Kratom

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Kratom
Mitragyna
speciosa



Scientific
classification

Kingdom:
Plantae

Division:
Magnoliophyta

Order:
Gentianales

Family:
Rubiaceae

Genus:
Mitragyna

Species:
M.
speciosa

Binomial
name

Mitragyna speciosa
Korth.
Kratom (Thai: กระท่อม), Mitragyna speciosa, is
a medicinal leaf harvested from a large tree in the Rubiaceae family native to Southeast Asia in the Indochina and Malesia floristic regions.[clarification needed] The
plant has been traditionally used for its medicinal properties.[clarification needed] It was
first formally documented by the Dutch colonial botanist Pieter Korthals. The genus was given its
Mitragyna name by Korthals because the stigmas in the first species he
examined resembled the shape of a bishop's mitre. It is botanically related to
the Corynanthe, Cinchona and Uncaria genera and shares some similar biochemistry.







Contents [hide]

• 1 Description
  
  
  
  • 1.1 Alkaloids


• 2 Effects
  
  
  
  • 2.1 Opiate
    dependence


• 3 Legal status
  
  
  
  • 3.1 Thailand
  
  
  • 3.2 United States
  
  
  • 3.3 Canada


• 4 See also


• 5 References
  
  
  
  • 5.1 Citations


• 6 Further
  reading

[edit] Description
Mitragyna speciosa, kratom trees, usually grow to a height of 12–30 ft
(3.7–9.1 m) tall and 15 ft (4.6 m) wide, although under the right conditions,
certain species can reach up to 40 ft (12 m)–100 ft (30 m) in height. The stem
is erect and branching. The leaves of the kratom tree are a dark green colour
and can grow to over 7 inches (180 mm) long and 4 inches (100 mm) wide.,
ovate-acuminate in shape, and opposite in growth pattern.


The flowers are yellow and grow in clusters. This genus is characterized by a
globular flowering head, bearing up to 120 florets each. During the flower bud
stage, the developing florets are surrounded and completely covered by numerous
overlapping bracteoles.[citation needed]


Kratom leaves are constantly being shed and being replaced, but there is some
quasi-seasonal leaf shedding due to environmental conditions. During the dry
season of the year leaf fall is more abundant, and new growth is more plentiful
during the rainy season.


When grown outside their natural tropical habitat, leaf fall occurs with
colder temperatures, around 4 degrees Celsius.[citation needed] The kratom
tree grows best in wet, humid, fertile soil, with medium to full sun exposure,
and an area protected from strong winds.


[edit] Alkaloids
Kratom contains many alkaloids including mitragynine (once thought to be the primary active
constituent), mitraphylline, and 7-hydroxymitragynine (which is currently the most
likely candidate for the primary active chemical in the plant).[1] Although
7-hydroxymitragynine and mitragynine are structurally related to yohimbine and other tryptamines, their pharmacology is quite different,
acting primarily as mu-opioid receptor agonists. Other active chemicals in
kratom include raubasine (best known from Rauwolfia serpentina) and some yohimbe
alkaloids such as corynantheidine.[2]


Also, as stated by and according to references on erowid.org, there are
several countries in which the cultivation and usage of this herb (flora) are
forbidden, some with very harsh sentencing recommendations. The native countries
(in the Eastern part of the world i.e. Thailand, etc.) have enacted laws
forbidding the plants' usage for any "medical" reason. There is limited research
on this plant because of the restrictions, and as of the past 10 (ten) years,
this plants' popularity as a "recreational" drug have become widely noticed.
References to this fact are countless; it can be bought as both whole leaf, or
"isolate" which has the active alkaloids in it. The claims that this drug can be
used as a "substitution" for opiate dependence are rare and the studies that do
exist are sparse; therefore, it is up to the reader to take note to the laws of
the country they reside in as to weather or not this plant bears ANY medical
use. There are varied reports that cannot be cited properly due to poor testing
conditions regarding the plant's supposed medical benefits. However, individual
experiences with this herb (flora) have shown results ranging from that of a
placebo effect to noticeable effects dealing with opiate withdraw. More studies
are needed before accurate citation is possible.


[edit] Effects



Kratom capsules



Dried kratom leaf
Kratom's primary pharmacology is mediated by the alkaloids 7-hydroxymitragynine and mitragynine. While these molecules share structural
similarities to the psychedelics, there is no psychedelic activity or
similarities in effects to such substances. Instead these alkaloids primarily
interact with the opioid receptors. Accordingly, kratom is known to prevent or
delay withdrawal symptoms in an opiate dependent individual, and it is often
used for this purpose. It can also be used for other medicinal purposes and is
sometimes used recreationally.


Kratom has been traditionally used in regions such as Malaysia, Thailand, and
Indonesia, but was discovered by Western civilization during the 19th century.
Besides kratom (or krathom), in Southeast Asia and the Pacific Islands it also
goes by the names ithang, biak biak, ketum, kakuam, and in southern regions,
thom. In these areas kratom has a history of use by laborers and in folk
medicine for opium dependence and diarrhea.


Of the two main active constituents, mitragynine has been studied more
thoroughly than 7-hydroxymitragynine. At lower doses, Mitragynine exhibits a
yohimbine-like binding to alpha-adrenergic receptors, as well as some binding to
the delta opioid receptors. As doses increase, binding to delta receptors
increases, and in yet higher doses, crossover to mu receptors occurs.


7-hydroxymitragynine was only recently understood to be the main active
ingredient. Limited animal research suggests it is a potent opiate agonist, but
with a ceiling effect that limits the potential for respiratory depression and
euphoria. No fatal overdose of kratom is known to have occurred.


