Russian Doping of a Different Sort: Russian and Eastern European Drugs Hiding in Plain Sight as Alternative Doping Agents

Russian doping has been at the forefront of people’s minds as the 2020 Tokyo Olympic Games fade in our memories and we prepare for the 2022 Beijing Olympics to begin in February. The state-sponsored doping that culminated at the 2014 Sochi Olympics continues to cast shade over Russian sport–excuse me, the Russian Olympic Committee (ROC)–and indeed global competition, as the ensuing discussion and veiled accusations mar the Olympic spirit. But perhaps people should also be concerned about Russian doping of a different sort, one that is not often considered but should be. History has shown that athletes use Russian and Eastern European drugs as doping agents and yet few are prohibited today.

The World Anti-Doping Agency (WADA) Prohibited List outlines the substances that are banned in international competition including the Olympics. The 2021 WADA Prohibited List consists of 333 compounds listed by name, but the inclusion of catch-all language also prohibits related substances in many product categories. To be found, however, drugs have to rise to a level of concern and be targeted first and the WADA list primarily focuses on drugs of Western origin. Only four drugs of Russian or Eastern European origin appear to be included. Certainly there are others out there that would be attractive as doping agents.

Let’s take a look at the four drugs on the WADA Prohibited List that are of Russian or Eastern European origin and explore alternatives that athletes may be using today.

The story starts with bromantan, which was developed in the 1980s at the Russian Academy of Medical Sciences in Moscow. It can be found under the brand name Ladasten and is technically an actoprotector. Research out of Korea in 2012 explored bromantan in The Pharmacology of Actoprotectors: Practical Application for Improvement of Mental and Physical Performance. The writers described actoprotectors as “synthetic adaptogens with a significant capacity to improve physical performance.” The literature noted, “Bromantan was first found in an athlete sample at the 1996 Atlanta Olympics and was officially banned in 1997 as a stimulant.” There have been 11 adverse findings for bromantan in the WADA system since 2006.

Perhaps this is not surprising as a perfect alternative, bemitil, also known as metaprot, is described in the literature above and remains widely available online today, often at sites that offer Russian medicines or nootropics. The paper above explains that “nowadays, bemitil is manufactured in Ukraine (commercial name: Antihot) and is widely used in preparing Ukrainian national sport teams for international competitions.” It also notes, “Bemitil was successfully employed in preparing the athletes of the USSR’s national team for the 1980 Olympic Games held in Moscow.”

“Bemitil was successfully employed in preparing the athletes of the USSR’s national team for the 1980 Olympic Games held in Moscow.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3762282/

Bemitil was added to the WADA monitoring program list in 2018, 38 years after the Moscow Olympics you will note, but is not yet prohibited. If it does get prohibited, fear not there are alternatives for it, too. A site that sells Eastern European drugs like bemitil, MOSPharma.com, suggests four related products including noopept (see below) and trekrezan “from Russian pharmaceutical company Usolye-Siberian CPP,” with activity that “increases endurance during physical and mental stress.”

Next on the list of Russian doping agents is mescocarb, a central nervous system (CNS) stimulant and a dopamine reuptake inhibitor patented originally in Russia in 1970 by Vni Khim Farmatsevtichesky. Also known as Armesocarb, it is currently in clinical trials as an antiparkinsonian drug from Melior Pharmaceuticals. It has been sold under the brand name Sydnocarb with a nod to the technical chemical category in which it fits, mesoionic sydnone imine. Mesocarb does not appear to be widely available today online. It has been prohibited in sport since at least 1996 based on references to it at that time, but it has only been responsible for two adverse analytical findings since 2006.

There are also Russian alternatives to CNS stimulants with semax as one option. A poster on black market products with suspiciously doping relevant ingredients – annual report from the 2016 Manfred Donike Workshop discussed that semax “acts as a nootropic agent on the central nervous system and regulates dopamine and serotonine levels.” MOSPharma.com describes semax as “100% original from the Russian CJSC INPC Peptogen,” and notes it is used “to stimulate the central nervous system and enhance memory, focus, mental and physical performance, analytical skills.”

