Temporary class drug

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A temporary class drug is a relatively new status for controlled drugs, which has been adopted in some jurisdictions, notably New Zealand and the United Kingdom, to attempt to bring newly synthesised designer drugs under legal control. The controlled drug legislation in these jurisdictions requires drug scheduling decisions to follow an evidence-based process, where the harms of the drug are assessed and reviewed so that an appropriate legal status can be assigned. Since many designer drugs sold in recent years have had little or no published research that could help inform such a decision, they have been widely sold as "legal highs", often for months, before sufficient evidence accumulates to justify placing them on the controlled drug schedules.

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This situation has been deemed to be undesirable, as every time a designer drug has been banned, novel compounds with similar effects have been quickly developed and brought to market, often with worse health consequences reported than the original compound. The temporary class drug status has been developed to circumvent the evidential requirements and allow drugs to be banned temporarily as soon as they are deemed by authorities to be causing harm to individuals or society. The temporary ban lasts for a period of 1 year, after which the drug would in theory be made legal again, if sufficient evidence to ban it permanently had not been forthcoming. During the period of the temporary ban, the temporary class drugs are treated equivalently to established illegal drugs, though with reduced or absent penalties for personal use amounts, and the main focus of enforcement being on importation and sale of the drugs.

United Kingdom

The Secretary of State has the authority to make temporary class drug orders under the Misuse of Drugs Act section 2A(1).

Initially, only the dissociative arylcyclohexylamine derivative methoxetamine was banned as a temporary class drug in the UK, effective from 5 April 2012. [1] [2] [3] On 26 February 2013 methoxetamine was banned as a Class B drug under the Misuse of Drugs Act [4] along with a large number of other arylcyclohexylamine derivatives under a 'catch-all' chemical structure clause. "In an attempt to prevent legal high manufacturers looking for a new ketamine analogue to sell, the government has placed countless other ketamine analogues into Class B and Schedule 1." [5]

On 10 June 2013, a total of 10 benzofuran and indole analogues and four NBOMe hallucinogens were classified as Temporary Class Drugs in the UK following an ACMD recommendation. Specifically these include 5-APB, 6-APB, 5-APDB, 6-APDB and their N-methyl derivatives 5-MAPB, 6-MAPB, 5-MAPDB and 6-MAPDB, as well as 5-IT and its isomer 6-IT, plus NBOMe-2C-C, NBOMe-2C-B, NBOMe-2C-I and NBOMe-2C-D. [6] This means that sale and import of the named substances are criminal offences and are treated as for Class B drugs. [7]

On 31 March 2015, five derivatives of methylphenidate were recommended to be banned in the UK as Temporary Class Drugs following their sale as uncontrolled stimulant drugs. The compounds listed for control were ethylphenidate, propylphenidate, isopropylphenidate, methylnaphthidate and 3,4-Dichloromethylphenidate. [8]

On 25 June 2015, two more derivatives of methylphenidate, 4-Methylmethylphenidate and ethylnaphthidate, were recommended to be banned in the UK as Temporary Class Drugs following their sale as uncontrolled stimulant drugs. [9] [10]

Following the ban on ethylphenidate authorities noticed that methiopropamine had replaced it as the stimulant of choice for injecting users. [11] A TCDO was announced a week later and it was banned 48 hours after this. [12]

New Zealand

In New Zealand, 35 drugs have been banned as temporary class drugs since August 2011, 24 of which have subsequently had the temporary ban renewed for a further year after reaching the end of the initial one-year ban period. These include; JWH-018, JWH-022, JWH-073, JWH-081, JWH-122, JWH-201, JWH-203, JWH-210, JWH-250, JWH-302, AM-694, AM-2201, RCS-4, RCS-4 butyl homologue, 2-methoxy isomer of RCS-4, and 2-methoxy isomer of RCS-4 butyl homologue, which were banned on 16 August 2011, JWH-019, JWH-200 and AM-1220, which were banned on 14 October 2011, AM-2233, banned on 29 December 2011, AM-1248, AM-2232 and UR-144, banned on 6 April 2012, and the stimulant methylhexanamine, banned on 9 April 2012. Another four cannabinoid compounds, namely CB-13, MAM-2201, AKB48 and XLR-11, were banned on 13 July 2012. [13] A further cannabinoid compound NNE1 was banned from 8 November 2012. [14] Two more cannabinoids APICA (also known as 2NE1) and its 5-fluoropentyl derivative STS-135 were banned from 22 November 2012. [15] Another cannabinoid EAM-2201 was banned from 6 December 2012. [16] Another stimulant, the phenyltropane derivative RTI-126, was banned from 27 December 2012. [17] Two more cannabinoids QUCHIC (also known as BB-22) and 5F-AKB48 were banned from 9 May 2013. [18]

