ANZCTR - Registration

The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12622001525774

Ethics application status

Approved

Date submitted

5/09/2022

Date registered

9/12/2022

Date last updated

30/08/2024

Date data sharing statement initially provided

9/12/2022

Type of registration

Prospectively registered

Titles & IDs

Public title

Developing Optimal Psychedelic Assisted Psychotherapy for Obsessive-Compulsive Disorder

Scientific title

Developing Optimal Psychedelic Assisted Psychotherapy: Investigating the Effect on Symptom Severity for Adults with Obsessive-Compulsive Disorder

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

Trial acronym

OPT-PAP

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Treatment Resistant Obsessive-Compulsive Disorder

Condition category

Condition code

Mental Health

Other mental health disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

MDMA + Exposure Response Prevention Intervention:
Session plan – minimum of 2 preparation sessions, 3 MDMA sessions (2-6 weeks apart), 4 integration sessions, for example:

Week 1 Preparation session 1
Week 2 Preparation session 2
Week 3 MDMA 1 + integration session 1
Week 4 Preparation session 3 (optional)
Week 5 MDMA 2 + Integration session 2
Week 6 Preparation session 4 (optional)
Week 7 MDMA 3 + Integration session 3
Week 8 Integration session 4

The therapists conducting these sessions are health/healing professionals (doctor, psychiatrist, psychologist, psychotherapist, counsellor, nurse) trained in the administration of psychedelic assisted psychotherapy.

Adherence will be recorded electronically through a session attendance checklists as part of their study file.

Overview of 2 x preparation sessions for MDMA:
There will be a minimum of two 90-minute preparation sessions conducted remotely or in person with a therapist. There also will be an opportunity for participants to engage in an optional preparation session prior to the second and third medication session. The participant will have the opportunity to meet the therapists/staff who will be present in the MDMA dosing session prior to dosing, during this preparation phase (more preparation sessions will be provided if deemed necessary by the therapist).

Preparation session 1:
Alliance development and formulation: the primary aims of the initial session will be the development of a therapeutic alliance, build trust and safety between the study therapists and the participant.
Clarify participant intentions for the MDMA session, anxieties and hopes for the experience.
Discuss ethical considerations and participant choices around use of touch, grounding techniques, and preferences such as music playlist, utilising eye mask, what will happen in the MDMA session, expectations and concerns and previous experience, media awareness or knowledge of psychedelic therapy.
Inform them about what to expect during the MDMA sessions, psychological and physiological effects, who will be present, and the integration process. Preparing social support and integration for after the dosing session. Support person should be informed of the nature of the study.
Gain an understanding of participant’s obsessional thoughts and associated avoidance, rituals or compulsive behaviours, and the situations which act as triggers for them. Eliciting and defining the range of OCD thoughts and behaviours via a thorough symptom review, using the Yale-Brown Obsessive Compulsive Scale (YBOCS).

Between session task: Participant completes an OCD self-monitoring worksheet (this will take no more than 5 minutes per day to complete).

Preparation Session 2:
Therapist/s continue to build trust and rapport with participant. Participant meets one or two of the therapists who will be present during the dosing session.
Review self-monitoring sheet and further clarify intentions, including exposure hierarchy, for the MDMA session.
Psychoeducation around exposure therapy, OCD, and the role of avoidance in maintaining OCD.
Goals are developed collaboratively between the therapists and the participant, based around anxiety provoking situations of increasing difficulty during MDMA sessions. With the therapist’s help the client identifies situations that trigger obsessions or compulsions (exposure), while refraining from the compulsive behaviours they usually perform (response prevention), during the MDMA session. Developing an anxiety hierarchy and an exposure response plan - this involves developing, for each exposure task, response prevention goals, where the client purposefully refrains from engaging in the usual OCD rituals or compulsions during the MDMA session.
Discuss common experiences in MDMA session including transpersonal, spiritual aspects and approaching difficult and intense experiences. Information on non-ordinary states of consciousness, preparing to be open and curious in observing what arises.
Practical guidance and safety instructions, including departure requirements.

