thesis about drug testing

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Random student drug testing as a school-based drug prevention strategy

Affiliation.

1 Institute for Behavior and Health, Inc., Rockville, MD 20852, USA. [email protected]
PMID: 22906236
PMCID: PMC3505268
DOI: 10.1111/j.1360-0443.2012.03978.x

Aim: This paper describes the goals and current practice of school-based random student drug testing (RSDT) as part of an overall drug prevention strategy, briefly explores the available literature evaluating its effectiveness and discusses the controversies related to RSDT.

Method: The authors describe the rationale for RSDT programs and the prevalence of RSDT and other drug testing programs in schools. Eight major criticisms and controversies in RSDT are discussed, including those related to acceptance of RSDT, program effectiveness, costs, legality and effects of drug testing on students. The limitations of the current literature are explored.

Findings: Although there is limited empirical evidence to support or refute the efficacy of RSDT in schools, there remains substantial opposition to such programs, which may contribute to the paucity of empirical studies of RSDT.

Conclusions: Rigorous long-term evaluations are needed to evaluate the effectiveness of various versions of RSDT programs to prevent drug use and identify students in need of assistance to become and stay drug-free.

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Conflict of interest statement

Declarations of Interest: Partial funding for this work was received from the National Institute on Drug Abuse (R01-DA14845 and P50-DA027841).

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Home > Graduate Research & Artistry > Theses & Dissertations > 1418

Graduate Research Theses & Dissertations

An overview of the legality of drug testing in the public and private sectors.

Sally A. Wakefield

Publication Date

Document type.

Dissertation/Thesis

First Advisor

Behrens, Curtiss K.

Degree Name

M.S. (Master of Science)

Legacy Department

Department of Management

Drugs and employment--Law and legislation--United States; Drug testing--Law and legislation--United States

This thesis presents an overview of public- and private-sector drug testing which is becoming increasingly controversial and important to the employment relationship. The purpose of this thesis is to provide an understanding of the legal complexities of the drug-testing issue in the public and private sectors and to offer recommendations for federal drug-testing legislation.

Includes bibliographical references (pages 58-60)

Recommended Citation

Wakefield, Sally A., "An overview of the legality of drug testing in the public and private sectors" (1989). Graduate Research Theses & Dissertations . 1418. https://huskiecommons.lib.niu.edu/allgraduate-thesesdissertations/1418

iv, 60 pages

Northern Illinois University

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Researchers develop 'organ on a chip' for better drug testing 

$2 million in funding has made it possible to 3D-print synthetic models, which mimic part of the human brain and could replace the use of animals in developing treatments. 

Alex Parrish

18 Jul 2024

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Jeff Schultz '03 inspects a 3D-printed organ on a chip at his lab in Charlotte, North Carolina. Photo by Alex Parrish for Virginia Tech.

Improving human quality of life with drug treatments is a complicated issue. Drug certification, including drug safety and reliability, entails a long series of tests and government approvals before the drug is available for anyone to use.

Testing drugs is challenged by ethical and biological concerns. Testing new drugs on humans is usually part of a clinical trial and occurs near the end of a drug's path to public use. Before that point, a large amount of testing has been conducted on animals. There is a growing call to phase out animal testing , partly because of the differences in animal and human biology . Simply put, just because something works for mice doesn't mean it will work for a human being.

A group of academic researchers across institutions have joined forces with Virginia Tech's Jeff Schultz to find a solution that could give human-oriented results with synthetic tools. Their approach requires no human subjects or animals. Instead, it uses new technologies to create testing environments that are highly customizable. Drugs can be tested with cells, not creatures.

Funded by a $1.8 million grant from the National Institutes of Health (NIH), the team includes:

Amrinder Nain , professor of mechanical engineering at Virginia Tech
Rafael Davalos , Margaret P. and John H. Weitnauer Jr. Chaired Professor at Georgia Tech
Seemantini Nadkarni , associate professor, Harvard Medical School and Massachusetts General Hospital
Jeff Schultz , co-founder of 3D-printed microfluidics company Phase Inc ., who also earned three degrees from the Virginia Tech Department of Material Science and Engineering

Breaking into the brain

Physiological barriers are common in the body, and one such barrier, called the blood-brain barrier, is made of a network of blood vessels and tissues. Its function is to allow helpful substances such as water and oxygen to enter the brain, but keep out harmful substances that could lead to disease or tumors. Recreating this intricate environment for drug testing has been challenging, and it is not uncommon for clinical trials to fail when they move from the lab.

"Therapeutics fail in clinical trials because they can't cross the blood-brain barrier," said Davalos. "The reality is that the devices that have been created in a lab don't work and they allow too much to pass through. This gives false information that molecules can get through, and when you get into a clinical trial, the drugs fail because the human brain conditions haven’t been properly duplicated."

The team is approaching the problem with Phase’s proprietary 3D-printing method, creating microfluidics at previously unattainable resolutions that also are highly reproducible and scalable. Microfluidics are remarkably small devices where cells and fluids can be manipulated to create an “organ on a chip” that mimics the behavior and function of human organs. While this project is focused on the blood-brain barrier, the core technology has wide-ranging applications for other organs such as the liver, lungs, and skin.

Schultz has spent his career inventing and scaling 3D-printing techniques for both startup companies and international conglomerates. Building on the strength of that experience, he turned his attention to apply the flexibility of 3D printing to the biomedical world.

“We’re building something that more realistically mimics the geometry of the body compared to other microfluidics,” said Schultz. “Harnessing the design freedom of 3D printing allows us to create devices that have the same curvature, size of veins, and functionality of the human body. We can put in valves similar to the heart that are accustomed to pulsating mechanical stresses. This gives us the opportunity to see results that are closer to real life than if the cells were laying flat in a dish, and is done in other conventional microfluidic devices, but has yet to be applied to the blood brain barrier.”

Synthetic devices and living cells

Schultz and Davalos have already collaborated on new methods for 3D printing medical devices using materials that had been problematic in drug trials up to that point. In phase one of this project, they devised a way to 3D-print polydimethylsiloxane (PDMS), a silicone polymer that could be used to mimic the blood-brain barrier. That project received $173,000 from the NIH.

"The challenge we set out to solve was with the materials," said Schultz. "There were no materials you could 3D-print for microfluidics that were widely accepted as safe for cells. PDMS was used for over two decades but wasn't 3D printable. We set out to develop a technology to 3D-print that material, which the NIH funded us to do in phase one of the project."

The material needed to be safe for cells so that cells could grow on the platform and provide conditions for testing the viability of various drugs. To make an artificial blood-brain barrier, the blood and tissue cells that form the barrier in a living body were grown on the 3D-printed piece, hence the “ organ on a chip. ” The advantage of 3D printing is that the framework creates different pathways and architectures, which might lead to customizing the synthetic blood-brain barrier to match the patient’s own.

After seeing success in the first phase, Schultz and Davalos saw possibilities in expanding the project. Amrinder Nain had expertise and tools ready for the task and had previously collaborated with Davalos.

Davalos’ team has developed other organ-on-a-chip platforms to test the behavior of biological processes at the small scale. Philip Graybill, a recent Virginia Tech graduate on Davalos’s team focused on developing such microfluidic models of the blood-brain barrier as well as how single cells respond to electromechanical cues using Nain’s nanofiber platform. Through their collaboration, Graybill recognized a chance to fold one technology into another to build a more accurate model of what occurs in the brain.

Making a mesh

Nain's specialty is research with nanofiber membranes that perform in much the same way as living tissues, created using a lattice of spun fibers that crisscross one another at the nanoscale. Those membranes became the key for the next evolution of the device and helped the team pick up a second round of NIH funding. Davalos and Nain's group recently published the first-ever ultra-thin and ultra-porous blood-brain barrier (BBB) that is roughly 70 percent thinner than other existing methods to study it.

"What's really nice about using Amrinder [Nain] 's fiber network is that it's so thin, you can have cells on either side that can communicate," said Davalos. "This creates tight junctions between cells to prevent therapeutics from passing through."

This is precisely the level of control that is required to match findings from clinical trials. With this development, the team has given future researchers a reliable and faster turn-around tool for drug testing in physiologically relevant environments while minimizing animal models.

"In the blood-brain barrier, there is a physical membrane," said Schultz. "Amrinder [Nain]'s nanofiber membrane mimics the thickness and porosity of the mechanism in a real brain better than most mimics used in similar devices. When we proposed phase two to the NIH, we proposed using those membranes integrated into our previous PDMS microfluidic device."

To create the organ-on-a-chip approach, every team member used their specialties. The process generally goes like this:

Nain's team produces the ultra-thin and nanoporous membrane mimics.
Schultz's team receives the membrane, constructs a design including it, then uses a system developed by Nadkarni's Harvard team to test the behavior of the material.
The finished pieces are sent to Davalos's team to outfit them with cells and conduct the biological tests.

“Organ-on-a-chip technologies are now projected to be standard lab protocols in the 21st century,” said Nain. “Our technological breakthroughs have enabled the thinnest BBB in the market. In future design iterations, we expect to meet the dimensions and architectures present in the human body to achieve physiological outputs in a lab setting. When realized, this will transform how we test drugs and study bioengineering and biophysics."

Chelsea Seeber

540-231-2108

Biomedical Engineering and Mechanics
Brain Research
College of Engineering
Good Health and Well-Being
Materials Science and Engineering
Mechanical Engineering
National Institutes of Health
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Shots - Health News

A scientist took a psychedelic drug — and watched his own brain 'fall apart'.

Jon Hamilton

A prominent brain scientist took psilocybin as part of his own brain study

A study finds that psilocybin can desynchronize networks in the brain, potentially enhancing its plasticity. Sara Moser/Washington University School of Medicine in St. Louis hide caption

In the name of science, Dr. Nico Dosenbach had scanned his own brain dozens of times. But this was the first time he'd taken a mind-bending substance before sliding into the MRI tunnel.

"I was, like, drifting deeper into weirdness," he recalls. "I didn't know where I was at all. Time stopped, and I was everyone."

Dosenbach, an associate professor of neurology at Washington University School of Medicine in St. Louis, had been given a high dose of psilocybin , the active substance in magic mushrooms, by his colleagues.

It was all part of a study of seven people designed to show how psilocybin produces its mind-altering effects.

The results, which appear in the journal Nature , suggest that psychedelic drugs work by disrupting certain brain networks, especially one that helps people form a sense of space, time and self.

Psychedelic drugs may launch a new era in psychiatric treatment, brain scientists say

"For the first time, with a really high degree of detail, we're understanding which networks are changing, how intensely they're changing and what persists after the experience," says Dr. Petros Petridis of New York University's Langone Center for Psychedelic Medicine, who wrote an editorial accompanying the study.

The research also provided a close look at how these drugs temporarily enhance the brain's ability to adapt and change, an ability known as plasticity.

The disruptions in brain networks appear to be "where the plasticity effects of psychedelics are coming from," says Dr. Joshua Siegel , a researcher at Washington University and the study's lead author.

If that's true, he says, it could explain why psychedelics appear to help people with addiction or depression.

A brainy trip

Dosenbach and other participants were randomly assigned to receive either a stimulant or 25 milligrams of psilocybin, a dose high enough to cause hallucinations.

"It was definitely an awesome experience for a neuroscientist," he says.

"It's really fascinating how your brain can fall apart — because how something breaks tells you how something works."

Dosenbach's trip took him places only a neuroscientist is likely to go.

"I was inside the brain, and I was riding brain waves, and I was Marc Raichle," he says, referring to Dr. Marcus Raichle, a colleague and co-author of the study, who also happens to be a towering figure in the world of neuroscience.

As part of the study, participants' brains were scanned an average of 18 times over a three-week period. Four repeated the experiment six to 12 months later.

