1.
Mouth
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It is also the cavity lying at the upper end of the alimentary canal, bounded on the outside by the lips and inside by the pharynx and containing in higher vertebrates the tongue and teeth. This cavity is known as the buccal cavity, from the Latin bucca. Some animal phyla, including vertebrates, have a digestive system, with a mouth at one end. Which end forms first in ontogeny is a used to classify animals into protostome and deuterostome. In the first multicellular animals there was probably no mouth or gut, the particles became enclosed in vacuoles into which enzymes were secreted and digestion took place intracellularly. The digestive products were absorbed into the cytoplasm and diffused into other cells, the vast majority of other multicellular organisms have a mouth and a gut, the lining of which is continuous with the epithelial cells on the surface of the body. A few animals which live parasitically originally had guts but have secondarily lost these structures, the original gut of multicellular organisms probably consisted of a simple sac with a single opening, the mouth. Indigestible waste is ejected through the mouth, in animals at least as complex as an earthworm, the embryo forms a dent on one side, the blastopore, which deepens to become the archenteron, the first phase in the formation of the gut. In deuterostomes, the blastopore becomes the anus while the gut tunnels through to make another opening. In the protostomes, it used to be thought that the formed the mouth while the anus formed later as an opening made by the other end of the gut. More recent research, however, shows that in protostomes the edges of the slit-like blastopore close up in the middle, apart from sponges and placozoans, almost all animals have an internal gut cavity which is lined with gastrodermal cells. In less advanced invertebrates such as the sea anemone, the mouth also acts as an anus, circular muscles around the mouth are able to relax or contract in order to open or close it. A fringe of tentacles thrusts food into the cavity and it can gape widely enough to large prey items. Food passes first into a pharynx and digestion occurs extracellularly in the gastrovascular cavity, annelids have simple tube-like gets and the possession of an anus allows them to separate the digestion of their foodstuffs from the absorption of the nutrients. Many molluscs have a radula which is used to scrape microscopic particles off surfaces, in invertebrates with hard exoskeletons, various mouthparts may be involved in feeding behaviour. Insects have a range of mouthparts suited to their mode of feeding and these include mandibles, maxillae and labium and can be modified into suitable appendages for chewing, cutting, piercing, sponging and sucking. Decapods have six pairs of appendages, one pair of mandibles. Sea urchins have a set of five sharp calcareous plates which are used as jaws and are known as Aristotles lantern, in vertebrates, the first part of the digestive system is the buccal cavity, commonly known as the mouth
2.
United States
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Forty-eight of the fifty states and the federal district are contiguous and located in North America between Canada and Mexico. The state of Alaska is in the northwest corner of North America, bordered by Canada to the east, the state of Hawaii is an archipelago in the mid-Pacific Ocean. The U. S. territories are scattered about the Pacific Ocean, the geography, climate and wildlife of the country are extremely diverse. At 3.8 million square miles and with over 324 million people, the United States is the worlds third- or fourth-largest country by area, third-largest by land area. It is one of the worlds most ethnically diverse and multicultural nations, paleo-Indians migrated from Asia to the North American mainland at least 15,000 years ago. European colonization began in the 16th century, the United States emerged from 13 British colonies along the East Coast. Numerous disputes between Great Britain and the following the Seven Years War led to the American Revolution. On July 4,1776, during the course of the American Revolutionary War, the war ended in 1783 with recognition of the independence of the United States by Great Britain, representing the first successful war of independence against a European power. The current constitution was adopted in 1788, after the Articles of Confederation, the first ten amendments, collectively named the Bill of Rights, were ratified in 1791 and designed to guarantee many fundamental civil liberties. During the second half of the 19th century, the American Civil War led to the end of slavery in the country. By the end of century, the United States extended into the Pacific Ocean. The Spanish–American War and World War I confirmed the status as a global military power. The end of the Cold War and the dissolution of the Soviet Union in 1991 left the United States as the sole superpower. The U. S. is a member of the United Nations, World Bank, International Monetary Fund, Organization of American States. The United States is a developed country, with the worlds largest economy by nominal GDP. It ranks highly in several measures of performance, including average wage, human development, per capita GDP. While the U. S. economy is considered post-industrial, characterized by the dominance of services and knowledge economy, the United States is a prominent political and cultural force internationally, and a leader in scientific research and technological innovations. In 1507, the German cartographer Martin Waldseemüller produced a map on which he named the lands of the Western Hemisphere America after the Italian explorer and cartographer Amerigo Vespucci
3.