On 18 July 2013, the Psychoactive Substances Act 2013 came into effect in New Zealand. This superseded the Temporary Class Drug scheme, as all novel psychoactive substances are restricted by default, except where specifically licensed. This Act promises to introduce strict toxicity testing and quality control standards for recreational psychoactive substances, with products that are proved to meet the safety criteria being allowed to be sold legally. Products that were on sale immediately prior to the introduction of the Act were allowed to continue to be on sale while the safety testing regime is implemented, but can be removed from sale if significant adverse events are reported. A number of interim licenses have been refused or revoked under this process, and by January 2014 a total of twelve more synthetic cannabis products had been removed from sale, containing ingredients such as ADB-CHMICA (SGT-7), 5F-PB-22, SGT-55 (CUMYL-BICA), SGT-56 (CUMYL-PICA), 4-F-AM-2201, 4-Cl-AM-2201 and PB-22. [19] [20] [21]

On 27 April 2014 it was announced that all 41 remaining untested "legal high" products, which had been allowed to continue to be on sale during an interim period, were to be banned on 9 May 2014. These were mainly synthetic cannabis products containing ingredients such as AB-FUBINACA, PB-22 (QUPIC), 5F-PB-22, SGT-24 (CUMYL-PINACA), CP 55,244, 4-F-AM-2201, 4-Cl-AM-2201, 5F-ADBICA and AB-005. There was also one cannabinoid pill containing SGT-42 (CUMYL-THPINACA), and several "party pill" products containing mixtures of ingredients such as caffeine, hordenine, synephrine and kava. [19] No "legal high" products will be allowed back on sale in New Zealand under the Psychoactive Substances Act until they have been tested in a manner yet to be determined, and found to present a "low risk of harm". This process is expected to take at least 18 months or more. [22] [23] [24] [25] [26] Six of the synthetic cannabis products were ordered to be immediately removed from sale by emergency recall on 1 May 2014, to ensure that users would not be able to stockpile supplies of these products before the general ban took effect on 9 May. [27]

See also

Related Research Articles

A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. Designer drugs include psychoactive substances that have been designated by the European Union as new psychoactive substances (NPS) as well as analogs of performance-enhancing drugs such as designer steroids. Some of these were originally synthesized by academic or industrial researchers in an effort to discover more potent derivatives with fewer side effects, and shorter duration and were later co-opted for recreational use. Other designer drugs were prepared for the first time in clandestine laboratories. Because the efficacy and safety of these substances have not been thoroughly evaluated in animal and human trials, the use of some of these drugs may result in unexpected side effects.

JWH-073 Chemical compound

JWH-073, a synthetic cannabinoid, is an analgesic chemical from the naphthoylindole family that acts as a partial agonist at both the CB1 and CB2 cannabinoid receptors. It is somewhat selective for the CB1 subtype, with affinity at this subtype approximately 5x the affinity at CB2. The abbreviation JWH stands for John W. Huffman, one of the inventors of the compound.

JWH-250 Chemical compound

JWH-250 or (1-pentyl-3-(2-methoxyphenylacetyl)indole) is an analgesic chemical from the phenylacetylindole family that acts as a cannabinoid agonist at both the CB1 and CB2 receptors, with a Ki of 11 nM at CB1 and 33 nM at CB2. Unlike many of the older JWH series compounds, this compound does not have a naphthalene ring, instead occupying this position with a 2'-methoxy-phenylacetyl group, making JWH-250 a representative member of a new class of cannabinoid ligands. Other 2'-substituted analogues such as the methyl, chloro and bromo compounds are also active and somewhat more potent.