Carphedon, otherwise known as phenylpiracetam, is the next on our list and one of a family called racetams that are generally considered nootropic drugs. In 2019, researchers from the Czech Republic considered Carphedon at the Crossroads: A Dangerous  Drug or a Promising Psychopharmaceutical? They explain this substance was “developed in Russia as a stimulant to keep astronauts awake on long missions, and occasionally used in Russia as a nootropic prescription for various types of neurological disease.” Carphedon “was synthesized in 1990 by Russian chemists as a combination of two drugs, nootropic piracetam and amphetamine stimulant.” A 2012 review of Piracetam and Piracetam-Like Drugs describes them as “modulators of cerebral functions,” used for, “various therapeutic interventions relating to the CNS, including (i) cognition/memory; (ii) epilepsy and seizure; (iii) neurodegenerative diseases; (iv) stroke/ischaemia; and (v) stress and anxiety.”

Handwritten notes from 1997 show carphedon was considered by my father, sports drug-testing guru Dr. Don H. Catlin, and colleagues at the IOC Medical Commission for addition to the prohibited list at the time. The notes describe carphedon as, “adaptogenic, registered in 1994 in Russian pharmacopeia that might help with space travel and improve workload.” The drug has caused 122 adverse analytical findings since 2006.

If you peruse the piracetam review highlighted above, you will find nine other racetam options that may be considered as doping agents. None is listed by WADA today. Neither is noopept, otherwise known as omberacetam, which has become one of the most popular nootropic agents on the market today. The National Institutes of Health (NIH) National Center for Advancing Translational Sciences (NCATS) notes that “noopept was patented by Russian-based pharmaceutical company JSC LEKKO Pharmaceuticals in 1996.” The information cites that the “research shows Noopept has similar effects, but works differently than other nootropics in the racetam-family.” A number of sites compare the effects of phenylpiracetam to noopept with nootriment.com, suggesting that “both are purported to have benefits for memory, concentration, mood and alertness.”

From a banned substance standpoint, phenylpiracetam is on the WADA Prohibited List while noopept is not listed nor is it targeted. A synthetic drug, noopept, is widely available in supplement form despite it not qualifying as a dietary supplement ingredient according to the Dietary Supplement Health and Education Act of 1994 (DSHEA), which defines legal supplement ingredients in the U.S. It shows up in 32 dietary supplement products in the NIH Office of Dietary Supplements Dietary Supplement Label Database. In 2016 a BSCG blog post I wrote considered noopept could be the next big doping agent hiding in plain sight. That still remains the case today.

Last but not least of the four Russian doping agents is meldonium, otherwise known as mildronate. One will remember the maelstrom that ensued when meldonium was added to the WADA Prohibited List in 2016. There were 515 positive drug tests for meldonium in 2016, making it the most common substance found that year in Olympic sport. Tennis star Maria Sharapova was among them. There were 269 more positives from 2017 to 2019 for a total of 784. Meldonium is included on the WADA Prohibited List as a metabolic modulator in category S4.

Scientists from the University of Latvia and the Latvian Institute of Organic Synthesis that created meldonium, described it as “an anti-ischemic drug.” Its performance-enhancing potential has been the subject of much debate likely because it is a complex substance that has a variety of effects. An excerpt from a 2005 paper written by the aforementioned scientists, Mildronate: An Antiischemic Drug for Neurological Indications, describes it as follows.

“Mildronate was designed to inhibit carnitine biosynthesis in order to prevent accumulation of cytotoxic intermediate products of fatty acid oxidation in ischemic tissues and to block this highly oxygen-consuming process. Mildronate is efficient in the treatment of heart ischemia and its consequences. Extensive evaluation of pharmacological activities of mildronate revealed its beneficial effect on cerebral circulation disorders and central nervous system (CNS) functions. The drug is used in neurological clinics for the treatment of brain circulation disorders. It appears to improve patients’ mood; they become more active, their motor dysfunction decreases, and asthenia, dizziness and nausea become less pronounced.”

