Drug information Analysis of 17 RC products reveals a very concerning trend

Hot off the heels of warnings from both Drugs-Forum and the Association of Police Officers in Scotland (ACPOS) regarding NRG-1, an excellent study published online in the British Medical Journal has revealed the extent of what is becoming an increasingly concerning market trend. A sample analysis of 17 research chemical products by chemists at John Moores University (Liverpool, UK) revealed that in most cases the active ingredients were both misrepresented and illegal to possess.

Of the 10 NRG-1 products tested, only one was found to contain naphthylpyrovalerone (Naphyrone), the most commonly proposed active ingredient for this brand. Concerningly the misrepresented batches of NRG-1 contained a range of beta-ketones that are class B controlled substances in the UK, including mephedrone, butylone, MDPV and 4-fluoromethcathinone (flephedrone). Only two of the 10 batches were found to be legal to possess; one truly containing Naphyrone, and another with no actives detected at all (cutely described as 'inorganic composition', which quite possibly means good old table salt).

Results for four tested batches of NRG-2 proved more consistent. In two cases it was found to contain mephedrone (mixed with benzocaine in one), while 4-methyl-N-ethylcathinone was found in the other two. The latter is a relatively novel research chemical, but is covered by UK cathinones law. All tested batches of NRG-2 were therefore found to be controlled substances.

Concerningly this trend extends beyond the branded products. Two samples sold as MDAI were found to contain mephedrone and an inactive inorganic compound respectively. The one batch of dimethocaine was tested and actually found to be a mixture of caffeine and lidocaine.

The conclusions are therefore quite striking. Only one of 17 samples was found to be as represented and legal to possess. Some of the batches of NRG-1 tested corroborate earlier reports on multiple NRG-1 products containing MDPV.

This suggests a catastrophic decline in research chemical market quality. The rampant misrepresentation of products extends beyond the NRG-x group, suggesting that the unregulated market has reached such a point that a majority of vendors either do not know or do not care what they are selling. The level of misrepresentation appears to be so great that it is impossible for the typical purchaser to know exactly what they might be purchasing. The repercussions of this may be serious, as it puts both the health and liberty of consumers at risk.

With growing public awareness of these misrepresented products, it is only a matter of time until legal action is taken against those distributing these controlled substances. Unfortunately the UK authorities have previously used vendor sales records as grounds for obtaining warrants to search the homes of their customers for controlled substances. It is therefore possible that a crackdown on vendors may be followed by a crackdown on thei customers, as was the case in Operation Ismene. Ignorance is no defence in the eyes of the law, so simply not knowing that the product was misrepresented and illegal to possess may not hold up as a defense in court.

The sad truth is the research chemical market is in a serious mess. The most sensible approach has to be boycotting any research chemical supplier that sells any of their products under ambiguous names such as these. These vendors simply cannot and should not be trusted.

Below is the report from the BMJ. Drugs-Forum will be attempting to contact this research group in due course to flesh out the details of their analysis.

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E-letter editorial response to 'What should be done about mephedrone?'
Editorial response published online 16th June 2010
Original article published in the British Medical Journal 340; c1605 (2010)

S.D. Brandt, H.R. Sumnall, F. Measham, and J. Cole
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK

Mephedrone and other cathinones have been brought under control of the Misuse of Drugs Act 1971 in Class B, Schedule I by way of a generic definition. As a consequence of this recent legislative change, cathinones such as mephedrone, MDPV (3,4-methylenedioxypyrovalerone) and butylone should have been removed from the product range offered on the internet. Since then, a number of alternative products were introduced and promoted such as NRG-1 (Energy 1), NRG-2, DMC (dimethocaine), and MDAI (5,6- methylenedioxy-2-aminoindane). One of the most prominently discussed of these second generation products, at least in the UK media, is NRG-1, also advertised as naphyrone. The structural representation provided by online sellers is naphthylpyrovalerone (O-2482) which represents a group of compounds previously published in the medicinal chemistry literature as a potential candidate for the treatment of cocaine abuse [1].

The immediate introduction of alternative ‘legal highs’ such as NRG-1 raised questions about the identity of these novel derivatives which meant that an initial assessment was warranted. A total number of seventeen products were purchased online from twelve UK-based websites over a period of six weeks following the ban on mephedrone. The results of the chemical characterisation is summarised in Table 1. Product compositions varied dramatically and the majority of products appeared to represent a range of cathinone derivatives which were recently banned.

