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Thug Drugs: Psychedelic Studies | Pain Pod · Pharmacy Podcast Network

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  Speaker 1: You are listening to the global network of podcasters dedicated
• 0:09
  Speaker 1: to the pharmacy profession. Welcome to the Pharmacy Podcast Network.
• 0:34
  Speaker 2: Welcome to The Pain Pod, the podcast for all things
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  Speaker 2: pain management, hosted by the pain guy, Dr.
• 0:43
  Speaker 1: Mark Groffoli.
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  Speaker 2: We'll be collaborating with numerous pain management experts, talking about
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  Speaker 2: substance usage disorders, the latest treatment modalities, and most important,
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  Speaker 2: focusing on the pain of our patients as leading providers
• 1:02
  Speaker 2: of pain care. And now here's our host, a man
• 1:08
  Speaker 2: wanted in all 50 states, a suburban city.
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  Speaker 1: Like mountain man. Without the beard.
• 1:16
  Speaker 2: From the hills of West Virginia and certified in weapons
• 1:21
  Speaker 2: of mass destruction response.
• 1:24
  Speaker 1: It's Dr. Mark Garofali. Welcome back, everyone, to The Pain Pod.
• 1:34
  Speaker 1: So yours truly, of course, Mark Pain Guy Garofoli here
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  Speaker 1: on the mic as usual. And, well, today we have
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  Speaker 1: a little situation of a follow-up episode here for The
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  Speaker 1: Pain Pod. Alas, if you did not tune in, listen in,
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  Speaker 1: or download the last episode of The Pain Pod that
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  Speaker 1: went over our mini-series of thug drugs, concentrating on psychedelics,
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  Speaker 1: If you haven't listened to it yet, no worries. Just
• 2:01
  Speaker 1: download it. It'll be your homework for next time, I guess.
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  Speaker 1: That's where we basically went into a review of the
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  Speaker 1: substances themselves, the classes, classifications, the groups, you name it,
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  Speaker 1: in the big picture there. I will say, although perhaps
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  Speaker 1: a little biased, maybe a little fun and learning. But
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  Speaker 1: what else would you expect from the PainPod, right? But
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  Speaker 1: here today, we're going to be going over, you know,
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  Speaker 1: continuing our Thug Drugs miniseries and reviewing psychedelic studies. It
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  Speaker 1: just kind of rolls off the tongue. But, you know,
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  Speaker 1: the big picture is there's been an uptick in the,
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  Speaker 1: you know, the bandwidth, the number of psychedelic substances being
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  Speaker 1: studied for FDA approval, actually. And, you know, it's one
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  Speaker 1: of those classic cases where, How many folks actually read
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  Speaker 1: the articles, right? You know, not to be the nerd
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  Speaker 1: in the room or anything, but it kind of helps out, right?
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  Speaker 1: And I know my student pharmacist self back in the
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  Speaker 1: days thinking, oh my goodness, what happened to him? But folks,
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  Speaker 1: you got to read the articles. There was a famous
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  Speaker 1: guy back in the 80s, 90s that said it too
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  Speaker 1: with a couple of picture books and all that, but
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  Speaker 1: it actually is important. So You know, here, though, I
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  Speaker 1: fully realize that everybody's time is valuable, and not everyone
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  Speaker 1: has the time to dedicate to reading every study on
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  Speaker 1: the planet, even though some we wonder, how'd that get published?
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  Speaker 1: And others are like, wow, it's about time that this
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  Speaker 1: gets published, right? But in the realm of psychedelic studies,
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  Speaker 1: there's a lot of hubbub, right? A lot of perceived
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  Speaker 1: to be debatable things. So let's, you know, clear the
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  Speaker 1: fog here. To do so, though, okay, first up, I'm
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  Speaker 1: just going to spend like maybe two minutes or so.
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  Speaker 1: Very brief, succinct review here of, you know, psychedelics, also
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  Speaker 1: known as hallucinogens, of course. So, you know, it turns out,
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  Speaker 1: you know, as a pharmacist, my usual equation that I
• 3:56
  Speaker 1: came up with of, you know, how we operate, how
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  Speaker 1: a pharmacist rolls, the things we consider, okay? How does
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  Speaker 1: it work, the mechanism, and how much? The dosage, right?
