Lords of Lysergamides: Positive Potentials for Psychedelics
Benedetto Maniscalco | April 21, 2022
Bryan Roth
Mental health is a topic that has gained more and more attention in the public eye in the last decade and throughout the ongoing COVID-19 pandemic. Psychedelic-assisted therapies have shown new possibilities and are on the trajectory to become more accessible to those suffering from an array of conditions.
Bryan Roth, Ph.D., a professor at University of North Carolina (UNC) Chapel Hill, noted issues in efficacy within current medical treatments of various psychological conditions like depression.
“Depression is a very serious condition and the vast majority of people who have depression are not adequately treated,” said Roth. “The medications, they're helpful but you know, it's the rare person whose depression is completely gone after they started an anti-depressant medication,” Roth said.
Roth works with UNC Chapel Hill developing compounds based on psychedelics in hopes to maximize their potential therapeutic value. He also works trying to understand how psychedelics work.
“But with the psychedelics, the reports are (that) people are fine, you don't know if this is a placebo effect because of the psychedelic experience or what, but it's pretty amazing from a clinical perspective. They basically take what we call a cosmic dose of psilocybin, they have a very intense psychedelic experience and then they're fine.”
Roth first became interested in psychedelics in the late 1960s when they were being used more widely for the first time, and when there was still very little actually known about them.
“I got interested in psychedelic drugs when I was a teenager, sort of at the tail end of the 60s,” Roth said. “Lots of people were taking psychedelic drugs and my mother had schizophrenia — she died — but I had heard that psychedelic drugs cause an experience similar to schizophrenia.
“Of course we know that's not true now, but I thought if I understood how psychedelic drugs work, I might ultimately be able to come up with new treatments for schizophrenia, so that was one motivating factor.”
Roth has spent decades working to understand the ways that psychedelic drugs work on a cellular level. Initially, he had not considered their potential in a therapeutic capacity. He has published several papers on the subject including his most recent, the Promises and Perils of Psychedelic Pharmacology for Psychiatry.
“The big thing now is legalization and medicalization of psychedelics,” Roth said. “I honestly never thought that would occur. For what it's worth, I was skeptical that they would have any therapeutic uses. I just thought it's interesting that these drugs alter how people view reality and I thought it would be important to find out how that occurs. I would say the big surprise has been that, at least in these preliminary clinical trials, they appear to have this remarkable effect.”
The idea that a small amount of a psychedelic substance can alter someone's view on life, and permanently shift the way they engage with the world, is something that has also interested David Nichols, Ph.D.
“For most people taking an effective dose of LSD can change the way they perceive the world,” Nichols said.
Since the 1970s, Nichols has researched and conducted lab syntheses of psychedelics, and for a long time was the only person funded to do this work. In his decades working with them, he has published a number of papers all pertaining to scientific topics and findings relating to psychedelics.
“The only other person that was doing any chemistry on psychedelics was Alexander Shulgin,” Nichols said. “So by the time I went to grad school in 1969, he had published maybe half a dozen papers in the field. So I got copies and read all those, but otherwise there wasn't really anybody else.”
Shulgin, described by Nichols as a renaissance man, has gained notoriety and a community of fans within the world of recreational psychedelic use.
“We were friends; a lot of the compounds in PiKHAL are compounds that I made, and I couldn't test them in humans so I'd send him samples and he'd put them into his group,” Nichols said. “He was an interesting guy, kind of a Renaissance man, really more of an al-chemist than a scientist. ”
Dave Nichols
Though his processes of seeing if he could make a substance, and then testing them on himself were questionable to some, he was a chemist who early on considered the potential for therapeutic uses within compounds like MDMA.
“We're not there yet but in another 10 years, we'll know a lot more,” Nichols said. “MDMA should be approved for PTSD in the next year or two — psilocybin for depression, probably a year or two after that.”
There are psychiatrists and physicians currently working on bringing psychedelic therapies to the public, including one here in Asheville.
“The training and resources required for psychedelic therapy are expensive, which means that the therapies themselves are expensive,” said Joshua Short, an owner and physician at Asheville Integrated Psychology.
Short mentioned just how difficult it can be to obtain these therapies affordably.
“Insurance doesn't pay for them, so all of a sudden we have access to these therapies that are providing new promise and new hope and psychiatry, but we can't make them as available as the traditional therapies,” Short said. “Which are less effective and potentially more dangerous.”
Asheville Integrated Psychology currently provides patients with the opportunity for ketamine-assisted therapies to treat depression. They focus on therapies that not only focus on psychedelics, but on nature as well.
“Our mission is to improve health through access to nature-connection, integrative therapies and psychedelic therapies,” Short said. “The primary goal there is to use those three things to nourish a person's inner healing intelligence — to promote health with decreased use of pharmaceutical therapies.”
Short explained the importance of context in psychedelic-assisted therapies. As the context informs the experience, it should be done in a controlled setting with the assistance of trained mental health officials.
“The idea that we can find a cure rate for PTSD with MDMA when there's been no cure before, and this affects so many of our veterans and emergency service providers, I think this message is really getting to places it hasn't gotten to before, that feels valuable to me,” Short said.
