What do psychedelics and weight loss meds have in common? Interventional Medicine
It started with a monster
In 1922, Leonard Thompson was a 14 year-old boy in Toronto, Canada, who weighed all of 65 lbs, was balding, and smelled of acetone (the same substance we use as nail polish remover). Diabetes was killing him. But then Dr. Banting and his student Charles Best gave him the life-saving solution of mashed up beef pancreas. With regular use of this animal insulin, Thompson went on to live another dozen years before succumbing to pneumonia.
Since then, we have seen a flurry of improving medications invented for this life-threatening endocrine disease. Insulin was drawn from cows and pigs until the ’80s, when we first started creating synthesized insulin. In 1959, we also developed the famous metformin which is related to a folk plant remedy from Medieval Southern and Eastern Europe (1).
But today we’re talking about the fascinating discovery and evolution of GLP-1 agonists. The original compound was isolated from the venom of the Gila monster, something I remember vividly from medical school because of the reptile’s terrifying appearance.
These GLP-1 agonists, known to many by the names of Wegovy and Ozempic (semaglutide), among others, are now at the forefront of a massive movement in weight loss that has swept the Western world. Billionaire Elon Musk and other celebrities have credited semaglutide for their dramatic weight loss transformations. A shortage which began shortly after they hit the market is still ongoing due to their popularity and success (2). GLP-1 agonists help patients lose anywhere from 4–10 lbs on average in a single month and have few side effects other than nausea and constipation, usually mild. They are so popular that I have had patients begging me to write for longer prescriptions so they can grab the last remaining boxes from their pharmacies.
Our modern-day twin epidemics
Today in most Western societies, we are fighting a battle against the twin epidemics of obesity and mental illness. 40% of US adults are obese as of 2020, and 25% of US adults have a diagnosable mental health condition in any given year (3). The two are connected in many ways — many people who suffer from metabolic diseases also suffer from mental health conditions, and vice versa. Both are massively difficult to tackle, requiring a set of lifestyle changes which are contrary to everything comfortable and easy. They also both have a history of unsavory medication options with bothersome, even dangerous, side affects. And both have been unfortunately exacerbated by the COVID pandemic.
In the fight against obesity and metabolic disorder, we now have GLP-1 agonists. And what do we have for mental health? Psychedelics.
Psychedelics for mental health
Most of you reading this will probably have read my other writings on psychedelics for health. But for those who are new to this topic, I’ll briefly note that psychedelics are immensely powerful medicines that can help rewire a person’s brain to be happier and healthier. Studies have shown incredible positive responses to just a few doses of psychedelics like ketamine, psilocybin, and MDMA for conditions from depression, substance use disorder, and PTSD (4, 5).
The way psychedelics work for mental health, at the very high level, is by resetting the brain to its healthy foundations. Many people have scars which are not only metaphorical but are also notable on neural analysis. These are results of events such as traumatic incidents and habitual, unhealthy thought patterns. Just like weight gain or insulin resistance in (type 2) diabetes, it takes significant effort and time to revert these scars. The psychedelic effect on the brain roughly translates to softening these scars to a more malleable clay so that we can more easily and quickly learn healthier habits. We call such changeability of the brain “neuroplasticity.”
What are Interventional vs Chronic Medications?
The word, “intervention,” brings to mind the image of a room you’ve just walked into, full of your best friends and family members, telling you that you need to stop drinking and then sending you to a detox and rehabilitation center. This tactic is actually quite effective when done well, but it requires a lot of coordination between said friends and medical professionals.
“Interventional medicine” used to be relegated to surgeries and procedures. An intervention used to mean you got cut open, or irradiated, or put in a machine to be electrocuted or magnetized for electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS). The only medications used interventionally used to be for such procedures, infectious diseases, and cancers — definitely not chronic illness. Which is a major reason why those diseases are chronic.
Those of us doctors in non-procedural fields (myself in internal medicine) had to treat the most common, chronic diseases like diabetes, high blood pressure, and depression with slow, similarly chronic medications which require a high level of willpower and adherence on the part of the patient to work.