While one study of Thai users reported that kratom has sedative effects in
low doses, changing over to stimulation in higher doses, this seems to be
incorrect. Most other sources say that it is a stimulant in lower doses,
becoming sedative in higher doses, which is consistent with mitragynine's
receptor binding profile. However, recent publications indicate that different
alkaloids may be at work to achieve stimulation versus sedation: whereas higher
concentrations of mitragynine are attributed to act as a stimulant,
7-hydroxymitragynine is the most significant alkaloid for sedation with more
potent analgesic activity than that of morphine.[1] Effects
come on within five to ten minutes after use, and last for several hours. The
feeling has been described as happy, strong, and active, with a strong desire to
do work. The mind is described as calm.


Side effects, although rare, may include dry mouth, increased or decreased
urination, loss of appetite, and nausea or vomiting. Heavy use can result in a
prolonged sleep. Possible side effects from long term use include anorexia and
weight loss, insomnia, and dependence. Comprehensive scientific and clinical
studies have yet to be conducted to establish the potential health risks
associated with consistent long term consumption of kratom.





Young kratom tree
Kratom has recently become more known and used in Europe and North America where it has been prized for its
applications to many conditions and ailments, primarily pain, depression,
anxiety, and opiate withdrawal.





Kratom leaf
[edit] Opiate
dependence





This section does not cite any references
or sources. Please help improve this section by adding citations to reliable
sources. Unsourced material may be challenged
and removed.
(April 2011)
Inspired by traditional use, H. Ridley reported In 1897 that the leaves of
Mitragyna speciosa were a cure for opium dependence. In more recent times,
mitragynine has been used in New Zealand for methadone dependence detox. Kratom
was smoked whenever the patient experienced withdrawal symptoms, over a 6 week
treatment period. Patients reported a visualization effect taking place at night
in the form of vivid hypnagogic dreams. While working on plans for ibogaine
experiments in the USA, Cures Not Wars activist Dana Beal suggested that
mitragynine could be used as an active placebo for comparison in the study.
Acting Deputy Director of the NIDA Charles Grudzinskas rejected the proposal,
however, saying that even less was known about mitragynine than ibogaine.


Although chemically similar, ibogaine and mitragynine work by different
pathways, and have different applications in treatment of drug dependence. While
ibogaine is intended as a one time treatment to cure opiate dependence,
mitragynine is used to gradually wean the user off opiates. The fact that
mitragynine's mu crossover is increased by the presence of opiate drugs may be
exploitable in the treatment of drug dependence, because it directs binding to
where it is needed, automatically regulating the attachment ratio and modulating
it towards the delta receptors over a short time. Within a few days, a person
dependent on opiates would stop use of opiates, and the cravings and withdrawal
will be moderated by the binding of mitragynine to the delta receptors.
Mitragynine could also perhaps be used as a substitution or maintenance drug to
manage dependence. In Southern Thailand, many heroin users have been using
kratom to break their dependence and to manage painful withdrawal symptoms.


In 1999, Pennapa Sapcharoen, director of the National Institute of Thai
Traditional Medicine in Bangkok said that kratom could be prescribed both for
opiate dependence and to patients suffering from depression, but stressed that
further research is needed. Chulalongkorn University chemists have isolated
mitragynine which researchers can obtain for study.


In 1897 Ridley reported the leaves and bark of Mitragyna speciosa as a cure
for the opium habit and this was quoted by Hooper (1907) In 1907 Holmes had
referred to the leaves and possibly, the leaves of M. parvifolia as well, as an
opium substitute. Certainly the leaves of M. speciosa have been chewed for many
years under the local name 'kratom' by the native population of Thailand as a
stimulant though the practice is now forbidden. As a consequence the leaves of
M. javanica are frequently used as a substitute but are not considered to be as
effective. The natives will also distinguish between different kratoms, for
example, those with red and those with green midribs (Tantivatana, 1965).


Mitragynine was the only constituent isolated from Mitragyna speciosa it was
assumed to be the physiologically active constituent having morphine-like
properties, Grewel (1932) reported to be a protozoal poison but in 1933
Raymond-Hamet and Millat undertook a more critical examination and reported it
to have markedly depressant properties. This was substantiated in 1934 by
Masson. More recently Macko, Weisbach and Douglas (1972) reported that
mitragynine possesses pain threshold elevating and antitussive properties but no
addictive properties.[citation needed]


Recent drug use trends in Thailand indicate that a emerging pattern and
profile is emerging in relation to kratom use. Around 2005, young people aged
between 13 to 30 years old started boiling kratom leaves (15 to 100 leaves at a
time) to produce a tea as a base for a cocktail coined 4x100 (สี่คูณร้อย). The
basic 4x100 cocktail includes the kratom tea, cough syrup, Coca-Cola, and ice.
The cocktail is generally prepared twice or more per day, depending on
availability of leaves and is consumed for recreational purposes.[citation needed]


Although kratom has been shown to help people suffering from opiate addiction
and withdrawal symptoms, kratom itself is believed to be similarly addictive if
abused. Daily kratom users can develop a dependency similar to that of opiate
addiction; however, withdrawals from kratom are said to be substantially less
severe and shorter in duration. If used responsibly and on a non-daily basis the
chances of developing a kratom dependency are shown to be remote.


[edit] Legal
status
Kratom is a controlled substance in Thailand, Bhutan, Australia, Finland,
Denmark, Poland, Lithuania and Sweden as of September, 1, 2011. [3] Malaysia
and Myanmar (Burma). In Malaysia, kratom is scheduled under the Poisons Act.


[edit] Thailand
The Thai government passed the Kratom Act 2486 which went into effect on
August 3, 1943. This law makes planting the tree illegal and requires existing
trees to be cut down. This law was not found effective, since the tree is
indigenous to the country. Today, kratom is scheduled in category 5 of the
Narcotics Acts (1979), in the same category as cannabis and magic mushrooms (the
least punitive category). A related species, Mitragyna javanica, is often used
as a substitute to get around the law, but it is not considered as effective.
The dominant alkaloid in this species is mitrajavine, which has not yet been
pharmacologically tested.[citation needed]


[edit] United
States
Kratom is currently an unscheduled substance.[4]


[edit] Canada
Although kratom has not been approved by Health Canada for human consumption,
it currently does not fall under the purview of the Controlled Drugs and
Substances Act [5] thus,
remaining largely unregulated.

