Neha Pathak, MD, FACP, DipABLM: Welcome to the WebMD Health Discovered Podcast. I'm Dr Neha Pathak, WebMD's Chief Physician Editor for Health and Lifestyle Medicine. Today we're gonna explore the topic of psychedelic-assisted therapy as a treatment option for mood disorders. We will take a step back from the stigma and instead look deeper into the science to understand what researchers actually know about how to use these compounds as a therapeutic tool.

We'll discuss real-world data about how psychedelics like ketamine, psilocybin, and MDMA work on the brain to alleviate mental health symptoms. We're also gonna explore what patients are best suited for psychedelic-assisted therapy and where it might not be the best option.

But first, let me introduce my guest, Dr Jeanette Leal. Dr Leal is a board-certified psychiatrist with training in internal medicine and psychiatry from the University of Iowa Hospitals and Clinics. Today, Dr Leal provides telepsychiatry services to expand access to personalized, patient-centered care. Her clinical philosophy blends medical expertise with integrative strategies, aiming to meet every patient where they are and support whole-person healing.

Welcome to the WebMD Health Discovered Podcast, Dr Leal.

Jeanette Leal, MD: Thank you. Thank you for having me here. It's a pleasure.

Pathak: Well, we are very excited to dig into our conversation for today, but before we do, I'd love to ask about your own personal health discovery. Can you start by sharing what drew you to explore psychedelic-assisted therapy after training in traditional psychiatry?

Leal: So this was both based on personal experience as well as my experience with seeing patients that just weren't responding well to how we provide traditional psychiatric treatment. In traditional medicine, or what we call biological medicine, there's very little emphasis on basic lifestyle modifications. We make assumptions that people already know that, but it's part of the American lifestyle, so maybe some people don't know. Maybe for a lot of people it's just difficult.

So, a couple of examples: I remember having a patient who used to go through a drive-through and get fast food every morning for breakfast. And when I suggested to him trying something else, he was very puzzled, sort of like, "But what do you have for breakfast if not fast food? Like, what do we do?" And having people drink a two-liter bottle of soda and fried chicken for dinner, not being aware that that wasn't healthy.

I remember working in a hospital setting when people would go to what's called partial hospital programs or intensive outpatient programs, where they go to the clinic or hospital, and there's programming throughout the day, but they go home at the end of the day. I suggested that they include in that an hour of exercise or maybe a cooking class—and there was resistance to that.

So that was part of it. And then also my own experience with struggling with depression, being on traditional medicines—which luckily for me were quite helpful—but wanting to come off of them. When the medication wasn’t on board, I was struggling. So I thought, there’s gotta be something else out there.

How do we do this differently? Because I don’t wanna be dependent on a medication for the rest of my life to stay well. What else can we do? And so that kind of led me down the rabbit hole of, "What are the other options?"

Pathak: I'd love for you to help us take a step back and help us define—what are psychedelics? What are we talking about when we use that term?

Leal: Yes. So most people know psychedelics as street drugs, which is part of where the stigma comes from when we talk about psychedelic-assisted treatment. The most common ones studied nowadays for mood are MDMA (known as ecstasy on the streets), psilocybin (or magic mushrooms), and ketamine.

Pathak: So can you tell us a little bit then about the science? What do we actually know from clinical trials and real-world data about these different psychedelics and how they impact our brains, and then how they work to alleviate mood symptoms?

Leal: So I'll start with psilocybin, which is the active compound in magic mushrooms. Psilocybin primarily works by interacting with serotonin receptors in the brain—it acts as an agonist, meaning it activates the receptor. This interaction is thought to disrupt normal brain activity.

It leads to the psychedelic effects that we experience, and by psychedelic we mean the change in perceptions or change in reality. For some people, that can mean having visual hallucinations—even when you close your eyes, you can see things. Thoughts, the perception of floating, being outside of your body. Some people, especially with psilocybin, see patterns or colors—a distorted perception of reality.