Drug
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A drug is any substance that, when inhaled, injected, smoked, consumed, absorbed via a patch on the skin, or dissolved under the tongue, causes a physiological change in the body. In pharmacology, a drug, also called a medication or medicine, is a chemical substance used to treat, cure, prevent. Traditionally drugs were obtained through extraction from plants, but more recently also by organic synthesis. Pharmaceutical drugs may be used for a duration, or on a regular basis for chronic disorders. Another major classification system is the Biopharmaceutics Classification System and this classifies drugs according to their solubility and permeability or absorption properties. Psychoactive drugs are chemical substances that affect the function of the nervous system, altering perception. They include alcohol, a depressant, and the nicotine and caffeine. These three are the most widely consumed psychoactive drugs worldwide and are also considered recreational drugs since they are used for rather than medicinal purposes. Other recreational drugs include hallucinogens, opiates and amphetamines and some of these are used in spiritual or religious settings. Some drugs can cause addiction and all drugs can have side effects, excessive use of stimulants can promote stimulant psychosis. Many recreational drugs are illicit and international such as the Single Convention on Narcotic Drugs exist for the purpose of their prohibition. The transitive verb to drug arose later and invokes the psychoactive rather than properties of a substance. A medication or medicine is a drug taken to cure or ameliorate any symptoms of an illness or medical condition, the use may also be as preventive medicine that has future benefits but does not treat any existing or pre-existing diseases or symptoms. In the United Kingdom, behind-the-counter medicines are called pharmacy medicines which can only be sold in registered pharmacies and these medications are designated by the letter P on the label. The range of medicines available without a prescription varies from country to country, medications are typically produced by pharmaceutical companies and are often patented to give the developer exclusive rights to produce them. Those that are not patented are called generic drugs since they can be produced by other companies without restrictions or licenses from the patent holder, pharmaceutical drugs are usually categorised into drug classes. A group of drugs will share a chemical structure, or have the same mechanism of action. Another major classification system is the Biopharmaceutics Classification System and this groups drugs according to their solubility and permeability or absorption properties
4.
Dopamine
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Dopamine is an organic chemical of the catecholamine and phenethylamine families that plays several important roles in the brain and body. It is an amine synthesized by removing a carboxyl group from a molecule of its precursor chemical L-DOPA, dopamine is also synthesized in plants and most multicellular animals. In the brain, dopamine functions as a neurotransmitter—a chemical released by neurons to send signals to nerve cells. The brain includes several distinct dopamine pathways, one of plays a major role in reward-motivated behavior. Most types of rewards increase the level of dopamine in the brain, other brain dopamine pathways are involved in motor control and in controlling the release of various hormones. These pathways and cell groups form a system which is neuromodulatory. Outside the central system, dopamine functions primarily as a local chemical messenger. With the exception of the vessels, dopamine in each of these peripheral systems is synthesized locally. Several important diseases of the system are associated with dysfunctions of the dopamine system. Parkinsons disease, a condition causing tremor and motor impairment, is caused by a loss of dopamine-secreting neurons in an area of the midbrain called the substantia nigra. Its metabolic precursor L-DOPA can be manufactured, and in its pure form marketed as Levodopa is the most widely used treatment for the condition. There is evidence that schizophrenia involves altered levels of dopamine activity, similar dopamine antagonist drugs are also some of the most effective anti-nausea agents. Restless legs syndrome and attention deficit hyperactivity disorder are associated with decreased dopamine activity, dopaminergic stimulants can be addictive in high doses, but some are used at lower doses to treat ADHD. A dopamine molecule consists of a structure with one amine group attached via an ethyl chain. As such, dopamine is the simplest possible catecholamine, a family that includes the neurotransmitters norepinephrine and epinephrine. The presence of a ring with this amine attachment makes it a substituted phenethylamine. Like most amines, dopamine is an organic base, as a base, it is generally protonated in acidic environments. The protonated form is highly water-soluble and relatively stable, but can become oxidized if exposed to oxygen or other oxidants, in basic environments, dopamine is not protonated
5.