Optional Preparation Session 3:
Occurs after the first MDMA session, and before the second MDMA session.
Review intentions for the second MDMA session flexibly, as these may have changed since the first MDMA session. Building upon the first integration session, reflect on insights gained.
Where applicable, collaboratively review exposure hierarchy, re-rate SUDS and set ERP plan for the second MDMA session.

Overview of dosing sessions:
The medication sessions will be conducted at Monarch Mental Health Group (MMHG) clinical facilities in Sydney and Melbourne.
There will be three dosing sessions conducted between 2 and 6 weeks apart. A single dose of 100mg MDMA in an oral capsule will be administered by a medical practitioner or nurse to the participant.
Each session will last up to 8 hours and will be conducted with each individual participant separately. Prior to the participant’s arrival, the room will be prepared such that it provides a safe, warm, private atmosphere with the provision for music, eye shades, gentle lighting, and the ability for the participant to lie down with an appropriate blanket and pillow.

Overview of 4 x MDMA integration sessions:
The participant will be engaged in a 90-minute debriefing / integration session within 72 hours after each medication session. These may be conducted in person or remotely. The purpose of the debriefing / integration sessions is to support the participant in their ability to reflect on the medication sessions and to help them to make meaning and clarify insights that may have been developed. The primary activity of the therapists in these sessions is to ask open-ended questions to elicit insights that the participant may have come to and how the insights can be generalised into their life and a variety of setting. Sessions may incorporate values work and setting ongoing ERP tasks between the MDMA dosing sessions. There may be some discussion of how the insights and changes in participant’s values may be reflected in alterations they may make in specific day-to-day behaviours, and clarification of intentions for the next dosing session. In addition, patients may be provided support to continue with ERP related therapeutic activities.

Integration session 1:
Occurs within a week after the first dosing.
Participant and therapist reflect on insights gained in the first dosing; any new adaptive information gained. Encourage ongoing ERP tasks between sessions and consolidate adaptive meaning making. Create space to discuss new concerns which may emerge in the medicine session, normalise experience and begin to establish intentions for the next MDMA session.

Integration session 2:
Occurs within a week after the second dosing.
As above, participant and therapist reflect on insights gained in the second dosing; any new adaptive information gained. Encourage ongoing ERP tasks between sessions and consolidate adaptive meaning making. Create space to discuss new concerns which may emerge in the medicine session, normalise experience and begin to establish intentions for the third and final MDMA session.

Integration session 3:
Occurs within a week after the third dosing.
As above, participant and therapist reflect on insights gained in the first dosing; any new adaptive information gained. Encourage ongoing ERP tasks between sessions and consolidate adaptive meaning making. Preparation for the end of the trial and plan for ongoing support and aftercare.

Integration session 4:
Occurs 2 weeks after the last dosing session.
Final session with study therapists and participant together, focused on consolidating insights and gains, review progress with ERP hierarchy and relapse prevention strategies. Values work. Importantly, the therapists acknowledge participant’s hard work, and provide warm handovers for any outstanding concerns. Identify any new goals in recovery. Explore barriers to accessing ongoing support and address same. Potential to bring in a family member or loved one for support with their plan for ongoing recovery.

EEG Component:
A subset of participants will also undergo an electroencephalogram (EEG) recording session on three occasions: at baseline, and following the first and third drug session. These recordings will be conducted by trained research staff. Please note, the subset of participants receiving EEG recordings will be determined by equipment availability.

Intervention code [1]

Treatment: Drugs

Intervention code [2]

Treatment: Other

Comparator / control treatment

Psilocybin + ACT Intervention:
The psilocybin + ACT intervention is adapted with permission from the Yale Psilocybin for Depression Manual.
Session plan – minimum of 2 preparation sessions, 3 Psilocybin sessions (2-6 weeks apart), 4 integration sessions, for example:

Week 1 Preparation session 1
Week 2 Preparation session 2
Week 3 Psilocybin 1 + integration session 1
Week 4 Preparation session 3 (optional)
Week 5 Psilocybin 2 + Integration session 2
Week 6 Preparation session 4 (optional)
Week 7 Psilocybin 3 + Integration session 3
Week 8 Integration session 4

The therapists conducting these sessions are health/healing professionals (doctor, psychiatrist, psychologist, psychotherapist, counsellor, nurse) trained in the administration of psychedelic assisted psychotherapy.
Adherence will be recorded electronically through a session attendance checklists as part of their study file.

