Pre-workout meth anyone?
Amphetamine analogue in pre-workout supplement Craze?
If you use the pre-workout supplement Craze, made by the American company Driven Sports, you may have noticed that it's no longer available through online stores. Labs have found an amphetamine analogue in Craze that has never been tested on humans, and that's being used as a recreational drug.
The downfall of Craze was heralded by research in laboratories at Harvard Medical School, the US FDA, the RIVM in the Netherlands and the South Korean National Forensic Service. The results of this research have appeared in two publications. [Forensic Toxicol. 2013, DOI: 10.1007/ s11419-013-0205-6.] [Drug Testing and Analysis. Article first published online: 14 Oct 2013. DOI: 10.1002/dta.1578.]
In the second of the articles mentioned above you can read about how reports from the WADA led to the joint study. According to the WADA, doping hunters had found methamphetamine analogues in athletes' urine that had never shown up in previous doping tests.
Because athletes who had been caught said they had used the pre-workout supplement Craze, researchers bought a few pots of the stuff and did a content analysis in the lab.
The label on the bottle states that Craze contains several analogues of beta phenylethylamine. Beta-Phenylethylamine [structural formula below] is a mild stimulant found naturally in chocolate and other foods, and also used in supplements. The same is true for some analogues of beta-phenylethylamine. But the Craze label also lists N,N-diethyl-phenylethylamine. And that's what triggered the researchers' suspicion.
Some underground supplement makers are masters at adding obscure steroids or amphetamines to their products and then listing a bastardised form on the label. Might N,N-diethyl-phenylethylamine in reality actually be N,alpha-di-ethylphenylethylamine? If that's the case - then Craze did indeed contain an amphetamine analogue.
Beta-Phenylethylamine is not very active. But if you attach a methyl group in the right place, you can boost the activity. The new methyl group protects the new substance from enzymes. In fact you've transformed the innocent beta-phenylethylamine into the hard drug amphetamine. Go one step further and attach not one but two methyl groups to beta-phenylethylamine, then you get the even stronger – and more dangerous – methamphetamine. That's a hard drug too.
The substance in Craze might just been an analogue of methamphetamine, the researchers thought. One that's created not by attaching two methyl groups, but two ethyl groups to beta-phenylethylamine. The name of the stuff is N,alpha-di-ethylphenylethylamine. And that's the compound the researchers found in Craze.
N,Alpha-Di-Ethylphenylethylamine was patented in 1988 by Knoll Pharmaceuticals. [WIPO Publication No. WO88/02254.] Knoll considered marketing N,alpha-di-ethylphenylethylamine as a stimulant that also suppresses pain sensation but in the end refrained from doing so. At Knoll they probably realised that it wouldn’t take long for N,alpha-di-ethylphenylethylamine to be labelled a hard drug.
The patent by the way only describes animal studies; no research was done on humans. On the basis of these animal studies, Knoll calculated that effective human doses of N,alpha-di-ethylphenylethylamine lay between 10 and 150 mg. The dose that Knoll regarded as most suitable was 30 mg. And surprise, surprise – when the researchers measured the concentration of N,alpha-di-ethylphenylethylamine in a couple of pots of Craze, it turned out to be between 21 and 35 mg per recommended dose. Just too much of a coincidence, they think.
When the researchers started to look for more information on N,alpha-di-ethylphenylethylamine, they stumbled on a publication from 2011. [Forensic Toxicol. 2013, 31, 54.] In this fellow researchers in South Korea described how they had found N,alpha-di-ethylphenylethylamine in a large consignment of raw materials that the police had confiscated.
The Koreans then bought a couple of pots of Craze and analysed them too. And yes, they too found N,alpha-di-ethylphenylethylamine. [Forensic Toxicol. 2013, DOI: 10.1007/ s11419-013-0205-6.]
Driven Sports, the manufacturer of Craze, has announced that the substance everyone is getting so worked up about occurs naturally in the Dendrobium orchid, and Craze contains extracts of this. [drivensports.com 2013.10.15]
Unlikely, say the researchers.
