Jordan
Hey, it’s Jordan. I’ve been hosting this podcast for four years now. We’ve done all right. More than 1000 episodes, a couple of awards, millions of downloads, lots of Canadian stories, and lots of fun, too. But there was one thing missing before I finally felt like a real big-time podcaster. That’s right, a mattress to test and report on in ad breaks. And I am happy to report that day has finally arrived. Over the next little while on this show, you will hear my unfiltered thoughts on the Douglas Mattress, a made-in-Canada eco-conscious mattress that comes with a 120-night guarantee. Personally, as I record this, I’m on night five with this mattress, and I like it a lot so far. That’s my very quick first impression. I’m not an expert, but it’s honest. I am also writing this spot while I work on the mattress, and this isn’t in any of their ad copy, but as somebody who’s been working from home for two-plus years now, a mattress that is firm enough to both sleep on and work on is important to me personally. One major thing I’m looking forward to testing is the cooling gel foam that is meant to keep me cool on hot nights. We’ve got a few of them coming up as I record this, so we’ll talk about that the next time. In the meantime, they are having a big sale in honour of sponsoring The Big Story, and you can head to Douglas.CA/Thebigstory, and get what many are calling Canada’s best mattress and follow along to see if I will eventually be joining them. That’s Douglas.CA/thebigstory.
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You’re listening to a Frequency Podcast Network production in association with CityNews.
Jordan
There is, to state the blindingly obvious, an awful lot of money in making new drugs. The most obvious recent example is the tens of billions of dollars that Pfizer alone made last year from its COVID vaccine. But really, it could be anything heart medication, antidepressants, painkillers, whatever. If you can develop and patent a new, effective drug, you’re going to be rich. And naturally, there is a lot of competition to do just that. So what if you went where there was more open space, fewer companies pouring millions into research, fewer chemists who understood the field, fewer already existing drugs for yours to compete with? And what if all that was true because the kind of drugs that you were making have typically been highly illegal has for decades had the stigma of hippie culture, underground chemical labs, and black markets? But what if all that was changing? Welcome to the newest arms race in the pharmaceutical industry developing brand new psychedelic drugs. I’m Jordan Heath-Rawlings. This is The Big Story. John Semley is a Canadian writer and researcher currently based in Philadelphia, where he recently wrote The High Stakes Race to Engineer New Psychedelic Drugs for Wired magazine. Hey John.
John Semley
Hi, thanks for having me.
Jordan
Of course. And maybe we can just start and we’ve covered this from a couple of angles on this show already, but just to lay the groundwork. Can you sort of tell us about the past several years and how the stigma or the view of psychedelics has shifted?
John Semley
Definitely, yeah. I mean, I think we are in the sort of middle of what’s been called a psychedelic renaissance that has been kind of unfolding over the past decade, almost more than a decade now. I think the big sort of thing that sparked this off was in 2006 there was a study done at Johns Hopkins University that using all the scientific rigour available, essentially proved that psilocybin, which is the active ingredient in magic mushrooms, can produce what they call mystical-type experiences when given to people. That means these sorts of intense, hallucinatory experiences that have a very powerful emotional impact. Now any old hippie could tell you that that’s the case, but I think the fact that it was proven with a sort of double blinding and like I say, scientific rigour, it sort of afforded these drugs a new seriousness in the clinical landscape. Since then you’ve seen sort of cultural shifts happen. The re-emergence of the popularity of Grateful Dead music and tie-dye t-shirts. You had the success of Michael Pollan’s book How to Change Your Mind, which is now a Netflix documentary miniseries. And I think that people’s attitudes about these drugs are changing. It’s no longer you’ll take LSD and fly out of a window or something like that. People are understanding that these drugs are powerful. These drugs are definitely weird and strange, but that power and weirdness and strangeness can be harnessed towards very productive ends.
Jordan
And there have also been limited programs using some of these drugs to microdose for depression and other mental health issues. Right?
John Semley
Absolutely. Microdosing became kind of a meme, I guess, which micro-dosing is taking a small amount of psilocybin or LSD on a daily basis, or a couple of times a week, sort of. Yeah, almost as a form of antidepressant or some people kind of use it even for the amphetamine effect of LSD. Like you hear about people micro-dosing and it makes them more productive. I don’t think the science behind micro-dosing is really quite there and personally, I think that it’s a placebo effect type thing where you become more productive and better adjusted because you think that you are. But I think that itself is telling. The brain is really the tool that is at the center of all of this and it’s something that we only have a kind of cursory understanding of. So the fact that people report positive benefits to micro-dosing. Just from a sort of placebo basis, I think speaks to the power of the brain, which again, is at the center of the power of psychedelic drugs.
