None listed
Conditions
Brief summary
Obsessive compulsive disorder (OCD), Body dysmorphic disorder (BDD), and anorexia nervosa (AN) are some of the most debilitating and chronic mental health conditions, sharing overlapping psychopathological determinants in terms of behavioural and cognitive impairments, neurobiological and neurocircuitry mechanisms, and poor response to conventional treatments. This trial aims to investigate the efficacy, safety and tolerability of psilocybin assisted psychotherapy (PAP) for treatment resistant OCD, BDD, and AN. 12 patients from each condition will be recruited in a basket design (multiple conditions) open label trial of 2 dosing sessions with non-directive support, including preparatory and integration therapy, and a 3-month follow up period. It is hypothesised that PAP will lead to statistically significant and clinically significant (35%) improvements in primary symptoms for each condition. Explorative outcomes will be investigated as potential mediators of changes in symptom severity, and lived experience insights will be gained. The outcomes of the trial will enhance scientific understanding and provide rationale for subsequent randomised controlled trials investigating PAP for obsessive-compulsive and body image disorders.
Interventions
The intervention involves psilocybin assisted psychotherapy. All participants will receive two psilocybin doses of 25mg, 4 weeks apart, and adjunct therapy-preparation, support during dosing, and integration. The psilocybin will be aministered orally, via a capsule.
A therapist dyad will provide non-directive psychotherapy, atleast one therapist will be a consultant psychiarist or psychiatry registrar. The psychotherapy will involve three distinct phases: (1) Preparation: emphasising therapeut
The intervention involves psilocybin assisted psychotherapy. All participants will receive two psilocybin doses of 25mg, 4 weeks apart, and adjunct therapy-preparation, support during dosing, and integration. The psilocybin will be aministered orally, via a capsule. A therapist dyad will provide non-directive psychotherapy, atleast one therapist will be a consultant psychiarist or psychiatry registrar. The psychotherapy will involve three distinct phases: (1) Preparation: emphasising therapeutic alliance, non-avoidance training, psychological and practical preparation for dosing sessions, nature of and relationship to distress, anxiety management strategies, the importance of set and setting, and intention formation; (2) Dosing session: establishing suitable set and setting, non-directive support; (3) Integration: focus on sustaining the change, emotion and body-focused therapy, meaning-centred integration into wider context, mindfulness training, ongoing peer- and professional support, and facilitating contextual changes to support outcomes. Preparatory sessions will take approximately 3 hours (across 1-2 sessions, based on participant preference), 1-week prior to the first dosing session. Two dosing sessions will take 8 hours each. Integration sessions will be conducted across 2 sessions following each dosing session; the first will be conducted within 2-days after each dosing session, and second within a week after the dosing session. Two integration will be provided following each dosing session- 4 in total. Any deviations from the intended therapeutic component of the trial will be monitored. Psychotherapy sessions will be conducted face-to-face. If it is not convenient for particpants to make all face-to-face sessions, they may participate in the second integration session online.
Sponsors
Swinburne University
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
i) Adults aged 18 to 65 years. ii) Primary diagnosis of OCD, BDD or AN according to the DSM-5, determined by Structured Clinical Interview for DSM-5 Disorder (SCID-5), The Body Dysmorphic Disorder Diagnostic Module (BDD-DM) and Eating Disorder Examination (EDE). iii) Moderate to severe symptom severity indicated as a score 18 or greater on the YBOCS, 20 or greater on the BDD-YBOCS, 3 or greater on the shape and/or weight subscales of the EDE. iv) Treatment resistance; defined as 1-year of illness with continuing symptoms for at least 6-months despite adequate engagement in conventional interventions for the condition. Specifically, conventional therapies for each condition are defined as: OCD: a course of selective serotonin reuptake inhibitors (SSRIs) and at least one course of cognitive behavioural therapy (CBT) which must include exposure and response prevention (ERP) (Pallanti and Quercioli, 2006). BDD: two courses of psychotherapy and/or pharmacology treatment, including at least one course of cognitive behavioural therapy (CBT), adequatea course of SSRIs or serotonin-norepinephrine reuptake inhibitor (SNRI). AN: two courses of psychotherapy and/or pharmacology treatment, including in-patient admission or day patient program, or extensive cognitive psychotherapy (>1-year), or multidisciplinary care approach (>1-year) or adequate course of SSRIs or SNRIs. v) Illness duration of at least 1- year vi) Absence of delusionality for participants with OCD and/or BDD as indicated by a score <3 on the YBOCS and BDD-YBOCS insight item. vii) Absence of mania symptoms (only minor) as indicated by a score 79 assessed by the Weschler Abbreviated Scale of Intelligence (WASI) to ensure that study instructions can be understood, and by a revised version of the Evaluation to sign an informed consent document for research to ensure appropriate understanding of trial requirements (DeRenzo et al., 1998).
