This was a very eventful week for Oscar Valdez.
On Tuesday, we learned that Valdez tested positive for a banned substance called phentermine as part of his pre-fight VADA testing. A few days later, it was confirmed that his B-sample was also positive, but the fight would continue as scheduled on September 10th.
On Friday, the WBC announced that Valdez would be put on “probation”, but not stripped of his super featherweight belt. Later that day, Valdez posted an Instagram video denying any use of banned substances for performance enhancing purposes.
But, what is phentermine? What does it do? Could it work as a performance enhancer? And, how likely is an accidental exposure?
For a better understanding of phentermine and how it affects the body and brain, Bad Left Hook spoke to Dr. Justin Seltzer, Medical Toxicology Fellow at the UC San Diego Department of Emergency Medicine.
Dr. Seltzer has no role in Valdez’s drug testing process, and no specific knowledge of Valdez’s VADA test results. But, he is someone who can make concepts like “anorexiants” and “sympathomimetics” comprehensible for a non-medical audience. He was kind enough to explain the chemical nature and medical purpose of phentermine, and, in general terms, share context and details for some of the most common questions about this situation.
Among the highlights of our conversation: Though phentermine is an amphetamine and a DEA controlled substance, it’s not something you’d see cooked up on “Breaking Bad”. Its primary purpose is as a prescribed part of a weight management plan. It could theoretically provide additional training value as a stimulant, but it’s not clear how significant that impact might be for a top-form athlete. And, though there’s no documented history of the FDA finding phentermine as an adulterant in any supplements, it is not an impossible or wildly unlikely possibility. In general, accidental exposure to unintended substances in supplements is a widespread, serious problem.
A transcript of our conversation, edited for length and clarity, follows.
BAD LEFT HOOK: The only time I hear the word “toxicology”, it’s in the context of a crime documentary or an old “Law & Order” rerun. Can you start off by giving us a short description of what it means that your specialty is as a Toxicologist?
DR. JUSTIN SELTZER: Medical toxicology is a medical subspecialty of emergency medicine, pediatrics, and preventative medicine; my personal primary training is in emergency medicine. We mainly manage acute and chronic poisonings, ranging from an overdose of painkillers to the aftermath of drinking lead-tainted water for 20 years.
Beyond that, things like toxic industrial and environmental exposures, chemical weapons and other weapons of mass destruction, and even jellyfish stings – we have our hands in quite a few areas. There are a lot of different ways the human body can be poisoned, and dealing with those things is our particular specialty.
The public is likely most familiar with poison centers or Poison Control, for which we also act as physician consultants. When someone calls Poison Control or goes to a hospital, a non-physician Specialist in Poison Information manages the initial call, and when they need additional resources or specific medical input, they call us.
Poison Control runs 24/7/365 as a service free to the public. If ever there is a question about a medication or drug, the national Poison Control number is 1-800-222-1222.
What exactly is phentermine, and what effects does it have? Does it have a legitimate medical or therapeutic use?
First, what is phentermine? Phentermine is actually a pharmaceutical drug. It can be prescribed in the United States, primarily for weight loss. That is what its FDA approved indication is.
Phentermine is part of a group of substances known as “substituted amphetamines.” Most people are broadly familiar with the word “amphetamine”, and it’s kind of a loaded word. You hear things like “methamphetamine”, and think it’s a street drug that’s dangerous. But there are lots and lots of different substituted amphetamines, many of which people use safely all the time.
The structure itself is valuable because it has desirable effects on both brain chemistry and the body, so it is used to derive a large number of medications. Common ones include bupropion, also known as the antidepressant Wellbutrin, and pseudoephedrine, also known as the over-the-counter decongestant Sudafed.
Most people are probably more familiar with phentermine than they realize, especially those who are old enough to remember Fen-Phen. It was very well known and popular, then taken off the market with a bit of a media flourish. Fen-Phen was actually two drugs, phentermine and fenfluramine together as a combination. The problem was that fenfluramine caused issues with the valves of the heart and the blood vessels that lead from the heart to the lungs. So fenfluramine was removed from the market, but phentermine still remains.
Moving on to the second part of the question, how is it used? Phentermine is approved for weight loss. The way it accomplishes that is primarily through its hunger reducing, or anorectic, effect. It’s a property shared with quite a few different amphetamines. Anyone who takes something like Adderall has likely experienced something similar. So, the anorexiant effects of amphetamines are well understood, and this drug was specifically marketed with this effect in mind.
