MicroDep trial

Moderate depression is a form of major depressive disorder with persistent symptoms that impact your life. Despite these challenges, many people with moderate levels of depression are able to perform regular life activities.

Symptoms of moderate depression can include:

• low mood
• reduced interest in activities
• changes in appetite or weight
• disrupted sleep
• low energy
• difficulty making decisions.

You do not need a prior formal diagnosis of depression to take part in this study. We will assess potential participants prior to enrolment.

We do not offer psychotherapy during this trial. Participants will undergo a thorough psychiatric screening and will be closely monitored by mental health professionals throughout the trial, however there is no psychotherapeutic component to our trial intervention.

• If you already see a psychotherapist, you may continue to see them while taking part in the trial.
• We are also able to give recommendations for further psychological support after the trial if requested.

Yes, with some limitations.

• To take part in this trial participants must agree to visit Macquarie University one to two times per week for a period of 10 weeks. Visits vary in length. Some are very short (less than 15 minutes) but some of the visits, particularly the early visits, will last around three hours.
• You may have to take some sick leave to participate. We can provide medical certificates.
• We will do what we can to accommodate your schedule when making appointments, however, we can only see participants on weekdays.
• If your job involves operating heavy machinery (including cars) or tasks that might endanger oneself or others, such as those requiring fine motor control, fast response times or real-time planning, you cannot return to your job for three hours following each dosing session.

You will come to the test site twice a week during the treatment phase of the study.

You will be asked to complete:

• physiological assessments including blood tests on four occasions
• computer-based tasks, including questionnaires and tests of cognitive ability, on most visits
• tasks in a driving simulator on some visits.

Some participants may be invited to take part in a neuroimaging study involving an MEG scan.

A placebo group is necessary to establish reliable results. Participation in a clinical trial such as this aids our understanding of treatment alternatives for depression and of psychedelic science.

• Half of the participants in the study will be allocated to the placebo condition. Neither you nor any of the clinical trial staff will know which condition you are in.
• If we find evidence that psilocybin is an effective treatment then participants in the placebo condition, who attend every visit required by the trial, will be offered the opportunity to access the active drug intervention after the trial is complete.

• Is this safe? Yes, psilocybin is a very safe drug with negligible risk of overdose and minimal risk of physical or psychological harm when administered by professionals. The doses we are using in this trial are far less than typical clinical or recreational doses.
• Is there a risk of addiction? No. While any drug has the potential for abuse, psilocybin does not interfere with the brain’s reward pathway or promote withdrawal symptoms to encourage dependence.
• What mushroom species do you use? We will not be using mushrooms. The active drug in this trial is synthetic psilocybin.
• Will I hallucinate or experience other psychedelic effects? Participants may notice some mild psychoactive effects but we do not expect participants to experience hallucinations or other strong drug effects. Many people liken microdosing to feeling alert and motivated, like after having a coffee.
• Are there any legal risks to taking part in this study? No, this is a completely legal, ethically approved clinical trial.

What is the total length of the study and for how long must I participate?

• The trial intervention lasts for 10 weeks. Prior to commencing, participants must also complete a screening and baseline visit. So the total study period will last for approximately 12 weeks. The active dosing period will be six weeks.
• In addition to this, three months and six months after the intervention you will be asked to complete an online follow-up questionnaire.

I have diagnoses other than depression, can I participate? Yes, so long as depression is your primary mental illness and the other diagnosis is not:

• a psychotic disorder
• bipolar disorder
• a personality disorder
• post-traumatic stress disorder
• a substance use disorder.

If you have historically been diagnosed with one of these conditions but do not currently have symptoms, you may be able to participate.

Do I have to disclose my involvement to my employer? You are under no obligation to share medical information, including your participation in this trial, with your employer.

How do I get the process started? If you are interested in taking part, you can complete our eligibility questionnaire.

Will I be paid? There are no financial payments for participation in this trial. We will organise transport for you for all study visits.

When will I get the results of the study; when will it be published? This is a relatively large trial that will run for a number of years. We do not anticipate publishing results until 2027/8. We will send a copy of the study manuscript to all participants that request it.