1.
Echinacea
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Echinacea /ˌɛkᵻˈneɪʃiə/ is a genus, or group of herbaceous flowering plants in the daisy family. The Echinacea genus has nine species, which are commonly called purple coneflowers and they are found only in eastern and central North America, where they are found growing in moist to dry prairies and open wooded areas. They have large, showy heads of flowers, blooming from early to late summer. The generic name is derived from the Greek word ἐχῖνος, meaning hedgehog and these flowering plants and their parts have different uses. Some species are cultivated in gardens for their showy flowers, Echinacea purpurea is used in folk medicine. Two of the species, E. tennesseensis and E. laevigata, are listed in the United States as endangered species, the DNA analysis allows researchers to reveal clear distinctions among species based on chemical differences in root metabolites. The research concluded that of the 40 genetically diverse populations of Echinacea studied, Echinacea species are herbaceous, drought-tolerant perennial plants growing up to 140 cm or 4 feet, in height. They grow from taproots, except E. purpurea, which grows from a caudex with fibrous roots. They have erect stems that in most species are unbranched, both the basal and cauline leaves are arranged alternately. The leaves are hairy with a rough texture, having uniseriate trichomes but sometimes they lack hairs. The basal leaves and the stem leaves have petioles. The leaf blades in different species may have one, three or five nerves, some species have linear to lanceolate leaves, and others have elliptic- to ovate-shaped leaves, often the leaves decrease in size as they progress up the stems. Leaf bases gradually increase in width away from the petioles or the bases are rounded to heart shaped, most species have leaf margins that are entire, but sometimes they are dentate or serrate. The flowers are collected together into single rounded heads at the ends of long peduncles, the inflorescences have crateriform to hemispheric shaped involucres which are 12–40 mm wide. The phyllaries, or bracts below the head, are persistent. The phyllaries are produced in a 2–4 series, the receptacles are hemispheric to conic. The paleae have orange to reddish purple ends, and are longer than the disc corollas, the paleae bases partially surrounding the cypselae, and are keeled with the apices abruptly constricted to awn-like tips. The ray florets number 8–21 and the corollas are purple to pale pink, white
2.
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
3.
Cannabinoid
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A cannabinoid is one of a class of diverse chemical compounds that acts on cannabinoid receptors in cells that alter neurotransmitter release in the brain. Ligands for these proteins include the endocannabinoids, the phytocannabinoids. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol, the psychoactive compound in cannabis. Cannabidiol is another constituent of the plant. There are at least 113 different cannabinoids isolated from cannabis, exhibiting varied effects, the discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate. These receptors are common in animals, and have found in mammals, birds, fish. At present, there are two types of cannabinoid receptors, termed CB1 and CB2, with mounting evidence of more. The human brain has more cannabinoid receptors than any other G protein-coupled receptor type, CB1 receptors are found primarily in the brain, more specifically in the basal ganglia and in the limbic system, including the hippocampus. They are also found in the cerebellum and in male and female reproductive systems. CB1 receptors are absent in the medulla oblongata, the part of the brain responsible for respiratory. CB1 is also found in the anterior eye and retina. CB2 receptors are found in the immune system, or immune-derived cells with the greatest density in the spleen. While found only in the nervous system, a report does indicate that CB2 is expressed by a subpopulation of microglia in the human cerebellum. CB2 receptors appear to be responsible for the anti-inflammatory and possibly other therapeutic effects of cannabis seen in animal models, the classical cannabinoids are concentrated in a viscous resin produced in structures known as glandular trichomes. At least 113 different cannabinoids have been isolated from the Cannabis plant To the right, the best studied cannabinoids include tetrahydrocannabinol, cannabidiol and cannabinol. All classes derive from cannabigerol-type compounds and differ mainly in the way this precursor is cyclized, the classical cannabinoids are derived from their respective 2-carboxylic acids by decarboxylation. CBG CBC CBL CBV THCV CBDV CBCV CBGV CBGM THC THCA CBD CBDA Tetrahydrocannabinol is the psychoactive component of the Cannabis plant. Delta-9-tetrahydrocannabinol and delta-8-tetrahydrocannabinol, mimic the actions of anandamide and 2-arachidonoylglycerol neurotransmitters produced naturally in the body and these cannabinoids produce the effects associated with cannabis by binding to the CB1 cannabinoid receptors in the brain
4.
