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Mike MacKinnon (MM): Welcome to We Can Answer That. I'm your host, Mike MacKinnon. Each week I sit down with an expert from the UCalgary community to ask five questions related to the topics that matter most in the world. Countries and states around the world are legalizing or decriminalizing various recreational drugs ranging from cannabis to heroin. A recent high-profile example is in the state of Oregon, where people voted to decriminalize personal possession of any drugs. But here's the really interesting part — the ballot measure also made psilocybin, or magic mushrooms, legal for medicinal use. In Canada, the federal government has also recently allowed exemptions for medicinal use. Interest in the therapeutic value of psilocybin mushrooms has been growing recently, with some evidence that they may help treat mental illnesses like anxiety and depression. Today we're joined by Dr. Peter Facchini, a professor of biochemistry in our Faculty of Science and chief scientific officer of MagicMed. We'll be talking about studying the medicinal properties of psilocybin and other drugs, and how synthesizing and improving them could lead to better mental health treatments. Peter, thanks for being here.

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Dr. Peter Facchini (PF): Thanks for having me.

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MM: Is legalization and decriminalization of controlled drugs making it easier to do research on them?

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PF: Certainly. This is one of the things that has limited research for many decades on compounds of, especially of natural origin, that have been used by people for many thousands of years. These include things like opiates, and cannabinoids, and psilocybin, and other hallucinogenic compounds. I think there's two reasons that legalization or decriminalization is improving the prospects to do research. One of them is that it's possible to get the necessary licensing in order to conduct the research, but it's also that, with growing social acceptance because of that move towards legalization, it's easier to get funding, and there's also less stigma, which is going to encourage more researchers to get involved in this type of work.

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MM: What's the benefit of studying controlled drugs?

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ÌýPF: Controlled substances, in general, include some of the most important medicines that are available to us, and some of those are already used clinically. As I mentioned, opiates have been for around many thousands of years and they're part of our pharmacopia, they're prescription medicines. They come, directly or indirectly, still entirely from plants. There's still an awful lot to be learned about not only how to make these compounds and to ensure that we have a stable supply, but also to create new derivatives of the natural substances that could potentially be better than what already is out there. The same would be true for hallucinogenic compounds like psilocybin. It's well known that psilocybin has hallucinogenic properties, but there hasn't been an awful lot of clinical work on derivatives of psilocybin that could potentially be used more precisely for the treatment of various mental illnesses.

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MM: Why is the interest so high right now in using psilocybin mushrooms as a treatment? Even in pop culture, micro dosing is a thing, and also the academic side of things, there seems to be a lot more interest. Why is that?

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PF: I think it's a lot of different factors that sort of all come together at the same time. You mentioned the fact that this whole legalization or growing social acceptance was led by cannabis. That's had sort of secondary effects of making people think a little bit more about things that have been out there on the fringes of society and have always been used as recreational drugs, but to reconsider what was being considered, often many decades ago. This was true for hallucinogens like LSD, and mescaline, and psilocybin, back in the 1950s. They were being investigated for various purposes, some not necessarily always for positive reasons. They kind of fell into the counter-culture of society in the 1960s and then became associated with illicit activities rather than something that could potentially be beneficial to people. I think factors just kind of all come together at the same time. Society starts to see that these compounds, anything, when used in moderation or appropriately, can potentially have value to people. I think also, the fact that there is such a growing increase in mental health issues, we've seen that happen extensively in the last year with the pandemic and all kinds of other factors that cause stress in people. So I think there's a need, there's a growing, sort of easing of negative stigma associated with these compounds. The momentum just shifts things into the right direction, and where we're at now, where you have an awful lot of people that are, as you say, micro dosing, and doing things that are becoming more acceptable in society.

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MM: What makes psilocybin effective in treating those mental health conditions that we're talking about?

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PF: There's a lot of clinical studies that are underway right now that are, some better designed than others, but I would say that most of them are pointing in the right direction, that there is a clinical value to hallucinogens in the treatment of variety of mental health conditions. PTSD and depression are a couple of them that widely seem to improve when you combine the hallucinogen with a sort of a psychiatric treatment as well. There's often a block. I'm not, obviously, a psychologist, but my understanding of it is that there's often a block in terms of the practitioner being able to get through to the patient, and begin treatment by somehow reaching the part of their psyche that needs to be addressed. These compounds, by simply altering the state of the psyche of the patient, opens them up to that sort of treatment. It's not the hallucinations per se, but it's other sort of consequences of the drugs that make them beneficial in treating these various mental health conditions.

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MM: So your lab looks at taking these compounds like psilocybin and synthesizing them or improving them. What are some of the ways that these compounds can be improved?

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PF: Nature provides us with an amazing pharmacopia, it's always been the first place that people historically have gone to look for medicines. But, nature provides kind of the foundation, and you see that with any class of compounds. There's morphine, but then there's derivatives that have been prepared that have been intended, or at least purported to be, better. Some of them are better in certain ways, like oxycodone is able to be formulated in a sustained release type of delivery as opposed to morphine, which is just an intravenous injection. The value of creating derivatives of natural products is effectively to create better versions of those drugs. I think this is especially important when you're talking about compounds that are being used to treat mental health conditions, just because there's such a broad range of underlying causes for these conditions, and a need for more precise medications to be tailored to individual patients. Effectively, the bottom line is you can have psilocybin, but then you can create many, many thousands, tens of thousands, even hundreds of thousands of derivatives of this molecule. And by systematically screening all those molecules and finding a collection of options for the practitioner to select from that could be more effective on individual patients, or could be used to treat subtly different, or even substantially different, conditions. It's basically just taking what nature gives you, and finding ways to make it better.

