Full Transcript Introduction: Trauma, Addiction, and Psychedelic Medicine 0:00 Trauma is so often part of the story in addiction. 0:04 Traum can fuel addiction, if you know me, you now I say that a lot. 0:08 Untreated or undertreated trauma is frequently a huge part in the addiction and relapse cycle. 0:15 Earlier this year, an executive order brought psychedelic medicine, specifically ibogaine, into the national conversation around addiction or trauma, 0:24 and also traumatic brain injury and treatment-resistant psychiatric illnesses. 0:28 Super exciting times for sure. 0:31 Aside from ibogaine though, there's been focus on three other compounds that are generating some of the most significant psychiatric research we've seen 0:39 in decades. 0:40 Psilocybin, LSD and MDMA. 0:44 These are not fringe compounds anymore. 0:46 They're now being evaluated in the same FDA framework used for traditional medicines like antidepressants, anti-psychotics, 0:54 medications for addiction and so much more. 0:56 Today, We're going to review, it's going be a little complicated, but we're gonna review exactly where the science stands now. 1:03 In 2026, what the clinical trial data actually shows, What phase two and phase three trials mean, and why these findings matter to anyone with or anyone 1:15 treating depression, trauma, PTSD, anxiety, substance use disorders. 1:21 I'm Dr. 1:21 Arwen Pedesta. 1:22 For those new to this channel, I am a functional and integrative psychiatrist, triple board certified in psychiatry, addiction medicine, 1:29 and forensic psychiaty. 1:31 My big focus is helping people understand and navigate the intersection of neuroscience, of addiction, trauma, mental health in general. 1:39 You know, one of the biggest misconceptions that I hear is that psychedelic medicine is either a miracle cure or just a dangerous fad. 1:49 And the reality is it's neither.
Psilocybin Phase 3 Results for Treatment-Resistant Depression 1:51 The question is not whether these compounds produce effects. 1:54 We know very well they do. 1:56 we've known that for decades. 1:58 the question, is whether they can repeatedly demonstrate safety and repeatable efficacy in rigorous randomized controlled trials. 2:09 That's the standard the FDA cares about, and that's what I care about as a prescriber. 2:14 And in 2026, we're actually starting to get those answers. 2:18 I keep saying it's a really exciting time to be in my field. 2:22 Exciting for me, exciting for patients in front of me. 2:26 So let's start with the compound that is closest to potentially entering mainstream psychiatry. 2:31 That is psilocybin. 2:33 It is the most advanced classic psychedelic and psychiatric development having completed two phase three clinical trials. 2:42 A company called Compass Pathways recently announced positive results from its second phase 3 trial evaluating its compound This doesn't matter, 2:51 but the compound is called COMP-360 for treatment-resistant depression. 2:56 Okay, treatment resistant depression, remember that and we're going to come back to that. 3:01 So this announcement about these two successful phase three trials is really important because The FDA generally expects at least two successful Phase 3 3:11 clinical trials before they consider approval. 3:14 Let's back up and start with Phase 1, the first step in pharmaceutical investigation showing whether a drug appears safe and identifying the side effects 3:22 it might have. 3:23 All right, in phase two is next. 3:25 In phase 2, we learn whether it works for a particular disease or condition and what dose might appear effective. 3:31 And then we get to phase 3. They're longer and that asks whether efficacy and safety can be replicated in very large patient populations. 3:41 Phase 3 is the final major hurdle before FDA review. 3:46 Well, psilocybin has now cleared that hurdle twice. 3:50 In two trials, patients receiving the synthetic psillocyban through this one company showed a statistically significant improvement in depressive symptoms 4:00 compared to placebo. 4:02 Now, the improvement in depression rating scores were three or four point differences. 4:06 Critics kind of think that might sound small. 4:09 But remember, these were real patients with real treatment resistant depression. 4:14 These are patients who have often failed multiple, multiple antidepressants, complicated medicine regimens, psychotherapeutic treatment failures, 4:23 and sometimes neuromodulation interventions as well. 4:26 So any reproducible improvement, in that population is meaningful. 4:32 And that's meaningful for data, sure, but really it's meaning for the individual. 4:37 But what I find most remarkable about this whole thing is not the magnitude of change. 4:41 It's actually the speed. 4:43 So check this out. 4:44 Improvement was measurable the day after treatment one day. 4:49 Think about that. 4:50 Most antidepressants require four to eight weeks before we even begin assessing meaningful response. 4:58 Almost two months, and here we're talking about changes observed within 24 hours. 5:04 And listen, by week six, a good number of patients achieved clinical meaningful improvement. 5:09 For those that did respond, benefits frequently persisted 26 weeks after only one or two doses. 5:16 The quickness, the durability, that's almost unheard of in psychopharmacology. 5:22 Let's reconnect this to addiction. 5:24 A common pattern clinically in addiction is a patient whose substance use is just intertwined with chronic depression, with hopelessness, 5:33 emotional pain, and trauma. 5:35 The substance becomes an attempt at self-regulation and self medication. 5:41 And if depression were to improve rapidly and meaningfully, then relapse risk would improve as well. 5:48 Also, there is research exploring psilocybin and alcohol use disorders and other addictions, not yet as far along as the treatment-resistant depression studies. 5:58 But even before we have addiction-specific indications available, reducing severe depression will indirectly reduce one of the major drivers of substance 6:09 use and substance relapse. 6:10 Well, effect is great, but at what cost? 6:13 Safety is also key, right? 6:15 That's part of that assessment. 6:17 Good news about this too, across more than 1,000 participants, the most common adverse effects resolved within 24 hours. 6:25 Safety, efficacy, onset, adherability, durability.