Tetrahydrocannabinol
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Tetrahydrocannabinol, or more precisely its main isomer -trans-Δ⁹-tetrahydrocannabinol, is the principal psychoactive constituent of cannabis. It can be a clear, amber or gold colored glassy solid when cold, like most pharmacologically-active secondary metabolites of plants, THC in Cannabis is assumed to be involved in self-defense, perhaps against herbivores. THC also possesses high UV-B absorption properties, which, it has been speculated, THC, along with its double bond isomers and their stereoisomers, is one of only three cannabinoids scheduled by the UN Convention on Psychotropic Substances. It was listed under Schedule I in 1971, but reclassified to Schedule II in 1991 following a recommendation from the WHO, based on subsequent studies, the WHO has recommended the reclassification to the less-stringent Schedule III. Cannabis as a plant is scheduled by the Single Convention on Narcotic Drugs and it is specifically still listed under Schedule I by US federal law under the Controlled Substances Act signed by the US Congress in 1970. A pharmaceutical formulation is available by prescription in the U. S. dronabinol is the INN for a pure isomer of THC, -trans-Δ⁹-tetrahydrocannabinol, which is the main isomer found in cannabis. It is used to treat anorexia in people with HIV/AIDS as well as for refractory nausea and it is safe and effective for these uses. An overdose of dronabinol usually presents with lethargy, decreased motor coordination, slurred speech, there was a single death rated by the investigator as possibly related to treatment. This person had a seizure followed by aspiration pneumonia, the paper does not describe whether this was one of the subjects from the epilepsy trials. The presence of these specialized cannabinoid receptors in the brain led researchers to the discovery of endocannabinoids, such as anandamide, THC targets receptors in a manner far less selective than endocannabinoid molecules released during retrograde signaling, as the drug has a relatively low cannabinoid receptor efficacy and affinity. In populations of low cannabinoid receptor density, THC may act to antagonize endogenous agonists that possess greater receptor efficacy, THC is a lipophilic molecule and may bind non-specifically to a variety of entities in the brain and body, such as adipose tissue. THC, similarly to cannabidiol, albeit less potently, is an allosteric modulator of the μ-. Due to its agonistic activity, THC appears to result in greater downregulation of cannabinoid receptors than endocannabinoids. However, this form of tolerance appears to be irregular throughout mouse brain areas, THC is metabolized mainly to 11-OH-THC by the body. This metabolite is still psychoactive and is oxidized to 11-nor-9-carboxy-THC. In humans and animals, more than 100 metabolites could be identified, metabolism occurs mainly in the liver by cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP3A4. More than 55% of THC is excreted in the feces and ~20% in the urine, the main metabolite in urine is the ester of glucuronic acid and THC-COOH and free THC-COOH. In the feces, mainly 11-OH-THC was detected, the discovery of THC, by a team of researchers from Hebrew University Pharmacy School, was first reported in 1964, with substantial later work reported by Raphael Mechoulam in June 1970
5.
