Dr. Corey Hilmas is a respected scientist, medical doctor, and former U.S. federal food regulator. After having completed his medical degree and doctorate in toxicology, working as a principal investigator for many years, and serving on behalf of the U.S. government at FDA, Dr. Hilmas combines his unique science skillset with extensive U.S. regulatory training. He served as an NDI notification reviewer and as a branch chief within the Division of Dietary Supplement Programs at the FDA. In addition to working on enforcement matters related to supplement labeling, claims, GMPs and fraud, he also served as an expert witness for the FDA and DOJ, resulting in an FDA Award of Merit from former FDA Commissioner Margaret Hamburg.
What first got you excited about the use of psychedelics as a therapeutic treatment?
I am a neurotoxicologist and neuropharmacologist by training. I was in graduate school at the time trying to figure out what it was I wanted to study for my dissertation PhD work. It was in an era where professors still preferred to compose handwritten, thoughtful congratulatory correspondence to colleagues or carefully crafted snide rebuttals to competitive rivals through the mail rather than use the latest desktop computer programs. I was in one of the premier electrophysiology labs in the world working to help further characterize nicotinic acetylcholine receptors (nAChRs) in the brain. My advisor was one of the preeminent authorities on ligand gated ion channels in muscle and in the brain. He discovered and characterized the various nAChR subtypes by electrophysiological means. It was known that schizophrenic patients used nicotine heavily and thought maybe they sought to self-medicate. Perhaps the nicotine, which does have an effect on nAChRs at physiological levels, alleviated some of the symptoms of schizophrenia. We set out to look at nAChRs as a central player in schizophrenia. It is often said that to understand schizophrenia is to understand mental health. I looked at drug models for schizophrenia to investigate how nAChRs could be involved. I selected drugs that were psychoactive and known to mimic some of the positive symptoms of schizophrenia (hallucinations, delusions, difficulty concentrating, confused/disorganized thought) - ketamine, phencyclidine, amphetamine, cocaine, etc. Ketamine and phencyclidine were the two I focused on most because they were considered true schizophrenomimetics. To make a long story short, what we thought we knew about ketamine and phencyclidine and how they worked wasn’t the whole story. We attribute their activities through NMDA-subtype glutamate receptors, but it wasn’t until four decades later that we discovered how they act on nAChRs.
I bypassed the post-doc life and became the PI of my own laboratory looking to develop neuroprotectants against toxic chemicals. I learned new tricks and techniques on the fly, learning from whoever would teach me. I learned how to sew biotelemetry implants into research animals to monitor EEG, EKG, EMG, blood pressure, diaphragmatic pressure, heart rate, respiratory rate, activity, etc. I was selected to give a talk to NATO, and the paper is out there. The essence of that research was to show for the first time that ketamine showed promise as a post-treatment and pretreatment in reducing the risk of nerve agent-induced seizures and death. Who would have ever imagined that ketamine, a dissociative anesthetic could rescue animals from some of the most toxic substances on the planet, reducing seizure activity and enabling them to survive such an insult? The paper also provided a mechanism as to how that was happening.
What is the most common misconception you hear about psychedelics?
I think they unfortunately get lumped into the category of “legal high botanicals” or people default to thinking about LSD. I think to some it conjures up images of substances used at parties without any regard for scientific pursuits. People like to think of psychedelics in terms of n=1 studies where. I think that stems from the fact that people associate the term psychedelic with substances that only cause hallucinations. But psychedelics don’t have to be hallucinogenic. The mind can be unlocked and consciousness expanded without hallucinations. Sometimes I use the more generalized term psychoactive or CNS-active instead of psychedelic to describe whether a substance may expand consciousness. While psychedelics can encompass botanicals or LSD, psychedelics are also drugs that have been studied over many decades, used in clinical trials, anesthetics used in veterinary medicine, historically used in pediatrics. And that is our fault as scientists; we do not do a good enough job of communicating the established science to the lay public. Think about how long it takes textbooks to be updated with new scientific information. They are always outdated.
You have unique experience in both science and working with regulations, from previously at the FDA. How has this helped you advance KGK’s work with psychedelics?