Roth backed up this fascination and appreciation for the potential therapeutic possibilities of MDMA.
“The results with ecstasy are astounding,” Roth said. “People take two doses, there's a fair amount of psychotherapy and working through the experience, but again, most of the people are fine which is astounding. It will revolutionize the treatment of post-traumatic stress disorder assuming it gets approved.”
Asheville Integrated Psychology will soon provide MDMA-assisted therapies and hope to offer psilocybin therapies as well. However, given this new field of therapy, there are questions about how it might look in the future.
“My concern is that we're going to move more and more towards the type of medicalization that we saw with medicalized cannabis,” Short said. “Where there are corner stores that sell a variety of products with a variety of information and sources. There's no real consistency or standard of care. So I think creating a standard of care now is going to be the thing that shapes the future.”
Nichols has high hopes for the ways that psychedelics and mental health might pan out in the next few decades.
“Some years ago a woman asked me, ‘what do you see as the future for psychedelics?’ And I said, ‘well someday, long after I'm dead probably, you'll be having a midlife crisis and your physician will send you down the corner to see shaman/psychiatrist, and he'll give you a session of a psychedelic and you'll gain a new perspective on your life.’”
For him it has been a long road of underfunded work lacking any major public interest, but Nichols is optimistic, even if it may take another 20-30 years.
“And she said ‘my god you think you'll be dead?’ And I said, ‘yeah probably,’ but I said, ‘at least if the vector’s pointing in the right direction, I'll be happy,’’’ Nichols said. “I could never have imagined that –– now there are 93 currently registered (clinical) trials of psilocybin.”
Nichols compared the efficacy of the heavily prescribed daily dose medications for mental health disorders, like SSRIs, and the possibilities of psychedelic therapies that require smaller doses to be taken very infrequently.
“How is it possible that a minuscule amount of a compound can diffuse into your brain, stay there for a few hours and come back out and for better or worse, you may not see the world the same way again ever,” Nichols said. “I mean that's pretty powerful, if you think about it, you know, how is that even possible?”
With the work in developing new versions of psychedelic compounds, Nichols believes the next point of focus lies in understanding what these already existing compounds do and why they do it.
“I'm not sure how much chemistry we need to do nowadays between the compounds that Shulgin made and that I made,” Nichols said. “There's probably two or three hundred of them out there that we know something about.“I think the more productive avenue would be for people to go into neuroscience and neuropharmacology to really focus on what they actually do.”
When compared to other categories of psychoactive drugs, psychedelics are still, in many ways, a mystery.
“We know what the receptor is but why do they have a psychedelic effect,” Nichols said. “When you get serotonin in your brain, it doesn't really do that, so what do they actually do? What are the biochemical signals they produce in the brain and now with all the therapeutic work that's been out there, how do they actually produce an antidepressant effect or disrupt addiction?”
This is something that Roth has focused on for years, and though there have been major accomplishments and discoveries, there is still a lot to figure out.
“I would say the big celebration was when we first got the structure of LSD in complex with one of its receptors,” Roth said. “This was probably six years ago and made the cover of the journal Cell. That was sort of a culmination of 30 years of work, basically, and I sort of made a joke to the people in my lab ‘well, now I can retire because I've done what I wanted to do.’”
Along with furthering the understanding of psychedelics and how they work, Nichols highlighted the importance of psychiatry for their future.
“It's really having a major impact on medicine and psychiatry, biological psychiatry and, ultimately, understanding how the drugs work to treat whatever, is going to give us insight into the underlying pathophysiology,” Nichols said. “So it's really going to inject a kind of a quantum leap in terms of our understanding of psychiatric illness.”
Nichols explained how throughout his years teaching he noticed the consistent disinterest in the field of psychiatry, with most modern medications being safe enough for physicians to prescribe, but with interest and acceptance of psychedelic therapies he has seen a rise in interest in the world of psychiatry.
“Now, since this has all started, I've had emails from at least three or four people saying, ‘I want to go into psychiatry. Do you think there's going to be a future for me if I do this?’’ said Nichols. “So I think that's rejuvenating the field.”
Roth provided some insight and advice for people interested in the future of psychedelics and mental health.
“It's an emerging field, so you're getting in early on something that's probably going to be really big,” Roth said. “My general recommendation is that it's not necessary, early in your research career, to study psychedelics. You need to get a firm grounding in whatever area of science that you're interested in, psychology or psychotherapy or chemistry or biology and then take those insights to study psychedelics.”
Roth also mentioned his gratitude for being able to do this sort of work with funding from the government that is only available because of tax paying citizens.
“Our work is supported by your tax dollars,” Roth said. “So thank you for paying your taxes, that's what I like to tell people.”
Roth, Short and Nichols expressed a great deal of excitement for how psychedelics will be used for treatment in the future.
“(It) will transform the way we treat serious mental illnesses around the world, it'll be a huge advance,” Roth said. “I think that's why everybody has gotten interested in it.”