Methoxetamine (MXE) or 3-MeO-2-Oxo-PCE is a chemical of the arylcyclohexylamine class. It is an analogue of ketamine that also contains structural features of eticyclidine and 3-MeO-PCP. Like ketamine, it is thought to behave as a NMDA receptor antagonist and dopamine reuptake inhibitor, though it has not been formally profiled pharmacologically. Methoxetamine differs from many other dissociative anesthetics of the arylcyclohexylamine class in that it was designed for grey-market distribution.[1] Methoxetamine is a product of rational drug design: its N-ethyl group was chosen to increase potency, lessening the risk of interstitial cystitis that can result from the accumulation of ketamine-like metabolites in the urinary bladder.[1]

[edit] See also

• Dissociatives
• Ketamine
• Phencyclidine
• Methoxydine

[edit] References

1. ^ a b [1], Morris, H. (11 February 2011). "Interview with a ketamine chemist: or to be more precise, an arylcyclohexylamine chemist". Vice Magazine. Retrieved 2011-02-11.

[edit] External links Erowid.org – Methoxetamine Information

Welcome to the Natural High Drug Information site on Drugs and there Effects
Our aim is to provide a wealth of knowledge on Chemical Research Drugs,Herbal Highs,so called Plant Food and all other forms or Drug Abuse including Perscribtion Drugs. This sites aim is to have open discussions on the health issues the addiction and the good effects of drugs we also have a forum for everyone to contribute.
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5-IAI From Wikipedia, the free encyclopedia Jump to: navigation, search 5-IAI Systematic (IUPAC) name 5-iodo-2,3-dihydro-1H-inden-2-amine Identifiers CAS number 132367-76-1 ATC code None PubChem CID 131506 ChemSpider 116224 Y Chemical data Formula C9H10IN  Mol. mass 259.087 g/mol SMILES eMolecules & PubChem InChI[show]

• InChI=1S/C9H10IN/c10-8-2-1-6-4-9(11)5-7(6)3-8/h1-3,9H,4-5,11H2 Y
  Key: BIHPYCDDPGNWQO-UHFFFAOYSA-N Y

Therapeutic considerations Pregnancy cat.  ? Legal status Uncontrolled Routes Oral, Insufflated, Rectal  Y(what is this?)  (verify)
5-Iodo-2-aminoindane (5-IAI) is a drug which acts as a releasing agent of serotonin, norepinephrine, and dopamine.[1] It was developed in the 1990s by a team led by David E. Nichols at Purdue University.[2] 5-IAI fully substitutes for MDMA in rodents and is a putative entactogen in humans.[2] Unlike related aminoindane derivatives like MDAI and MMAI, 5-IAI causes some serotonergic neurotoxicity in rats, but is substantially less toxic than the its corresponding amphetamine homologue pIA, with the damage observed barely reaching statistical significance.[1]

[edit] See also

• 2-Aminoindane (2-AI)
• para-Iodoamphetamine (pIA)
• 6-Chloro-2-aminotetralin (6-CAT)

[edit] References

1. ^ a b Johnson MP, Conarty PF, Nichols DE (July 1991). "[3H]monoamine releasing and uptake inhibition properties of 3,4-methylenedioxymethamphetamine and p-chloroamphetamine analogues". European Journal of Pharmacology 200 (1): 9–16. PMID 1685125. 
2. ^ a b Nichols DE, Johnson MP, Oberlender R (January 1991). "5-Iodo-2-aminoindan, a nonneurotoxic analogue of p-iodoamphetamine". Pharmacology, Biochemistry, and Behavior 38 (1): 135–9. PMID 1826785. http://linkinghub.elsevier.com/retrieve/pii/0091-3057(91)90601-W.

NRG2 From Wikipedia, the free encyclopedia Jump to: navigation, search edit Neuregulin 2 Identifiers Symbols NRG2; Don-1; HRG2; NTAK External IDs OMIM: 603818 HomoloGene: 75024 GeneCards: NRG2 Gene [show]Gene Ontology Molecular function • growth factor activity
Cellular component • membrane
• integral to membrane
Biological process • anti-apoptosis
• signal transduction
• cell-cell signaling
• embryonic development
Sources: Amigo / QuickGO RNA expression pattern More reference expression data Orthologs Species Human Mouse Entrez 9542 n/a Ensembl ENSG00000158458 n/a UniProt O14511 n/a RefSeq (mRNA) XM_001129975 n/a RefSeq (protein) XP_001129975 n/a Location (UCSC) Chr 5:
139.21 - 139.4 Mb n/a PubMed search [1] n/a Neuregulin 2, also known as NRG2, is a protein which in humans is encoded by the NRG2 gene.[1][2][3]

Function Neuregulin 2 (NRG2) is a novel member of the neuregulin family of growth and differentiation factors. Through interaction with the ErbB family of receptors, NRG2 induces the growth and differentiation of epithelial, neuronal, glial, and other types of cells. The gene consists of 12 exons and the genomic structure is similar to that of neuregulin 1 (NRG1), another member of the neuregulin family of ligands. NRG1 and NRG2 mediate distinct biological processes by acting at different sites in tissues and eliciting different biological responses in cells. The gene is located close to the region for demyelinating Charcot-Marie-Tooth disease locus, but is not responsible for this disease. Alternative transcripts encoding distinct isoforms have been described.[1]

References

1. ^ a b "Entrez Gene: NRG2 neuregulin 2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9542. 
2. ^ Chang H, Riese DJ, Gilbert W, Stern DF, McMahan UJ (May 1997). "Ligands for ErbB-family receptors encoded by a neuregulin-like gene". Nature 387 (6632): 509–12. doi:10.1038/387509a0. PMID 9168114. 
3. ^ Carraway KL, Weber JL, Unger MJ, Ledesma J, Yu N, Gassmann M, Lai C (May 1997). "Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases". Nature 387 (6632): 512–6. doi:10.1038/387512a0. PMID 9168115. 

