Editing Designer drug (section)

==History==
{{Globalize|section|date=May 2010}}

===United States===

====1920s–1930s====
Following the passage of the second [[International Opium Convention]] in 1925, which specifically banned [[morphine]] and the [[acetyl|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 have 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.<ref>{{cite journal|url= http://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1953-01-01_2_page009.html |title=Esters of Morphine |journal=UNODC Bulletin on Narcotics |year=1953 |issue=2 |pages=36–38}}</ref> 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 beverage]]s in a number of countries.<ref>{{cite book | vauthors = Brecher EM |title=The Consumers Union Report on Licit and Illicit Drugs |publisher=Consumer Reports Magazine. |year=1972 }}</ref>

====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 [[2,5-Dimethoxy-4-methylamphetamine|DOM]] in [[San Francisco]] in 1967.<ref>{{cite journal |vauthors=Snyder SH, Faillace L, Hollister L |title=2,5-dimethoxy-4-methyl-amphetamine (STP): a new hallucinogenic drug |journal=Science |volume=158 |issue=3801 |pages=669–70 |year=1967 |pmid=4860952 |doi=10.1126/science.158.3801.669 |bibcode=1967Sci...158..669S |s2cid=24065654 }}</ref> 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. One significant court case from this period was in 1973, when [[Tim Scully]] and [[Nicholas Sand]] were prosecuted for making the acetyl amide of [[Lysergic acid diethylamide|LSD]], known as [[ALD-52]].{{Citation needed|date=December 2019}} 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 1960s also saw the introduction of various analogues of [[phencyclidine]] (PCP) to the illicit market, with [[Eticyclidine]] (PCE) first being detected in 1969.<ref>{{Cite journal |last1=Morris |first1=Hamilton |last2=Wallach |first2=Jason |date=July 2014 |title=From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs |url=https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/dta.1620 |journal=Drug Testing and Analysis |language=en |volume=6 |issue=7–8 |pages=614–632 |doi=10.1002/dta.1620 |pmid=24678061 |issn=1942-7603|url-access=subscription }}</ref>

====1980s–early 1990s====
The modern use of the term designer drug was coined in the 1980s to refer to various synthetic [[opioid]] drugs, based mostly on the [[fentanyl]] molecule (such as [[Alphamethylfentanyl|α-methylfentanyl]]).<ref>{{cite conference | url = http://www.erowid.org/library/books_online/future_synthetic/future_synthetic.shtml| vauthors = Cooper DA | title = Future Synthetic Drugs of Abuse | conference = Proceedings of the international symposium on the forensic aspects of controlled substances | date = March 1988 | page = 79 | publisher = Drug Enforcement Administration | location = McLean, Virginia }}</ref> 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, [[Desmethylprodine|MPPP]], was found in some cases to contain an impurity called [[MPTP]], which caused brain damage that could result in a syndrome identical to late stage [[Parkinson's disease]], from only a single dose.<ref>{{cite journal |title=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 |year=1996 |volume=335 |issue=26 |pages=2002–2003 |vauthors=Fahn S |journal=The New England Journal of Medicine |doi=10.1056/NEJM199612263352618}}</ref> Other problems were highly potent fentanyl analogues that caused many accidental overdoses.<ref>{{cite journal |vauthors=Henderson GL |title=Designer drugs: past history and future prospects |journal=J. Forensic Sci. |volume=33 |issue=2 |pages=569–75 |year=1988 |pmid=3286815 |doi=10.1520/JFS11976J }}</ref>