The meldonium saga more than demonstrated athletes around the world had recognized an obscure anti-ischemia agent as a doping option and had started to use it. When it was prohibited, Russian scientists boasted they already had alternatives. As reported in USA Today from Moscow, “Federal Medical-Biological Agency head Vladimir Uiba says Russia has found ‘several drugs which are not banned and work significantly better than meldonium.’”

You don’t have to look far. Mexidol is broadly available on sites that cater to Russian medicine as well as on a site called DrDoping.com; very subtle. It is also available on Amazon from Pharmasoft at $21 for 50 tablets with a label that suggests it be used for “Anxiety Relief, Anti-Stress, and Ischemic Condition.” Mexidol, an anti-oxidant, was patented in 2002 in Russia with the patent describing the “invention relates to preparations used for prophylaxis and treatment of different forms of cardiac ischemia disease, atherosclerosis and acute circulation disturbances, cerebral insults.” With indications for ischemic conditions, it certainly appears similar to meldonium.

In a 2007 paper, Mexidol effects in extreme conditions, T.A. Varonina with the Institute of Pharmacology, Russian Academy of Medical Sciences notes, “Mexidol can be prescribed to humans to maintain efficiency in all kinds of extreme situations.” Could hundreds of Olympic athletes be using mexidol as an alternative to meldonium today?

A 2019 review from Russia of Pharmacoeconomic analysis of the neuroprotective medicines in the treatment of ischemic stroke compares mexidol to actovegin, which gained some notoriety as a potential doping agent around 2009 as explored in the Daily News. Actovegin, which DrDoping.com carries in pill form, is an extract from calf blood and is not on the WADA Prohibited List. In the article Olivier Rabin, WADA’s science director, suggests, “Actovegin could be used as a component of sophisticated blood doping methods, in which athletes withdraw, manipulate, and re-inject their blood to boost their endurance, or in conjunction with the use of erythropoietin, or EPO.”

When we ran independent drug-testing programs for several leading cycling teams in the peloton years ago, a key member of a team said to me after an event, “You know, Oliver, we aren’t doing anything that is over the line but we are doing everything we can up to the line.” That simple philosophy likely rings true across sport today.

People often ask if the Olympics or sport in general is clean today. To answer that simply, the system is very good at finding drugs that are currently defined as prohibited substances. None of the Russian or Eastern European drugs we note here–bemitil, trekrezan, semax, noopept and other racetams, actovegin, or mexidol–is on the WADA Prohibited List today. These Russian or Eastern European drugs certainly seem to be potential alternatives to prohibited drugs, but if they are not yet defined as such then using them is not yet considered doping. If sites like DrDoping.com has found them, who else might have them?

Oliver Catlin is the longtime president and co-founder of BSCG (Banned Substances Control Group), an international third-party certification and testing provider. With a background in sports anti-doping, he is widely regarded as a thought-leader in the field of sports nutrition and dietary supplements.

House of Representatives Passes ‘Rodchenkov Anti-Doping Act’

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By Ryan Connolly

Earlier this week, the United States Congress moved closer to establishing federal criminal penalties for international doping fraud conspiracies, such as the Russian Doping scandal that rocked the Olympic world in 2016. “The Rodchenkov Anti-Doping Act of 2019”–controversially named after a chief perpetrator and eventual whistleblower of the aforementioned scandal–was passed by the House of Representatives on October 22. If signed into law, H.R. 835 would establish significant criminal penalties–up to 10 years in prison and $250,000 in fines for an individual–and make it unlawful to “knowingly carry out…a scheme…to influence by use of a prohibited substance or prohibited method any major international sports competition.” Under the Act, such an international competition must (1) have at least one U.S. athlete participating, (2) have at least three non-U.S. athletes participating, (3) be governed by the World Anti-Doping Code, and (4) receive sponsorship or broadcast rights money from a U.S.-based organization.

