1.
Regulation of therapeutic goods
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The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the level by a single agency. In other jurisdictions they are regulated at the level, or at both state and national levels by various bodies, as is the case in Australia. The role of therapeutic goods regulation is designed mainly to protect the health, regulation is aimed at ensuring the safety, quality, and efficacy of the therapeutic goods which are covered under the scope of the regulation. In most jurisdictions, therapeutic goods must be registered before they are allowed to be marketed, there is usually some degree of restriction of the availability of certain therapeutic goods depending on their risk to consumers. Therapeutic goods in Australia are regulated by the Therapeutic Goods Administration, there are 5 main categories, Normal Medicines - Cough, cold and fever medicines, antiseptics, vitamins and others. Sold freely in pharmacies and some large supermarkets, red Stripe Medicines - These medicines are sold only with medical prescription. Antibiotics, Anti allergenics, Anti inflammatories, and other medicines, in Brazil, governmental control is loose on this type, it is not uncommon to buy this type of prescription medicine over the counter without a prescription. Red Stripe Psychoactive Medicines - These medicines are only with a Special Control white medical prescription with carbon copy. The original must be retained by the pharmacist after the sale, Drugs include anti-depressants, anti-convulsants, some sleep aids, anti-psychotics and other non-habit-inducing controlled medicines. Though some consider them habit inducing, anabolic steroids are also regulated under this category, black Stripe Medicines - These medicines are sold only with the Blue B Form medical prescription, which is valid for 30 days and must be retained by the pharmacist after the sale. Includes sedatives, some anorexic inducers and other habit-inducing controlled medicines, includes amphetamines and other stimulants, opioids and other strong habit-forming controlled medicines. In Canada, regulation of goods are governed by the Food and Drug Act. In addition, the Controlled Drugs and Substances Act requires additional regulatory requirements for controlled drugs, the regulation of drugs in Burma is governed by the Food and Drug Administration and Food and Drug Board of Authority. The regulation of drugs in China is governed by the China Food, Medicines for Human Use in the United Kingdom are regulated by the Medicines and Healthcare products Regulatory Agency. The availability of drugs is regulated by classification by the MHRA as part of marketing authorisation of a product, Medicines in the Republic of Ireland are regulated according to the Misuse of Drugs Regulations 1988. Controlled drugs are divided into five categories based on their potential for misuse, cD1, cannabis, lysergamide, coca leaf, etc. Use prohibited except in limited circumstances where a license has been granted, CD2, amphetamine, methadone, morphine, fentanyl, oxycodone, tapentadol, etc
2.
Controlled Substances Act
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The Controlled Substances Act is the statute establishing federal U. S. drug policy under which the manufacture, importation, possession, use and distribution of certain substances is regulated. It was passed by the 91st United States Congress as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970, the Act also served as the national implementing legislation for the Single Convention on Narcotic Drugs. The legislation created five Schedules, with varying qualifications for a substance to be included in each, classification decisions are required to be made on criteria including potential for abuse, currently accepted medical use in treatment in the United States, and international treaties. The nation first outlawed addictive drugs in the early 1900s and the International Opium Convention helped lead international agreements regulating trade, the Food and Drugs Act of 1906 was the beginning of over 200 laws concerning public health and consumer protections. Others were the Federal Food, Drug, and Cosmetic Act, in 1969, President Richard Nixon announced that the Attorney General, John N. Shafer—to study cannabis abuse in the United States. It implies an overwhelming indictment of the behavior which we believe is not appropriate, the actual and potential harm of use of the drug is not great enough to justify intrusion by the criminal law into private behavior, a step which our society takes only with the greatest reluctance. According to David T. Courtwright, the Act was part of a reform package designed to rationalize. It eliminated mandatory minimum sentences and provided support for drug treatment, king notes that the rehabilitation clauses were added as a compromise to Senator Jim Hughes, who favored a moderate approach. The bill, as introduced by Senator Everett Dirksen, ran to 91 pages, since its enactment in 1970, the Act has been amended several times, The Medical Device Amendments of 1976. The Psychotropic Substances Act of 1978 added provisions implementing the Convention on Psychotropic Substances, the Controlled Substances Penalties Amendments Act of 1984. The Ryan Haight Online Pharmacy Consumer Protection Act of 2008 The Electronic Prescriptions for Controlled Substances 2010, the Controlled Substances Act consists of 2 subchapters. Subchapter II describes the laws for exportation and importation of controlled substances, again specifying fines, the Drug Enforcement Administration was established in 1973, combining the Bureau of Narcotics and Dangerous Drugs and Customs drug agents. When a petition is received by the DEA, the agency begins its own investigation of the drug and this request is sent to the Assistant Secretary of Health of HHS. Under certain circumstances, the Government may temporarily schedule a drug without following the normal procedure, an example is when international treaties require control of a substance. In addition,21 U. S. C. §811 allows the Attorney General to temporarily place a substance in Schedule I to avoid an imminent hazard to the public safety, in any case, once these proceedings are complete, the temporary order is automatically vacated. Unlike ordinary scheduling proceedings, such orders are not subject to judicial review. The CSA also creates a system of distribution for those authorized to handle controlled substances. The cornerstone of this system is the registration of all those authorized by the DEA to handle controlled substances
3.
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
4.
PubChem
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PubChem is a database of chemical molecules and their activities against biological assays. The system is maintained by the National Center for Biotechnology Information, a component of the National Library of Medicine, PubChem can be accessed for free through a web user interface. Millions of compound structures and descriptive datasets can be downloaded via FTP. PubChem contains substance descriptions and small molecules with fewer than 1000 atoms and 1000 bonds, more than 80 database vendors contribute to the growing PubChem database. PubChem consists of three dynamically growing primary databases, as of 28 January 2016, Compounds,82.6 million entries, contains pure and characterized chemical compounds. Substances,198 million entries, contains also mixtures, extracts, complexes, bioAssay, bioactivity results from 1.1 million high-throughput screening programs with several million values. PubChem contains its own online molecule editor with SMILES/SMARTS and InChI support that allows the import and export of all common chemical file formats to search for structures and fragments. In the text search form the database fields can be searched by adding the name in square brackets to the search term. A numeric range is represented by two separated by a colon. The search terms and field names are case-insensitive, parentheses and the logical operators AND, OR, and NOT can be used. AND is assumed if no operator is used, example,0,5000,50,10 -5,5 PubChem was released in 2004. The American Chemical Society has raised concerns about the publicly supported PubChem database and they have a strong interest in the issue since the Chemical Abstracts Service generates a large percentage of the societys revenue. To advocate their position against the PubChem database, ACS has actively lobbied the US Congress, soon after PubChems creation, the American Chemical Society lobbied U. S. Congress to restrict the operation of PubChem, which they asserted competes with their Chemical Abstracts Service
5.
DrugBank
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The DrugBank database is a comprehensive, freely accessible, online database containing information on drugs and drug targets. As both a bioinformatics and a resource, DrugBank combines detailed drug data with comprehensive drug target information. Because of its scope, comprehensive referencing and unusually detailed data descriptions. As a result, links to DrugBank are maintained for nearly all drugs listed in Wikipedia, DrugBank is widely used by the drug industry, medicinal chemists, pharmacists, physicians, students and the general public. Its extensive drug and drug-target data has enabled the discovery and repurposing of a number of existing drugs to treat rare, the latest release of the database contains 8227 drug entries including 2003 FDA-approved small molecule drugs,221 FDA-approved biotech drugs,93 nutraceuticals and over 6000 experimental drugs. Additionally,4270 non-redundant protein sequences are linked to these drug entries, each DrugCard entry contains more than 200 data fields with half of the information being devoted to drug/chemical data and the other half devoted to drug target or protein data. Four additional databases, HMDB, T3DB, SMPDB and FooDB are also part of a suite of metabolomic/cheminformatic databases. The first version of DrugBank was released in 2006 and this early release contained relatively modest information about 841 FDA-approved small molecule drugs and 113 biotech drugs. It also included information on 2133 drug targets, the second version of DrugBank was released in 2009. This greatly expanded and improved version of the database included 1344 approved small molecule drugs and 123 biotech drugs as well as 3037 unique drug targets. Version 2.0 also included, for the first time, withdrawn drugs and illicit drugs, version 3.0 was released in 2011. This version contained 1424 approved small molecule drugs and 132 biotech drugs as well as >4000 unique drug targets, version 3.0 also included drug transporter data, drug pathway data, drug pricing, patent and manufacturing data as well as data on >5000 experimental drugs. Version 4.0 was released in 2014 and this version included 1558 FDA-approved small molecule drugs,155 biotech drugs and 4200 unique drug targets. Version 4.0 also incorporated information on drug metabolites, drug taxonomy, drug spectra, drug binding constants. Table 1 provides a complete statistical summary of the history of DrugBank’s development. All data in DrugBank is non-proprietary or is derived from a non-proprietary source and it is freely accessible and available to anyone. In addition, nearly every item is fully traceable and explicitly referenced to the original source. DrugBank data is available through a web interface and downloads
6.
