RX Graveyard

Diphenidine was first synthesized in 1924 using a Bruylants reaction similar to the one later employed in the discovery of phencyclidine in 1956.⁠^[1] Following the 2013 UK ban on arylcyclohexylamines, diphenidine and the related compound methoxphenidine emerged on the grey market.⁠^[1]

Its two enantiomers differ sharply at the NMDA receptor: the (S)-enantiomer is approximately 40 times more potent than the (R)-enantiomer.⁠^[1] Vendors claimed from 2013 that it acts on the dopamine transporter, but supporting data only became available in 2016; besides the NMDA receptor, it binds with submicromolar affinity to the σ1 receptor, σ2 receptor and dopamine transporter.⁠^[1][2] In dogs it shows greater antitussive (cough-suppressing) potency than codeine phosphate.⁠^[1]

Since 2014 it has been detected in Japanese herbal incense blends, mixed with other research chemicals, particularly synthetic cannabinoids and stimulants. One product, "Aladdin Spacial [sic] Edition" from Shizuoka Prefecture, contained 289 mg/g of diphenidine and 55.5 mg/g of 5F-AB-PINACA.⁠^[1]

In the United States the DEA proposed placing diphenidine in Schedule I of the Controlled Substances Act on 26 May 2026 (Docket No. DEA1155), with comments closing on 25 June 2026.⁠^[3] The final rule, published on 21 September 2026, places diphenidine, including its salts, isomers and salts of isomers, in Schedule I. DEA says the action is taken, in part, to enable the United States to meet its obligations under the 1971 Convention on Psychotropic Substances.⁠^[4]

Methaqualone was first synthesized in India in 1951 by Indra Kishore Kacker and Syed Husain Zaheer, who were looking for new antimalarial medications.⁠^[1] It was patented in the United States in 1962, and by 1965 it was the most commonly prescribed sedative in Britain.⁠^[1] In 1972 it was the sixth-bestselling sedative in the US, sold under the brand name Quaalude, a portmanteau of "quiet interlude".⁠^[1][2]

Its reputation outran its prescriptions. When the maker sold the rights in 1978, Rorer's chairman said "Quaalude accounted for less than 2% of our sales, but created 98% of our headaches."⁠^[1]

Methaqualone was first placed in Schedule I of the UN Convention on Psychotropic Substances and moved to Schedule II in 1979.⁠^[1] In the United States it was withdrawn from the market in 1983 and made a Schedule I drug in 1984.⁠^[1][3]

BZP was first synthesized by Burroughs Wellcome & Company in 1944.⁠^[1][2] In the 1970s it was investigated as a possible antidepressant, but was rejected when research found it had amphetamine-like effects; that 1973 study said BZP "should be placed under statutory control similar to those regulating the use of amphetamine".⁠^[1][3]

In 1996 the US Drug Enforcement Administration noted it was being used recreationally in California. Its use grew worldwide around 2000, which was soon followed by legislative control in Europe and the United States.⁠^[1][2] It was federally classified as a Schedule I controlled substance in the United States in 2002.⁠^[1]

New Zealand was where it lived largest. It was initially legal there, restricted in 2005, and reclassified as Class C in 2008.⁠^[1][2] An estimated 5 million pills were sold in New Zealand in 2007.⁠^[1][4] Retailers marketed it as a "dietary supplement", a "pepper extract" or a "herbal high", when the drug is entirely synthetic and has not been found to occur naturally.⁠^[1][4][5]

Bromo-DragonFLY was first synthesized by David E. Nichols and colleagues in 1998.⁠^[1] It is taken orally, with a delayed onset of up to 6 hours and a very long duration of up to 1 to 3 days.⁠^[1][2]

Sweden classified it as a "health hazard" on 15 July 2007, then listed it as a narcotic from 3 January 2008.⁠^[1] Denmark banned it on 3 December 2007.⁠^[1][3] Australia lists it in Schedule 9 of the Poisons Standard, and Canada added it to Schedule III on 12 October 2016.⁠^[1]