Specifically, psilocybin is converted to a substance called psilocin, which binds to serotonin receptors and is involved in changing mood and cognition. It has been shown to affect a brain network called the Default Mode Network, or DMN.

The Default Mode Network is associated with introspection, self-referential thoughts, or the thoughts we have about ourselves, our lives, and the meanings we give to them. In depression and anxiety, that network is hyperactive, and we tend to be caught in a loop that's hard to break, which causes depression. Studies show psilocybin decreases connectivity in the Default Mode Network, allowing it to rewire—or allowing us to think differently about how we see ourselves and our lives, and hopefully change that.

The second one is MDMA, or ecstasy. There have been a lot of studies on MDMA for PTSD. The biggest study was done in the VA, treating PTSD. MDMA is more complex—it targets many different neurotransmitters: serotonin, dopamine, norepinephrine. It starts to facilitate new learning or extinguishing fear related to traumatic memories.

Numerous neurotransmitters released by MDMA can theoretically manipulate modulators of emotional learning and memory during psychotherapy in key brain regions such as the amygdala, hippocampus, and prefrontal cortex. MDMA recently went to the FDA for approval but did not get approved—though the results for PTSD in therapy were quite promising.

And then last but not least is ketamine. Ketamine has a rapid antidepressant effect believed to stem from its ability to quickly initiate a chain of events in the brain that enhance neuroplasticity. Neuroplasticity is the brain’s ability to change itself. We used to think the brain couldn’t do that—that once you were done developing around 25 or 26, that was it. But more recently, we’ve learned that’s not true.

Ketamine can promote the growth and strengthening of neuronal connections by modulating neurotransmitter activity. It allows the brain to be more adaptable, to create new pathways, and it gives people an opportunity to develop different thoughts and behaviors—which tends to be difficult, especially as we get older and become "hardwired."

Ketamine acts on NMDA receptors, blocking them, which causes the release of glutamate. Glutamate in the synapses can trigger a cascade of signaling pathways, increasing what’s called BDNF—brain-derived neurotrophic factor—which is like a brain fertilizer, crucial for neuronal growth and new connections. Ketamine is also thought to have an anti-inflammatory effect in the brain, which is linked to depression and other mental health disorders.

Pathak: That’s really helpful in breaking down the research. So, amongst all of these different psychedelics that you’ve introduced to us that are being studied or used, can you tell us from your own perspective—is there one that you think is showing the most promise right now, based on the evidence?

Leal: They’re all effective in different ways, but for practical reasons and accessibility, ketamine is legal and FDA-approved. There’s one version of ketamine, which is a nasal spray that’s FDA-approved. Your psychiatrist can give it to you in the office, and it’s covered by most insurances.

There are also affordable at-home treatments for the appropriate patient who is stable enough to do ketamine at home. MDMA is not approved, it’s not legal, and psilocybin is legal in just a couple of states. So, ketamine right now is the most available, and it’s incredibly effective for mood disorders.

Pathak: And a lot of us are hearing different media stories about these different drugs. So in your clinical experience, how do you identify the best patient for various treatments?

Leal: There are a lot of people who have been struggling for years with mood disorders and don’t respond well to traditional antidepressants—either because they don’t work for them, or the side effects are too much and they can’t tolerate them. These people can respond really well to ketamine.

The other good thing about psychedelics is that traditional medications are, in a way, a band-aid. You’re not feeling well, you take this pill, you feel better for as long as you’re on the medication. But unless you’re working on the underlying cause of your mood disorder, once you stop the medication, you’re back to feeling depressed or anxious.

I think psychedelics, in conjunction with good psychotherapy, can uncover everything that’s in the subconscious—or what I call “under the rug.” It puts you in a better state, less reactive, and able to pull out all the dirt from under the rug, look at it, reorganize it, clean it up—without getting triggered or retraumatized. Whether it’s PTSD, a traumatic memory, or depression symptoms, psychedelics allow for that reprocessing.