LSD Research for Anxiety and Neuroplasticity 6:31 This is why so many psychiatrists and people in the field are excited about psilocybin, likely to be the first classic psychedelic approved through modern 6:41 FDA pathways. 6:42 And if, well, when approved, it will represent one of the most significant paradigm shifts in psychiatric treatments in decades, 6:51 in my career for sure. 6:53 We're going to move over and talk about another exciting compound. 6:56 Actually, it's LSD. 6:59 MindMed, which is now under the name Definium, is a company studying a compound called MM120. 7:05 That name doesn't matter, but it is the pharmaceutical formulation of LST. 7:09 And they recently reported positive phase three results in generalized anxiety, Which obviously is frequent driver of substance relapse too. 7:19 This is a major milestone. 7:21 Phase 3 success means the FDA now has a large-scale efficacy and safety data to evaluate. 7:29 The most amazing finding in this one, guess what? 7:31 A single administration produced clinically meaningful reductions in anxiety symptoms. 7:37 Not daily treatment, not weekly treatment. 7:40 One. 7:41 Uno. 7:42 Administration. 7:43 And improvements remained measurable for approximately 12 weeks. 7:47 Blowing my mind, right? 7:49 Hopefully it's blowing your mind. 7:50 So let's think about how different that is from what we use with our conventional treatment. 7:55 I use SSRIs all the time. 7:57 They can be extraordinarily helpful, but they require daily taking, daily adherence, often taking weeks to even start working and frequently with side 8:07 effects or even losing effect over time, and here we have evidence suggesting a single administration of LSD can produce months of benefit for anxiety. 8:18 Wow, researchers find that least part of this effect involves modulation of what's called the default mode network. 8:27 This is a huge topic and another video will do for sure, but in broad strokes, the Default Mode Network is associated with kind of self-referential thinking. 8:38 with rumination, with repetitive negative thoughts and that rigid cognitive pattern we commonly see so frequently in depression, 8:46 in PTSD and in addiction. 8:49 And when patients describe feeling trapped in that same emotional loop, that's exactly the circuitry these researchers are targeting. 8:58 Not only that, but LSD also appears to promote neuroplasticity. 9:02 What's that? 9:03 Well, simply it may temporarily increase the brain's capacity to form new connections and new patterns. 9:12 I call brain stuff, all of the brain staff, the neuroplasticity, new connections, and new patterns. 9:18 It definitely matters for addiction because addiction is often the result of deeply ingrained neural pathways. 9:25 All right, think about it. 9:27 A treatment that increases psychological flexibility may help patients develop alternatives to those entrenched reward pathways and behaviors that they 9:37 know through their substance use disorder, through depression, et cetera. 9:42 So historically, LSD has shown intriguing findings in alcohol use disorder, actually. 9:48 Several studies dating back way long ago, decades and decades ago suggest reductions in problematic drinking following psychedelic assisted interventions. 9:57 Modern research is revisiting those observations with contemporary methodologies. 10:02 Although PTSD-specific data remain earlier in the development than the anxiety studies, researchers are increasingly interested in LSD's potential role 10:12 in trauma-related disorders because of its effects on emotional processing, on fear extinction, cognitive flexibility. 10:19 Doesn't that sound very hopeful? 10:22 Again, these hypotheses are still being tested, but the rationale is very compelling, because if trauma locks patients into survival mode, 10:32 treatments that help loosen those rigid patterns may have profound implications, which brings us to the psychedelic most directly linked to trauma itself, 10:43 and that's MDMA. 10:45 Right, current psilocybin studies are looking at depression, LSD studies looking anxiety.