Rigorous Study Backs A Psychedelic Treatment For Major Depression

"You're bringing in single individuals many times," Siegel says, "and that allows you to get a very detailed and precise map of their brain networks."

The scans showed that psilocybin caused swift and dramatic changes to certain brain networks. Usually the neurons in a given network become active at the same time — often in tandem with other networks too.

"What's going on during psilocybin is that populations of neurons that are normally in synchrony are out of synchrony," Siegel says.

The brain "falls apart." And it appears to respond by entering a state of enhanced plasticity that can last for weeks.

"Desynchronization probably is a critical clue as to where the plasticity effects of psychedelics are coming from," Siegel says.

The loss of synchrony was greatest in a brainwide group of neurons called the default mode network, which is active when the brain is daydreaming or otherwise not focused on the outside world.

This network was discovered by scientists including Raichle, the man who became Dosenbach's alter ego in the scanner.

The default mode network is critical to self-referential memory, which helps the brain keep track of information like, Who am I? And what was I doing? Siegel says.

Changing your mind

The study hints at how psychedelic drugs could be incorporated into the treatment of people with addiction, depression or post-traumatic stress.

"There seems to be this time of increased change that could be taken advantage of by therapists," Petridis says.

A patient with addiction, for example, might be able to reframe their relationship with substances in the days and weeks following a dose of psilocybin, he says.

But the approach has risks, says Dr. Ginger Nicol , a psychiatrist at Washington University whose husband was in the study and took psilocybin twice.

"He had an almost religious experience the first time," she says. "The second time, he saw demons."

Even so, psychedelics may offer a way to help psychiatric patients recognize their own capacity to change, Nicol says.

"It takes years to figure that out in therapy," she says. "This gives us a different way of thinking about learning and recovery."

brain health
Brain development
human brain
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magic mushrooms

UFC's Jon Jones charged in incident with drug testing agent

UFC heavyweight champion Jon Jones has been charged with two misdemeanors stemming from an incident with a drug testing agent on March 30. Public records on the New Mexico Courts website show that Jones has been charged with assault and interference with communications.

If convicted, Jones could face less than a year of jail time and be fined up to $500 for the assault charge -- a petty misdemeanor -- and $1,000 for the second charge.

A police report obtained by ABQ Raw said that an agent for the UFC's anti-doping partners at Drug Free Sport went to Jones' home in Albuquerque in an attempt to collect a random sample. The report said Jones "appeared agitated" when he was unable to provide a urine sample and was, instead, offered the opportunity to submit a blood sample.

The report said he allegedly took the testing agent's cellphone, questioned why the agents arrive so early in the day and said "Do you know what happens to people who come to my house? They end up dead." In an Instagram post, which has since been deleted, Jones said he was "caught off guard by the unprofessionalism" of the testing agent and admitted to using profanity. But he denied threatening the agent with violence and denounced the accusations as "baseless."

A virtual bond hearing has been scheduled for July 17 at 9:15 a.m. MT in Albuquerque Metropolitan Court, at which time Jones will enter a plea.

Jones is preparing to make his return to the Octagon to defend his UFC heavyweight championship. Although a date has not been formally announced, he has insisted that he will defend against former champion Stipe Miocic in New York at Madison Square Garden in November.

V. I. Lenin

Theses on fundamental tasks of, the second congress of the communist international.

Written: 30 June, 1920 First Published: July of 1920 Source: Lenin’s Collected Works , 4th English Edition, Progress Publishers, Moscow, 1965, Volume 31 , pages 184-201 Translated: Julius Katzer Transcription\HTML Markup: David Walters & R. Cymbala Copyleft: V. I. Lenin Internet Archive (www.marx.org) 2002. Permission is granted to copy and/or distribute this document under the terms of the GNU Free Documentation License

The Essence of the Dictatorship of the Proletariat and of Soviet Power

What Immediate and Universal Preparation for the Dictatorship of the Proletariat Should Consist of

Rectification of the Political Line—Partly Also the Composition—of Parties Affiliated or Desiring to Affiliate to the Communist International

1.The present stage in the development of the international communist movement is marked by the fact that the finest representatives of the revolutionary proletariat in all capitalist countries have fully grasped the fundamental principles of the Communist International, viz., dictatorship of the proletariat and Soviet power, and have ranged themselves with unbounded enthusiasm on the side of the Communist International. An even bigger and more important step forward is the definite sympathy with these fundamental principles that has everywhere taken shape among the broadest masses; not only of the urban proletariat, but of the advanced section of the rural workers as well.

On the other hand, two errors, or failings, are to be observed in the very rapidly growing international communist movement. One, which is very grave and constitutes an immense and immediate danger to the success of the cause of proletarian emancipation, is that a section of the old leaders and of the old parties of the Second International—some yielding half-unconsciously to the wishes and pressure of the masses, and some deliberately deceiving the masses in order to retain their function of agents and assistants of the bourgeoisie within the working-class movement—declare their qualified or even unqualified adherence to the Third International, while actually remaining in all their practical party and political work, on the level of the Second International. Such a state of affairs is absolutely intolerable, because it leads to downright corruption of the masses, detracts from the Third International’s prestige, and threatens a repetition of the same acts of treachery as were perpetrated by the Hungarian Social-Democrats, who so hastily assumed the title of Communists. The other error, which is far less significant and is more in the nature of growing pains of the movement, consists in a tendency towards “Leftism” which results in a wrong appraisal of the role and the tasks of the party with regard to the class and the masses, and a wrong attitude towards the revolutionary Communists’ obligation to work in bourgeois parliaments and reactionary trade unions.

Communists are in duty bound, not to gloss over shortcomings in their movement, but to criticise them openly so as to remedy them the more speedily and radically. For this purpose it is necessary: first, to define as concretely as possible, particularly on the basis of the practical experience already acquired, the content of the concepts “dictatorship of the proletariat” and “Soviet power”; second, to specify the precise content of the immediate and systematic preparatory work to be carried on in all countries so as to give effect to these slogans; and third, to specify the methods and means of rectifying the faults in our movement.

The Essence Of The Dictatorship Of The Proletariat and of Soviet Power

2.The victory of socialism (as the first stage of communism) over capitalism requires that the proletariat, as the only really revolutionary class, shall accomplish the following three tasks. First—overthrow the exploiters, and first and foremost the bourgeoisie, as their principal economic and political representative; utterly rout them; crush their resistance; absolutely preclude any attempt on their part to restore the yoke of capital and wage-slavery. Second—win over and bring under the leadership of the Communist Party, the revolutionary vanguard of the proletariat, not only the entire proletariat, or its vast majority, but all who labour and are exploited by capital; educate, organise, train and discipline them in the actual course of a supremely bold and ruthlessly firm struggle against the exploiters; wrest this vast majority of the pqpulation in all the capitalist countries from dependence on the bourgeoisie; imbue it, through its own practical experience, with confidence in the leading role of the proletariat and of its revolutionary vanguard. Third—neutralise, or render harmless, the inevitable vacillation between the bourgeoisie and the proletariat, between bourgeois democracy and Soviet power, to be seen in the class of petty proprietors in agriculture, industry and commerce—a class which is still fairly numerous in nearly all advanced countries, although comprising only a minority of the population—as well as in the stratum of intellectuals, salary earners, etc., which corresponds to this class.

The first and second tasks are independent ones, each requiring its own special methods of action with regard to the exploiters and to the exploited respectively. The third task follows from the first two, and merely requires a skilful, timely and flexible combination of methods of the first and second type, depending on the specific circumstances in each separate instance of vacillation.

3.In the concrete situation created throughout the world, and above all in the most advanced, powerful, enlightened and free capitalist countries, by militarism, imperialism, the oppression of colonies and weak countries, the world wide imperialist butchery and the “Peace” of Versailles—in that situation the very idea of the capitalists peacefully submitting to the will of the majority of the exploited, the very idea of a peaceful, reformist transition to socialism, is not merely sheer philistine stupidity but also down right deception of the workers, embellishment of capitalist wage-slavery, and concealment of the truth. That truth consists in the bourgeoisie, even the most enlightened and democratic, no longer hesitating at any fraud or crime, even the massacre of millions of workers and peasants, so as to preserve private ownership of the means of production. Only the forcible overthrow of the bourgeoisie, the confiscation of its property, the destruction of the entire bourgeois state apparatus from top to bottom—parliamentary. judicial, military, bureaucratic, administrative, municipal, etc.—right down to the wholesale deportation or internment of the most dangerous and stubborn exploiters and the institution of strict surveillance over them so as to foil their inevitable attempts to resist and to restore capitalist slavery—only such measures can ensure real submission of the whole class of exploiters.

On the other hand, the idea, common among the old parties and the old leaders of the Second International, that the majority of the exploited toilers can achieve complete clarity of socialist consciousness and firm socialist convictions and character under capitalist slavery, under the yoke of the bourgeoisie (which assumes an inIinite variety of forms that become more subtle and at the same time more brutal and ruthless the higher the cultural level in a given capitalist country) is also idealisation of capitalism and of bourgeois democracy, as well as deception of the workers. In fact, it is only after the vanguard of the proletariat, supported by the whole or the majority of this, the only revolutionary class, overthrows the exploiters, suppresses them, emancipates the exploited from their state of slavery and-immediately improves their conditions of life at the expense of the expropriated capitalists—it is only after this, and only in the actual process of an acute class strugg]e, that the masses of the toilers and exploited can be educated, trained and organised around the proletariat under whose influence and guidance, they can get rid of the selfishness, disunity, vices and weaknesses engendered by private property; only then will they be converted into a free union of free workers.

4.Victory over capitalism calls for proper relations between the leading (Communist) party, the revolutionary class (the proletariat) and the masses, i.e., the entire body of the toilers and the exploited. Only the Communist Party, if it is really the vanguard of the revolutionary class, if it really comprises all the finest representatives of that class, if it consists of fully conscious and staunch Communists who have been educated and steeled by the experience of a persistent revolutionary struggle, and if it has succeeded in linking itself inseparably with the whole life of its class and, through it, with the whole mass of the exploited, and in completely winning the confidence of this class and this mass—only such a party is capable of leading the proletariat in a final, most ruthless and decisive struggle against all the forces of capitalism. On the other hand, it is only under the leadership of such a party that the proletariat is capable of displaying the full might of its revolutionary onslaught, and of overcoming the inevitable apathy and occasional resistance of that small minority, the labour aristocracy, who have been corrupted by capitalism, the old trade union and co-operative leaders, etc.—only then will it be capable of displaying its full might, which, because of the very economic structure of capitalist society, is infinitely greater than its proportion of the population. Finally, it is only after they have been really emancipated from the yoke of the bourgeoisie and of the bourgeois machinery of state, only after they have found an opportunity of organising in their Soviets in a really free way (free from the exploiters), that the masses, i.e., the toilers and exploited as a body, can display, for the first time in history, all the initiative and energy of tens of millions of people who have been crushed by capitalism. Only when the Soviets have become the sole state apparatus is it really possible to ensure the participation, in the work of administration, of the entire mass of the exploited, who, even under the most enlightened and freest bourgeois democracy, have always actually been excluded 99 per cent from participation in the work of administration. It is only in the Soviets that the exploited masses really begin to learn—not in books, but from their own practical experience—the work of socialist construction, of creating a new social discipline and a free union of free workers.

What Immediate And Universal Preparation for the Dictatorship of the Proletariat Should Consist of

5.The present stage in the development of the international communist movement is marked by the fact that in the vast majority of capitalist countries, the proletariat’s preparations to effect its dictatorship have not been completed, and, in many cases, have not even been systematically begun. From this it does not, however, follow that the proletarian revolution is impossible in the immediate future; it is perfectly possible, since the entire economic and political situation is most inflammable and abounds in causes of a sudden flare-up; the other condition for revolution, apart from the proletariat’s preparedness, viz., a general state of crisis in all the ruling and in all bourgeois parties, also exists. However, it does follow that the Communist Parties’ current task consists not in accelerating the revolution, but in intensifying the preparation of the proletariat. On the other hand, the facts cited above from the history of many socialist parties make it incumbent on us to see that “recognition” of the dictatorship of the proletariat shall not remain a more matter of words.

