Psychedelic drugs are, after a nearly 50-year absence from research, back in fashion. There are several milestones by which a neutral outsider might measure the extent of the psychedelic revival. They do have their own Netflix show (in fact, they now have several) but have not yet been approved by the United States Food and Drug Administration. A smaller, but nonetheless significant sign that the tide around psychedelic science is changing is the decision of the organizers of the recent Federation of European Neuroscience Societies (FENS) conference, the largest event of its kind. in neuroscience in Europe, to carve out a place in this booming field. Of research.
Previous editions of FENS had little mention of psychedelics. While some sessions briefly touched on the antidepressant abilities of the non-conventional psychedelic ketamine, FENS 2022 broke new ground, with both a mini-conference, organized in collaboration with the European College of Neuropsychopharmacology, and a symposium examining the advent of psychedelic compounds without hallucinogenic effects.
Technology networks attended this latest symposium, which included presentations by Dr. Kim Kuypers from Maastricht University, Dr. Lindsay Cameron from Stanford University, Dr. Scott Thompson from the University of Maryland and Rafael Moliner from the University of Helsinki. The symposium aimed to address the idea, increasingly popular among researchers, that the deployment of potential psychedelic drugs might be limited by the hallucinatory trips these compounds induce.
Psychedelics without travel
“If psychedelics can be disentangled from therapeutic effects, that would be helpful in reducing the amount of time a patient has to spend. In preparation, during drug administration, with follow-up – that’s a lot of time on the patient’s side” , says Cameron in an interview with Technological networks.
Cameron also hopes that making psychedelics hallucination-free could reduce costs for patients and reassure people who are unsure of the effects of a trip that could potentially last hours and require close monitoring by a nurse or of a therapist throughout.
Cameron and his mentor, University of California Professor Davis David Olson, have made the development of non-hallucinogenic psychedelics the focus of their research. Cameron marked a significant breakthrough with the publication of an article on a compound called tabernanthalog, a psychedelic ibogaine analogue.
Ibogaine, a compound produced by plants in the Apocynaceae family, has shown some potential in preliminary trials for the treatment of addiction. However, its effects are long-lasting, and concerns have been raised about the compound’s toxicity and its cardiac side effects.
Tabernanthalog, by comparison, is non-hallucinogenic and non-toxic. In a small rat study, Cameron showed that the compound could reduce alcohol- and heroin-seeking behavior, raising the possibility that it may mimic the anti-addiction function of ibogaine in humans. “The idea here,” Cameron explains, “is that we have a compound that appears to be therapeutically active but would no longer produce hallucinations. Our lab coined the term ‘psychoplastogen’ as something that is capable of causing this change, to shape brains.” Throughout the symposium, speakers returned to this focus on the brain structure-altering, or neuroplastic, effect of psychedelics.
A debate on serotonin
While the presenters were aligned on their interest in exploring non-hallucinogenic compounds, their data was not always in sync. Three researchers – Thompson, Cameron and Moliner – have each examined the role of serotonin 5-HT2A receptor, widely believed to be essential to the hallucinatory action of psychedelics. It is not clear at this time whether the antidepressant effects of these compounds are too derived from signaling by this receptor. Cameron’s data suggested that tabernanthalog, at least, required 5-HT2A activation to produce its effects. Thompson, working in rodents with psilocybin, studied how the drug affects the brain’s reward system in the context of chronic stress – a process his results suggest is independent of 5-HT.2A. A final talk by Moliner highlighted why such conflicting data will be common at this early stage in our understanding of the molecular action of psychedelics: these brain processes are incredibly difficult to pin down.
Moliner showed data suggesting that ketanserin, a compound widely used in preclinical research as a pharmacological tool to block 5-HT2A receptors, might not be very selective at all, acting instead to additionally block other 5-HT receptor subtypes. Understanding how these different molecular players mediate the psychedelic experience will be essential not only for developing better hallucinogenic and non-hallucinogenic compounds, but for understanding how depression and other mental disorders occur in the brain.
These different paradigms within a field are part of what makes scientific conferences so stimulating for better research. But there are debates surrounding psychedelics that were largely ignored at FENS 2022.
Getting out of the taboo of psychedelics
Dr. Muad Abd El Hay, postdoctoral researcher at the Ernst Strüngmann Institute in Frankfurt, attended all the psychedelic conferences he could at FENS; he says Technology networks that he has “attended specialist conferences on psychedelics since 2014”. For El Hay, the presence of a psychedelic slot machine at FENS represents a huge change from previous years. In the past, he explains,[psychedelics] was taboo… to get it right, you kind of had to sacrifice careers.
Now the field has flipped, says El Hay. As major labs – known for their breakthroughs in non-psychedelic scientific fields – began to publish landmark papers, the taboo faded. But El Hay says FENS’ decision to focus on the non-hallucinatory effects of psychedelics was potentially an unrepresentative introduction to the field: “The narrative at the end was, ‘We don’t need this psychedelic effect for whatever either occur in mice, neuroplasticity is everything and we don’t even need 5-HT2A receiver.’ That was really cool data, but a lot of people would disagree with that. They were not represented here.
“What I knew to be a very collaborative field is suddenly turning into a very competitive field.” ~Dr. Mouad Abd El Hay
There are still many key questions to be answered regarding psychedelics, but as they begin to gain wider recognition in neuroscience, there is an undeniable sense of momentum. “We’re finally starting to make progress in getting them as therapeutics,” Cameron says.
What seems less clear is whether the culture of psychedelic research will survive the evolution of the field towards big times. For El Hay, there was a noticeably different mood among the researchers he spoke to at FENS compared to those at psychedelics-only conferences. “I feel a bit sad because what I knew was a very collaborative field suddenly turns into a very competitive field,” he says.
This change may be inevitable as psychedelic research increasingly dominates the headlines. The first day joint symposium featured a speaker from the growing and ambitious psychedelic pharmaceutical company Compass Pathways, which has come under fire for its aggressive patenting of psychedelic molecules.
A non-hallucinogenic, synthetic, and more corporate future for psychedelics might be needed to reach more patients and help more people, but it’s hard to see how that’s compatible with the field’s past mindset when it comes to sharing. and collaboration. El Hay, however, says he still managed to meet future collaborators and FENS and have fruitful discussions, even if they didn’t come as easily as in previous psychedelic get-togethers. “I’m not giving up on this [field]but it’s a bit sad to see these problems happening,” he says.