MDMA
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3, 4-Methylenedioxymethamphetamine, commonly known as ecstasy, is a psychoactive drug used primarily as a recreational drug. Desired effects include increased empathy, euphoria, and heightened sensations, when taken by mouth, effects begin after 30–45 minutes and last 3–6 hours. It is also sometimes snorted or smoked, as of 2017, MDMA has no accepted medical uses. Adverse effects of MDMA use include addiction, memory problems, paranoia, difficulty sleeping, teeth grinding, blurred vision, sweating, use may also lead to depression and fatigue. Deaths have been reported due to increased temperature and dehydration. MDMA increases the release and slows the reuptake of the serotonin, dopamine. It has stimulant and psychedelic effects, the initial increase is followed by a short-term decrease in the neurotransmitters. MDMA belongs to the substituted methylenedioxyphenethylamine and substituted amphetamine classes of drugs, MDMA was first made in 1912. It was used to improve psychotherapy beginning in the 1970s and became popular as a drug in the 1980s. MDMA is commonly associated with parties, raves, and electronic dance music. It is often mixed with other substances such as ephedrine, amphetamine. In 2014, between 9 and 29 million people between the ages of 15 and 64 used ecstasy and this was broadly similar to the percentage of people who use cocaine, amphetamines, and opioids, but fewer than for cannabis. In the United States, about 0.9 million people used ecstasy in 2010, MDMA is generally illegal in most countries. Limited exceptions are made for research. Researchers are investigating whether a few low doses of MDMA may assist in treating severe, in November 2016, phase 3 clinical trials for PTSD were approved by the United States Food and Drug Administration to assess effectiveness and safety. As of 2017, MDMA has no accepted medical indications, before it was widely banned, it saw limited use in therapy. A small number of therapists continue to use MDMA in therapy despite its illegal status, MDMA is often considered the drug of choice within the rave culture and is also used at clubs, festivals and house parties. In the rave environment, the effects from the music
6.
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
7.
Alexander Shulgin
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Alexander Theodore Sasha Shulgin was an American medicinal chemist, biochemist, organic chemist, pharmacologist, psychopharmacologist, and author. In 1991 and 1997, he and his wife Ann Shulgin authored the books PIHKAL and TIHKAL, Shulgin performed seminal work into the descriptive synthesis of many of these compounds. Some of Shulgins noteworthy discoveries include compounds of the 2C* family, due in part to Shulgins extensive work in the field of psychedelic research and the rational drug design of psychedelic drugs, he has since been dubbed the godfather of psychedelics. Shulgin was born in Berkeley, California to Theodore Stevens Shulgin and his father was born in Russia, while his mother was born in Illinois. Both Theodore and Henrietta were public school teachers in Alameda County, Shulgin began studying organic chemistry as a Harvard University scholarship student at the age of 16. In 1943 he dropped out of school to join the U. S. Navy, while serving on USS Pope in the Navy during World War II, Shulgin was given a glass of orange juice by a nurse prior to surgery for a thumb infection. Shulgin drank the juice and, assuming that the powder at the bottom of the glass was a sedative, upon waking he learned that the powder was undissolved sugar. The experience made him aware of the influence of placebos over the human mind, after serving in the Navy, Shulgin returned to Berkeley, California, and in 1954 earned his Ph. D. in biochemistry from the University of California, Berkeley. Through the late 1950s Shulgin completed post-doctoral work in the fields of psychiatry and pharmacology at University of California, after working at Bio-Rad Laboratories as a research director for a brief period, he began work at Dow Chemical Company as a senior research chemist. At this time he had a series of experiences that helped to shape his further goals and research. I first explored mescaline in the late 50s, I learned there was a great deal inside me. I understood that our universe is contained in the mind. We may choose not to access to it, we may even deny its existence, but it is indeed there inside us. Shulgins professional activities continued to lean in the direction of psychopharmacology, but during this period he was unable to do much independent research. His opportunity for further research came in 1961 after his development of Zectran, the first biodegradable pesticide, in his book PIHKAL, Shulgin limits his pesticide days at Dow Chemical to one sentence in 978 pages. Dow Chemical Company, in return for Zectrans valuable patent, gave Shulgin great freedom, during this time, he created and patented drugs when Dow asked, and published findings on other drugs in journals such as Nature and the Journal of Organic Chemistry. Eventually, Dow Chemical requested that he no longer use their name on his publications, in late 1966, Shulgin left Dow in order to pursue his own interests. He first spent two years studying neurology at the University of California, San Francisco School of Medicine, leaving to work on a consulting project and he set up a home-based lab on his property, known as the Farm, and became a private consultant
8.