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  Speaker 1: Those things lead to safety and efficacy. That's my pharmacist equation, okay,
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  Speaker 1: or pharmacology for that matter. You name it, okay? So
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  Speaker 1: when we're talking about psychedelics or hallucinogens, you know, they
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  Speaker 1: got some aliases here and some street names. We went
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  Speaker 1: over last time, right? But, you know, when you think
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  Speaker 1: about how they work, you know, the bottom line nutshell
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  Speaker 1: to review is that, you know, being agonists, generally speaking,
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  Speaker 1: get dopamine and selective serotonin receptors. Get nitty-gritty granular, usually
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  Speaker 1: serotonin subtype 2. and other things. But that's like the core.
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  Speaker 1: And we got to remember that that's basically the exact opposite,
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  Speaker 1: but same ballpark as our second generation atypical antipsychotics. You know,
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  Speaker 1: that escalated quickly, right? So what we mean there is
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  Speaker 1: that the second generation atypical antipsychotics, just say that one.
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  Speaker 1: I'm just going to say it once, one and done, okay?
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  Speaker 1: Those gents are antagonists at dopamine and serotonin, usually subtype 2.
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  Speaker 1: And again, they have other attributes as far as mechanisms
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  Speaker 1: as well, but generally speaking. So when you're looking at those,
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  Speaker 1: I'm breaking my rule, I'm saying it again, second generation
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  Speaker 1: atypical antipsychotics, you know, they add on that serotonergic action
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  Speaker 1: compared to the first generation, which would be antagonists only
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  Speaker 1: at dopamine. But those are working as antagonists in the
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  Speaker 1: same ballpark where psychedelics come in as agonists, okay? So
• 5:30
  Speaker 1: it's the age-old, you know, Yankee fan at Fenway Park. Ooh,
• 5:34
  Speaker 1: that's going to be a rough weekend, right? Well, what
• 5:37
  Speaker 1: about when the, you know, the Sox fan goes to
• 5:41
  Speaker 1: the Bronx? That's a rough weekend too, right? And hopefully
• 5:44
  Speaker 1: some fun along the way. and whatever other rivalry you
• 5:47
  Speaker 1: want to do out there, right? I'll pull up my
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  Speaker 1: own where, you know, I went to Pitt, I work
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  Speaker 1: at WU, you're thinking, golly, is there psychedelic utilization around there? Nope, nope, nope.
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  Speaker 1: That's just a backyard brawl for your East Coast football,
• 5:58
  Speaker 1: basketball fans, and any other sport you can think of
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  Speaker 1: these days, because that has resurged, right? But anyways, the
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  Speaker 1: bottom line is psychedelics, hallucinogens, are, you know, in the
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  Speaker 1: same ballpark that dopamine and serotonergic receptors, but they're working
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  Speaker 1: as agonists, whereas the uh, atypical antipsychotics or the antagonist there. Okay.
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  Speaker 1: And very briefly, you know, we covered, uh, well, yours
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  Speaker 1: truly his own classification of psychedelics, uh, you know, but nothing,
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  Speaker 1: you know, like rocket science here, you know, just classifying as,
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  Speaker 1: you know, how they're working, where they come from, things
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  Speaker 1: like that. We had our, uh, belladonna alkaloids, things like nightshade, um,
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  Speaker 1: mandrake root, Jimson weed, got lots of stories with those like,
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  Speaker 1: you know, Harry Potter group, you name it, or a
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  Speaker 1: plant that was growing even in my backyard. at a
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  Speaker 1: contractor thinking that we were growing hallucinogens, when it turns
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  Speaker 1: out it was just something that grew with the rest
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  Speaker 1: of the weeds. Not weed, but weeds, okay? Then we have,
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  Speaker 1: of course, as far as psychedelics go, the dissociative anesthetics,
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  Speaker 1: things like Special K or ketamine, PCP, Mexi or methoxetamine.
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  Speaker 1: Then we have our tryptamines, they're serotonin-like. They were thinking
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  Speaker 1: like Thanksgiving turkey dinner. LSD, psilocybin, you're going to hear
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  Speaker 1: a bunch here today. In a succinct episode, but a
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  Speaker 1: bunch regarding psilocybin as far as studies go. Dimethyltryptamine or DMT,
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  Speaker 1: businessman special, ayahuasca. You can think of, well, a bunch
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  Speaker 1: of celebrities that have gone on a rant about that recently.
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  Speaker 1: The next classification we had was phenylethylamines. Those are dopamine-like,
• 7:34
  Speaker 1: so we had some, well, interesting things named bromo dragonfly, mescaline.
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  Speaker 1: What's another? 2-C-B, NBOM. That one rolls right off the tongue.