In September 2007 a Swedish man needed parts of his feet and several fingers amputated after a massive overdose, because the drug acted as a long-acting vasoconstrictor.⁠^[1][4] Seizures have also been reported.⁠^[1][5]

The synthesis of mephedrone was first reported in 1929 by Saem de Burnaga Sanchez, but it stayed an obscure product of academia until 2003, when an underground chemist under the pseudonym "Kinetic" re-discovered and publicised it on The Hive website.⁠^[1]

It spread fast. Mephedrone was first seized in France in May 2007, Europol became aware of it in 2008, and by May 2010 it had been detected in all 22 EU member states that reported to Europol.⁠^[1] In the UK it was not covered by the Misuse of Drugs Act, but selling it for human consumption was an offence under the Medicines Act, so it was often sold as "plant food" or "bath salts".⁠^[1]

It was first made illegal in Israel in January 2008.⁠^[1] After a young woman's death in Sweden in December 2008 was linked to mephedrone, it was classified as a hazardous substance a few days later.⁠^[1] 2010 was the year of its many funerals: Croatia and Germany in January, a UK import ban on 29 March, Class B status in the UK from 16 April, and in December 2010 a ban throughout the EU.⁠^[1] The US temporarily placed it in Schedule I in October 2011, and control became permanent on 9 July 2012 through the Synthetic Drug Abuse Prevention Act.⁠^[1]

JWH-018 is one of many compounds that organic chemist John W. Huffman synthesized at Clemson University to study the endocannabinoid system, with an affinity for the CB1 receptor five times greater than that of THC.⁠^[1]

On 15 December 2008, German pharmaceutical companies reported finding it as an active ingredient in at least three versions of Spice, a grey-market product sold as incense since 2006.⁠^[1] Austria announced on 18 December 2008 that Spice would be controlled, and Germany banned JWH-018 on 22 January 2009.⁠^[1] The United Kingdom followed on 23 December 2009.⁠^[1] The US scheduled it temporarily on 1 March 2011 and permanently on 9 July 2012.⁠^[1]

Naphyrone was derived from pyrovalerone and acts as a serotonin–norepinephrine–dopamine reuptake inhibitor.⁠^[1][2] It emerged as a new legal high in the United Kingdom only months after the ban of mephedrone.⁠^[1]

It was marketed as "NRG-1", but when Liverpool John Moores University researchers tested ten products labelled NRG-1, only one actually contained naphyrone. The others held MDPV, flephedrone, mephedrone, butylone and caffeine, and one was inorganic.⁠^[1][3]

On 12 July 2010 the Home Office announced that naphyrone had been banned and made a Class B drug, following a report from the Advisory Council on the Misuse of Drugs.⁠^[1]

MDPV was first developed in the 1960s by a team at Boehringer Ingelheim and stayed an obscure stimulant until around 2004, when it was reportedly sold as a designer drug.⁠^[1] In the US, products labeled as "bath salts" containing MDPV were sold in gas stations until it was banned in 2011.⁠^[1][2]

Finland listed it as a controlled substance on 28 June 2010, and the UK made it Class B in 2010 alongside the other cathinones.⁠^[1] In the US, Florida and Louisiana banned it first, and on 21 October 2011 the DEA used its emergency powers to place it temporarily in Schedule I.⁠^[1]

New Jersey's ban, Pamela's Law, is named after Rutgers student Pamela Schmidt, who was murdered in March 2011 by an alleged user of MDPV. A toxicology report later found no "bath salts" in his system.⁠^[1]

Unlike ketamine and PCP, which were developed as anaesthetics, methoxetamine was designed specifically to increase the antidepressant effects of ketamine.⁠^[1][2] Its effects were first described online in May 2010, and it went on sale on a small scale that September.⁠^[1][2] By July 2011, the EMCDDA had found 58 websites selling it.⁠^[1]

Canada controlled it from January 2011 and Russia from October 2011.⁠^[1] In the UK it was placed under a temporary class drug order in April 2012, after the ACMD advised that "the evidence shows that the use of methoxetamine can cause harm to users", and it became Class B on 26 February 2013.⁠^[1] The UN made it a Schedule II drug in November 2016, and the US DEA published a final rule placing it in Schedule I on 6 June 2022.⁠^[1]

