ANZCTR - Registration

Registration number

ACTRN12626000246381

Ethics application status

Approved

Date submitted

9/02/2026

Date registered

26/02/2026

Date last updated

13/05/2026

Date data sharing statement initially provided

26/02/2026

Type of registration

Prospectively registered

Titles & IDs

Public title

Mindfulness and Psilocybin in Healthy Adults: A Comparative Study

Scientific title

The Mindful Psilocybin Study: A three-arm, open-label, randomised controlled trial in healthy volunteers examining the interaction between mindfulness training and psilocybin on wellbeing and psychological, physiological and behavioural measures

Additional trial identifiers [1]

none

Universal Trial Number (UTN)

U1111-1330-5883

Trial acronym

Psil-oMM

Related trial records

Health condition

Health condition(s) studied:

Mental Wellbeing

Condition category

Condition code

Mental Health

Studies of normal psychology, cognitive function and behaviour

Intervention/exposure

Study type

Interventional

Description of the intervention or exposure

This study includes three intervention conditions:

1. Psilocybin alone
2. Mindfulness alone (described under Comparator/Control Treatment)
3. Combined mindfulness plus psilocybin

Psilocybin intervention
Participants will receive a single oral dose of psilocybin (25 mg tablet) administered on-site under medical and psychological supervision.

The intervention includes:
-Preparation: two sessions (one online ~2 weeks prior; one in-person ~1 week prior)
-Dosing session: supervised administration with two trained facilitators; safety screening conducted on the day (pregnancy, alcohol, and drug use); participants must nominate a support person for transport
-Integration: two sessions (one in-person the day after dosing; one online within the following week)

All procedures follow established best-practice approaches for participant preparation, safety monitoring, and psychological support used in prior clinical psilocybin trials.

Adherence/accountability: on-site administration under staff supervision with full drug accountability.

Combined intervention
Participants complete the 4-week online mindfulness program (see Comparator/Control) followed by psilocybin dosing in Week 5, with identical preparation, dosing, and integration procedures as above.

Intervention code [1]

Treatment: Drugs

Intervention code [2]

Behaviour

Description of the comparator or control

Comparator/control treatment – Active control: Online mindfulness training

The control condition is a structured online mindfulness program (Mindfulness for Peak Performance and Wellbeing, Monash University), delivered over 4 weeks with continued access for 3 additional weeks (total duration 7 weeks). This active control is compared with the psilocybin intervention.

Content and modules:
Week 1: Introduction to mindfulness and present-moment awareness
Week 2: Stress response and emotion regulation
Week 3: Attention and cognitive performance
Week 4: Integrating mindfulness into daily life

Materials:
Short instructional videos (approximately 5–10 minutes) introducing key concepts and practices
Guided audio meditations (e.g. breath awareness, body scan)
Written materials and brief readings outlining theory and practice instructions

Source:
Pre-existing, publicly available course developed by Monash University

Expected use:
Participants are instructed to complete 1–2 hours of course content per week
Daily meditation practice (~10 minutes/day) following the weekly structure

Adherence monitoring:
Participant self-reported daily practice logs
Weekly written reflections within the course platform

Control group

Active

Outcomes

Primary outcome [1]

Wellbeing

Timepoint [1]

Baseline (5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group), primary endpoint (3 weeks post-dose/3 weeks after the end of the structured mindfulness training), long-term follow-up (3, 6 and 12 months post-primary endpoint)

Secondary outcome [1]

Acceptance

Timepoint [1]

The Acceptance and Action Questionnaire-II will be assessed at: Baseline (T1) - 5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment) T5, T6, T7 (3, 6, 12 months after T4 outcome measures)

Secondary outcome [2]

Intolerance of Uncertainty

Timepoint [2]

Baseline (T1) - 5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment) T5, T6, T7 (3, 6, 12 months after T4 outcome measures)

Secondary outcome [3]

Avoidance

Timepoint [3]

Baseline (T1) - 5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment) T5, T6, T7 (3, 6, 12 months after T4 outcome measures)

Secondary outcome [4]

Self-compassion

Timepoint [4]

Baseline (T1) - 5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment) T5, T6, T7 (3, 6, 12 months after T4 outcome measures)

Secondary outcome [5]

Heart rate Variability

Timepoint [5]

Baseline (T1) - 5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group T3 (one day post-T2 / post-dosing) T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment)

Secondary outcome [6]

Pain sensitivity

Timepoint [6]

Baseline (T1) - 5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group T3 (one day post-T2 / post-dosing) T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment)

Secondary outcome [7]

Life satisfaction

Timepoint [7]

Baseline (T1) - 5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment) T5, T6, T7 (3, 6, 12 months after T4 outcome measures)

Secondary outcome [8]

Sensitivity to bodily signals of anxiety

Timepoint [8]

Baseline (T1) - 5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment) T5, T6, T7 (3, 6, 12 months after T4 outcome measures)

Secondary outcome [9]

Depression, anxiety, stress

Timepoint [9]

Baseline (T1) - 5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment) T5, T6, T7 (3, 6, 12 months after T4 outcome measures)

Secondary outcome [10]

