We’re All One Crisis Away From Taking Unlicensed Research Peptides

“Unfounded and reckless” is how Dr. Eric Topol described the use of gray market peptides in a recent New York Times article. In some cases, I have to agree. (“You’re taking a drug without knowing what it is?”) But the implicit message in his statement, and in numerous recent articles critical of self-treatment with GLP-1s, is that deferring to the medical establishment is safe by definition, and everyone who steps outside the protections of the system does so in disregard of the danger. I would love for the former to be true, but reality has disappointed me.

For my whole life, I’ve had a set of nebulous symptoms no one quite knew what to do with. Eating protein or fiber left me feeling like something died inside me. I had the immune system of a toddler in day care and the energy levels of an attractive woman in her second-to-last scene in a Victorian novel. When I complained, mainstream doctors would test me for three things and throw their hands up if all the tests came back negative. Some people are just meant to spend 11 hours a day in bed, I guess.

So I tried alternative practitioners — people who use the words “integrative,” “functional,” or “naturopathic” on their websites. These people always advertise themselves as seeking and curing root causes rather than playing whack-a-mole with symptoms like mainstream doctors. Sometimes, this worked just like I wanted — a nutrition-focused psychiatrist paid attention when I said that drinking soda made protein and fiber more tolerable and proposed I had low stomach acid, a condition that is easy to test for and treat.¹ For a while I hoped this was my magic cure, and it did help a great deal, but I still didn’t have the energy or immune system of a normal person. 

I tried multiple alternative practitioners to fix the remaining problems, but it was all cycles of hope and disillusionment. I spent a year on leave from work for five dental surgeries to clear out infections in all four wisdom tooth-removal sites (the last infection was large enough that it needed two procedures). I took some devastating antibiotics that gave me seasonal affective disorder, but not much else (based on information from a friend, I tried inositol, which fixed it). Multiple providers told me that if I wasn’t going to eat one gram of protein per pound of bodyweight (which was impossible even with the stomach acid supplements), I was wasting their time.

Then, in April 2022, I fortuitously caught COVID-19. The actual sickness was quite bad, laying me up for five weeks. Even after my tests came back negative, I was exhausted and in constant pain. My doctor at the time was very good, which other people had noticed, so she was also very busy. If I wanted to see someone quickly, I had to see one of her underlings, whom we will call Dr. Lucky Idiot.

Dr. Lucky Idiot free-associated his way to prescribing me five different herbal interventions. A younger me might have demanded he explain what they did, or at least investigated them herself. But I was exhausted and already getting suspicious that research wasn’t all it was cracked up to be. I took every pill. 

A few weeks later, I felt better. Actually, certain things were a lot better. Going into COVID-19, I’d been working very hard on protein consumption. I could get up to 50 grams a day if I made it my hobby and tolerated moderate discomfort. A few weeks into the herbs, I looked down one day at an empty tub of cottage cheese and realized I’d eaten 50 grams of protein in a sitting and felt fine. Good, even.

This was exciting in its own right — protein is crucial for approximately everything in the body — but I was also excited to learn what this said about my underlying issue. Surely this would be the clue that let us unravel the mystery of What Was Wrong With Me, which would suggest more treatments and possibly even a cure.

Dr. Lucky Idiot was less excited. When I asked why the particular herb (it turned out to be Boswellia, aka frankincense) was so transformative, he mumbled something about inflammation and considered the question resolved. As if I hadn’t taken 40 other herbs marketing themselves as anti-inflammatory. 

That success was the exact moment I gave up on understanding my problems as the way to solve them. Careful cultivation had already solved all the problems it was going to solve.² What was left was trying shit until something worked. I still use doctors as sources of ideas, but at the end of the day, I’m the one running the experiments and judging the results. 

So when I see people buying exotic peptides from uncredentialed sources, I don’t see daredevils or lunatics abandoning a system that works. I see people with problems the system isn’t solving refusing to give up on themselves. And when people condemn this, I hear, “You don’t deserve a cure.”

I would take the invalidation of my problems with more grace if I believed they were truly rare. But when I look around, I see millions of people in the same boat. And not just the mysteriously chronically ill — there are people with crisp diagnoses who still find their doctors useless or have great doctors but need to move faster than medical regulations will allow. These people are also driven to hack their own health. 