The stimulant effects that come from amphetamines are also well known, and phentermine is no exception. Strong stimulant effects like euphoria, agitation, high heart rate and blood pressure, and so on are comparatively less pronounced with phentermine, especially at the low doses used for weight loss. But it may still cause some meaningful stimulant effects.
When an athlete fails a drug test, we generally categorize the reason as being a recreational drug, a performance enhancer, or a masking agent taken to purge or cover up one of the first two. Does phentermine fall clearly into one particular category?
I think to answer that question, we have to better understand its clinical effects.
Amphetamines generally are what we call “sympathomimetics.” They mimic the effects of your body’s fight or flight response by artificially triggering release of those hormones. Think back to a time when you’ve been frightened or in a tense situation. You feel your heart pound and that sense of sudden focus, wakefulness, and energy. Sometimes a sense of restlessness, nervousness, or even euphoria. Based on that, I think you can extend to a role in sports generally – this stimulant effect gives you “fight-or-flight” energy you might not otherwise have.
Here, I mean amphetamines broadly, not specifically phentermine. For example, “greenies” that baseball players used to use were also amphetamines, and had the same purpose. It not only increases energy, but also reduces the sensation of fatigue.
So now we get into a discussion about applications to sport. First of all, phentermine reduces your feelings of hunger, and that has obvious applications in cutting weight. So, in a sport where that is important, maintaining or cutting weight? It has potential value.
Second, the stimulant effect? I can’t comment on phentermine’s effect compared to other stimulants like caffeine. What I can say is that if you’re training, say, five hours a day? If that gets you an extra hour, or if that makes your five hours 20% more intense? That also has potential value.
But, for example, compared to an anabolic steroid? Phentermine doesn’t have that same direct effect. You may or may not ultimately benefit from it. But it certainly could confer some theoretical advantage in terms of weight loss, fatigue resistance, and physical intensity.
You also asked if it could function as a masking agent specifically. The answer to that would be no, unless you’re taking other amphetamines. Routine urine drug screening would come back positive for amphetamines, so the only masking it could do in that context is covering for other amphetamines. As a result, its value as a masking agent would be very low.
So, there could be some value for general strength and fitness, and maybe more significant value given the weight loss component for someone that has to manage a strict weight limit?
I can answer only in broad terms, and I’m not commenting specifically about this particular situation or even this particular sport. But, if someone wanted a medication that provided both potential weight loss as well as stimulant effects? This medication can provide those two things.
And that’s the reason it was used in pharmaceutical weight loss in the first place. Say you have an obese person that needs help losing weight, and as part of a diet and exercise regimen you give them phentermine? The medication may give them the energy and suppression of hunger necessary to accomplish that weight loss.
But it’s hard to comment on the value to someone already in top physical form and what it would do for them. What I can say is, there is a possibility that phentermine could be valuable.
Is phentermine something that lingers in the body? Or, is it something with a shorter duration that an athlete could ‘cycle on and off’ to avoid scheduled drug tests if they time things carefully?
This question is tricky, but you should expect reliable detection within about four to five, maybe out to six days, though this number is not set in stone.
Generally, when we talk about the effective elimination of a drug from the body, we go by half-life, or the time it takes to reduce the concentration by 50%. After five half-lives, about 97% of the drug has cleared, and by seven half-lives, we expect over 99%.
Phentermine has a half-life of roughly 20 hours – five to seven half-lives would be 100-140 hours. So four to six days is a reasonable range. Importantly, everyone is a little different, every drug is a little different, and the particular test’s detection level varies, but that’s the back-of-the-hand math that we use.
You asked: Could you cycle off of it? If you waited a week, it would be out of your system, though it may still be detectable for a longer duration depending on the method of testing and threshold to qualify as a positive test. But yes, theoretically you could use the drug while training, stop a week before, and likely pass a routine urine drug screening.
Is phentermine a controlled substance, or something that’s prescription-only?
It is prescription only, and it is a controlled substance, DEA Schedule IV.
That’s the second lowest tier of the scheduled drugs. The DEA schedules drugs based on accepted medical uses and relative abuse potential. Schedule IV drugs are considered to have a “a low potential for abuse relative to substances in Schedule III.” For reference, some other amphetamines such as amphetamine and methamphetamine are Schedule II drugs, along with most opioid pain medications.