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  Speaker 1: Things like, you know, even our substituted amphetamines like methylene, dioxin,
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  Speaker 1: methamphetamine or ecstasy, cathinones, and even nutmeg because of the
• 7:55
  Speaker 1: myristicin within it. Certainly needing that. Remember, how does it
• 7:59
  Speaker 1: work and then how much? A little bit more of
• 8:02
  Speaker 1: a dose that's in an average pantry regardless of the
• 8:05
  Speaker 1: time of year. And finally, there was the piperazines, the
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  Speaker 1: benzyl and phenyl piperazines. So that's the five groups of
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  Speaker 1: psychedelics overall. It probably took me more than two minutes.
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  Speaker 1: My apologies. But that's the quick down and dirty when
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  Speaker 1: it goes to the most basic components of what we
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  Speaker 1: want to prime this conversation for psychedelics today. So let's
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  Speaker 1: jump into the studies. What we're going to do here
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  Speaker 1: is go over the past psychedelics. and then kind of
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  Speaker 1: some recommendations reflective from the FDA, and then the present
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  Speaker 1: slash future, okay? A little hot tub time machine as usual,
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  Speaker 1: but in this accord, it's psychedelic studies, okay? So one
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  Speaker 1: place to look, you know, when you're thinking about the
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  Speaker 1: previous studies that are out there, there was a review
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  Speaker 1: article back in 2022, it was from Curious, basically just,
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  Speaker 1: you know, taking a snapshot. Like, what's the landscape look like?
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  Speaker 1: In that particular review article of psychedelic clinical trials, they
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  Speaker 1: found that there was over 100 trials. It was actually
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  Speaker 1: just over 100. I believe 105, but just over 100.
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  Speaker 1: The tricky part was that like half of them were cannabis.
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  Speaker 1: And that brings up this little conundrum of like, do
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  Speaker 1: people classify cannabis as a psychedelic or hallucinogen? Or is
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  Speaker 1: it its own little group? Or is it, you know,
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  Speaker 1: sedative with properties, you know, like the psychoactive components of THC?
• 9:27
  Speaker 1: it's got a lot going on, right? In fact, we've
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  Speaker 1: got multiple episodes of the pain pot, even dedicated to
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  Speaker 1: thug drugs and cannabis and the whole gang overall. Okay. Uh,
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  Speaker 1: but you know, one thing when you say, Oh, there's
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  Speaker 1: over a hundred, there was over a hundred trials. Well,
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  Speaker 1: if half of them are cannabis and if folks are saying, well,
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  Speaker 1: that's kind of its own thing and not necessarily in
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  Speaker 1: the psychedelic grouping, well, that kind of downplays the number
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  Speaker 1: a little bit. Right. And, um, About 70% of those
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  Speaker 1: were actually in our country, United States of America, and
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  Speaker 1: involved things like substance use disorder, addiction, PTSD, depression, pain,
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  Speaker 1: you name it. So that was basically the landscape in
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  Speaker 1: the big picture. Now, if you go a little bit
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  Speaker 1: more granular, and what I'd like to do here is
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  Speaker 1: kind of go into, you know, pick a substance or two,
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  Speaker 1: a psychedelic or two to go a little bit more
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  Speaker 1: granular from some of those studies that were reviewed. Okay.
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  Speaker 1: So we're going to start with psilocybin. I gave it
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  Speaker 1: the little drum roll earlier, of course. But again, back
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  Speaker 1: in about 2022, there was a New England Journal of
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  Speaker 1: Medicine published study, you know, regarding psilocybin utilization for treatment
• 10:35
  Speaker 1: resistant major depression. Okay. What they were looking for would
• 10:40
  Speaker 1: be appreciable decreases in that said depression, and then they're
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  Speaker 1: going to assess adverse events as well, so safety and efficacy.
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  Speaker 1: Lo and behold, in that study, the higher the dose,
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  Speaker 1: the incremental increase in the percentage of participants with side effects.