ChemSpider
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ChemSpider is a database of chemicals. ChemSpider is owned by the Royal Society of Chemistry, the database contains information on more than 50 million molecules from over 500 data sources including, Each chemical is given a unique identifier, which forms part of a corresponding URL. This is an approach to develop an online chemistry database. The search can be used to widen or restrict already found results, structure searching on mobile devices can be done using free apps for iOS and for the Android. The ChemSpider database has been used in combination with text mining as the basis of document markup. The result is a system between chemistry documents and information look-up via ChemSpider into over 150 data sources. ChemSpider was acquired by the Royal Society of Chemistry in May,2009, prior to the acquisition by RSC, ChemSpider was controlled by a private corporation, ChemZoo Inc. The system was first launched in March 2007 in a release form. ChemSpider has expanded the generic support of a database to include support of the Wikipedia chemical structure collection via their WiChempedia implementation. A number of services are available online. SyntheticPages is an interactive database of synthetic chemistry procedures operated by the Royal Society of Chemistry. Users submit synthetic procedures which they have conducted themselves for publication on the site and these procedures may be original works, but they are more often based on literature reactions. Citations to the published procedure are made where appropriate. They are checked by an editor before posting. The pages do not undergo formal peer-review like a journal article. The comments are moderated by scientific editors. The intention is to collect practical experience of how to conduct useful chemical synthesis in the lab, while experimental methods published in an ordinary academic journal are listed formally and concisely, the procedures in ChemSpider SyntheticPages are given with more practical detail. Comments by submitters are included as well, other publications with comparable amounts of detail include Organic Syntheses and Inorganic Syntheses
7.
ChEMBL
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ChEMBL or ChEMBLdb is a manually curated chemical database of bioactive molecules with drug-like properties. It is maintained by the European Bioinformatics Institute, of the European Molecular Biology Laboratory, based at the Wellcome Trust Genome Campus, Hinxton, the database, originally known as StARlite, was developed by a biotechnology company called Inpharmatica Ltd. later acquired by Galapagos NV. The data was acquired for EMBL in 2008 with an award from The Wellcome Trust, resulting in the creation of the ChEMBL chemogenomics group at EMBL-EBI, the ChEMBL database contains compound bioactivity data against drug targets. Bioactivity is reported in Ki, Kd, IC50, and EC50, data can be filtered and analyzed to develop compound screening libraries for lead identification during drug discovery. ChEMBL version 2 was launched in January 2010, including 2.4 million bioassay measurements covering 622,824 compounds and this was obtained from curating over 34,000 publications across twelve medicinal chemistry journals. ChEMBLs coverage of available bioactivity data has grown to become the most comprehensive ever seen in a public database, in October 2010 ChEMBL version 8 was launched, with over 2.97 million bioassay measurements covering 636,269 compounds. ChEMBL_10 saw the addition of the PubChem confirmatory assays, in order to integrate data that is comparable to the type, ChEMBLdb can be accessed via a web interface or downloaded by File Transfer Protocol. It is formatted in a manner amenable to computerized data mining, ChEMBL is also integrated into other large-scale chemistry resources, including PubChem and the ChemSpider system of the Royal Society of Chemistry. In addition to the database, the ChEMBL group have developed tools and these include Kinase SARfari, an integrated chemogenomics workbench focussed on kinases. The system incorporates and links sequence, structure, compounds and screening data, the primary purpose of ChEMBL-NTD is to provide a freely accessible and permanent archive and distribution centre for deposited data. July 2012 saw the release of a new data service, sponsored by the Medicines for Malaria Venture. The data in this service includes compounds from the Malaria Box screening set, myChEMBL, the ChEMBL virtual machine, was released in October 2013 to allow users to access a complete and free, easy-to-install cheminformatics infrastructure. In December 2013, the operations of the SureChem patent informatics database were transferred to EMBL-EBI, in a portmanteau, SureChem was renamed SureChEMBL. 2014 saw the introduction of the new resource ADME SARfari - a tool for predicting and comparing cross-species ADME targets
8.
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
9.
Chemical formula
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These are limited to a single typographic line of symbols, which may include subscripts and superscripts. A chemical formula is not a name, and it contains no words. Although a chemical formula may imply certain simple chemical structures, it is not the same as a full chemical structural formula. Chemical formulas can fully specify the structure of only the simplest of molecules and chemical substances, the simplest types of chemical formulas are called empirical formulas, which use letters and numbers indicating the numerical proportions of atoms of each type. Molecular formulas indicate the numbers of each type of atom in a molecule. For example, the formula for glucose is CH2O, while its molecular formula is C6H12O6. This is possible if the relevant bonding is easy to show in one dimension, an example is the condensed molecular/chemical formula for ethanol, which is CH3-CH2-OH or CH3CH2OH. For reasons of structural complexity, there is no condensed chemical formula that specifies glucose, chemical formulas may be used in chemical equations to describe chemical reactions and other chemical transformations, such as the dissolving of ionic compounds into solution. A chemical formula identifies each constituent element by its chemical symbol, in empirical formulas, these proportions begin with a key element and then assign numbers of atoms of the other elements in the compound, as ratios to the key element. For molecular compounds, these numbers can all be expressed as whole numbers. For example, the formula of ethanol may be written C2H6O because the molecules of ethanol all contain two carbon atoms, six hydrogen atoms, and one oxygen atom. Some types of compounds, however, cannot be written with entirely whole-number empirical formulas. An example is boron carbide, whose formula of CBn is a variable non-whole number ratio with n ranging from over 4 to more than 6.5. When the chemical compound of the consists of simple molecules. These types of formulas are known as molecular formulas and condensed formulas. A molecular formula enumerates the number of atoms to reflect those in the molecule, so that the formula for glucose is C6H12O6 rather than the glucose empirical formula. However, except for very simple substances, molecular chemical formulas lack needed structural information, for simple molecules, a condensed formula is a type of chemical formula that may fully imply a correct structural formula. For example, ethanol may be represented by the chemical formula CH3CH2OH
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.
Simplified molecular-input line-entry system
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The simplified molecular-input line-entry system is a specification in form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules, the original SMILES specification was initiated in the 1980s. It has since modified and extended. In 2007, a standard called OpenSMILES was developed in the open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. The Environmental Protection Agency funded the project to develop SMILES. It has since modified and extended by others, most notably by Daylight Chemical Information Systems. In 2007, a standard called OpenSMILES was developed by the Blue Obelisk open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, in July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is generally considered to have the advantage of being slightly more human-readable than InChI, the term SMILES refers to a line notation for encoding molecular structures and specific instances should strictly be called SMILES strings. However, the term SMILES is also used to refer to both a single SMILES string and a number of SMILES strings, the exact meaning is usually apparent from the context. The terms canonical and isomeric can lead to confusion when applied to SMILES. The terms describe different attributes of SMILES strings and are not mutually exclusive, typically, a number of equally valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol, algorithms have been developed to generate the same SMILES string for a given molecule, of the many possible strings, these algorithms choose only one of them. This SMILES is unique for each structure, although dependent on the algorithm used to generate it. These algorithms first convert the SMILES to a representation of the molecular structure. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database, there is currently no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, and these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES
12.
International Chemical Identifier
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Initially developed by IUPAC and NIST from 2000 to 2005, the format and algorithms are non-proprietary. The continuing development of the standard has supported since 2010 by the not-for-profit InChI Trust. The current version is 1.04 and was released in September 2011, prior to 1.04, the software was freely available under the open source LGPL license, but it now uses a custom license called IUPAC-InChI Trust License. Not all layers have to be provided, for instance, the layer can be omitted if that type of information is not relevant to the particular application. InChIs can thus be seen as akin to a general and extremely formalized version of IUPAC names and they can express more information than the simpler SMILES notation and differ in that every structure has a unique InChI string, which is important in database applications. Information about the 3-dimensional coordinates of atoms is not represented in InChI, the InChI algorithm converts input structural information into a unique InChI identifier in a three-step process, normalization, canonicalization, and serialization. The InChIKey, sometimes referred to as a hashed InChI, is a fixed length condensed digital representation of the InChI that is not human-understandable. The InChIKey specification was released in September 2007 in order to facilitate web searches for chemical compounds and it should be noted that, unlike the InChI, the InChIKey is not unique, though collisions can be calculated to be very rare, they happen. In January 2009 the final 1.02 version of the InChI software was released and this provided a means to generate so called standard InChI, which does not allow for user selectable options in dealing with the stereochemistry and tautomeric layers of the InChI string. The standard InChIKey is then the hashed version of the standard InChI string, the standard InChI will simplify comparison of InChI strings and keys generated by different groups, and subsequently accessed via diverse sources such as databases and web resources. Every InChI starts with the string InChI= followed by the version number and this is followed by the letter S for standard InChIs. The remaining information is structured as a sequence of layers and sub-layers, the layers and sub-layers are separated by the delimiter / and start with a characteristic prefix letter. The six layers with important sublayers are, Main layer Chemical formula and this is the only sublayer that must occur in every InChI. The atoms in the formula are numbered in sequence, this sublayer describes which atoms are connected by bonds to which other ones. Describes how many hydrogen atoms are connected to each of the other atoms, the condensed,27 character standard InChIKey is a hashed version of the full standard InChI, designed to allow for easy web searches of chemical compounds. Most chemical structures on the Web up to 2007 have been represented as GIF files, the full InChI turned out to be too lengthy for easy searching, and therefore the InChIKey was developed. With all databases currently having below 50 million structures, such duplication appears unlikely at present, a recent study more extensively studies the collision rate finding that the experimental collision rate is in agreement with the theoretical expectations. Example, Morphine has the structure shown on the right, as the InChI cannot be reconstructed from the InChIKey, an InChIKey always needs to be linked to the original InChI to get back to the original structure
13.