Earlier studies exploring the motivation for use of ‘legal highs’ [2] suggested that the consumer’s quest for legal psychoactive drugs reflected their perception that these substitutes were more likely to be of higher purity than street drugs, carry a lower risk of physical harm, and not face the possibility of criminal sanctions associated with the consumption of drugs controlled under the Misuse of Drugs Act.

The data reported here provides an initial snapshot of the post-ban situation and suggests that both consumers and online retailers (unlike manufacturers and wholesalers) are, most likely unaware that they are purchasing the recently controlled cathinones rather than ‘new’ psychoactive substances, and are therefore unaware of the crime and health risks they may be taking. Without a firm body of literature investigating the health effects of these drugs, users are likely to generate and disseminate an experientially derived and possibly flawed form of harm reduction [3]. Observation of user-orientated online discussion forums suggests that this is already occurring.

References:

[1] Meltzer PC, Butler D, Deschamps JR, Madras BK. 1-(4-methylphenyl) -2-pyrrolidin-1-yl-pentan-1-one (pyrovalerone) analogues: A promising class of monoamine uptake inhibitors. J Med Chem 2006;49:1420-1432.

[2] Measham F, Moore K, Newcombe R, Welch Z. Tweaking, Bombing, Dabbing and Stockpiling: The emergence of mephedrone and the perversity of prohibition. Drugs Alcohol Today 2010;10:14-21.

[3] Gamma A, Jerome L, Liechti ME, Sumnall HR. Is ecstasy perceived to be safe? A critical survey. Drug Alcohol Depend 2005;77:185-193.

Competing interests: None declared

Column 1	Column 2	Column 3	Column 4	Column 5	Column 6	Column 7
Sample #	Brand Name	Proposed Identity	Identified Substances	As represented?	Psychoactive?	Legal to Possess (UK)?
1	NRG-1	Naphyrone	Butylone + MDPV	No	Yes	No
2	NRG-1	Naphyrone	Flephedrone (4-FMC)	No	Yes	No
3	NRG-1	Naphyrone	Flephedrone (4-FMC) + MDPV	No	Yes	No
4	NRG-2	None	4-methyl-N-ethylcathinone	N/A	Yes	No
5	NRG-1	Naphyrone	Flephedrone (4-FMC) + MDPV	No	Yes	No
6	NRG-1	Naphyrone	Caffeine + Mephedrone (trace)	No	Yes	No
7	NRG-1	Naphyrone	Naphyrone	Yes	Yes	Yes
8	NRG-1	Naphyrone	Butylone + MDPV	No	Yes	No
9	MDAI	MDAI	Inorganic Composition	No	No	Yes
10	NRG-1	Naphyrone	Mephedrone	No	Yes	No
11	NRG-1	Naphyrone	Inorganic Composition	No	No	Yes
12	NRG-2	None	Mephedrone + Benzocaine	N/A	Yes	No
13	NRG-1	Naphyrone	Mephedrone	No	Yes	No
14	NRG-2	None	Mephedrone	N/A	Yes	No
15	DMC	Dimethocaine	Caffeine + Lidocaine	No	No	Yes
16	MDAI	MDAI	Mephedrone	No	Yes	No
17	NRG-2	None	4-methyl-N-ethylcathinone	N/A	Yes	No

 

Admittedly caffeine is a psychoactive drug, but at the doses recommended for these drugs it'd amount to little more than a strong cup of coffee. It certainly isn't the sort of psychoactive effect that consumers purchasing a 'mephedrone replacement' are likely to be seeking/expecting.

 

Another supportive analysis of products has now been published. 18 products were purchased before the change to UK law on cathinones in April 2010, and 6 further products were purchased after the law change. Misrepresentation was once again found to be rife with products sold under brand names. The situation seems to have become far worse since the law amendment, with only one of the six products purchased after April 2010 found to be as represented. Five of six post-law change products contained class B controlled substances.

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Quarterly Journal of Medicine (QJM), Available online 30th July 2010

J. Ramsey (1), P.I. Dargan (2), M. Smyllie (3), S. Davies (3), J. Button (3), D.W. Holt (3) and D.M. Wood (2)

(1) TICTAC Communications Ltd, St George's, University of London, UK
(2) Clinical Toxicology Service, Guy's and St. Thomas’ NHS Foundation Trust and King's Health Partners, UK
(3) Forensic Toxicology Service, Analytical Unit, St George's, University of London, UK

Background: Recreational drug use in the UK is common; sources of recreational drugs are changing, with increasing purchase of legal highs from the Internet. Previous studies have shown that there is not consistency of active ingredient(s) in legal highs purchased from the Internet.