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MM: So I'm only supposed to ask you five questions, but I'm going to go off on a tangent here, because I can't resist. In particular with psilocybin or mushrooms, the effect is quite intense, so how would you limit that? Or control that? Or steer it to your advantage? How do you engineer that in the compound?

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PF: That's a great question. I'll start from the Brave New World end of this. In this space, you hear a lot about artificial intelligence. I think in general, there's the expectation or the hope that computers are going to be programmable to predict these things for us, so you don't have to do all this empirical work of making the compounds, and then testing them and seeing what they do. We might get there one day, but right now, we're not there. It's simply because there are simply too many variables that are going to affect how, especially these compounds work with respect to our physiology, and in particular, the receptors in our bodies that these compounds bind to. There are many different receptors, the compounds will bind with different strengths, different affinities. They'll get to the receptors in different ways, of course you take them orally, if it's a prescription medicine. If it's psychedelic mushrooms, you can smoke them, but one way or the other, there has to be a delivery mechanism. You can go on from there in terms of all the variables that can affect, not just the efficacy, but the specific pharmacological effects of these compounds. The bottom line is that any modification you make has the potential to change, for example, how tightly the compound will bind to a receptor, or how easy it'll cross the barrier between the blood and the brain, and so on. The only real way of addressing that and getting the golden nugget at the end of the day, of the best suite of drugs, is to make them, prepare the library, or the psybrary, as we call it at MagicMed, as an actual physical collection of compounds, and then start testing them. When we have enough information on the relationship between different structural modifications and consequences in terms of physiological effects, then maybe we'll be able to predict the weather better. I think that's a pretty good analogy, I mean, our weather prediction now is much better than it was 20 years ago because we have better computational models and we can inform those models with more data input. I think we can get there, as well, with this, but right now it's kind of a brute force process.

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MM: What have some of the barriers been to investigating these compounds? Why would big pharma, for example, not investigate these or take them up? Why is this only coming up now?

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PF: I think part of that is what we spoke of earlier, and that's the fact that many of these compounds were not considered to be of real medicinal value. They thought to be recreational drugs. And when something is categorized that way, as opposed to a potential real medicine, then I think it's harder for the corporate world maybe to get their heads around pursuing research in this area. I don't think that there are specific scientific reasons that it hasn't advanced for so many decades up until recently, but certainly there are business reasons. For example, for why psilocybin... Psilocybin certainly is, in itself, the drug of choice for the first generation to actually start bringing this technology to bear on treating people that that can benefit from these drugs. But going forward, you need to be able to create these new derivatives and there's going to be a lot of money required to take the derivatives and the sort of laboratory scale assessment of whether they're effective or valuable as new drugs, and bring them all the way through animal testing, clinical testing in people, and actually turning them into approved drugs. It takes a lot of time, it takes a lot of money. That money and the mandate to do it is going to come because, whether we like it or not, big pharma is not going to develop a generic. They're going to develop something that they can invest in and expect to have a return on their investment, and that's going to be associated with intellectual property and patents, and so on. You play by the rules of the corporate world, and that's one of the reasons that MagicMed's pursuit of this, in addition to the state-of-the-art science, is to make sure that we have a really extensive portfolio of patents that covers all of these compounds that we're making.

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MM: I know this isn't your area of expertise, but what kind of uptake are you seeing in the medical practitioner community?

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PF: Uptake in what way?

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MM: Adopting psilocybin as a therapeutic treatment.

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PF: I can only sort of speak anecdotally to this, but my sense is that it is seen as something that is effective and has great potential. It's not only the clinical that are kind of lending to those sort of positive conclusions from the medical community, but even people that I've spoken to that are psychiatrists and so on are certainly very much in favor of developing these technologies. I think there are other initiatives here at the Áù¾ÅÉ«Ìà that I'm aware of that are intending to pursue exactly that. That's to bring the development of the use of psilocybin and related hallucinogenic or psychedelic compounds further into the clinic. There's every indication, as far as I can tell, that this isn't a wishful thinking on the part of scientists or people in the corporate world that are hoping to make a buck on this, but it's actually, a pull from the medical community that this is seen as having immense potential to treat this serious issue that's clearly only getting worse in our society as we're subjected to more difficult times.

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MM: This has been We Can Answer That. Edited and produced by Nate Luit and hosted and produced by me, Mike MacKinnon. We've been talking with Dr. Peter Facchini, a professor of biochemistry and chief scientific officer of MagicMed, about studying drugs like magic mushrooms and mescaline for their medicinal benefits. You can subscribe to We Can Answer That on Apple, Google, or Spotify, or by visiting ucalgary.ca/podcasts. We Can Answer That is a production of the Áù¾ÅÉ«ÌÃ. Thanks for listening.

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