25I-NBOMe was described by Heim in his 2003 dissertation and studied further by David Nichols's team at Purdue University from 2006 to 2008.⁠^[1] It was encountered as a recreational drug by 2010, often misrepresented as LSD.⁠^[1][2] By 2012, NBOMe drugs had for a time eclipsed LSD and psilocybin mushrooms in popularity.⁠^[1][3]

Russia was the first country to pass specific rules on the NBOMe series, banning all of them in October 2011.⁠^[1][4] Sweden scheduled it on 1 August 2013, and on 15 November 2013 the US DEA used its emergency powers to place it in Schedule I.⁠^[1] The European Union banned it in all member states in September 2014.⁠^[1]

MDAI was first described by David E. Nichols and colleagues at Purdue University in 1989.⁠^[1][2] It started being sold online around 2007 and peaked between about 2010 and 2012, after the mephedrone bans came into effect.⁠^[1][3]

Many internet products claimed to be MDAI were shown to contain mephedrone or other cathinones, and generally no MDAI at all.⁠^[1][3] Switzerland controlled it from December 2011, Denmark from September 2015 and China from October 2015.⁠^[1] In the UK it falls under the Psychoactive Substances Act, in effect from 26 May 2016.⁠^[4]

Ethylphenidate is the ethyl analogue of methylphenidate, a norepinephrine–dopamine reuptake inhibitor that appeared as a novel psychoactive substance sold through unregulated channels, where purity, dosage and composition may vary.⁠^[1]

Austria banned it under its New Psychoactive Substances Act from 1 January 2012, Sweden from 15 December 2012 and Denmark from 1 February 2013.⁠^[1] The UK placed it under a temporary class drug order on 10 April 2015.⁠^[1] Its role in deaths in east and west Scotland was reviewed in a 2015 forensic study.⁠^[1][2] The US placed it in Schedule I effective 21 November 2024.⁠^[1]

AH-7921 was discovered in the 1970s by a team at Allen and Hanburys in the United Kingdom, an opioid with around 90% of the potency of morphine when taken orally.⁠^[1][2] It never progressed to clinical trials.⁠^[1] From 2012 it was sold online as a "research chemical", sometimes as "doxylam", which is not to be confused with doxylamine.⁠^[1][3][4]

Israel banned its distribution from December 2013. The UK made it Class A in January 2015, China controlled it from October 2015, and the US placed it in Schedule I on 16 May 2016.⁠^[1]

α-PVP was first described in the literature in 1963.⁠^[1] Colloquially it is known as flakka or gravel.⁠^[1]

On 28 January 2014 the US DEA listed it, with nine other synthetic cathinones, as a temporary Schedule I substance effective 27 February 2014.⁠^[1] In New South Wales it was explicitly banned after two people died from using it, one by jumping off a balcony and another from a heart attack after a state of delirium.⁠^[1] The UN placed it under international control in November 2016, and EU member states were required to ban it by 3 July 2017.⁠^[1][2]

MT-45 was invented in the 1970s by Dainippon Pharmaceutical. It is a piperazine derivative, structurally unrelated to most other opioids, and the racemic mixture has around 80% of the potency of morphine.⁠^[1][2]

It became a Class A drug in the UK on 11 March 2015. Canada made it Schedule I in 2016, and the US placed it in Schedule I effective 12 January 2018.⁠^[1]

U-47700 was developed by a team at Upjohn in the 1970s and has around 7.5 times the potency of morphine in animal models.⁠^[1][2] It has never been studied in humans.⁠^[1][3]

After it spread as a designer drug, Sweden banned it on 26 January 2016, and Ohio emergency-scheduled it on 3 May 2016.⁠^[1] The US DEA placed it in Schedule I effective 14 November 2016, under a press release headed "46 confirmed deaths linked to dangerous opioid in '15 and '16 spark emergency action".⁠^[1] It became Class A in the UK in 2017 and permanently Schedule I in the US in April 2018.⁠^[1]