Psychedelics for Treating Anxiety, Depression and PTSD: Current Research and Guidelines

Hey there everybody, and welcome to today's presentation on psychedelics in the treatment of anxiety, depression and PTSD. I'm your host, Dr. Donnellice Snipes. In this presentation we're going to explore how researchers think psychedelics work in general. And then we'll explore the clinical applications for the use of psilocybin in behavioral health settings. This is the first of a three part series. The next two videos will explore the research on the use of mdma. And then the last one, we'll look at ketamine, selective serotonin reuptake inhibitors or SSRIs. And atypical antipsychotics are what we call antagonists of the postsynaptic 5H2A serotonin receptor. So SSRIs and atypical antipsychotics actually blunt the action of the 5H2A postsynaptic receptors. They work against them, so they antagonize them. 5H2A receptor antagonists interfere with dopamine activity and may provide the basis for new therapies for drug dependence. So that's good to know. Some people with depression have more 5H2A receptors than non depressed patients, which suggests that 5Ht2A over density has a potential to cause depression. Now we know there are a lot of things that can cause depression. So this isn't just the aha, this is what causes it. But we do know that in some people this is an issue. And for those people, SSRIs and atypical antipsychotics often work. However, for more than 50% of the clinical population, SSRIs and atypic antipsychotics do not work. Underscoring the multiplicity of causes of depression, severe psychological and existential suffering can rob people of feeling that their life is worth living. Suicide rates have risen 24% over the past two decades, particularly among men who who are often motivated to commit suicide by non physical suffering, including loss of autonomy, 91%, decreased ability to enjoy life 89% and loss of dignity 77%. So it's important that we recognize the need to address that 50% of the clinical population who is not responding to typical treatments. So they don't feel that their life is not worth living. We want to help them feel that they can remain autonomous and they can enjoy life and live with dignity. Psychedelics like LSD, mescaline and psilocybin are 5H2a and to a lesser extent 5H2C receptor agonists, which may result in antidepressant activity. So remember I said that SSRIs and atypical antipsychotics are antagonists. They work against 5ht2a. Well, your psychedelics work in the opposite direction. The 5ht2a receptor impacts depression. Both agonists and, and antagonists can help relieve symptoms of depression. So that's kind of interesting that depending on the person, some people respond better to agonists and some to antagonists. Agonists like psychedelics tend to reduce the norepinephrine release from the locus coriolis. Glutamate release in the prefrontal cortex is, is increased. Dopamine in the prefrontal cortex is increased. Unfortunately, anxiety can also be increased, as can positive and negative symptoms of schizophrenia. So it's not a panacea when we start monkeying with serotonin. It's not just about depression and it can actually Precipitate other problems. 5HT2C impacts dopamine release into the mesocorticolimbic pathway. So agonists actually decrease the amount of dopamine released into that pathway. Acetylcholine is increased in the prefrontal cortex. With psychedelics, dopaminergic and noradrenergic activity in the frontal cortex is suppressed. So it's important to recognize that dopamine is actually in certain parts of the brain is actually being suppressed and in other parts of the brain is being increased. Significant effectiveness and few adverse effects have been found when psilocybin, ketamine or MDMA are administered as adjuncts to psychotherapy to carefully screened patients under medical supervision. And we're going to talk about why that's so important as we go through this. But it's important to recognize that this is not a tool that should be in every treatment plan. You know, there are only certain people that are probably going to be a good fit for trying psychedelics. Psychedelics initiate a cascade of neurobiological changes that manifest in multiple ways and ultimately culminate in the relaxation of high level beliefs. So our long held core beliefs that we really have difficulty letting go of when people are under the influence of psychedelics. And it attenuates the oscillatory power of the default mode network. So what does that mean? Well, our default mode network is our autopilot, if you will, when we are triggered, when we are in fight or flight, we are operating from the default mode network. We are not thinking about, oh, what's the best course of action? We are thinking, save me. I am going to just, I'm not going to process. I'M going to do what's always worked in the past and I'm going to keep doing it. When we are relaxing too, we are engaging the default mode network. Have you ever driven to work and really not remembered every stop and turn and twist you took? Well, you are engaging that default mode network. When people are stressed and when, especially people with ptsd, for example, and the amygdala is really active, it integrates with that default mode parts of the brain that are involved with the default mode network. So when they are stressed, the default mode network is really, really strong and their executive control network can't get a word in edgewise. So under psychedelics, by calming down that default mode network not it doesn't become nearly as powerful, nearly as overbearing. So the executive control network can potentially be activated to address, even alter some of these long held beliefs. The purpose of psychedelic therapy is to harness the opportunity afforded by this belief relaxation to achieve a healthy revision of pathological beliefs. Psilocybin and LSD are classified as athenogens and associated with introspection and new insights, shifts of perspective and reframing of experience and relationship to others and the world. So it's a very cognitive, if you will, drug. Most studies of psilocybin assisted psychotherapy have been open label and and a very small sample size. Now when people take psychedelics, they know they've taken it. You're not going to give somebody a sugar pill and go, hey, I just gave you a psychedelic and have them believe that. So that's important to