Importantly, a person’s intention is a key element of the section of the Act establishing criminal penalties. A person must knowingly intend to influence an international competition through doping fraud to violate the Act. Unless the actions of the person are fairly blatant and backed by evidence demonstrating an intent to cheat the system, establishing the “knowingly” element may be a significant bar for a federal prosecutor to clear in many cases. This should largely alleviate concerns of criminal penalties for certain actors who are inadvertently responsible for positive doping tests. This includes dietary supplement companies and executives whose products are found to be contaminated (unintentionally) with a banned substance. However, such potentially negligent actors may still be found responsible for the consequences and face significant civil damages and penalties, as is reaffirmed by the Act.

Another significant aspect of the Act is related to information sharing between the United States government and the United States Anti-Doping Agency (USADA), a non-governmental Colorado non-profit corporation that conducts anti-doping activities for Olympic sports in the United States. Under the Act, the U.S. Department of Justice (DOJ), the Department of Homeland Security (DHS), and the Food and Drug Administration (FDA) are required to coordinate with USADA with regard to any investigation related to an international doping fraud conspiracy, unless the integrity of that agency’s criminal investigation would be affected. This coordination specifically includes that the agencies must “shar[e] with USADA all information in [their] possession…which may be relevant to any such potential violation” of the Act. If the Act is signed into law, this new information sharing requirement could prove to yield a treasure trove of knowledge that may have been previously inaccessible to USADA.

View the text of H.R. 835 at Congress.gov.

Ryan Connolly is a Los Angeles-based attorney serving as counsel to various businesses, individuals, and dietary supplement / anti-doping-related organizations, including Banned Substances Control Group (BSCG).

Lives in the Balance: Why Doping Control Matters

As the Tour de France rolls onto stage 7, few in the general public know of the story of 21-year-old Linas Rumsas, but they need to consider it. Especially on this day, July 13, 2018, the 51st anniversary of cyclist Tommy Simpson’s death.

People ask us all the time why doping control matters. Some argue that it doesn’t and that we should just let folks use what they want. A doping free-for-all. Cynics might say that plenty of dopers have already escaped through the net in sports, at least for a time: Lance Armstrong, Tim Montgomery, Marion Jones, to name a few.

Linas Rumsas

Linas Rumsas was an up-and-coming cyclist whose life was cut short after he abused performance-enhancing drugs. Photo: Team Altopack-Eppela

The story of young Linas, a promising cyclist whose life was cut short after abusing performance-enhancing drugs, reminds us that doping can kill. We would be wise to remember that it has happened before. Linas’ story is one of the saddest we have come across and it powerfully demonstrates why many of us who have chosen to pursue anti-doping continue to do so. This one story illuminates in no uncertain terms the realities of what we all face with the scourge of doping, and yet outside of Italy and frequent readers of Cycling News, few sports fans have probably heard of it.

There have been others who have perished from doping. According to ProCon, which provides a comprehensive historical timeline of doping in sports, the first modern athlete chronicled to have died from doping was the Danish cyclist Knut Jensen at the Summer Olympics in Rome in 1960. Heat was the initial culprit but his autopsy found traces of Ronicol. ProCon describes Ronicol as an amphetamine, but Ronicol would be described more accurately as a vasodilator and can be used as an anti-ischemia drug. Though it is not on the 2018 WADA Prohibited List, it is similar to meldonium in many ways.

Stop to consider that the first drug to have been implicated in the death of an athlete in the Olympics in 1960 is not banned today! Ronicol, otherwise known as nicotinyl alcohol, is not prohibited as confirmed by the Global DRO. Its cousin meldonium wasn’t prohibited by WADA until 2016, when it caused hundreds of athletes to test positive. Some might like to think that doping is behind the peloton, but we fear it may still be in the middle. Just in a form we don’t currently define as doping, like Ronicol.