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  Speaker 1: I'm sure most would have guessed that. And you guessed
• 11:02
  Speaker 1: it as well, headache, nausea, dizziness, fatigue, everything you hear
• 11:04
  Speaker 1: on a DTC, direct-to-consumer commercial these days, right? There was
• 11:09
  Speaker 1: also a little bit more granular information as far as
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  Speaker 1: suicidal ideation, but not huge takeaway pearls overall. There were
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  Speaker 1: other clinical trials as well for psilocybin. Even back in 2022,
• 11:24
  Speaker 1: same thing, there was a little bit over two dozen
• 11:27
  Speaker 1: patients that were in a trial that was in the
• 11:30
  Speaker 1: Journal of Psychopharmacology, in case you checked that one out recently,
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  Speaker 1: really looking at major depressive disorder. And then there was actually,
• 11:39
  Speaker 1: or I guess I should say is, all the way
• 11:42
  Speaker 1: back in 2014, so well over a decade ago now,
• 11:45
  Speaker 1: the ongoing trials at the University of Wisconsin-Madison. There was
• 11:50
  Speaker 1: actually four clinical trials. There's the Hootie One, the Primus,
• 11:54
  Speaker 1: the Poesis, And then Enhance, I guess we'll call it.
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  Speaker 1: So I just mentioned them in case you ever want
• 12:01
  Speaker 1: to look them up or whatnot. I could always provide
• 12:03
  Speaker 1: things in the show notes, of course. But the big
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  Speaker 1: picture there was really looking at the grander picture that, again,
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  Speaker 1: more studies on psilocybin, right? And that's an important thing
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  Speaker 1: to keep in mind. So much so that psilocybin actually
• 12:19
  Speaker 1: was granted breakthrough designation by the FDA, okay? And that
• 12:24
  Speaker 1: was to a specific formulation, of course. It was CYB003. Boy,
• 12:29
  Speaker 1: that rolled off the tongue more than I thought. It
• 12:30
  Speaker 1: was from Cybin. It was basically a deuterated psilocybin analog.
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  Speaker 1: So no one was eating mushrooms. Let's just start there, right?
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  Speaker 1: And it was being studied for major depressive disorder. So
• 12:42
  Speaker 1: what's this? It's a little reminder. Maybe original learning. But
• 12:46
  Speaker 1: that BTD, Breakthrough Therapy Designation, Basically, the FDA gets involved
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  Speaker 1: in the phase three studies followed by an expedited review process.
• 12:56
  Speaker 1: It's not necessarily that it speeds things up, although that
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  Speaker 1: is inherent. It gets involvement, so the reviews are a
• 13:03
  Speaker 1: little bit more granular and along the way. All right. Now,
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  Speaker 1: let's jump over. We touched on psilocybin in the past.
• 13:12
  Speaker 1: How about MDMA or ecstasy? That, of course, is being
• 13:15
  Speaker 1: studied for PTSD. This is going to get hot and
• 13:19
  Speaker 1: heavy pretty quick, folks. So there were two phase three
• 13:23
  Speaker 1: clinical trials that had about almost like 200 patients. They
• 13:26
  Speaker 1: were looking to treat moderate to severe PTSD. Okay. Both
• 13:31
  Speaker 1: trials involved MDMA, a form of ecstasy. It was methamphetamine
• 13:37
  Speaker 1: given in three eight-hour therapy sessions, and they were four
• 13:40
  Speaker 1: weeks apart. So, you know, not just your usual pill
• 13:44
  Speaker 1: a day, right? Participants also had shorter talk therapy sessions
• 13:49
  Speaker 1: before and after getting the medicine or even before or
• 13:52
  Speaker 1: after the placebo as well, too, of course. The authors
• 13:54
  Speaker 1: concluded that the MDMA product works better than a placebo
• 13:59
  Speaker 1: in reducing the severity of PTSD symptoms. Then what, though? Well,
• 14:03
  Speaker 1: then the FDA is going to review things, right? So
• 14:06
  Speaker 1: back in December of 2023, basically the new drug application
• 14:08
  Speaker 1: was submitted to the FDA. as MDMA-assisted therapy, because there
• 14:18
  Speaker 1: were those talk sessions as well, for the treatment of PTSD.
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  Speaker 1: The panel evaluated and voted on both safety and efficacy.
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  Speaker 1: They voted 9-2 against for safety and voted 10-1 against
• 14:31
  Speaker 1: for efficacy. Whoa, that doesn't gel with what the author said, right?
• 14:37
  Speaker 1: That being said, there was actually a quote. The panel
• 14:40
  Speaker 1: chair said, I'm not convinced at all that this drug,
• 14:43
  Speaker 1: I usually would say medication, is effective based on the
• 14:45
  Speaker 1: data I saw, okay? So the FDA advisory panel declined
• 14:50
  Speaker 1: to recommend MDMA for PTSD. Now, that's a panel, though.