Further reading

• Chang H, Riese DJ, Gilbert W, et al. (1997). "Ligands for ErbB-family receptors encoded by a neuregulin-like gene.". Nature 387 (6632): 509–12. doi:10.1038/387509a0. PMID 9168114. 
• Carraway KL, Weber JL, Unger MJ, et al. (1997). "Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases.". Nature 387 (6632): 512–6. doi:10.1038/387512a0. PMID 9168115. 
• Busfield SJ, Michnick DA, Chickering TW, et al. (1997). "Characterization of a neuregulin-related gene, Don-1, that is highly expressed in restricted regions of the cerebellum and hippocampus.". Mol. Cell. Biol. 17 (7): 4007–14. PMC 232253. PMID 9199335. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=232253. 
• Higashiyama S, Horikawa M, Yamada K, et al. (1998). "A novel brain-derived member of the epidermal growth factor family that interacts with ErbB3 and ErbB4.". J. Biochem. 122 (3): 675–80. PMID 9348101. 
• Reddy PH, Stockburger E, Gillevet P, Tagle DA (1998). "Mapping and characterization of novel (CAG)n repeat cDNAs from adult human brain derived by the oligo capture method.". Genomics 46 (2): 174–82. doi:10.1006/geno.1997.5044. PMID 9417904. 
• Ring HZ, Chang H, Guilbot A, et al. (1999). "The human neuregulin-2 (NRG2) gene: cloning, mapping and evaluation as a candidate for the autosomal recessive form of Charcot-Marie-Tooth disease linked to 5q.". Hum. Genet. 104 (4): 326–32. doi:10.1007/s004390050961. PMID 10369162. 
• Yamada K, Ichino N, Nishii K, et al. (2000). "Characterization of the human NTAK gene structure and distribution of the isoforms for rat NTAK mRNA.". Gene 255 (1): 15–24. doi:10.1016/S0378-1119(00)00309-7. PMID 10974560. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Nakano N, Higashiyama S, Ohmoto H, et al. (2004). "The N-terminal region of NTAK/neuregulin-2 isoforms has an inhibitory activity on angiogenesis.". J. Biol. Chem. 279 (12): 11465–70. doi:10.1074/jbc.M311045200. PMID 14722120. 
• Ponomareva ON, Ma H, Dakour R, et al. (2005). "Stimulation of acetylcholine receptor transcription by neuregulin-2 requires an N-box response element and is regulated by alternative splicing.". Neuroscience 134 (2): 495–503. doi:10.1016/j.neuroscience.2005.04.028. PMID 15961242. 
• Fan BJ, Ko WC, Wang DY, et al. (2007). "Fine mapping of new glaucoma locus GLC1M and exclusion of neuregulin 2 as the causative gene.". Mol. Vis. 13: 779–84. PMC 2768763. PMID 17563728. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2768763.

From Wikipedia, the free encyclopedia Jump to: navigation, search Benzofuran IUPAC name[hide] 1-Benzofuran Other names[hide] Coumarone, benzo[b]furan Identifiers CAS number 271-89-6 Y PubChem 9223 ChemSpider 8868 Y KEGG C14512 Y ChEMBL CHEMBL363614 Y SMILES[show]

• o2c1ccccc1cc2

InChI[show]

• InChI=1S/C8H6O/c1-2-4-8-7(3-1)5-6-9-8/h1-6H Y
  Key: IANQTJSKSUMEQM-UHFFFAOYSA-N Y InChI=1/C8H6O/c1-2-4-8-7(3-1)5-6-9-8/h1-6H
  Key: IANQTJSKSUMEQM-UHFFFAOYAU

Properties Molecular formula C8H6O Molar mass 118.13 g mol−1 Melting point -18 °C, 255 K, -0 °F

Boiling point 173 °C, 446 K, 343 °F

 Y(what is this?)  (verify)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox references Benzofuran is the heterocyclic compound consisting of fused benzene and furan rings. This colourless solid is a component of coal tar. Benzofuran is the "parent" of many related compounds with more complex structures. For example, psoralen is a benzofuran derivative that occurs in several plants.

Contents[hide]

• 1 Production
  • 1.1 Laboratory methods
• 2 Related compounds
• 3 Safety
• 4 References

[edit] Production Benzofuran is extracted from coal tar. It is also obtained by dehydrogenation of 2-ethylphenol.[1]

[edit] Laboratory methods Benzofuran can be prepared by O-alkylation of salicylaldehyde with chloroacetic acid followed by dehydration of the resulting ether.[2] In another method called the "Perkin rearrangement"[3][4] a coumarin is reacted with a hydroxide:

[edit] Related compounds

• Furan, an analog without the fused benzene ring.
• Indole, an analog with a nitrogen instead of the oxygen atom.
• Isobenzofuran, the isomer with oxygen in the adjacent position.
• Aurone

[edit] Safety The LD50 in mice is 500 mg/kg.[1]

[edit] References

1. ^ a b Gerd Collin, Hartmut Höke "Benzofurans" in Ullmann's Encyclopedia of Industrial Chemistry, 2007, Wiley-VCH, Weinheim. doi: 10.1002/14356007.l03_l01
2. ^ Albert W. Burgstahler and Leonard R. Worden “Coumarone” Organic Syntheses, Collected Volume 5, p.251 (1973). http://www.orgsyn.org/orgsyn/pdfs/CV5P0251.pdf
3. ^ W. H. Perkin, J. Chem. Soc., 1870, 23, 368; 1871, 24, 37.
4. ^ Reactions of carbonyl compounds in basic solutions. Part 32.1 The Perkin rearrangement Keith Bowden and Sinan Battah J. Chem. Soc., Perkin Trans. 2, 1998, 1603 - 1606, doi:10.1039/a801538d

Designer drug From Wikipedia, the free encyclopedia   (Redirected from Research chemicals) Jump to: navigation, search Not to be confused with Drug design. The examples and perspective in this article may not represent a worldwide view of the subject. Please improve this article and discuss the issue on the talk page. Designer drug is a term used to describe drugs which are created (or marketed, if they had already existed) to get around existing drug laws, usually by modifying the molecular structures of existing drugs to varying degrees,[1][dubious – discuss] or less commonly by finding drugs with entirely different chemical structures that produce similar subjective effects to illegal recreational drugs. For example mephedrone is a designer drug.