Overview of 2 x preparation sessions for psilocybin:
There will be a minimum of two 90-minute preparation sessions conducted remotely or in person with a therapist. There also will be an opportunity for participants to engage in an optional preparation session prior to the second and third medication session. The participant will have the opportunity to meet the therapists/staff who will be present in the psilocybin dosing session prior to dosing, during this preparation phase (more preparation sessions will be provided if deemed necessary by the therapist).

Preparation session 1:
Alliance development and formulation: the primary aims of the initial session will be the development of a therapeutic alliance, build trust and safety between the study therapists and the participant.
Listening to participant’s narrative of depression and treatment history to understand patterns of psychological inflexibility that are most prominent.
Clarify participant intentions for the psilocybin session, anxieties and hopes for the experience.
Discuss ethical considerations and participant choices around use of touch, grounding techniques, and preferences such as music playlist, utilising eye mask, what will happen in the psilocybin session, expectations and concerns and previous experience, media awareness or knowledge of psychedelic therapy.
Psychoeducation around psychological and physiological effects of psilocybin, who will be present, and the integration process. Preparing social support and integration for after the dosing session. Support person should be informed of the nature of the study.
Introduce ACT, concept of psychological flexibility and observing experience with curiosity and openness, rather than avoidance.
Grounding exercises and scripts for difficult experience, information on non-ordinary states of consciousness, based on the study manual.

Preparation Session 2:
Therapist/s continue to build trust and rapport with participant. Participant meets one or two of the therapists who will be present during the dosing session.
Review valued living questionnaire and further clarify intentions, for the psilocybin session.
Introduce ACT hexaflex model. Prime the participant to register elements of the psilocybin sessions as reflecting ACT-defined shifts in thinking, behaviour, and awareness of values.
Collaboratively set intentions for the medicine session.
Discuss common experiences in psilocybin session including transpersonal, spiritual aspects and approaching difficult and intense experiences with openness and curiosity
Grounding exercises i.e., breathing techniques
Practical guidance and safety instructions, including departure requirements.

Optional Preparation Session 3:
Occurs after the first psilocybin session, and before the second psilocybin session.
Conduct psychoeducation regarding the cognitive processes and behaviours that contribute to OCD from an ACT perspective (i.e., cognitive fusion, experiential avoidance, etc). How patterns can be changed through an interactive process between the principles of ACT and the experience with psilocybin, and mindfulness practice.
Review intentions for the second psilocybin session flexibly, as these may have changed since the first session. Building upon the first integration session, reflect on insights gained.

Overview of dosing sessions:
The medication sessions will be conducted at Monarch Mental Health Group (MMHG) clinical facilities in Sydney and Melbourne.
There will be three dosing sessions conducted between 2 and 6 weeks apart. A single dose of 25mg psilocybin in an oral capsule will be administered by a medical practitioner or nurse to the participant.

Each session will last up to 8 hours and will be conducted with each individual participant separately. Prior to the participant’s arrival, the room will be prepared such that it provides a safe, warm, private atmosphere with the provision for music, eye shades, gentle lighting, and the ability for the participant to lie down with an appropriate blanket and pillow.

Overview of 4 x psilocybin integration sessions:
The participant will be engaged in a 90-minute debriefing / integration session within 72 hours after each medication session. These may be conducted in person or remotely. The purpose of the debriefing / integration sessions is to support the participant in their ability to reflect on the medication sessions and to help them to reach insights that may have been developed. The primary activity of the therapists in these sessions is to ask open-ended questions to elicit insights that the participant may have come to. The therapist may identify elements of the participant’s narrative consistent with ACT principles and help them to understand their experience in this context. The integration sessions may also involve an exploration of values and how these may have evolved through the process of the treatment sessions. There may be some discussion of how the insights and changes in participant’s values may be reflected in alterations they may make in specific day-to-day behaviours. An ACT framework will be used to guide this process.