Because the government was powerless to prosecute people for these drugs until after they had been marketed successfully, laws were passed to give the [[Drug Enforcement Administration|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.<ref>{{Cite web |url=http://www.thedea.org/drughistory.html |title=TheDEA.org: The History of MDMA<!-- Bot generated title --> |access-date=2008-03-27 |archive-date=2016-07-14 |archive-url=https://web.archive.org/web/20160714221547/http://thedea.org/drughistory.html |url-status=dead }}</ref> The emergency scheduling power has subsequently been used for a variety of other drugs including [[2C-B]], [[Alphamethyltryptamine|AMT]], and [[Benzylpiperazine|BZP]]. In 2004, a [[piperazine]] drug, [[Trifluoromethylphenylpiperazine|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, the most notable ones being [[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.<ref>{{cite book | vauthors = Jenkins P | title = Synthetic Panics: The Symbolic Politics of Designer Drugs | publisher = NYU Press | date = 1999 | isbn = 978-0-8147-4244-0 }}</ref>

====Late 1990s–2004====
In the late 1990s and early 2000s, there was a huge explosion in designer drugs being sold over the internet.<ref>{{cite journal |vauthors=Cole MD, Lea C, Oxley N |title=4-Bromo-2,5-dimethoxyphenethylamine (2C-B): a review of the public domain literature |journal=Sci. Justice |volume=42 |issue=4 |pages=223–4 |year=2002 |pmid=12632938 |doi=10.1016/S1355-0306(02)71832-7 }}</ref><ref>{{cite journal |vauthors=de Boer D, Bosman I |title=A new trend in drugs-of-abuse; the 2C-series of phenethylamine designer drugs |journal=Pharm World Sci |volume=26 |issue=2 |pages=110–3 |year=2004 |pmid=15085947 |doi=10.1023/b:phar.0000018600.03664.36 |s2cid=35546712 }}</ref><ref>{{cite journal |vauthors=Uchiyama N, Kikura-Hanajiri R, Kawahara N, Goda Y |title=[Analysis of designer drugs detected in the products purchased in fiscal year 2006] |journal=Yakugaku Zasshi |volume=128 |issue=10 |pages=1499–505 |year=2008 |pmid=18827471 |doi=10.1248/yakushi.128.1499 |doi-access=free }}</ref> The term and concept of "research chemicals" was coined by some marketers of designer drugs (in particular, of [[psychedelic drug]]s in the [[tryptamine]] and [[phenethylamine]] family). The idea was that, by selling the chemicals as for "scientific research" rather than human consumption, the [[Mens rea|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 drugs|psychedelic]] or [[Psychedelics, dissociatives and deliriants|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 drugs such as [[psilocybin]] and [[mescaline]]. As with other hallucinogens, these substances are often taken for the purposes of facilitating [[spirituality|spiritual]] [[entheogen|processes]], [[Psychedelic drug|mental reflection]] or [[recreational drug|recreation]]. Some research chemicals on the market were not psychoactive, but can be used as [[Precursor (chemistry)|precursors]] in the [[chemical synthesis|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 [[Alexander Shulgin]], who presented syntheses and [[pharmacology|pharmacological]] explorations of hundreds of substances in the books ''[[TiHKAL]]'' and ''[[PiHKAL]]'' (co-authored with [[Ann Shulgin]]), and 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 micrograms 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 steroid]]s 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.<ref>{{cite journal |vauthors=Malvey TC, Armsey TD |title=Tetrahydrogestrinone: the discovery of a designer steroid |journal=Curr Sports Med Rep |volume=4 |issue=4 |pages=227–30 |year=2005 |pmid=16004834 |doi=10.1097/01.csmr.0000306213.87433.11 |s2cid=220574624 |doi-access=free }}</ref>