Jordan
So as that whole shift has happened over a decade or more, how have the traditional pharmaceutical giants reacted to it?
John Semley
Well, the traditional giants, I think, are still kind of at arm’s length. Johnson and Johnson have created a nasal spray based on ketamine, which is not really a psychedelic, it’s more of a disassociated. Their version, which is called Esketamine. I have heard it said that it has kind of psychedelic effects. But there have certainly been a number of biopharma, biotech startups that have taken a huge interest in this and have invested huge sums of money into clinically trialling and developing psychedelic drugs in the hopes that they may become maybe pharmaceutical drugs that you get over the counter or maybe sort of treatments and licensed therapies. I mean, you already see some of these therapies occurring, whether it be ketamine therapies, which happen throughout North America or in certain jurisdictions, magic mushroom therapies, which are, I believe, legal in Oregon, in the US and in Canada, there’s a group called TheraCell that has been doing magic mushroom therapy by getting sort of special dispensations from the Canadian government to say that people have the right to try these medicines and use them in this capacity. But yeah, I think as far as these sort of antidepressive effects that people are looking at, the big pharma industry has so much invested in SSRIs and Zoloft and all these things that I don’t think they’re quite on board yet.
Jordan
So what about these new startups then? And you went inside one, or at least as far inside as they would allow you to go? Maybe. Tell me about Jason Wallach. Who is he and what is the Discovery Center?
John Semley
Yeah, so the Discovery Center, it’s a lab, it’s a program, it’s a sponsored research agreement between I have to get this right, it’s St. Joseph University. It used to be called the University of Sciences in Philadelphia, which is actually in one form, the oldest pharmacological college in the United States. So it’s an agreement between them and Compass Pathways, which is a UK-based biotech start-up. They’re one of the kind of biggest publicly traded psychedelic startups. And Compass’s core business right now is trying to get a psilocybin-based drug and therapy to market. But they’re also investing heavily in what’s called drug discovery, which means trying to find new drugs, trying to trial new drugs. And Jason is kind of the person at Compass who’s leading the charge on this. And to me, what interested me about it is this could be if you believe the people who are investing in it, the new frontier of mental health treatment you know. And you go to this lab and it’s like Jason’s in his mid-30s, you have grad students for lack of a better word, kids, basically. And they’re so invested in this and it’s so exciting. And it’s like this is basically a career field that had never existed before or at least hasn’t existed for about 50 or 60 years when all of this research was forced underground due to the Controlled Substances Act. So it’s a really kind of exciting environment where you have young, brilliant chemists who are really at the forefront of a renaissance in psychopharmacology, or at least psychedelic psychopharmacology, which is a mouthful.
Jordan
So how does it work? How does one actually go about concocting new psychedelic drugs?
John Semley
Yeah. So basically the key to the work done at Compass involves a cellular protein in the brain called the 5-HT2A receptor. Now, I’m not good at the chemistry stuff, even myself, but the analogy I would like to use is the 5-HT2A receptor is think of it like a keyhole, right? It regulates serotonin. It can affect everything from appetite to sexual arousal. And a lot of the traditional classical psychedelics, like LSD or psilocybin or DMT, they work by sort of playing on the 5-HT2A receptor. So what the people at the Drug Discovery Center are doing is trying to find new drugs that can affect that receptor. Like I say, think of the receptor-like a keyhole, right? They’re basically trying to find new ways to pick the lock and get inside there. So what they do is they take the structures of drugs that might exist, like psilocybin or DMT or LSD, and they sort of play with that structure. They move a molecule over here, they move a molecule over there. They try to see what kind of new drugs and new drug experiences can be created with the sort of known architecture of psychedelics that is well documented.
Jordan
And how do you know if the drugs they create are actually psychoactive psychedelics? Tell me about the mice. How do you figure this out?
John Semley
Okay, well, back in the old days when this stuff was underground, you would synthesize a drug and then just take it and then you would know if it works or not.
Jordan
The good old days.