An interventional medication such as a GLP-1 agonist or a psychedelic is far more powerful in a shorter amount of time. With one course of treatment — usually a few months total — a person can lose over a hundred lbs or go from being suicidal to being a fulfilled, happy being. In the case of GLP-1 agonists, your appetite is diminished radically due to the medication (taken weekly) slowing down your gut’s movements and thus keeping you full with less food. With psychedelics, your unhealthy thoughts are quieted so you can finally focus on becoming the happy person you want to be.
Lifestyle changes are needed
I have had so many patients ask me how many sessions of ketamine they need. I always give them a forewarning before my answer, because the truth is, it depends. It depends on how severe your condition is and how ready or supported you are for the intervention (see the next section).
The hard part comes after the initial intervention. With the room-of-loved-ones type of intervention, you still need to build a new life around sobriety. This usually means new friends, new habits, new ways to relax and enjoy your time. With GLP-1 agonists, you either have to adopt new routines around diet and fitness or expect to be on weekly shots forever (not recommended). Psychedelics similarly do not protect you from your past mental habits and relationships with your surroundings, work, people, and even yourself. You need to learn emotional resiliency skills and build up a practice of mindfulness and mental wellbeing in order to sustain the gains from a psychedelic treatment.
It is hard, when you are dealing with the inflammatory and often devastating effects of chronic illness, to pull yourself together at the heroic levels required for some of these difficult, all-encompassing lifestyle changes. The “magic” of such interventions as GLP-1 agonists and psychedelics is in creating a jumpstart many people need and cannot find within themselves while they are ill.
Support is key
Depending on a person’s prior preparation and circumstances, they may need more or less support through and after an intervention like GLP-1 agonists and psychedelics. Some people are simply bouncing back after a temporary period of obesity or depression and can use self-help books, or app-supported meditation, or fitness apps to support an ongoing healthy lifestyle. Others need a professional such as a personal trainer, coach, therapist, nutritionist, or doctor to guide their “integration” of new learnings, habits, and skills. There is no one solution for every person — sometimes you might even need a professional to even help you determine what degree of support you need.
The trouble with a lot of medicine, interventions included, is that we do not have a system that rewards support. The US healthcare system is largely fee-for-service in terms of its reimbursement, which is a topic too large and complex for this article, but simply stated it does not reward activities like education, coaching, motivational speeches, or other such activities that would equal support for the patient. It unfortunately incentivizes more procedures and other reimbursable actions (some people will note accurately that it therefore incentivizes ongoing illness — this is another important topic that requires a much longer post to discuss).
You have to want it
I once had a patient, let’s call him Alex, who was metaphorically dragged in for care by his wife. She took care of every aspect of his care, including his schedule of sessions and replying to our questions about how he was feeling. This was a show of immense support, which is needed for dramatic changes (see above), but unfortunately it was also a sign of the patient’s lack of self-initiative in his care. Alex was in deep denial about his condition. He stated he was well when he wasn’t, and that he was sober when he still drank a fifth of liquor each night. He simply did not want to change.
This may sound harsh, but it is also true and very much a normal part of the change process. The transtheoretical model (TTM) of behavioral change is an integrative theory of therapy which explains, among other details, the stages of change a person goes through.
Precontemplation is simply the stage when you don’t even realize you have a problem.
Contemplation is when you recognize the problem and start thinking about the pros and cons of the behavior — “The first step is knowing you have a problem.”
Preparation is when you start to make plans and even take small steps towards solving the problem you’ve identified. This is about when we at Curio typically start working with patients.
Action is exactly what it sounds like, when you are full-heartedly taking action towards your goals.
Maintenance is when you’ve achieved a level of success in your change that it is easy to maintain the new lifestyle or status. There are varying beliefs about whether a person can even do this with absolutely no effort (an additional stage sometimes called termination) — but in most cases, people will face temptations or challenges which need active effort to work against. Without proper maintenance, a person can fall back to the problem state or relapse (6).
Alex was not at all at the stage of preparation when his wife brought him in. He was not even in contemplation. The denial of his ongoing conditions put him squarely in precontemplation, which made it relatively useless to try and force him into action.
Many people unknowingly cling to their unhealthy lifestyles for different reasons. Some, like Alex, do it because they derive pleasure and are enabled by loving family members who are unable or unwilling to see the severity of disease enough to take drastic action. Others do not want to change because it would necessitate overturning a comfortable lifestyle, albeit not the one that fulfills their greatest potential.
