The benefits of psychedelic medicine could expand into long-lasting and transformative therapeutics to treat depression better than selective serotonin reuptake inhibitors (SSRIs).
Pharmacy Times welcomes Adi Zuloff-Shani, PhD, founder of Clearmind Medicine, as she talks to us about psychedelic medicine for treating unmet needs, being an elephant that is stuck on a path, and the benefits of psychedelics in overcoming mental disorders like alcoholism.
Q: How is psychedelic research disrupting medicinal development today?
Adi Zuloff-Shani, PhD: So, I think I need to start with the word today because I cannot acknowledge that there was extensive psychedelic research between the 50s and the 70s- which had shown some very good initial results and showed very good potential for psychedelics. And unfortunately, it was banned for decades. But I'm super excited that now we're back. And research is back. And there's openness from everyone across the board- physicians, psychotherapists, regulatory bodies, and also the history, which is extremely, extremely important. I'm very glad that I not only live in such an area, but also that I am the CEO of a company who develops pharmaceuticals based on psychedelic compounds.
But going back to your question, I think that for the first time in decades we can offer something that is a radically different approach to acute challenges of mental health. And if we're looking at traditional pharmaceutical solutions, it's mostly focusing on a specific mechanism of action. We are very complicated creatures if you will. So when we come to offer some kind of a solution, we need to look at it in a more holistic way, and not just a targeted, very specific, and very narrow solution. And I think that psychedelics give you just that because they work on so many levels. That they can (and this is what we see from clinical trials, double blind, placebo controlled clinical trials, which are extremely important). We see these very positive, very optimistic results. And I think that's the that's the main promotion, if you will, that psychedelic treatment has started to offer. And I do believe that will continue to offer to mental health disorders.
Q: What are some of the mental health disorders that currently have unmet needs regarding treatment?
Zuloff-Shani, PhD: I think that the list is almost endless because I think that there's no question about it. We are in a current crisis, a mental health crisis. I think that in the United States, it was also already announced—but also worldwide. COVID obviously did not help that. I would start with depression and PTSD, OCD, and many addictions.
I really want to focus on alcoholism because this is something that we develop at Clearmind. We develop a treatment for alcoholism. So not only that, but there’s also a huge unmet need (and not good and satisfactory treatments) for alcoholism. I don't believe that many understand the magnitude of this problem. And I think that's the elephant in the room have mental health challenges. As I said, without any effective treatment- and if you look at the numbers- the numbers are really striking. Alcohol consumption is an ongoing epidemic with more than 25,000 deaths a year just in the US. Worldwide it is much higher. It's not an epidemic of North America. It is in Europe, western Europe, and in the Far East- there are 3 million deaths around the world.
COVID-19, as I said, didn’t really help that. And, something that I'm not sure that everyone is aware of, but alcohol is a legal drug. And it's a legal drug that more people are addicted to than any other substances. Not only that, but it’s also associated with a lot of diseases like cancer, liver, obviously failure. Also, it's not just impacting the person who uses alcohol, but community-wise it affects his family, it affects the community. We, as a society, spent a lot of money treating people with alcoholism. It's really a mental health problem that needs a good solution. And, of course, I believe that our treatment can be a very good solution to solve this problem.
Q: How do SSRIs and MDMA treat depression differently?
Zuloff-Shani, PhD: I think that I just started to chat to touch on that, when I said that when you look at some of the, let's say, traditional pharmaceutical treatments, like SSRIs, that we have available, we're speaking about something that is quite focused. So taking SSRIs- we have serotonin in our brain and we need a secretion of serotonin. But we must be very precise. We must have a balance. When we have some kind of a neurotransmitter that is being secreted, like serotonin, there will immediately be some kind of a protein that will be in charge of a protein that will have to remove the axis of serotonin, because we have to have this balance. When this balance is interrupted, and you want to offer someone a treatment to try and fix this imbalance (or increase the amount of serotonin it delivers in the brain), then you have SSRIs.
The problem is that first of all, it's a very, very focused solution. But also, it's very transient. Let's say the most known episode from a Hollywood movie as an example. When you have this beautiful girl, and her boyfriend just, you know, left her, she is now very sad- she's depressive. So she will go to the refrigerator take ice cream, and enjoy the ice cream. But she will enjoy it for just for a few minutes because she enjoys this very creamy, sugary texture of the of the ice cream. But then, immediately afterwards, she maybe she will feel nauseous. Maybe her head will hurt because she ate all this ice cream.
What I was trying to do with this example is explain that SSRIs are very transient solution. It affects the mood, but it's very transient. Afterwards, I'm going back to this depression that I've suffered from before. And we have to remember that SSRIs (because it looks at one very specific part of a mechanism of action) is not very effective. I would say that at least one-third of people who will be treated by SSRIs will have no effect whatsoever. Two-third will have some kind of effect (we cannot say how much is because of the placebo effect) and also there's the question of tolerability to the usability, which means that you have to increase the effective dose.
When you increase effective dose of a treatment that is already associated with multiple adverse events, you just make the adverse events even worse. So no surprise that there's a reluctance to use those drugs. And no surprise that it's not a good solution. When we look at psychedelics, they have so many levels. And I must be very cautious and say "potentially" or "speculated" because not a lot of the mechanism of action of psychedelics has been revealed. But on the other hand, we have those wonderful results starting to come out from clinical studies.
Psychedelics treatment can really affect people in many, many layers. One of them would be to affect our consciousness and allow us to look differently at the problem that we experienced before that.I just spoke with a very well-known psychiatrist. There's something in psychiatry that cause "elephant path", meaning that elephants will always go in the same path, they will never change the path. We are very similar, in that when we have this memory or thinking of something that traumatize us- it causes PTSD, depression, alcoholism. Whatever the reason is why we started to do something that is not good for us is because we started to be affected by something. We always continue to relive this picture, event, or whatever cause, as I said, for alcoholism, whatever. It's like we are resistant, in a way, to psychotherapy, and we are resistant to handle the problem that caused us to be alcoholics in the first place, for example.
And because there's a dimension of mind changing with psychedelics, it takes off all the fences and we are more open to think differently, or to take another path. I will go back to the example of the elephants who travel another path. This is something that you can see in MRIs. There are new connections between neurons in the mind. We are, on one hand, more susceptible for either treatment or to digest the problem that made us whatever we suffer from.
In addition, unlike SSRIs, there are multiple layers that those psychedelics' effects. MDMA, for instance, is not just affecting serotonin secretion, it also affects dopamine, norepinephrine, and many neurotransmitters. And as I said, we're very complicated creatures. When we have a certain problem, it's more complicated. So, we need to address not only serotonin and secretion, but other neurotransmitters that are very, very important. I think all this together really shows the difference between MDMA SSRIs. But I can use a lot of psychedelics as an example, to show how it works differently from traditional pharmaceutical treatment that we have today for mental health problems.
Q: How might psychedelics impact the future of pharmaceutical research and development?
Zuloff-Shani, PhD: I think (I'm trying to be cautious when I speak, I don't want to use the word too early to predict) we still need additional clinical trials to better understand that. But I think that the opportunity to offer a more holistic treatment, rather than a very focused treatment, can really revolutionize mental health treatment. I think that approaching the root causes for any kind of mental health disorder that we suffered from differently, we really open the options for a better solution. Not only am I a true believer in the potential of psychedelics to treat mental health disorders, but I'm really, optimistic and encouraged by everything that we are seeing now. I can also say that we are a company who is on the verge of going into clinical trials. We're still in the preclinical stage, but what we see is so phenomenal that I must be very optimistic about how psychedelics can completely change the way we treat mental health disorders today.