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New drugs coming our way - what are they and how do we detect them?

Coolio

Greenlighter
Joined
Feb 29, 2004
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Leslie A King

UK Focal Point on Drugs

EMCDDA Conference: Identifying Europe’s information needs for effective drug policy, Lisbon,
6-8 May 2009

The political-legal background of EU initiatives

* ‘Joint Action’ on New Synthetic Drugs (1997)
* The Early Warning System (EWS)
* Council Decision 2005/387/JHA on the information exchange, risk assessment and control of new psychoactive substances
* The ‘Phenethylamine/tryptamine period’
* Recent developments






3

‘Joint Action’ on New Synthetic Drugs (1997-2005)

* Focus on substances (NSD) not already listed in UN1971 Convention, but with similar potential for harm as psychotropic drugs already in Schedules I or II



* New means newly-abused – not necessarily newly-discovered



* Before 1997 these substances were often known as designer drugs – e.g. fentanyl and α-prodine derivatives






4

The Early Warning System (EWS)

Three stages:

* Information collection/dissemination in MS
* Risk assessment by EMCDDA scientific committee
* Control in EU






5

The 2005 Council Decision:
New Psychoactive Substances (NPAS)



* Extends scope to include both psychotropics (i.e. UN1971 candidates) and narcotics (i.e. UN1961 candidates)



* Not restricted to synthetic materials – plant products also covered (e.g. Salvia divinorum)



* Allows information collection (but not risk assessment) on misuse of medicinal products and their precursors






6

The ‘Phenethylamine/tryptamine period’

* PIHKAL and TIHKAL
* Search for the ‘new ecstasy’
* Tablets > powders > capsules
* Risk assessments (1999 – 2004):

MBDB, 4-MTA, PMMA, TMA-2, 2C-T-2, 2C-T-7, 2C-I

* By 2004 over 20 illicit phenethylamine derivatives discovered in EU
* Tryptamines less common – all hallucinogens






7

Recent developments

* ‘Designer drugs’ now often called ‘legal highs’
* Phenethylamines/tryptamines increasingly uncommon
* Wide diversity of new substances
* Substituted piperazines
* Substituted cathinones
* Misused medicinal products
* Plant products
* Miscellaneous synthetic drugs
* Spice






8

Substituted piperazines

* By 2006, 1(3-chlorophenyl)piperazine (mCPP) found in 10% of ‘ecstasy’ tablets in EU. More seizures, larger quantities than any other substance since 1997
* 2007: EMCDDA risk assessment on 1-benzylpiperazine (BZP) leads to expected EU-wide control in 2009
* Others include TFMPP, DBZP, FPP
* Critical review of six piperazine derivatives by ECDD/WHO in 2009



BZP

mCPP





9

Substituted cathinones

* Over 20 illicit substances derived from cathinone (e.g. mephedrone, methylone, MDPV)
* Available from websites and shops
* They are β-keto analogues of phenethylamines
* Mostly CNS stimulants



Cathinone





10

Misused medicinal products

* Dextromethorphan (DMX)
* Glaucine
* Benzydamine
* Phenazepam






11

Plant products

* Salvia divinorum (Mexican Sage) - salvinorin A



* Mitragyna speciosa (Kratom) - mitragynine



* Piper methysticum (Kava) - kavalactones



* Argyreia nervosa (Hawaiian Baby Woodrose) - lysergamide






12

Miscellaneous synthetic drugs

* Indans, tetralines etc. - aryl-variants on the phenethylamine theme



* Difuranyl-phenethylamines (2CB-Fly and Bromodragonfly)



* Fluorotropacocaine – the first designer drug based on cocaine



* Many other synthetic psychoactive substances are being sold via websites, but misuse remains low, e.g. the phencyclidine derivative 4-Meo-PCP, the pipradrol derivative dipenylpyrrolidinylmethanol (D2PM), p-fluoroamphetamine, etc.




Bromodragonfly





13

Spice Gold smoking mixture


* Marketed since ~ 2006; imported from China
* Contains unidentified herbal matter
* The claimed plant constituents are innocuous
* About €20 for 3g
* Produces a ‘cannabis-like’ effect
* Related products: Yucatan Fire, Spice Diamond etc.






