Psychopharmacology
September 5, 2022
Matthew Butler, Luke A. Jelen, James Rucker
91 citations
Expectancy and unblinding in psychedelic trials likely cause overestimation of treatment effects, but this problem is not unique to psychedelics. The authors argue that premature hype directly inflates participant expectations, yet placebo-controlled RCTs are imperfect for many therapies and blinding issues should not automatically disqualify medications from approval. Practical measures like independent raters and active placebos can partially mitigate these effects, and alternative methods such as naturalistic studies can supplement RCT results. Early data should neither be dismissed nor taken as firm evidence of effectiveness.
Frontiers in Psychiatry
June 9, 2021
Simon Ruffell, Nige Netzband, WaiFung Tsang et al.
74 citations
A naturalistic study of 63 people who participated in ayahuasca ceremonies at a retreat in the Peruvian Amazon found significant improvements in depression, anxiety, and overall psychological distress, along with increased self-compassion, immediately after the retreat and sustained at six months. Depression scores on the Beck Depression Inventory dropped from 13.9 to 6.1, anxiety scores on the State-Trait Anxiety Inventory fell from 44.4 to 34.3, and scores on the Clinical Outcomes in Routine Evaluation-Outcome Measure decreased from 37.3 to 22.3. Changes in memory valence were linked to these improvements. Epigenetic results were inconclusive but suggested further research on the SIGMAR1 gene is warranted.
Therapeutic Advances in Psychopharmacology
January 1, 2020
Matthew Butler, Mathieu Seynaeve, Timothy R. Nicholson et al.
38 citations
Functional neurological disorder (FND), previously called conversion disorder, is common in neurology clinics and causes substantial disability, but treatment options are limited. Psychedelics like psilocybin and LSD may help by altering brain circuits involved in self-representation, which is thought to be disrupted in FND. A systematic review of nine studies from 1954 to 1967, involving 26 patients, found that most received psychotherapy with variable adjunctive psychedelic use (psycholytic therapy). Of those treated, 69% (18 patients) showed at least some recovery on subjective clinician-rated criteria. Adverse events were mostly mild, though one patient withdrew due to distressing effects. All studies were low quality, lacking controls and valid outcome measures, so no conclusions on efficacy can be drawn.
Headache The Journal of Head and Face Pain
September 20, 2024
James Rucker, Sadie Hambleton, Catherine Bird et al.
12 citations
A small open-label trial tested low doses of psilocybin (5, 7.5, and 10 mg) with psychological support in four patients with chronic short-lasting unilateral neuralgiform headache attacks (SUNHA), a severe headache disorder. The study was terminated early due to recruitment difficulties; three participants completed all sessions. No significant adverse events occurred. Cognitive testing during the acute drug experience was not possible because participants reported high subjective dose intensity. Headache impact remained severe throughout the trial. Mean daily attack frequency decreased by more than 50% in two participants at final follow-up. Thematic analysis of clinical notes suggested psychological insights, including reconfigured relationships to headache pain, were key features of participants' experience. The clinical results provide no conclusive evidence for psilocybin in SUNHA.
Acta Neuropsychiatrica
November 4, 2025
Chiranth Bhagavan, Alexander Bryson, Olivia Carter et al.
4 citations
Combining psychedelics with physiotherapy may offer a new treatment for motor functional neurological disorder (FND), a condition with no effective medications and often persistent disability. This protocol describes the first trial testing two psilocybin-assisted physiotherapy regimens in 24 people with refractory motor FND. Participants are randomly assigned to either 15 mg psilocybin with movement tasks during the drug's acute effects or 25 mg psilocybin alone. All receive two physiotherapy sessions before dosing and six after, with follow-ups at one and four weeks. The study assesses tolerability, feasibility, symptom severity, and brain imaging to inform a larger definitive trial.
Wellcome Open Research
April 22, 2025
Matthew Butler, Catherine Bird, Carolina Maggio et al.
3 citations
Functional neurological disorder (FND) is a common, debilitating condition linked to abnormal brain networks, dissociation, interoception, and motor agency. This open-label neuroimaging protocol will administer 25 mg of oral psilocybin with psychological support to 24 people with chronic FND. Resting-state and task-based functional MRI sequences will be compared before and after psilocybin. Additional measures include interoception, somatisation, illness perceptions, suggestibility, and dissociation. Participants will be followed for three months. The study aims to probe mechanisms underlying FND and assess the safety and feasibility of psychedelic administration with psychological support in this population.
Psychiatric Research and Clinical Practice
July 23, 2024
Chiranth Bhagavan, Richard Kanaan, Olivia Carter et al.
2 citations
A protocol for the first study testing whether movement tasks can be performed safely while under the influence of psilocybin. Twelve healthy participants will each receive three different doses (5 to 20 mg) in a randomized, blinded order at least one week apart. Motor function, safety, brain activity via fMRI, and subjective experience will be measured during the acute drug effects. The study aims to inform future research combining psychedelics with motor retraining for conditions involving motor dysfunction.
Frontiers in psychiatry
January 1, 2023
Simon G D Ruffell, Nige Netzband, WaiFung Tsang et al.
1 citation
correction
This is a correction notice for a previously published article. It provides no new findings, arguments, or data.
Journal of psychopharmacology (Oxford, England)
June 16, 2026
Alice Caulfield, Matthew Butler, Mitul A. Mehta
Psychedelics show promise for treating neuropsychiatric conditions, but their Schedule 1 status creates regulatory and economic hurdles for research. Rigorous human mechanistic studies are needed to understand how psychedelics produce therapeutic effects. This article offers practical guidance on study design, legislation, and drug sourcing, based on the authors' experience setting up non-clinical studies in the UK. The guidance aims to help researchers navigate the complex process of establishing human psychedelic studies, with some content applicable to investigator-initiated studies more broadly.