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High hopes: Psychedelics and mental health Exploring the potential of psychedelics in mental health treatment with Dr John R Kelly , psychiatrist and Associate Professor at Trinity and Tallaght University Hospital
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T here has been academic research into psychedelics since the 1940s but, according to Dr John R Kelly, a leading researcher in the field, we still don’t fully understand how they work: ‘What we do know is that psychedelics activate certain serotonin receptors in the brain, can alter brain connectivity, and appear to change neuroplasticity. These effects suggest real potential for using psychedelic therapy to treat various mental health conditions, including depression, anxiety, and substance use disorders.’ Driven by this potential, Dr Kelly and his team have established the Psychedelic Research Group at Trinity and Tallaght University Hospital. ‘We first got involved six years ago when we became the Irish site for Compass Pathways’ phase two trial in psilocybin therapy for treatment-resistant depression,’ Dr Kelly explains. ‘Psilocybin is the psychoactive compound in magic mushrooms. Other psychedelics frequently used in research include ketamine and MDMA.’ Compass Pathways, a biotechnology company, conducts trials internationally, with sites across the USA, UK, and Europe. In the phase two trial, participants received a single dose of psilocybin – either 1 mg, 10 mg, or 25 mg – accompanied by psychological support before, during, and after the administration. ‘Among those receiving the highest dose, approximately 40% showed a significant response, with their depression scores improving by 50% or more,’ says Dr Kelly. This is a more realistic figure than the inflated claims that were being made in early days of the research renaissance into psychedelic therapy. ‘Our current position, based on the best available evidence, is that for some patients, psychedelics could indeed offer therapeutic benefits, particularly when administered in a supportive environment with psychological backing.’ Dr Kelly is now participating in phase three clinical trials with Compass Pathways, a crucial step in determining whether psilocybin therapy will become an approved treatment. He notes, ‘The road to approval for any new medication is arduous, and it may be several years before psychedelic therapies are offered routinely. There are significant challenges ahead, such as the difficulty of blinding the effects of psychedelics in trials and the variability in how individuals respond to these substances.’ This variability was evident across all trial groups and even within the same doses of psilocybin. ‘Such differences are not entirely surprising,’ Dr Kelly explains, ‘given the complexity of people and of conditions like depression. Not everyone responds to conventional treatments such as SSRIs, and responses to psychedelics are particularly variable. A key area of interest for us is understanding the relationship between the subjective experiences induced by psychedelics – such as feelings of oceanic boundlessness or emotional breakthroughs – and the therapeutic outcomes. Why do some people experience these profound effects while others do not?’ Another intriguing aspect of the research involves the potential combination of psychedelics with existing treatments for depression, such as SSRIs: ‘In the phase two Compass trial, participants were required to discontinue their antidepressants to participate. However, in another study we were involved in where participants remained on their SSRIs, the response rate to psychedelic therapy was roughly the same. Although this study involved only 19 participants and larger studies are needed, it raises an important question: could combining psychedelics with existing therapies offer a broader range of treatment options, particularly for those hesitant to stop their current medications?’ Looking ahead, Dr Kelly sees the therapeutic effects of psychedelics likely extending to several disorders, meaning they will have transdiagnostic effects. With funding from the HRB, his group is preparing to launch a pilot feasibility study called POSITRON, which will explore the use of psilocybin as a therapy for cocaine use disorder: ‘Sponsored by Trinity, this study aims to begin recruiting participants next year and marks the first European exploration of psilocybin therapy for this condition.’ This new study builds on promising research into the use of psychedelics for treating alcohol use disorder and smoking. Dr Kelly mentions collaborations with experts like Peter Hendricks from the University of Alabama at Birmingham, who is conducting exploratory studies into cocaine use disorder. ‘The pilot study, like others in this field, will incorporate therapy with trained therapists before, during and after the psilocybin dosage,’ he explains. ‘Participants will be encouraged to lie down, wearing an eye shade and headphones, often listening to curated playlists, typically featuring tribal music, as they journey inward during their experience.’ For many patients, conventional treatments are ineffective, leading to significant suffering for them and their families. ‘I’m delighted that we’re at this stage of building a Psychedelic Research Group at Trinity and Tallaght University Hospital,’ Dr Kelly reflects. ‘Our goal is to create a centre of excellence for psychedelic research in Ireland, fostering national and international collaborations, to bring high-quality psychedelic therapy to patients across the country.’