Exclusion criteria
Psychiatric exclusions i) Lifetime history of serious suicide attempts requiring hospitalisation or current suicidal ideation with intent warranting immediate hospitalisation. ii) Current or past history of psychosis; DSM-5 criteria for Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), Bipolar I or II Disorder or Mania, determined by medical history and MINI assessment. iii) First degree relative with diagnosed Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), Bipolar I or II Disorder or Mania. iv) Presence of significant neurodevelopmental disorder (e.g., ADHD, autism, unremitting Tourette’s syndrome) that would reasonably impact the therapeutic effect of psilocybin. v) Currently meets DSM-5 criteria for Dissociative Disorder, Bulimia Nervosa, or significant personality disorder judged to be incompatible with establishment of rapport or safe exposure to psilocybin, determined by clinical interview. vi) Any current personal or situational factors that, in the opinion of the research team, might interfere with participation (for example, lacking social support, lacking a stable living situation, current domestic violence, or other ongoing trauma). vii) A history of childhood trauma or other factors leading to a complex case of OCD, BDD, or AN. In addition, the clinician involved in the care of each of the participants (n=36), will be contacted for a semi-structured clinical interview. For inclusion in the study they will be part of an enrolled participant's current care time. General medical exclusions i) Any disorder with known CNS involvement or disease, including seizures ii) Hepatic dysfunction as indicated by the following values: iii) -- GGT > 3 x ULN (upper limit of norm) iv) -- AST > 3 x ULN v) -- ALT > 3 x ULN vi) -- Tot Bili > 3.0 mg/dL vii) Known conditions putting participant at risk for hypercalcaemia, Cushing's syndrome, hypoglycaemia, syndrome of inappropriate antidiuretic hormone secretion, or carcinoid syndrome. viii) Cardiovascular conditions: uncontrolled hypertension (Systolic >140 and diastolic >90), angina, a clinically significant ECG abnormality (e.g., atrial fibrillation), TIA in the last 6 months, stroke, or cerebrovascular disease, peripheral or pulmonary vascular disease (no active claudication). This could include patients presenting with abnormal QT interval prolongation at screening or with a history of this (QTc at screening above 440 ms for men and above 470 ms for women). ix) Renal insufficiency (creatinine clearance < 40 mL/min using the Cockcroft and Gault equation). x) Insulin-dependent diabetes; if taking oral hypoglycaemic agents only excluded if they also have a history of hypoglycaemia. xi) Females who are pregnant or nursing or are trying to get pregnant, or become pregnant during the study. xii) Current hypothyroidism not responsive to treatment or untreated hypothyroidism. xiii) Patients who weigh less than 40 kg or have a BMI 3 kg) during screening period, orthostatic heart rate or blood pressure. xv) Long-acting opioid pain medications (e.g., oxycodone sustained release, morphine sustained release -- which are usually taken at 12-hour intervals) will be allowed if the last dose occurred at least 6 hours before psilocybin administration; such medication will not be taken again until at least 6 hours after psilocybin administration. xvi) Macro-dose (i.e., dose large enough to have perceivable hallucinogenic/psychedelic effects) of any hallucinogen or psychedelic (including psilocybin, MDMA, LSD, mescaline, DMT, and other similar hallucinogenic compounds) compounds within the past 12 months or > 10 macro-doses across lifetime. xvii) Micro-dose of any hallucinogen or psychedelic compound within the past 6 months xviii) Taking a contraindicated medication (SSRIs, SNRIs, MAOIs), which they do not wish to taper off, or is deemed inappropriate for them to taper by their treating clinician. xix) Current or past history within the last 5 years of meeting DSM-5 criteria for alcohol or drug dependence (excluding caffeine and nicotine) determined by the MINI, DAST-10 and AUDIT. xx) Use of illicit or extra-medical drugs or alcohol within the 2 days prior to each dosing session xxi) Currently using any of the following potent metabolic inducers or inhibitors: Inducers - Rifamycin (rifampin, rifabutin, rifapentine), anticonvulsants (carbamazepine, phenytoin, phenobarbital), nevirapine, efavirenz, paclitaxel, St John's Wort; Inhibitors - all HIV protease inhibitors, itraconazole, ketoconazole, erythromycin, clarithromycin, troleandomycin. xxii) If medically required to receive any of the following drugs with low therapeutic index within 12 hours after receiving psilocybin: ergot alkaloids, pimozide, midazolam, triazolam, lovastatin, simvastatin, fentanyl. xxiii) Any significant, uncorrected visual impairments, to ensure appropriate understanding of visual material. xxiv) Participants will be excluded if they are non-binary or do not gender identify with their biological sex. xxv) Unable to swallow tablets. xxvi) Enrolled in another interventional trial
Outcome results
None listed