International Standard Serial Number
An International Standard Serial Number is an eight-digit serial number used to uniquely identify a serial publication, such as a magazine. The ISSN is helpful in distinguishing between serials with the same title. ISSN are used in ordering, interlibrary loans, other practices in connection with serial literature; the ISSN system was first drafted as an International Organization for Standardization international standard in 1971 and published as ISO 3297 in 1975. ISO subcommittee TC 46/SC 9 is responsible for maintaining the standard; when a serial with the same content is published in more than one media type, a different ISSN is assigned to each media type. For example, many serials are published both in electronic media; the ISSN system refers to these types as electronic ISSN, respectively. Conversely, as defined in ISO 3297:2007, every serial in the ISSN system is assigned a linking ISSN the same as the ISSN assigned to the serial in its first published medium, which links together all ISSNs assigned to the serial in every medium.
The format of the ISSN is an eight digit code, divided by a hyphen into two four-digit numbers. As an integer number, it can be represented by the first seven digits; the last code digit, which may be 0-9 or an X, is a check digit. Formally, the general form of the ISSN code can be expressed as follows: NNNN-NNNC where N is in the set, a digit character, C is in; the ISSN of the journal Hearing Research, for example, is 0378-5955, where the final 5 is the check digit, C=5. To calculate the check digit, the following algorithm may be used: Calculate the sum of the first seven digits of the ISSN multiplied by its position in the number, counting from the right—that is, 8, 7, 6, 5, 4, 3, 2, respectively: 0 ⋅ 8 + 3 ⋅ 7 + 7 ⋅ 6 + 8 ⋅ 5 + 5 ⋅ 4 + 9 ⋅ 3 + 5 ⋅ 2 = 0 + 21 + 42 + 40 + 20 + 27 + 10 = 160 The modulus 11 of this sum is calculated. For calculations, an upper case X in the check digit position indicates a check digit of 10. To confirm the check digit, calculate the sum of all eight digits of the ISSN multiplied by its position in the number, counting from the right.
The modulus 11 of the sum must be 0. There is an online ISSN checker. ISSN codes are assigned by a network of ISSN National Centres located at national libraries and coordinated by the ISSN International Centre based in Paris; the International Centre is an intergovernmental organization created in 1974 through an agreement between UNESCO and the French government. The International Centre maintains a database of all ISSNs assigned worldwide, the ISDS Register otherwise known as the ISSN Register. At the end of 2016, the ISSN Register contained records for 1,943,572 items. ISSN and ISBN codes are similar in concept. An ISBN might be assigned for particular issues of a serial, in addition to the ISSN code for the serial as a whole. An ISSN, unlike the ISBN code, is an anonymous identifier associated with a serial title, containing no information as to the publisher or its location. For this reason a new ISSN is assigned to a serial each time it undergoes a major title change. Since the ISSN applies to an entire serial a new identifier, the Serial Item and Contribution Identifier, was built on top of it to allow references to specific volumes, articles, or other identifiable components.
Separate ISSNs are needed for serials in different media. Thus, the print and electronic media versions of a serial need separate ISSNs. A CD-ROM version and a web version of a serial require different ISSNs since two different media are involved. However, the same ISSN can be used for different file formats of the same online serial; this "media-oriented identification" of serials made sense in the 1970s. In the 1990s and onward, with personal computers, better screens, the Web, it makes sense to consider only content, independent of media; this "content-oriented identification" of serials was a repressed demand during a decade, but no ISSN update or initiative occurred. A natural extension for ISSN, the unique-identification of the articles in the serials, was the main demand application. An alternative serials' contents model arrived with the indecs Content Model and its application, the digital object identifier, as ISSN-independent initiative, consolidated in the 2000s. Only in 2007, ISSN-L was defined in the
A designer drug is a structural or functional analog of a controlled substance, designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. Designer drugs include psychoactive substances that have been designated by the European Union as new psychoactive substances as well as analogs of performance-enhancing drugs such as designer steroids; some of these were synthesized by academic or industrial researchers in an effort to discover more potent derivatives with fewer side effects and were co-opted for recreational use. Other designer drugs were prepared for the first time in clandestine laboratories; because the efficacy and safety of these substances have not been evaluated in animal and human trials, the use of some of these drugs may result in unexpected side effects. The development of designer drugs may be considered a subfield of drug design; the exploration of modifications to known active drugs—such as their structural analogues and derivatives—yields drugs that may differ in effects from their "parent" drug.
