Safety, tolerability, and clinical and neural effects of single-dose psilocybin in obsessive–compulsive disorder: protocol for a randomized, double-blind, placebo-controlled, non-crossover trial

Abstract

BackgroundPsilocybin may help treat obsessive–compulsive disorder (OCD). To date, only one open-label study of psilocybin for OCD exists, necessitating further investigation with a randomized controlled design. The neural correlates of psilocybin’s effects on OCD have also not been studied.ObjectivesThis first-of-its-kind trial aims to evaluate the feasibility, safety, and tolerability of psilocybin in the treatment of OCD, provide preliminary evidence on the effects of psilocybin on OCD symptoms, and elucidate neural mechanisms that may mediate psilocybin’s effects on OCD.DesignWe use a randomized (1:1), double-blind, placebo-controlled, non-crossover design to examine the clinical and neural effects of either a single dose of oral psilocybin (0.25 mg/kg) or active placebo-control agent (250 mg of niacin) on OCD symptoms.Methods and analysisWe are enrolling 30 adult participants at a single site in Connecticut, USA who have failed at least one trial of standard care treatment (medication/psychotherapy) for OCD. All participants will also receive unstructured, non-directive psychological support during visits. Aside from safety, primary outcomes include OCD symptoms over the past 24 h, assessed by the Acute Yale-Brown Obsessive–Compulsive Scale and Visual Analog Scale ratings. These are collected by blinded, independent raters at baseline and the primary endpoint of 48 h post-dosing. Total follow-up is 12 weeks post-dosing. Resting state neuroimaging data will be collected at baseline and primary endpoint. Participants randomized to placebo will be offered the chance to return for an open-label dose of 0.25 mg/kg.Ethics statementAll participants will be required to provide written informed consent. The trial (protocol v. 5.2) was approved by the institutional review board (HIC #2000020355) and registered with ClinicalTrials.gov (NCT03356483).DiscussionThis study may represent an advance in our ability to treat refractory OCD, and pave the way for future studies of neurobiological mechanisms of OCD that may respond to psilocybin.

Safety, feasibility, tolerability, and clinical effects of repeated psilocybin dosing combined with non-directive support in the treatment of obsessive-compulsive disorder: protocol for a randomized, waitlist-controlled trial with blinded ratings

“…Participants will be randomized to receive treatment either immediately or at a later time (i.e., delayed treatment after a 7-week waitlist phase) (see Figure 1 ). As with prior research ( 39 , 56 , 57 ), participants will receive non-directive psychological support during each dosing session, during the two preparatory sessions in the week prior to the first dosing week, as well as during the two integration sessions in the same week following each dosing (i.e., 1 day and 4 days post-dosing). All preparatory and integration sessions last for up to 2 h each.…”

“…In response, in 2018, our group launched a randomized, double-blind, active placebo-controlled trial examining the feasibility, tolerability, safety, and clinical effects of a single moderate dose (0.25 mg/kg) of psilocybin paired with unstructured, non-directive psychological support in participants with treatment-refractory OCD ( 39 ). While this trial is still ongoing, early observations with a subsample of completers indicated clinically significant response on the Y-BOCS (i.e., < 35% reduction) at 48 h post-dosing for participants who received psilocybin ( 40 ).…”

Psilocybin - new remedy for patients with psychiatric disorders? Critical analysis of the current state of knowledge

“…Also resting state neuroimaging data will be stored both at baseline and primary endpoint. It is expected that psilocybin might lead to a rapid and substantial reduction in OCD symptoms, hence it would be able to treat refractory OCD [36]. According to clinicaltrial.gov (last update mid-July 2023) the trial is still in the recruiting phase.…”

Uso de psilocibina e seus efeitos sobre os sintomas do Transtorno Obsessivo-Compulsivo: revisão integrativa da literatura

“…O tratamento tradicionalmente indicado ao TOC baseia-se em terapia medicamentosa em conjunto com psicoterapia cognitivo-comportamental (TCC) sendo realizada a prevenção de exposição à resposta (PER). Dentre a classe dos medicamentos de primeira linha estão os inibidores seletivos da recaptação da serotonina (ISRSs), e embora os ISRS tenham se mostrado eficazes em ensaios clínicos randomizados controlados por placebo, até 60% dos pacientes não respondem e muitos pacientes com TOC classificados como respondedores em estudos de ISRS e TCC/PER permanecem sintomáticos e com restrições em suas vidas, sobretudo na realização das atividades de vida diária, com recidiva após a interrupção ou conclusão da TCC (Ching, et al;. Novos horizontes no tratamento do TOC sugerem a possível ação efetiva da psilocibina, e a partir de pesquisas relacionadas a outros transtornos, foram ampliados os estudos correspondentes sobre o potencial terapêutico da substância para o tratamento do TOC.…”