14

‘Spice’ – recent developments

* December 2008: Analysis by THC Pharma, Germany showed Spice contains JWH-018 and other synthetic cannabinoid receptor agonists
* January 2009: Germany controls JWH-018 and several CP compounds under narcotic laws. Similar action by Austria using medicines legislation
* February 2009: France controls 5 synthetic cannabinoids under narcotic laws
* May 2009: Controls planned in further MS






15

Synthetic cannabinoid agonists

* Analogues of Δ9-THC (e.g. HU-210, Nabilone)



* Cyclohexylphenols (Pfizer CP-compounds)



* Naphthoylindoles, naphthoylpyrroles (JWH compounds)



* Others (fatty acid amides?, etc.)






16

Δ9-THC

HU-210

CP 47,497

JWH-018

Δ9-THC and three synthetic cannabinoids





17

Detecting new psychoactive substances

Problem areas:

* Pure reference materials and analytical data are often not available in the early stages
* Not all forensic/toxicological laboratories in the EU have the means to identify new substances - the EWS often relies on those with NMR spectroscopy
* Examining non-scheduled drugs is not a priority for forensic science organisations in some countries
* Some substances may be active at doses below 1mg; detection in body fluids if not in dosage units may be challenging






18

Can new substances be anticipated?

* The Early Warning System is reactive



* But almost all new psychoactive substances were previously described in the scientific literature



* The Internet may provide information on new substances:
o drug ‘chat rooms’
o purchases from websites selling ‘legal highs’



* We could use this knowledge and devise a set of rules based on previous experience






19

A rule-based system for prediction?

* Synthetic drugs will continue to dominate – herbal products will remain uncommon
* Precursor chemicals or essential reagents should be commercially available or readily synthesised and not controlled
* The method of synthesis should be straightforward
* The end-product should be either a stimulant or have MDMA-like properties, but not be a synthetic hallucinogen
* The end-product should be active orally and the required dose should be no more than 100mg
* Further PIHKAL substances are unlikely to appear
* More synthetic cannabinoids can be expected






20

Summary

* A formal mechanism to monitor, assess and control new drugs has been in operation within the EU since 1997
* In that time over 90 new psychoactive substances have been reported
* Most are synthetic compounds; plant/herbal products remain uncommon
* Most have not been widespread and most did not survive for long on the illicit market
* Risk assessments were carried out on 10 substances, of which 7 were recommended for control
* Nearly all presented analytical challenges when first encountered
* For many, little was and still is known about their pharmacology/toxicology
* Nearly all substances had been described in the scientific literature, often many years ago; they are effectively ‘failed’ pharmaceutical agents
* In the early years, most substances were either phenethylamine or tryptamine derivatives
* In the past 5 years there has been a great diversity of chemical structures, although most are stimulants, or are ‘MDMA-like’ or, less-commonly, hallucinogens
* Rather than be reactive, it should be possible to anticipate new substances given a knowledge of the literature and the use of rules

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Super interesting. It's interesting that benzydamine is listed, because I think it's almost never abused; I think I might have been the first person to even mention it here. Weird.

Someone who worked with entirely novel drugs could make a killing these days.
 
How is it going to do that? None of these drugs are novel, and most have been described in the literature. Even more, they have all been mentioned publicly online dozens to hundreds of times.

Google MDPV or Phenazepam.

Clandestine chemistry rarely involves a chemist that looks for really new, novel stuff. They make what they know will sell, and sell easily.
 
How is it going to do that? None of these drugs are novel, and most have been described in the literature. Even more, they have all been mentioned publicly online dozens to hundreds of times.

Google MDPV or Phenazepam.

Clandestine chemistry rarely involves a chemist that looks for really new, novel stuff. They make what they know will sell, and sell easily.

I was thinking the EU would try to discover new drugs to ban them before anyone ever takes them, but clandestine chemists would find out and make these drugs.
 
Interesting article! 10% of ecstasy pills in europe containing piperazines in 2006, wonder how many it is now? This is a disturbing trend that seems to be happening to a huge extent the world over.