So, I couldn’t necessarily go out to the pharmacy or grocery store and buy something with phentermine in it on my own because it’s a controlled substance?
That you know of. And that’s an important point I want to make related to incidental exposure.
Well then, let me ask: How likely is an accidental exposure? Could I, a non-athlete, take something or consume something with a significant amount of phentermine and not realize it?
I’ll answer broadly, because there’s a lot of adulteration of supplements. I think we all chuckle from the back of the room when we hear something like “herbal tea” from athletes trying to explain a positive test. But, if you look at the data, they’re actually not off base. It’s a humongous problem.
There’s a 2018 study by Tucker and colleagues from the California Department of Public Health, published in the Journal of the American Medical Association, that talks about adulteration of supplements. Over a nine-year period between 2007 and 2016, 776 supplements were found by the FDA to be adulterated with at least one pharmaceutical drug, some of which are not approved in the US. Over 20% of those had two or more. These range from antidepressants, to high blood pressure medications, to weight loss drugs like sibutramine, which was withdrawn from the US market in 2010 due to adverse effects on the heart. If you go on the FDA website, you can find hundreds more examples in their database, which is current up to March of 2021.
Another issue cited in that study was that over 97% of those inappropriate ingredients I mentioned were not noted on the label. So it isn’t even a matter of “you should have looked at the label.” Almost all had one and a good number of them had at least two items of clinical significance that were just plainly not on the label. Unless you’re an analytical chemist, you’re going to have a hard time figuring that out.
And that’s where it becomes very complicated. It’s difficult to navigate this space. So, when we talk about the potential for incidental exposure, we really have to take that seriously. I can’t comment on whether someone took something intentionally. But, I think it’s reasonable, if you did not take something intentionally, to immediately look at supplements you’re taking and wonder if there’s something you didn’t know was in there.
Is there any documentation of that happening with phentermine before?
I looked through FDA records, and couldn’t find any supplements that were specifically adulterated with phentermine. Probably due to the fact that it’s a controlled substance, and a lot more difficult to get into the United States. But, it’s not impossible that something imported from other parts of the world or ordered off the internet could include it.
The broader point here is that incidental exposure to things you don’t know you’re taking from supplements in particular is a big problem. It is distinctly possible that what you think you’re taking is adulterated with a problematic or undesired ingredient.
That is not a figment of people’s imaginations. Whether it creates a clinically meaningful effect or is just there because of poor manufacturing processes is a different story. However, it cannot be initially discounted as a potential source of any exposure.
I can’t speak to what happened here, but I can say generally that this is a topic of significant concern to toxicologists and the FDA.
Are there any potential short-term side effects of long-term health consequences that could arise from the use of phentermine?
Yes! Phentermine is generally prescribed for a short term, usually a few weeks. From the FDA’s perspective, a lot of the short-term side effects are therapeutic. The reduced hunger, the weight loss, the stimulant effect? That’s what you’re paying for.
That’s also why it has a limitation on how long it can be prescribed. When you start talking about long-term amphetamine use, that’s when you face the question of addiction and dependence. You can become chemically dependent over time and your body withdraws from them when you don’t take them. Like many other amphetamines, phentermine has potential for dependency and addiction. That’s the primary long-term side effect.
It’s generally considered a pretty safe drug, and I think that’s important to note. But the short-term effects are what are being prioritized as part of its therapeutic effect. The long-term addiction effects are less commonly seen with phentermine because it is only supposed to be prescribed in short courses, but can be inferred from other amphetamines.
This was very helpful, and thank you for taking the time to explain it all in such thorough but understandable detail. Any other thoughts or conclusions you want to share with our readers?
I have two parting thoughts. First, if you’re going to take weight loss medications or supplements of any type? Talk to a doctor. Visit a certified weight loss physician. Go to a reputable weight loss clinic and, if they feel you may benefit from medication, have it prescribed under proper supervision.
Second, if you’re going to use over-the-counter supplements? Be mindful of the possibility that those supplements may contain something you don’t know is there. There are ways of checking or certifying that supplements contain what they say they contain, such as the NSF “Certified Sport” labeling. And it’s worth the little bit of extra effort it takes to do that to make sure you aren’t exposed to something that you don’t want or need.
Dr. Seltzer asked that we share the following resources with our audience:
Special thanks to Dr. Heather Buschman of UC San Diego Health for her assistance with this interview.