Amphetamine analogue in pre-workout supplement Craze?
If you use the pre-workout supplement Craze, made by the American company Driven Sports, you may have noticed that it's no longer available through online stores. Labs have found an amphetamine analogue in Craze that has never been tested on humans, and that's being used as a recreational drug.
The downfall of Craze was heralded by research in laboratories at Harvard Medical School, the US FDA, the RIVM in the Netherlands and the South Korean National Forensic Service. The results of this research have appeared in two publications. [Forensic Toxicol. 2013, DOI: 10.1007/ s11419-013-0205-6.] [Drug Testing and Analysis. Article first published online: 14 Oct 2013. DOI: 10.1002/dta.1578.]
In the second of the articles mentioned above you can read about how reports from the WADA led to the joint study. According to the WADA, doping hunters had found methamphetamine analogues in athletes' urine that had never shown up in previous doping tests.
Because athletes who had been caught said they had used the pre-workout supplement Craze, researchers bought a few pots of the stuff and did a content analysis in the lab.
The label on the bottle states that Craze contains several analogues of beta phenylethylamine. Beta-Phenylethylamine [structural formula below] is a mild stimulant found naturally in chocolate and other foods, and also used in supplements. The same is true for some analogues of beta-phenylethylamine. But the Craze label also lists N,N-diethyl-phenylethylamine. And that's what triggered the researchers' suspicion.
Some underground supplement makers are masters at adding obscure steroids or amphetamines to their products and then listing a bastardised form on the label. Might N,N-diethyl-phenylethylamine in reality actually be N,alpha-di-ethylphenylethylamine? If that's the case - then Craze did indeed contain an amphetamine analogue.
Beta-Phenylethylamine is not very active. But if you attach a methyl group in the right place, you can boost the activity. The new methyl group protects the new substance from enzymes. In fact you've transformed the innocent beta-phenylethylamine into the hard drug amphetamine. Go one step further and attach not one but two methyl groups to beta-phenylethylamine, then you get the even stronger – and more dangerous – methamphetamine. That's a hard drug too.
The substance in Craze might just been an analogue of methamphetamine, the researchers thought. One that's created not by attaching two methyl groups, but two ethyl groups to beta-phenylethylamine. The name of the stuff is N,alpha-di-ethylphenylethylamine. And that's the compound the researchers found in Craze.
N,Alpha-Di-Ethylphenylethylamine was patented in 1988 by Knoll Pharmaceuticals. [WIPO Publication No. WO88/02254.] Knoll considered marketing N,alpha-di-ethylphenylethylamine as a stimulant that also suppresses pain sensation but in the end refrained from doing so. At Knoll they probably realised that it wouldn’t take long for N,alpha-di-ethylphenylethylamine to be labelled a hard drug.
The patent by the way only describes animal studies; no research was done on humans. On the basis of these animal studies, Knoll calculated that effective human doses of N,alpha-di-ethylphenylethylamine lay between 10 and 150 mg. The dose that Knoll regarded as most suitable was 30 mg. And surprise, surprise – when the researchers measured the concentration of N,alpha-di-ethylphenylethylamine in a couple of pots of Craze, it turned out to be between 21 and 35 mg per recommended dose. Just too much of a coincidence, they think.
When the researchers started to look for more information on N,alpha-di-ethylphenylethylamine, they stumbled on a publication from 2011. [Forensic Toxicol. 2013, 31, 54.] In this fellow researchers in South Korea described how they had found N,alpha-di-ethylphenylethylamine in a large consignment of raw materials that the police had confiscated.
The Koreans then bought a couple of pots of Craze and analysed them too. And yes, they too found N,alpha-di-ethylphenylethylamine. [Forensic Toxicol. 2013, DOI: 10.1007/ s11419-013-0205-6.]
Driven Sports, the manufacturer of Craze, has announced that the substance everyone is getting so worked up about occurs naturally in the Dendrobium orchid, and Craze contains extracts of this. [drivensports.com 2013.10.15]
Unlikely, say the researchers.