Synthetic cannabinoids Designer drugs

Synthetic cannabinoids are a class of designer drug molecules that bind to the same receptors to which cannabinoids in cannabis plants attach. These novel psychoactive substances should not be confounded with synthetic phytocannabinoids or synthetic endocannabinoids from which they are in many aspects distinct.

4-Methylmethylphenidate

threo-4-Methylmethylphenidate (4-MeTMP) is a stimulant drug related to methylphenidate. It is slightly less potent than methylphenidate and has relatively low efficacy at blocking dopamine reuptake despite its high binding affinity, which led to its investigation as a possible substitute drug for treatment of stimulant abuse. On the other hand, several other simple ring-substituted derivatives of threo-methylphenidate such as the 4-fluoro and 3-chloro compounds are more potent than methylphenidate both in efficacy as dopamine reuptake inhibitors and in animal drug discrimination assays.

6-APB Psychoactive drug

6-APB is an empathogenic psychoactive compound of the substituted benzofuran and substituted phenethylamine classes. 6-APB and other compounds are sometimes informally called "Benzofury" in newspaper reports. It is similar in structure to MDA, but differs in that the 3,4-methylenedioxyphenyl ring system has been replaced with a benzofuran ring. 6-APB is also the unsaturated benzofuran derivative of 6-APDB. It may appear as a tan grainy powder. While the drug never became particularly popular, it briefly entered the rave and underground clubbing scene in the UK before its sale and import were banned. It falls under the category of research chemicals, sometimes called "legal highs." Because 6-APB and other substituted benzofurans have not been explicitly outlawed in some countries, they are often technically legal, contributing to their popularity.

25C-NBOMe

25C-NBOMe is a psychedelic drug and derivative of the psychedelic phenethylamine 2C-C. 25C-NBOMe appeared on online vendor sites in 2010 but was not reported in the literature until 2011. It acts as a potent agonist of the 5HT2A receptor, and has been studied in its 11C radiolabelled form as a potential ligand for mapping the distribution of 5-HT2A receptors in the brain, using positron emission tomography (PET).

UR-144

UR-144 (TMCP-018, KM-X1, MN-001, YX-17) is a drug invented by Abbott Laboratories, that acts as a selective full agonist of the peripheral cannabinoid receptor CB2, but with much lower affinity for the psychoactive CB1 receptor.

MAM-2201

MAM-2201 is a drug that presumably acts as a potent agonist for the cannabinoid receptors. It had never previously been reported in the scientific or patent literature, and was first identified by laboratories in the Netherlands and Germany in June 2011 as an ingredient in synthetic cannabis smoking blends. Like RCS-4 and AB-001, MAM-2201 thus appears to be a novel compound invented by "research chemical" suppliers specifically for grey-market recreational use. Structurally, MAM-2201 is a hybrid of two known cannabinoid compounds JWH-122 and AM-2201, both of which had previously been used as active ingredients in synthetic cannabis blends before being banned in many countries.

XLR-11

XLR-11 (5"-fluoro-UR-144 or 5F-UR-144) is a drug that acts as a potent agonist for the cannabinoid receptors CB1 and CB2 with EC50 values of 98 nM and 83 nM, respectively. It is a 3-(tetramethylcyclopropylmethanoyl)indole derivative related to compounds such as UR-144, A-796,260 and A-834,735, but it is not specifically listed in the patent or scientific literature alongside these other similar compounds, and appears to have not previously been made by Abbott Laboratories, despite falling within the claims of patent WO 2006/069196. XLR-11 was found to produce rapid, short-lived hypothermic effects in rats at doses of 3 mg/kg and 10 mg/kg, suggesting that it is of comparable potency to APICA and STS-135.