Hence, from the point of view of the international proletarian movement, it is the Communist parties ’ principal task at the present moment to unite the scattered Communist forces, to form a single Communist Party in every country (or to reinforce or renovate the already existing Party) in order to increase tenfold the work of preparing the proletariat for the conquest of political power—political power, moreover, in the form of the dictatorship of the proletariat. The ordinary socialist work conducted by groups and parties which recognise the dictatorship of the proletariat has by no means undergone that fundamental reorganisation, that fundamental renovation, which is essential before this work can be considered communist work and adequate to the tasks to be accomplished on the eve of proletarian dictatorship.

6.The proletariat’s conquest of political power does not put a stop to its class struggle against the bourgeoisie; on the contrary, it renders that struggle most widespread, intense and ruthless. Owing to the extreme intensification of the struggle all groups, parties and leaders in the working-class movement who have fully or partly adopted the stand of reformism, of the “Centre”, etc., inevitably side with the bourgeoisie or join the waverers, or else (what is the most dangerous of all) land in the ranks of the unreliable friends of the victorious proletariat. Hence, preparation for the dictatorship of the proletariat calls, not only for an intensification of the struggle against reformist and “Centrist” tendencies, but also for a change in the character of that struggle. The struggle cannot be restricted to explaining the erroneousness of these tendencies; it must unswervingly and ruthlessly expose any leader of the working-class movement who reveals such tendencies, for otherwise the proletariat cannot know who it will march with into the decisive struggle against the bourgeoisie. This struggle is such that at any moment it may—and actually does, as experience has shown—substitute criticism with weapons for the weapon of criticism. [6] Any inconsistency or weakness in exposing those who show themselves to be reformists or “Centrists” means directly increasing the danger of the power of the proletariat being overthrovn by the bourgeoisie, which tomorrow will utilise for the counter-revolution that which short-sighted people today see merely as “theoretical difference”.

7.In particular, we must not restrict ourselves to the usual repudiation, in principle, of all collaboration between the proletariat and the bourgeoisie, of all “collaborationism”. Under the dictatorship of the proletariat, which will never be able, at one stroke, to abolish private property completely, mere defence of “liberty”’ and “equality”, while private ownership of the means of production is preserved, turns into “collaboration” with the bourgeoisie, and undermines the rule of the working class. The dictatorship of the proletariat means that the state uses its whole machinery of power to uphold and perpetuate “no-liberty” for the exploiters to continue their oppression and exploitation, “inequality” between the owner of property (i.e., one who has appropriated for himself certain means of production created by social labour) and the non-owner. That which, prior to the victory of the proletariat, seems merely a theoretical difference on the question of “democracy” inevitably becomes, on the day following victory, a question that is settled by force of arms. Consequently, even preliminary work in preparing the masses to effect the dictatorship of the proletariat is impossible without a radical change in the entire character of the struggle against the “Centrists” and the “champions of democracy “.

8.The dictatorship of the proletariat is the most determined and revolutionary form of the proletariat’s class struggle against the bourgeoisie. This struggle can be successful only when the most revolutionary vanguard of the proletariat has the backing of the overwhelming majority of the proletariat. Hence, preparation for the dictatorship of the proletariat entails not only explanation of the bourgeois character of all reformism, of all defence of democracy, while private ownership of the means of production is preserved; it entails, not only exposure of such trends, which are in fact a defence of the bourgeoisie within the labour movement; it also calls for old leaders being replaced by Communists in proletarian organisations of absolutely every type—not only political, but also trade union, co-operative, educational, etc. The more complete, lengthy and firmly established the rule of bourgeois democracy has been in a given country, the more the bourgeoisie will have succeeded in securing the appointment to such leading posts of people whose minds have been moulded by it and imbued with its views and prejudices, and who have very often been directly or indirectly bought by it. These representatives of the labour aristocracy, bourgeoisified workers, should be ousted from all their posts a hundred times more sweepingly than hitherto, and replaced by workers—even by wholly inexperienced men, provided they are connected with the exploited masses and enjoy their confidence in the struggle against the exploiters. The dictatorship of the proletariat will require the appointment of such inexperienced workers to the most responsible posts in the state; otherwise the workers’ government will be impotent and will not have the support of the masses.

9.The dictatorship of the proletariat means that all toiling and exploited people, who have been disunited, deceived, intimidated, oppressed, downtrodden and crushed by the capitalist class, come under the full leadership of the only class trained for that leadership by the whole history of capitalism. That is why the following is one of the methods whereby preparations for the dictatorship of the proletariat should be started everywhere and immediately:

In all organisations, unions and associations without exception, and first and foremost in proletarian organisations, but also in those of the non-proletarian toiling and exploited masses (political, trade union, military, co-operative, educational, sports, etc., etc.), groups or cells of Communists should be formed—preferably open groups, but underground groups as well, the latter being essential whenever there is reason to expect their suppression, or the arrest or banishment of their members on the part of the bourgeoisie; these cells, which are to be in close touch with one another and with the Party centre, should, by pooling their experience, carrying on work of agitation, propaganda and organisation, adapting themselves to absolutely every sphere of public life and to every variety and category of the toiling masses, systematically educate themselves, the Party, the class, and the masses by means of such diversified work.

In this connection, it is of the utmost importance that necessary distinctions between the methods of work should be evolved in practice: on the one hand, in relation to the “leaders”, or “responsible representatives”, who are very often hopelessly beset with petty-bourgeois and imperialist prejudices—such “leaders” must be ruthlessly exposed and expelled from the working-class movement—and, on the other hand, in relation to the masses, who, particularly after the imperialist holocaust, are for the most part inclined to listen to and accept the doctrine that the guidance from the proletariat is essential, as the only way of escape from capitalist slavery. We must learn to approach the masses with particular patience and caution so as to be able to understand the distinctive features in the mentality of each stratum, calling, etc., of these masses.

10.In particular, there is a group or cell of Communists that deserves exceptional attention and care from the Party, i.e., the parliamentary group of Party members, who are deputies to bourgeois representative institutions (primarily the national, but also local, municipal, etc., representative institutions). On the one hand, it is this tribune which is held in particular regard by large sections of the toiling masses, who are backward or imbued with petty-bourgeois prejudices; it is therefore imperative for Communists to utilise this tribune to conduct propaganda, agitation and organisational work and to explain to the masses why the dispersal of the bourgeois parliament by the national congress of Soviets was legitimate in Russia (and, at the proper time, will be legitimate in any country). On the other hand, the entire history of bourgeois democracy, particularly in the advanced countries, has converted the parliamentary rostrum into one of the principal, if not the principal, venues of unparalleled fraudulency, financial and political deception of the people, careerism, hypocrisy and oppression of the working people. The intense hatred of parliaments felt by the best representatives of the revolutionary proletariat is therefore quite justified. The Communist parties and all parties affiliated to the Third International—especially those which have not arisen by splitting away from the old parties and by waging a long and persistent struggle against them, but through the old parties accepting (often nominally) the new stand—should therefore adopt a most strict attitude towards their parliamentary groups; the latter must be brought under the full control and direction of the Central Committees of the Parties; they must consist, in the main, of revolutionary workers; speeches by members of parliament should be carefully analysed in the Party press and at Party meetings, from a strictly communist standpoint; deputies should be sent to carry on agitational work among the masses; those who manifest Second International leanings should be expelled from the parliamentary groups, etc.

11.One of the chief causes hampering the revolutionary working-class movement in the developed capitalist countries is the fact that because of their colonial possessions and the super-profits gained by finance capital, etc., the capitalists af these countries have been able to create a relatively larger and more stable labour aristocracy, a section which comprises a small minority of the working class. This minority enjoys better terms of employment and is most-imbued with a narrow-minded craft spirit and with petty-bourgeois and imperialist prejudices. It forms the real social pillar of the Second International, of the reformists and the “Centrists”; at present it might even be called the social mainstay of the bourgeoisie. No preparation of the proletariat for the overthrow of the bourgeoisie is possible, even in the preliminary sense, unless an immediate, systematic, extensive and open struggle is waged against this stratum, which, as experience has already fully shown, will no doubt provide the bourgeois White guards with many a recruit after the victory of the proletariat. All parties affiliated to the Third International must at all costs give effect to the slogans: “Deeper into the thick of the masses”, “Closer links with the masses”—meaning by the masses all those who toil and are exploited by capital, particularly those who are least organised and educated, who are most oppressed and least amenable to organisation.

The proletariat becomes revolutionary only insofar as it does not restrict itself to the narrow framework of craft interests, only when in all matters and spheres of public life, it acts as the leader of all the toiling and exploited masses; it cannot achieve its dictatorship unless it is prepared and able to make the greatest sacrifices for the sake of victory over the bourgeoisie. In this respect, the experience of Russia is significant both in principle and in practice. The proletariat could not have achieved its dictatorship there, or won the universally acknowledged respect and confidence of all the toiling masses, had it not made the most sacrifices, or starved more than any other section of those masses at the most crucial moments of the onslaught, war and blockade effected by the world bourgeoisie.

In particular, the Communist Party and all advanced proletarians must give all-round and unstinted support especially to the spontaneous and mass strike movement, which, under the yoke of capital, is alone capable of really rousing, educating and organising the masses, of imbuing them with complete confidence in the leadership of the revolutionary proletariat. Without such preparation, no dictatorship of the proletariat is possible; those who are capable of publicly opposing strikes, such as Kautsky in Germany and Turati in Italy, cannot possibly be tolerated in the ranks of parties affiliated to the Third International. This applies even more, of course, to those trade union and parliamentary leaders who so often betray the workers by using the experience of strikes to teach them reformism, and not revolution (for instance, in Britain and in France in recent years).

12.In all countries, even in those that are freest, most “legal”, and most “peaceful” in the sense that the class struggle is least acute there, it is now absolutely indispensable for every Communist Party to systematically combine legal and illegal work, legal and illegal organisations. Notwithstanding their false and hypocritical declarations, the governments of even the most enlightened and freest of countries, where the bourgeois-democratic system is most “stable”, are already systematically and secretly drawing up blacklists of Communists and constantly violating their own constitutions so as to give secret or semi-secret encouragement to the whiteguards and to the murder of Communists in all countries, making secret preparations for the arrest of Communists, planting agents provocateurs among the Communists, etc., etc. Only a most reactionary philistine, no matter what cloak of fine “democratic” and pacifist phrases he may don, will deny this fact or the conclusion that of necessity follows from it viz., that all legal Communist parties must immediately form illegal organisations for the systematic conduct of illegal work and for complete preparations for the moment the bourgeoisie resorts to persecution. Illegal work is most necessary in the army, the navy and the police because, since the imperialist holocaust, governments the world over have begun to stand in dread of people’s armies which are open to the workers and peasants, and are secretly resorting to all kinds of methods to set up military units specially recruited from the bourgeoisie and equipped with the most up-to-date weapons.

On the other hand, it is likewise necessary that, in all cases without exception, the parties should not restrict themselves to illegal work, but should conduct legal work as well, overcoming all obstacles, starting legal publications, and forming legal organisations under the most varied names, which should be frequently changed if necessary. This is being practised by the illegal Communist parties in Finland, Hungary, partly in Germany, Poland, Latvia, etc. It should be practised by the Industrial Workers of the World in the U.S.A. and by all Communist parties at present legal, should public prosecutors see fit to take proceedings against them on the grounds of resolutions adopted by Congresses of the Communist International, etc.