Pathak: I think a lot of people—back to our earlier point—hear about these things and start thinking about them, particularly as some psychedelics are portrayed in the media as miracle cures for depression, PTSD, or other mood symptoms that haven’t been processed—whether from adulthood or childhood. So, what’s your take on that? How should people be thinking about psychedelics as an option and part of their treatment?

Leal: Whenever I hear the words “miracle cure,” that’s a red flag for me. It is definitely a very good option, but the word “miracle” came up because it was such a breakthrough for mental health. For years, we had been stuck with medications that worked in very similar ways.

When we started discovering psychedelics for mental health—and they had such a different mechanism of action—everybody got really excited. They definitely opened the door for healing in a way that’s very different from traditional antidepressants, but it still takes doing the work.

You still have to take the medication, process it in therapy, and be willing to change your mind—which, believe it or not, we are resistant to. We want to stick to our old ways. The medication makes it easier, but you still have to do the work.

So it’s not a miracle in the sense of, “You sprinkle on psychedelics and suddenly you’re fixed.” But it’s definitely an excellent option.

Pathak: So tell us some other misconceptions. When we’re thinking about psychedelics and their use in medicine or treatment, what are some of these misconceptions you really want to address today?

Leal: The first one is: “It’s a drug, and people are just using it to get high.” Right away, a lot of people stop there—“It’s a drug, you get high, it’s not good.” Of course, if you’re feeling bad and then you’re high, that’s not medicine. But that’s not the case when you’re using it as a therapeutic tool.

Yes, all of the agents we listed—magic mushrooms, ecstasy, even ketamine—can be used as street drugs. But it’s a completely different experience than when they’re used as medicine in a therapeutic setting. Completely different experience.

If we can get past the fact that these substances are sometimes used as street drugs and instead consider the therapeutic benefits when used in the right setting with the right support, that changes the conversation.

Pathak: So then talk to us a little bit about that. What is that experience like? How do you help people understand—when you’re counseling a patient and suggesting this tool—what does that guided therapeutic experience look like?

Leal: Yes. So it's very different from using one of those substances as a street drug. So as a guided therapy, you come into your therapist's office, you are using a medicine that you know where it's coming from, and it's not made in a home lab with substances that you don't know, which is called the laced substance or what you can get out in the street. So you know that you're getting medicine that is safe, you're in a safe setting, you have a therapist with you, and you feel safe enough to allow for thoughts, feelings, and traumas to come up and process that in real time with your therapist in a way that's safe.
The medicine allows for those repressed memories to come up, but also, in the way that your body is relaxed — and it really is — you're less aroused. So you don't have the release of adrenaline, you don't have the panic that would come up otherwise if you get triggered by something out in your day-to-day life.
So you're able to bring it up, talk about what's coming up, what does that feel like? Is that even real and applicable to you today? And does it make sense to hold onto that fear and then use the medicine to allow you to reprogram those thoughts, those memories, and have them be just memories? But allow your system, your body, and your nervous system to see them as that.

Pathak: So talk a little bit about what kind of training somebody needs to be able to do this work, that you are at less risk for some of the more concerning parts of what might happen as you're on this treatment journey.

