are equipped with escape tunnels or routes. In at least one species, the design of a burrow is a genetic trait. Breeding onset is at about 50 days of age in females and males, although females may have their first estrus at 25–40 days. Mice are polyestrous and breed year round, ovulation is spontaneous, the duration of the estrous cycle is 4–5 days and estrus itself lasts about 12 hours, occurring in the evening. Vaginal smears are useful in timed matings to determine the stage of the estrous cycle, mating is usually nocturnal and may be confirmed by the presence of a copulatory plug in the vagina up to 24 hours post-copulation. The presence of sperm on a smear is also a reliable indicator of mating. Female mice housed together tend to go into anestrus and do not cycle, if exposed to a male mouse or the pheromones of a male mouse, most of the females will go into estrus in about 72 hours. This synchronization of the cycle is known as the Whitten effect
7.
NMDA receptor
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The N-methyl-D-aspartate receptor, is a glutamate receptor and ion channel protein found in nerve cells. It is activated when glutamate and glycine bind to it, the NMDA receptor is very important for controlling synaptic plasticity and memory function. The NMDAR is a type of ionotropic glutamate receptor. The NMDA receptor is named this because the agonist molecule N-methyl-D-aspartate binds selectively to it, activation of NMDA receptors results in the opening of an ion channel that is nonselective to cations, with a reversal potential near 0 mV. While the opening and closing of the ion channel is primarily gated by ligand binding, extracellular magnesium and zinc ions can bind to specific sites on the receptor, blocking the passage of other cations through the open ion channel. Ca2+ flux through NMDARs is thought to be critical in synaptic plasticity, the opening and closing of the NMDA receptor is complex. While it is primarily a ligand-gated channel, it does display weaker voltage-dependence modulation of the ligand-dependent gating, the ligand gating requires co-activation by two ligands, glutamate and either D-serine or glycine. The voltage-dependence of current through the channel is due to binding of Mg2+ or Zn2+ ions to the protein as described above. The activity of the NMDA receptor is affected by many drugs such as phencyclidine, alcohol. The anaesthetic effects of the drugs ketamine and nitrous oxide are partially because of their effects on NMDA receptor activity, the NMDA receptor forms a heterotetramer between two GluN1 and two GluN2 subunits, two obligatory NR1 subunits and two regionally localized NR2 subunits. A related gene family of NR3 A and B subunits have an effect on receptor activity. Multiple receptor isoforms with distinct brain distributions and functional properties arise by selective splicing of the NR1 transcripts, NR1 subunits bind the co-agonist glycine and NR2 subunits bind the neurotransmitter glutamate. The agonist-binding module links to a domain, which consists of three transmembrane segments and a re-entrant loop reminiscent of the selectivity filter of potassium channels. The membrane domain contributes residues to the pore and is responsible for the receptors high-unitary conductance, high-calcium permeability. This has revealed a common fold with amino acid-binding bacterial proteins, there are eight variants of the NR1 subunit produced by alternative splicing of GRIN1, NR1-1a, NR1-1b, NR1-1a is the most abundantly expressed form. Strong evidence shows that the genes encoding the NR2 subunits in vertebrates have undergone at least two rounds of gene duplication and they contain the binding-site for the neurotransmitter glutamate. More importantly, each NR2 subunit has a different intracellular C-terminal domain that can interact with different sets of signalling molecules, unlike NR1 subunits, NR2 subunits are expressed differentially across various cell types and control the electrophysiological properties of the NMDA receptor. One particular subunit, NR2B, is present in immature neurons and in extrasynaptic locations
8.