A combination of illegal and legal work is an absolute principle dictated, not only by all features of the present period, that of the eve of the proletarian dictatorship, but also by the necessity of proving to the bourgeoisie that there is not, nor can there be, any sphere of activity that cannot be won by the Communists; above all, it is dictated by the fact that broad strata of the proletariat and even broader strata of the non-proletarian toiling and exploited masses still exist everywhere, who continue to believe in bourgeois-democratic legality and whom we must undeceive without fail.

13.In particular, the conditions of the working-class press in most advanced capitalist countries strikingly reveal the utter fraudulency of liberty and equality under bourgeois democracy, as well as the necessity of systematically combining legal work with illegal work. Both in vanquished Germany and in victorious America, the entire power of the bourgeoisie’s machinery of state and all the machinations of the financial magnates are employed to deprive the workers of their press, these including legal proceedings, the arrest (or murder by hired assassins) of editors, denial of mailing privileges, the cutting off of paper supplies, and so on and so forth. Besides, the news services essential to daily newspapers are run by bourgeois telegraph agencies, while advertisements, without which a large newspaper cannot pay its way, depend on the “good will” of the capitalists. To sum up: through skulduggery and the pressure of capital and the bourgeois state, the bourgeoisie is depriving the revolutionary proletariat of its press.

To combat this, the Communist parties must create a new type of periodical press for mass distribution among the workers: first, legal publications, which, without calling themselves communist and without publicising their links with the Party, must learn to make use of any legal opportunity, however slight, just as the Bolsheviks did under the tsar, after 1905; secondly, illegal leaflets, even the briefest and published at irregular intervals, but reprinted at numerous printshops by workers (secretly, or, if the movement has become strong enough, by the revolutionary seizure of printshops), and providing the proletariat with outspoken revolutionary information and revolutionary slogans.

Preparations for the dictatorship of the proletariat is impossible without a revolutionary struggle, into which the masses are drawn, for the freedom of the communist press.

Rectification Of The Political Line— Partly Also Of The Composition— Of Parties Affiliated Or Desiring To Affiliate To The Communist International

14.The measure in which the proletariat in countries most important from the viewpoint of world economics and politics is prepared to establish its dictatorship can be seen with the greatest objectivity and precision in the fact that the most influential parties of the Second International, viz., the French Socialist Party, the Independent Social-Democratic Party of Germany, the Independent Labour Party of Great Britain and the Socialist Party of America, [7] have withdrawn from this yellow International, and have decided—the first three conditionally, the latter even unconditionally—to affiliate to the Third In ternational. This proves that not only the vanguard of the revolutionary proletariat but its majority too have begun to come over to our side, convinced by the entire course of events. The main thing now is the ability to consummate this process and to consolidate firmly in point of organisation what has been achieved, so as to advance all along the line, without the slightest wavering.

15.All the activities of the parties mentioned (to which should be added the Socialist Party of Switzerland, [8] if the telegraph reports of its decision to join the Third International are true) show—as any periodical of these parties will strikingly confirm—that they are not yet communist, and quite often run directly counter to the fundamental principles of the Third International, viz., the recognition of the dictatorship of the proletariat and Soviet government in place of bourgeois democracy.

Accordingly, the Second Congress of the Communist International must resolve that it cannot immediately accept the affiliation of these parties; that it endorses the reply given by the Executive Committee of the Third International to the German “Independents” [9] ; that it confirms its readiness to conduct negotiations with any party that withdraws from the Second International and desires to enter into closer relations with the Third International; that it will admit the delegates of such parties in a deliberative capacity to all its congresses and conferences; that it sets the following conditions for the complete adhesion of these (and similar), parties with the Communist International:

1)All decisions of all Congresses of the Communist International and of its Executive Committee to be published in all the periodicals of the parties concerned;

2)These decisions to be discussed at special meetings of all sections or local organisations of the parties;

3)After such discussion, special congresses of the parties to be convened to sum up the results, and for the purpose of—

4)Purging the parties of elements that continue to act in the spirit of the Second International;

5)All periodical publications of the parties to be placed under exclusively Communist editorship.

The Second Congress of the Third International should instruct its Executive Committee formally to accept these and similar parties into the Third International after ascertaining that all these conditions have actually been met and that the activities of the parties have assumed a communist character.

16.As to the question of the conduct of Communists now holding a minority of the responsible posts in these and similar parties, the Second Congress of the Communist International should resolve that, in view of the obvious growth of sincere sympathy for communism among working men belonging to these parties, it would be undesirable for Communists to resign from the latter, as long as they can carry on work within them for the recognition of the dictatorship of the proletariat and Soviet government, and as long as it is possible to criticise the opportunists and Centrists who still remain in these parties.

At the same time, the Second Congress of the Third International should declare in favour of Communist groups and organisations, or groups and organisations sympathising with communism, joining the Labour Party in Great Britain, despite its membership in the Second International. As long as this party ensures its affiliated organisations their present freedom of criticism and freedom to carry on work of propaganda, agitation and organisation in favour of the dictatorship of the proletariat and Soviet government, and as long as this party preserves the character of a federation of all trade union organisations of the working class, it is imperative for Communists to do everything and to make certain compromises in order to be able to exercise their influence on the broadest masses of the workers, to expose their opportunist leaders from a higher tribune, that is in fuller view of the masses, and to hasten the transfer of political power from the direct representatives of the bourgeoisie to the “labour lieutenants of the capitalist class”, so that the masses may be more quickly weaned away from their last illusions on this score.

17.Concerning the Socialist Party of Italy, the Second Congress of the Third International considers that the criticism of that party and the practical proposals submitted to the National Council of the Socialist Party of Italy in the name of the party’s Turin section, [10] as set forth in L’Ordine Nuovo of May 8, 1920, are in the main correct and are fully in keeping with the fundamental principles of the Third International.

Accordingly, the Second Congress of the Third International requests the Socialist Party of Italy to convene a special congress to discuss these proposals and also all the decisions of the two Congresses of the Communist International for the purpose of rectifying the party’s line and of purging it, particularly its parliamentary group, of non-Communist elements.

18.The Second Congress of the Third International considers erroneous the views on the Party’s relation to the class and to the masses, and the view that it is not obligatory for Communist parties to participate in bourgeois parliaments and in reactionary trade unions. These views have been refuted in detail in special decisions of the present Congress, and advocated most fully by the Communist Workers’ Party of Germany, and partly by the Communist Party of Switzerland [11] , by Kommunismus , organ of the East-European Secretariat of the Communist International in Vienna, by the now dissolved secretariat in Amsterdam, by several Dutch comrades, by several Communist organisations in Great Britain, as, for example, the Workers’ Socialist Federation, etc., and also by the Industrial Workers of the World in the U.S.A. and the Shop Stewards’ Committees in Great Britain, etc.

Nevertheless, the Second. Congress of the Third International considers it possible and desirable that those of the above-mentioned organisations which have not yet officially affiliated to the Communist International should do so immediately; for in the present instance, particularly as regards the Industrial Workers of the World in the U.S.A. and Australia, as well as the Shop Stewards’ Committees in Great Britain, we are dealing with a profoundly proletarian and mass movement, which in all essentials actually stands by the basic principles of the Communist International. The erroneous views held by these organisations regarding participation in bourgeois parliaments can be explained, not so much by the influence of elements coming from the bourgeoisie, who bring their essentially petty-bourgeois views into the movement—views such as anarchists often hold—as by the political inexperience of proletarians who are quite revolutionary and connected with the masses.

For this reason, the Second Congress of the Third International requests all Communist organisations and groups in the Anglo-Saxon countries, even if the Industrial Workers of the World and the Shop Stewards’ Committees do not immediately affiliate to the Third International, to pursue a very friendly policy towards these organisations, to establish closer contacts with them and the masses that sympathise with them, and to explain to them in a friendly spirit—on the basis of the experience of all revolutions, and particularly of the three Russian revolutions of the twentieth century—the erroneousness of their views as set forth above, and not to desist from further efforts to amalgamate with these organisations to form a single Communist party.

19.In this connection, the Congress draws the attention of all comrades, particularly in the Latin and Anglo-Saxon countries, to the fact that, since the war, a profound ideological division has been taking place among anarchists all over the world regarding the attitude to be adopted towards the dictatorship of the proletariat and Soviet government. Moreover, a proper understanding of these principles is particularly to be seen among proletarian elements that have often been impelled towards anarchism by a perfectly legitimate hatred of the opportunism and reformism of the parties of the Second International. That understanding is growing the more widespread among them, the more familiar they become with the experience of Russia, Finland, Hungary, Latvia, Poland and Germany.

The Congress therefore considers it the duty of all Communists to do everything to help all proletarian mass elements to abandon anarchism and come over to the side of the Third International. The Congress points out that the measure in which genuinely Communist parties succeed in winning mass proletarian elements rather than intellectual, and petty-bourgeois elements away from anarchism, is a criterion of the success of those Parties.

July 4, 1920

[6] Lenin is quoting from Marx’s work “Zur Kritik der Hegelschen Rechtsphilosophie” (see Marx/Engels, Werke , Bd. 1, S. 385).

[7] The American Socialist Party was formed in July 1901 at a congress held in Indianapolis, as the result of a merger of groups that had broken away from the Socialist Workers’ Party and the Social-Democratic Party of the U.S.A. Among the new party’s organisers was Eugene Debs, a popular figure in the U.S. labour movement. The social composition of the party was not uniform, it contained native-born and immigrant workers, as well as small farmers and people of petty-bourgeois origin. The Centrist and the Right-wing opportunist leaders of the party (Victor Berger, Morris Hillquit and others) denied the necessity of the proletarian dictatorship, renounced revolutionary methods of struggle, and reduced all party activities to participation in election campaigns. During the First World War (1914-18) three trends appeared in the Socialist Party: the social-chauvinists, who supported the imperialist policy of the Administration, the Centrists, who opposed the imperialist war only in word, and the revolutionary minority, who took an internationalist stand and struggled against the war.

The Socialist Party’s Left wing, headed by Charles Ruthenberg, William Foster, William Haywood and others, relying on the proletarian elements, waged a struggle against the party’s opportunist leadership, for independent proletarian action and the formation of industrial trade unions based on the principles of the class struggle. In 1919 a split took place in the Socialist Party. The party’s Left wing broke away, bccoming the initiator and nucleus of the Communist Party of the U.S.A. At present the Socialist Party is a small sectarian organisation.

[8] The Social-Democratic Party of Switzerland (known as the Swiss Socialist Party) was formed in the seventies of the last century and affiliated to the First International. The party was re-formed in 1888. The opportunists were very influential in the party, and during the First World War took a social-chauvinist stand. In the autumn of 1916, the Party’s Right wing broke away to form their own organisation. The majority, headed by Robert Grimm, took a Centrist, social-pacifist stand, while the Left wing of the party adhered to an internationalist stand. The Great October Socialist Revolution in Russia influenced and strengthened the Left wing which, in December 1920, broke away and joined the Communist Party of Switzerland in 1921 (see Note 69).

[9] “Draft (or the Theses) of the R.C.P.’s Reply to a Letter from the German Independent Social-Democratic Party” (see present edition, Vol. 30, pp. 337-44).

[10] The Turin section accused the Italian Socialist Party with its conciliatory leadership, of failing to give a correct analysis of events, in the conditions of the revolutionary upsurge in Italy (1919-20) that had created the possibility of the seizure of political power by the proletariat, and of having failed to advance any slogan acceptable to the revolutionary masses, and expel the reformists from its ranks. The section made a number of practical proposals: the expulsion of the opportunists from the party; the formation of communist groups in each factory, in the trade unions, co-operatives, and army barracks, the setting-up of factory T.U. committees to organise control of production in industry and agriculture. The section demanded that work to prepare the working masses for the creation of Soviets should be begun at once.