MDMA Studies for PTSD and Social Anxiety 10:51 Well, MDMA studies that are in the works right now are look at PTSD. 10:56 That makes it so relevant to addiction medicine because trauma is often the hidden engine driving substance use. 11:05 For years, Mdma assisted therapy has demonstrated some of the largest effect sizes ever observed in psychiatric research for PTSD, 11:13 Many clinicians expected FDA approval after a certain number of studies done around 2024. Well, guess what? 11:22 That didn't happen. 11:23 Nope. 11:24 The FDA declined approval and requested additional evidence. 11:28 Some interpreted that as a failure. 11:30 Not me. 11:31 You know, science is almost never a straight line because what happened next is actually more important. 11:38 Researchers continued to study the molecule. 11:41 New formulations entered development. 11:43 new study styles were approached. 11:46 New indications were explored. 11:48 One recent phase two study evaluated a propriety formulation of MDMA for social anxiety disorder, and the results were so encouraging. 11:59 So patients receiving active treatment experienced a greater reduction on a particular social-anxiety scale versus the placebo arm. 12:08 Clinically, nearly 50% of the treatment arm responded, those taking the MDMA, versus 15% percent of those that got placebo. 12:16 And the number needed to treat was approximately three, which is quite impressive for clinicians and for patients. 12:24 Even more notable, these results occurred only after two administrations. 12:29 Two, not chronic daily medicines, no years of treatment, two sessions. 12:35 All right, so let's get back to talking about PTSD. 12:39 MDMA remains one of the most extensively studied trauma-focused interventions in psychiatric history. 12:46 The reason is understandable. 12:48 Unlike classic psychedelics like LSD and psilocybin, MDM appears to decrease fear response while preserving emotional engagement. 12:58 Patients often describe being able to revisit traumatic memories without becoming overwhelmed by them. 13:03 And that might help explain why MDMA has consistently demonstrated strong effects in trauma-focused psychotherapy settings. 13:11 For addiction specialists like myself, this matters enormously. 13:15 Many patients don't relapse because they forgot their recovery skills. 13:20 They relapsed because of unresolved trauma, which continues to generate distress. 13:26 I see it time and time again. 13:28 If trauma remains untreated, recovery often remains fragile at best. 13:33 While MDMA's future depends on additional confirmatory studies, of course, but the molecule is far from dead. 13:40 In many ways, we're watching the next chapter of its development rather than the end. 13:46 All right, let's go back to the big picture of psychedelics at the moment. 13:51 psilocybin. 13:52 It's shown to positive phase three trials for treatment resistant depression. 13:57 LSD has generated positive Phase three data and anxiety disorders and holds FDA breakthrough therapy designation. 14:05 That's cool. 14:07 MDMA continues advancing through new clinical studies focused on trauma and on anxiety-related conditions. 14:14 And what we're watching, what were witnessing is the transition from an anecdote to scientific evidence, randomized controlled trials, 14:23 from counterculture and fringe to clinical science. 14:26 I do want to emphasize something crucial. 14:29 These compounds are not replacements for current evidence-based care. 14:34 If someone has opioid use disorder today, medications like buprenorphine and methadone and naltrexone saves lives. 14:41 Naloxone, saves, lives if someone, has an alcohol use, disorder safe stopping and then medical stabilization.
Big Picture: Psychedelics in Modern Psychiatry 14:49 and then maintenance medications such as naltrexone and acamprosate and more remain essential tools. 14:56 If someone has PTSD, trauma-informed therapy and other types of therapy, medication management, communication remains foundational and it will continue 15:07 to be so. 15:08 Psychedelics really eventually become powerful additions to our current toolbox. 15:14 and soon it seems, but they're certainly not a replacement or a reason to delay treatment today. 15:20 And they are not reason stop using interventions that already work. 15:25 The most exciting part of the story isn't the compounds themselves, it's what they represent. 15:30 For decades, many patients with severe depression, with PTSD, anxiety, and substance use disorder, they just cycle through treatment after treatment without 15:40 meaningful relief. 15:41 And for the first time in a long time, we're seeing entirely new therapeutic mechanisms emerge, and some will succeed. 15:49 You know, some are bound to fail and that's how science works. 15:51 That's what we're doing here. 15:53 But the overall direction is very encouraging, very positive for me and for my patients. 16:00 We're entering the new era of psychiatry, one that focuses not only on symptom suppression, but on facilitating meaningful psychological and neurological change. 16:10 Neuroadaptation, neuroplasticity, wellness, that is what I want. 16:15 And for patients whose trauma, whose anxiety, who's depression continue to complicate addiction, that possibility is definitely worth paying attention to. 16:24 If you enjoyed this update, be sure to watch my previous video explaining why trauma feels addiction and why treating trauma is often the key to sustainable recovery. 16:33 Thank you for staying curious. 16:34 Let's keep building better outcomes together.
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