====2005–2021====
While through recent history 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 [[sedative]]s such as [[methylmethaqualone]] and [[premazepam]], and designer analogues of [[sildenafil]] (Viagra), which have been reported as active compounds in "herbal" aphrodisiac products.<ref>{{cite journal |vauthors=Reepmeyer JC, Woodruff JT, d'Avignon DA |title=Structure elucidation of a novel analogue of sildenafil detected as an adulterant in an herbal dietary supplement |journal=J Pharm Biomed Anal |volume=43 |issue=5 |pages=1615–21 |year=2007 |pmid=17207601 |doi=10.1016/j.jpba.2006.11.037 |url= https://zenodo.org/record/1259163 }}</ref><ref>{{cite journal |vauthors=Venhuis BJ, Blok-Tip L, de Kaste D |title=Designer drugs in herbal aphrodisiacs |journal=Forensic Sci. Int. |volume=177 |issue=2–3 |pages=e25-7 |year=2008 |pmid=18178354 |doi=10.1016/j.forsciint.2007.11.007 }}</ref> Designer [[cannabinoid]]s are another recent development, with two compounds [[JWH-018]] and (C8)-[[CP 47,497]] initially found in December 2008 as active components of "[[Spice (drug)|herbal smoking blends]]" sold as legal alternatives to marijuana.<ref>{{cite web | url = http://www.badische-zeitung.de/nachrichten/panorama/spice-enthaelt-chemischen-wirkstoff--9211606.html | title = Spice enthält chemischen Wirkstoff | trans-title = Spice contains chemical agent | language = German | date = December 2008 | work = Badishce Zietung }}</ref> Subsequently, a growing range of [[Synthetic cannabinoids|synthetic cannabinoid]] agonists have continued to appear, including by 2010, novel compounds such as [[RCS-4]], [[RCS-8]], and [[AB-001]], which had never been reported in the literature, and appear to have been invented by designer drug manufacturers themselves. Another novel development is the use of research ligands for [[Cosmeceutical|cosmetic]] rather than strictly recreational purposes, such as [[grey-market]] internet sales of the non-approved alpha-[[melanocyte-stimulating hormone]] [[Sunless tanning|tanning]] drugs known as [[Melanotan (disambiguation)|melanotan]] peptides.<ref>{{cite journal |vauthors=Evans-Brown M, Dawson RT, Chandler M, McVeigh J |s2cid=43121906 |title=Use of melanotan I and II in the general population |journal=BMJ |volume=338 |pages=b566 |year=2009 |pmid=19224885 |doi=10.1136/bmj.b566 }}</ref>

{{blockquote|"...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."|[[European Monitoring Centre for Drugs and Drug Addiction|EMCDDA]] director Wolfgang Goetz (November 2009).<ref>{{Cite news|url= http://news.bbc.co.uk/2/hi/europe/8343989.stm |title=EU struggles to curb hard drugs |work=BBC News |date=5 November 2009}}</ref><ref>{{cite web|url= http://www.emcdda.europa.eu/attachements.cfm/att_93236_EN_EMCDDA_AR2009_EN.pdf|title= 2009 Annual report: the state of the drugs problem in Europe.|publisher= European Monitoring Centre for Drugs and Drug Addiction (EMCDDA)|location= Lisbon|access-date= 2009-11-05|archive-date= 2009-11-16|archive-url= https://web.archive.org/web/20091116202814/http://www.emcdda.europa.eu/attachements.cfm/att_93236_EN_EMCDDA_AR2009_EN.pdf|url-status= dead}}</ref>}}

[[File:Meph pack.jpg|thumb|A sample of [[mephedrone]].<br>Note the label: "<i>Not for human consumption. For technical use only</i>"]]
Mephedrone and the [[cathinone]]s marked somewhat of a turning point for designer drugs, turning them from little known, ineffective substances sold in [[head shops]] to powerful substances able to compete with classical drugs on the black market. Mephedrone especially experienced a somewhat meteoric rise in popularity in 2009<ref name=Measham>{{cite journal |vauthors=Measham F, Moore K, Newcombe R, Smith Z |date=12 March 2010|title=Tweaking, bombing, dabbing and stockpiling: the emergence of mephedrone and the perversity of prohibition |journal=Drugs and Alcohol Today|volume=10|issue=1|pages=14–21|doi=10.5042/daat.2010.0123|url=https://usir.salford.ac.uk/id/eprint/49745/ |url-access=subscription}}{{subscription required}}</ref> and the resulting media panic resulted in its prohibition in multiple countries. Following this there was a considerable emergence of other cathinones which attempted to mimic the effects of mephedrone, and with a newly attracted customer base, plenty of money to drive innovation.