In some instances, designer drugs have similar effects to other known drugs, but have dissimilar chemical structures. Despite being a broad term, applicable to every synthetic drug, it is used to connote synthetic recreational drugs, sometimes those which have not been designed at all. In some jurisdictions, drugs that are similar in structure to a prohibited drug are illegal to trade regardless of that drug's legal status. In other jurisdictions, their trade is a legal grey area; some jurisdictions may have analogue laws which ban drugs similar in chemical structure to other prohibited drugs, while some designer drugs may be prohibited irrespective of the legal status of structurally similar drugs. Following the passage of the second International Opium Convention in 1925, which banned morphine, the diacetyl ester of morphine, a number of alternative esters of morphine started to be manufactured and sold; the most notable of these were dibenzoylmorphine and acetylpropionylmorphine, which have identical effects to heroin but were not covered by the Opium Convention.
This led the Health Committee of the League of Nations to pass several resolutions attempting to bring these new drugs under control leading in 1930 to the first broad analogues provisions extending legal control to all esters of morphine and hydromorphone. Another early example of what could loosely be termed designer drug use, was during the Prohibition era in the 1930s, when diethyl ether was sold and used as an alternative to illegal alcoholic beverages in a number of countries. During the 1960s and 1970s, a number of new synthetic hallucinogens were introduced, with a notable example being the sale of potent tablets of DOM in San Francisco in 1967. There was little scope to prosecute people over drug analogues at this time, with new compounds instead being added to the controlled drug schedules one by one as they became a problem, but one significant court case from this period was in 1973, when Tim Scully and Nicholas Sand were prosecuted for making the acetyl amide of LSD, known as ALD-52.
At this time ALD-52 was not a controlled drug, but they were convicted on the grounds that in order to make ALD-52, they would have had to be in possession of LSD, illegal. The late 1970s saw the introduction of various analogues of phencyclidine to the illicit market; the modern use of the term designer drug was coined in the 1980s to refer to various synthetic opioid drugs, based on the fentanyl molecule. The term gained widespread popularity; when the term was coined in the 1980s, a wide range of narcotics were being sold as heroin on the black market. Many were based on meperidine. One, MPPP, was found in some cases to contain an impurity called MPTP, which caused brain damage that could result in a syndrome identical to full-blown Parkinson's disease, from only a single dose. Other problems were potent fentanyl analogues, which were sold as China White, that caused many accidental overdoses; because the government was powerless to prosecute people for these drugs until after they had been marketed laws were passed to give the DEA power to emergency schedule chemicals for a year, with an optional 6-month extension, while gathering evidence to justify permanent scheduling, as well as the analogue laws mentioned previously.
Emergency-scheduling power was used for the first time for MDMA. In this case, the DEA scheduled MDMA as a Schedule I drug and retained this classification after review though their own judge ruled that MDMA should be classified Schedule III on the basis of its demonstrated uses in medicine; the emergency scheduling power has subsequently been used for a variety of other drugs including 2C-B, AMT, BZP. In 2004, a piperazine drug, TFMPP, became the first drug, emergency-scheduled to be denied permanent scheduling and revert to legal status; the late 1980s and early 1990s saw the re-emergence of methamphetamine in the United States as a widespread public health issue, leading to increasing controls on precursor chemicals in an attempt to cut down on domestic manufacture of the drug. This led to several alternative stimulant drugs emerging, the most notable ones being methcathinone and 4-m
Cannabidiol is a phytocannabinoid discovered in 1940. It is one of some 113 identified cannabinoids in cannabis plants, accounting for up to 40% of the plant's extract; as of 2018, preliminary clinical research on cannabidiol included studies of anxiety, movement disorders, pain. Cannabidiol can be taken into the body in multiple ways, including by inhalation of cannabis smoke or vapor, as an aerosol spray into the cheek, by mouth, it may be supplied as CBD oil containing only CBD as the active ingredient, a full-plant CBD-dominant hemp extract oil, dried cannabis, or as a prescription liquid solution. CBD does not have the same psychoactivity as THC, may affect the actions of THC. Although in vitro studies indicate CBD may interact with different biological targets, including cannabinoid receptors and other neurotransmitter receptors, as of 2018 the mechanism of action for its biological effects has not been determined. In the United States, the cannabidiol drug Epidiolex has been approved by the Food and Drug Administration for treatment of two epilepsy disorders.