“Health hackers” are the asthmatic cousins to the much better-known biohackers. Where biohackers put magnets in their fingers or padding in their shins for better Muay Thai showings, health hackers are trying to get themselves back to baseline, or the baseline they wish they had — to ensure they’ll live through the night or not hate the body they see in the mirror. 

This isn’t a crisp distinction. The classic biohackers I talked to often also did some health hacking, and r/nootropics might say it’s about superhuman performance, but reading the comments shows that at least half of them are dealing with serious mental health or neurodivergence issues. The headlines treat gray market GLP-1 usage as unprecedented, but when I compared users to health hackers with problems ranging from diabetes to gender dysphoria, their attitudes were almost identical. Everyone I talked to treated their interventions as experiments, acknowledged the risks inherent in experimentation, but felt the greater risk (as measured by their gut) was in not trying and would never have started hacking if the formal medical system had met their needs.

“The risk was in not doing it.”

Dana Lewis was blessed with a problem doctors recognized and knew how to treat, more or less. Her body didn’t produce enough insulin. The treatment for this condition is straightforward — more insulin — but it requires exquisitely precise dosing. If a diabetic injects too much insulin,   their blood sugar will crash, which, left unchecked, can be fatal. Administering too little risks high blood sugar, which slowly damages organs.³

Today, diabetics can monitor their blood sugar and choose their insulin dose with wearable continuous glucose monitors, which alert them when it falls or spikes to dangerous levels. But back in 2014, when Dana’s story started, continuous glucose monitors (CGMs) were new to the consumer market and not yet considered reliable. Their function was to trigger a blood stick check or serve as a last-minute alert to catastrophically low blood sugar. 

But these monitors aren’t perfectly reliable, and they were even less so in 2014. The sensor in Dana’s could be thrown into a panic just by lying on the arm it was attached to, so false alarms were common. After numerous false alarms, she learned to sleep through the alerts. She complained to the manufacturer, who told her, “It works for most people” — as if that solved her problem.

Dana’s biggest fear was having a hypoglycemic episode in her sleep and dying before she had a chance to do something about it. She did not find the fact that the app woke up other people in time very comforting. So she and her new boyfriend (now husband) Scott Leibrand set to work on a solution. 

First, they needed real-time access to the data from the CGM, the only way to identify problems as they happened. Luckily John Costik, a software engineer and parent of a diabetic preschooler, had already created Nightscout, a program to extract data from CGMs and upload it to cloud storage. Scott, also a software engineer, wrote a program to monitor these uploads, and if they reported low blood sugar levels for too long, call his phone so he could wake up and drive to Dana’s house to revive her. 

This solved the immediate problem of Dana sleeping through her own death but still left her with the problem of managing diabetes during the day. This process was time-consuming at best, and many people didn’t manage it well, spending long periods of time with their blood sugar damagingly high or dangerously low. 

In addition to continuous glucose monitors, state-of-the-art diabetic treatment included an insulin pump. These still required users to calculate their dose based on a mix of scientific literature and their personal history, and manually program the device, but allowed for more complicated dosing schedules over longer periods of time, instead of a single large bolus from a needle. 

So Dana, Scott, and other collaborators set out on a bigger project to “close the loop.” They wrote an algorithm that pulled the data from the CGM, applied the same math patients did by hand, and fed it to a hacked insulin pump.⁴ This created much more responsive, sophisticated dosing that gave them more time in the ideal blood sugar range and less risk of catastrophic failure while requiring less attention.

One reason Dana felt safe writing her own pancreas was that she could do so in very small steps. OpenAPS programmers erred on the side of undersupplying insulin, but the user could get more aggressive over time. OpenAPS also respected the built-in limits of the insulin pump, which meant the system would have to work very hard to do more harm than a human could do from inattention.

When I asked how she thought about the risk of writing her own pancreas, Dana said that all of her risk was in accepting the status quo. She knew a pharma company would release their own closed-loop system eventually — the idea was too obvious and too valuable not to — but she was unwilling to risk dying in the meantime.