• 14:56
  Speaker 1: So then, you know, it goes to the actual FDA
• 14:59
  Speaker 1: leadership to make those decisions. So a little bit extra
• 15:02
  Speaker 1: info came, and this is where, if you're not on
• 15:04
  Speaker 1: the edge of the seat, scoochie forward, folks, okay? And
• 15:08
  Speaker 1: this is public information, okay? I'm not just pulling this
• 15:12
  Speaker 1: from the internets and the whole misinformation thing. This is public,
• 15:16
  Speaker 1: substantiated information, okay? So that panel brought up that there
• 15:20
  Speaker 1: was blinding and sexual misconduct concerns within the trial. And
• 15:24
  Speaker 1: if I don't have your attention yet, well, pay attention now, okay?
• 15:29
  Speaker 1: So the FDA panel stated that Lycos Pharmaceuticals trial data
• 15:32
  Speaker 1: was marred by inconsistencies, poor study design, and allegations of misconduct. Interesting. Interesting.
• 15:38
  Speaker 1: All of a sudden, we're all on board for doing
• 15:40
  Speaker 1: a journal club, right? Due to the profound alterations in mood, sensation, suggestibility,
• 15:45
  Speaker 1: and cognition, most of the trial participants were able to
• 15:48
  Speaker 1: accurately guess which treatment they had received after the study ended,
• 15:51
  Speaker 1: which resulted in the study being nearly impossible to blind.
• 15:54
  Speaker 1: And if you think about it, that's not to one company.
• 15:56
  Speaker 1: That's just a concern in general, you know, the actual effects, right,
• 16:02
  Speaker 1: on the psychological side. So the FDA panelists raised concerns
• 16:07
  Speaker 1: about the case of a female trial patient who, in 2015,
• 16:12
  Speaker 1: said that she was sexually abused by a male therapist
• 16:14
  Speaker 1: during a trial treatment session. That patient actually testified via
• 16:18
  Speaker 1: a surrogate in June 2024, almost a decade later, pointing
• 16:22
  Speaker 1: to a publicly available video of her session, which showed
• 16:26
  Speaker 1: the therapist pinning her down and then cuddling and stroking her.
• 16:29
  Speaker 1: Sometimes I can't believe what I read, and this would
• 16:35
  Speaker 1: be one of those times, of course. Now, certainly feel
• 16:38
  Speaker 1: free to dive deeper in there, but boy, that's not
• 16:41
  Speaker 1: what we typically see when we're going over recommendations from
• 16:44
  Speaker 1: an FDA panel or doing a quote-unquote journal club for
• 16:48
  Speaker 1: an article. So what comes from that? In general, not
• 16:52
  Speaker 1: just that situation, but remember our overall timeline here today,
• 16:56
  Speaker 1: kind of going to go over the past ones, relatively recent,
• 16:58
  Speaker 1: then FDA recommendations, and going forward. So the FDA actually
• 17:02
  Speaker 1: published some clinical trial recommendations when it comes to psychedelic substances, okay?
• 17:11
  Speaker 1: There's a decent laundry list. I'll go through them here, but,
• 17:13
  Speaker 1: you know, basically they want the pharmacokinetics and pharmacodynamics. The
• 17:17
  Speaker 1: PK and PD should be adequately characterized in silico, meaning virtual,
• 17:22
  Speaker 1: you know, on the computer, in vitro, or in the glass,
• 17:26
  Speaker 1: and in vivo, in life. That's in us, you know, animals, humans, right?
• 17:31
  Speaker 1: They also said that there should be two monitors, okay?
• 17:35
  Speaker 1: That would be the people. So someone, you know, grad
• 17:38
  Speaker 1: level health care provider with experience and then someone else
• 17:41
  Speaker 1: along the way. The FDA also said there should be
• 17:43
  Speaker 1: inert placebo alternatives, including other psychedelics or low, mid or
• 17:48
  Speaker 1: even high dose and placebo controls put in place. Being
• 17:52
  Speaker 1: able to distinguish that, you know, some participant, a patient
• 17:56
  Speaker 1: not knowing inherently which treatment they got or which option.
• 18:02
  Speaker 1: Also must justify treatment psychotherapy inclusion because that can certainly
• 18:05
  Speaker 1: affect the efficacy results. Is it chicken or the egg?
