Psilocybin-Assisted Therapy Has Potential for Treatment of Binge Eating Disorder

In an interview with Pharmacy Times, Jim Gilligan, PhD, interim CEO, president, and chief scientific officer of Tryp Therapeutics, discussed a new trial investigating the potential use of psilocybin-assisted therapy for the treatment of binge eating disorder. In the interview, Gilligan said psychedelic medicines like psilocybin work to re-wire the brain, potentially addressing the root cause of eating disorders rather than the symptoms.

Aislinn Antrim: Hi, I'm Aislinn Antrim with Pharmacy Times, and I'm here with Jim Gilligan, interim CEO at Tryp Therapeutics, to discuss their new trial investigating psilocybin-assisted therapy for patients with binge eating disorder. And so, from my understanding, the first patient has been enrolled in this trial. I've heard a lot about the use of psychedelics for depression, PTSD, etc. But I haven't heard much about its use for eating disorder treatments. How could this therapy help patients with eating disorders?

Jim Gilligan, PhD: You know, when I was looking at the questions and trying to get prepared, I was trying to think what would be the best answer. Well, it turns out they have a common denominator, and that is that in all these instances it emanates from the [central nervous system], so the etiologic factor driving this comes from the brain. And so many times what happens in our treatment paradigms is, we spend more time treating the symptoms rather than going and trying to see what the cause of the problem is. And if you think about the situation with obesity, and binge eating, it's a behavioral problem where you have an obsession around food, or an inability to control how much food you eat, and so it's really that the signals are coming from the brain. So how do you go in and try to correct that, versus just trying to take a pill that may lessen your appetite? But every day is the problem still persists?

Aislinn Antrim: Absolutely, it's a very good way of putting it. Can you discuss TRP-8802 and what it is?

Jim Gilligan, PhD: Sure, that's fine. So, I've been in drug development for over 35 years, and there's a lot of risks in drug development, it's difficult. And so, what we elected to do is TRP-8802 is just our synonym for oral psilocybin. It's what's used in all the studies that you alluded to, for PTSD and things. And we wanted to use it as a tool to determine if there's a good signal in different indications. So, in addition to binge eating disorders, we're also looking at what's called nosaplastic pain and that includes things like fibromyalgia, complex regional pain syndrome, phantom limb, and in these instances, we're going after areas that have not been really examined as thoroughly as some of the others. We wanted to use this as a tool to determine if there's a good signal and this was the quickest way for us to get to the clinic, using what's currently out there. If we do get a signal, we'll migrate over to our proprietary product, which is TRP-8803. So, one number more than 8802.

Aislinn Antrim: Very interesting. What did phase one data show, or what other data support this approach to treatment?

Jim Gilligan, PhD: So, one of the advantages of working with psilocybin is that the biology is well known. You know, one of the problems in drug development is you come up with a new molecule, and you really don't know what to expect. In this case, we know psilocybin has an effect and induces a psychedelic effect, we know what receptors it binds to. So, in the case of overeating, we know one of the receptors that binds who is called 5-HT2A, that's the serotonin receptor. And that's what induces the psychedelic state. It also, interestingly, binds to another receptor called 5-HT2C and that actually has an effect on appetite and satiety. So, you would see that it could have an effect in overeating. But I have a PhD in pharmacology, and one of the things I know for certain is if you give a drug like psilocybin, it's gone after 24 hours. Yet, if you look at the results for these types of drugs, it persists for 3 weeks, 4 weeks, 3 months, 6 months. So certainly, it's not the drug that's currently there. It's the effect that it's had in the brain, it's the changes that it's caused. And so, we really didn't have to go back to the phase 1, we know what dose to give to get the desired effect. So, we were able to sort of jumpstart and go right into patients.

Aislinn Antrim: Wonderful. What are current treatment approaches for binge eating disorder and specifically pharmaceutical approaches?

Jim Gilligan, PhD: So, if you think about it, it goes back to my first comment, and that is that we all too often treat the symptoms. I mentioned, you know, fibromyalgia [and] what do we treat? We treat the pain. We're not treating what's causing the pain. And here, most of the drugs that are approved have to do with things that will either diminish absorption of nutrients out of the intestine or satiety. Actually, back when I was at Unigene Labs 15 years ago, we worked on peptides that would inhibit your appetite [and] satiety. And if you look at some of the things you see on TV now, they're originally diabetes peptides like doraglutide and semaglutide. They bind to what's called the GLP-1 receptor or they have an effect on amylin and they have an effect on satiety. But the issue, the problem is that the behavioral problem that's causing overeating is still there, you're just tamping down satiety. A good example is bariatric surgery. I mean, that's, you know, pretty heavy duty. And even there, after about 5 years, you can see people starting to gain the weight back. Why? Because, you know, they targeted the stomach and they reduced caloric input. But that factor, the driving factor you continue to eat hasn't been corrected. So, the things that are out there are either appetite suppressant stimulants or things that may affect satiety.

