Two thousand and twenty-four could be a watershed year for psychedelic science. In the first few weeks of January alone, new clinical trial results have been reported, in-depth research has unveiled findings about how these drugs work at the molecular level and the first fully legal prescription for therapeutic 3,4-methylenedioxymethamphetamine (MDMA) has been issued in Australia.
Technology Networks spoke to researchers in the field to find out more about the landmark psychedelic science events that will define 2024.
A long-expected approval?
Our interviewees each highlighted multiple milestones, but all of them opened by mentioning what could be the biggest development in the history of psychedelic research – the US Food and Drug Administration (FDA)’s possible approval of MDMA-assisted therapy for post-traumatic stress disorder (PTSD).
The approval is sought by Lykos Therapeutics, formerly a non-profit known as the Multidisciplinary Association for Psychedelic Studies (MAPS) Public Benefit Corporation, which has been working towards this goal of approval since 1986.
The approval would be “a major step,” said Michiel van Elk, an associate professor at Leiden University’s Institute of Psychology. Van Elk has published multiple articles that have sought to calm the hype around psychedelics. A 2023 paper co-authored with Leiden colleague Eiko Fried warned that psychedelic science risked repeating mistakes that led to the field’s collapse in the mid-1960s.
“I’ve been very critical. But it’s beyond doubt that MDMA therapy for this specific indication – PTSD – seems to be relatively safe and seems to be working quite well. The data look good,” said van Elk.
Nolan Williams, an associate professor in the Department of Psychiatry and Behavioral Sciences at Stanford University, says that Lykos’ drug will be “important” for the field, and will potentially pave the way for other upcoming Phase 3 trials in the space. This includes Compass Pathways’ trial of psilocybin therapy for treatment-resistant depression, named COMP360, and the Usona Institute’s trial of PSIL201 – a single dose of psilocybin for the treatment of major depressive disorder.
But Lykos’ drug approval isn’t a “done thing”, according to Jules Evans, policy director at the Centre for the History of Emotions at Queen Mary University of London. Evans is also director of the Challenging Psychedelic Experiences Project, which studies people who have extended difficulties following psychedelic use. “If I was a gambler, I would look for the odds on it not getting FDA approval, because it feels like the entire industry is betting that it will,” Evans added.
Ironically, Evans says that the biggest challenge to approval for MDMA, a banned party drug, is that it is paired in Lykos’ protocols with psychotherapy. “The FDA is not set up to assess psychotherapy,” said Evans. Predictable, standardized effects are a valuable asset in securing approval, but psychotherapy is an inherently personalized treatment that cannot easily be homogenized. Evans also mentions ethical issues that arose in Lykos’ psychedelic trials, including allegations of sexual assault during the drug’s Phase 2 trials. In the next year, we’ll know whether Lykos’ data will convince regulators that these issues are worth overlooking on the path to approval. “There’s a lot of pressure on this,” said Williams.
After legalization, what next?
In 2024, scientists and the general public will both grapple with the consequences of psychedelic legalization. The hype and promise around psychedelic drug trials have accelerated legislation to liberalize access to these compounds. In the US, Oregon and Colorado have set out ahead of other states. Both states have legalized psychedelic-assisted therapy while decriminalizing or drastically reducing penalties on the personal possession of drugs. June 2023 saw the opening of Oregon’s first psilocybin service center in Eugene. One month later, and 8,000 miles away, Australia’s regulator, the Therapeutic Goods Administration (TGA) reclassified psilocybin and MDMA, allowing them to be prescribed by authorized psychiatrists.
Evans says that legalization or decriminalization measures could spread to other states – particularly California – this year. The shape and scope of that legislation will be crucial, he adds, pointing to criticism of the Oregon system. “Some people think that this is a bad piece of legislation because it has legalized psychedelics but facilitated by people without medical training,” he explained. A paper published in the journal Psychiatric Services by psychiatrist Dr. Brian Holoyda warned that Oregonian facilities were setting themselves up for litigation and that the legislations that legalized the clinics, ORS 475A and OAR 333-333, are “rife with flaws”.
Psychedelic drug development has attempted a delicate balancing act between ensuring rigor in trials while drumming up enough hype to secure investment and wider public interest. How quickly legalization efforts move in 2024 – and whether any backlash emerges – will show how well that balance has been struck.
“Ineffable” experiences power new drug options
While psilocybin and MDMA wrestle with the consequences of their rapid movement through clinical trials, other psychedelics remain at earlier stages in the development process. These compounds have unique properties, which developers see as routes to bypassing some of the limitations faced by more advanced drugs.
One of these compounds, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), was mentioned by more than one of our interviewees. This compound, a relative of DMT, is secreted by the Colorado River toad and is produced by many plant species.
“It’s triggered a lot of interest,” said van Elk. The drug produces intense but short-lived hallucinations. “It’s an experience of only 10 to 15 minutes,” he added. “Many people are now interested in applying this for depression and addiction, etcetera.”
The compound’s uptake reflects a desire by drug companies to find a compound that shortens the 6–8-hour trip induced by psilocybin and other psychedelics. These long durations severely limit the compounds’ flexibility and massively increase their potential cost to insurers.
Van Elk, true to form, remains skeptical of the drug’s potential. The drug’s effects are “completely ineffable,” he added. Unlike the geometric patterns or distortion reported by users of LSD or mescaline, 5-MeO-DMT produces almost no visual effect, but instead users experience a dissociative state. Van Elk quotes Michael Pollan’s seminal book, How to Change Your Mind, saying the drug is like a “nuclear blast happening inside your mind.” The experience, says van Elk, can be difficult to make sense of. For people with little prior psychedelic usage, “I find it difficult to see how that could be of benefit,” he said.
He does add one exception to this rule, however. Perhaps this ego-wiping psychic bombshell could help people facing end-of-life anxiety. “It’s basically giving users a near-death experience, right?” said van Elk. “I would be particularly interested in whether it can reduce fear of death from a life-threatening illness.” Even as some psychedelics continue to hog the limelight, other compounds will continue to be explored into 2024.
Beyond the peak of psychedelic hype?
Psychedelics’ hype engine has fired the field’s rapid progress over the last decade. But excitement among the general public, media and overzealous researchers has often threatened to undermine the field too. By heaping pressure on lawmakers to legalize compounds, hype has made it more likely that poor legislation, that puts patients at risk, will be passed. Further, hype has created expectancy issues that likely inflate the effectiveness of psychedelics in clinical trials, an effect that sets the compounds up for failure when those same efficacy levels are not met in non-clinical settings.
According to Van Elk, we might finally be past the peak of psychedelic hype. “I really see a kind of backlash, indeed, in the discourse around psychedelics and also an increased attention in the scientific community to adverse events,” he said. This has been reflected in the plummeting value of many psychedelic startups, even as big pharma companies circle the field, unsure of whether to take the plunge into a volatile market.
As legalization efforts accelerate, compounds reach the cusp of approval and new, powerful drugs are explored, a bit of post-hype skepticism might be exactly what the field needs, says van Elk. “Now we see a corrective mechanism, with more sober and realistic conversation about what psychedelics potentially can do for the mental health system,” he concluded.