John Semley
The good old days. And I mean, that is an attitude. I’m not saying that this happens at the Drug Discovery Center good Lord. But that is the sort of this is the thing about the underground is it’s almost easier in that way, right? I mentioned in the article the chemist Alexander Shulgin who developed hundreds of psychedelics and recorded his experiences with them, and this guy is like a saint. The people at Drug Discovery Center but when you have to be above board and you can’t have scientists running around dosing themselves in the lab, you have to find more kind of scientifically grounded methods. The key one that they use at the lab is they test the drugs on mice. There have been multiple studies showing that when the 5-HT2A receptor of a mouse is affected. They sort of do these head twitchy gestures, right? So you can measure the head twitches and that gives you a pretty good idea of if the drug will be powerful psychedelically and just how powerful it will be. Now, as I said in the article, obviously a mouse can’t be like wow, I saw my dead grandfather and they led me into a realm of pure love and understanding. So really what they’re gaining through the mouse is only an understanding of if these things work and how powerful they might be. The next steps, which are testing and trialling on humans. I mean, I think that is still a ways off.
Jordan
So how many drugs have they made so far? What kinds of drugs? And I know I’m asking you this question when there’s a lot of secrecy involved here.
John Semley
Yeah, I mean, I think it’s like this is an interesting thing about private investment coming into this space is it is becoming, I guess, more secretive.
Jordan
Right.
John Semley
The development and trialling of these drugs. These are things that are made with an eye towards patents and profit now. So that creates a sort of a bit of a closed book structure. I mean there’s still an exchange of information and ideas but even when I was in the lab I felt like in Willy Wonka, like that guy Slugworth, he’s always sleeping around trying to steal the everlasting gobstopper. That was kind of how I felt. People are turning labels away from me the whole time. As if I know anything about this. Right? I like to see a diagram of a new psychedelic. It just looks like a bunch of intersecting hexagons and lines to me. But yes, they have made I would say my estimate is at least 150 new drugs in intermediate stages and drugs that haven’t been totally refined and finalized. There’s probably much more than that now. I guess the next question if I can ask it, is what do you do with 150 psychedelics? I think this is part of the kind of patent play of this. Again, this is part of the new corporate climate is if you think of a sort of space on a board that are potential combinations of psychedelic drugs. Part of the race to patent these drugs is just to have the patent on them. Right. You can claim the space and no one else can claim it because you have an exclusive right to it. Even if you have no idea if it will be profitable, even if you have no intention of ever using it, you’re precluding people from also using it. That is where in this space there’s a lot of criticism, right, that it’s stifling invention. Again, I think the land grab analogy kind of works. Or think of it like a Monopoly board. There are so many spaces on a Monopoly board right now. The counterpoint to this is like the potential combinations of chemicals that you can make is unfathomable. It’s like imagining stars in the galaxy or the universe. So to say that Jason made 150, and that’s a lot. It is a lot. But within the sort of universe of potential chemical compounds and even potential psychedelic compounds, it’s a drop in the bucket.
Jordan
Hey, it’s Jordan. I’ve been hosting this podcast for four years now. We’ve done all right, more than 1000 episodes, a couple of awards, millions of downloads, lots of Canadian stories, and lots of fun, too. But there was one thing missing before I finally felt like a real big-time podcaster. That’s right, a mattress to test and report on in ad breaks. And I am happy to report that day has finally arrived. Over the next little while on this show, you will hear my unfiltered thoughts on the Douglas Mattress, a made-in-Canada eco-conscious mattress that comes with a 120-night guarantee. Personally, as I record this, I’m on night five with this mattress and I like it a lot so far. That’s my very quick first impression. I’m not an expert, but it’s honest. I am also writing this spot while I work on the mattress, and this isn’t in any of their ad copy, but as somebody who’s been working from home for two plus years now, a mattress that is firm enough to both sleep on and work on is important to me personally. One major thing I’m looking forward to testing is the cooling gel foam that is meant to keep me cool on hot nights. We’ve got a few of them coming up as I record this, so we’ll talk about that the next time. In the meantime, they are having a big sale in honour of sponsoring The Big Story, and you can head to Douglas.CA/Thebigstory and get what many are calling Canada’s best mattress and follow along to see if I will eventually be joining them. That’s DouglaS.CA/Thebigstory.
Jordan
So I know you probably can’t tell me what drugs exactly they’ve created, and that’s good because I probably wouldn’t understand them anyway. But what are they trying to get at with this research? Like, what kind of trips do they want people to have? How would they be different from traditional psychedelics?