[11] In October 1918, part of the Social-Democrat Left wing united to form the Communist Party of Switzerland. It was not a big party at the time, being represented by two delegates at the Second Congress of the Comintern.

In December 1920, the Left wing of the Swiss Social-Democratic Party broke away from it, and raised the question of forming a strong section of the Communist International in Switzerland. At a congress held in Zurich in March 1921, attended by 28 delegates from the Communist Party and 145 delegates representing the former Left wing of the Social-Democratic Party, the two groups officially united to form a single Communist Party of Switzerland.

Collected Works Volume 31 Collected Works Table of Contents Lenin Works Archive

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Forensic Sci Int Synerg

A review of the newly identified impurity profiles in methamphetamine seizures

Isaac onoka.

a Department of Chemistry, College of Natural and Mathematical Sciences, University of Dodoma, P.O Box 259, Dodoma, Tanzania

Andrew Toyi Banyika

Protibha nath banerjee, john j. makangara, laurence dujourdy.

b Agrosup Dijon, Department of Engineering and Process Science, Research Support Service Agrosup Dijon - DSIP - Bât. Longelles 26 bd Dr Petitjean, BP 87999 21079, Dijon Cedex, France

Forensic intelligence of synthetic illicit drugs suffers a problem of continuous introduction of new synthetic methods, modification of the existing routes of manufacture, and adulterations practiced by criminal networks. Impurity profiling has been indispensable in methamphetamine intelligence based on precursors, synthetic routes, and chemical modifications during trafficking. Law enforcement authorities maintain the credibility and integrity of intelligence information through constant monitoring of the chemical signatures in the illicit drug market.

Changes in the synthetic pattern result in new impurity profiles that are important in keeping valuable intelligence information on clandestine laboratories, new synthetic routes, trafficking patterns, and geographical sources of illicit Methamphetamine.

This review presents a critical analysis of the methamphetamine impurity profiles and more specifically, profiling based on impurity profiles from Leuckart, Reductive amination, Moscow, Emde, Nagai, Birch, Moscow route; a recent nitrostyrene route and stable isotope signatures. It also highlights the discrimination of ephedrine from pseudoephedrine sources and the emerging methamphetamine profiling based on stable isotopes.

1. Introduction

Methamphetamine is a schedule II controlled substance according to the Single Convention on Narcotic drugs [ 1 ] and the United Nations Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances, 1988 [ 2 ]. It is highly addictive drug with a potent central nervous system (CNS) stimulant properties [ 3 , 4 ]. The United Nations Office on Drugs and Crime (UNODC) report MA as the most abused drugs worldwide [ 3 , 5 , 6 ]. For the last two decades, the use of MA has been increasing in many countries worldwide [ 3 , [6] , [7] , [8] , [9] , [10] ]. In Japan, about 15,000 drug arrests were from cases related to MA [ 11 ] accounting for 90% of all reported violations [ 12 ]. Previous studies have documented the prevalence of methamphetamine over other synthetic drugs elsewhere [ 13 , 14 ].

The impurity profiling of MA provides the linkage of illicit drug seizures based on the chemical signatures contained in the seized illicit drugs [ [15] , [16] , [17] ]. The method uses organic and inorganic impurities which are by-products of reactions in the final formulation of MA. It has successfully been used to establish intelligence information in France [ 18 , 19 ], Australia [ 20 , 21 ], Thailand [ 22 , 23 ], China [ 24 ], Philipines [ 25 ], Japan [ 22 , 26 , 27 ], USA [ 28 ], Spain [ 29 ], Korea [ 30 , 31 ] and in many other places worldwide [ 7 , 19 , [32] , [33] , [34] , [35] ]. Recently, the emerging complementary profiling method based on stable isotopes has drawn the interest of many researchers [ [36] , [37] , [38] ]; its details will be included in this review.

The chemical analysis of illegal drugs provides valuable information about the conspiracy links and trafficking routes, categorizing the seizures based on the signatures, thereby identifying their origins [ 39 , 40 ]. As a complementary law enforcement investigative work, it provides a background intelligence information concerning the number of sources of drugs, whether those sources are within a country or are internationally based and also unveiling the points of distribution and distribution networks. Similarly, the impurity profiles identifies the emergence of new clandestine laboratories and their associated synthetic methods, which, in turn, provides background intelligence information [ 41 ]. Chemical profiling marks the principal purpose of the intelligence of illicit drugs by establishing a link between the clandestine laboratories, suppliers, and users. The chemical information obtained from a drug can indicate its synthetic method, adulterations during trafficking, and the operations of the criminal networks [ 42 ].

Generally, the fundermental role of a forensic chemist in drug profiling is extract the chemical signatures that can be used to establish the degree of commonality of seizures with their origins or a specific group of other samples [ 6 , 43 ] as well as linking the signatures with the possible synthetic methods, conditions, and post-production modifications. A comprehensive examination and comparison of the chemical signatures has found a growing application strategically at the macro level [ 6 ] and tactically at the micro-level [ 35 ]. These advances have helped the police and criminal investigators at both national and global scales to establish the dynamics of illicit drug markets, locate the drug traffickers, establish conspiracies links between dealers and users [ 11 , 43 , 44 ].

In this decade, extensive number of research studies on the chemical profiling of MA and its derivatives are focusing on the determination of organic and inorganic impurities [ 19 , 45 ], determination of synthetic routes [ 46 ], synthesis of the impurities [ 17 , 46 ] identification of the impurities [ 17 , 39 , 40 ] concentration in body fluids [ 47 ] characterization [ 48 ] and the extraction and separations of the impurities [ 49 , 50 ].

In this paper, we critically analyze the impurity profiles of MA synthesized from ephedrine, pseudoephedrine, and 1-phenyl-2-propanone (P2P) precursors and subsequently analyze their potential use for intelligence perspective.

1.1. The synthetic schemes of methamphetamine and the specific-route impurities

The Forensic intelligence of illicit drugs is an exciting subject and very challenging. In totality, it embraces the determination, identification, and characterization of the individual components in the final formulation of illicit drugs regarded in this review as the impurities, intermediates, and the contaminants. Depending on the level of operation of a clandestine laboratory, an illegal drug is an assemblage of constituents carrying the information about the synthetic route [ 16 , 32 ], condition-specifics [ 19 ], reagents [ 30 ], adulterations during trafficking, synthetic batches and sometimes the chemical process level of the cooks (purity) [ 40 , 51 ].

Like in any other reaction, each synthetic scheme has by-products emanating from the conversion of the precursors to MA. For instance, some constituents are by-products of the reaction conditions; others are formed from the conversion of precursors to intermediates and from intermediates to MA while others are intentionally added as cutting agents for potency or weight [ 52 ] and as artifacts described by Broséus et al. [ 53 ]. Therefore, the final formulation of MA is charceterized by a variation of the relative abundance of the major by-products, intermediates, and impurities that defines a chemical signature.

Although different MA seizures produced from the same precursor, using similar route and the same reagents have related impurity profiles; some intra and inter batch variations may still occur due to varying reaction conditions. This variation is essential to distinguish chemists (cooks) by attaching a specific profile to reaction conditions practiced by a particular clandestine laboratory.

Based on a certain probability of a link corresponding to the calculation of a threshold, two or more exhibits will have the same chemical profiles supporting the fact that they originate from the same batch, with the strength of support increasing as profiles become more complex [ 54 ]. Otherwise, a range not meeting the threshold can only distinguish the samples rather than discriminating against their cooks.

For quite a long time, the clandestine synthesis of MA employs three major precursors, namely ephedrine, pseudoephedrine, and the 1-phenyl-2-propanone (P2P) [ [55] , [56] , [57] , [58] , [59] ]. With P2P ( Fig. 1 ), the Leuckart route (VI) and reductive amination are the most commonly used routes for the synthesis of MA [ 48 , 60 ]. In contrast, ephedrine/pseudoephedrine precursors ( Fig. 2 ) convert to MA through the Nagai (I) [ 52 , 61 ], Emde (II) [ 52 , 61 ], Hypo (III) [ 62 ], Moscow (IV) [ 63 ] Rosenmund (V) [ 64 , 65 ] and Birch/Nazi (VI) pathways [ 66 , 67 ].

Synthesis of MA from P2P routes: (I) Pd/H 2 /NH 2 CH 3 , (II) NaBH 4 /NH 2 CH 3 , (III) NaBH 3 CN/NH 2 CH 3 , (IV) Hg/Al/NH 2 CH 3 , (V) Pt/H 2 /NH 2 CH 3 (VI) HCl/H 2 O.

Ephredine/Pseudoephredine synthetic routes: (I) Nagai route, (II) Emde route, (III) Hypo route, (IV) Moscow route (V) Rosenmund and (VI) Nazi/Birch route.

As one of the main MA precursors, P2P reaction scheme involves the reductive amination reactions Fig. 1 (I–V) and the Leuckart (HCL/H 2 O). The reductive amination reaction of P2P to MA is achieved through Pd/H 2 /NH 2 CH 3 , NaBH 4 /NH 2 CH 3 , NaBH 3 CN/NH 2 CH 3 , HCl/H 2 O, Pt/H 2 /NH 2 CH 3 , and Hg/Al/NH 2 CH 3 , however, the aluminum/mercury (Al/Hg) amalgam in a slightly acidic media method is reported to be the most commonly used method in Europe and USA [ 48 ]. Although the method has long history, 1-phenyl-2-propanol formed from the direct reduction the precursor, P2P, remains the potential intelligence impurity profile [ 48 , 68 ].

Described by Verweij in 1989 [ 68 ], the Leuckart route (Fig. 1VI) is achieved by the addition of N- methylformamide, methylamine or formic acid followed by H 2 SO 4 or HCl to form MA. By means of N- methylformamide, the reaction result in a Leuckart route determinant; the N- formylmethamphetamine disputed by Qi et al. [ 20 ] and Barron et al. [ 69 ]; and non-synthetic route determinants namely dibenzylketone, R -benzyl- N -methylphenethylamine, and N- methyldiphenethylamine [ 70 ]. The synthetic-route character of N- formylmethamphetamine argumented by Barron et al. and Qi et al. was resolved by the identification of α,α′- dimethyldiphenethylamine and N , α,α′- trimethyldiphenethylamine by Barron et al. The two impurities were later confirmed by Vanitha et al. [ 48 ] having identified them in Leuckart based MAs only.

The Nagai route ( Fig. 2 (I)) is associated with the formation of (2 E ) -N- methyl-3-phenyl -N- (1-phenylpropan-2-yl)prop-2-enamide, iodoephedrine, N- methyl -N- ( α -methylphenyl)amino-1-phenyl-2-propanone and ( Z ) -N- methyl -N- ( α -methylphenylethyl)-3-phenylpropanamide [ 65 , 71 ].The impurities are formed from the nucleophilic substitution reaction of – OH group of ephedrine/pseudoephedrine to form idoephedrine or iodopseudoephedrine. The intermediary iodine is liable to internal nucleophilic attack from the adjacent nitrogen to form cis - and trans -1,2-dimethyl-3-phenylaziridines which is reduced to MA or hydrolysed to P2P [ 72 ]. In a prolonged acidic conditions, the latter undergo condensation to form 1,3-dimethyl-2-phenylnaphthalene and 1-benzyl-3-methylnaphthalene reported to be the specific synthetic route signatures [ 73 , 74 ].