• 18:09
  Speaker 1: The serotonin receptor subtypes binding evaluation is recommended. In fact,
• 18:13
  Speaker 1: they must include serotonin subtype 2B. And they should characterize
• 18:17
  Speaker 1: the durability of response. Is it more than three months? Doses, intervals,
• 18:21
  Speaker 1: and repeat dose safety and efficacy. Now, by now, you
• 18:25
  Speaker 1: might be thinking, well, you know, this list is growing,
• 18:27
  Speaker 1: but it is pretty basic things for getting, you know,
• 18:30
  Speaker 1: medication FDA approved, right? Should be able to determine dose-response
• 18:34
  Speaker 1: relationships for both safety and efficacy? Of course. They also
• 18:38
  Speaker 1: want folks to evaluate the effect of a high-fat meal
• 18:42
  Speaker 1: when you're talking about oral dosages. That gets pretty specific,
• 18:45
  Speaker 1: but it's, you know, to the tune of concerns that
• 18:47
  Speaker 1: have been observed. There's also the physical dependence abuse potential
• 18:52
  Speaker 1: assessment data, along with a proposed controlled substance classification scheduling.
• 18:59
  Speaker 1: And all in all, the FDA may consider the public
• 19:02
  Speaker 1: health effects of the drug as part of the overall
• 19:04
  Speaker 1: benefit risk assessment, basically saying, even if you do all
• 19:07
  Speaker 1: of this, we have to look at the big picture overall. Now,
• 19:10
  Speaker 1: there's one that's kind of the culminating recommendation or statement, really,
• 19:15
  Speaker 1: but One other thing was, you know, the evaluation of
• 19:18
  Speaker 1: drug-drug interactions, and obviously that's where, you know, us pharmacists
• 19:21
  Speaker 1: hear us roar, right? But the potential concerns that the
• 19:24
  Speaker 1: FDA said for any psychedelic trials and studies, you know,
• 19:28
  Speaker 1: to definitively evaluate would be your serotonergic subtype 2A antagonists,
• 19:35
  Speaker 1: things like trazodone, lopromazine, risperidone, you name it. Also dopamine antagonists.
• 19:41
  Speaker 1: We've got a bunch of those, of course. SSRIs, MAOIs, TCAs, lithium, reserpine,
• 19:47
  Speaker 1: pindolol specifically, and even niacin. Which vitamin B3 is that? Hmm.
• 19:54
  Speaker 1: Let's see. I think somebody came up with the remembering,
• 19:58
  Speaker 1: you know, 1, 2, 3, and 6, and so on.
• 20:02
  Speaker 1: The registered nurse is PC. So niacin being vitamin B3, right? TRN.
• 20:07
  Speaker 1: N is the third one, vitamin B3. Oh, P1s, you're welcome.
• 20:12
  Speaker 1: Or the rest of us, you're thinking, where did that
• 20:14
  Speaker 1: come from? Anyways, we're on a psychedelic trial journey here, okay?
• 20:19
  Speaker 1: What I wanted to highlight, though, is that the FDA
• 20:21
  Speaker 1: went very granular on assessing drug-drug interactions as a recommendation
• 20:25
  Speaker 1: for psychedelic clinical trials. Speaking of those trials, let's jump into, well,
• 20:30
  Speaker 1: things that are more recent and current along the way.
• 20:34
  Speaker 1: So we've got, of course, that synthetic psilocybin. So again,
• 20:37
  Speaker 1: not the mushroom. It's synthetic. There's a SIBIN Phase 3 trial,
• 20:43
  Speaker 1: in of which trial participants can continue their current antidepressant.
• 20:48
  Speaker 1: Previous studies didn't allow that. And there's a longer three-month
• 20:52
  Speaker 1: blinded period to really maximize the number of patients that
• 20:56
  Speaker 1: remain blinded along the way. In addition, there's another company
• 21:01
  Speaker 1: that has two phase three trials out there. It's COMP005
• 21:07
  Speaker 1: and COMP006, the COMP, as I'm saying. So COMP005 had
• 21:14
  Speaker 1: three main parts proposed anyway. Part A, I believe that's
• 21:17
  Speaker 1: already concluded easily, where Um, you know, it was blinding
• 21:20
  Speaker 1: through six weeks, uh, for looking at synthetic psilocybin. So again,
• 21:24
  Speaker 1: a synthetic product. Uh, then the second part, part B
• 21:28
  Speaker 1: per se, uh, continued that blinding through week 26. Um,
• 21:31
  Speaker 1: I believe that's actually already been done. And then part C,
• 21:35
  Speaker 1: the third part was proposed for, um, you know, open
• 21:38
  Speaker 1: label treatment going to the rest of an entire year,
• 21:41
  Speaker 1: 52 weeks. Okay. So that's a big time to know.