Monoamine neurotransmitter
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Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group that is connected to an aromatic ring by a two-carbon chain. All monoamines are derived from amino acids like phenylalanine, tyrosine, tryptophan. Drugs used to increase the effect of monoamine are sometimes used to treat patients with psychiatric disorders, including depression, anxiety, after release into the synaptic cleft, monoamine neurotransmitter action is ended by reuptake into the presynaptic terminal. There, they can be repackaged into synaptic vesicles or degraded by the enzyme oxidase, which is a target of monoamine oxidase inhibitors. As demonstrated by the existence of monoamine transmitters, an organisms ability to modify its behavior is advantageous to its survival. This system is found in species such as nematodes, lobsters, desert locusts, hens, mice. Disorders of monoamine neurotransmitters exist, part of a number of neurotransmitter disorders identified. Such disorders are responsible for degradation and difficulty in transporting neurotransmitters such as dopamine, norepinephrine, epinephrine. Monoamine neurotransmitter disorders mimic the symptoms of other more prevalent neurological disorders and thus are frequently misdiagnosed
14.
Alkaloid
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Alkaloids are a group of naturally occurring chemical compounds that mostly contain basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties, some synthetic compounds of similar structure are also termed alkaloids. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen, sulfur and, more rarely, other such as chlorine, bromine. Alkaloids are produced by a variety of organisms including bacteria, fungi, plants. They can be purified from crude extracts of these organisms by acid-base extraction, many have found use in traditional or modern medicine, or as starting points for drug discovery. Other alkaloids possess psychotropic and stimulant activities, and have used in entheogenic rituals or as recreational drugs. Although alkaloids act on a diversity of systems in humans and other animals. The boundary between alkaloids and other nitrogen-containing natural compounds is not clear-cut, Compounds like amino acid peptides, proteins, nucleotides, nucleic acid, amines, and antibiotics are usually not called alkaloids. Natural compounds containing nitrogen in the position are usually classified as amines rather than as alkaloids. Some authors, however, consider alkaloids a special case of amines, the name alkaloids was introduced in 1819 by the German chemist Carl Friedrich Wilhelm Meißner, and is derived from late Latin root Latin, alkali and the suffix Greek, -οειδής – like. However, the term came into use only after the publication of a review article by Oscar Jacobsen in the chemical dictionary of Albert Ladenburg in the 1880s. There is no method of naming alkaloids. Many individual names are formed by adding the suffix ine to the species or genus name, for example, atropine is isolated from the plant Atropa belladonna, strychnine is obtained from the seed of Strychnine tree. If several alkaloids are extracted from one plant then their names often contain suffixes idine, anine, aline, inine etc. There are also at least 86 alkaloids whose names contain the root vin because they are extracted from plants such as Vinca rosea. Alkaloid-containing plants have been used by humans since ancient times for therapeutic, for example, medicinal plants have been known in the Mesopotamia at least around 2000 BC. The Odyssey of Homer referred to a given to Helen by the Egyptian queen. It is believed that the gift was an opium-containing drug, a Chinese book on houseplants written in 1st–3rd centuries BC mentioned a medical use of Ephedra and opium poppies
15.
Shrub
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A shrub or bush is a small to medium-sized woody plant. It is distinguished from a tree by its multiple stems and shorter height, plants of many species may grow either into shrubs or trees, depending on their growing conditions. Small, low shrubs, generally less than 2 m tall, such as lavender, periwinkle, an area of cultivated shrubs in a park or a garden is known as a shrubbery. When clipped as topiary, suitable species or varieties of shrubs develop dense foliage, many shrubs respond well to renewal pruning, in which hard cutting back to a stool results in long new stems known as canes. Other shrubs respond better to selective pruning to reveal their structure, shrubs in common garden practice are generally considered broad-leaved plants, though some smaller conifers such as mountain pine and common juniper are also shrubby in structure. Species that grow into a shrubby habit may be deciduous or evergreen
16.
Khat
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Catha edulis is a flowering plant native to the Horn of Africa and the Arabian Peninsula. Among communities from these areas, khat chewing has a history as a custom dating back thousands of years. Khat contains an alkaloid called cathinone, an amphetamine-like stimulant. In 1980, the World Health Organization classified it as a drug of abuse that can produce psychological dependence, the plant has been targeted by anti-drug organizations such as the DEA. Consumption of the leaves in its natural state is also permitted in Israel. In the African Great Lakes region, where Catha edulis is in some cultivated, it is known as miraa, muhulo. In South Africa, the plant is known as Bushmans Tea, other names for khat include Chat Tree and Flower of Paradise. Khat is a shrub or tree that typically attains a height of between 1 and 5 m. However, it can reach heights of up to 10 metres in equatorial areas, the plant usually grows in arid environments, at a temperature range of 5 to 35 °C. It has evergreen leaves, which are 5–10 cm long and 1–4 cm broad, the shrubs flowers are produced on short axillary cymes that are 4–8 cm in length. Each flower is small, with five white petals, the samara fruit is an oblong, three-valved capsule, which contains one to three seeds. The khat plant is known by a variety of names, such as qat and gat in Yemen, qaat and jaad in Somalia and it is also known as jimaa in the Oromo language and mayirungi in Luganda Language. Khat has been grown for use as a stimulant for centuries in the Horn of Africa, there, chewing khat predates the use of coffee and is used in a similar social context. In Uganda it is grown in Central region, kasenge Nakawuka road, in Kenya it is grown in Meru County. The shrub is today scattered in the KwaZulu-Natal, Eastern Cape, Western Cape and Mpumalanga provinces of South Africa, in addition to Swaziland and Mozambique. Its fresh leaves and tops are chewed or, less frequently, dried and consumed as tea, to achieve a state of euphoria and stimulation, it also has anorectic side effects. The leaves or the part of the stem can be chewed with either chewing gum or fried peanuts to make it easier to chew. Traditionally, khat is used as a drug as in Yemen where khat-chewing is predominantly a male habit
17.
Ephedrine
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Ephedrine is a medication and stimulant. It is often used to prevent low blood pressure during spinal anesthesia and it has also been used for asthma, narcolepsy, and obesity but is not the preferred treatment. It is of benefit in nasal congestion. It can be taken by mouth or by injection into a muscle, vein, onset with intravenous use is fast, while injection into a muscle can take 20 min, and by mouth can take an hour for effect. When given by injection it lasts about an hour and when taken by mouth it can last up to four hours, common side effects include trouble sleeping, anxiety, headache, hallucinations, high blood pressure, fast heart rate, loss of appetite, and inability to urinate. Serious side effects include stroke, heart attack, and abuse, while likely safe in pregnancy its use in this population is poorly studied. Use during breastfeeding is not recommended, ephedrine works by turning on the α and β adrenergic receptors. Ephedrine was first isolated in 1885 and it is on the World Health Organizations List of Essential Medicines, the most effective and safe medicines needed in a health system. It is available as a generic medication, the wholesale cost in the developing world is about 0.69 to 1.35 USD per dose. In the United States it is not very expensive and it can normally be found in plants of the Ephedra type. Dietary supplements that contain ephedrine are illegal in the United States, an exception is when used in traditional Chinese medicine. Both ephedrine and pseudoephedrine increase blood pressure and act as bronchodilators, ephedrine promotes modest short-term weight loss, specifically fat loss, but its long-term effects are unknown. Methylxanthines such as caffeine and theophylline have an effect with ephedrine with respect to weight loss. This led to creation and marketing of compound products, one of them, known as the ECA stack, contains caffeine and aspirin besides ephedrine. It is a popular supplement taken by bodybuilders seeking to cut body fat before a competition, as a phenethylamine, ephedrine has a similar chemical structure to amphetamines and is a methamphetamine analogue having the methamphetamine structure with a hydroxyl group at the β position. The most popular method for reducing ephedrine to methamphetamine is similar to the Birch reduction, in that it uses anhydrous ammonia, the second-most popular method uses red phosphorus, iodine, and ephedrine in the reaction. Through oxidation, ephedrine can be synthesized into methcathinone. Ephedrine is listed as a table-I precursor under the United Nations Convention Against Illicit Traffic in Narcotic Drugs, ephedrine may be quantified in blood, plasma, or urine to monitor possible abuse by athletes, confirm a diagnosis of poisoning, or assist in a medicolegal death investigation
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Cathine
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Cathine, also known as d-norpseudoephedrine and -norpseudoephedrine, is a psychoactive drug of the phenethylamine and amphetamine chemical classes which acts as a stimulant. Along with cathinone, it is naturally in Catha edulis. It has approximately 10-14% the potency of amphetamine, like amphetamines, cathinone, and ephedrine, cathine acts as a norepinephrine releasing agent. It also acts as a releasing agent to a lesser extent. Cathine is one of the four stereoisomers of phenylpropanolamine, the World Anti-Doping Agencys list of prohibited substances bars cathine in concentrations of over 5 micrograms per milliliter in urine. Cathine is a Schedule III drug under the Convention on Psychotropic Substances, in the United States, it is classified as a Schedule IV controlled substance. In Australia, Cathine is officially a schedule 4 drug but is not yet available or approved for any use, in Hong Kong, cathine is regulated under Schedule 1 of Hong Kongs Chapter 134 Dangerous Drugs Ordinance. Unlawful possession is punishable by fines and imprisonment. L-Norpseudoephedrine, an enantiomer Phenylpropanolamine Catha edulis Cathinone Methcathinone Ephedra sinica Ephedrine Pseudoephedrine Phenethylamine Amphetamine Methamphetamine
19.