Somatic symptom burden

Timepoint [10]

Baseline (T1) - 5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment) T5, T6, T7 (3, 6, 12 months after T4 outcome measures)

Secondary outcome [11]

Interoceptive Awareness

Timepoint [11]

Baseline (T1) - 5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment) T5, T6, T7 (3, 6, 12 months after T4 outcome measures)

Secondary outcome [12]

Physical Activity

Timepoint [12]

Baseline (T1) - 5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment) T5, T6, T7 (3, 6, 12 months after T4 outcome measures)

Secondary outcome [13]

Diet

Timepoint [13]

Baseline (T1) - 5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment) T5, T6, T7 (3, 6, 12 months after T4 outcome measures)

Secondary outcome [14]

Nicotine consumption

Timepoint [14]

Baseline (T1) - 5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment) T5, T6, T7 (3, 6, 12 months after T4 outcome measures)

Secondary outcome [15]

Alcohol Consumption

Timepoint [15]

Baseline (T1) - 5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment) T5, T6, T7 (3, 6, 12 months after T4 outcome measures)

Secondary outcome [16]

Mindfulness

Timepoint [16]

Baseline (T1) - 5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment) T5, T6, T7 (3, 6, 12 months after T4 outcome measures)

Secondary outcome [17]

Perceived barriers to meditation

Timepoint [17]

Baseline (T1) - 5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment)

Secondary outcome [18]

Time spent practicing

Timepoint [18]

Baseline (T1) - 5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment) T5, T6, T7 (3, 6, 12 months after T4 outcome measures)

Secondary outcome [19]

Meditative depth

Timepoint [19]

Primary endpoint (3 weeks post-dose/post-mindfulness training), long-term follow-up (3, 6 and 12 months post-primary endpoint)

Secondary outcome [20]

Mystical experiences (psilocybin-only and combined psilocybin/mindfulness groups only)

Timepoint [20]

1-day post-dose

Secondary outcome [21]

Acceptance and avoidance during acute effects of psilocybin

Timepoint [21]

1-day post-dosing

Secondary outcome [22]

Challenging experiences during the acute effects of psilocybin

Timepoint [22]

1-day post-dose

Secondary outcome [23]

Altered states of consciousness (psilocybin-only and combined psilocybin/mindfulness groups only)

Timepoint [23]

1-day post-dose

Secondary outcome [24]

Insight

Timepoint [24]

T3 (one day post-T2 / post-dosing) T5 (3 months after T4 outcome measures)

Secondary outcome [25]

Absorption

Timepoint [25]

Baseline (T1) T3 (one day post-T2 / post-dosing) T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment) T5, T6, T7 (3, 6, 12 months after T4 outcome measures)

Secondary outcome [26]

Aberrant meaning making

Timepoint [26]

Baseline (T1) T2 (during dosing for psilocybin groups; end of structured phase for mindfulness-only group) - approximately 4 hours post-dosing T3 (one day post-T2 / post-dosing) T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment)

Secondary outcome [27]

Pattern recognition

Timepoint [27]

Baseline (T1) T2 (during dosing for psilocybin groups; end of structured phase for mindfulness-only group) - approximately 4 hours post-dosing T3 (one day post-T2 / post-dosing) T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment)

Secondary outcome [28]

Convergent/divergent thinking

Timepoint [28]

Baseline (T1) T2 (during dosing for psilocybin groups; end of structured phase for mindfulness-only group) - approximately 4 hours post-dosing T3 (one day post-T2 / post-dosing) T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment)

Secondary outcome [29]

Insight misattribution

Timepoint [29]

Baseline (T1) T2 (during dosing for psilocybin groups; end of structured phase for mindfulness-only group) - approximately 4 hours post-dosing T3 (one day post-T2 / post-dosing) T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment)

Secondary outcome [30]

Explore-exploit dynamics

Timepoint [30]

Baseline (T1) T2 (during dosing for psilocybin groups; end of structured phase for mindfulness-only group) - approximately 4 hours post-dosing T3 (one day post-T2 / post-dosing) T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment)

Secondary outcome [31]

Hysteresis effect

Timepoint [31]

Baseline (T1) T2 (during dosing for psilocybin groups; end of structured phase for mindfulness-only group) - approximately 4 hours post-dosing T3 (one day post-T2 / post-dosing) T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment)

Secondary outcome [32]

Safety measure: Adverse Events

Timepoint [32]

Baseline (T1) T2 (during dosing for psilocybin groups; end of structured phase for mindfulness-only group) T3 (one day post-T2 / post-dosing) T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment) T5, T6, T7 (3, 6, 12 months after T4 outcome measures)

Secondary outcome [33]

Safety measure: Hallucinogen persisting perception disorder

Timepoint [33]

T5 (3 months after T4 outcome measures)

Secondary outcome [34]

Pain tolerance

Timepoint [34]

Baseline (T1) - 5 weeks pre-dose in psilocybin-only group, one day before start of mindfulness intervention in mindfulness-only and combined group T3 (one day post-dose/post T2) T4 (3 weeks post-dosing/post-T2; 9 weeks post-enrolment)

Eligibility

Key inclusion criteria

-Be aged 18 to 75 years.
-Be medically stable, as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood laboratory tests.
-If of childbearing potential, must not be pregnant or breast-feeding at screening, must have a negative pregnancy test prior to dosing session, and must agree to use adequate birth control from screening through 10 days after the dosing session.