Rat
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Rats are various medium-sized, long-tailed rodents of the superfamily Muroidea. True rats are members of the genus Rattus, the most important of which to humans are the black rat, Rattus rattus, many members of other rodent genera and families are also referred to as rats, and share many characteristics with true rats. Rats are typically distinguished from mice by their size, generally, when someone discovers a large muroid rodent, its common name includes the term rat, while if it is smaller, the name includes the term mouse. The muroid family is broad and complex, and the common terms rat, scientifically, the terms are not confined to members of the Rattus and Mus genera, for example, the pack rat and cotton mouse. The best-known rat species are the black rat and the brown rat, the group is generally known as the Old World rats or true rats, and originated in Asia. Rats are bigger than most Old World mice, which are their relatives, the term rat is also used in the names of other small mammals which are not true rats. Examples include the North American pack rats, a number of species loosely called kangaroo rats, Rats such as the bandicoot rat are murine rodents related to true rats, but are not members of the genus Rattus. Male rats are called bucks, unmated females are called does, pregnant or parent females are called dams, a group of rats is referred to as a mischief. The common species are opportunistic survivors and often live with and near humans, therefore and they may cause substantial food losses, especially in developing countries. However, the distributed and problematic commensal species of rats are a minority in this diverse genus. Many species of rats are island endemics and some have become endangered due to loss or competition with the brown. Wild rodents, including rats, can carry many different zoonotic pathogens, such as Leptospira, Toxoplasma gondii, another zoonotic disease linked to the rat is the foot-and-mouth disease. The average lifespan of any given rat depends on species is being discussed. The black and brown rats diverged from other Old World rats during the beginning of the Pleistocene in the forests of Asia, specially bred rats have been kept as pets at least since the late 19th century. Pet rats are typically variants of the brown rat, but black rats. Pet rats behave differently from their wild counterparts depending on how many generations they have kept as pets. Pet rats do not pose any more of a risk than pets such as cats or dogs. Tamed rats are generally friendly and can be taught to perform selected behaviors, in 1895, Clark University in Worcester, Massachusetts established a population of domestic albino brown rats to study the effects of diet and for other physiological studies
9.
HEK 293 cells
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HEK293 cells have been widely used in cell biology research for many years, because of their reliable growth and propensity for transfection. They are also used by the industry to produce therapeutic proteins. HEK293 cells were generated in 1973 by transformation of cultures of human embryonic kidney cells with sheared adenovirus 5 DNA in Alex van der Ebs laboratory in Leiden. The cells were obtained from a single, apparently healthy, legally aborted fetus under Dutch law, the identity of the mother, the cells were cultured by van der Eb, the transformation by adenovirus was performed by Frank Graham, a post-doc in van der Ebs lab. They were published in 1977 after Graham left Leiden for McMaster University, Graham performed the transformation a total of eight times, obtaining just one clone of cells that were cultured for several months. After presumably adapting to culture, cells from this clone developed into the relatively stable HEK293 line. Subsequent analysis has shown that the transformation was brought about by inserting ~4.5 kilobases from the arm of the viral genome. For many years it was assumed that HEK293 cells were generated by transformation of either a fibroblastic, however, the original adenovirus transformation was inefficient, suggesting that the cell that finally produced the HEK293 line may have been unusual in some fashion. The HEK293 pattern most closely resembled that of adrenal cells, given the location of the adrenal gland, a few adrenal cells could plausibly have appeared in an embryonic kidney derived culture, and could be preferentially transformed by adenovirus. Adenovirus transforms neuronal lineage cells much more efficiently than typical human kidney epithelial cells, an embryonic adrenal precursor cell therefore seems the most likely origin cell of the HEK293 line. As a consequence, HEK293 cells should not be used as an in vitro model of typical kidney cells, HEK293 cells have a complex karyotype, exhibiting two or more copies of each chromosome and with a modal chromosome number of 64. They are described as hypotriploid, containing less than three times the number of chromosomes of a normal human cell. Chromosomal abnormalities include a total of three copies of the X chromosome and four copies of chromosome 17 and chromosome 22, the presence of multiple X chromosomes and the lack of any trace of Y chromosome derived sequence suggest that the source fetus was female. HEK293 cells are straightforward to grow in culture and to transfect and they have been used as hosts for gene expression. Typically, these experiments involve transfecting in a gene of interest, the widespread use of this cell line is due to its transfectability by the various techniques, including calcium phosphate method, achieving efficiencies approaching 100%. Viruses offer an efficient means of delivering genes into cells, which evolved to do. However, as pathogens, they present a risk to the experimenter. This danger can be avoided by the use of viruses which lack key genes, in order to propagate such viral vectors, a cell line that expresses the missing genes is required
10.