“I find the idea of a doctor recommending that a trans patient do anything at all to be laughable.”

I talked to three different trans women. They all asked for anonymity, but as it happens their stories were so similar I feel perfectly comfortable combining them into a single composite story, whose protagonist I will call Emily.

Emily started out confused and uncertain. When she first shared obvious symptoms of gender dysphoria with her therapist, the therapist said, “I can’t help you.” She does not believe there was any set of symptoms she could have taken to a doctor at the time that would have led them to suggest hormone replacement therapy.  So she did her own research, mostly talking to other trans women. By 2010, she knew she wanted HRT, but the standard of care at the time — called the medical model — required she spend months proving her emotional stability to multiple therapists before she was allowed to try to convince an endocrinologist to take her case.

Instead, she went to a clinic practicing the informed consent model, which is based on the assumption that estrogen is not that fun and nobody seeks it out recreationally. If someone asks for it, a doctor’s role is to inform them of the risks and let them make their own decision.⁵ In Emily’s estimation, they did the latter half  (and that just barely). She found them absolutely useless as a source of information.

For example, Emily was offered spironolactone, which suppresses testosterone production. This was common at the time and may still be. But by 2010 the trans community lore was that spiro was outdated and not worth the risk of side effects, which include neurological issues.⁶ Emily turned it down.

Then there’s the matter of estrogen. Naturally produced estrogen comes in three forms: E1, E2, and E3. E2 is the only form used in gender-affirming HRT. But E2, aka estradiol, comes in many forms itself. It can be injected, swallowed, or absorbed through the skin via a patch. 

Patches were out because Emily was allergic, and oral didn’t allow a high enough dose, so injectable it was. But there are also different chemical formulations to choose from, like estradiol cypionate or estradiol valerate. Each method and molecule has different pharmacokinetics, and the same method and molecule might have different pharmacokinetics across different people. Going on HRT always initially involves frequent blood tests of estradiol levels to make sure the extremes aren’t too high, which can cause heart issues, or too low, which risks osteoporosis. 

Everyone knew that estradiol cypionate had the longest half-life, which lowers the gap between the highs and lows while allowing longer intervals between injections. But exactly how big the advantage is varies by person. To know which group she was in, Emily asked her doctor to prescribe cypionate and give her two weeks of daily lab orders to check her estradiol levels. Her doctor complied, and Emily learned that while cypionate did last longer, it wasn’t enough to justify the increase in price for her. The experiment let her choose the cheaper estradiol valerate.

Unfortunately, all estradiols left Emily with brutal abdominal cramping and blood in her semen. Based on talking to other trans women and confirmed by her reading, she thought progesterone might help. Her cooperative doctor wrote the prescription, and she found it enormously helpful for the pain. Unfortunately, it also weakened her joints to the point that she repeatedly injured herself, a trade-off she ultimately decided was not worth it. Instead, she takes periodic breaks from estrogen.

Emily felt safe experimenting with hormones because the negative effects were either front-loaded or easy to detect with testing. That may be why the HRT stories of the three women I talked to were so similar that I had to constantly check my notes to make sure I wasn’t confusing them: When running tests is cheap and knowledge is local, community metis goes into designing an experimental regimen. 

When I asked Emily how she thought about the risks of hormone treatment, she said she put a lot of work into managing them, but it was ultimately worth it for moving toward the body she wanted. When it came to the risks of any particular experiment (a new dose or a new formulation) she felt confident that downsides would be easy to detect and mostly reversible. Despite having fairly different reactions to different estrogens, which ultimately led to different regimens (an alternate universe version of Emily found estradiol cypionate well worth fighting the insurance company for), I got the sense they all started in roughly the same place, and if their experimental results were swapped, their decisions would follow.

But when it comes to irreversible surgery, the composite falls apart. The three women I talked to, with access to roughly the same information, chose completely different paths. One decided against bottom surgery, one accepted it with some reservations, and one would accept it only from the superior surgeons in Thailand. Clearly they weren’t sharing a script, after all, but were weighing highly personal trade-offs as best they could.