The conversion of ephedrine/pseudoephedrine to MA via Emde route is the dominant synthetic route in the South East Asia [ 73 ]. In contrast to the Nagai route, the Emde reaction scheme is augmented by S N 1 substitution (intramolecular nucleophilic displacement) or S N 2 substitution (intermolecular displacement) of the –OH in ephedrine/pseudoephedrine with chloride to form a racemic mixture of (+)-chloropseudoephedrine and (-)-chloroephedrine of variable impurity concentrations [ 75 , 76 ]. The (+)-chloropseudoephedrine and (-)-chloroephedrine can then undergo a cyclic ring closure to form cis -1,2-dimethyl-3-phenylaziridines and trans -1,2-dimethyl-3-phenylaziridines, respectively. Accordingly, (+)-norpseudoephedrine and (-)-norephedrine alternative precursors undergo similar reaction to form (+)-chloromethylpseudoephedrine and (-)-chloromethylephedrine. These intermediates may eliminate the HCl to form 1-propenylbenzene and 2-propenylbenzene or can undergo a rearrangement to form 1-dimethylamino-1-phenyl-2-chloropropane [ 77 ]. The route specific potential of the intermediary aziridines was contradicted by Ko et al. [ 37 ] and Salouros et al. [ 59 ] having identified 1-methylamino-1-phenyl-2-chloropropane as a vapour-phase nucleophilic product of the aziridine and N -methyl-1-(4-[2-(methylamino)propyl]phenyl)-1-phenylpropan-2-amine. The latter was recogonized in “Moscow” and Nagai related methods and could not qualify as a route specific impurity for Emde route [ 63 , 78 ]. Ko et al. instead identified and proposed 1-methylamino-1-phenyl-2-chloropropane (chloroephedrine/chloropseudoephedrine as route specific impurity for the Emde method. Other non-route specific impurities include methyephedrine, N- formylephedrine, N- acetylephedrine, N,O- diacetylephedrine and N -acetylamphetamine.

“Moscow” method Fig. 2 (IV) is achieved by a reaction between ephedrine/pseudoephedrine with red phosphorus and iodine in water [ 59 ]. Its mechanism is treasured in the regenerative role of red phosphorus [ 79 ]. Skinner [ 73 ] as supported by NicDaéid et al. [ 45 ] proposed a scheme based on the oxidation of P by I 2 to diphosphorus tetraiodide (P 2 I 4 ) followed by the decomposition of P 2 I 4 in water to form phosphoric acid and phosphonium iodide. The mixture them converts to hydroiodic acid (HI) and phosphine (PH 3 ) upon heating. The former protonates the –OH of ephedrine/pseudoephedrine to form aziridine intermediates which potentially reduce to MA as in the case of the Nagai route [ 73 ].

Birch/Nazi route ( Fig. 2 (VI) ) is a reduction reaction of ephedrine/psedoephedrine using excess alkali metal e.g., lithium/sodium in liquid ammonia to form 1-(1ʹ,4ʹ-cyclohexadienyl)-2-methylaminopropane (CMP) [ 54 ], notated as ( S )– N -Methyl-1-(1,4-cyclohexadienyl)-2-propanamine [ 66 ]. The impurity is the most commonly encountered MA impurity prepared by the Birch route. Its reaction scheme is based on the role of alkali metals preferably lithium as a proton source for the –OH of ephedrine/pseudoephedrine. As lithium protonates the precursor, NH 3 facilitate the reduction of the aromatic rings to form 1-(1,4-cyclohexadienyl)-2-methylaminopropane [ 80 ]. This primary impurity associated with the lithium - ammonia method normally results in high CMP:MA ratio limiting the isolation of the impurity. Martinez et al. [ 81 ] proposed potassium permanganate and aquous base for effective CMP isolation.

1.2. A paradigm shift in methamphetamine precursor production

As a result of the crackdown measures taken against the production, trafficking and the availability of the P2P and ephedrine/pesudoephedrine, access to the precursors has shifted to the illicit manufacture of the precursors through readily available starting materials with new routes leading to the emergence of new impurity profiles [ [82] , [83] , [84] ].

For quite a long time, the synthesis of phenyl-2-propanone is through a vast number of starting materials such as α -phenylacetoacetonitrile [ 83 , 84 ], α -phenyl- β -methyleneglycol [ 85 ], α -phenylisopropyl alcohol [ 86 ] phenylacylmalonic ester [ 87 ] phenylacetyl chloride [ 88 ] α -methylstyrene with thallium nitrate, and benzene via o,o-diprotonated nitro olefin [ 89 ], β -methyl- β-N itrostyrene, and phenylacetic acid (PAA).

Although several P2P synthetic schemes were available in the 1980s, the illicit production of P2P was mainly through Phenylacetic acid (PAA) via acetic anhydride and lead (II) acetate; and β -methyl- β-N itrostyrene via Fe/H + [ 65 ].

A recent twist in the production of P2P has recently involved the nitrostyrene method (NTS) [ 82 ]. This emerging synthetic scheme results in nitrostyrene recently identified in MA samples seized in Mexico [ 55 ] and the USA [ 82 ]. The NTS method uses benzaldehyde and nitroethane in Knoevenagel reaction to form a nitrostyrene, yellow solid, which converts to P2P in the presence of iron powder and hydrochloric acid [ [82] , [83] , [84] , [85] , [86] , [87] , [88] , [89] , [90] ].

The evolution of the P2P clandestine chemistry is further confirmed by the re-emergence of a new impurity profile in place of α -benzyl -N -methylphenethylamine and trans-N -methyl-4-methyl-5-phenyl-4-penten-2-amine from the usual foul-smelting of a crystalline PAA [ 82 ]. The synthesis of P2P from PAA ( Fig. 3 (a)) utilizes the then easily available ethyl phenylacetate (EtPA). However, a recent decline of EtPA and its associated esters and amides resulted in a shift in the P2P precursors ( Fig. 3 (b)) resulting in the emergence of new characteristic impurities recently reported in the in Australia [ 91 ] and observed in the USA [ 82 ].

A paradigm shift in MA precursor production: (a) PAA method,(b) nitrostyrene (NTS) method (c) 1–5 synthetic routes of P2P to MA.

The P2P produced from the PAA method and nitrostyrene (NTS) convert to MA with route-specific markers intelligently used to trace the sources of P2P.

The dynamics of the operations of criminal MA networks is one of the exciting profiling topics appealing to close monitoring by intelligence agencies. A recent Drug Enforcement Administration (DEA) MA Profiling Program (MPP) done in the USA [ 82 , 92 ] recorded trade-off impurity profiles assigned to pseudoephedrine route to those assigned to P2P precursors. According to the MA impurity profiles documented by this program, the impurity profiles derived from pseudoephedrine decreased significantly since 2007 with increasing impurity profiles derived from P2P. This shift was associated with a spike in unknown synthetic route assignments and a sharp decrease (84%) in samples assigned to a P2P-based recipe in the first quarter of 2015 [ 82 , 91 ].

1.3. The emerging methamphetamine impurity profiles

In response to the crackdown measures imposed on the production and trafficking of MA and its precursor chemicals, clandestine laboratories circumvent the law enforcement authorities by deriving the precursors from uncontrolled substances such as phenyl acetic Acid (PAA) [ 40 ], nitrostyren [ 82 ], and legal medicine [ 93 ] resulting into the emergence of new impurity profiles.

The emergence of impurity profiles such as dimethylamphetamine and p -methoxyamphetamine was recently documented by Stojanovska et al. [ 54 ] and supported by a literature collection of impurity profiles and synthetic route of manufacture of methylamphetamine, 3,4-methylenedioxymethylamphetamine, amphetamine, dimethylamphetamine, and p -methoxyamphetamine as well as the recently identified less potent l -methamphetamine in place of d -methamphetamine in the United States [ 57 ].

Since their identification in seized MA, several MA impurity profiling [ 19 , 53 , 76 , 91 ] reveal profiles that are potentially important for strategic, tactical and operational intelligence of MA in the USA [ 57 ], France [ 18 ] Australia [ 20 , 44 , [94] , [95] , [96] ] Korea [ 30 ], Iran [ 97 ], China [ 24 ], Philipines [ 25 ], Japan [ 98 ] and Thailand [ 22 ].

1.3.1. Impurities from metal catalytic hydrogenation

Metal catalytic hydrogenation of ephedrine/pseudoephedrine and P2P is one of the oldest MA synthetic methods [ 35 , 40 , [99] , [100] , [101] ]. Using ephedrine/pseudoephedrine, the clandestine laboratories often use palladium via the Rosenmund route [ 101 ], lithium/NH 3 via Birch route, and nickel via Emde route [ 100 ]. The reaction involves the reduction of the C-X (X-halo, phosphate, and sulfate) ( Fig. 4 ) rather than the benzylic OH group to form methamphetamine [ 100 ].

C-X reduction to form MA: X = Cl - , SO 4 -2 , H 2 PO 4 , and ClO 4 .

Using P2P, an imine intermediate MA base is formed from a reaction of between P2P with methylamine. The MA freebase is then distilled and directly converted to hydrochloride salt [ 99 , 100 ]. Fig. 5 represents a reductive amination for the conversion of P2P to MA hydrochloride.

Imine reduction to Methamphetamine: (I) P2P, (II) Methylamine, (III) Phenyl acetone methylimine (IV), Methamphetamine freebase, (V) Methamphetamine hydrochloride salt. (a) Removal of water, (b) reduction of imine to amine, (c) addition of hydrogen chloride.

Reaction (c) occurs through heterogeneous reactions with internal or external sources of hydrogen in the presence of Pd, Pd/C, Pd/BaSO4, Pt, Pt/C, CuO, CaSO4, BaSO4, Raney Nickel (Ni-Al) [ 100 ]. Tracking the traces of metals in the final formulation of MA has been used to determine the synthetic routes. MA manufactured from ephedrine/pseudoephedrine through the Emde and Nagai methods was found to contain N- methyl-1-{4-[2-(methylamino) propyl]phenyl}-1-phenylpropan-2-amine and (1 S ,2 S )-1-methylamino-1-phenyl-2-chloropropane as route-specific impurities [ 61 ]. Since their identification, they have been used as Emde route-specific signatures [ 61 , 76 , 77 ].

Furthermore, (1 S ,2 S )-1-methylamino-1-phenyl-2-chloropropane has recently been used as an additional route-specific marker impurity synthesized from ephedrine via chloroephedrine by the Emde route ( Fig. 6 ) [ 64 ]. The metal catalysis reaction of (1 R , 2 S )-(+)-ephedrine or (1 S , 2 S )-(+)-pseudoephedrine results in the formation of chloroephedrine/chloropseudoephedrine which is hydrogenated to ( S )-(+)-Methamphetamine.

Metal catalytic reduction of (1 R , 2 S )-(+)-ephedrine or (1 S , 2 S )-(+)-pseudoephedrine.

Recent profiling of reductive amination of P2P made from PAA/lead (II) based MA [ 102 ] elucidated trans-N -methyl-4-methyl-5-phenyl-4-penten-2-amine and α -benzyl -N -methylphenethylamine. Trans-N -methyl-4-methyl-5-phenyl-4-penten-2-amine used as a route-specific marker was presumed acetone and P2P condensation product, however, this assumption could not explain why the little amount of the impurity and its associated intermediates produced even if the P2P was refluxed in acetone for a long time.

Furthermore, an attempt to produce P2P using a Dakin-West and lead (II) acetate conditions [ 102 ] were futile and could not yield the expected trans-N -methyl-4-methyl-5-phenyl-4-penten-2-amine as an impurity.

The best reasoning so far centers the argument on the role of a low-level 4-carbon acetate unit as an intermediate. Since acetic acid undergoes decarboxylation in aqueous solution over a range of temperatures, a route-specific marker impurity, trans-N -methyl-4-methyl-5-phenyl-4-penten-2-amine results from an intramolecular reaction of lead acetate with P2P via chelation controlled transition states followed by decarboxylation [ 102 , 103 ]. Fig. 7 shows the proposed mechanism for the formation of this route-specific marker.

The reaction mechanism for the formation of trans-N -methyl-4-methyl-5-phenyl-4-penten-2-amine.

