Psilocybin-assisted psychotherapy for Generalised Anxiety Disorder

INTERVENTION: Psilocybin‐assisted Psychotherapy This will be the first clinical trial to investigate the use of psilocybin‐assisted‐psychotherapy in the treatment of Generalised Anxiety Disorder. The intervention is a combined pharmacological and psychological treatment. Dosing sessions The experimental drug is psilocybin, taken orally. There will be two dosing sessions approximately 3 weeks apart. Dose 1 = 25mg psilocybin; Dose 2 = 25 or 30mg psilocybin. Doses will be maintained at 25mg across both sessions unless the participant exhibits limited acute subjective response during the first session (as determined by acute effects questionnaires) without substantial adverse effects, in which case the dose will be increased to 30mg for the second session. A range of extra‐pharmacological parameters are specified to optimise safety and efficacy. Psychotherapy The psychotherapy is conducted by qualified and experienced mental healthcare therapists who have also undergone an extensive trial‐specific psychedelic therapist training program with supervised practice. All psychotherapy and dosing sessions will take part at BrainPark, Monash University, within comfortably furnished and aesthetically pleasing rooms. The psychological treatment comprises preparatory psychotherapy, dosing support, and integrative psychotherapy. *Preparatory psychotherapy includes a range of approaches supporting safe and effective dosing sessions, and sustained outcomes. 3‐to‐5 x 90‐minute sessions will take place approximately weekly preceding the first dosing session. *Dosing session support occurs on the day of psilocybin administration, and is based on best‐practice in psychedelic therapies, including a range of approaches that support safe and effective administration and sustained CONDITION: Generalised Anxiety Disorder; ; Generalised Anxiety Disorder Mental Health ‐ Anxiety PRIMARY OUTCOME: Change in Hamilton Anxiety Ratings Scale (HAM‐A). The HAM‐A is a gold standard clinician‐rated instrument that comprises 14 items measuring both psychological and physiological aspects of anxiety on a rating scale of 0 (not present) to 4 (very severe).[Baseline, Week 11] SECONDARY OUTCOME: Acceptability of the intervention, assessed using the Acceptability of Intervention Measure (AIM)[Week 8] Appropriateness of the intervention, assessed using the Intervention Appropriateness Measure (IAM) [Week 8] Change in alcohol misuse, assessed using the Alcohol Use Disorders Identification Test (AUDIT) ; [At conclusion of the study] Rates of clinical remission as assessed by change in HAM‐A[Baseline, week 11, week 23] Rates of clinical response as assessed by change in HAM‐A [Baseline, week 11, week 23] INCLUSION CRITERIA: *Adults experiencing severe GAD. *Proficiency in English. *Provide a contact (relative, spouse, close friend or other Support Person) who can transport and provide support to participant following two or three experimental sessions. *Taper and cease of certain excluded medications is deemed appropriate, agreeable, and under supportive care, and successful following confirmation of preliminary enrolment. Note, prospective participants are not required to taper and cease prior to preliminary enrolment. *Agree to all study‐related requirements. ; [Baseline, week 11, week 23] Change in anxiety severity assessed using Generalized Anxiety Disorder 7‐item Scale (GAD‐7)[Baseline, week 11, week 23] Change in disability, assessed using Sheehan Disability Scale (SDS)[Baseline, week 11, week 23] Change in drug misuse, assessed using the Drug Use Disorders Identification Test (DUDIT)[Baseline, week 11, week 23] Change in Hamilton Anxiety Ratings Scale (HAM‐A)[Baseline, week 23] Change in quality of life, assessed using Personal Wellbeing Inventory (PWI)[Baseline, week 11, week 23] Change in suicidality, as assessed using the Ultra Brief Checklist for Suicidality (UBCS)[Baseline; weekly (weeks 7‐16); three‐weekly (weeks 16‐23)] Change in symptoms of agoraphobia, assessed using the Agoraphobia Dimensional Scale (AG‐D)[Baseline, week 11, week 23] Change in symptoms of depression, assessed using the Quick Inventory of Depression (QIDS‐SR)[Baseline, week 11, week 23] Change in symptoms of panic disorder, assessed using the Panic Disorder Severity Scale ‐ Self Rated (PDSS‐SR)[Baseline, week 11, week 23] Change in symptoms of social anxiety, assessed using the Mini‐Social Phobia Inventory (Mini‐SPIN)[Baseline, week 11, week 23] Change in tobacco misuse, assessed using the self‐reported number of cigarettes smoked[Baseline, week 11, week 23] Feasibility of the intervention, assessed using the Feasibility of Intervention Measure (FIM)[Week 8] Frequency of Adverse Events and Serious Adverse Events associated with participation in the trial, as measured using trial AE/SAE report forms that follow the CTCAE v5.[At conclusion of the study] Proportion of participants who complete both dosing sessions and Primary Endpoint assessment, according to audit of study records