The allure of a ‘legal’ drug, undetectable by any workplace test is tempting workers in the mining industry who are chasing that synthetic high, which often rivals the effects of the more common illicit substances. Chemical pathologist Dr Charles Appleton discusses the manufacture and use of synthetic drugs.
Case Study
EMERGING DRUGS OF ABUSE
The manufacture and use of synthetic “recreational” drugs is not new. We tend to think of lysergic acid diethylamide (LSD), first synthesised just prior to the Second World War, when considering “trendy” drugs. But methylenedioxymethamphetamine (MDMA, ecstasy) celebrates its 100th anniversary since first synthesised this year, and its close cousins, methamphetamine and amphetamine have been around for more than 25 years longer than MDMA. Admittedly, these sympathetomimetic agents were initially produced for non-recreational purposes.
The “new” synthetic agents can trace their beginnings back to the work of an organic chemist in the USA, John W Huffman, in 1984. He was developing substances to assist in management of several medical conditions and his group developed over 800 novel chemicals.
However, use of these substances was confined to a relatively small group of users until we saw the emergence of Spice in Europe in 2004. Promoted as a unique blend of natural herbs and spices which together gave the user a natural and legal high, it took German chemists four years to determine that the mix contained two members of the synthetic cannabinoid class of drugs and was anything but natural.
The manufacture and synthesis of new drugs accelerated in the late 2000s as a result of two factors. The supply of MDMA became scarce and expensive as a result of a global crackdown on the main substrate chemical from which it is synthesised.
In addition to this, I believe that the Beijing Olympic Games in 2008 played a significant role. Prior to the games, the Chinese authorities moved to markedly control the industrial pollution which plagued Beijing by moving the industries to new purpose-built chemical factories outside of the city.
These factors – an increased demand for new drugs to fill the gap vacated by MDMA and a capacity to meet the demand – fed the rise in use of new drugs.
Popular use of the synthetic cannabinoids in Australia began in Western Australia and, in particular, in the mining industry. The mine employees were relatively well-paid at that time and there were potentially severe penalties for use of drugs, including cannabis. These new substances were much more expensive than cannabis but they were promoted as being safe, legal and undetectable in any testing. Their popularity was assured.
Once we began testing, we saw detection rates rapidly falling in Western Australia. However, the public and occupation concern had an effect across northern Australia and industries in these regions began testing and then finding workers using the drugs. Because these substances were not detectable using the usual screens, unless an industry considered it to be worth the cost of the additional testing required, any use by workers would be undetected.
Currently, our referrals still come primarily from mines and other safety-sensitive sites, but there are many referrals which come from Departments of Child Safety, as well as bail and parole management organisations.
In most screening laboratories, the detection rate is now low, but this does not mean that the substances have fallen from popularity.
THE CHEMISTRY – MOVE & COUNTERMOVE
The synthetic drug industry is backed by a number of chemical factories which employ very talented chemists. These experts are capable of modifying existing substances or creating new substances de novo to order. The suppliers are capitalising on the “goldstandard” detection laboratory technology.
When a test is performed to detect the presence of a drug, there are in general two approaches which may be taken.
The test developer may create an antibody to the drug such that in the testing situation, if the antibody in the test kit recognises enough of the substance which it has been developed to target, it returns a non-negative result.
However, these test antibodies do not actually recognise any specific drug at all. Instead, they recognise and bind to a molecule which has a corner with a particular shape, size, charge distribution, etc, and if there is enough of that molecular species present (or even several molecular species which bind to the antibody in the test), the test returns a non-negative.
However, the antibody screens are not specific – they will detect any molecule which has that particular structure, regardless of whether it truly belongs to that drug class or not. The reader may be aware that some drug testing kits will return a non-negative result for cannabinoids in workers taking Plaquenil for their arthritis, some will return a non-negative for benzodiazepines in workers taking Zoloft for depression, and so on.
“These new substances were much more expensive than cannabis but they were promoted as being safe, legal and undetectable in any testing. Their popularity was assured.”
So we follow the non-negative screen result with a confirmation test – gas chromatograpy/mass spectrometry (GCMS), liquid chromatography/ mass spectrometry (LCMS), or one of a number of closely related analytical approaches which are viewed as the “gold standard”.
With this approach, the chromatography stage simply separates substances within the sample out from each other prior to their passing through the MS stage. This then matches each substance against a unique molecular fingerprint so as to achieve an absolute identification of the substance.
But herein lies the weakness – if the computer library behind the MS has never encountered the substance before or has never been taught to recognise its fingerprint, the substance passes unrecognised. It is, for all intents and purposes, invisible.
Coming back to the new drugs, if the supplier simply sends the chemist a “blueprint” for a new drug which is a slightly modified form of an old drug, and the chemist supplies that slightly modified drug, then that drug will not be recognisable in the confirmation laboratory. Even if it happens to cross-react with the initial screen to give a non-negative finding (remembering that it will have a structure very similar to previous substances), it cannot be identified and confirmed in the MS confirmation and hence will be labelled a “false positive”.