EAM-2201

EAM-2201 is a drug that presumably acts as a potent agonist for the cannabinoid receptors. It had never previously been reported in the scientific or patent literature, and was first identified by laboratories in Japan in July 2012 as an ingredient in synthetic cannabis smoking blends Like the closely related MAM-2201 which had been first reported around a year earlier, EAM-2201 thus appears to be another novel compound invented by designer drug suppliers specifically for recreational use. Structurally, EAM-2201 is a hybrid of two known cannabinoid compounds JWH-210 and AM-2201, both of which had previously been used as active ingredients in synthetic cannabis blends before being banned in many countries.

PB-22

PB-22 is a designer drug offered by online vendors as a cannabimimetic agent, and detected being sold in synthetic cannabis products in Japan in 2013. PB-22 represents a structurally unique synthetic cannabinoid chemotype, since it contains an ester linker at the indole 3-position, rather than the precedented ketone of JWH-018 and its analogs, or the amide of APICA and its analogs.

25N-NBOMe Chemical compound

25N-NBOMe is a derivative of the hallucinogen 2C-N. The pharmacological properties of 25N-NBOMe have not been described in the scientific literature, but it is believed to act in a similar manner to related compounds such as 25I-NBOMe and 25C-NBOMe, which are potent agonists at the 5HT2A receptor. 25N-NBOMe has been sold as a street drug and has only been described in the literature in terms of identification by forensic analysis.

5F-AMB

5F-AMB (also known as 5F-MMB-PINACA and 5F-AMB-PINACA) is an indazole-based synthetic cannabinoid from the indazole-3-carboxamide family, which has been used as an active ingredient in synthetic cannabis products. It was first identified in Japan in early 2014. Although only very little pharmacological information about 5F-AMB itself exists, its 4-cyanobutyl analogue (instead of 5-fluoropentyl) has been reported to be a potent agonist for the CB1 receptor (KI = 0.7 nM).

Mepirapim

MEPIRAPIM is an indole-based cannabinoid which differs from JWH-018 by having a 4-methylpiperazine group in place of the naphthyl group and has been used as an active ingredient in synthetic cannabis products. It was first identified in Japan in 2013, alongside FUBIMINA.

HDEP-28

HDEP-28 or ethylnaphthidate is a piperidine based stimulant drug, closely related to ethylphenidate, but with the benzene ring replaced by naphthalene. It is even more closely related to HDMP-28, which acts as a potent serotonin–norepinephrine–dopamine reuptake inhibitor with several times the potency of methylphenidate and a short duration of action.

NNE1

NNE1 (also known as NNEI, MN-24 and AM-6527) is an indole-based synthetic cannabinoid, representing a molecular hybrid of APICA and JWH-018 that is an agonist for the cannabinoid receptors, with Ki values of 60.09 nM at CB1 and 45.298 nM at CB2 and EC50 values of 9.481 nM at CB1 and 1.008 nM at CB2. It was invented by Abbott and has a CB1 receptor pEC50 of 8.9 with around 80x selectivity over the related CB2 receptor. It is suspected that metabolic hydrolysis of the amide group of NNE1 may release 1-naphthylamine, a known carcinogen, given the known metabolic liberation (and presence as an impurity) of amantadine in the related compound APINACA, and NNE1 was banned in New Zealand in 2012 as a temporary class drug to stop it being used as an ingredient in then-legal synthetic cannabis products. NNE1 was subsequently found to be responsible for the death of a man in Japan in 2014.

5F-JWH-398

5F-JWH-398 is a recreational designer drug which is classed as a synthetic cannabinoid. It is from the naphthoylindole family, and produces cannabis-like effects. It was legally sold in New Zealand from 2012-2014 under the psychoactive substances scheme but was discontinued in May 2014 following the end of the interim approval period under the Psychoactive Substances Act 2013. Subsequently it has appeared on the illicit market around the world and was identified in Germany in May 2019.