• 21:45
  Speaker 1: Then the counterpart there, comp 006, because the previous one
• 21:49
  Speaker 1: was ended with five, that had the three, you know,
• 21:53
  Speaker 1: proposed parts as well, blinding through nine weeks and then
• 21:56
  Speaker 1: blinding through 26 weeks, so half a year. And then
• 21:59
  Speaker 1: the final part being, you know, open label for the
• 22:02
  Speaker 1: final six months of the year overall. You know, hundreds
• 22:06
  Speaker 1: of patients involved and really distinguishing dosages along the way
• 22:10
  Speaker 1: as well, too. So TBD to be determined for published results,
• 22:16
  Speaker 1: you know, for all parts inherently coming through here. But again,
• 22:19
  Speaker 1: big picture, we're looking at like all of these scenarios,
• 22:22
  Speaker 1: it's synthetic along the way. Speaking of which, let's jump
• 22:26
  Speaker 1: to another synthetic, synthetic LSD. There's a D-tartrate that also
• 22:32
  Speaker 1: got the breakthrough BTD designation from the FDA. So in
• 22:37
  Speaker 1: this trial case, there's a single-dose synthetic LSD D-tartrate. It's
• 22:42
  Speaker 1: known as MM120 from MindMed. And that's being trialed and
• 22:46
  Speaker 1: studied for GAD, generalized anxiety disorder. It's actually the fifth
• 22:51
  Speaker 1: psychedelic to receive that breakthrough designation. It was just weeks, actually,
• 22:58
  Speaker 1: after psilocybin products. All right, so there's the phase 2B trial,
• 23:04
  Speaker 1: and that's MMED008, and that was really assessing the dose
• 23:09
  Speaker 1: response for generalized anxiety disorder, looking at basically four different doses,
• 23:14
  Speaker 1: all micrograms and placebo. And what was found there was
• 23:18
  Speaker 1: that the single 100-microgram dose showed significant durable anxiety reduction
• 23:22
  Speaker 1: for up to three months with high remission rates. There
• 23:25
  Speaker 1: were side effects, though, of course, visual effects and nausea
• 23:28
  Speaker 1: increasing with the dosage. Then we also have, well, a couple.
• 23:33
  Speaker 1: There's at least three other. There'll be more. Phase III
• 23:37
  Speaker 1: trials for synthetic LSD. There's the VOYAGE study. That's MM120-301.
• 23:45
  Speaker 1: That's actually the first phase three trial for generalized anxiety disorder.
• 23:48
  Speaker 1: It started at the end of 2024. And then there's
• 23:53
  Speaker 1: also the PANORAMA study labeled as MM120-302. So just one
• 23:59
  Speaker 1: in addition to the other one. Basically another phase three
• 24:01
  Speaker 1: generalized anxiety disorder trial started in the first half of 2025.
• 24:07
  Speaker 1: And then the EMERGE study is also a phase three
• 24:10
  Speaker 1: trial for major depressive disorders. So we see all these
• 24:13
  Speaker 1: clinical trials really honing in on the mental health aspects,
• 24:17
  Speaker 1: the psychological side, whether depression, anxiety, different designations and diagnoses
• 24:22
  Speaker 1: along the way. All right, one more, folks. How about
• 24:24
  Speaker 1: special K? Ketamine, right? There's the MORE CARE study. So
• 24:28
  Speaker 1: that's actually a phase three in the United Kingdom, currently
• 24:33
  Speaker 1: recruiting to test infusion ketamine for alcohol use disorder. So
• 24:37
  Speaker 1: I kind of lined that up where a lot of the,
• 24:38
  Speaker 1: you know, the previous studies were for different, you know,
• 24:41
  Speaker 1: collective genres of care. Uh, but this, uh, this more
• 24:45
  Speaker 1: care studies, basically a follow-up to a phase one study
• 24:47
  Speaker 1: that had a little bit over two dozen people in
• 24:49
  Speaker 1: it and a phase two study of a proprietary sublingual
• 24:53
  Speaker 1: S ketamine, one of the mirror images for alcohol use disorder.