Contents[hide]

• 1 History
  • 1.1 United States
  • 1.2 1920s-1930s
  • 1.3 1960s-1970s
  • 1.4 1980s-early 1990s
  • 1.5 Late 1990s-2004
  • 1.6 2005-2010
• 2 Safety
• 3 Law
• 4 Common designer drugs
  • 4.1 Opioids
  • 4.2 Hallucinogens
  • 4.3 Dissociatives
  • 4.4 Piperazine-based
  • 4.5 Entactogens
  • 4.6 Stimulants
  • 4.7 Sedatives
  • 4.8 Cannabinoids
  • 4.9 Anabolic Steroids
  • 4.10 Erectile dysfunction
• 5 See also
• 6 References
• 7 External links

// [edit] History The examples and perspective in this article or section might have an extensive bias or disproportional coverage towards one or more specific regions. Please improve this article or discuss the issue on the talk page. [edit] United States [edit] 1920s-1930s The term "designer drug" was first coined by law enforcement in the 1980s, and has gained widespread use. However the first appearance of what would now be termed designer drugs occurred well before this, in the 1920s. Following the passage of the second International Opium Convention in 1925 which specifically banned morphine and the diacetyl ester of morphine, heroin, a number of alternative esters of morphine quickly started to be manufactured and sold. The most notable of these were dibenzoylmorphine and acetylpropionylmorphine, which has virtually identical effects to heroin but were not covered by the Opium Convention. This then led the Health Committee of the League of Nations to pass several resolutions attempting to bring these new drugs under control, ultimately leading in 1930 to the first broad analogues provisions extending legal control to all esters of morphine, oxycodone and hydromorphone.[2] 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.[3]

[edit] 1960s-1970s During the 1960s and 1970s, a number of new synthetic hallucinogens were introduced, with a notable example being the sale of highly potent tablets of DOM in San Francisco in 1967.[4] 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, which was illegal. The late 1970s also saw the introduction of various analogues of phencyclidine (PCP) to the illicit market, although few of them were well accepted by users with only TCP and PCE becoming widely used.

[edit] 1980s-early 1990s The modern use of the term designer drug was coined in the 1980s to refer to various synthetic opioid drugs, mostly based on the fentanyl molecule (such as α-methylfentanyl).[5] The term gained widespread popularity when MDMA (ecstasy) experienced a popularity boom in the mid 1980s. 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 fentanyl or 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.[6] Other problems were highly potent fentanyl analogues, which were sold as China White, that caused many accidental overdoses.[7]

Because the government was powerless to prosecute people for these drugs until after they had been marketed successfully, 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, even though their own judge ruled that MDMA should be classified Schedule III on the basis of its demonstrated uses in medicine.[8] The emergency scheduling power has subsequently been used for a variety of other drugs including 2C-B, AMT, and BZP. In 2004, a piperazine drug, TFMPP, became the first drug that had been emergency-scheduled to be denied permanent scheduling and revert to legal status.

The late 1980s and early 1990s also 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, most notably methcathinone and 4-methylaminorex, but despite attracting enough attention from authorities to provoke legal scheduling of these compounds, their distribution was relatively limited in extent and methamphetamine continued to dominate the illicit synthetic stimulant market overall.[9]

[edit] Late 1990s-2004 In the late 1990s and early 2000s, there was a huge explosion in designer drugs being sold over the internet.[10][11][12] The term and concept of "research chemicals" was coined by some marketers of designer drugs (particularly of psychedelic drugs in the tryptamine and phenethylamine family). The idea was that by selling the chemicals as for "scientific research" rather than human consumption, the intent clause of the U.S. analogue drug laws would be avoided. Nonetheless the DEA raided multiple suppliers, first JLF Primary Materials, and then multiple vendors (such as RAC Research) several years later in Operation Web Tryp. This process was accelerated greatly when vendors began advertising via search engines like Google by linking their sites to searches on key words such as chemical names and terms like psychedelic or hallucinogen. Widespread discussion of consumptive use and the sources for the chemicals in public forums also drew the attention of the media and authorities.

In 2004, the US Drug Enforcement Administration raided and shut down several internet based research chemical vendors in an operation called Web Tryp. With help from the authorities in India and China, two chemical manufacturers were also closed. Many other internet based vendors promptly stopped doing business, even though their products were still legal throughout much of the world.

Most substances that were sold as "research chemicals" in this period of time are hallucinogens and bear a chemical resemblance to well-known drugs, such as psilocybin and mescaline. As with other hallucinogens, these substances are often taken for the purposes of facilitating spiritual processes (see entheogen), mental reflection (see psychedelic) or recreation. Some research chemicals on the market were not psychoactive, but can be used as precursors in the synthesis of other potentially psychoactive substances, for example, 2C-H which could be used to make 2C-B and 2C-I among others. Extensive surveys of structural variations have been conducted by pharmaceutical corporations, universities and independent researchers over the last century, from which some of the presently available research chemicals derive. One particularly notable researcher is Dr. Alexander Shulgin, who presented syntheses and pharmacological explorations of hundreds of substances in the books TiHKAL and PiHKAL (co-authored with Ann Shulgin), and has served as an expert witness for the defense in several court cases against manufacturers of psychoactive drugs.