References

  1. ↑ "First 'legal high' to be banned under new powers". UK Home Office. 28 March 2012. Retrieved 28 March 2012.
  2. ↑ "Legal high drug 'mexxy' banned under new government powers". The Guardian. London. 28 March 2012.
  3. ↑ "Drug misuse and dependency - GOV.UK". homeoffice.gov.uk. Retrieved 30 November 2017.
  4. ↑ "MXE is now a Class B drug" . Retrieved 5 July 2013.
  5. ↑ "ISCD ~ Independent Scientific Committee on Drugs". drugscience.org.uk. Archived from the original on 18 June 2013.
  6. ↑ "Temporary class drug order report on 5-6APB and NBOMe compounds". UK Home Office. 4 June 2013. Retrieved 13 June 2013.
  7. ↑ "'NBOMe' and 'Benzofury' banned". UK Home Office. 4 June 2013. Retrieved 13 June 2013.
  8. ↑ "Methylphenidate-based NPS: A review of the evidence of use and harm. Advisory Council on the Misuse of Drugs, 31 March 2015" (PDF). Retrieved 30 November 2017.
  9. ↑ "Letter to Mike Penning on methylphenidate-based novel psychoactive substances". Advisory Council on the Misuse of Drugs. 25 June 2015. Retrieved 25 June 2015.
  10. ↑ "Ministerial response to the Advisory Council on the Misuse of Drugs about 2 new methylphenidate-based substances". Home Office. 25 June 2015. Retrieved 25 June 2015.
  11. ↑ Advisory Council on the Misuse of Drugs (25 November 2015). "Methiopropamine (MPA): A review of the evidence of use and harm" (PDF). UK Home Office. Retrieved 27 November 2015.
  12. ↑ "The Misuse of Drugs Act 1971 (Temporary Class Drug) (No. 3) Order 2015". UK Government. 23 November 2015.
  13. ↑ "Temporary Class Drug Notices" . Retrieved 30 November 2017.
  14. ↑ "New Zealand Gazette". dia.govt.nz. Retrieved 30 November 2017.
  15. ↑ New Zealand Government Gazette, Notice Number 7444, 15 November 2012
  16. ↑ "Dunne bans substance found in K2 testing - Scoop News". scoop.co.nz. Retrieved 30 November 2017.
  17. ↑ "New Zealand Gazette". dia.govt.nz. Retrieved 30 November 2017.
  18. ↑ "Dunne bans further two substances found in K2 - Scoop News". scoop.co.nz. Retrieved 30 November 2017.
  19. 1 2 "Home - Psychoactive Substances Regulatory Authority". health.govt.nz. Retrieved 30 November 2017.
  20. ↑ "The Risk Assessment Score Table. New Zealand Ministry of Health, 27 September 2013" (PDF). Archived from the original (PDF) on 8 January 2014. Retrieved 30 November 2017.
  21. ↑ @nickjonesnzer, Nicholas Jones Political reporter, NZ Herald nicholas jones@nzherald co nz (26 January 2014). "Legal highs pulled off the shelves". The New Zealand Herald. Retrieved 30 November 2017.
  22. ↑ "Legal highs to be banned". Stuff. 28 April 2014. Retrieved 30 November 2017.
  23. ↑ "Use our legal high law, says Labour". Stuff. 27 April 2014. Retrieved 30 November 2017.
  24. ↑ @isaac_davison, Isaac Davison Political reporter, NZ Herald isaac davison@nzherald co nz (27 April 2014). "Government to ban all legal highs within two weeks". The New Zealand Herald. Retrieved 30 November 2017.
  25. ↑ Rychert M, Wilkins C. Legal high industry business and lobbying strategies under a legal market for new psychoactive substances (NPS, 'legal highs') in New Zealand. Int J Drug Policy. 2016 Nov;37:90-97. doi: 10.1016/j.drugpo.2016.08.011. PMID   27639994
  26. ↑ Rychert M, Wilkins C, Witten K. Issues with monitoring the safety of psychoactive products under a legal regulated market for new psychoactive substances ('legal highs') in New Zealand. Drug Alcohol Rev. 2017 Feb 23. doi: 10.1111/dar.12507. PMID   28229493
  27. ↑ @nickjonesnzer, Nicholas Jones Political reporter, NZ Herald nicholas jones@nzherald co nz (1 May 2014). "Legal highs pulled from shelves". The New Zealand Herald. Retrieved 30 November 2017.
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