The reductive amination of P2P is also associated with the formation of α -benzyl -N -methylphenethylamine as a synthetic route characteristic impurity. The MPP identified the contaminant at the DEA’s Special Testing and Research Laboratory [ 102 ].

The emergence of new impurity profiles in MA analysis suggests, possibly, a change in the synthetic route parameters or the synthesis of precursor chemicals. The foul-smelting of a crystalline PAA results in new impurity profiles monitored in seized MA samples. The impurities associated with the modified P2P synthetic pathway are α -benzyl -N -methylphenethylamine and trans-N -methyl-4-methyl-5-phenyl-4-penten-2-amine) [ 82 ]. They have been used to track MA synthesized from PAA.

The emergence of N- butylamphetamine and N- cyclohexylamphetamine in seized MA has recently triggered the nitroalkene chemistry. The two impurities result from a Knoevenagel reaction of benzaldehyde and nitroethane to form a nitrostyrene [ 90 ].

Toske et al. [ 82 ] referred to this method as a nitrostyrene method (NTS) or a nitropropene method. The catalytic activities of butylamine/cyclohexylamine influence the conversion of the P2P precursors. The catalysts react with benzaldehyde to form imine, which then reacts with the nitroalkane to form a nitrostyrene as an intermediate [ 82 ]. The reaction mixture at this step contains nitrostyrene and extractable cyclohexylamine/butylamine with a significant reaction potential. Based on a reaction proposed by Hass et al. [ 90 ], nitrostyrene converts to P2P in the presence of iron powder and hydrochloric acid. The extractable cyclohexylamine/butylamine can then react with P2P to form the stable N- butylamphetamine, and N- cyclohexylamphetamine elucidated in MA seizures. Fig. 8 (a) and (b) represents the formation of N- butylamphetamine and N- cyclohexylamphetamine.

Impurity profiles for NTS synthetic method. (a) N- Butylamphetamine synthetic route, (b) N- Clyclohexylamphetamine route.

Since 2015, the two impurities were detected in MA seizures collected in the USA [ 82 ]. The identification of the two impurities has been fundamental in tracking the P2P based MA synthesized by the nitrostyrene chemistry.

1.3.2. Emerging impurity profiles from pharmaceutical compounds

In response to the crackdown measures taken against controlled substances, ephedrine, and pseudoephedrine, other adaptation strategies used by clandestine laboratories are co-ingredients of legal medicines, direct extraction from ephedra plants [ 77 , 93 , 103 , 104 ] as well as direct synthesis from easily available starting materials [ 83 , 84 ]. Although Lee et al. [ 31 ] reports less common MA crystals containing pharmaceutical impurities, Barker and Antia [ 77 ] had a different opinion on the most common sources of ephedrine and pseudoephedrine used to synthesize crystal MA. The latter as supported by Liu et al. [ 93 ] who also considered medicinal drugs as the most common sources of pseudoephedrine and ephedrine.

Synthesis from legal medicines is the most common coping strategy practiced by clandestine laboratories to avoid strict measures from the law enforcement authorities [ 77 ]. The legal medicines approach result in MA whose final formulation contains pharmaceutical signatures that used to reflect the trends in precursor chemicals, manufacturing sources, and the trafficking patterns organized by the criminal networks. Unlike by-products, there is limited literature linking pharmaceutical impurities to the synthetic route of MA.

More recently, the MA profiling based on synthetic pharmaceutical signatures has been done in Korea [ 31 ], Iran [ 97 ], China [ 24 ], Japan [ 98 ] and Thailand [ 22 ]. several studies have been done in this field, more research is required to unveil the potential of pharmaceutical impurities beyond their existence as sole impurities into the final MA formulations. Tracking the by-products down to their origin and their point of entry may provide the potential of establishing synthetic routes using pharmaceutical contaminants.

In a profiling program conducted in Korea between 2006 and 2011, Acetaminophen, Caffeine, Phenacetin, Ambroxol, Chlorpheniramine, Desloratadine, Barbital, Ketamine, Procaine, and Dimethylsulfone were elucidated as characteristic pharmaceutical impurities [ 31 ]. The profiling program linked these impurities with cold medicines, cold relievers, ingredients of analgesic drugs [ 105 ], expectorant, and dietary supplements extracted together with ephedrine/pseudoephedrine. In contrast, others added as adulterants during trafficking. While the pharmaceutical medicines demonstrate growing intelligence phenomena, tracking the specific legal drugs used in the MA production and the post-production modifications is an area of utmost interest.

Interestingly, in 2010, chlorpheniramine was identified in both Korea [ 31 ] and Iran [ 106 ], indicating a cross-border operation of the criminal networks. The emergence of these impurities was a direct indication of the use of legal medicines and their associated analgesic and co-ingredients containing ephedrine or pseudoephedrine.

Furthermore, Lee et al. [ 31 ] identified a pharmaceutical recipe based dimethyl sulfone from seized MA in Korea. The impurity was associated with the recipe used in medicinal drugs containing ephedrine/pseudoephedrine as well as an adulterant used in cutting MA. The impurity was previously identified in Korea (1996–2003) and USA (1996–2003) [ 30 , 107 ] emerged in Australia (1998–2002) [ 21 ], re-surfaced in (USA 2007) [ 108 ], Korea (2006–2011) [ 31 ] and Japan (2006–2007) [ 98 ]. The observed trend in the occurrence and re-emergence of dimethyl sulfone in the seized MA is potentially important in linking the operation of criminals in the countries. Although the determination of homogeneity might be very challenging, linking the dimethyl sulfone to its common source is essential for integrated intelligence.

Unlike other countries, a new profiling program based on pharmaceutical impurities conducted China recorded a new trend of impurity profiles of MA synthesized from ephedrine/pseudoephedrine [ 93 ]. Liu et al. reported tablets with Theophylline-Ephedrine, Ephedrine-Diphenhydramine, Pseudoephedrine, Dextromethorphan, and Chlorpheniramine as a new set of legal medicines commonly used as a source of ephedrine/pseudoephedrine. These drugs contain alkaline substances such as chlortrimeton, diphenhydramine, dextromethorphan, and triprolidine with the potential to form characteristic impurities. Their profiles information is not only used for monitoring the routine trends in precursor chemicals but also for the identification of the seized materials, smuggling patterns, and the determination of the synthetic routes [ 31 , 109 ].

Liu et al. systematically determined N 1 , N 1 , N 2 -trimethyl -N 2 -(1-phenylpropan-2-yl)ethane-1,2-diamine, which was assigned a characteristic impurity derived from pharmaceutical products containing ephedrine/pseudoephedrine and diphenhydramine. Unlike other pharmaceutical contaminants, the impurity is a product of a reaction between MA and traces of diphenhydramine derivative, which is co-extracted with ephedrine/pseudoephedrine. As a pharmaceutical co-extract of ephedrine/ephedrine derived diphenhydramine, the traces of the P2P precursor undergo band dissociation with HI in an I/P route to form 2-iodo -N , N -dimethylethanamine as an intermediate and traces of diphenyl methanol. The 2-iodo -N , N- dimethylethanamine then reacts with MA to form N 1 , N 1 , N 2 -trimethyl -N 2 -(1-phenylpropan-2-yl)ethane-1,2-diamine as shown in Fig. 9 .

A synthetic mechanism of N 1 ,N 1 ,N 2 -trimethyl-N 2 -(1-phenylpropaN-2-yl)ethane-1,2-diamine from diphenhydramine: (a) formation of methamphetamine, (b) dissociation of diphenhydramine to imine and diphenyl methanol, (c) reaction between imine and methamphetamine to form N 1 ,N 1 ,N 2 -trimethyl-N 2 -(1-phenylpropan-2-yl)ethane-1,2-diamine. Source [ 93 ].

In this reaction, the diphenhydramine is present as co-ingredients of legal medicine used for the synthesis of ephedrine/pseudoephedrine. The control of such drugs is essential for monitoring and identification of illicit production of ephedrine/pseudoephedrine from legal medicines.

1.3.3. Impurities discriminating ephedrine and pseudoephedrine synthetic routes

Ephedrine and pseudoephedrine are the basic precursors commonly used to synthesize MA beside the Phenyl-2-propanone [ 10 , 44 , 104 , 106 ]. A synthetic method using each of the precursor chemicals is associated with specific impurities that can intelligently discriminate against the MA synthetic method. From a forensic chemist’s viewpoint, tracking the impurities down to the level of discrimination ephedrine and pseudoephedrine is an ultimate goal. Many MA profiling methods based on ephedrine/pseudoephedrine end up with non-discriminatory results, deriving their conclusions from an unresolved analytical process.

Precursor discrimination based on identified impurities is another interesting intelligence work. In a recent study by Dujourdy et al. [ 19 ], 43 target impurities in MA were successfully characterized and discriminated using chemometric methods. Through clustering, the impurities identified from ephedrine, pseudoephedrine, and benzylmethylketone. In their work, 1-benzyl-3-methyl-naphthalene, and 1,3-dimethyl-2-phenyl-naphthalene were used to signify a route associated with ephedrine precursor.

Previously, N- formylmethamphetamine was considered a route-specific impurity for Leuckart route based MA [ 69 , 110 ]; however, the impurity has recently been identified in reductive amination based route for MA [ 20 , 99 ].

A realization of this challenge was reported by Khajeamiri et al. [ 106 ] in their work involving the reduction of ephedrine/pseudoephedrine with HI/red P. In their viewpoint, both ephedrine and pseudoephedrine react with HI/red P to form iodoephedrine, which undergoes a ring-opening to form commonly used route-specific impurities; the cis and trans -1,2-dimethyl-3-phenylaziridine [ 73 ].

Khajeamiri et al. articulated that 1,2-dimethyl-3-phenylaziridine is derivatized into N- methylmethamphetamine, N- ethylmethamphetamine, N- acetylmethamphetamine, acetic acid, N- benzyl-2-methylaziridine, methoxyphenyloxime amphetaminil, d -proline-1-phenylmethyl-methylester N- formylmethamphetamine, and dextromethorphane.

Reporting N- benzyl-2-methylaziridine as an emerging impurity, Khajeamiri et al. associated its formation with the conversion of 1,2-dimethyl-3-phenylaziridine into N- benzyl-2-methylaziridine during the formation of MA from ephedrine and pseudoephedrine.

Additionally, Khajeamiri et al. reported for the first time in 2012 the presence of Chlorpheniramine as a pharmaceutical-based impurity in MA. The impurity was later reported in Korea (2013) [ 31 , 49 ] and Iran [ 111 ]. The reports associated the impurity with pharmaceutical tablets used to synthesize pseudoephedrine precursors. Because chlorpheniramine is co-ingredient of pseudoephedrine tables only [ 49 ], it discriminates ephedrine and pseudoephedrine based MA.

1.3.4. Emerging signatures from stable isotopes

Stable isotopes composition in a MA sample has recently been used to profile MA seized in the USA [ 92 ] and Japan [ 112 ]. The technique employs natural abundance stable δ 13 C, δ 12 C, δ 15 N, δ 14 N, δ 2 H, δ 1 H and, δ 16 O, δ 17 O, δ 18 O and δ 32 S, δ 33 S, δ 34 S, δ 36 S compositions in samples to establish chemical signatures for evaluating the links between MA seizures and their production batches [ [113] , [114] , [115] , [116] ]. The isotopes have specific natural rations; however, compartmental isotope ratios vary as per the geographical origin of the source [ 36 ] which is the basis for MA profiling based on stable isotopes.

The stable isotope ratio presented in delta values, δ in per mill where (“mil” = 1000), written ‰). The calculation of delta value as proposed by Barrie [ 117 ] is shown in the equation below.

Where R Sample represents the ratio of the heavy to the light isotope measured for the sample while R Standard is the equivalent ratio for the standard.