The European Monitoring Centre for Drugs and Drug Addiction gathers vast amounts of drug-related data from participating European countries. Their annual reports have been documenting accelerating notifications of “new”, never-before reported substances since 2009.
In 2014, the most recent year for which the data is available, there were one to three new drugs notified each week, a total of 102 for the year. Many of these would have been purchased over the internet by individuals or entrepreneurs and imported into Australia, and there is no testing laboratory in the world which can keep up with the identification of this flood of new drugs.
THE QUESTION OF IMPAIRMENT
It is true that no or very limited trials have been performed on subjects using these substances. Indeed in view of the rapidly evolving nature of this area, it is unlikely that any drug which was included in a clinical trial (if it was possible to receive Ethics Committee approval) today would still be in use by the time the trial concluded.
However, all of these drugs are known to interact with the same brain and other body tissue receptors which the more traditional drugs target. Although the specifics of the interaction are likely to differ from that of the traditional substance, the broad effects are expected to be similar. That is, if use of traditional cannabis is likely to produce an impairment of performance, then use of a synthetic form would be expected to have similar effects.
SAFETY OF THESE NEW DRUGS
When a new therapeutic drug is released onto the medical market, it will have at least 10 years of research behind it. It’s therapeutic effects, adverse effects, dosage information, risk of unexpected individual responses, etc, will have been well-investigated. This process will have cost the manufacturer many millions of dollars, and as we have seen with recent tragedies, many drugs which have gone well down this pathway have to be discontinued because of unexpected, occasionally disastrous, adverse effects.
When a new member of these new groups is released, be it a synthetic cannabinoid, a synthetic cathinone (synthetic amphetamine), synthetic hallucinogen (synthetic LSD) or other, the first time that the substance will be tested on any “guinea pig” is when the purchaser rolls an amount into some cigarette paper and lights up.
The safety record of these drugs is frightening.
The medical literature and even the public media carry frequent stories of adverse effects and deaths resulting from the use of these substances. Many of the deaths and injuries are as a result of the user meeting with an “accident” while his mentation was impaired, but there are mounting reports of deaths directly due to use of the substances.
The reader may recall the deaths and hospital admissions associated with use of synthetic cannabinoids in Mackay, Queensland, toward the end of 2014. Last year, the New England Journal of Medicine reported on hundreds of people experiencing serious adverse effects each cluster geographically isolated from others. There were many deaths.
Here in Australia, we have been dismayed by reports of illness and death resulting from these drugs in music festivals in major cities.
I believe that these reports illustrate the current “business model” put into practice by the suppliers. Because these substances are new and untested, rather than release the new drug across the whole of his client base, the supplier will release a limited amount of the new batch in a confined geographical area.
If the feedback coming in to his web page is positive or at least neutral, he will make it generally available to all customers. However, if the user feedback is unfavourable (or if as in these cases, triggers a medical disaster), he will cease distributing that substance and proceed to the next.
DETECTION CHALLENGES
We are seeing a new phenomenon at present. Never before has it been so easy to design and produce new substances which, because of the highly specific nature of confirmation testing, can reliably be expected to be undetectable using “gold standard” testing.
We are seeing an industry which is growing around the design and production of substances which bear some structural and possibly pharmaceutical relationship to known substances, but which are being designed and distributed predominantly with the intention of being undetectable to current testing methods.
The consideration of safety to users appears to play a secondary role or indeed no role at all.
THE LEGAL SITUATION
Finally, how good are the current Australian laws banning these substances?
The “first pass” of federal law (July, 2011) banning these substances failed. Specific members of the group were nominated, and of course, the manufacturers simply released modified forms of these drugs and avoided the legal problem.
Subsequently, state laws banned substances which were chemically related to known banned substances or whose clinical effects were similar to known banned substances. This overcame the deficiency in the legislation. People found to be using or trafficking a substance with either or both of these characteristics face serious legal consequences.
Unfortunately, the weakness remains that when an unknown substance is purchased and used, the content will not be identifiable with current analytical techniques, and unless it produces adverse effects which bring the users to medical attention, its existence is likely to remain unknown.
CONCLUSION
The problem of workers in safety sensitive roles using drugs which are likely to affect performance and which are designed to avoid detection remains. With the current approach to drug manufacture and distribution, it is difficult to determine the size of the problem but it is certain that it has not disappeared.
AUTHOR PROFILE
DR CHARLES APPLETON
Dr Charles Appleton is medically trained and after graduating in 1977, specialised in Chemical Pathology. This branch of pathology not only deals with heart, liver and endocrine diseases, but also is responsible for drug testing in blood (generally therapeutic) and urine, oral fluid and hair (generally toxicological). He has been director of Biochemistry and Toxicology in Queensland Medical Laboratory (QML Pathology) for 30 years. QML provides drug testing services and expert consultation for medical patients as well as for industry, Departments of Child Safety and Community Services, Family Law Court, Australian Health Professional Registration Authority and others.
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