The side effects of long-term use of the drug include somnolence, decreased appetite, fatigue, weakness, sleeping problems. The U. S. Drug Enforcement Administration has assigned Epidiolex a Schedule V classification, while non-Epidiolex CBD remains a Schedule I drug prohibited for any use. Cannabidiol is not scheduled under any United Nations drug control treaties, in 2018 the World Health Organization recommended that it remain unscheduled. There has been little high-quality research into the use of cannabidiol for epilepsy, what there is is limited to refractory epilepsy in children. While the results of using medical-grade cannabidiol in combination with conventional medication shows some promise, they did not lead to seizures being eliminated, were associated with some minor adverse effects. An orally administered cannabidiol solution was approved by the US Food and Drug Administration in June 2018 as a treatment for two rare forms of childhood epilepsy, Lennox-Gastaut syndrome and Dravet syndrome.
Preliminary research on other possible therapeutic uses for cannabidiol include several neurological disorders, but the findings have not been confirmed by sufficient high-quality clinical research to establish such uses in clinical practice. Preliminary research indicates that cannabidiol may reduce adverse effects of THC those causing intoxication and sedation, but only at high doses. Safety studies of cannabidiol showed it is well-tolerated, but may cause tiredness, diarrhea, or changes in appetite as common adverse effects. Epidiolex documentation lists sleepiness and poor quality sleep, decreased appetite and fatigue. Laboratory evidence indicated that cannabidiol may reduce THC clearance, increasing plasma concentrations which may raise THC availability to receptors and enhance its effect in a dose-dependent manner. In vitro, cannabidiol inhibited receptors affecting the activity of voltage-dependent sodium and potassium channels, which may affect neural activity. A small clinical trial reported that CBD inhibited the CYP2C-catalyzed hydroxylation of THC to 11-OH-THC.
Little is known about potential drug interactions but CBD-mediates decrease in clobazam metabolism. Cannabidiol has low affinity for the cannabinoid CB2 receptors. Cannabidiol may be an antagonist of GPR55, a G protein-coupled receptor and putative cannabinoid receptor, expressed in the caudate nucleus and putamen in the brain, it may act as an inverse agonist of GPR3, GPR6, GPR12. CBD has been shown to act as a serotonin 5-HT1A receptor partial agonist, this action may be involved in its antidepressant and neuroprotective effects, it is an allosteric modulator of the μ- and δ-opioid receptors as well. The pharmacological effects of CBD may involve PPARγ intracellular calcium release; the oral bioavailability of CBD is 13 to 19%, while its bioavailability via inhalation is 11 to 45%. The elimination half-life of CBD is 18–32 hours. Cannabidiol is metabolized in the liver as well as in the intestines by CYP2C19 and CYP3A4 enzymes, UGT1A7, UGT1A9, UGT2B7 isoforms. CBD may have a wide margin in dosing.
Nabiximols is a patented medicine containing THC in equal proportions. The drug was approved by Health Canada in 2005 for prescription to treat central neuropathic pain in multiple sclerosis, in 2007 for cancer related pain. In New Zealand, Sativex is "approved for use as an add-on treatment for symptom improvement in people with moderate to severe spasticity due to multiple sclerosis who have not responded adequately to other anti-spasticity medication." Cannabidiol is soluble in organic solvents such as pentane. At room temperature, it is a colorless crystalline solid. In basic media and the presence of air, it is oxidized to a quinone. Under acidic conditions it cyclizes to THC, which occurs during pyrolysis; the synthesis of cannabidiol has been accomplished by several research groups. Cannabis produces CBD-carboxylic acid through the same metabolic pathway as THC, until the next to last step, where CBDA synthase performs catalysis instead of THCA synthase. Cannabinoids were isolated from the cannabis plant in 1940 by Roger Adams, its chemical structure was established in 1963.
Cannabidiol is the generic name of the drug and its INN. Food and beverage products containing CBD were introduced in the United States in 2017. Similar to energy drinks and protein bars which may contain vitamin or herbal additives and beverage items can be infused with CBD as an alternative means of ingesting the substance. In the United S
Simplified molecular-input line-entry system
The simplified molecular-input line-entry system is a specification in the 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 been extended. In 2007, an open standard called. Other linear notations include the Wiswesser line notation, ROSDAL, SYBYL Line Notation; the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. Acknowledged for their parts in the early development were "Gilman Veith and Rose Russo and Albert Leo and Corwin Hansch for supporting the work, Arthur Weininger and Jeremy Scofield for assistance in programming the system." The Environmental Protection Agency funded the initial project to develop SMILES. It has since been modified and extended by others, most notably by Daylight Chemical Information Systems.