In vitro
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In vitro studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. In contrast, in studies are those conducted in animals, including humans. In vitro studies are conducted using components of an organism that have been isolated from their biological surroundings, such as microorganisms, cells. For example, microrganisms or cells can be studied in artificial culture media, colloquially called test-tube experiments, these studies in biology, medicine, and their subdisciplines are traditionally done in test tubes, flasks, Petri dishes, etc. They now involve the range of techniques used in molecular biology. In contrast, studies conducted in living beings are called in vivo, polymerase chain reaction is a method for selective replication of specific DNA and RNA sequences in the test tube. Protein purification involves the isolation of a protein of interest from a complex mixture of proteins. In vitro fertilization is used to allow spermatozoa to fertilize eggs in a culture dish before implanting the resulting embryo or embryos into the uterus of the prospective mother and these ADME process parameters can then be integrated into so called physiologically based pharmacokinetic models or PBPK. In vitro studies permit a species-specific, simpler, more convenient, just as studies in whole animals more and more replace human trials, so are in vitro studies replacing studies in whole animals. This complexity makes it difficult to identify the interactions between individual components and to explore their basic biological functions, in vitro work simplifies the system under study, so the investigator can focus on a small number of components. Another advantage of in vitro methods is that cells can be studied without extrapolation from an experimental animals cellular response. Investigators doing in vitro work must be careful to avoid over-interpretation of their results, for example, scientists developing a new viral drug to treat an infection with a pathogenic virus may find that a candidate drug functions to prevent viral replication in an in vitro setting. However, before this drug is used in the clinic, it must progress through a series of in vivo trials to determine if it is safe and effective in intact organisms. Results obtained from in vitro experiments cannot usually be transposed, as is, building a consistent and reliable extrapolation procedure from in vitro results to in vivo is therefore extremely important. However, increasingly sophisticated in vitro experiments collect increasingly numerous, complex, mathematical models, such as systems biology models, are much needed here. In pharmacology, IVIVE can be used to approximate pharmacokinetics or pharmacodynamics and that indicates that extrapolating effects observed in vitro needs a quantitative model of in vivo PK. Physiologically based PK models are generally accepted to be central to the extrapolations, in these conditions, developing a simple PD model of the dose–response relationship observed in vitro, and transposing it without changes to predict in vivo effects is not enough
9.
Substituted amphetamine
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The compounds in this class span a variety of pharmacological subclasses, including stimulants, empathogens, and hallucinogens, among others. Some of amphetamines substituted derivatives occur in nature, for example in the leaves of Ephedra and these have been used since antiquity for their pharmacological effects. Amphetamine was first produced at the end of the 19th century, by the 1930s, amphetamine and some of its derivative compounds found use as decongestants in the symptomatic treatment of colds and also occasionally as psychoactive agents. Their effects on the nervous system are diverse, but can be summarized by three overlapping types of activity, psychoanaleptic, hallucinogenic and empathogenic. Various substituted amphetamines may cause these actions either separately or in combination, amphetamines are a subgroup of the substituted phenethylamine class of compounds. Substitution of hydrogen results in a large class of compounds. Natives of Yemen and Ethiopia have a tradition of chewing khat leaves to achieve a stimulating effect. The active substances of khat are cathinone and, to a lesser extent, amphetamine was first synthesized in 1887 by Romanian chemist Lazăr Edeleanu, although its pharmacological effects remained unknown until the 1930s. MDMA was produced in 1912 as an intermediate product, however, this synthesis also went largely unnoticed. In the 1920s, both methamphetamine and the dextrorotatory optical isomer of amphetamine, dextroamphetamine, were synthesized and this synthesis was a by-product of a search for ephedrine, a bronchodilator used to treat asthma extracted exclusively from natural sources. Over-the-counter use of substituted amphetamines was initiated in the early 1930s by the pharmaceutical company Smith, Kline & French, as a medicine for colds and nasal congestion. Subsequently, amphetamine was used in the treatment of narcolepsy, obesity, hay fever, orthostatic hypotension, epilepsy, Parkinsons disease, alcoholism, the reinforcing effects of substituted amphetamines were quickly discovered, and the misuse of substituted amphetamines had been noted as far back as 1936. During World War II, amphetamines were used by the German military to keep their tank crews awake for long periods and it was noticed that extended rest was required after such artificially induced activity. The widespread use of substituted amphetamines began in postwar Japan and quickly spread to other countries, modified designer amphetamines gained popularity since the 1960s, such as MDA and PMA. In 1970, the United States adopted the Controlled Substances Act that limited non-medical use of substituted amphetamines, street use of PMA was noted in 1972. MDMA emerged as a substitute to MDA in the early 1970s, american chemist Alexander Shulgin first synthesized the drug in 1976 and through him the drug was briefly introduced into psychotherapy. Recreational use grew and in 1985 MDMA was banned by the US authorities in an emergency scheduling initiated by the Drug Enforcement Administration, since the mid-1990s, MDMA has become a popular entactogenic drug among the youth and quite often non-MDMA substances were sold as ecstasy. Ongoing trials are investigating its efficacy as an adjunct to psychotherapy in the management of treatment-resistant post-traumatic stress disorder
10.