After my miracle cure, things looked good for about 18 months. Thanks to the Boswellia and, no kidding, copious amounts of watermelon and potatoes, I lost 30 pounds and had more energy than I had in years. Everything was going great until the start of what I call my mold winter. The mold wrecked me metabolically before aggravating an underlying subclinical infection, which required prolonged antibiotics. I regained all the weight I’d lost and then some. 

After I cleared the mold, my old trick of Boswellia + potatoes + fruit worked … until I got pneumonia, necessitating another round of microbiome-ruining antibiotics.⁷ As soon as I could eat, my weight started creeping up again. I was facing this body-ruining cycle a third time, knowing that health risks were piling up and I was unable to do anything about them. 

So I asked my doctor for Tirzepatide, a more advanced cousin to Ozempic/Wegovy/semaglutide. She was happy to comply, but insurance rejected my request. I had a decision to make: accepting the loss of all of my weight progress and starting over again, paying $1500 per month,⁸ or doing what my friends did and going gray market for an experimental GLP-1 known as retatrutide. 

What I’ll say about that decision is that I wasn’t willing to go back to the starting line a third time. I did what I needed to do for my health and my sense of control over my own body, and I was deeply grateful to have the option. 

The people I talked to who definitely solved their weight problem on the gray market had similar stories. Excess weight has a lot of consequences, and not just for health. Susan (a pseudonym) noticed people were nicer and more helpful to her after her GLP-1 aided weight loss. Ben was happy to see himself in the mirror for the first time — but this paled next to the potential of a different peptide to speed up his recovery after multiple spinal surgeries. 

When I asked how they thought about risk, the universal response was: “I couldn’t afford the risk of not taking it.” The potential upside to weight loss was too big. Like trans women taking HRT, they felt comfortable experimenting because the most likely failure modes were obvious and recoverable, and success was easy to measure. They were, by and large, unconcerned with risks that were very small or very far in the future. 

The blogger Cremieux, who wrote what is by far the most commonly referenced blog post on how to obtain gray market peptides, claimed that “people generally don't try to quantify tail risks.” Among the people I talked to, this is true. But it was not the case that they were highly risk-seeking or unconcerned with their safety. Even the man who described himself as “unusually risk-tolerant” told me he’d never, ever ride a motorcycle.

The health hackers I talked to all have certain traits in common.  They’re poorly served by the medical system. They experiment, and they’re aware their experiments carry risks. They make decisions by gut rather than math, possibly because they stick to experiments where the math is easy. Most of all, they feel a sense of responsibility for their own health outcomes. They might go to doctors for advice, but the final decision rests with them. 

Academics describe people who put themselves in the driver’s seat of life as having an internal locus of control.” Psychologists might say someone has an internal locus of control if they tend to believe that their life outcomes are primarily the result of their own actions or decisions (and an external locus of control if they don’t). 

There is a large body of research that applies this concept to health outcomes. Are patients with an internal health locus of control — that is, people who think their health outcomes depend more on their own choices than on doctors’ orders or genetic luck — healthier than those without it? 

I ran some AI lit reviews, and the results were better than an author could wish for: Internal HLOC is indeed correlated with better results. And when one turns to risk-taking, people with an internal financial locus of control showed the same complex relationship with risk I saw in my interview subjects: They engaged in more overtly risky-looking behavior, but were also more likely to make risk-mitigating moves like buying insurance. It’s a perfect fit for what I found from a few dozen interviews, most of which were with people from my extended social network.

Unfortunately, I don’t put much stock in this literature. I always knew it wouldn’t apply perfectly: The questionnaires measuring HLOC are aimed at beliefs like “taking my pills helps,” not “I can outperform a doctor at choosing my pills.” But when I dug into the details, it was worse than that: While high internal HLOC is correlated with more doctor-endorsed behavior and with better feelings around health, there was no predictive correlation with objective outcomes like hospital visits or cholesterol levels. So what we’ve learned is that not being depressed is nice, and perhaps that people with lots of health problems have trouble believing in themselves.⁹  

Which, in some ways, is the perfect metaphor for my relationship with the medical system: an extensive literature which promises answers but ultimately leaves me with my own inadequate attempts to find them for myself.