Magic mushrooms could reap a consciousness-expanding harvest of billions of dollars if psilocybin is approved to treat severe depression, leading to a host of other applications.
Mental health disorders including anorexia, bipolar type II depression, body dysmorphic disorder and chronic cluster headaches are the next targets for the treatment, known as COMP360, being developed by Nasdaq-listed COMPASS Pathways PLC. Psilocybin — derived from the active compound found in magic mushrooms and first synthesized by Swiss scientist Albert Hofmann in 1958 — is the only medicine in the London and New York-based company's pipeline, but the company intends to expand to other psychedelics in time, CEO George Goldsmith told S&P Global Market Intelligence.
Although the mushroom had been used for hundreds of years by indigenous people in South America as part of religious rituals, Hofmann, who accidentally discovered LSD in 1938 while isolating compounds in medicinal plants at the Swiss laboratories of Sandoz Inc., was the first to develop a synthetic version. Promising early use of psilocybin by psychiatrists for alcoholism and other addictions was halted after U.S. authorities became concerned with increasing recreational abuse of psychedelics in the 1960s and the attention generated by Timothy Leary's Harvard Psilocybin Project.
But the lack of meaningful advances in treating a host of psychiatric disorders and addictions by conventional pharmaceutical companies sparked a renewed interest in psilocybin in the 1990s at academic institutions including Johns Hopkins University and Imperial College London. In 2016, researchers at Imperial carried out the first-ever study into the effects of psilocybin using modern brain imaging. Neuroimaging studies into MDMA and DMT — the psychoactive compounds found in ecstasy and the hallucinogenic plant ayahuasca — are also ongoing.
"All my work in depression and other disorders has come from the brain imaging: We showed that, to our amazement, this drug switches off the parts of the brain that we know are overactive in depression," David Nutt, Edmond J. Safra professor of neuropsychopharmacology at Imperial, said in an interview with S&P Global Market Intelligence. "The clinical effects are profound and that meant Compass got interested."
Capitalizing on Spravato
The effect of psilocybin on the brain.
Source: Compass Pathways PLCIn addition to ongoing studies of a single dose administered in a closely supervised session, Compass intends to complete a phase 2 trial of COMP360 and traditional antidepressants, or SSRIs, to confirm COMP360 works best alone. Approval and a possible U.S. launch in 2024 will allow the company to capitalize on the first U.S. approval ever for a psychedelic medicine, Johnson & Johnson's ketamine-derived nasal spray for treatment-resistant depression called Spravato, or esketamine, in 2019.
Berenberg analyst Esther Hong believes COMP360 could generate $2.7 billion in peak U.S. sales by 2032, with 2.7 million adults initially eligible. Hong assumes an annual price of $22,000 per patient with a 6% annual increase, compared with $33,000-$49,000 for esketamine. While Compass' CEO referred to accountable care models in the U.S., he would not be drawn on pricing.
Hong said the drug could capitalize on the shortcomings of the esketamine launch to achieve higher penetration, "including leveraging the infrastructure created by esketamine clinics, and better reimbursem*nt codes specific to psilocybin-assisted therapy." Furthermore, full reimbursem*nt for the psychological support sessions before and after dosing, and psilocybin therapy-specific reimbursem*nt codes, could potentially make COMP360 a more attractive therapy compared to esketamine and electroconvulsive therapy if costs are reasonable, Hong said in a research note.
It doesn't last forever
But while the impact of psilocybin on the brain is clear, the length of its duration and how often it might need to be administered has yet to be clarified. Nutt said the mood results were "spectacular, the most powerful impact of a single treatment drug on resistant depression ever seen."
"It was a concept-shattering discovery and people were much improved, some even cured, within a day of taking psilocybin — people who had been ill for two decades," the professor said. "The problem, and this is the problem we're all facing now, is it doesn't last forever."
Nutt has carried out a head-to-head study comparing psilocybin with an antidepressant called Lexapro and the results are expected imminently. One idea is that patients with severe depression receive psilocybin every 4-6 months or an SSRI is introduced as the effects wear off and the depression sneaks back.
"We've got very nice data suggesting that SSRIs work very differently, [on] different parts of the brain even, to psilocybin. That's what interests me: the brain mechanisms," Nutt said.
The professor believes people with so-called internalizing disorders will respond well to psilocybin, as it breaks down the brain process that locks those with obsessive compulsive disorder, anorexia and drug addiction into a certain mindset. In other words, it resets the brain.
Some 340 million people globally live with depression, which is the most common mental health disorder, according to the World Health Organization. With an estimated $71 billion spent on ineffective treatments — SSRIs are estimated to only be effective in about 40%-50% of people and can have side effects — there is an urgent need for new therapy options.
Hesitance regarding the use of psilocybin in psychiatry stems from early studies that did not involve consistent rigorous scientific controls and showed that they are not universally beneficial.
"In vulnerable brains, especially in uncontrolled and unsupported environments, psychedelics can induce or exacerbate paranoid and disordered thinking," John Kelly, of Trinity College Dublin's department of psychiatry, wrote in the Irish Journal of Psychological Medicine in 2019.
"Irrespective of psychiatry's future trajectory, psychedelic research, provided it progresses in a scientific and evidenced-based manner, will advance our understanding of the human brain," said Trinity's Kelly, who is carrying out a phase 2 trial at Tallaght University Hospital in Dublin, funded by Compass.
"In parallel, and of greater importance, psychedelic-assisted psychotherapy, or psychotherapy-assisted psychedelic treatment, may offer a powerful therapeutic tool that, if used correctly, may benefit many people," Kelly added.
