Investigators continue to conduct regulated and controlled clinical trials to build compelling, high-quality evidence on their therapeutic potential.
Pharmacy Times is delighted to be joined by Mark Bleackley, PhD, the chief scientific officer at Incannex Healthcare Limited in Melbourne, Australia. Bleackley dives into the scheduling of psychedelics (i.e., psilocybin and MDMA), and how this impacts research efforts. He also discusses our evolving understanding of psychedelic’s pharmacology, efforts of current trials in address dose, safety, and impact, and the potential of these drugs to improve psychotherapy.
PT Staff: How are psychedelics currently scheduled and regulated and does this affect provider, pharmacist, or patient perception of psychedelics?
Mark Bleackley, PhD: Currently psychedelics are schedule 1. So [when] we're talking about psychedelics— most of our focus is on psilocybin and 3,4-methylenedioxymethamphetamine (MDMA)—the scheduling of these 2 molecules [is] currently Scheduled 1 in the United States, which means that they are the most controlled [and] there's no currently accepted medical application.
This is something that the research community is working on, but it means there's a lot of restrictions, a lot of permits that are required to be able to do this research. And I think when you look, maybe not so much at the scheduling but at the public perception of these molecules from the 1960s through to today, there is definitely a cultural bias that they are drugs of abuse, is this is a potential in the eyes of the DEA that that's why their schedule one.
I definitely think it means there's a bit of work to do in convincing the medical community, the pharmaceutical community, and the patient community that these have pharmaceutical value. And I also think, as the medical use becomes better understood and these products start getting approved, the scheduling will change accordingly.
PT Staff: How does that affect your research?
Mark Bleackley, PhD: It can be administratively quite a burden if we want to partner with preclinical groups, particularly at universities. Trying to get the licenses and the permits to be able to store these molecules and work with them, shipping them [and] importing them even within the US [and] shipping them across state lines… there's a whole series of permits that need to be obtained.
And when we look at manufacturing, formulation, development, and packaging… again, all those vendors/partners that we work with, they need to have the licenses the permits in place to be able to handle these molecules. There is special containment that must be done, [and so] compared to a new molecule or molecule that wasn't Schedule 1, it means that there's an extra set of questions we have to ask and an extra set of boxes that we have to tick before we start working with partners and doing the research ourselves.
PT Staff: What is the pharmacology of some of these more common [psychedelic] drugs that you are studying?
Mark Bleackley, PhD: I think part of the excitement is we don't really understand how these drugs work yet. We know that the psilocybin binds to 5-HT2A receptors, and that's how it induces its sort of classical psychedelic effects— those effects that have been the traditional use for these molecules (and more or less in the recreational and the wellness space) [and] are thought to relate to how these drugs can improve the potential for psychotherapy.
But there's also been some more recent studies that have looked at other interactions that psilocybin has that can relate to the antidepressant/anti-anxiety effects, which is about the tropomyosin receptor kinase B (TrkB) receptors. This is a pathway that classical antidepressants are known to interact with.
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I think when you look at how these molecules are being studied, you've got the psychedelic in combination with psychotherapy (which is being done in in humans and clinical trials) whereas you also have a lot of animal studies that are being done, where you can't really provide psychotherapy to an animal, but there's still an effect.
So it seems like there's a pleiotropic effect of these molecules. They're targeting different pathways [and] providing different potential mechanisms by which they're the therapeutic effect.
PT Staff: You mentioned that they target multiple pathways. How does this promote healing and how does it differ from your traditional antidepressant that does also target that pathway?
Mark Bleackley. PhD: I think you have the effects that are directly working on those pathways (that have the antidepressant effect) but I think the real potential with psychedelics is the neuroplasticity that psilocybin produces in particular.
What that means is it makes the brain more receptive, makes the patient more receptive, to psychotherapy, and that can lead to actual lasting treatment effects. So when you look like an SSRI, or a traditional antidepressant and anxiolytic, your have patients taking it every day and it's sort of a chemical pharmacology; whereas, with psychedelics (maybe you have an aspect of that playing into it) but the real potential is in that that synergistic effect of the psychedelic and the psychotherapy— being able to provide a lasting treatment effects. So, you don't need to take these drugs every day. It's about facilitating that psychotherapy provide providing a lasting treatment effect that is quite robust.
PT Staff: It's like the saying “It's here for a good time, not a long time,” in the sense that (not good time like whoa, party!) but it packs a punch, quickly. And because of that, you actually don't need to come back to it?
Mark Bleackley, PhD: What's likely going to happen is, as with most diseases, different patients respond differently. So understanding how how to best structure the combination of the psychedelic and a psychotherapy, how frequently it has to be done, what the sort of triggers or the signals are that say, “Okay, maybe it's time for another treatment session.”
It’s definitely there, [although] there's a lot of intricacies that we're still working out. I don't think it's going to be a magic one and done cure-all, but I think that, what we've seen so far, is the treatment effects are quite robust and they're lasting a long time.
PT Staff: Howcan psychedelic therapy act as an extension or expansion of a person's current therapeutic regime?
Mark Bleackley, PhD: This is another part of the psychedelic-assisted/psychotherapy field that’s really exciting. There's a lot of different methods of psychotherapy that are currently used in different treatment settings, and part of what the trials that are happening right now are trying to address is, “What's the best-” (maybe not the best but) “What forms of psychotherapy work well with psychedelics, the amount of psychotherapy, the frequency of the psychedelic sessions, the structure of the psychotherapy sessions?”
There’s a lot of a lot of variables still to figure out. And I think that it's going to be integrated into the current modalities that are used to treat these diseases. I imagine there will be particular therapies that maybe work better, but again, we're still figuring out exactly how this works. And I imagine that over the coming years, and then as these molecules get better accepted, I think that'll be something that as a research community we really start figuring out.
PT Staff: I heard you mentioned this point a lot, where you're still trying to figure out the right psychedelic to use. The right combination. When, and if, this does potentially become more ubiquitous as a treatment option, how can pharmacists and other providers help assist figuring out dosing? I still think that's going to be something that's a bit of a gray area for a while.
Mark Bleackley, PhD: This is a part of clinical trials and clinical research as a whole, working through the comparison of those doses in controlled settings. It's something that's a part of the discussions we've had with the FDA, they really strongly encourage us to look at different dose strengths, to understand how much molecule you need, where that risk/benefit (the balance) lies between safety and efficacy.
As with any drug, as we continue to build the high-quality evidence from well-regulated, well controlled clinical trials, that's what helps inform that the pharmacists and the physicians on how those things should be done. How patients should be selected to be identified should be monitored. And I think the best way to guide those decisions is with high quality evidence, and that's what we're in the business of generating.