Methcathinone
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Methcathinone is a monoamine alkaloid and psychoactive stimulant, a substituted cathinone. It is usually snorted, but can be smoked, injected, methcathinone was first synthesized in 1928 in the United States and was patented by Parke Davis in 1957. It was used in the Soviet Union during the 1930s and 1940s as an anti-depressant, methcathinone has long been used as a drug of abuse in the Soviet Union and Russia. Circa 1994, the United States government recommended to the UN Secretary-General that methcathinone should be listed as a Schedule I controlled substance in the Convention on Psychotropic Substances. In parts of Europe this drug is not listed as a drug and is under review by the authorities in the United Kingdom where at the moment it is a Class B drug. They want it reclassified as a class A drug when it is dissolved in water for use just as amphetamine is. Methcathinone is a beta-keto N-methylamphetamine and is related to the naturally occurring compounds. It is also closely related to methamphetamine, differing by only the β-ketone substituent. Its carbon skeleton is identical to pseudoephedrine and methamphetamine and it differs from pseudoephedrine in that the hydroxide beta to the aromatic ring is oxidized to a ketone. Methcathinone possesses a chiral carbon atom, and therefore two enantiomers are possible, when it is made semi-synthetically from pseudo/ephedrine as a starting material, then only a single enantiomer is produced. Given that the center is adjacent to the carbonyl group. Methcathinone production utilizes the oxidation of pseudoephedrine or ephedrine, the former being preferred because of higher yields achieved. Oxidation of pseudoephedrine to methcathinone requires little chemistry experience, making it easy to synthesize, potassium permanganate is most commonly used as the oxidant. In clandestine laboratories, synthesizing methcathinone using potassium permanganate is considered undesirable because of the low yields, a method that yields more methcathinone is oxidizing ephedrine with chromium compounds. If done in a laboratory using the proper procedures, however. Methcathinone as free base is very unstable, it loses its ketone group. Structurally, this occurs when the C=O bond at the Rβ-position is converted into a C-OH bond, additionally, a dimerization reaction has been observed in solutions of freebase methcathinone, which yields a biologically inactive compound. In other words, basic methcathinone will turn into pseudoephedrine, from which it was synthesized, methcathinone hydrochloride increases spontaneous rodent locomotor activity, potentiates the release of dopamine from dopaminergic nerve terminals in the brain, and causes appetite suppression
20.
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
21.
Stimulant
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Stimulants is an overarching term that covers many drugs including those that increase activity of the body, drugs that are pleasurable and invigorating, or drugs that have sympathomimetic effects. Due to their rendering a characteristic up feeling, stimulants are also referred to as uppers. Depressants or downers, which decrease mental and/or physical function, are in stark contrast to stimulants and are considered to be the functionally opposite drug class, Stimulants are widely used throughout the world as prescription medicines as well as without a prescription as performance-enhancing or recreational drugs. The most frequently prescribed stimulants as of 2013 were lisdexamfetamine, methylphenidate and it is estimated that the percent of the population that has abused amphetamines, cocaine and MDMA combined is between. 8% and 2. 1%. Stimulants in therapeutic doses, such as given to patients with ADHD, increases ability to focus, vigor, sociability, libido. However, in higher doses stimulants may actually decrease the ability to focus, in higher doses stimulants may also produce euphoria, vigor, and decrease need for sleep. Many, but not all, stimulants have ergogenic effects, Drugs such as ephedrine, pseudoephedrine, amphetamine and methylphenidate have well documented ergogenic effects, while drugs such as cocaine and methamphetamine have the opposite effect. In some cases psychiatric phenomenon may emerge such as stimulant psychosis, paranoia, acute toxicity has been reportedly associated with a homicide, paranoia, aggressive behavior, motor dysfunction, and punding. The violent and aggressive behavior associated with acute stimulant toxicity may partially be driven by paranoia, most drugs classified as stimulants are sympathomimetics, that is they stimulate the sympathetic branch of the autonomic nervous system. This leads to such as mydriasis, increased heart rate, blood pressure, respiratory rate. When these changes become pathological, they are called arrhythmia, hypertension, and hyperthermia, however given the complexity of the mechanisms that underly these potentially fatal outcomes of acute stimulant toxicity, it is impossible to determine what dose may be lethal. Assessment of the effects of stimulants is relevant given the large population currently taking stimulants. A systematic review of cardiovascular effects of prescription stimulants found no association in children, a review over a four-year period found that there were few negative effects of stimulant treatment, but stressed the need for longer term studies. A review of a long period of prescription stimulate use in those with ADHD found that cardiovascular side effects were limited to transient increases in blood pressure only. Initiation of stimulant treatment in those with ADHD in early childhood appears to carry benefits into adulthood with regard to social and cognitive functioning, Abuse of prescription stimulants or of illicit stimulants carries many negative health risks. Abuse of cocaine, depending upon route of administration, increases risk of disease, stroke. Cocaine may also increase risk for disease, as well as damage nasal cartilage. Abuse of methamphetamine produces similar effects as well as marked degeneration of dopaminergic neurons, Drugs used to treat sleep disorders such as excessive daytime sleepiness are called eugeroics, and include notable stimulants such as modafinil
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Ketone
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In chemistry, a ketone /ˈkiːtoʊn/ is an organic compound with the structure RCR, where R and R can be a variety of carbon-containing substituents. Ketones and aldehydes are simple compounds that contain a carbonyl group and they are considered simple because they do not have reactive groups like −OH or −Cl attached directly to the carbon atom in the carbonyl group, as in carboxylic acids containing −COOH. Many ketones are known and many are of importance in industry. Examples include many sugars and the industrial solvent acetone, which is the smallest ketone, the word ketone is derived from Aketon, an old German word for acetone. According to the rules of IUPAC nomenclature, ketones are named by changing the suffix -ane of the parent alkane to -anone, the position of the carbonyl group is usually denoted by a number. For the most important ketones, however, traditional names are still generally used. The common names of ketones are obtained by writing separately the names of the two alkyl groups attached to the group, followed by ketone as a separate word. The names of the groups are written alphabetically. When the two groups are the same, the prefix di- is added before the name of alkyl group. The positions of other groups are indicated by Greek letters, the α-carbon being the adjacent to carbonyl group. If both alkyl groups in a ketone are the same then the ketone is said to be symmetrical, although used infrequently, oxo is the IUPAC nomenclature for a ketone functional group. Other prefixes, however, are also used, for some common chemicals, keto or oxo refer to the ketone functional group. The term oxo is used widely through chemistry, for example, it also refers to an oxygen atom bonded to a transition metal. The ketone carbon is often described as sp2 hybridized, a description that includes both their electronic and molecular structure, ketones are trigonal planar around the ketonic carbon, with C−C−O and C−C−C bond angles of approximately 120°. Ketones differ from aldehydes in that the group is bonded to two carbons within a carbon skeleton. In aldehydes, the carbonyl is bonded to one carbon and one hydrogen and are located at the ends of carbon chains, ketones are also distinct from other carbonyl-containing functional groups, such as carboxylic acids, esters and amides. The carbonyl group is polar because the electronegativity of the oxygen is greater than that for carbon, thus, ketones are nucleophilic at oxygen and electrophilic at carbon. Because the carbonyl group interacts with water by bonding, ketones are typically more soluble in water than the related methylene compounds
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Functional group
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In organic chemistry, functional groups are specific groups of atoms or bonds within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of, however, its relative reactivity can be modified by other functional groups nearby. The atoms of functional groups are linked to other and to the rest of the molecule by covalent bonds. Any subgroup of atoms of a compound also may be called a radical, and if a covalent bond is broken homolytically, Functional groups can also be charged, e. g. in carboxylate salts, which turns the molecule into a polyatomic ion or a complex ion. Complexation and solvation is also caused by interactions of functional groups. In the common rule of thumb like dissolves like, it is the shared or mutually well-interacting functional groups give rise to solubility. For example, sugar dissolves in water because both share the functional group and hydroxyls interact strongly with each other. Combining the names of groups with the names of the parent alkanes generates what is termed a systematic nomenclature for naming organic compounds. In traditional nomenclature, the first carbon atom after the carbon that attaches to the group is called the alpha carbon, the second, beta carbon. IUPAC conventions call for numeric labeling of the position, e. g. 4-aminobutanoic acid, in traditional names various qualifiers are used to label isomers, for example isopropanol is an isomer is n-propanol. The following is a list of functional groups. In the formulas, the symbols R and R usually denote an attached hydrogen, or a side chain of any length. Functional groups, called hydrocarbyl, that only carbon and hydrogen. Each one differs in type of reactivity, there are also a large number of branched or ring alkanes that have specific names, e. g. tert-butyl, bornyl, cyclohexyl, etc. Hydrocarbons may form charged structures, positively charged carbocations or negative carbanions, examples are tropylium and triphenylmethyl cations and the cyclopentadienyl anion. Haloalkanes are a class of molecule that is defined by a carbon–halogen bond and this bond can be relatively weak or quite stable. In general, with the exception of fluorinated compounds, haloalkanes readily undergo nucleophilic substitution reactions or elimination reactions, the substitution on the carbon, the acidity of an adjacent proton, the solvent conditions, etc. all can influence the outcome of the reactivity. Compounds that contain nitrogen in this category may contain C-O bonds, compounds that contain sulfur exhibit unique chemistry due to their ability to form more bonds than oxygen, their lighter analogue on the periodic table