Integration session 1:
Occurs within a week after the first dosing.
Participant and therapist reflect on insights gained in the first dosing; any challenges or new adaptive information gained. Therapist elicits complete narrative of participant’s experience during medication session. Identify and explore aspects of the participant’s narrative that engage with ACT principles, as well as instances when they moved toward or away from psychological flexibility. Create space to discuss new concerns which may emerge in the medicine session, normalise experience and begin to establish intentions for the next psilocybin session.

Integration session 2:
Occurs within a week after the second dosing.
As above, participant and therapist reflect on insights gained in the second dosing; any challenges or new adaptive meaning-making. Therapist and participant continue to review and reflect on the participant’s psilocybin experience, including any emotional, mental, or lifestyle changes that followed the dosing session. Reflect on values, by discussing the participant’s completed Valued Living Questionnaire, and relative importance of valued domains of living. Reflect on experiences living in accordance with or not living in alignment with their values. Create space to discuss new concerns which may emerge in the medicine session, normalise experience and begin to establish intentions for the third and final psilocybin session.

Integration session 3:
Occurs within a week after the third dosing.
As above, participant and therapist reflect on insights gained in the third dosing; any challenges or new adaptive information gained. Therapist elicits complete narrative of participant’s experience during medication session, exploring aspects of the experience in relation to ACT principles discussed previously. Therapist may use Metaphors derived from psilocybin experience or from ACT to aid in understanding of the principles, such as self-as-context. Preparation for the end of the trial and plan for ongoing support and aftercare.

Integration session 4:
Occurs 2 weeks after the last dosing session.
Final session with study therapists and participant together, focused on consolidating insights and gains during the study. Therapist continues to explore and reinforce adaptive meanings gained from the psilocybin experience, while assessing for changes in psychological flexibility. Discussion around where the dosing and therapy sessions brought each ACT process to light, using the ACT hexaflex. Discussion of relevant ACT concepts, values-based action and successful behavioural changes and committed actions taken. Relapse prevention utilising meditation and mindfulness practices and other concrete ways the study experience can be translated into lasting changes. Importantly, the therapists acknowledge participant’s hard work, and provide warm handovers for any outstanding concerns. Identify any new goals in recovery. Explore barriers to accessing ongoing support and address same. Potential to bring in a family member or loved one for support with their plan for ongoing recovery.

EEG Component:
A subset of participants will also undergo an electroencephalogram (EEG) recording session on three occasions: at baseline, and following the first and third drug session. These recordings will be conducted by trained research staff. Please note, the subset of participants receiving EEG recordings will be determined by equipment availability.

Control group

Active

Outcomes

Primary outcome [1]

Total score on the Yale-Brown Obsessive-Compulsive Scale (YBOCS).

Timepoint [1]

Baseline compared to study timepoints: Post Drug therapy session 1, Post Drug therapy session 2, Post Drug therapy session 3, End Integration Therapy (8 weeks post-baseline) (primary timepoint), and 1, 3 and 6 months post-integration therapy completion

Secondary outcome [1]

Total score on the Self-rated version of the Montgomery Asberg depression rating scale

Timepoint [1]

Baseline compared to study timepoints: Post Drug therapy session 1, Post Drug therapy session 2, Post Drug therapy session 3, End Integration Therapy (8 weeks post-baseline), and 1, 3 and 6 months post-integration therapy completion

Secondary outcome [2]

Patients Global Impression of Improvement Scale (PGI-I)

Timepoint [2]

End Integration Therapy (8 weeks post-baseline) compared to study timepoints: 1, 3 and 6 months post-integration therapy completion

Secondary outcome [3]

Depression, Anxiety and Stress Scale (DASS10)

Timepoint [3]