Pharmacokinetics
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Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as, pharmaceutical drugs, pesticides, food additives, cosmetic ingredients, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, both together influence dosing, benefit, and adverse effects, as seen in PK/PD models. Pharmacokinetic properties of chemicals are affected by the route of administration and these may affect the absorption rate. Models have been developed to simplify conceptualization of the processes that take place in the interaction between an organism and a chemical substance. The various compartments that the model is divided into are commonly referred to as the ADME scheme, absorption - the process of a substance entering the blood circulation. Distribution - the dispersion or dissemination of substances throughout the fluids, metabolism – the recognition by the organism that a foreign substance is present and the irreversible transformation of parent compounds into daughter metabolites. Excretion - the removal of the substances from the body, in rare cases, some drugs irreversibly accumulate in body tissue. The two phases of metabolism and excretion can also be grouped together under the title elimination, the study of these distinct phases involves the use and manipulation of basic concepts in order to understand the process dynamics. All these concepts can be represented through mathematical formulas that have a graphical representation. The model outputs for a drug can be used in industry or in the application of pharmacokinetic concepts. Clinical pharmacokinetics provides many performance guidelines for effective and efficient use of drugs for human-health professionals, in practice, it is generally considered that steady state is reached when a time of 4 to 5 times the half-life for a drug after regular dosing is started. Noncompartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph, compartmental methods estimate the concentration-time graph using kinetic models. Noncompartmental methods are more versatile in that they do not assume any specific compartmental model. The final outcome of the transformations that a drug undergoes in an organism, a number of functional models have been developed in order to simplify the study of pharmacokinetics. These models are based on a consideration of an organism as a number of related compartments, the simplest idea is to think of an organism as only one homogenous compartment. However, these models do not always reflect the real situation within an organism
11.
Para-Methoxyamphetamine
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Para-Methoxyamphetamine, also known as 4-methoxyamphetamine, is a designer drug of the amphetamine class with serotonergic effects. PMA has been found in tablets touted as MDMA although its effects are different compared to those of MDMA. The consequences of such deception has often been hospitalizations and deaths among unwitting users, PMA has been associated with numerous adverse reactions including death. At high doses unpleasant effects such as nausea and vomiting, severe hyperthermia, while PMA alone may cause significant toxicity, the combination of PMA with MDMA has a synergistic effect that seems to be particularly hazardous. PMA overdose can be a medical emergency that may occur at only slightly above the usual recreational dose range. Characteristic symptoms are pronounced hyperthermia, tachycardia, and hypertension, along with agitation, confusion, PMA overdose also tends to cause hypoglycaemia and hyperkalaemia, which can help to distinguish it from MDMA overdose. Complications can sometimes include more serious symptoms such as rhabdomyolysis and cerebral hemorrhage, there is no specific antidote, so treatment is symptomatic, and usually includes both external cooling, and internal cooling via IV infusion of cooled saline. Benzodiazepines are used initially to control convulsions, with stronger anticonvulsants such as phenytoin or thiopental used if convulsions continue, blood pressure can be lowered either with a combination of alpha blockers and beta blockers, or with other drugs such as nifedipine or nitroprusside. Serotonin antagonists and dantrolene may be used as required, PMA acts as a selective serotonin releasing agent with weak effects on dopamine and norepinephrine transporters. However, relative to MDMA, it is less effective as a releaser of serotonin with properties more akin to a reuptake inhibitor in comparison. It evokes robust hyperthermia in rodents while producing only modest hyperactivity and serotonergic neurotoxicity, substantially lower than that caused by MDMA, and only at very high doses. Accordingly, it is not self-administered by rodents unlike amphetamine and MDMA, amphetamines, especially serotonergic analogues such as MDMA, are strongly contraindicated to take with MAOIs. Many people taking PMA try to get rid of the heat by taking off their clothes, taking cold showers or wrapping themselves in wet towels, PMA first came into circulation in the early 1970s, where it was used intentionally as a substitute for the hallucinogenic properties of LSD. It went by the names of Chicken Powder and Chicken Yellow and was found to be the cause of a number of drug overdose deaths in the United States. Between 1974 and the mid-1990s, there appear to have no known fatalities from PMA. Several deaths reported as MDMA-induced in Australia in the mid-1990s are now considered to have been caused by PMA, there have been a number of PMA-induced deaths around the world since then. In July 2013, seven deaths in Scotland were linked to tablets containing PMA that had been mis-sold as ecstasy, several deaths in Northern Ireland, Particularly East Belfast were also linked to Green Rolex pills during that month. In 2014,2015 and early 2016, PMA sold as ecstasy was attributed for more deaths in the United States, United Kingdom, Netherlands, the pills containing the drug were reported to be red triangular tablets with a Superman logo