In 2007, an open 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 considered to have the advantage of being more human-readable than InChI; the term SMILES refers to a line notation for encoding molecular structures and specific instances should be called SMILES strings. However, the term SMILES is commonly used to refer to both a single SMILES string and a number of SMILES strings; the terms "canonical" and "isomeric" can lead to some confusion when applied to SMILES. The terms are not mutually exclusive. A number of 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; this SMILES is unique for each structure, although dependent on the canonicalization algorithm used to generate it, is termed the canonical SMILES.
These algorithms first convert the SMILES to an internal representation of the molecular structure. Various algorithms for generating canonical SMILES have been developed and include those by Daylight Chemical Information Systems, OpenEye Scientific Software, MEDIT, Chemical Computing Group, MolSoft LLC, the Chemistry Development Kit. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database; the original paper that described the CANGEN algorithm claimed to generate unique SMILES strings for graphs representing molecules, but the algorithm fails for a number of simple cases and cannot be considered a correct method for representing a graph canonically. There is 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, double bond geometry; these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES.
A notable feature of these rules is. The term isomeric SMILES is applied to SMILES in which isotopes are specified. In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph; the chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses are used to indicate points of branching on the tree; the resultant SMILES form depends on the choices: of the bonds chosen to break cycles, of the starting atom used for the depth-first traversal, of the order in which branches are listed when encountered. Atoms are represented by the standard abbreviation of the chemical elements, in square brackets, such as for gold. Brackets may be omitted in the common case of atoms which: are in the "organic subset" of B, C, N, O, P, S, F, Cl, Br, or I, have no formal charge, have the number of hydrogens attached implied by the SMILES valence model, are the normal isotopes, are not chiral centers.
All other elements must be enclosed in brackets, have charges and hydrogens shown explicitly. For instance, the SMILES for water may be written as either O or. Hydrogen may be written as a separate atom; when brackets are used, the symbol H is added if the atom in brackets is bonded to one or more hydrogen, followed by the number of hydrogen atoms if greater than 1 by the sign + for a positive charge or by - for a negative charge. For example, for ammonium. If there is more than one charge, it is written as digit.
Synthetic cannabinoids are a class of molecules that bind to cannabinoid receptors in the body. They are designer drugs that are sprayed onto plant matter and are smoked, although since 2016 they have been consumed in a concentrated liquid form in the US and UK, they have been marketed as herbal incense, or “herbal smoking blends” and sold under common names like K2, Synthetic Marijuana. They are labeled “not for human consumption” for liability defense; when the herbal blends went on sale in the early 2000s, it was thought that they achieved psychoactive effects from a mixture of natural herbs. Laboratory analysis in 2008 showed instead. Since 2016 synthetic cannabinoids are the most common new psychoactive substances. From 2008 to 2014, 142 synthetic cannabinoids were reported to the European Monitoring Centre for Drugs and Drug Addiction. A large and complex variety of synthetic cannabinoids are designed in an attempt to avoid legal restrictions on cannabis, making synthetic cannabinoids designer drugs.
Most synthetic cannabinoids are agonists of the cannabinoid receptors. They have been designed to be similar to THC, the natural cannabinoid with the strongest binding affinity to the CB1 receptor, linked to the psychoactive effects or "high" of marijuana; these synthetic analogs have greater binding affinity and greater potency to the CB1 receptors. There are several synthetic cannabinoid families classified based on the base structure. Reported user negative effects include palpitations, intense anxiety, vomiting, poor coordination, seizures. There have been reports of a strong compulsion to re-dose, withdrawal symptoms, persistent cravings. There have been several deaths linked to synthetic cannabinoids; the Centers for Disease Control and Prevention found that the number of deaths from synthetic cannabinoid use tripled between 2014 and 2015. In 2018 the United States Food and Drug Administration warned of significant health risks from synthetic cannabinoid products that contain the rat poison brodifacoum, added because it is thought to extend the duration of the drugs' effects.