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Methylenedioxypyrovalerone
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Methylenedioxypyrovalerone is a stimulant of the cathinone class which acts as a norepinephrine-dopamine reuptake inhibitor. It was first developed in the 1960s by a team at Boehringer Ingelheim, MDPV remained an obscure stimulant until around 2004 when it was reportedly sold as a designer drug. The hydrochloride salt exists as a fine, hygroscopic, crystalline powder that tends to clump to itself. Its color can range from white to a yellowish-tan and has a slight odor that strengthens as it colors. Impurities are likely to consist of either pyrrolidine or alpha-dibrominated alkylphenones from either excess pyrrolidine or incomplete amination, respectively and these impurities likely account for its discoloration and fishy or bromine-like odor, which worsens upon exposure to air, moisture, or bases. Methylenedioxypyrovalerone has no record of FDA approved medical use, other drugs with a similar chemical structure include α-pyrrolidinopropiophenone, 4-methyl-α-pyrrolidinopropiophenone,3, 4-methylenedioxy-α-pyrrolidinopropiophenone and 1-phenyl-2--1-pentanone. MDPV acts as a stimulant and has reported to produce effects similar to those of cocaine, methylphenidate. The primary psychological effects have a duration of roughly 3 to 4 hours, with effects such as tachycardia, hypertension. It has also been noted for inducing irresistable cravings to re-administer. Reported modalities of intake include oral consumption, insufflation, smoking, rectal and it is supposedly active at 3–5 mg, with typical doses ranging between 5–20 mg. Also, these behavioural changes are related to alterations of factor expression directly related to addiction. No free pyrrolidine will be detected in the urine, molecularly, this is seen as demethylenation of methylenedioxypyrovalerone, followed by methylation of the aromatic ring via catechol-O-methyl transferase. Blood or plasma MDPV concentrations are expected to be in a range of 10–50 μg/L in persons using the drug recreationally, >50 μg/L in intoxicated patients, MDPV is specifically listed as a controlled substance in Finland, Denmark and Sweden. In Sweden a 33-year-old man has been sentenced to six years in prison by a court, Hovrätt. In Western Australia, MDPV has been banned under the Poisons Act 1964, the Director of Public Prosecutions for Western Australia announced that anyone intending to sell or supply MDPV faces a maximum $100,000 fine or 25 years in jail. Users face a fine or two years jail. Therefore, anyone caught with MDPV can be charged with possession, canadian Health Minister Leona Aglukkaq announced on June 5,2012 that MDPV would be listed on Schedule I of the Controlled Drugs and Substances Act, which was realized on September 26,2012. In the United States, MDPV is a DEA federally scheduled drug, on October 21,2011, the DEA issued a temporary one-year ban on MDPV, classifying it as a schedule I substance. Prior to the Federal ban being announced, it was banned in Louisiana
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Mephedrone
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Mephedrone, also known as 4-methyl methcathinone or 4-methyl ephedrone, is a synthetic stimulant drug of the amphetamine and cathinone classes. Slang names include drone, M-CAT, White Magic and meow meow and it is chemically similar to the cathinone compounds found in the khat plant of eastern Africa. It comes in the form of tablets or a powder, which users can swallow, snort or inject, producing similar effects to MDMA, amphetamines, in addition to its stimulant effects, mephedrone produces side effects, of which teeth grinding is the most common. The metabolism of mephedrone has been studied in rats and humans, Mephedrone was first synthesised in 1929, but did not become widely known until it was rediscovered in 2003 at which point it was legal to produce and possess in many countries. Mephedrone was first made illegal in Israel in 2008, followed by Sweden later that year, in 2010, it was made illegal in many European countries and in December 2010, the EU ruled it illegal. In Australia, New Zealand and the United States, it is considered an analog of other illegal drugs, in September 2011, the US temporarily classified mephedrone as a Schedule I drug, effective October 2011. This classification was made permanent in July 2012 with the passage of the Synthetic Drug Abuse Prevention Act, of 70 Dutch users of mephedrone,58 described it as an overall pleasant experience and 12 described it as an unpleasant experience. In a survey of UK users who had taken cocaine, most users found it produced a better-quality. The users were asked to compare the risk, and they answered that it was equal. A study of users in Northern Ireland found they did not equate the fact that mephedrone was legal with it being safe to use and this was contrary to another study in New Zealand, where users of benzylpiperazine thought that because it was legal, it was safe. Mephedrone can come in the form of capsules, tablets or white powder that users may swallow, snort, inject, smoke or use rectally. When taken orally, users reported they could feel the effects within 15–45 minutes, when snorted, the effects last for between two and three hours when taken orally or nasally, but only half an hour if taken intravenously. It is sometimes mixed with methylone in a product called bubbles in the UK and also mixed with other cathinones. One published study that analysed samples of mephedrone bought using the internet in the UK in 2010 found it was racemic, an unpublished study of six samples also ordered off the internet in the UK in 2010 found they contained very few organic impurities. Four products sold in Irish head shops were tested in 2010 and were found to contain between 82% and 14% mephedrone, with products containing benzocaine and caffeine. They noted the most severe effects appear anecdotally to be linked with high doses or prolonged use, when snorted, it can also cause nose bleeds and nose burns. They reported none of their patients suffered from cold or blue peripheries, the patients also reported polydrug use of a variety of compounds. Neurotoxic effect of mephedrone on serotonin and dopamine systems remains controversial, persistent serotonergic deficits were observed after binge like treatment in a warm environment and in both serotonergic and dopaminergic nerve endings at high ambient temperature
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Antidepressant
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They may be prescribed alone or in combination with other medications. St Johns wort is used in the treatment of depression. For depression, the Hamilton Depression Rating Scale is often used to measure the severity of depression, the maximum score for the 17-item HAM-D questionnaire is 52, the higher the score, the more severe the depression. Options may include pharmacotherapy, psychotherapy, electroconvulsive therapy, transcranial magnetic stimulation or light therapy, conflicting results have arisen from studies analyzing the efficacy of antidepressants by comparisons to placebo in people with acute mild to moderate depression. Stronger evidence supports the usefulness of antidepressants in the treatment of depression that is chronic or severe and their study consisted of a meta analysis incorporating data from both published studies and unpublished data obtained from the FDA via a Freedom of Information Act request. Overall, antidepressant pills worked 18% better than placebos, a significant difference. In a later publication, Kirsch concluded that the effect of new-generation antidepressant medication is below recommended criteria for clinical significance. In 2014 the U. S. FDA published a review of all antidepressant maintenance trials submitted to the agency between 1985 and 2012. The Cochrane Collaboration recently performed a review of clinical trials of the tricyclic antidepressant amitriptyline. The study concluded that in spite of evidence for publication bias. A2004 review concluded that antidepressant studies that failed to support efficacy claims were dramatically less likely to be published than those that did support favorable efficacy claims, similar results were obtained for a study of publication of clinical trials of antidepressants in children. A2015 investigation of meta-analyses of antidepressant studies found that 79% of them had sponsorship or authors who were industry employees and/or had conflicts of interest, a 2012 meta-analysis found that fluoxetine and venlafaxine were effective for major depression in all age groups. The authors also found no evidence of a relationship between baseline severity of depression and degree of benefit of antidepressants over placebo, a review published in 2012 found a negative correlation between study year and efficacy of antidepressants as measured by response rate. The change in rate was largely driven by increase in placebo response. However the authors concluded that antidepressants were effective in treating depression. The authors found that TCAs were the most effective drug, followed by SNRIs, MAOIs, SSRIs, the largest and most expensive study conducted to date, on the effectiveness of pharmacological treatment for depression, was commissioned by the National Institute of Mental Health. The study was dubbed The Sequenced Treatment Alternatives to Relieve Depression Study, participants in the trial were recruited when they sought medical care at general medical or psychiatric clinics. No advertising was used to recruit subjects in order to maximize the generalizability of the study results, participants were required to have a minimum score of 14 point on the Hamilton Depression Scale in order to be enrolled in the trial
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Euphoria