Although the conventional analytical techniques through the existing GC [ 98 ], HPLC [ 110 ], GC-MS [ 33 ], and LC-MS-MS, ICP-MS [ [118] , [119] , [120] ], NMR [ 33 , 120 ] have been very effective in determining the type of precursor chemicals [ 100 , 121 ] synthetic route [ 16 ], and adulteration of illicit MA [ 28 , 48 , 54 , 122 ]; it has not been able to discriminate the precursors produced by different methods in the sense of identifying their origins. Furthermore, reductive amination routes usually have few impurity profiles that may not grant a successful impurity profiling [ 114 ]. The conventional techniques are also ineffective in traceability beyond sources of the starting materials [ 123 ].

In such circumstances, stable isotope analysis is a complementary technique that can individualize illicit MA samples based on the sources of their starting materials. Elsewhere, the method has successfully used in tracing studies in food [ 124 , 125 ], identification of illegal migrants [ 126 ], past human activities [ 122 ], and reconstruction of human diet [ 127 ].

In forensic intelligence of illicit drugs, stable isotopes technique unveil the hidden intrinsic precursor signatures that break the limits of the conventional impurity profiling by linking the seized MA and their batches to their synthetic origin [ 123 ]. Stable isotopes add value to the intelligence of illicit drugs based on impurity profiling.

MA produced by the same hidden laboratories, following the same method with the same kind of a precursor but different sources distinguished by examining their δ 13 C and δ 15 N values of their precursors [ 104 ]. In this respect, the variation of stable isotopes in seized MA can also trace the diversion of medicinal ephedrine for the illicit manufacture of MA.

Illicit ephedrine based MA was initially produced through a biosynthetic approach from the ephedra plant ( Fig. 10 (a)); however, a growing trend of total chemical synthesis ( Fig. 10 (b)) and semi-synthesis ( Fig. 10 (c)) have dominated the market.

Different sources of ephedrine: (a) extraction from ephedra plant, (b) chemosynthesis, (c) semi-synthesis.

The ephedrine produced through methods (a), (b) and (c) above will have different stable isotopic compositions used to track MA seizures. In principle, isotopic variation is due to different enrichment factors during the biochemical synthesis of raw materials for the precursor chemicals as well as the isotopic fractionation during the synthetic processes [ 60 ]. Although chemical synthesis a reliable source of ephedrine, the extraction from natural sources is another potential source for clandestine laboratories [ 104 ]. Therefore, an integrated approach with intelligence information collected beyond the starting materials is key to linking the operation of the criminal networks.

A complementary study on the use of stable isotopes techniques in evaluating the links between different MA seizures was reported by Iwata et al. [ 112 ] Benson et al. [ 36 ] and Billault et al. [ 123 ]. In a study by Billault et al., a variation of δ 13 C and δ 15 N was used to cluster seized MA and successfully established a link between different MA cases. The study successfully discriminated against semi-synthetic ephedrine from bio-synthetic or synthetic ephedrine by using δ 13 C. However; based on the fact the δ 13 C values of acetaldehyde from sugar are more optimistic compared to C 3 -photosynthetic plants or products derived from petroleum, it could not differentiate biosynthetic ephedrine from synthetic ephedrine.

Recently, a stable isotopes technique was used to investigate the unique profiles of stable nitrogen isotopic composition in seized MA samples [ 128 ]. In this work, the stable isotopes variation can be due to the isotopic variations in the starting materials, isotopic fractionation during the synthetic processes, and due to analytical errors. It is therefore essential to draw a conclusion based on the magnitude of the variation to eliminate the influence of isotopic fractionation and analytical errors. A variation of 0.9‰ δ 15 N evidenced a difference in batches of production and subsequently, different ephedrine sources used as starting materials for the production of MA. Iwata et al. [ 128 ] further used the stable isotope technique to classify the MA seizures based on their synthetic batches. Based on the criteria proposed by Iwata et al. [ 128 ], Δδ < 0.4‰ represents a significant variation in batches.

Interestingly, stable isotope technology is making an in-road towards the discrimination of illicit synthetic/semi-synthetic illegal drugs based on their synthetic routes and their associated reactions conditions beyond its conventional use in discriminating the sources for MA. As a growing profiling method, it complements the impurity profiling by linking the synthetic routes to isotopes ratios.

Billault et al. reported startling scientific research that seems to confirm the use of stable isotopes in linking MA batches to their respective synthetic routes. These results were the first to be reported in linking the δ 13 C values of the precursors in distinguishing synthetic routes of seized MA and their derivatives. Having investigated the relationship between δ 13 C and δ 15 N of the precursors and those of 45 samples of MDMA, the authors demonstrated how the number of synthesis steps influenced the value of δ 13 C in the seized MA samples and consequently discriminated the synthetic routes possessing more than one step.

Similarly, the discrimination of synthetic routes using stable isotopes is established by comparing the δ 15 N values of the origin precursors and the seized MA. The values of δ 15 N in MA are dependent on the source of nitrogen used, the route by which the MDMA is synthesized [ 114 , 115 ], and the experimental conditions employed [ 116 , 123 , 129 ].

Previous work by Billault et al. discriminated MA based on their synthetic origins, synthetic routes as well a close variation of the stable isotopes based reaction conditions of MA tested.

2. Conclusion

In this review, we have discussed the impurities and stable isotopes signatures found in illicit MA. The signatures are critical in the intelligence of illegal drugs, linking the illegal drugs with their sources, synthetic methods, synthetic batches, and their geographical origin. Although stable isotopes have been influential in discriminating seizures based on their origin, it is evident from this review that its potential in profiling MA has not been fully explored.

The review highlights further how the integration of impurity profiling with stable isotopes signatures coupled with chemometric techniques complements the existing intelligence gaps. The review illustrates how an assortment of legally available chemicals and medicines used to mask the controlled substances. It has also been shown in this review how precursor chemicals come with their corresponding stable isotopes and tracking them down to their stable isotopes has been essential in discriminating the seizures based on their original starting materials resulting in comprehensive profiling.

Studies linking stable isotope technique in profiling MA are undoubtedly limited, perhaps because of the advanced instrumentations. In furtherance of monitoring the dynamics of the MA, drug markets, and the advances of the criminal networks, future research is indispensable. Future research should focus on the diversity of both licit and illicit starting materials, complementing impurity profiling with stable isotopes, building knowledge with regards to the newly identified MA profiles, and finally; coupling the methods with chemometric techniques.

CRediT authorship contribution statement

Isaac Onoka: Conceptualization, Writing - original draft. Andrew Toyi Banyika: Writing - review & editing. Protibha Nath Banerjee: Supervision. John J. Makangara: Supervision, Writing - review & editing. Laurence Dujourdy: Resources, Writing - review & editing.

Declaration of competing interest

The authors declare that there is no conflict of interest.

Acknowledgment

Thanks to the University of Dodoma, Tanzania for allowing the ongoing study on the profiling of methamphetamine. We would also like to thank Dr. Mellony Manning for proofreading and checking the language.

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Jon Jones fights charges stemming from alleged hostility during a drug test at his home

FILE - Jon Jones speaks during the UFC 152 pre-fight press conference at the Real Sports Bar and Grill in Toronto, Sept. 20, 2012. The UFC heavyweight champion is due in court Wednesday, July 17, 2024, to face a pair of misdemeanor charges that stem from a drug test at his New Mexico home in March in which he was accused of being hostile. (Matthew Sherwood/The Canadian Press via AP, File)

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ALBUQUERQUE, N.M. (AP) — UFC heavyweight champion Jon Jones pleaded not guilty Wednesday to a pair of misdemeanor charges stemming from a drug test at his New Mexico home in which he was accused of being hostile.

Jones appeared seated next to his attorney as the pleas were entered on his behalf during a virtual hearing. An Albuquerque judge granted the attorney’s request that Jones remain free pending trial on charges of assault and interference with communication in connection with the March testing session.

Jones has vowed to fight the charges. When the allegations first became public, he called them baseless, posting on social media that he had been taken off guard by what he called the unprofessionalism of one of the testers and acknowledged cursing after getting frustrated.

“However, I want to emphasize that at no point did I threaten, get in anyone’s face, raise my voice to anyone or engage in any form of assault,” Jones said in a social media post.

Considered one of the top MMA fighters, Jones took the heavyweight title more than a year ago with a first-round submission over Ciryl Gane. It was Jones’ first fight in three years and his first in the heavyweight division. He already was the best light heavyweight by winning a record 14 title fights.

Jones was suspended for a year in 2016 for a failed drug test and had his 2017 victory over Daniel Cormier turned into a no-contest after another drug test came up positive. Jones argued later that he would have passed under standards that were revised in 2019 by the U.S. Anti-Doping Agency, which changed the criteria for what constituted a positive test.

A woman who worked for Drug Free Sport International, which conducts tests for professional athletes, initially filed a report with police in April. She accused Jones of threatening her, taking her phone and cursing at her while she and a colleague were at Jones’ home for a drug test.

A criminal complaint states that the woman described Jones as cooperative at first but that he became agitated.

Jones told police that he thought it was his phone that he picked up and that he apologized for swearing at the woman and her co-worker at the end of the test. He posted video from what appears to be a home camera system showing the woman giving him a high-five before leaving. He said neither appeared scared during the interaction.

What Is CrowdStrike?

CrowdStrike’s cybersecurity software is used by scores of industries, including airlines, hospitals and retailers, to prevent hacks and data breaches.

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By Claire Moses

July 19, 2024, 6:30 a.m. ET

Until Friday morning, many people had either not heard of — or were not thinking about — CrowdStrike. But as flights were canceled, broadcasters went off air, trains did not run and medical procedures were delayed around the world, its name quickly spread around the internet.

So, what is it?

CrowdStrike, which was founded in 2011, is a cloud-based cybersecurity platform whose software is used by scores of industries around the world to protect against hackers and outside breaches.

“Once CrowdStrike is installed, it actively scans for threats on your machine without having to manually run virus scans,” according to an explanation on the University of Denver’s website, which offers the platform to students and staff.

Cybersecurity software like CrowdStrike’s has broad privileges to run across a computer system, including into sensitive areas. That means when errors occur, the ripple effect can be significant.

CrowdStrike updates its security software automatically and silently. It seems that a flawed update on Friday morning, of its Falcon Sensor software, resulted in crashes of machines running Microsoft Windows operating system and caused the worldwide chaos.

In a posting on X, CrowdStrike’s chief executive, George Kurtz, confirmed that the outage was not “security incident or cyberattack.”

An updated fix of the software has been sent to computers, but Lukasz Olejnik, an independent cybersecurity researcher and consultant, said outages would probably persist because it was not clear how to fix computers that had already been affected.

It is not the first time CrowdStrike is in the news: Its analysts investigated the data breach of the Democratic National Convention in 2016 and determined that two groups of Russian operatives had breached a DNC server.

Claire Moses is a Times reporter in London, focused on coverage of breaking and trending news. More about Claire Moses

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A review of the newly identified impurity profiles in methamphetamine seizures

Andrew Toyi Banyika

1. Introduction

1.1. The synthetic schemes of methamphetamine and the specific-route impurities

1.2. A paradigm shift in methamphetamine precursor production

1.3. The emerging methamphetamine impurity profiles

1.3.1. Impurities from metal catalytic hydrogenation

1.3.2. Emerging impurity profiles from pharmaceutical compounds

1.3.3. Impurities discriminating ephedrine and pseudoephedrine synthetic routes

1.3.4. Emerging signatures from stable isotopes

2. Conclusion

CRediT authorship contribution statement

Declaration of competing interest

Acknowledgment

Jon Jones fights charges stemming from alleged hostility during a drug test at his home

What Is CrowdStrike?

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Researchers develop 'organ on a chip' for better drug testing 