For a generation that grew up with “Just Say No” as a recurring theme, the idea of taking psychedelics with nicknames such as acid (LSD), magic mushrooms (psilocybin), Special K (ketamine) and ecstasy (MDMA) suggests uncontrolled hallucinations and all the danger that might go with them, but that predisposition is changing. As a mental health epidemic continues to plague the population, researchers are considering new avenues of treatment – or in the case of psychedelic substances, novel approaches to an old idea. Psychedelic substances have long been known as “mind-altering drugs,” but researchers are exploring how those mind-altering properties can rewire neural pathways with a positive effect.
The Unmet Need
Drug therapy for mental health disorders hasn’t seen innovation since the selective serotonin reuptake inhibitors (SSRIs) of the 1980s. “There are plenty of people who wouldn’t be here if it weren’t for SSRIs,” says Fred Barrett, a cognitive neuroscientist at the Johns Hopkins Center for Psychedelic and Consciousness Research. Even those innovative drugs had significant limitations.
When doctors prescribe Prozac, an SSRI, to treat depression, the patient needs to titrate up, and may not feel its effects for as many as six weeks. If the medicine isn’t working for them, patients need to taper off before trying another SSRI. Even those prescribed an SSRI who achieved a desired response often experienced side effects such as weight gain, depleted libido and sleep issues. This slow-paced trial and error, with associated side effects, has been the dynamic in mental health drug therapies for decades, but when it comes to therapies based on psychedelic drugs, the paradigm may change.
Studies in the mid-2010s of psychedelics, specifically psilocybin, by respected institutions including the University of California, Los Angeles, Johns Hopkins University, New York University, Imperial College London, and the University of Zurich, demonstrated rapid and enduring effects when treating small groups of patients with treatment-resistant depression and existential distress (the psychological turmoil people may feel when facing death).
Patients not only saw initial benefit, but experienced lasting effects after just one or two doses without the side effects associated with SSRIs. “That really changes the entire model on how we approach and treat psychiatric disorders,” says Barrett, who was a co-author of some of the first studies.
From “On the Street” to Main Street
Psychedelics as well as other “illicit substances” are slowly making their way into the mainstream of mental health therapies. In 2019, Johnson & Johnson’s Janssen Pharmaceuticals received U.S. Food and Drug Administration (FDA) approval for Spravato for treatment-resistant depression. The nasal spray, which is prescribed in tandem with an antidepressant, contains the S enantiomer of ketamine. This drug is used as an anesthetic, but is also a known “party drug” under the moniker Special K. While not a psychedelic compound, ketamine is a substance previously known for abuse, now used to treat mental illness.
In 2021, researchers from the Multidisciplinary Association for Psychedelic Studies (MAPS) published results of a Phase III clinical trial in Nature in which patients diagnosed with post-traumatic stress disorder (PTSD) took three doses of MDMA (a party drug known as ecstasy) four weeks apart along with psychotherapy. Patients experienced rapid and sustained improvement for as long as two months after treatment. Dr. Bryan Roth, who studies the pharmacology of psychoactive substances at the University of North Carolina at Chapel Hill, treated veterans with PTSD and says the rapid and sustained improvement experienced with MDMA in the Phase III trial are astounding in comparison with current treatment options. “There was nothing we could offer them that did much of anything.” Even if MDMA is only partially effective when larger trials are conducted, Roth says, the results will still be “a huge advance for psychiatry.”
Even with early indications of the possible benefits of psychedelic drugs in clinical trials, skeptics remain. Steven J. Zalcman of the National Institute of Mental Health acknowledges that the current options for many mental illnesses are only moderately successful but claims studies with psychedelics don’t necessarily show a clear therapeutic benefit. “From the NIH’s point of view, the rigor underlying those trials has not really been sufficient to justify that sort of conclusion.”
Social Stigmas Make Way for Logistical Challenges
In addition to differences in viewpoint about the clinical benefit, adding psychedelics as a treatment option for mental health disorders faces other challenges:
- The Catch-22 of regulated substances. In the U.S., psychedelics are classified as Schedule I Illegal Drugs, meaning they are prone to abuse and have demonstrated no medical benefit. Because they are Schedule I, it is exceedingly difficult to obtain permission from the U.S. Drug Enforcement Agency (DEA), to use these substances in clinical trials. Without the clinical trials, it is impossible to prove these substances have medical benefit. Some argue that the regulation of Schedule I substances in clinical trials should be managed by a scientific body, rather than an agency that was developed to prevent abuse of substances, but that change remains to be seen.
- When they know it is a placebo. The gold standard in determining efficacy is a double-blind clinical trial, where a control group receives a placebo. Aidan Hampson, a senior adviser at the NIH’s National Institute on Drug Abuse explains that participants can quickly ascertain whether they’ve received an active drug or a sugar pill, making it difficult to definitively attribute any improvement to the medicine. The way researchers are addressing this challenge is to eliminate the true placebo group and have one group take a very low dose of the active drug.
- Not being able to include people who might benefit from the medicine. There are populations that researchers suspect could benefit from the therapy, such as patients with bipolar disorder, which can’t participate in clinical trials. These patients are disqualified because bipolar disorders put them at greater risk of a psychotic episode after taking a psychedelic, but researchers argue that is the exact reason they should be included. If they aren’t represented in clinical trials, there is no way to determine if psychedelics could help treat the disorder.
- And at what cost? Both clinical studies and treatment regimens based on psychedelics can be expensive. The cost of MDMA-assisted PTSD psychotherapy ranges from $4,000 to $20,000 per patient. That said, more than 90% of that cost are fees associated with the intensive therapy that goes with administration of the medicine. Depending on how long-lasting the therapeutic response is, the treatment might be more cost effective than conventional drug therapy, but much of that will be decided based on insurance companies’ willingness to pay the large, up-front cost – a dubious prospect at best.
Hats in the Ring
Despite these challenges, a number of researchers and pharmaceutical manufacturers have initiated studies with the hopes of bringing psychedelics to market as a much-needed added treatment option for mental health disorders. In Part 2 of this blog, we will review the studies in progress, researchers’ efforts to manufacture molecules for the desired effect without the “psychedelic experience,” as well as those funding the efforts and investing in the potential.
QPS is a GLP- and GCP-compliant contract research organization (CRO) delivering the highest grade of discovery, preclinical and clinical drug research development services. Since 1995, it has grown from a tiny bioanalysis shop to a full-service CRO with 1,100+ employees in the U.S., Europe and Asia. Today, QPS offers expanded pharmaceutical contract R&D services with special expertise in neuropharmacology, DMPK, toxicology, bioanalysis, translational medicine and clinical development. An award-winning leader focused on bioanalytics and clinical trials, QPS is known for proven quality standards, technical expertise, a flexible approach to research, client satisfaction and turnkey laboratories and facilities. Through continual enhancements in capacities and resources, QPS stands tall in its commitment to delivering superior quality, skilled performance and trusted service to its valued customers. For more information, visit www.qps.com or email [email protected].