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Euphoria is an affective state in which a person experiences pleasure or excitement and intense feelings of well-being and happiness. Certain drugs, many of which are addictive, can cause euphoria, similarly, certain natural rewards and social activities, such as aerobic exercise, laughter, listening to emotionally arousing music, music-making, and dancing, can induce a state of euphoria. Euphoria is also a symptom of certain neurological or neuropsychiatric disorders, romantic love and components of the human sexual response cycle are also associated with the induction of euphoria. According to Kent Berridge, an affective neuroscientist, intense euphoria occurs from the activation of every hedonic hotspot within the brains reward system. The word euphoria is derived from the Ancient Greek terms εὐφορία, εὖ eu meaning well and it is semantically opposite to dysphoria. A1706 English dictionary defined euphoria as the bearing of the Operation of a Medicine. A1903 article in The Boston Daily Globe refers to euphoria as pleasant excitement, in 1920 Popular Science magazine described euphoria as a high sounding name meaning feeling fit, normally making life worth living, motivating drug use, and ill formed in certain mental illnesses. In 1940 The Journal of Psychology defined euphoria as a state of well being. However, in 1957 British pharmacologist D. A. Cahal did not regard opioid euphoria as medically undesirable, the 1977 edition of A Concise Encyclopaedia of Psychiatry called euphoria a mood of contentment and well-being, with pathologic associations when used in a psychiatric context. As a sign of disease, it was described as bland and out of context. Many different types of stimuli can induce euphoria, including drugs, natural rewards. Affective disorders such as mania or bipolar disorder can involve euphoria as a symptom. Euphoria can occur as a result of dancing to music, music-making, neuroimaging studies have demonstrated that the reward system plays a central role in mediating music-induced pleasure. Pleasurable emotionally arousing music strongly increases dopamine neurotransmission in the pathways that project to the striatum. A euphoriant is a type of drug which tends to induce euphoria. Most euphoriants are addictive drugs due to their properties and ability to activate the brains reward system. Dopaminergic stimulants like amphetamine, methamphetamine, cocaine, MDMA, nicotine is a parasympathetic stimulant that acts as a mild euphoriant in some people. Certain depressants can produce euphoria, some of the euphoriant drugs in this class include drinking alcohol in moderate doses, γ-hydroxybutyric acid, some barbiturates and benzodiazepines may cause euphoria
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Yemen
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Yemen, officially known as the Republic of Yemen, is an Arab country in Western Asia, occupying South Arabia, the southern end of the Arabian Peninsula. Yemen is the second-largest country in the peninsula, occupying 527,970 km2, the coastline stretches for about 2,000 km. It is bordered by Saudi Arabia to the north, the Red Sea to the west, the Gulf of Aden and Arabian Sea to the south, although Yemens constitutionally stated capital is the city of Sanaa, the city has been under rebel control since February 2015. Because of this, Yemens capital has been relocated to the port city of Aden. Yemens territory includes more than 200 islands, the largest of these is Socotra, Yemen was the home of the Sabaeans, a trading state that flourished for over a thousand years and probably also included parts of modern-day Ethiopia and Eritrea. In 275 AD, the region came under the rule of the later Jewish-influenced Himyarite Kingdom, Christianity arrived in the fourth century, whereas Judaism and local paganism were already established. Islam spread quickly in the century and Yemenite troops were crucial in the expansion of the early Islamic conquests. Administration of Yemen has long been notoriously difficult, several dynasties emerged from the ninth to 16th centuries, the Rasulid dynasty being the strongest and most prosperous. The country was divided between the Ottoman and British empires in the twentieth century. The Zaydi Mutawakkilite Kingdom of Yemen was established after World War I in North Yemen before the creation of the Yemen Arab Republic in 1962, South Yemen remained a British protectorate known as the Aden Protectorate until 1967 when it became an independent state and later, a Marxist state. The two Yemeni states united to form the modern republic of Yemen in 1990, Yemen is a developing country, and the poorest country in the Middle East. Under the rule of President Ali Abdullah Saleh, Yemen was described as a kleptocracy, according to the 2009 international corruption Perception Index by Transparency International, Yemen ranked 164 out of 182 countries surveyed. President Saleh stepped down and the powers of the presidency were transferred to Vice President Abd Rabbuh Mansur Hadi, the transitional process was disrupted by conflicts between the Houthis and al-Islah, as well as the al-Qaeda insurgency. In September 2014, the Houthis took over Sanaa, later declaring themselves in control of the government in a coup détat, since then, a Saudi-led intervention has taken place, however, it could not stop the civil war. Instead, the Saudis and the others have destroyed some hospitals, schools and homes, Yemen was mentioned in Old South Arabian inscriptions as Yamnat. In Arabic literature, the term includes much greater territory than that of the republic of Yemen. It stretches from the northern Asir Region in southwestern Saudi Arabia to Dhofar Governorate in southern Oman, one etymology derives Yemen from yumn, meaning felicity, as much of the country is fertile. The Romans called it Arabia Felix, as opposed to Arabia Deserta, al-Yaman significantly plays on the notion of the land to the right, when in Mecca facing the dawn, complementary to Al-Sham, the Land to the Left, referring to the Levant
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Kenya
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Kenya, officially the Republic of Kenya, is a country in Africa and a founding member of the East African Community. Its capital and largest city is Nairobi and it is bordered by Tanzania to the south and southwest, Uganda to the west, South Sudan to the north-west, Ethiopia to the north and Somalia to the north-east. Kenya covers 581,309 km2, and had a population of approximately 48 million people in January 2017, Kenya has a warm and humid tropical climate on its Indian Ocean coastline. The climate is cooler in the grasslands around the capital city, Nairobi, and especially closer to Mount Kenya. Further inland are highlands in Central and Rift Valley regions where tea, in the West are Nyanza and Western regions, there is an equatorial, hot and dry climate which becomes humid around Lake Victoria, the largest tropical fresh-water lake in the world. This gives way to temperate and forested areas in the neighbouring western region. The north-eastern regions along the border with Somalia and Ethiopia are arid and semi-arid areas with near-desert landscapes, Kenya is known for its world class athletes in track and field and rugby. The African Great Lakes region, which Kenya is a part of, has been inhabited by humans since the Lower Paleolithic period, by the first millennium AD, the Bantu expansion had reached the area from West-Central Africa. Bantu and Nilotic populations together constitute around 97% of the nations residents, European and Arab presence in coastal Mombasa dates to the Early Modern period, European exploration of the interior began in the 19th century. The British Empire established the East Africa Protectorate in 1895, which starting in 1920 gave way to the Kenya Colony, Kenya obtained independence in December 1963. Following a referendum in August 2010 and adoption of a new constitution, Kenya is now divided into 47 semi-autonomous counties, the capital, Nairobi, is a regional commercial hub. The economy of Kenya is the largest by GDP in East, agriculture is a major employer, the country traditionally exports tea and coffee and has more recently begun to export fresh flowers to Europe. The service industry is also an economic driver. Additionally, Kenya is a member of the East African Community trading bloc, the Republic of Kenya is named after Mount Kenya. The origin of the name Kenya is not clear, but perhaps linked to the Kikuyu, Embu and Kamba words Kirinyaga, Kirenyaa, if so, then the British may not so much have mispronounced it, as misspelled it. In the 19th century, the German explorer Johann Ludwig Krapf was staying with the Bantu Kamba people when he first spotted the mountain. On asking for the name of the mountain, he was told Kĩ-Nyaa or Kĩĩma- Kĩĩnyaa probably because the pattern of black rock, the Agikuyu, who inhabit the slopes of Mt. Kenya, call it Kĩrĩma Kĩrĩnyaga in Kikuyu, which is quite similar to the Kamba name. Ludwig Krapf recorded the name as both Kenia and Kegnia believed by most to be a corruption of the Kamba version, others say that this was—on the contrary—a very precise notation of a correct African pronunciation /ˈkɛnjə/
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Madagascar
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Madagascar, officially the Republic of Madagascar, and previously known as the Malagasy Republic, is an island country in the Indian Ocean, off the coast of Southeast Africa. The nation comprises the island of Madagascar, and numerous smaller peripheral islands, consequently, Madagascar is a biodiversity hotspot, over 90% of its wildlife is found nowhere else on Earth. The islands diverse ecosystems and unique wildlife are threatened by the encroachment of the growing human population. The first archaeological evidence for human foraging on Madagascar dates to 2000 BC, human settlement of Madagascar occurred between 350 BC and AD550 by Austronesian peoples arriving on outrigger canoes from Borneo. These were joined around AD1000 by Bantu migrants crossing the Mozambique Channel from East Africa, other groups continued to settle on Madagascar over time, each one making lasting contributions to Malagasy cultural life. The Malagasy ethnic group is divided into 18 or more sub-groups of which the largest are the Merina of the central highlands. Until the late 18th century, the island of Madagascar was ruled by an assortment of shifting sociopolitical alliances. Beginning in the early 19th century, most of the island was united and ruled as the Kingdom of Madagascar by a series of Merina nobles, the monarchy collapsed in 1897 when the island was absorbed into the French colonial empire, from which the island gained independence in 1960. The autonomous state of Madagascar has since undergone four major constitutional periods, since 1992, the nation has officially been governed as a constitutional democracy from its capital at Antananarivo. However, in an uprising in 2009, president Marc Ravalomanana was made to resign. Constitutional governance was restored in January 2014, when Hery Rajaonarimampianina was named president following a 2013 election deemed fair, Madagascar is a member of the United Nations, the Organisation Internationale de la Francophonie and the Southern African Development Community. Madagascar belongs to the group of least developed countries, according to the United Nations, Malagasy and French are both official languages of the state. The majority of the population adheres to traditional beliefs, Christianity, ecotourism and agriculture, paired with greater investments in education, health, and private enterprise, are key elements of Madagascars development strategy. As of 2017, the economy has been weakened by the 2009-2013 political crisis, in the Malagasy language, the island of Madagascar is called Madagasikara and its people are referred to as Malagasy. The islands appellation Madagascar is not of origin, but rather was popularized in the Middle Ages by Europeans. On St. Laurences Day in 1500, Portuguese explorer Diogo Dias landed on the island, polos name was preferred and popularized on Renaissance maps. At 592,800 square kilometres, Madagascar is the worlds 47th largest country, the country lies mostly between latitudes 12°S and 26°S, and longitudes 43°E and 51°E. Neighboring islands include the French territory of Réunion and the country of Mauritius to the east, as well as the state of Comoros, the nearest mainland state is Mozambique, located to the west