Subsequently, the market rapidly expanded, with more and more substances being detected every year. In 2009, the EMCDDA's early warning system discovered 24 new drugs. In 2010, it found another 41; in 2011, another 49; and in 2012, there were 73 more.<ref name="mikepower">{{cite news|url= https://www.theguardian.com/science/2013/oct/31/drugs-legal-high |title=Drugs unlimited: how I created my very own legal high |work=The Guardian |date=2014-10-31 |access-date=7 August 2014 | vauthors = Power M }}</ref> In 2013, a further 81 were identified:<ref name=EMCDDA2013>{{cite web|url= http://www.emcdda.europa.eu/publications/implementation-reports/2013 |title=EMCDDA–Europol 2013 Annual Report on the information exchange, risk assessment and control of new&nbsp;psychoactive substances (implementation of Council Decision 2005/387/JHA) |publisher=[[EMCDDA]] |date=July 2014 |access-date=8 August 2014 }}</ref> a total of 268 new drugs in just four years. These have not been limited to cathinones, with 35% being cannabinoids and the rest being composed of stimulants, [[benzodiazepine]]s, psychedelics, dissociatives and to a lesser extent, every other class of drugs, even ibogoids and [[nootropics]]. The largest group of drugs being monitored by the [[European Monitoring Centre for Drugs and Drug Addiction|EMCDDA]] is [[synthetic cannabinoids]], with 209 different [[synthetic cannabinoids]] reported between 2008 and 2021 - including 11 new cannabinoids identified for the first time in 2020.<ref>{{cite web | author = European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) | date = 2021 | title = Synthetic cannabinoids in Europe – a review | publisher = Publications Office of the European Union | location = Luxembourg | url = https://www.emcdda.europa.eu/system/files/publications/14035/Synthetic-cannabinoids-in-Europe-EMCDDA-technical-report.pdf }}</ref>

Since 2019, highly potent [[nitazenes]] ([[List of benzimidazole opioids|benzimidazole opioids]]) have proliferated as ″new synthetic opioids″ in the North American and European narcotics markets and as such have become a formative component of the [[opioid epidemic in the United States]]. Overdoses of nitazene opioids have led to several hundred documented fatalities.

==== 2022–present ====
In the early 2020s, safety and legal difficulty of regulating peptides spurred the growth of grey-market [[synthetic peptide hormone]] vendors.<ref>{{Cite web |last1=Gilbertson |first1=Annie |last2=Keegan |first2=Jon |date=2020-09-17 |title=Labeled "Research" Chemicals, Doping Drugs Sold Openly on Amazon.com – The Markup |url=https://themarkup.org/banned-bounty/2020/09/17/amazon-sales-peptides-doping-drugs |access-date=2023-10-24 |website=themarkup.org |language=en}}</ref> These peptides are marketed as non-recreational and sold for their purported anti-aging, performance enhancing and cosmetic benefits,<ref>{{Cite journal |last1=Turnock |first1=Luke |last2=Gibbs |first2=Nick |date=2023-06-01 |title=Click, click, buy: The market for novel synthetic peptide hormones on mainstream e-commerce platforms in the UK |journal=Performance Enhancement & Health |volume=11 |issue=2 |pages=100251 |doi=10.1016/j.peh.2023.100251 |issn=2211-2669|doi-access=free }}</ref> such vendors may employ medical professionals using legal ambiguity for their operations.<ref>{{Cite web |date=2017-06-29 |title=Uncovering the peptide 'grey market' sweeping Australia |url=https://www.9news.com.au/national/peptides-australia-9news-investigation/e6be39d3-bd39-47fe-9cb7-1fce938239b5 |access-date=2023-10-24 |website=www.9news.com.au}}</ref>