John Semley
Yeah. I mean, even if I knew, I couldn’t tell you because of NDAs. But I think the main thing that a lot of these companies, including Compass, are driving after, which is something that I can talk about, is trying to find what’s sometimes called a sweet spot between the intensity of the experience and the duration of the experience. Right. I mean, Psilocybin has proven very powerful and very effective in certain clinical settings and therapies but a Psilocybin trip can be 6 to 8 hours. There’s processing before, there’s processing after. And when you’re thinking of incorporating this in some sort of for-profit clinical model, that is not very cost-effective. Right. DMT contrarily and 5-MeO-DMT, which is a wild drug has also proven very effective but they’re extremely short-acting, 10/15 minutes, intense ego death experiences that people sometimes have a hard time even making sense of. You go almost in and out of this other world so quickly that you don’t know what to do with that experience. So I think what a lot of these companies are trying to do are trying to find drugs that are powerful, that can create those psychedelic experiences, but that can create these experiences within what they would call a container that is manageable, that doesn’t span half a dozen or in the case of LSD, sometimes a dozen hours. And that is where, again, this sort of balance between the power of the experience and the sort of clinical cost-effectiveness comes into play.
Jordan
How far do we have to go before and let’s assume, just for the sake of this conversation, that one of those 150 or so drugs they make, they find that sweet spot, they think it’s effective, how far do they have to go before you can actually get approval for this kind of drug? Get it to market? Like, as I understand it, in many parts of the US and Canada, these drugs are still pretty highly illegal, right?
John Semley
Yes and no. I think the core psychedelics, LSD, psilocybin, DMT, they are by and large illegal outside of certain jurisdictions in certain places. One of the other things about creating new psychedelic drugs is a lot of these drugs, in fact, most of them, and probably all of them, are not scheduled in any sort of controlled substance act. In fact, if you create a drug that hasn’t existed yet, there’s no legal framework that exists around it. Right?
Jordan
Right.
John Semley
I mean, sometimes you can get into trouble with that because you could say, I’m not making LSD, I’m making ALD 25. And then a cop will say, well you had to create a chemical precursor that is illegal to make it blah blah blah, blah blah. But part of the thing about creating new drugs is that they don’t fall under drug laws that exist now. Does that mean that you can push them to market in a conventional above-board way? No. You have to go through, at least in the US Food and Drug Administration approval as far as how far out these things are right now. There’s an MDMA drug. MDMA sometimes is called an empathogen. It’s not really a psychedelic. It doesn’t quite work in the same way that traditional psychedelics work, but it is being developed by a nonprofit called Maps, the Multidisciplinary Association for Psychedelic Studies. And they’re at stage three of their FDA trial, which after stage three comes approval. So they’re the furthest ahead. Compasses psilocybin treatment is at stage two. A company called MindMed has an LSD treatment at stage two. So these things are happening and they are moving along the board. But I would say we’re still five years out from seeing these in a sort of traditional pharmaceutical medical context. What is happening in certain states in certain jurisdictions and certain doctors are getting legal exemptions to conduct these therapies despite the broad illegality of these drugs? Now the other side of this coin, which is something I couldn’t quite get into in the article, is there’s a lot of sort of cultural hubbub about this, right? This is also corporate, it’s all patents and blah, blah blah. That’s true and I understand that complaint. But the other thing is for anyone interested in these drugs, in the sort of traditional, by which I mean underground way, any patent that’s created on a new drug is essentially a recipe card for an underground chemist. When these 150 drugs go to the patent board and the process of making them is publicly divulged, anyone who wants to cook them up in their basement can do so. Not only is it going to create a sort of landscape of potentially profitable psychedelic drugs in a pharmaceutical context, but it’s also going to create an explosion in the still legal psychedelic underground which I think is itself very exciting for people.
Jordan
I want to talk about that psychedelic underground in just a minute, but first, to get a sense of what’s at stake, you touched on this at the beginning, that there are a lot of startups doing this right now. Do we have a sense of the size of this nascent industry?
John Semley
Yeah, I think it’s like anything, there are a number of unserious groups that will probably fall away but god, I can’t count them right? But I’d say about a dozen that are sort of serious players. There’s Compass, MindMed, LifeSciences, Numinous, Wellness, Siben. These are just off the top of my head. And then there’s also, as I mentioned, some nonprofits like MAPS, which is a decades-old organization that has been advocating for this for a long time. The Usona Institute is doing a lot of research, etc and etc. And eventually, I think a lot of these groups will kind of consolidate and fall away. But we’re still kind of in that early stage where it’s a bit of a foot race and there’s a lot of people still in that foot race.