• 24:57
  Speaker 1: So more to come on that bottom line, folks, that's
• 24:59
  Speaker 1: a lot of studies, right? Uh, and, uh, Some big points, though,
• 25:04
  Speaker 1: when you're thinking about it. At no point did I
• 25:06
  Speaker 1: say that folks were ingesting a mushroom or a cactus
• 25:10
  Speaker 1: or anything just directly out of the ground. These things
• 25:13
  Speaker 1: that are being studied are actually synthetic. And if you
• 25:17
  Speaker 1: think about that, we've been down this road before for
• 25:18
  Speaker 1: things like cannabis. We've talked about this in the paint
• 25:20
  Speaker 1: pot before where, you know, we've had for decades, we've
• 25:24
  Speaker 1: had FDA approved cannabinoids. Things like dronabinol, you name it
• 25:29
  Speaker 1: along the way, right? And then more recently, even natural CBD, Epidiolex.
• 25:33
  Speaker 1: It's extracted naturally, right? So, you know, we see that
• 25:38
  Speaker 1: as a potential here for psychedelic studies, future medications potentially
• 25:43
  Speaker 1: as well. But so far, we're really looking at a
• 25:45
  Speaker 1: lot of synthetics along the way. And that's an important
• 25:48
  Speaker 1: thing to bring up, of course, because, you know, if
• 25:50
  Speaker 1: you want the conversation to continue, you got to go
• 25:53
  Speaker 1: over the basic facts along the way. And I hope
• 25:55
  Speaker 1: that this, you know, relatively rapid review here of psychedelic
• 25:59
  Speaker 1: studies helps along the way with that for you. So,
• 26:04
  Speaker 1: you know, I'd be remiss to say, well, like, where
• 26:05
  Speaker 1: do we fit in as pharmacists, of course, right? So
• 26:08
  Speaker 1: you got to keep in mind, we touched on the
• 26:10
  Speaker 1: last episode, there are FDA approved medications that are a
• 26:13
  Speaker 1: form of psychedelics, like ketamine, of course, you know, on
• 26:17
  Speaker 1: the who list of should be in every hospital, you know,
• 26:20
  Speaker 1: whether anesthesiology or pain management, you name it. But also
• 26:25
  Speaker 1: the S-ketamine is an FDA-approved product along the way of
• 26:29
  Speaker 1: the nasal spray. Also, as pharmacists, we want to appreciate
• 26:33
  Speaker 1: the difference between clinical trial synthetics and natural products. It's
• 26:37
  Speaker 1: not saying thumbs up, thumbs down to either of those.
• 26:40
  Speaker 1: It's just a reality that's out there, right? And always,
• 26:43
  Speaker 1: just as the FDA recommended, but it's one of our specialties,
• 26:47
  Speaker 1: review for drug-drug interactions when a patient shares current utilization
• 26:50
  Speaker 1: of psychedelics. Not even in the trials, but if somebody's
• 26:53
  Speaker 1: sharing that information for you, Now we have some pretty
• 26:55
  Speaker 1: granular recommendations for what to look for for drug interactions, right?
• 27:01
  Speaker 1: And also being a trusted source of ongoing psychedelic clinical
• 27:04
  Speaker 1: trial data, keeping up with these things along the way.
• 27:07
  Speaker 1: Perhaps even future episodes of The Pain Pod, right? It's
• 27:11
  Speaker 1: a lot of information that's out there, a lot to digest,
• 27:14
  Speaker 1: but we're all in it together, folks. And as always,
• 27:17
  Speaker 1: I really want to thank you for your time here today.
• 27:19
  Speaker 1: I hope it was worth your time for a rather
• 27:22
  Speaker 1: rapid rundown of multiple, if not many, psychedelic clinical trials
• 27:26
  Speaker 1: and studies that are out there. So I hope you
• 27:28
  Speaker 1: enjoyed our Thug Drugs mini-series continuation here with psychedelic studies.
• 27:33
  Speaker 1: And I certainly look forward to, well, doing the next
• 27:37
  Speaker 1: episode of The Pain Pot, of course. But as always,
• 27:39
  Speaker 1: I want to thank you for your time. As far
• 27:40
  Speaker 1: as I'm concerned, it's our most valuable resource. And of course,
• 27:44
  Speaker 1: I want to wish you a great day. Every day.
• 27:47
  Speaker 2: If you'd like to join Mark on the Pain Pod,
• 27:50
  Speaker 2: send us an email to publisher at pharmacypodcast.com. And make
• 27:56
  Speaker 2: sure to share the show and subscribe on your favorite
• 27:58
  Speaker 2: podcast directory.
• 28:00
  Speaker 1: Thanks for listening.