Aim: The aim of this study was to determine the impact of the 16 April 2010 change to the Misuse of Drugs Act (1971) on the content of ‘legal highs’ purchased over the Internet and supplied within the UK.

Methods: Legal highs were purchased from a number of different Internet suppliers and the active ingredients determined by analysis undertaken within a Home Office approved and licensed laboratory set in a UK academic institution. The active ingredient(s) detected on screening were then compared to the UK legislation in force at the time of purchase to determine whether each individual ‘legal’ high was in fact legal or not.

Results: All 18 products purchased prior to the change in the UK legislation contained active ingredients that were legal under the Misuse of Drugs Act (1971) in force at that time. Six products were purchased and analysed after the changes to the UK Misuse of Drugs Act (1971) on the 16 April 2010. Five of the products contained information, either on the Internet site or the packaging, stating that the product contained legal substances; the final product did not specify the active ingredient and so purchasers would be unable to determine if this was truly a legal product. Five of the six products contained an active ingredient that is a Class B drug under the Misuse of Drugs Act (1971); the other product contained an unlicensed medicine not controlled under the Misuse of Drugs Act (1971).

Conclusions: We have shown in this study that some drugs sold as ‘legal’ highs contain drugs that are controlled under the Misuse of Drugs Act (1971). Under current UK legislation, individuals purchasing legal highs that contained controlled drugs would be subject to the same penalties as if they had knowingly purchased a controlled drug. Dissemination of information on the harm associated with the use of legal highs should also inform individuals that they may be purchasing controlled substances and the potential legal consequences of this.

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Products purchased prior to April 2010 law change on cathinones:

Column 1	Column 2	Column 3	Column 4	Column 5
Product	Proposed Identity	Identified Substances	As represented?	Legal to possess before April 2010* (UK)?
Methylone	Methylone (bk-MDMA)	Methylone (bk-MDMA)	Yes	Yes
Butylone	Butylone (bk-MBDB)	Butylone (bk-MBDB)	Yes	Yes
NRG-1	Naphthylpyrovalerone (Naphyrone)	MDPV + Butylone	No	Yes
MDAI	MDAI	MDAI	Yes	Yes
Ultimate Sextacy	No active ingredients listed	MDPV	No	Yes
Vanilla Sky	No active ingredients listed	MDPV	No	Yes
Hyper X Ultra	'Ketones'	MDPV	Ambiguous	Yes
Dynamite NRG Ultra	'Ketones'	MDPV	Ambiguous	Yes
Head Rush Ultra	'Ketones'	Butylone (bk-MBDB)	Ambiguous	Yes
Doves Original	'Ketones'	Mephedrone + Butylone	Ambiguous	Yes
Doves Red	No active ingredients listed	MDPV	No	Yes
Doves Ultra	No active ingredients listed	Butylone (bk-MBDB)	No	Yes
Rocket Fuel Ultra	'Ketones'	Butylone (bk-MBDB)	Ambiguous	Yes
Speed Freak Ultra	'Ketones'	MDPV	Ambiguous	Yes
Diablos XXX Extreme	'Ketones'	Butylone (bk-MBDB)	Ambiguous	Yes
Space Trips Ultra	'Ketones'	MDPV	Ambiguous	Yes
Exotix Ultra	'Ketones'	MDPV + Butylone	Ambiguous	Yes
Xtacy Ultra	'Ketones'	Butylone (bk-MBDB)	Ambiguous	Yes

* NOTE: All products listed above other than MDAI are now class B controlled substances in the UK as a result of the law change on cathinones in April 2010.


Products purchased after April 2010 law change on cathinones:

Column 1	Column 2	Column 3	Column 4	Column 5
Product	Proposed Identity	Identified Substances	As represented?	Legal to possess after April 2010 (UK)?
NRG-1	Naphthylpyrovalerone (Naphyrone)	Mephedrone	No	No
NRG-2	Undeclared	Flephedrone (4-FMC)	No	No
Dimethocaine	Dimethocaine	Dimethocaine	Yes	Yes
D2PM	Diphenylprolinol	3-fluoromethcathinone (3-FMC)	No	No
MDAI	MDAI	Methylone (bk-MDMA)	No	No
Jolly Green Granules	Prolintane analogue	Mephedrone	No	No