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.
Journal of Neuropsychiatry
May 17, 2022
Matthew Butler, Mathieu Seynaeve, Abigail Bradley‐Westguard et al.
6 citations
Almost half of people with functional neurological disorder (FND) report having tried legal psychoactive substances—nicotine, alcohol, and cannabidiol—to manage their symptoms, finding them modestly effective. Fifteen percent have used illicit substances, mostly cannabis, reporting moderate effectiveness and minimal side effects. Many respondents (46%) would be willing to try medically supervised psychedelic therapy if proven safe and effective. The findings highlight that people with FND often seek alternative symptom management outside usual medical care and suggest that further research into novel treatments, including psychedelics, may be warranted.
Wellcome Open Research
January 1, 2024
Matt Butler, Catherine Bird, Carolina Maggio et al.
4 citations
Functional neurological disorder (FND) causes seizures and movement disorders, is debilitating, and often has a poor prognosis. Brain imaging suggests FND involves multiple networks, and mechanisms like dissociation and abnormal motor agency may play a role. Psychedelics disrupt brain networks and are being tested for neuropsychiatric disorders. This open-label neuroimaging study will give 25 mg oral psilocybin with psychological support to 24 people with chronic FND. Resting-state and task-based fMRI, plus measures of interoception, somatisation, and dissociation, will be collected before and after psilocybin, with three-month follow-up. The study aims to probe FND mechanisms and assess safety and feasibility of psychedelic administration in this population.
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.
Translational Psychiatry
April 24, 2026
Matt Butler, Ellen Moore, James Rucker et al.
1 citation
Hallucinogen persisting perception disorder (HPPD) involves episodes of altered perception after past psychoactive drug use, causing distress and impairment. In a large retrospective cohort study using electronic health records from 25,778 individuals diagnosed with HPPD, high rates of prior comorbidities were found, including depressive episodes (29.2%), anxiety disorders (26.2%), chronic pain (15.9%), headache syndromes (14.7%), post-viral fatigue (12.3%), ADHD (6.6%), and fibromyalgia (6.7%). Anxiety and functional somatic syndromes were more common in HPPD patients than in psychedelic-using controls. Anxiety (odds ratio 1.5) and post-viral fatigue (odds ratio 1.9) predicted HPPD development among psychedelic users. After diagnosis, HPPD was associated with increased risk of subsequent functional somatic syndromes (odds ratio 2.0) and psychiatric disorders (odds ratio 1.4) compared to psychedelic-using controls.
Journal of Neurology Neurosurgery & Psychiatry
July 20, 2020
Matthew Butler, Mathieu Seynaeve, Timothy R. Nicholson et al.
Functional neurological disorder (FND) causes significant disability, yet treatment options are limited. A systematic review of nine studies from 1954–1967 involving 26 patients found that psychedelics, primarily LSD (25–2,000 mcg) and psilocybin (3–15 mg), were used alongside psychotherapy. After treatment, 69% of patients showed at least some recovery, and 23% fully recovered. Adverse events were mild and transient. Although the studies were low quality and lacked control groups, the degree of improvement suggests psychedelics may be a promising treatment for FND, warranting modern research.
Frontiers in Psychiatry
July 20, 2026
Bruce Tamilson, Michael Chitolie, Jan Coebergh et al.
Functional neurological disorder (FND) is a common and disabling condition with limited effective treatments. This systematic review synthesized evidence on ketamine and esketamine use in FND. Thirteen studies were identified, mostly case reports and small case series. Some patients showed improvement in functional motor symptoms, functional dissociative seizures, and other presentations after receiving ketamine or esketamine. However, interpretation is limited by uncontrolled study designs, heterogeneous diagnoses and outcomes, and potential publication and expectancy bias. Adverse effects were variably reported but generally transient in supervised settings. The evidence is insufficient to establish efficacy, though the data suggest that further prospective controlled trials are justified.
The lancet. Psychiatry
May 1, 2026
Joseph J Taylor, Balázs Szigeti, Noah D Silverberg et al.
Placebo effects remain a major paradox in medical research, with more data available from placebo-controlled trials than on any treatment, yet little deep analysis of how they are measured, appraised, and interpreted. This review shifts focus from clinical practice to clinical trials, examining established and emerging approaches for managing placebo effects in randomized controlled trials. It highlights three key challenges in contemporary psychiatric research: blinding and expectancy in psychedelic trials, large placebo responses in interventional psychiatry trials (device or procedure-based treatments), and the implications of overlapping neurobiological mechanisms between placebo effects and psychiatric treatments.