Leal: Yeah, fortunately, nowadays there's more and more both psychiatrists and therapists that are trained in psychedelic treatment and psychedelic integration. And just like you mentioned, ideally your psychiatrist and your therapist are working together. One person is prescribing the ketamine, the other one is doing the therapy.
They don't necessarily need to be done at the same time. So in the case of at-home ketamine treatment, for the patient that's appropriate for that, you can do your session at home and then the next day, or soon thereafter, discuss with your therapist what's coming up.
Psychedelics for a lot of people can bring up abstract images and thoughts that don't really make sense at the time, and then you bring it to a trained sort of outside eye the next day or whenever your therapy session is, and you'd be surprised how helpful they can be in guiding you into understanding: How does that apply to you? How does that apply to your life? And what is your subconscious showing you?
So definitely having people that are trained to work together. Most people with depression and anxiety and good health are safe to use a medication such as ketamine. They are appropriate for a home treatment. People with more complex mental health history — so in the case of bipolar disorder, for instance, and people with severe trauma, sometimes personality disorders — are better off doing the treatment in the office with more supervision.
So then in that case, you want to be aware ketamine is administered in the office and you have either the psychiatrist or the therapist there. One thing that is very common nowadays are the IV ketamine clinics, and I know patients who have benefited from the experience, but I also know several people who go get an IV infusion and the clinic doesn't offer any more services or follow-up.
So then they go home, things will come up. There are people who wake up the next day feeling suicidal, and the setting has nothing to offer. You'll just send them to the emergency room. So I would look into that and make sure that if you're looking into ketamine treatment, that you're in a system that can offer you a little more support in case difficult things come up, that you can call your provider, you can call your clinic, and they have support to offer you. That has come up quite a few times with people that went to a clinic, got an IV treatment, and then they're on their own, and that can be a little tricky.

Pathak: What else should people know before embarking on this kind of treatment in terms of physical risks, psychological risks — you've talked about that a little bit — anything else we need to know? And then ethical risks.

Leal: So you definitely want to be assessed by a clinician that is familiar with — and I'm gonna use ketamine as an example — that's familiar with ketamine, its risks, and side effects. So medications that you're currently on, health risks, is your blood pressure well controlled? Ketamine can raise your blood pressure during the sessions.
Do you have any history of stroke? Do you have a brain aneurysm? Those can all be issues. Other medications that you're on — there are medications that will prevent ketamine from working well, and an example would be benzodiazepines or anti-seizure medications. So you want to tell your clinician about that and they can make adjustments around that.
People who are prone to psychosis are not the ideal candidate for psychedelic treatment because basically that's what psychedelic induces. It will put you in a state of altered reality, and if that's already an issue for you at baseline, and you're trying to get that controlled, psychedelic is not the best choice.
So you definitely want to stick to other options. And then lastly, but not any less important, is the risk of addiction. So you may be using this in a controlled setting as a medicine, but if you're prone to addiction and you tend to look for substances to feel relaxed, to feel better, to escape intense emotions, that can definitely open a door. That might not be the best door for you to go down. So just things to be aware of. Yeah.

Pathak: So how do you think about psychedelics as treatment? Is this something that someone should consider as something that they might need lifelong? Is this something that is really considered a short-term treatment strategy? Can you help us understand timeline?

Leal: Yeah, somewhere in the middle. So it can be short-term for some people, and that's where that term "miracle treatment" — one of the places where it comes from — is that some people will do one or two sessions and have incredible insights and that changes their lives. And that's all they need. Some people need more sessions, and again, I'm gonna go back to ketamine, which is the one I'm most familiar with.
Some people need several sessions. They will feel better for a few days after one session and then go back to their sort of default way of doing things, do another session, until we are able to rewire the brain enough that our new default is the new thoughts and the new patterns, and you stop sort of going back to your old ways.
For some people that takes a little longer. I have a handful of patients that do ketamine as maintenance. So they started doing it twice a week, and then once a week, and then every other week, now once a month, and then eventually once every six months when they're going through something that's intense, that they're struggling with, and they feel that they need help processing. Ideally, you will not substitute one medication that you are dependent on for another. That would just be a swap. That wouldn't be a solution. You want to be able to work on changing a brain, rewiring a brain, thinking differently, feeling differently, and hopefully being able to feel better.

Pathak: What's one thing you wish more people understood about psychedelic-assisted therapy?

Leal: Give it a chance to be used as a medicine, and let the thought of "this is a drug that's making me high" — put that on the side. Because for most people, they heard of all those agents as drugs first and not as a medicine. If you feel like you could benefit from one of them, look for a provider that's well-versed in using those agents. Do your research. Ask people that have used them as medicine, and then see if having your own experience is the right thing for you and whether it works for you or not.

Pathak: That's great. So for someone who is listening or who has a loved one that they think might benefit, what's the next step? How do they identify someone who's trained? How do they identify a safe place to experience this type of treatment?

