Norrsken Mind is supporting the Open Psilocybin Study (OPS), an innovative multi-session experimental study at Leiden University and the Centre for Human Drug Research (CHDR), designed to investigate how low-to-medium doses of psilocybin affect the brain, body, and self-perception compared to placebo. The study will recruit 40 healthy participants and is led by Associate Professor Michiel van Elk, in collaboration with researchers at the CHDR.
Psilocybin, the psychoactive ingredient in magic mushrooms, has shown therapeutic potential for conditions such as treatment-resistant depression, addiction, and end-of-life anxiety. Yet, the broader scientific literature still faces key methodological limitations, including small samples, reliance on self-report, placebo effects, and difficulties maintaining blinding. This hinders our understanding of how the subjective and therapeutic effects of psilocybin come about.
To address these problems, OPS is designed as a stand-alone mechanistic study in healthy participants. Using robust within-subjects, double-blind, placebo-controlled crossover design involving four closely spaced small-to-moderate doses (0, 5, 10, 15 mg), OPS enables the team to test how psilocybin affects the brain, body and self-perception and pharmacodynamics, while systematically investigating placebo- and dose-guessing effects.
Participants undergo multiband fMRI to assess brain activation and resting-state connectivity, alongside pharmacological and psychophysiological measurements. Behavioral tasks, including state-of-the-art experimental techniques to probe how psilocybin induces changes in body perception (e.g., feelings of connectedness and ego-dissolution). Subjective experiences are captured using validated measures and a newly developed self-perception scale.
The study also sets a new benchmark for methodological transparency. OPS integrates preregistration, Bayesian statistics, open sharing of data and protocols, and a many-analyst approach involving adversarial collaborators, ensuring that findings are robust, replicable, and free from researcher bias. The results aim to clarify the mechanisms underlying low- and medium-dose psilocybin effects, a dose range relevant for emerging psycholytic therapy models, that place more contrast on the importance of the therapeutic process than the psychedelic experience alone.
By combining advanced neuroimaging, psychophysics, and open-science practices, OPS contributes important foundational insights to inform future clinical trial design and the development of safe and effective psychedelic-assisted interventions.
Project Leads
Collaborators: dr. Gabriël Jacobs, dr. Laura Borghans, Soma Makai-Bölöni, Alissa, Haj Yahya, Centre for Human Drug Research
