Psilocybin 2.0: Why Do We Have Reason to Believe?

Research into psychedelics and the potential to treat mental health disorders.

Posted Dec 21, 2020

Damir Omerović/Unsplash
Source: Damir Omerović/Unsplash

by Dr. Thomas Insel

Mental health statistics are stark. Depression is the leading cause of disability and ill-health worldwide, affecting more than 300 million people. Somebody dies from suicide every 40 seconds and 20 more people attempt suicide in that time.

As the COVID-19 pandemic rages on, it brings with it a new wave of mental health stressors, exacerbating the existing mental health crisis.

We do have treatments, both medical and psychological. But they don’t work for everyone and, sadly, medical and psychological approaches are rarely combined to optimize outcomes. Too many people are not helped by existing medicines and very few have access to the kind of mental health care that integrates the best scientifically-based interventions.

Patients deserve better. One area of innovation has been focused around the combination of a psychedelic substance with psychotherapy, for example in psilocybin therapy. Research in psychedelic substances and their potential to treat rapidly a range of mental health disorders is one of the most exciting developments in clinical psychopharmacology. Combining these medications with psychotherapy could finally move the treatment field beyond the chronic divide between medication and psychotherapy, creating a much better option for patients.

It’s an approach that’s getting a lot of attention right now. Last month, Oregon voters passed Measure 109, or the Oregon Psilocybin Services Act, meaning Oregon will become the first state to formally legalize the medical use of psilocybin to treat mental health conditions in licensed facilities using registered therapists. This is a direct result of our growing mental health epidemic and the search for new treatment options and better patient outcomes.

What’s it all about? Psychedelic research was popular in the 1960s and then disappeared. Are we right to bring it back? Does it hold all the answers? And is it safe?

The History of Psychedelic Research

Psychedelics (from the Greek term meaning “mind-manifesting”) are drugs that cause an altered cognitive state or perception. Natural psychedelic compounds found in mushrooms, cacti, and other plants have a long history of medicinal use, potentially going back hundreds of years. From the middle of the 20th-century scientists also began developing drug products with psychedelic effects.

By the middle of the 1960s, more than 40,000 patients with mental illness were engaged in psychedelic research studies and treated with these synthesized drugs. But this clinical research was soon overtaken by the broader of these drugs to “turn on and tune out” in the cultural tumult of the late 1960s. As part of the War on Drugs, launched by President Nixon in 1971, regulators put many psychedelic substances (synthesized and natural) on restrictive “schedules,” describing them as unsafe, with potential for abuse and harm. Over the next two decades, research on psychedelics virtually stalled. But it didn’t go away.

A New Generation of Research

In the last decade, the growing need for innovation to tackle the global mental health crisis has sparked a more open debate about the lack of available treatments and a resurgence of interest in these once-promising psychedelics. Gone is the tie-dye culture of the “psychedelic '60s” and the use and misuse of these medicines as recreational drugs. Instead, psychedelic medicine is back in the scientist’s lab and a new generation of research is underway, originally with some bold and persistent pioneers, and now in a number of institutions including two major centers for psychedelic research that have been established at Johns Hopkins University in Baltimore and at Imperial College London in the UK.

Over the last three years, the FDA has given Breakthrough Therapy designation to three psychedelic research programs, one in MDMA (to MAPS, the Multidisciplinary Association for Psychedelic Studies in 2017) and two in psilocybin (to COMPASS Pathways in 2018 and to Usona Institute in 2019).

Psilocybin therapy in particular, in which synthesized psilocybin is administered in a healthcare setting with psychological support from specially trained therapists, is gaining traction in the medical research community as a highly promising innovation in the treatment of various disorders including depression, anxiety, and addiction. More than 20 clinical studies are currently underway to understand the therapeutic potential of psilocybin and its mechanism of action.

It’s too early to draw conclusions about psilocybin therapy, but preliminary results are promising. Combining psilocybin with psychological support in this way has been shown to provide rapid reductions in depression symptoms after a single dose, with effects lasting up to six months after treatment. In one psilocybin study, more than two-thirds of patients described psilocybin therapy as among the top five most meaningful experiences of their lives, alongside the birth of a child or the death of a parent, six months after their psilocybin therapy session.

We believe the benefits of psilocybin are largely derived from its mechanism of action. Psilocybin activates the serotonin system in the brain, notably the 5-HT2A receptors. These are particularly densely expressed in an area of the brain called the default mode network (DMN). This is not an anatomical circuit but a system of functional connections. Some have linked the DMN to the “ego”—a collection of cognitive, emotional, and behavioural patterns associated with the concept of self. We don’t know exactly how psilocybin works but one hypothesis suggests that when psilocybin activates local 5-HT2A receptors, the DMN shifts gears and new patterns of functional connectivity emerge across the brain. This leads to an experience that can be described as “ego-dissolution,” in which people look at their lives from a new vantage point, and not from the perspective of entrenched patterns, or established thinking.

The psychological support element of psilocybin therapy is as important as the psilocybin itself and is provided by specially trained therapists. The therapist’s role during the psilocybin session is to establish psychological safety, minimizing anxiety, and encouraging openness to all emerging experiences. The session takes place in a room designed to be ambient, comfortable, and calming, with therapists present throughout the entire experience. In the days following the psilocybin experience, therapists hold integration sessions to help patients process the range of emotional and physical experiences facilitated by psilocybin and to generate insights that can lead to cognitive and behavioural changes.

Meeting the Highest Standards of Scientific Integrity

What we know already about psilocybin suggests it holds great potential as a medicine when combined with psychological support. However, we can’t rely solely on anecdotal information or the studies conducted in the 1960s and more recently in academic centers. Before we move to patient populations of hundreds of thousands of people, we will need strong evidence and robust data generated in large-scale clinical trials that meet the highest standards of scientific integrity. We must work carefully to set the right standards and to balance the rush for action with the Hippocratic medical oath of “first, do no harm.” 

Having worked in the mental health field for most of my professional life, I have seen firsthand the suffering among those affected by mental health challenges who are not helped by the existing system and existing therapies. Psilocybin therapy, bridging medication, and psychotherapy, are some of the most hopeful things I have seen in a while. We’re not there yet, but by continuing with clinical trials and evidence-based research, we have the opportunity to provide a solution for one of the world’s greatest healthcare challenges. I think that’s something worth waiting for.

Image Courtesy of Dr. Thomas Insel
Source: Image Courtesy of Dr. Thomas Insel

Thomas R. Insel, M.D., is a psychiatrist and neuroscientist who served (2002-2015) as Director of the US National Institute of Mental Health (NIMH), the component of the US National Institutes of Health (NIH) committed to research on mental disorders. He is also a member of the US National Academy of Medicine. He is Co-founder of Humanest Care and is an investor in and scientific advisor for COMPASS Pathways plc.

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