Jordan
But it does kind of feel like a very big corporate 180 from the era that most of us associate with psychedelics. You mentioned the Grateful Dead music and the tie-dye shirts. What does that community that has advocated for these drugs for so long, while they were highly restricted, think about them becoming what at least appears to be if you want to take a cynical view of it, a race for pure profit?
John Semley
Yeah, I mean, well, people don’t like it and I think there’s a couple of reasons for this. That said, there have been people who have successfully moved from the underground to the corporate world in their own way. I mentioned one in the story, a chemist named peter Vanderheyden, who’s Canadian, he works out of Calgary, he used to be a clandestine chemist who is now working above ground developing and producing psychedelic drugs with the licenses to do so. And good for him. If there’s anyone who I think deserves to profit off this new investment, it’s people like Peter who had to work underground and spent time in jail creating an appetite and an awareness for these drugs. Now that said, this idea that corporations are coming in and turning it into this kind of white collar thing, yeah, it rubs a lot of people the wrong way. And I think that there’s that cultural element that you mentioned. These drugs are associated with the hippie culture of peace and love and understanding. I mean, most of those hippies eventually sold out and bought Jerry Garcia neckties in the 80s anyway. But at a deeper level, I think it has something to do with how these drugs work. I mean, people who have psychedelic experiences talk about these profound feelings of love and connectedness and peace and these values that seem totally counterintuitive to the sort of cutthroat corporate world as we know it. So I think a lot of those criticisms are totally valid. Now from the other side of the coin, I mentioned MAPS and their MDMA drug, right? Maps have been working for three decades to get a drug to phase three of FDA approval and they’ve done amazing work. And MAPS is an incredible organization. But with the power of private corporate investment and the money that flows into it, groups like Compass are right on their tail and they’ve only been operating for a couple of years. It’s hard to argue with that. I think it depends on A, your values and B, how you want to share those values with a belief in those drugs. If you believe that these drugs can really help people and that we should be trying to get them to people as soon as possible, then maybe corporate investment is the best way to do that. I’m personally a little bit ambivalent and undecided, but it’s hard to argue when a company can raise as much money in five years as another has in 30.
Jordan
This is my last question. What are you most curious to see happen next? It does feel just from this conversation like at some point there’s going to be a tipping point here, right?
John Semley
Yeah, I think with a lot of this stuff, even if you look at the investment into psychedelics, I mean, these companies came out of the gate and were way overvalued and now the market is totally trunk. There’s been a natural contraction because there are no products. But that corporate stuff. And this stuff about patents, to me it’s like the least interesting part of it.
Jordan
So what’s the most interesting part?
John Semley
The drugs. The drugs. What drugs are going to be created? What experiences will be produced by them? I mean, you have people working with drugs that say it will just affect your ability to hear sound. You’ll have no visual hallucinations. We’re talking about creating a whole new mode of experience at the end of the day, right? And I think that is ultimately what is driving the chemists and I think it’s what drives me to be interested in them in a lot of ways. I had someone say to me recently if we could create a drug that would allow you to see the world in black and white, wouldn’t that be useful just on its own or wouldn’t it be interesting just on its own? So these things that come. That comes out. The things that they suggest and illuminate about how our brain works. How consciousness works. I mean, I think there are ways in which psychedelics can illuminate age-old questions and I sound like an old hippie saying stuff like that.
Jordan
I was going to say.
John Semley
But those questions and the potential answers to those questions and the way in which people are now able to pursue them without having to work out of stinky drug bunkers and being chased around by the DEA. That to me is much more exciting than what German biotech is going to come out on top in five years.
Jordan
It’s an exciting time and I would like to see the world in black and white and I would like to be able to buy it at my pharmacy for $12.95
John Semley
And Canada, hopefully free.
Jordan
Yes. Thanks, John.
John Semley
Thanks very much for having me.
Jordan
John Semley writing in Wired magazine. That was The Big Story. For more from us, head to thebigstorypodcast.ca. If you would like to listen to a couple of our other episodes on psychedelics, just scroll down to the bottom and type that in the search bar if you can spell it, you can also find us on Twitter at @TheBigStoryFPN via email at [click here!] or leave us a voicemail. The number is 416-935-5935. If you’ve taken psychedelics, definitely call and ramble for a while. This episode of The Big Story was produced by Rajpreet Sahota and you can find this podcast wherever you get your favourite ones if they let you. Please rate and review. Thanks for listening. I’m Jordan Heath-Rawlings. We’ll talk tomorrow.
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