So this is not some hokey saying, or the lyrics to some pop song. “You have to want it” is actually one of the basic tenets of health that you have to want to change to make a real difference with most chronic conditions. This doesn’t work for certain diseases, like cancer, broken bones, or COVID unfortunately (although it definitely helps with adherence to treatment plans). But it is absolutely true for conditions which are heavily based on lifestyle factors — metabolic diseases and mental health conditions included.
The work never ends
In the case of metabolic disease and mental health, if you go back to unhealthy habits (eating junk food, cutting into your full night’s sleep, thinking negatively about yourself, etc), the obesity, diabetes, hypertension, depression, or anxiety will come back. That is, maintenance always requires some level of work for these chronic conditions. There is no forever cure that will guard you against future relapses. This is very similar to what is taught in 12-Step Programs for addiction — that one is an addict no matter how long ago their last drink was, and one must recognize that in order not to fall back into the addictive behavior (7).
This might all sound devastating, but shouldn’t. Once you reach a degree of happiness and satisfaction with your new, happy, mentally and physically well life, it will feel very natural. If you’ve ever tried cutting out desserts that after a few days, you may have noticed that your cravings for the sugary treats diminished. This works for social media, poor sleeping schedules, bad TV, and most other unhealthy triggers after a period of weaning down and abstinence. (Note that some substance dependencies require a medical team to assist with safe quitting in case of withdrawal effects.)
Again, it is incredibly important to maintain a support system — the people around you — who truly believe in your healthy lifestyle. If those closest to you are not willing to be happy for you, it will be even harder to maintain your newfound superpowers (because they are!).
After a while, this work of changing your lifestyle to support your health becomes your new life. It becomes your habits, your relationships, and even the way you think. You see this in people who join running groups, or book clubs, or yoga studios. It may feel far away when you are deep in a state of depression or long-lasting obesity, but with the proper intervention and support, positive transformations are very much possible.
Interventional medicine’s legacy
My hope for the future of health and wellness is that we will use interventional medicines like GLP-1 agonists and psychedelics to their maximum benefit. This will require them to be wrapped around by supportive care services, like coordination and coaching, preferably in close conjunction to the medication intervention. We will then be able to successfully fight against the worsening twin epidemics of metabolic disease and mental illness. There are existing incentive systems which may endanger this future — we may end up using GLP-1 agonists and psychedelics like chronic medications rather than like the interventions they have the potential to be. There needs to be systemic and cultural change to fulfill the greatest benefits of interventional medicine, and our society (as well as our economy) desperately needs such changes.
References
- White JR Jr. A Brief History of the Development of Diabetes Medications. Diabetes Spectr. 2014 May;27(2):82–6. doi: 10.2337/diaspect.27.2.82. PMID: 26246763; PMCID: PMC4522877.
- Yang, A. (2022, October 21). What to know about Ozempic, TikTok’s favorite weight loss drug [web log]. Retrieved November 29, 2022, from https://www.nationalgeographic.com/science/article/ozempic-tiktoks-favorite-weight-loss-drug-is-unproven.
- Mental health disorder statistics. Mental Health Disorder Statistics | Johns Hopkins Medicine. (2019, November 19). Retrieved November 29, 2022, from https://www.hopkinsmedicine.org/health/wellness-and-prevention/mental-health-disorder-statistics
- Psychedelic research papers. Blossom. (2022, November 29). Retrieved December 1, 2022, from https://blossomanalysis.com/papers/
- Psychedelics Drug Development Tracker. Psychedelic Alpha. (n.d.). Retrieved December 1, 2022, from https://psychedelicalpha.com/data/psychedelic-drug-development-tracker
- Wikipedia contributors. (2022, October 1). Transtheoretical model. In Wikipedia, The Free Encyclopedia. Retrieved 14:58, December 1, 2022, from https://en.wikipedia.org/w/index.php?title=Transtheoretical_model&oldid=1113447540
- 12-step programs. Addiction Center. (2022, November 29). Retrieved November 30, 2022, from https://www.addictioncenter.com/treatment/12-step-programs/