Minimum age

18 Years

Maximum age

75 Years

Sex

Both males and females

Healthy volunteers

Yes

Key exclusion criteria

-Have a lifetime history of meeting DSM-5 criteria for Schizophrenia, other Psychotic Disorder, Dissociative Identity Disorder, or Bipolar I or II Disorder or other mood disorder with psychotic features.
-Have a first-degree relative with diagnosed Schizophrenia, other Psychotic Disorder or Bipolar I disorder or mood disorder with psychotic features.
-Have a current or past year history of meeting criteria for any DSM-5 disorder or other subclinical psychiatric symptoms determined by the PI or Study Physician to be incompatible with inclusion in a healthy sample
-Have current suicide risk.
-Have any current contextual problem which, in the opinion of the PI or Study Physician might interfere with safe participation.
-At screening, use of excluded medications, unless explicitly agreed in writing by the Study Physician.
-Require ongoing concomitant therapy with a psychiatric medication for management of suicidal ideation.
-Require ongoing concomitant therapy with an excluded medication.
-Are above thresholds for prior use of a classical psychedelic.
-Are above thresholds for prior mindfulness experience.
-Have cardiovascular conditions, as specified in the study protocol.
-Have a disorder with known CNS involvement, or other major CNS disease.
-Have a diagnosis of epilepsy or previous seizures.
-Have certain chronic medical conditions, as specified in the study protocol.
-Weigh less than 48 kilograms or BMI < 17.
-Are pregnant or nursing, or able to become pregnant and are not willing to practice contraception.

Study design

Statistical methods / analysis

Primary analyses will use linear mixed-effects models (LMMs) to accommodate the repeated-measures design and missing data. Group (Mindfulness, Psilocybin, Mindfulness + Psilocybin) and time (baseline, post-intervention, follow-up) will be specified as fixed effects, with a group × time interaction to test whether change over time differs between groups. Participant will be included as a random intercept to account for within-participant correlation. The primary outcome will be WEMWBS measured at each timepoint. Planned contrasts will compare groups as specified a priori, with p-values adjusted for multiple comparisons using a false discovery rate procedure. Effect sizes will be reported as standardized mean differences (Cohen’s d) with 95% confidence intervals. Model assumptions (normality and homoscedasticity) will be assessed by visual inspection of residual plots, and robust standard errors will be used if assumption violations are detected. Secondary analyses will be conducted using the same modelling approach and the same assessment timepoints as the primary analysis. Post-hoc exploratory analyses not specified in the protocol or Statistical Analysis Plan may also be undertaken to further interrogate the data and will be clearly identified as exploratory in the final clinical study report.

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

25/05/2026

Actual

Date of last participant enrolment

Anticipated

1/10/2027

Actual

Date of last data collection

Anticipated

30/11/2028

Actual

Sample size

Target

45

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Funding & Sponsors

Funding source category [1]

University

Name [1]

Monash University

Country [1]

Australia

Funding source category [2]

Charities/Societies/Foundations

Name [2]

Three Springs Foundation

Country [2]

Australia

Primary sponsor type

University

Name

Monash University

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Monash University Human Research Ethics Committee

Ethics committee address [1]

https://www.monash.edu/researchoffice/ethics

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

20/11/2025

Approval date [1]

27/01/2026

Ethics approval number [1]

50048

Summary

Brief summary

Mindfulness training and psilocybin interventions are both promising approaches for supporting mental health and wellbeing, and may have complementary or synergistic effects when used together.

The Psil-oMM study aims to examine the combined and independent effects of mindfulness training and psilocybin by comparing three conditions in 45 healthy volunteers: a 4-week mindfulness intervention, a single high-dose psilocybin session with psychological support, and a combined mindfulness plus psilocybin intervention. The primary outcome is wellbeing, assessed using the Warwick–Edinburgh Mental Wellbeing Scale (WEMWBS).

Trial website

https://www.monash.edu/medicine/scs/clinical-psychedelic-lab/participant-information

Public notes

To find out more information and to apply, email mindfulpsilocybin@monash.edu

Contacts

Principal investigator

Name

Dr Paul Liknaitzky

Address

Clinical Psychedelic Lab, Level 1, Building 2, 270 Ferntree Gully Rd, 3168, Notting Hill VIC

Country

Australia

Phone

+61399052038

Email

[email protected]

Contact person for public queries

Name

Cammy Mitchell

Address

Clinical Psychedelic Lab, Level 1, Building 2, 270 Ferntree Gully Rd, 3168, Notting Hill VIC

Country

Australia

Phone

+61399052038

Email

[email protected]

Contact person for scientific queries

Name

Cammy Mitchell

Address

Clinical Psychedelic Lab, Level 1, Building 2, 270 Ferntree Gully Rd, Notting Hill VIC

Country

Australia

Phone

+61399052038

Email

[email protected]

Trial Review

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