Cannabidiol
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Cannabidiol is one of at least 113 active cannabinoids identified in cannabis. It is a major phytocannabinoid, accounting for up to 40% of the plants extract, Dravet syndrome is a rare form of epilepsy that is difficult to treat. It is a form of intractable epilepsy that begins in infancy. Initial seizures are most often prolonged events and in the year of life other seizure types begin to emerge. A number of profile and anecdotal reports have sparked interest in treatment of Dravet syndrome with cannabidiol. Some cannabis/hemp extract preparations containing CBD are marketed as dietary supplements, one such preparation is marketed under the tradename Charlottes Web Hemp Extract. GW Pharmaceuticals is seeking FDA approval to market a liquid formulation of pure plant-derived CBD, Epidiolex was granted fast-track status and is in late stage trials following positive early results from the drug. A2014 review stated that cannabidiol has been claimed, anecdotally, information in the review stated that there is no established mechanism of action and the lack of high-quality evidence in this area precluded conclusions being drawn. A2016 review states that because of the quality of available data. There is tentative evidence that CBD had an effect. Cannabidiol may also extend the duration of the effects of THC via inhibition of the cytochrome P450 CYP3A, cannabidiol has been found to act as an antagonist of the GPR55, a G protein-coupled receptor and putative cannabinoid receptor that is expressed in the caudate nucleus and putamen. It has also shown to act as a 5-HT1A receptor partial agonist, and this action may be involved in the antidepressant, anxiolytic. It is a modulator of the μ and δ-opioid receptors as well. Cannabidiols pharmacological effects have additionally been attributed to PPARγ agonism and intracellular calcium release and it has also been speculated that some of the metabolites of CBD have pharmacological effects that contribute to the biological activity of CBD. Despite this, the evidence in humans suggests no significant effect of CBD on THC plasma levels. Nabiximols is an aerosolized mist for oral administration containing a near 1,1 ratio of CBD, the drug was approved by Canadian authorities in 2005 to alleviate pain associated with multiple sclerosis. Epidiolex, a drug with cannabidiol as its active pharmaceutical ingredient, Epidiolex is an oil formulation of CBD extracted from the cannabis plant undergoing clinical trials for refractory epilepsy syndromes. Cannabidiol is insoluble in water but soluble in solvents such as pentane
6.
Synthetic cannabinoids
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Synthetic cannabinoids are a class of chemicals that are different from the cannabinoids found in cannabis but which also bind to cannabinoid receptors. They are often marketed as designer drugs or sold in products with claims that they give the effects of cannabis, when these chemicals are sprayed or otherwise soaked into a plant or other base material the blend is sometimes misleadingly referred to as synthetic marijuana. These synthetic marijuana products are sold for recreational drug use, when synthetic cannabinoid blends first went on sale in the early 2000s, it was thought that they achieved an effect through a mixture of natural herbs. They have been sold under brand names, online, in head shops. Studies have associated synthetic cannabinoid use with psychotic episodes days after use and these blends are often marketed as herbal incense or herbal smoking blends, and the products are usually consumed through smoking. Although synthetic cannabinoids may not produce results in drug tests for cannabis. The synthetic cannabinoids contained in these products have made illegal in many countries. Synthetic cannabinoids are used for drug use, however many were designed for research purposes. Studies are ongoing to examine their therapeutic potential, the drug is used in an attempt to get the effects of cannabis or similar effects. Part of the appeal of the drug is that it is marketed as being like natural cannabis, in comparison with cannabis, it is inexpensive and can be easy to get as a commercial product through convenience stores, tobacco shops, or head shops. A standard drug test will not identify a user of synthetic cannabinoids whereas that would happen with natural cannabis, Synthetic cannabinoids have been legal in the past, or at least, not illegal to sell or possess. There are many different chemicals which are called synthetic cannabinoids and many of them are regulated by different laws or not mentioned in laws, Synthetic cannabinoids frequently produce adverse effects which lead to hospitalization or referrals to poison control centers. Synthetic cannabinoids can be any of a number of different drugs, there is no way to describe general effects among all the different chemicals because they all have different effects. Many compounds have been banned in the U. S. and numerous countries, although loopholes remain. No official studies have been conducted on the effects of cannabinoids on humans. However, reports describing effects seen in patients seeking medical care after taking synthetic cannabinoids have been published, other symptoms included epileptic seizures, and acute psychosis. At least one death has been linked to overdose of synthetic cannabinoids and this may further explain the increased toxicity of synthetic cannabinoids compared to THC. Professor John W. Huffman, who first synthesised many of the used in synthetic cannabis mimics, is quoted as saying
7.