recognize. It's also important to recognize, and we're going to talk about it more in a minute, that the effect effects of psychedelics are greatly influenced by people's expectations, by their beliefs, by their feeling of safety in the environment in which they are located when they ingest the substance. And so giving somebody a psychedelic without preparing them ahead of time is strongly ill advised. So most of these studies are open label, which means people know that they are getting a psychedelic and a very small sample size. However, they have shown positive benefit in treating alcohol and nicotine addiction, anxiety and depression. Although limited conclusions can be drawn from open label trials. Tolerability is good, effect sizes large and symptom improvements appeared rapidly after just two treatment sessions and have often been retained for six months post treatment. And in this particular situation, it was in a cohort of people with treatment resistant depression. So how awesome would that be for somebody who has tried multiple antidepressants, gotten no relief, or very little relief to be able to engage in psilocybin assisted psychotherapy and two times and then have six months where they're retaining their their progress, their gains. Now, there have been some researchers that have attempted to do double blind placebo controlled stuff. In one study, psilocybin had a significant and moderate clinical effect size on the reduction of depression depressive symptoms in patients with a mood disorder, both acutely and in a 60 day follow up. Another study assessed the effects of acute administration of psilocybin versus placebo on amygdala reactivity to negative stimuli in volunteers using a blood ox level dependent functional magnetic resonance imaging. So in this case they weren't relying on the person to report how do you feel? Feel they were looking at the psilocybin versus the placebo on an mri. What's it doing in the brain on the amygdala. And since it was double blind, it means the researchers didn't know whether the person got the psychedelic or whether they got the sugar pill. Again, you could argue about the ethics with that since people who are not adequately prepared may experience more negative side effects, but theoretically they were preparing everyone as if they were going to get the psychedelic. A recent meta analysis of eight double blind placebo controlled experiments analyzing the acute and persisting effects of 227 psilocybin sessions across 110 healthy volunteers. This is still really small sample size, eight studies and there were only 110 healthy volunteers across all eight studies. However, 60% of the volunteers rated their psilocybin experience as very enriching and 90% rated it as moderately enriching between 8 and 16 months after administration. I think that's pretty phenomenal too. The United States Food and Drug Administration, the FDA are, you know, we've heard so much about that over the past few months. The FDA granted breakthrough therapy status to psilocybin in 2019. So this wasn't very long ago. Concluding that the initial data indicate that it may provide a substantial improvement over existing treatments for people with treatment resistant depression. So for that 50% that are not responding well to standard treatments, this might be helpful. So what is psilocybin assisted therapy anyway? It doesn't just mean, hey, take this pill. There's a lot more to it than that. Psilocybin assisted therapy involves administration of psilocybin when exploring a specific set of core or default beliefs with the goal of healing and transformation. There are three distinct therapy phases. The preparation phase is when the person meets generally with two clinicians and for multiple times before they even ingest the Psilocybin, they meet with two clinicians to create safety and create rapport, but also create a feeling of safety in that environment, to identify core beliefs that are going to be addressed and to prepare the person for what to expect. And in multiple articles that I read, the phrase set and setting kept coming up. And the experience somebody has when they're under the influence of psychedelics is greatly influenced by their mindset going in. If they are anxious about it, if they are worried about it, whatever they're feeling prior to going into it has the possibility of being magnified and enhanced under the influence. So encouraging them, helping them have an empowered mindset where they feel safe in their environment is really important. The setting is also important. If they don't feel relaxed in that environment, then as they undergo perceptual changes as a result of the psychedelic, they may get freaked out and it may precipitate high levels of anxiety and panic and those sorts of things. So it's going to be important for somebody to feel safe enough in that setting where when they're having those perceptual changes, they experience it and explore it with curiosity instead of terror. The second phase is the acute psychedelic experience, in which the psilocybin is administered in part to help the person slow the oscillation of that default mode network when processing their beliefs. So basically we're telling the amygdala to chill the heck out for a second. Now, the acute psychedelic experience only lasts a couple of hours, but psilocybin assisted therapy is typically one session, typically lasts six to eight hours. So there's the preparation, there's the experience, and then there's this the end where they call it integration. And it's during the experience as well as the person comes out of the psychedelic experience processing and integrating what happened with the therapist. The psychotherapeutic elements of this approach are essential for both effectiveness and safety. So the positive effects of psilocybin are many. But some people may not, and I have it in quotes, because some people may not perceive these as positive effects. Some people may see these things and go, oh, no. So positive effects is sort of in the eye of the beholder, as we will say. Visual distortions are very common under psychedelics, and some people find that curious and interesting. It's important, again that the person feels safe, safe. So these visual distortions do not feel terrifying. They have vivid imagery with their eyes open or closed. And this is something. It's not that something that they can like, close their eyes and make go away. So it's