The majority of chemical suppliers sold research chemicals in bulk form as powder, not as pills, as selling in pill form would invalidate the claims that they were being sold for non-consumptive research. Active dosages vary widely from substance to substance, ranging from sub-microgram levels to hundreds of milligrams, but while it is critical for the end user to weigh doses with a precision scale, instead of guessing ("eyeballing"), many users did not do this and this led to many emergency room visits and several deaths, which were a prominent factor leading to the emergency scheduling of several substances and eventually Operation Web Tryp. Some compounds such as 2C-B and 5-Meo-DiPT did eventually increase in popularity to the point that they were sold in pill form to reach a wider market, and acquired popular street names ("Nexus" and "Foxy" respectively). Once a chemical reaches this kind of popularity, it is usually just a matter of time before it is added to the list of scheduled (i.e. illegal) drugs.

The late 1990s and early 2000s also saw the first widespread use of novel anabolic steroids by athletes in competition. Steroids had been banned by the International Olympic Committee since 1976, but due to the large number of different anabolic agents available for human and veterinary use, the ability of laboratories to test for all available drugs had always lagged behind the ability of athletes to find new compounds to use. The introduction of increasingly formalised testing procedures, especially with the creation of the World Anti-Doping Agency in 1999, made it much more difficult for athletes to get away with using these drugs without detection, which then led to the synthesis of novel and potent anabolic steroid drugs such as tetrahydrogestrinone (THG) which were not detectable by the standard tests.[13]

[edit] 2005-2010 While historically most designer drugs had been either opioids, hallucinogens or anabolic steroids, the range of possible compounds is limited only by the scientific and patent literature, and recent years have been characterised by a broadening of the range of compounds sold as designer drugs. These have included a wide variety of designer stimulants such as geranamine, mephedrone, MDPV and desoxypipradrol, several designer sedatives such as methylmethaqualone and premazepam, and designer analogues of sildenafil (Viagra), which have been reported as active compounds in supposedly "herbal" aphrodisiac products.[14][15] Designer cannabinoids are another recent development, with two compounds JWH-018 and (C8)-CP 47,497 initially found in December 2008 as active components of "herbal smoking blends" sold as legal alternatives to marijuana,[16] and subsequently a growing range of synthetic cannabinoid agonists have continued to appear. The relative market saturation with the wide variety of opioid and hallucinogenic drugs already available has slowed the emergence of new compounds in these areas, although with some exceptions such as the popularisation and widespread internet sale of the opioid-bearing plant Mitragyna speciosa (Kratom) and its extracted active component 7-hydroxymitragynine,[17] as well as the continuing trickle of novel hallucinogens and dissociatives such as NBOMe-2CC (cf. NBOMe-2CI) and 3-MeO-PCP. Another novel development is the use of research ligands for cosmetic rather than strictly recreational purposes, such as grey-market internet sales of the non-approved alpha-melanocyte-stimulating hormone tanning drugs known as melanotan peptides.[18]

“...what is new is the wide range of substances now being explored, the aggressive marketing of products that have been intentionally mislabelled, the growing use of the internet, and the speed at which the market reacts to control measures.” --EMCDDA director Wolfgang Goetz (November 2009).[19][20] [edit] Safety The safety of research chemicals is untested and little if any research has been done on the toxicology or pharmacology of most of these drugs. Few, if any, human or animal studies have been done. Unlike better known drugs like alcohol or cannabis, which have been used by billions of people worldwide for centuries or even millennia, research chemicals are new and may only have been used by a few thousand people for a few months although some of the more popular drugs such as 2C-B, MDMA and BZP have been used by millions of people. Many research compounds have produced unexpected side effects and adverse incidents due to the lack of screening for off-target effects prior to marketing; both bromo-dragonfly and mephedrone seem to be capable of producing pronounced vasoconstriction under some circumstances which has resulted in several deaths,[21] although the mechanism remains unclear. More commonly adverse incidents and overdoses arise accidentally, from poor handling of potent chemicals where the margin of error is too narrow for guesswork, or simply from excessive abuse of the drug.

[edit] Law Due to the recent development of many designer drugs, laws banning or regulating their use have not been developed yet, and in recent cases novel drugs have appeared directly in response to legislative action, to replace a similar compound that had recently been banned.[22] Many of the chemicals fall under the various drug analogue legislations in certain countries, but most countries have no general analogue act or equivalent legislation and so novel compounds may fall outside of the law after only minor structural modifications. In the United States, the Controlled Substances Act was amended by the Controlled Substance Analogue Enforcement of 1986, which attempted to ban designer drugs pre-emptively by making it illegal to manufacture, sell, or possess chemicals that were substantially similar in chemistry and pharmacology to Schedule I or Schedule II drugs. Other countries have dealt with the issue differently. In some, they simply ban new drugs as they become a concern, as do Germany, Canada, and the United Kingdom. Some countries, such as Australia and New Zealand, have gone the opposite direction and enacted sweeping bans based on chemical structure only, making chemicals illegal even before they are created—if a theoretical chemical fits a set of rules regarding substitutions and alterations of an already banned drug, it too is banned. The controlled substance analogue law under both Australian Federal law and that of some individual states such as New South Wales, is so broad that it would cover millions of compounds that have never been made, simply on the basis that they bear a vague resemblance to one of the drugs on the illegal list. However it would still not cover drugs which have no structural similarity to any controlled drug, even if they produced similar effects.[23][24]

[edit] Common designer drugs Most of the best known research chemicals are structural analogues of tryptamines or phenethylamines, but there are also many other completely unrelated chemicals which can be considered as part of the group. It is very difficult to determine psychoactivity or other pharmaceutical properties of these compounds based strictly upon structural examination. Many of the substances have common effects whilst structurally different and vice versa (see also SAR paradox). As a result of no real official naming for some of these compounds, as well as regional naming, this can all lead to (and is anecdotally known to have led to) potentially hazardous mix ups for users.[25]

[edit] Opioids

• α-methylfentanyl, became well known as "China White" on the heroin market
• parafluorofentanyl
• 3-methylfentanyl, extremely potent opioid, allegedly used as a chemical weapon by the Russian military in the Moscow theater hostage crisis
• MPPP, especially infamous due to an impurity in some batches called MPTP which caused permanent Parkinsonism with a single use[26][27]
• 7-Acetoxymitragynine
• O-Desmethyltramadol
• 4'-Nitromethopholine

[edit] Hallucinogens Lysergamide-based

• ALD-52, N-acetyllysergic acid diethylamide, famously believed to have been the active ingredient in the "Orange Sunshine" acid of the 1960s
• ETH-LAD, which has been sold by some research chemical suppliers.
• AL-LAD, which has been sold by some research chemical suppliers.
• PRO-LAD, which has been sold by some research chemical suppliers.

