While the psychedelic renaissance continues to gather steam, there is a growing uneasiness about the pace of the industry development.
The excitement has been fueled specifically by three events: the report of MDMA going into Phase 3 clinical trial, the final phase of research on the road to FDA approval; the development of legalized psilocybin programs in Oregon (Measure 109) and elsewhere in the country; and the movements to decriminalize certain psychedelics that now includes 20 states (or a local government within the state) either already decriminalizing or looking into doing it soon.
There are 24 psilocybin clinical trials that have either begun or are recruiting in 2022 alone; and there are six new MDMA clinical trials this year, among 60 clinical MDMA trials since 2010.
Not So Fast
But not everyone is on board with the pace of development. The voice of the Oregon Psychiatric Physician Association was clear on the matter: “We remain concerned that psilocybin is not FDA approved, clinical trials are still ongoing, and psilocybin administration would not require medical oversight for the treatment of Oregonians with mental health conditions,” adding that “Measure 109 is unsafe and makes misleading promises to Oregonians who are struggling with mental illness.”
Some Oregon counties are also saying “not so fast.” For example, Umatilla County in eastern Oregon will be putting another vote on the November ballot to ban psilocybin manufacturing and service centers. Linn County and Jackson County in Oregon are planning a similar referendum—even as a city in Jackson County, Ashland, is planning a psilocybin therapeutic retreat.
Other issues relate to the research structure itself. There have been complaints and observations about the proper blinding of participants in psychedelics trials—because of the profound effect of psilocybin or other psychedelics, it is argued that any participant can easily identify if they have taken a placebo or not.
Some clinical trial participants even reported that they feel the psychedelic effect from the placebo alone, with a study reporting that the current trend towards micro-dosing may have a strong placebo component due to widespread cultural expectations. “While psychedelic randomized control trials (RCT) have generally shown promising results, with large effect sizes reported, we argue that treatment effect sizes in psychedelic RCTs are likely over-estimated due to de-blinding of participants and high levels of response expectancy,” one study concluded. “Careful attention should be paid to clinical trial design and the instructions given to participants to allow these confounds to be reduced, estimated and removed from effect size estimates. We urge caution in interpreting effect size estimates from extant psychedelic RCTs.”
And researchers are still not exactly sure what is happening even after trials have been completed. “There’s a lot that psychiatry can learn from psychedelics, not only related to social processing,” Katrin Preller, a neuropharmacology professor at Yale University told Mind Foundation in an interview. “But we have a major knowledge gap here, and that is about the exact mechanism of action: Why do these substances help people? I think figuring out what exactly it is that psychedelics do to help patients can have a huge impact on psychiatry.”
Another study funded by the Imperial College London’s Centre for Psychedelic Research revealed that psilocybin may have antidepressant properties, but that “direct comparisons between psilocybin and established treatments for depression are lacking,” calling for “larger and longer trials” to compare psilocybin with established antidepressants.
So there’s an uneasy balance of going forward faster, teetering between the need for more careful research on a group of classic and powerful psychedelics, and the huge and growing demand for new and novel treatments for mental health issues.
Over 47 million Americans—19 percent of American adults—are experiencing a mental issue, according to statistics from a 2021 Mental Health America report. Of that figure, almost half (26 million) are not getting mental health treatment.
Investors and business developers say that is why the psychedelics industry should ramp up developments. In 2021 alone, 45 different investments led to a $595 million windfall into the psychedelic medicine industry, according to The Guardian. By 2029, the industry is expected to nearly triple what it was in 2021—up to $6.4 billion.
“Neuropsychiatry is desperate to find effective medicines for treating diseases such as depression and PTSD which are among the greatest contributors to disability worldwide,” David Olson, professor in the Department of Chemistry, University of California, Davis, wrote in a pharmacology science publication. “While psychedelics have demonstrated enormous promise for combatting these illnesses, we must guard against hype, move cautiously toward therapeutic applications, and most importantly, conduct psychedelic research with the rigor demanded of modern science.”
October 5, 2022 at 9:03 am
Thank you for the article, David. Regardless of the potential positive impacts of psilocybin it is crucial to maintain scientific rigor when assessing the drug. To me, the most important takeaway from the dozen or so clinical trial summaries and meta-studies is that the rate of serious adverse events is near or at zero, and the rate of adverse events is low single digits. We will never overcome the unblinding problem with psilocybin, so the effect size is going to be difficult to know with a high degree of accuracy, but the downsides seem limited. That said, longer-term studies need to be completed to make sure we are capturing all side effects. Thanks again. We need people like you who take a cautious view so we don’t get carried away and make bad decisions.