As soon as these substances are identified and banned they will just find new ones to make and sell. I think the day where all psychoactive drugs have been discovered AND outlawed is a long day away, hopefully the world wakes up and goes pro legalization before this happens.
 
thanks for posting. i particularly liked the 'plants of abuse section' salvia, kratom, kava and HBWR? kava?? for real??? no mention of dmt containing plants or mescaline containing cacti. i love how the govt can be so fucking ignorant of reality :)
 
They left out nutmeg. What about caffeine or cough syrup? People will somehow always get drugs whether they are banned or not. They can lock drug users up in prison and they will still get their drugs. It's time to scale back the drug war, not escalate it.

By the way, prescription drugs kill more people than illicit drugs.
 
Cough syrup was mentioned: dextromethorphan

Leaving out DMT and mescaline containing plants makes sense: these aren't new drugs of abuse. They're super old drugs of abuse. So is caffeine.

Nutmeg, on the other hand, while a really old drug of abuse, is very interesting, of course, since it's never really caught on anywhere. I don't know that it really merits inclusion because it's unlikely to ever reach major levels.
 
^
because nutmeg and delriants in general, are dogshit and dysphoric?
 
They are always way behind the trends. Sometimes the media and/or government create drug trends (the so-called 'OxyContin Epidemic' starting in the late 1990's was entirely fictitious: however, the saturated coverage actually created a real OxyContin Epidemic).

Take a good look at Russia for the future; I believe that in a few years you guys in the EU will start becoming more and more familiar with Desomorphine. Given the ease with which OTC Codeine products are purchased, I think somthing similar to the homemade Methamphetamine labs of the US will be mirrored in Eastern/Western Europe in the form of homemade Desomorphine labs, using OTC chemicals. The new Heroin.

January 21, Ufa, "Bashinform", Elena Makushina
The number of cases of Desomorphine consumption grew up in Bashkortostan. Desomorphine is a home-made drug, which components can be freely purchased at drugstores. News-service of Federal Drug Circulation Control Service in RB reports in 2007 drug police has revealed 70 cases of Desomorphine production, storage and sales - four times more than in 2006.

http://eng.bashinform.ru/index.php?id=12434

This drug has attracted recent attention in Russia due to an upsurge in clandestine production, presumably due to its relatively simple synthesis from codeine.[4] It is prepared from α-chlorocodide, which is itself obtained by reacting thionyl chloride with codeine. By catalytic reduction, α-chlorocodide gives dihydrodesoxycodeine, which yields desomorphine on demethylation.

http://en.wikipedia.org/wiki/Desomorphine
 
How does it compare to heroin's high? Specifically euphoria, rush, and duration?
 
I haven't had the pleasure; though from what I gather, in terms of subjective high, Desomorphine, Nicomorphine and Diamorphine are all very similar.

I'd guess that no one could tell the difference if their bags had Deso or Nico instead of Diacetyl.
 
They are always way behind the trends. Sometimes the media and/or government create drug trends (the so-called 'OxyContin Epidemic' starting in the late 1990's was entirely fictitious: however, the saturated coverage actually created a real OxyContin Epidemic).

Take a good look at Russia for the future; I believe that in a few years you guys in the EU will start becoming more and more familiar with Desomorphine. Given the ease with which OTC Codeine products are purchased, I think somthing similar to the homemade Methamphetamine labs of the US will be mirrored in Eastern/Western Europe in the form of homemade Desomorphine labs, using OTC chemicals. The new Heroin.



http://eng.bashinform.ru/index.php?id=12434



http://en.wikipedia.org/wiki/Desomorphine

I wouldn't say that thionyl chloride is an easy and friendly chemical at all......
 
I wouldn't say that thionyl chloride is an easy and friendly chemical at all......

More than one way to skin a cat. Clandestine chemists are some of the most resourceful people around (the ALD-52 reverse engineering to stay within the law was brilliant; thousands of examples of similar ingenuity coming from illicit drug makers).

I'm sure the Wiki author was speaking only of Eastern Europe/Russia, where I'd be willing to bet the farm there are far fewer impedements to acquiring chemical reagants and precursors.
 
Its a pretty comprehensive list, being really into the legal highs scene I must say...They got most of them there.
 
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