Aislinn Antrim: Definitely. What gaps in care could psilocybin assisted treatment fill?

Jim Gilligan, PhD: So, I think what we're hoping, and we think is, first of all, there's tremendous unmet medical need, and in the areas that we've looked at, things really don't work very well. We're trying to get to a point where you don't have to have chronic therapy, because of all the side effects associated with different pharmaceuticals that are administered over long periods of time. And what we believe is that if you use a psychedelic in conjunction with psychotherapy, or trials have a psychotherapy component to that, that you're actually able to go in through the neuroplasticity of the brain and realign some of the neural networks that are causing this obsession over food. And I know this doesn't sound like a good analogy, but when I first started looking at this, one of the areas I said was pain. And I was talking with a specialist, and he goes “Jim, the best way to think about this is as phantom limb pain and phantom limb pain.” Through a tragedy or trauma, someone loses a limb and yet, after a while, they have really horrible pain in an extremity that doesn't exist anymore. So, it clearly points that the pain signal emanates in the brain. And in dealing with the folks at University of Michigan, they go, “Jim, our job is to turn that pain signal off, turn the switch off.” Well, if you think about that in overeating, same thing, we want to turn off that switch that's driving this overeating phenomenon. And if we do that, we could look at intermittent therapy over time where the person's eating behavior in relationship to food has changed. So, I don't want to say that we're curing them, but we're certainly helping correct the factor that's causing the overeating problem to begin with.

Aislinn Antrim: That's really interesting. What is the timeline like for this research? And what do you think the future of this treatment looks like?

Jim Gilligan, PhD: It's always too long, right? Everybody says that. But what we're looking at right now, as we said, we started our study down at University of Florida with Dr. Jennifer Miller, who's just fantastic. She's so knowledgeable, she's so great to work with. And so, that's a small study, it's only 10 patients, it's open label, everyone gets psilocybin, so they know they're getting the drug. And we're looking at a change in their behavior. And since Dr. Miller knows a lot of her patients, she'll be able to tell us whether or not we're getting the benefit we hope to see. Once we see that, we'll then move over towards TRP-8803, which is Tryp’s proprietary product. And so, you know, that will take several months, and hopefully we'll see a signal, and we expect to see a signal. And then we can start our next studies with 8803, which would be more traditional, multi-site studies at many different sites with more patients. Now, the thing I like about our approach is that a lot of these patients have a constellation of symptoms, it's not just overeating. They might have anxiety around food, they might be depressed because they're eating too much. They might not be able to sleep, whatever it is. And so, in our studies, we're measuring many things. We're not just looking at what how much weight the person loses. We're doing neuro imaging, so we're looking at brain scans to see if we can understand what's changing. Will that be a benefit? Is that going to help us in the next generation for treating patients? So, we're taking, I have to say, a very rigorous scientific approach to this so that we understand, we can explain to people hey, this is working because we're changing certain areas in your brain or we're improving things that are going to help you cope with your eating disorder.

Aislinn Antrim: Yeah, that's really fascinating. Is there anything else that you would like to add or anything that I didn't think to ask about?

Jim Gilligan, PhD: No, I appreciate just having the opportunity to discuss this. But it's funny for me because my background was cardiovascular and endocrine and I fell into the same trap everybody else does. So, all the things I was working on, I realized to a large extent, we were treating the symptoms. And when I was invited to join the Tryp team, I really hadn't worked in CNS. And so, I had to do a lot of homework, you know, I had to do a lot of work to get myself onto a learning curve. And to me, it was fascinating to see what the clinical potential is, and you're seeing that in the industry. You know, they're looking at addiction, and you know, at Johns Hopkins, and they've had a lot of luck. And there's a corollary here, you can see this as a food addiction. They're looking at anxiety, they're looking at PTSD, they're looking at a number of areas. So, it seems that there could be a fair amount of potential with use of psychedelics. I think the key for us in research is, how do you leverage that? How do you harness that potential for the patients to drive a beneficial outcome? So, I'm really pretty excited about where we are. I like the idea of, you know, getting answers soon to understand whether we have a benefit. All of us get into this field, you get in with an altruistic tendency, meaning you want to help patients, you want to come in, you want to develop drugs, you want to do something to help the sick, and I feel that this has afforded me a great opportunity to achieve that.

Aislinn Antrim: Wonderful, thank you so much for talking with me about this.

Jim Gilligan, PhD: Well, thank you for giving the opportunity to speak with you