Fifty one years ago today on July 13, 1967, Tommy Simpson infamously died on the slopes of Mount Ventoux during Stage 13 of the Tour at the age of 29. His death was one of the central moments in anti-doping history. Shortly thereafter that same year the International Olympic Committee (IOC) created the IOC Medical Commission and the first drug testing began at the Olympics in 1968, with narcotics and stimulants making up the initial prohibited list. Steroids were not added until 1975.

There have been other examples of athlete deaths that have been seminal. MLB pitcher Steve Bechler, of the Baltimore Orioles, died during drills in 2003. Ephedrine was indicated as a contributing cause in his premature death, which played a role in the regulation of ephedrine as a dietary supplement ingredient in the United States.

Steroids have played a role in the demise of many young athletes, including Taylor Hooton, Efrain Marrero, and just two days ago, a young 18-year-old Irishman in Limerick. Numerous stories exist of athletes who went too far with blood doping, or performed transfusions the wrong way, leading to dire consequences. Many stories are out there but few are known to the broader sporting public.

Linas Rumsas’ story reminds us that the scourge of doping is still present and that it is just as deadly today as it was in 1967 when amphetamines derailed the promising life and career of Mr. Simpson.

Linas Rumsas is the son of Raimondas Rumsas, who himself was a professional cyclist and took third place in the 2002 Tour de France. After Raimondas’ wife Edita was caught with a van full of drugs on the way home from that Tour, they both received four-month suspended sentences in 2006. Raimondas later tested positive for EPO during the 2003 Giro d’Italia. Sadly, this experience did not seem to deter them from apparently assisting their two children with doping.

Linas rode for the Altopack-Eppela squad in Italy and had already been a national road race champion. But in May 2017, he died at age 21 of a heart attack. It was nearly 50 years to the day after Mr. Simpson had died.

Upon Linas’ death, police searched his family’s home and seized a number of banned substances and medications. In September 2017, his older brother Raimondas Jr. tested positive for the prohibited substance GHRP-6, a peptide that produces natural growth hormone. It seems a cocktail of banned substances and other medications were being used at the family home.

The result of all this has been one family torn apart, again, from doping. Perhaps doping didn’t matter to the Rumsas family either until their son died. But Linas didn’t just die, if the allegations in this case hold true. He died as a result of family support and encouragement to dope.

It gets worse. In the course of the investigation, six people have been arrested in an apparent team-sponsored doping program including the team owner, directeur sportif, pharmacist, and trainer, who stand accused of providing drugs to riders. Seventeen other people are being investigated. Sadly, however, it is too late for Linas.

Unfortunately, the recent decision to allow Chris Froome to ride again with no sanctions after testing positive for elevated levels of salbutamol has called into question the validity and utility of the anti-doping system, again, at least in some people’s eyes. WADA has tried to explain the reasoning now, including clarifying the levels (1,428 ng/ml of urine, when adjusted for specific gravity, which is above the decision limit of 1,200 ng/ml). The reasons may not satisfy everyone, or anyone, but Froome’s case is certainly not a reason to give up on anti-doping.

Linas’ story personifies why giving up on anti-doping is simply not an option and should remind us all that doping is a significant matter. In fact, it is all the more reason to recognize that the failures of the anti-doping system are largely due to a lack of resources and money. For that to change, more people will need to truly understand what is at stake when athletes dope and to demonstrate the will to do more to combat the problem.

– Oliver Catlin

2018 PyeongChang Winter Olympic Games Review

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Don Catlin, M.D., at Vancouver 2010 Opening Ceremony – Photo by Oliver Catlin

We watched with the rest of the world as the 2018 PyeongChang Winter Olympic Games unfolded. In the face of tense politics, doping scandals, and other controversy, the Olympic ideals still shined through, sometimes in unexpected ways. Having been fortunate to attend six amazing Winter Olympic Games (Don got to go to seven, I think), we figured why not provide some perspective on these. Here is our 2018 PyeongChang Winter Olympic Games Review.