Jmol
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Jmol is computer software for molecular modelling chemical structures in 3-dimensions. Jmol returns a 3D representation of a molecule that may be used as a teaching tool and it is written in the programming language Java, so it can run on the operating systems Windows, macOS, Linux, and Unix, if Java is installed. It is free and open-source software released under a GNU Lesser General Public License version 2.0, a standalone application and a software development kit exist that can be integrated into other Java applications, such as Bioclipse and Taverna. A popular feature is an applet that can be integrated into web pages to display molecules in a variety of ways, for example, molecules can be displayed as ball-and-stick models, space-filling models, ribbon diagrams, etc. Jmol supports a range of chemical file formats, including Protein Data Bank, Crystallographic Information File, MDL Molfile. There is also a JavaScript-only version, JSmol, that can be used on computers with no Java, the Jmol applet, among other abilities, offers an alternative to the Chime plug-in, which is no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS9. Jmol requires Java installation and operates on a variety of platforms. For example, Jmol is fully functional in Mozilla Firefox, Internet Explorer, Opera, Google Chrome, fast and Scriptable Molecular Graphics in Web Browsers without Java3D
11.
European Chemicals Agency
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ECHA is the driving force among regulatory authorities in implementing the EUs chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and it is located in Helsinki, Finland. The Agency, headed by Executive Director Geert Dancet, started working on 1 June 2007, the REACH Regulation requires companies to provide information on the hazards, risks and safe use of chemical substances that they manufacture or import. Companies register this information with ECHA and it is freely available on their website. So far, thousands of the most hazardous and the most commonly used substances have been registered, the information is technical but gives detail on the impact of each chemical on people and the environment. This also gives European consumers the right to ask whether the goods they buy contain dangerous substances. The Classification, Labelling and Packaging Regulation introduces a globally harmonised system for classifying and labelling chemicals into the EU. This worldwide system makes it easier for workers and consumers to know the effects of chemicals, companies need to notify ECHA of the classification and labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100000 substances, the information is freely available on their website. Consumers can check chemicals in the products they use, Biocidal products include, for example, insect repellents and disinfectants used in hospitals. The Biocidal Products Regulation ensures that there is information about these products so that consumers can use them safely. ECHA is responsible for implementing the regulation, the law on Prior Informed Consent sets guidelines for the export and import of hazardous chemicals. Through this mechanism, countries due to hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have effects on human health and the environment are identified as Substances of Very High Concern 1. These are mainly substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment, other substances considered as SVHCs include, for example, endocrine disrupting chemicals. Companies manufacturing or importing articles containing these substances in a concentration above 0 and they are required to inform users about the presence of the substance and therefore how to use it safely. Consumers have the right to ask the retailer whether these substances are present in the products they buy, once a substance has been officially identified in the EU as being of very high concern, it will be added to a list. This list is available on ECHA’s website and shows consumers and industry which chemicals are identified as SVHCs, Substances placed on the Candidate List can then move to another list
12.
Phencyclidine
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Phencyclidine, also known as angel dust and Sernyl among others, is a dissociative drug. PCP was brought to market in the 1950s as a pharmaceutical drug but was taken off the market in 1965 due to the high prevalence of dissociative hallucinogenic side effects. Moreover, the discovery of ketamine by Parke-Davis researchers was thought to represent an alternative for use as an anesthetic medication. Since this time a number of derivatives of PCP have been sold as dissociative drugs for recreational and non-medical use. In chemical structure, PCP is a member of the arylcyclohexylamine class, PCP works primarily as an NMDA receptor antagonist. As an addictive drug, PCP is associated with compulsive abuse, as a recreational drug, PCP may be ingested orally, smoked, insufflated or injected. PCP began to emerge as a drug in major cities in the United States in 1967. In 1978, People magazine and Mike Wallace of 60 Minutes called PCP the countrys 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 school students admitting to trying PCP at least once fell from 13% in 1979 to less than 3% in 1990. PCP comes in powder and liquid forms, but typically it is sprayed onto leafy material such as cannabis, mint, oregano, tobacco, parsley, or ginger leaves. PCP is a Schedule II substance in the United States and its ACSCN is 7471 and its manufacturing quota for 2014 was 19 grams. 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, PCP can be ingested through smoking. Fry is a term for marijuana or tobacco cigarettes that are dipped in PCP. PCP hydrochloride can be insufflated, depending upon the purity, the free base is quite hydrophobic and may be absorbed through skin and mucus membranes. 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 will produce analgesia and anesthesia, high doses may lead to convulsions. Users frequently do not know how much of the drug they are taking due to the tendency of the drug to be produced illegally in uncontrolled conditions, psychological effects include severe changes in body image, loss of ego boundaries, paranoia, and depersonalization. Hallucinations, euphoria, and suicidal impulses are also reported, as well as aggressive behavior
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