important that they not only feel safe in their environment, but the people, the therapists who are guiding this activity are able to help them feel calm and safe and at peace as they go through this experience. Auditory and visual hallucinations. Again, people need to know that the therapists that are facilitating the experience are there to protect them and that they're safe. Feelings of expansiveness, oneness, and connection with the universe. This underpins some of the therapeutic effects where people are able to kind of let go of themselves and feel more at one with everything that's going on. They are able to be a little bit more vulnerable, which can be liberating, but it can also be terrifying if it's not done right. Heightened emotions, As I said, if people are feeling anxious going into it, then these heightened emotions may become intensified under the effects. There's reduced amygdala reactivity during emotional processing. And that's what we've talked about multiple different ways. But this is really important because when we are in fight or flight, when that amygdala is firing on all cylinders, it is very hard to access our executive control network. It's very hard to access our wise mind, as Linehan would call it, order to process what's going on. So the reduced amygdala activity can be a gateway for people to actually access memories and thoughts and feelings about an event without feeling completely consumed by them. In some instances, it's been found that psilocybin reduces avoidance and increases access to traumatic memories. Some people experience heightened cognitive clarity. They have these aha moments where all of a sudden things start to make sense. And some people experience increased introspection and insightfulness. Previously unrecognized or unquestioned assumptions about situations may suddenly be available for reconsideration. Dr. Roland Griffiths is one of the preeminent researchers in the field of psychedelic medicine, and he works at the center for Psychedelic and Consciousness Research at Johns Hopkins University. So I encourage you to look at some of his work if you want to learn more about this other than what we're covering now. The negative effects of psilocybin can include panic attacks, anxiety, panic, paranoia, dysphoria, irrational or reckless behavior, disorientation, flashbacks, muscle weakness, and light sensitivity. Now, some of the dangers of psilocybin experiences occur when people start having perceptual distortions, because then it's harder to move through space and time and in. Or move through space in a safe fashion. You know, if it seems like everything is moving, it's hard to get through it and not trip or run into something or fall or whatever. So people can need to be in an environment in which they are physically safe. And if they get up and they start moving around, they are not going to injure themselves. Some people, you know, obviously walking around the house or around the office is dangerous enough. Some people try to drive under the influence of psilocybin and you can only imagine how extremely dangerous that can be. So it's important when somebody's under the influence that they do have safeguards in place to keep them physically safe as well as to help them feel emotionally and cognitively safe. Now, a lot of times when we start talking about psychedelics, people bring up hallucinogenic persistent perceptive disorder. HPPD is in the DSM. HPPD1 is a generally short term, non distressing, benign and reversible state accompanied by a pleasant affect. So some people call this a free trip, they have a flashback, but it's positive and enjoyable and enlightening. HPPD2 is a generally long term and it can last five or more years. Distressing, pervasive, sometimes irreversible, non benign state accompanied by unpleasant affect. So people are terrified, they have panic, they have anxiety, and they have these flashbacks and experiences that may be more or less persistent and are ongoing. Thankfully, a large variety of medications may be used to alleviate this condition, but with differential results suggesting that there may be several subtypes of hppd, we are really just now starting to look at psychedelics again. You know, this is something that was looked at many, many years ago and then we just started looking at it again. So there's a big old time gap in research, and in that time we've developed technology that helps us understand a little bit better exactly how the psychedelics are working within the brain. But we still don't understand everything about how they psychedelics have the exact effects that they have in terms of psilocybin and ptsd. Psilocybin has been shown to facilitate feedback extinction. So again, we're talking about that Amygdala and people who undergo psilocybin assisted psychotherapy are often more effectively able to extinguish the fear, decouple the fear response from the memory. It's also been shown to promote neuroplasticity, neurogenesis and synaptogenesis. So a lot of good things going on in the brain as that fear is extinguished. When your brain is not frequently or constantly bathed in a neurotoxic environment from ptsd, then it's able to start repairing itself. Which is a great thing. Before PTSD was added to the DSM in 1980, I. I had no idea that PTSD hadn't been in the DSM before 1980, but so before it was added in 1980, psilocybin was used in the Netherlands to treat what was then called concentration camp syndrome, which is basically what we call PTSD today. The core of the therapy consisted of enabling clients to re experience the traumatic event with the ability to purge their emotional distress under therapeutic guidance. So this back in 1980 in the Netherlands was sort of the beginning of the psilocybin assisted psychotherapy. Due to the relative ineffectiveness of standard treatments for up to 50% of the clinical population, there's been a renewed interest in psychedelics. Psilocybin assisted psychotherapy is highly dependent on set and setting and a single session lasts six to eight hours. Effects from a single session, however, may persist for six or more months. It's important to note that bad trips and hallucinogenic persistent perceptual disorder are possible, albeit rare, when used as a tool in a broader therapeutic protocol. The next two videos will focus on the use of ketamine and MDA in the treatment MDMA in in the treatment of behavioral health disorders.