Tryptamine-based

• 4-Acetoxy-DiPT, N,N-diisopropyl-4-acetoxytryptamine
• 4-Acetoxy-DMT, 4-acetoxy-dimethyltryptamine
• 4-HO-MET, 4-hydroxy-N-methyl-N-ethyltryptamine
• 5-MeO-AMT, 5-methoxy-alpha-methyltryptamine
• 5-MeO-DiPT, 5-methoxy-di-isopropyltryptamine (also known as "Foxy" or "Foxy Methoxy")
• 5-MeO-MiPT, 5-methoxy-methylisopropyltryptamine
• AMT, α-methyltryptamine
• DiPT, N,N-diisopropyl-tryptamine
• DPT, N,N-dipropyltryptamine
• 5-MeO-DALT (N-allyl-N-[2-(5-methoxy-1H-indol-3-yl)ethyl]prop-2-en-1-amine)

Phenethylamine-based

• 2C-B, 4-bromo-2,5-dimethoxyphenethylamine
• 2C-C, 2,5-dimethoxy-4-chlorophenethylamine
• 2C-D, 2,5-dimethoxy-4-methyl-phenethylamine
• 2C-E, 2,5-dimethoxy-4-ethyl-phenethylamine
• 2C-G, 3,4-dimethyl-2,5-dimethoxyphenethylamine
• 2C-I, 2,5-dimethoxy-4-iodophenethylamine
• 2C-T-2, 2,5-dimethoxy-4-ethylthiophenethylamine
• 2C-T-4, 2,5-dimethyoxy-4-(i)-propylthiophenethylamine
• 2C-T-7, 2,5-dimethoxy-4-(n)-propylthiophenethylamine
• 2C-T-21, 2,5-dimethoxy-4-(2-fluoroethylthio)phenethylamine
• 2CB-FLY
• Bromodragonfly
• DOB, 2,5-dimethoxy-4-bromoamphetamine
• DOC, 2,5-dimethoxy-4-chloroamphetamine
• DOM, 2,5-dimethoxy-4-methylamphetamine
• TMA-2, 2,4,5-Trimethoxyamphetamine
• MDAT (5,6,7,8-tetrahydrobenzo[f][1,3]benzodioxol-7-amine)

[edit] Dissociatives

• 3-MeO-PCP
• 4-MeO-PCP [28]
• Dizocilpine (MK-801; (+)-5-methyl-10,11- dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine)
• Eticyclidine (PCE; CI-400; N-ethyl-1-phenylcyclohexylamine)
• Methoxetamine (2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone)
• PCPr
• Rolicyclidine (PCPy; 1-(1-phenylcyclohexyl)pyrrolidine)
• Tenocyclidine (TCP; 1-(1-(2-Thienyl)cyclohexyl)piperidine)
• 3-MeO-PCE (2-(3-methoxyphenyl)-2-(ethylamino)cyclohexane)

[edit] Piperazine-based

• BZP, 1-benzylpiperazine
• mCPP, 1-(3-chlorophenyl)piperazine
• MeOPP, 1-(4-methoxyphenyl)piperazine
• pFPP, 1-(4-fluorophenyl)piperazine
• TFMPP, 3-trifluoromethylphenylpiperazine, has the unique distinction of being the only drug in the USA to be emergency scheduled into Schedule I and then allowed to become legal because the DEA was unable to justify permanent scheduling

[edit] Entactogens

• 4-MTA
• 5-Me-MDA
• 6-APB
• AET, α-ethyltryptamine
• Butylone
• Ethylone
• IAP
• MBDB
• MDAI
• MDMA, 3,4-methylenedioxymethamphetamine
• MDEA, 3,4-methylenedioxy-N-ethylamphetamine
• Methylone
• MMA
• PMA, a highly dangerous amphetamine derivative responsible for many accidental deaths
• PMMA, similar to PMA
• PMEA, also similar to PMA

[edit] Stimulants

• α-Pyrrolidinopropiophenone (α-PPP)
• 2-Fluoroamphetamine
• 4-Fluoroamphetamine
• 4-Methylaminorex (4-MAR)
• Buphedrone
• Desoxypipradrol
• Dimethocaine
• Diphenylprolinol
• Ethcathinone
• Flephedrone (4-FMC), and its 3-fluoro isomer 3-FMC
• Geranamine
• MDPV
• Mephedrone
• Methedrone
• Naphyrone
• Pentylone

[edit] Sedatives

• 1,4-Butanediol, another GHB analogue
• GBL, gamma-butyrolactone, both a precursor to and substitute for GHB
• GHV, gamma-hydroxyvaleric acid (4-methyl-GHB)
• GVL, gamma-valerolactone
• Methylmethaqualone, an analogue of the sedative methaqualone
• Mebroqualone
• Phenazepam (7-bromo-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one)

[edit] Cannabinoids

• AM-694
• CP 47,497 and its (C8) homologue cannabicyclohexanol
• CP 55,940
• HU-210
• JWH-018
• JWH-073
• JWH-200
• JWH-250
• THC-O-acetate

[edit] Anabolic Steroids

• Madol (sometimes confusingly referred to as "DMT")
• Methasterone
• Norbolethone
• Prostanozol
• THG, "The Clear"