Most Amazing Victory – Ester Ledecka. Who knew someone could win a gold medal in snowboarding and skiing! Some people don’t think that the two sports are compatible, some don’t even want both sports on the same mountain. This woman just went out and ripped it up, twice, however many planks were strapped to her feet. Well done, Ester.

Clean Athlete Awards – Jessica Diggins and Kikkan Randall. In an Olympics marred by the Russian doping scandal, we always appreciate it when you can literally see that athletes are clean. Not that we advocate that a visual determination replace anti-doping testing, but some people you can just tell are not doping. We thoroughly enjoyed watching these ladies win clean, and with amazing smiles! We also appreciate the other courageous cross-country skiers who signed the letter in 2016 demanding a stronger stance on doping, including notably the four Russian women who signed. Thanks to all of you for working to defend your sport from the scourge of doping.

Classiest Athlete – Yevgenia Medvedeva. OK, we admit we watched the ladies figure skating final and it was pretty amazing. The talent and class displayed by all the young ladies is unbelievable. However, one shined above the rest. Despite missing the gold medal by a heartbreaking 1.31 points that even experts could not decipher, this woman took disappointment with amazing class for an 18-year old. She genuinely embraced her younger upstart Alina Zagitova and accepted her silver medal with a smile. She could be overheard saying she “did everything she could.” That statement represents what Olympic athletes are all about. We don’t know much about this Russian athlete otherwise, but in PyeongChang this little Anna Karenina showed enormous class.

Most Notable Olympic Farewell – Lindsey Vonn. Although you leave the 2018 PyeongChang Olympic Games with a bronze medal, which most people could only hope for, you will always be the golden girl of American skiing. You took yourself to the pinnacle of your sport and beyond, and you brought your country with you. Along the way you’ve inspired generations of Olympians for years to come. We wouldn’t be surprised to see a woman like you one more time in Beijing four years from now, but if not thank you for all the amazing Olympic moments.

Strangest Doping Incident – Doping in Curling, really? We thought people drank beer during curling, but doping? Of course it would be an Olympic Athlete from Russia with meldonium as the offending substance, such perfect irony.

Ugliest Controversy – The ugliest controversy in these Olympics goes to the argument between Dick Pound and others in the IOC over whether or not to allow the Russian delegation to be permitted to fly the state colors during the closing ceremonies. It took long enough to finally get some kind of ban enacted and the corresponding statement made that state-sponsored doping is unacceptable, and it was going to be overturned during the Games? Way to go Dick Pound for sticking up for clean sport, as always! Or should we thank the second Olympic Athlete from Russia for doping and closing the door on that argument.

Most Inspiring Olympic Athlete – One athlete that epitomized the ideals of the Olympic movement and displayed them proudly in every fiber of his being by bringing athletes from all nations together sadly was not present in PyeongChang, but he was there is spirit. And his spirit we know will continue to inspire generations of Olympians for years to come. The Olympic Family lost Steven Holcomb, a beloved member of the bobsled community, in May 2017. But in the true spirit of the Olympic movement he went down the track many times in PyeongChang in the form of tribute bracelets on the wrists of many of his sliding colleagues, his parents cheering with tears in their eyes in the stands. Despite not being present, this man, and his spirit, made for the most inspiring Olympic athlete of this Games. We wish we could have known him and been inspired by his spirit.

Most Amazing Olympic Moment – It was hard to miss the unity demonstrated at the Opening Ceremonies with South Korea and North Korea marching together as one. This was a powerful symbol of the peaceful celebration of sport that the Olympics represent. We appreciate that this unity was achieved during the Games, and I think we all hope the peace was more than just for show and lasts.

The Olympics are truly an amazing gathering of athletes from all different countries, politics, races, sizes, sexes, orientations, faiths, and more. For all these moments and more, the Olympic Games remain one of the most amazing spectacles of human interaction and accomplishment in this world. They deserve to be truly appreciated, celebrated, and protected. We can’t wait for the years to pass to see what amazing feats and memorable moments Tokyo, Beijing, Paris, and Los Angeles will produce.