I am always asked about my time at FDA and government life. I think it was a critical part of my career path. I can’t do what I do and help companies with regulatory issues unless I spent any significant amount of time there. You can read the regulations but that won’t give you the ability to create solutions for companies. An understanding of how FDA works -- their mission to protect the US food supply, the process by which drugs are approved, their thresholds for taking enforcement action to protect the public – is fundamental in providing regulatory solutions for our clients. Reading articles from the trade press won’t make you a better regulator. You have to have experience in dealing with those questions as a federal regulator, directly or indirect, or at the very least you have to know where you can go in that massive organization to find your answer. I worked with many bright colleagues during my time at FDA, most of which are still there, and I know how the Agency thinks on most subjects. Companies are looking for that type of insight, for example, in bringing new ingredients or actives to the market.
I also spent time as the Agency’s expert witness on labeling, claims, and toxicity of ingredients. I replaced someone in that role who retired, and I was handed a tremendous opportunity to learn about a commodity I knew nothing about and to be a government expert in court. When I started, there was very little enforcement activities, GMP inspections were being done, but there was no playbook we had to say this is the evidence required to demonstrate lack of compliance. All of that experience has helped to forge a new regulatory business unit at KGK dedicated to bringing products to the market. We help companies with claims after completing their clinical trials, but we are much more. We are a one-stop shop for almost anything regulatory from writing Citizen Petitions, safety dossiers, regulatory status letters to compiling Adverse Event Reports, substantiation files for ingredients, and offering labeling and regulatory consulting advice. Psychoactives can be botanicals that could meet the definition for dietary supplements or they could be drugs, excluding their use in foods. For example, Kanna (Sceletium tortuosum) is a psychedelic and may elevate mood while decreasing anxiety, stress, and tension. While it can cause euphoria, it is not hallucinogenic. It could qualify as a food. On the other hand, ketamine could never qualify as a food. So psychedelics are a broad enough category that some can be foods while others drugs.
Can you explain KGK Science's relationship with Ketamine One? What will you be focused on building together now that Ketamine One has acquired KGK Science?
Under the terms of the recent acquisition, KGK Science is a subsidiary of Ketamine One. KGK Science brings regulatory bench depth at both US FDA and Health Canada.so it is a synergistic relationship. KGK also has over 24 years of experience in designing and conducting clinical trials on nutraceuticals, topicals, and pharmaceuticals. Ketamine One clinics are where those 2 vectors meet to accomplish Ketamine One’s goals to conduct compelling, innovative, and rigorous scientific research using psychedelics. However, we also do clinical trials for others in the psychedelic, food and nutraceutical spaces. We conduct those studies in-house or at multiple clinic sites in North America or elsewhere to accomplish the goals of our clients.
The narrative of ketamine for mental health is a great story to tell. Here you have an anesthetic being used for treatment resistant depression. We will look to build on that story in future clinical studies. The plan is to rewrite the overall narrative on psychedelics and to unlock their potential to ameliorate a wide variety of mental health disorders.
Can you tell us about some of the clinical trials KGK is working on that are focused on psychedelics?
I don’t know how much I can state without express permission from clients. I can only say that interest surrounding psychedelics is at an all-time high. We are in a renaissance or reawakening over their applicability as useful therapeutics or nutraceuticals. The 1960s are in the rearview mirror. This time around, the approach is more methodical and regulatory driven. We will apply gold standard scientific tools and hypotheses to address very specific scientific, regulatory, and medical questions.
Can you share some of the psychedelic focused companies you are currently working with and helping advance clinical research for?
The nutraceutical and psychedelic industries understand that KGK Science brings insight into how federal agencies think and how products should be brought to the market lawfully. Therefore, the companies we help are typically the ones who want to do things the right way. They want to go through the front door with regulatory agencies like FDA. We provide a number of services to help our clients: 1) a pathway to market analysis to better understand the pros/cons of the various routes and identify the most appropriate one going forward; 2) a gap assessment to describe the regulatory distance in how far away they are in achieving their goal; 3) a regulatory strategy for how to bridge that gap; 4) the detailed studies and costs required to achieve a regulatory goal; 5) the timelines required to allow C-suite executives to plan and make informed decisions; 6) a trusted, experienced toxicology group to interface with preclinical service providers; and 7) a dedicated team of scientists and clinicians capable of providing novel, adaptive protocol designs for clinical trials.