[edit] Erectile dysfunction

• Acetildenafil
• Aminotadalafil
• Homosildenafil
• Hydroxyacetildenafil
• Hydroxyhomosildenafil
• Piperidino-acetildenafil
• Piperidino-vardenafil
• Thiomethisosildenafil
• Thiosildenafil

[edit] See also

• cf. Drug design
• Controlled Substances Act
• Controlled Substance Analogue Enforcement of 1986
• JLF
• Operation Web Tryp
• Pharmaceutical company

[edit] References

1. ^ Buchanan JF, Brown CR. Designer drugs. A problem in clinical toxicology. Medical Toxicology and Adverse Drug Experience. 1988 Jan-Dec;3(1):1-17.
2. ^ Esters of Morphine. UNODC Bulletin on Narcotics, 1953; Issue 2:36-38.
3. ^ Brecher, Edward M. (1972). The Consumers Union Report on Licit and Illicit Drugs. Consumer Reports Magazine.. 
4. ^ Snyder SH, Faillace L, Hollister L. 2,5-dimethoxy-4-methyl-amphetamine (STP): a new hallucinogenic drug. Science. 1967 Nov 3;158(801):669-70. PMID 4860952
5. ^ Donald A. Cooper. Future Synthetic Drugs of Abuse. Drug Enforcement Administration, McLean, Virginia
6. ^ Fahn, Stanley. The Case of the Frozen Addicts: How the Solution of an Extraordinary Medical Mystery Spawned a Revolution in the Understanding and Treatment of Parkinson's Disease. The New England Journal of Medicine. Dec 26, 1996. Vol. 335, Iss. 26; pg. 2002
7. ^ Henderson GL. Designer Drugs: Past History and Future Prospects. Journal of Forensic Sciences 1988; 33(2):569-575.
8. ^ TheDEA.org: The History of MDMA
9. ^ Philip Jenkins. Synthetic Panics: The Symbolic Politics of Designer Drugs. NYU Press 1999. ISBN 978-0-8147-4244-0
10. ^ Cole MD, Lea C, Oxley N. 4-Bromo-2,5-dimethoxyphenethylamine (2C-B): a review of the public domain literature. Science and Justice. 2002 Oct-Dec;42(4):223-4. PMID 12632938
11. ^ de Boer D, Bosman I. A new trend in drugs-of-abuse; the 2C-series of phenethylamine designer drugs. Pharmacy World and Science. 2004 Apr;26(2):110-3. PMID 15085947
12. ^ Uchiyama N, Kikura-Hanajiri R, Kawahara N, Goda Y. Analysis of designer drugs detected in the products purchased in fiscal year 2006. (Japanese). Yakugaku Zasshi. 2008 Oct;128(10):1499-505. PMID 18827471
13. ^ Malvey TC, Armsey TD 2nd. Tetrahydrogestrinone: the discovery of a designer steroid. Current Sports Medicine Reports. 2005 Aug;4(4):227-30. PMID 16004834
14. ^ Reepmeyer JC, Woodruff JT, d'Avignon DA. Structure elucidation of a novel analogue of sildenafil detected as an adulterant in an herbal dietary supplement. Journal of Pharmaceutical and Biomedical Analysis. 2007 Apr 11;43(5):1615-21. PMID 17207601
15. ^ Venhuis BJ, Blok-Tip L, de Kaste D. Designer drugs in herbal aphrodisiacs. Forensic Science International. 2008 May 20;177(2-3):e25-7. PMID 18178354
16. ^ Spice enthält chemischen Wirkstoff (German)
17. ^ Babu KM, McCurdy CR, Boyer EW. Opioid receptors and legal highs: Salvia divinorum and Kratom. Clinical Toxicology (Philadelphia). 2008 Feb;46(2):146-52. PMID 18259963
18. ^ Evans-Brown M, Dawson RT, Chandler M, McVeigh J. Use of melanotan I and II in the general population. British Medical Journal. 2009 Feb 17;338:b566. doi:10.1136/bmj.b566 PMID 19224885
19. ^ EU struggles to curb hard drugs. BBC News Thursday, 5 November 2009
20. ^ 2009 Annual report: the state of the drugs problem in Europe. EMCDDA, Lisbon, November 2009
21. ^ Andreasen MF, Telving R, Birkler RI, Schumacher B, Johannsen M. A fatal poisoning involving Bromo-Dragonfly. Forensic Science International. 2009 Jan 10;183(1-3):91-6. PMID 19091499
22. ^ Lindigkeit R, Boehme A, Eiserloh I, Luebbecke M, Wiggermann M, Ernst L, Beuerle T. Spice: A never ending story? Forensic Science International. 2009 Oct 30;191(1-3):58-63. PMID 19589652
23. ^ DRUG MISUSE AND TRAFFICKING ACT 1985 - SCHEDULE 1
24. ^ Commonwealth Criminal Code Act 1995 s 314.1(2)
25. ^ Shimizu E, Watanabe H, Kojima T, Hagiwara H, Fujisaki M, Miyatake R, Hashimoto K, Iyo M. Combined intoxication with methylone and 5-MeO-MIPT. Progress in Neuropsychopharmacology and Biological Psychiatry. 2007 Jan 30;31(1):288-91. PMID 16876302
26. ^ Davis GC, Williams AC, Markey SP, Ebert MH, Caine ED, Reichert CM, Kopin IJ. Chronic Parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry Research. 1979 Dec;1(3):249-54.
27. ^ Wallis, Claudia (2001-06-24). "Surprising Clue to Parkinson's - TIME". Time. http://www.time.com/time/magazine/article/0,9171,1101850408-141542,00.html. Retrieved 2010-05-01. 
28. ^ [King LA. New drugs coming our way - what are they and how do we detect them? EMCDDA Conference, Lisbon, 6–8 May 2009 http://www.emcdda.europa.eu/attachements.cfm/att_78745_EN_4_King.pps]