Leal: Yeah, so I would look for providers in your area that are using ketamine or psychedelics, depending on the state you're in. In some states, psilocybin is legal, so you can look for that as well. But there are databases. One good place to go is the IPI, Integrative Psychiatry Institute. They have a list of all the providers that are trained through them that will do psychedelic-assisted treatment, that are trained in integrative psychiatry, and I would look for that. If you know people that have had good results, then word of mouth is always the best. You can go to their providers. But otherwise, do some research. Find providers in your area. Find people that have had good experiences and go from there.

Pathak: That's really helpful advice, and I'd love to end our time together by opening it up to you. Is there anything else you wish I had asked you?

Leal: I think for people that struggle with mental health and haven't had a good experience with either psychiatrists or traditional medication, don't give up. Keep trying. Psychiatry is a branch of medicine like any other, and we are always learning. Medicine is always changing. We're always discovering new things, and I think psychedelics is the new thing in psychiatry that's quite promising and is helping a lot of people.
So keep trying, keep looking for the things that will work for you. Sometimes it's finding a different therapist, somebody that you connect well with. I think it comes down to being willing to change your mind about how you go about you and your life.

Pathak: That's really beautifully, beautifully said. And then I'd love to just close our episode and our time together by asking you to speak directly to our audience and give some examples of how someone can introduce this topic to a health professional that they're already working with, to ask for their advice and their help on taking this journey.

Leal: So most people go to their primary care providers first when they're struggling with mood, and I would let 'em know, like, “Hey Doc, I've been trying this medication for a while. It's helped some, but it hasn't helped all the way. I heard about psychedelics. Are you able to refer me to somebody who works with that?”
Sometimes your provider will be familiar with people. Some offices have different providers of different specialties inside the office. Sometimes they're not. Speaking for myself as a physician and the physicians I know, when we are not familiar with something, we tend to say, “Maybe it's a new thing, maybe stay away.”
So, you can start there, but if your provider is not familiar with this modality of therapy, keep looking around. If you're lucky and they are, they may be able to refer you to where to go, how to get it. Is it an IV ketamine clinic? Is it one of the home ketamine therapy places? If you are a good candidate for that, those are affordable and readily available. So keep asking.

Pathak: Really helpful. I wanna thank you so much, Dr Leal, for this conversation.

Leal: Of course. Thank you so much for having me.

Pathak: Thank you so much for being with us today. We've talked with Dr Jeanette Leal about psychedelics and health. My key takeaways from this discussion are that psychedelics like ketamine, psilocybin, and MDMA are showing promise in treatment-resistant mood disorders. There's an entire science behind how they work, from the science of neuroplasticity to network modulation, essentially allowing us to potentially rewire our thought patterns and potentially lead to lasting changes in mood and cognition.

Psychedelics are not a miracle cure-all and definitely require medical supervision. While psychedelic-assisted therapy may be life-changing for some, this treatment is not a quick fix. It requires patient participation, ongoing therapeutic work with a professional, and it may not be for everyone.

It's so important to work with an experienced clinician in a safe setting—a crucial part of the effectiveness of the treatment. Really critical, I think, is also that not all patients are ideal candidates, so it's really important to ensure that your healthcare professional is screening for important mood disorders and weighing additional health factors to clarify if this is the right treatment option for you.

Also critical was our discussion around stigma and misconceptions about psychedelic-assisted therapy. It's really important to reframe that medically guided psychedelic treatment is not the same as illicit drug use. These compounds can be used as therapeutic tools when administered in a safe and medically supervised context.

I really wanna thank Dr Leal for all of her insights. To find out more information about Dr Jeanette Leal, make sure to check out our show notes. Thank you so much for listening. Please take a moment to follow, rate, and review this podcast on your favorite listening platform. If you'd like to send me an email about topics you are interested in or questions for future guests, please send me a note at [email protected].
This is Dr Neha Pathak for the WebMD Health Discovered Podcast.