Cannabigerol
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Cannabigerol is a non-intoxicating cannabinoid found in the Cannabis genus of plants. CBG is the form of cannabigerolic acid, the parent molecule from which many other cannabinoids are made. CBG has been found to act as a high affinity α2-adrenergic receptor agonist, moderate affinity 5-HT1A receptor antagonist and it also binds to the CB2 receptor as an antagonist. CBG does not trigger THC-like activity in mice, rats, gerbils and non-human primates, moreover, CBG was without effect up to 80 mg/kg in the mouse tetrad test of cannabimimetic activity. It has been shown to improve a model of inflammatory disease, ulcerative colitis. CBG induces production of the natural skin moisturizers, holding promise for dry-skin syndromes. Cannabigerol has been shown to relieve pressure, which may be of benefit in the treatment of glaucoma. CBG has been shown to have properties and may prove promising for the treatment of neurodegenerative diseases such as Huntington’s disease. CBG is known to have properties and research suggests that it might be effective against the superbug MRSA. CBG is showing promising properties in vitro for the treatment of a broad range of cancers including breast, liver, lung, pancreatic, skin, ovarian, renal, bladder. CBG is not scheduled by Convention on Psychotropic Substances, CBG is not scheduled at the federal level in the United States. The biosynthesis of CBG begins by loading a hexanoyl CoA onto a ketide synthetase assembly protein and subsequent condensation with three malonyl CoA molecules
8.
Cannabinol
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Cannabinol is a psychoactive cannabinoid found only in trace amounts in Cannabis sativa and Cannabis indica. Pharmacologically relevant quantities are formed as a metabolite of tetrahydrocannabinol, CBN acts as a partial agonist at the CB1 receptors, but has a higher affinity to CB2 receptors, however, with lower affinities in comparison to THC. Degraded or oxidized cannabis products, such as low-quality baled cannabis and traditionally produced hashish, are high in CBN, cannabinol has been shown to have analgesic properties. Unlike other cannabinoids, CBN does not stem from cannabigerol but rather is the product of THC. If cannabis is exposed to air or ultraviolet light for a period of time. CBN is then formed by decarboxylation of CBNA, in contrast to THC, CBN has no double bond isomers nor stereoisomers. Both THC and CBN activate the CB1 and CB2 receptors, CBN is not listed in the list of scheduled controlled substances in the USA. It is also possible that CBN may not meet the standard of an analogue for the purposes of bringing forth a prosecution under the Federal Analogue Act. Erowid Compounds found in Cannabis sativa
9.
11-Hydroxy-THC
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11-Hydroxy-Δ9-tetrahydrocannabinol is the main active metabolite of Tetrahydrocannabinol which is formed in the body after cannabis is consumed. The conversion from THC to 11-OH-THC is relatively high when cannabis is consumed in the form of cannabis edibles and, compared to oral consumption, 11-OH-THC is more potent than THC and crosses the blood–brain barrier more easily. 11-Hydroxy-THC has been shown to be active in its own right and this might partially explain the biphasic effects of cannabis, whereby some effects such as increased appetite tend to be delayed rather than occurring immediately when the drug is consumed. Fresh cannabis contains Tetrahydrocannabinolic acid, which is converted into THC after heating, 11-Hydroxy-THC is subsequently metabolised further to 11-nor-9-carboxy-THC, which is not psychoactive but might still play a role in the analgesic and anti-inflammatory effects of cannabis
10.
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
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.
RCS-4
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RCS-4, or 1-pentyl-3-indole, is a synthetic cannabinoid drug sold under the names SR-19, BTM-4, or Eric-4, but originally, OBT-199. RCS-4 is a potent cannabinoid receptor agonist, with EC50 values of 146 nM for human CB1 receptors, all methoxyphenyl regioisomers, and N-butyl homologues of RCS-4 and its regioisomers also display potent agonist activities at CB1 and CB2 receptors. RCS-4 was banned in Sweden on 1 October 2010 as a hazardous good harmful to health and it was outlawed in Denmark on 11 March 2011. As of October 2015 RCS-4 is a substance in China. AM-630 AM-679 RCS-8 Pravadoline Structural scheduling of synthetic cannabinoids
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