Severe illnesses and death have resulted from this contamination. Many of the early synthetic cannabinoids that were synthesized for use in research were named after either the scientist who first synthesized them or the institution or company where they originated. For example, JWH compounds are named after John W. Huffman and AM compounds are named after Alexandros Makriyannis, the scientists who first synthesized those cannabinoids. HU compounds are named after Hebrew University in Jerusalem, the institution where they were first synthesized, CP compounds are named after Carl Pfizer, the company where they were first synthesized; some of the names of synthetic cannabinoids synthesized for recreational use were given names to help market the products. For example, AKB-48 is the name of a popular Japanese girl band. Now many synthetic cannabinoids are assigned names derived from their chemical names. For example, APICA comes from N--1-pentyl-1H-indole-3-carboxamide and APINACA comes from N--1-pentyl-1H-indazole-3-carboxamide.
Use of the term “synthetic marijuana” to describe products containing synthetic cannabinoids is controversial and, according to Dr. Lewis Nelson, a medical toxicologist at the NYU School of Medicine, a misnomer. Nelson claims that relative to marijuana, products containing synthetic cannabinoids “are quite different, the effects are much more unpredictable. It’s dangerous.” Since the term synthetic does not apply to the plant, but rather to the cannabinoid that the plant contains, the term synthetic cannabinoid is more appropriate. Synthetic cannabinoids are known by a number of brand names including K2, Black Mamba, Bombay Blue, Zohai, Banana Cream Nuke, Lava Red, many more. In some Spanish-speaking countries, such as Chile and Argentina, such preparations are referred to as "cripy", they are called “synthetic marijuana”, “natural herbs”, “herbal incense”, or “herbal smoking blends” and labeled “not for human consumption”. They are offered in e-cigarette form as "c-liquid" with brand names such as Kronic.
According to the Psychonaut Web Mapping Research Project, synthetic cannabinoids, sold under the brand name “Spice”, were first released in 2005 by the now-dormant company The Psyche Deli in London, UK. In 2006, the brand gained popularity. According to the Financial Times, the assets of The Psyche Deli rose from £65,000 in 2006 to £899,000 in 2007; the EMCDDA reported in 2009 that Spice products were identified in 21 of the 30 participating countries. Synthetic cannabinoids were made for cannabinoid research focusing on tetrahydrocannabinol, the main psychoactive and analgesic compound found in the cannabis plant. Synthetic cannabinoids were needed due to legal restrictions on natural cannabinoids, which make them difficult to obtain for research. Tritium-labelled cannabinoids such as CP-55,940 were instrumental in discovering the cannabinoid receptors in the early 1990s; some early synthetic cannabinoids were used clinically. Nabilone, a first generation synthetic THC analog, has been used as an antiemetic to combat vomiting and nausea, since 1981.
Synthetic THC has been used as an antiemetic since 1985 and an appetite stimulant since 1991. In the early 2000s, s
Cannabinol is a non-psychoactive cannabinoid found only in trace amounts in Cannabis, is found in aged Cannabis. Pharmacologically relevant quantities are formed as a metabolite of tetrahydrocannabinol. CBN has a higher affinity to CB2 receptors. Degraded or oxidized cannabis products, such as low-quality baled cannabis and traditionally produced hashish, are high in CBN. Unlike other cannabinoids, CBN does not stem directly from cannabigerol or cannabigerolic acid, but rather is the degraded product of tetrahydrocannabinolic acid. If cannabis is exposed to air or ultraviolet light for a prolonged period of time, THCA will convert to cannabinolic acid. CBN is formed by decarboxylation of CBNA. In contrast to THC, CBN stereoisomers. Both THC and CBN activate the CB2 receptors. Chemically, CBN is related to cannabidiol. CBN is not listed in the schedules set out by the United Nations' Single Convention on Narcotic Drugs from 1961 nor their Convention on Psychotropic Substances from 1971, so the signatory countries to these international drug control treaties are not required by these treaties to control CBN.
In Canada, CBN is a Schedule II controlled substance as defined by the Controlled Drugs and Substances Act. In the United States and state laws regarding the legality of cannabis products are confusing and at times contradictory. CBN is not listed in the list of scheduled controlled substances in the USA. However, it is possible that CBN could be considered an analog of THC or CBD, both of which are Schedule I substances, therefore sales or possession could be prosecuted under the Federal Analogue Act, it is possible that CBN may not meet the legal standard of an analogue for the purposes of bringing forth a prosecution under the Federal Analogue Act. In December 2016, the Drug Enforcement Administration added marijuana extracts, which are defined as any "extract containing one or more cannabinoids, derived from any plant of the genus Cannabis, other than the separated resin", to Schedule I; this action has led to additional uncertainty about the legal status. Erowid Compounds found in Cannabis sativa