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Placebo
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A placebo is a substance or treatment with no active therapeutic effect. A placebo may be given to a person in order to deceive the recipient into thinking that it is an active treatment. This phenomenon, in which the recipient perceives an improvement in condition due to personal expectations, research about the effect is ongoing. Placebos are an important methodological tool in medical research, common placebos include inert tablets, vehicle infusions, sham surgery, and other procedures based on false information. Placebo effects are the subject of research aiming to understand underlying neurobiological mechanisms of action in pain relief, immunosuppression, Parkinsons disease. Brain imaging techniques done by Emeran Mayer, Johanna Jarco and Matt Lieberman showed that placebo can have real, in other cases, like asthma, the effect is purely subjective, when the patient reports improvement despite no objective change in the underlying condition. The placebo effect is a phenomenon, in fact, it is part of the response to any active medical intervention. The placebo effect points to the importance of perception and the role in physical health. The use of placebos as treatment in clinical medicine is ethically problematic as it introduces deception, the United Kingdom Parliamentary Committee on Science and Technology has stated that. prescribing placebos. Usually relies on some degree of patient deception and prescribing pure placebos is bad medicine and their effect is unreliable and unpredictable and cannot form the sole basis of any treatment on the NHS. In 1955, Henry K. Beecher proposed that placebos could have important effects. The article received a flurry of criticism, but the later published a Cochrane review with similar conclusions. A placebo has been defined as a substance or procedure and that is objectively without specific activity for the condition being treated. Under this definition, a variety of things can be placebos. Likewise, the effects of stimulation from implanted electrodes in the brains of those with advanced Parkinsons disease are greater when they are aware they are receiving this stimulation, sometimes administering or prescribing a placebo merges into fake medicine. Common placebos include pills or saline injections, fake surgeries have also seen some use. An example is the Finish Meniscal Legion Study Group’s trial published in The New England Journal of Medicine, while examples of placebo treatments can be found, defining the placebo concept remains elusive. A placebo electronic cigarette contains 0 mg of nicotine, instead they introduced the term meaning response for the meaning that the brain associates with the placebo, which causes a physiological placebo effect
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Arabian Peninsula
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The Arabian Peninsula, simplified Arabia is a peninsula of Western Asia situated northeast of Africa on the Arabian plate. From a geological perspective, it is considered a subcontinent of Asia and it is the largest peninsula in the world, at 3,237,500 km2. The Arabian Peninsula consists of the countries Yemen, Oman, Qatar, Bahrain, Kuwait, Saudi Arabia, the Arabian Peninsula plays a critical geopolitical role in the Middle East and the Arab world due to its vast reserves of oil and natural gas. Before the modern era, it was divided into four regions, Hejaz, Najd, Southern Arabia. Hejaz and Najd make up most of Saudi Arabia, Southern Arabia consists of Yemen and some parts of Saudi Arabia and Oman. Eastern Arabia consists of the coastal strip of the Persian Gulf. The most prominent feature of the peninsula is desert, but in the southwest there are mountain ranges, harrat ash Shaam is a large volcanic field that extends from the northwestern Arabian Peninsula into Jordan and southern Syria. The peninsulas constituent countries are Kuwait, Bahrain, Qatar, the island nation of Bahrain lies off the east coast of the peninsula. Six countries form the Gulf Cooperation Council, however, this is a disputed term. The Kingdom of Saudi Arabia covers the part of the peninsula. The majority of the population of the live in Saudi Arabia. The peninsula contains the worlds largest reserves of oil, Saudi Arabia and the UAE are economically the wealthiest in the region. Qatar, a peninsula in the Persian Gulf on the larger peninsula, is home of the Arabic-language television station Al Jazeera. Kuwait, on the border with Iraq, is an important country strategically, though historically lightly populated, political Arabia is noted for a high population growth rate - as the result of both very strong inflows of migrant labor as well as sustained high birth rates. The population tends to be young and heavily skewed gender ratio dominated by males. In many states, the number of South Asians exceeds that of the local citizenry, the four smallest states, which have their entire coastlines on the Persian Gulf, exhibit the worlds most extreme population growth, roughly tripling every 20 years. In 2014, the population of the Arabian Peninsula was 77,983,936. Listed here are the human Y-chromosome DNA haplogroups in Arabia Haplogroup J is the most abundant component in the Arabian peninsula and its two main subclades, show opposite latitudinal gradients in the Middle East
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East Africa
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East Africa or Eastern Africa is the easterly region of the African continent, variably defined by geography or geopolitics. The first five are included in the African Great Lakes region. Burundi and Rwanda are sometimes considered to be part of Central Africa. Djibouti, Eritrea, Ethiopia and Somalia – collectively known as the Horn of Africa, Comoros, Mauritius and Seychelles – small island nations in the Indian Ocean. Réunion and Mayotte – French overseas territories also in the Indian Ocean, Mozambique and Madagascar – often considered part of Southern Africa, on the eastern side of the sub-continent. Madagascar has close ties to Southeast Asia and the islands of the Indian Ocean. Malawi, Zambia and Zimbabwe – often also included in Southern Africa, Egypt, Sudan and South Sudan – collectively part of the Nile Valley. Situated in the portion of the continent, and Egypt. Also members of the Common Market for Eastern and Southern Africa free trade area, the geography of East Africa is often stunning and scenic. Shaped by global plate tectonic forces that have created the East African Rift, East Africa is the site of Mount Kilimanjaro and Mount Kenya and it also includes the worlds second largest freshwater lake Lake Victoria, and the worlds second deepest lake Lake Tanganyika. The climate of East Africa is rather atypical of equatorial regions, in fact, on the coast of Somaliland and Puntland, many years can go by without any rain whatsoever. Unusually, most of the falls in two distinct wet seasons, one centred on April and the other in October or November. Annual rainfall here ranges from over 1,600 millimetres on the slopes to around 1,250 millimetres at Addis Ababa and 550 millimetres at Asmara. In the high rainfall can be over 2,500 millimetres. Temperatures in East Africa, except on the hot and generally humid coastal belt, are moderate, with maxima of around 25 °C, at altitudes of above 2,500 metres, frosts are common during the dry season and maxima typically about 21 °C or less. The unique geography and apparent suitability for farming made East Africa a target for European exploration, exploitation and colonialization in the nineteenth century, today, tourism is an important part of the economies of Kenya, Tanzania, Seychelles, and Uganda. The easternmost point of the continent, that is Ras Hafun in Somalia, is of archaeological, historical and economical importance, there are differing theories on whether there was a single exodus or several, a multiple dispersal model involves the Southern Dispersal theory. A growing number of researchers suspect that North Africa was instead the home of the modern humans who first trekked out of the continent
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Ethiopia