For example, we are working with a company called Psyched Wellness. They have an interesting ingredient with a considerable, historical use record as a food. They want to bring an Amanita muscaria mushroom extract (AME) product to market. People have eaten these mushrooms for centuries, but an extract of the mushroom has never navigated the FDA’s or Health Canada’s scientific and regulatory waters necessary for bringing it to the North American marketplace. When bringing a product to market for the first time, this company is an example of how one should follow the complicated steps and rules of the road set forth by federal regulators.
And of course we are working with Ketamine One to achieve their goals. They are pioneers in clinical research with psychedelics. It will be exciting to synergize forces with their team of experts and participate as their regulatory and clinical trial partner.
What excites you the most about KGK’s future in the psychedelic space?
Personally, I have watched our regulatory division grow since I came here. We grew under the CBD/cannabis sector, and now we have an opportunity to help grow the psychedelic space. We can be the first to conduct clinical trials on ground breaking mental health studies and the first to bring new psychedelic ingredients to market in the nutraceutical space. We can help companies provide substantiation for new claims on products. We will be sought to draft new Citizen Petitions for health and qualified health claims. We will bring new products to the marketplace. The regulatory outcomes achieved by our clients is what drives me on a daily basis. Helping to bring innovative products to the market that are compliant, safe, efficacious, and demonstrate quality is exciting. How many people can say they have lawfully brought 5 or 10, or however many different ingredients/products to the market and received no comment letters from the FDA or other regulatory agency. We are regulatory and science nerds but masters of our craft.
Where do you see the psychedelic medicine opportunity going and how impactful could it be on healthcare?
On one hand you can say, it has taken a long time to get where we are today. And on the other hand, you could say that we have come far in such a short time. Who is right? The attorney would say “it depends”. I think both answers are right. The basic science, pharmacology, physiology, and biochemistry are known for some substances, and It took decades to reach that plateau. Regarding other psychedelics, we need to do more basic science work on the pharmacology and physiology of these substances as well as preclinical studies on their safety. We have only scratched the surface in terms of understanding exactly where they act and how they act.
For the substances that have been around for decades, we are still uncovering new mechanisms as to how they act 40 and 50 years later. The next knowledge gap to address are clinical trials to identify specific diseases they are useful as therapeutics or to evaluate their usefulness as nutraceuticals to promote a healthy lifestyle. The clinical trials will determine how impactful they will be on the future of healthcare.
Regarding ketamine, I think it has already shown tremendous promise as a third-line agent in the treatment of major depressive disorder. Ketamine has a chance to help when there are fewer options left in the setting of treatment resistant depression. It will be interesting to see expansion of off-label use of ketamine into other areas of mental health outside of major depressive disorder. Could ketamine be used for depression in ways other than as a third-line therapeutic? To answer that question will require more time and clinical studies.
In parallel with psychedelic clinical trials, we will see new tech opportunities in this industry. We will start to see validation of equipment designed to record real-time biomarkers of brain activity in response to psychedelic treatments. There are virtual devices being developed to look at electrophysiological markers and waveforms that are altered or disrupted in certain disease and mental health states. This is no different than monitoring EKGs for changes in electrical activity of the heart. It will be only a matter of time before the right electrophysiological signal wave forms in the brain are found or to monitor treatment progress or to predict treatment success.
What obstacles need to be overcome to bring psychedelic therapies to patients? What do you think fundamentally needs to change in order for there to be broader medical accessibility?
Well for one, you often need preclinical safety in order to conduct clinical trials. Some of these psychedelics have considerable preclinical safety, while others have not. If there are barriers to conducting preclinical studies because of exporting and importing regulations affecting that ingredient across international lines or even across state lines, then those regulatory hurdles can seriously hinder progress made in clinical trials. It would be nice to see those barriers to certain psychedelics, like DEA scheduled substances, removed, but we understand why those rules have been put into place. Obtaining DEA and other site licenses to work with psychedelic drugs is no longer as difficult as it once was, so there have been efforts made to lessen those regulatory burdens for companies determined to bring products to market the correct way; however, not every country has lessened those barriers. There are cultural obstacles to bringing psychedelic therapies to patients. Some cultures have created stigmas over these substances. In order to remove the stigma surrounding certain psychedelics, we need more preclinical data as well as data on their clinical safety and efficacy.