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Ethiopia, officially the Federal Democratic Republic of Ethiopia, is a country located in the Horn of Africa. It shares borders with Eritrea to the north and northeast, Djibouti and Somalia to the east, Sudan and South Sudan to the west, and Kenya to the south. With nearly 100 million inhabitants, Ethiopia is the most populous landlocked country in the world and it occupies a total area of 1,100,000 square kilometres, and its capital and largest city is Addis Ababa. Some of the oldest evidence for modern humans has been found in Ethiopia. It is widely considered as the region from modern humans first set out for the Middle East. According to linguists, the first Afroasiatic-speaking populations settled in the Horn region during the ensuing Neolithic era, tracing its roots to the 2nd millennium BC, Ethiopia was a monarchy for most of its history. During the first centuries AD, the Kingdom of Aksum maintained a unified civilization in the region, subsequently, many African nations adopted the colors of Ethiopias flag following their independence. It was the first independent African member of the 20th-century League of Nations, Ethiopias ancient Geez script, also known as Ethiopic, is one of the oldest alphabets still in use in the world. The Ethiopian calendar, which is seven years and three months behind the Gregorian calendar, co-exists alongside the Borana calendar. A slight majority of the population adheres to Christianity, while around a third follows Islam, the country is the site of the Migration to Abyssinia and the oldest Muslim settlement in Africa at Negash. A substantial population of Ethiopian Jews, known as Bete Israel, resided in Ethiopia until the 1980s, Ethiopia is a multilingual nation with around 80 ethnolinguistic groups, the four largest of which are the Oromiffa, Amhara, Somali, and Tigrayans. Most people in the country speak Afroasiatic languages of the Cushitic or Semitic branches, additionally, Omotic languages are spoken by ethnic minority groups inhabiting the southern regions. Nilo-Saharan languages are spoken by the nations Nilotic ethnic minorities. Ethiopia is the place of origin for the coffee bean which originated from the place called Kefa and it is a land of natural contrasts, with its vast fertile West, jungles, and numerous rivers, and the worlds hottest settlement of Dallol in its north. The Ethiopian Highlands are Africas largest continuous mountain ranges, and Sof Omar Caves contain Africas largest cave, Ethiopia has the most UNESCO World Heritage Sites in Africa. Ethiopia is one of the members of the UN, the Group of 24, the Non-Aligned Movement, G-77. In the 1970s and 1980s, Ethiopia suffered from civil wars, the country has begun to recover recently however, and now has the largest economy in East Africa and Central Africa. According to Global Fire Power, Ethiopia has the 42nd most powerful military in the world, the origin of the word Ethiopia is uncertain
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Djibouti
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Djibouti, officially the Republic of Djibouti, is a country located in the Horn of Africa. It is bordered by Eritrea in the north, Ethiopia in the west and south, the remainder of the border is formed by the Red Sea and the Gulf of Aden at the east. Djibouti occupies an area of just 23,200 km2. In antiquity, the territory was part of the Land of Punt and then the Sabean, nearby Zeila was the seat of the medieval Adal and Ifat Sultanates. It was subsequently renamed to the French Territory of the Afars, a decade later, the Djiboutian people voted for independence. This officially marked the establishment of the Republic of Djibouti, named after its capital city, Djibouti joined the United Nations the same year, on 20 September 1977. In the early 1990s, tensions over government representation led to armed conflict, Djibouti is a multi-ethnic nation with a population of over 846,687 inhabitants. Arabic and French are the two official languages. About 94% of residents adhere to Islam, a religion that has been predominant in the region for more than 1,000 years, the Somali Issa and Afar make up the two largest ethnic groups. Both speak Afroasiatic languages, which serve as recognized national languages, Djibouti is strategically located near some of the worlds busiest shipping lanes, controlling access to the Red Sea and Indian Ocean. It serves as a key refueling and transshipment center, and is the principal port for imports from. A burgeoning commercial hub, the nation is the site of various military bases. The Intergovernmental Authority on Development regional body also has its headquarters in Djibouti City, the Djibouti area has been inhabited since at least the Neolithic. According to linguists, the first Afroasiatic-speaking populations arrived in the region during this period from the familys proposed urheimat in the Nile Valley, other scholars propose that the Afroasiatic family developed in situ in the Horn, with its speakers subsequently dispersing from there. Pottery predating the mid-2nd millennium has been found at Asa Koma, the sites ware is characterized by punctate and incision geometric designs, which bear a similarity to the Sabir culture phase 1 ceramics from Malayba in Southern Arabia. Long-horned humpless cattle bones have likewise been discovered at Asa Koma, rock art of what appear to be antelopes and a giraffe are also found at Dorra and Balho. Handoga, dated to the fourth millennium BP, has in turn yielded obsidian microliths, additionally, between Djibouti City and Loyada are a number of anthropomorphic and phallic stelae. The structures are associated with graves of rectangular shape that are flanked by vertical slabs, the Djibouti-Loyada stelae are of uncertain age, and some of them are adorned with a T-shaped symbol
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Caffeine
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Caffeine is a central nervous system stimulant of the methylxanthine class. It is the worlds most widely consumed psychoactive drug, unlike many other psychoactive substances, it is legal and unregulated in nearly all parts of the world. There are several mechanisms of action to explain the effects of caffeine. The most prominent is that it blocks the action of adenosine on its receptor. Caffeine also stimulates certain portions of the nervous system. Caffeine is a bitter, white crystalline purine, a methylxanthine alkaloid and it is found in the seeds, nuts, or leaves of a number of plants native to South America and East Asia and helps to protect them against predator insects and prevent germination of nearby seeds. The most well known source of caffeine is the coffee bean, beverages containing caffeine are ingested to relieve or prevent drowsiness and to improve performance. To make these drinks, caffeine is extracted by steeping the plant product in water, caffeine-containing drinks, such as coffee, tea, and cola, are very popular, in 2005, 90% of North American adults consumed caffeine daily. Caffeine can have positive and negative health effects. It can treat and prevent the premature infant breathing disorders bronchopulmonary dysplasia of prematurity, Caffeine citrate is on the WHO Model List of Essential Medicines. It may confer a modest protective effect against some diseases, including Parkinsons disease, some people experience insomnia or sleep disruption if they consume caffeine, especially during the evening hours, but others show little disturbance. Evidence of a risk during pregnancy is equivocal, some authorities recommend that pregnant women limit consumption to the equivalent of two cups of coffee per day or less. Tolerance to the effects of increased blood pressure and heart rate. Caffeine is classified by the Food and Drug Administration as generally recognized as safe, toxic doses, over 10 grams per day for an adult, are much higher than typical doses of under 500 milligrams per day. A cup of coffee contains 80–175 mg of caffeine, depending on what bean is used, thus it requires roughly 50–100 ordinary cups of coffee to reach a lethal dose. However pure powdered caffeine, which is available as a dietary supplement, Caffeine is used in, Bronchopulmonary dysplasia in premature infants for both prevention and treatment. It may improve weight gain during therapy and reduce the incidence of cerebral palsy as well as reduce language, on the other hand, subtle long-term side effects are possible. Apnea of prematurity as a treatment, but not prevention
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Convention on Psychotropic Substances
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The Single Convention on Narcotic Drugs of 1961 could not ban the many newly discovered psychotropics, since its scope was limited to drugs with cannabis, coca, and opium-like effects. The Convention, which contains import and export restrictions and other rules aimed at limiting drug use to scientific and medical purposes, as of 2013,183 member states are Parties to the treaty. Many laws have passed to implement the Convention, including the U. S. Psychotropic Substances Act, the UK Misuse of Drugs Act 1971. Adolf Lande, under the direction of the United Nations Office of Legal Affairs, the Commentary, published in 1976, is an invaluable aid to interpreting the treaty and constitutes a key part of its legislative history. This treaty, signed in 1988, regulates precursor chemicals to drugs controlled by the Single Convention and it also strengthens provisions against money laundering and other drug-related crimes. International drug control began with the 1912 International Opium Convention, a treaty which adopted import and export restrictions on the opium poppys psychoactive derivatives, after the United Nations was formed in 1945, those enforcement functions passed to the UN. During the 1960s, drug use increased in Western developed nations, young people began using hallucinogenic, stimulant, and other drugs on a widespread scale that has continued to the present. In many jurisdictions, police had no laws under which to prosecute users and traffickers of these new drugs, LSD, the language of the Single Convention and its legislative history precluded any interpretation that would allow international regulation of these drugs under that treaty. A new convention, with a scope, would be required in order to bring those substances under control. Using the Single Convention as a template, the Commission prepared a draft convention which was forwarded to all UN member states, the Secretary-General of the United Nations scheduled a conference for early 1971 to finalize the treaty. Meanwhile, countries had already begun passing legislation to implement the draft treaty, in 1969, Canada added Part IV to its Food and Drugs Act, placing a set of restricted substances, including LSD, DMT, and MDA, under federal control. In 1970, the United States completely revamped its existing drug laws by enacting the Controlled Substances Act. In 1971, the United Kingdom passed the Misuse of Drugs Act 1971, a host of other nations followed suit. The conference convened on 11 January 1971, Nations split into two rival factions, based on their interests. According to a Senate of Canada report, One group included mostly developed nations with powerful pharmaceutical industries, the other group consisted of developing states. with few psychotropic manufacturing facilities. The organic drugmaking states that had suffered economically from the Single Conventions restrictions on cannabis, coca, the synthetic drug-producing states opposed those restrictions. The Conventions adoption marked a milestone in the development of the global drug control regime. As of June 2013, there are 183 state parties to the convention and this total includes 182 member states of the United Nations and the Holy See
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