Psychedelic-assisted Group Program for First Responders

This study is a two-group feasibility study of oral psilocybin combined with a 12-week group-based program, customized for firefighters. Trained facilitators will help create a trauma-informed space for the group (n = 6-8) to thrive and promote cognitive resilience. The topics covered throughout the 12 weeks include breath-work, mindfulness, self-compassion, embodiment, and Internal Family Systems work.

Group 1 (control): 12-week group-based program, with a breathwork day at week 10

Group 2 (intervention): 12-week group-based program, with a 10mg dose of psilocybin (PEX010) at Week 10

Assessment timepoints:

* Baseline
* Mid-program (Week 6)
* End of program (Week 12)
* 6-month follow up

All participants will undergo a 12-week, group-based program (one session per week, for 12 weeks). The first group session, as well as the Week 10 session will occur in-person. The remainder of the sessions will occur remotely. Each week, trained facilitators will help create a trauma-informed safe space for the group to thrive and promote cognitive resilience. The topics covered throughout the 12-week program include breath-work, mindfulness, self-compassion, embodiment, and Internal Family Systems work.

During Week 10, participants will be provided with either psilocybin (active group) or complete a breathwork day (control group). For participants randomized to the active group, they will receive 10mg of psilocybin on Week 10. A clinician certified and trained in the therapeutic use of psilocybin will be on site for participants in the psilocybin group. During the dosing session, the clinicians will respond to whatever needs arise. This may include escorting them to the bathroom, giving them a drink of water. At least two staff (one facilitator and one clinician) will be on site during dosing days.

The dose will be administered in clear capsules with approximately 500ml of water. Aside from the dose provided, the weekly session will continue as usual, with a focus on breath-work, embodiment, and gentle movement on dosing days.

Psilocybin in the study comes in the form of the study drug, PYEX. PYEX is a drug substance which is a partially purified fraction of the extract of Psilocybe cubensis mushroom fruiting bodies. It is a mixture of indole alkaloids, other mushroom fruiting body components and stabilization excipients. The major indole alkaloids present include psilocybin and psilocin (dephosphorylated psilocybin). PEX010 is a capsule for oral administration and is manufactured with PYEX (12.5-14.0% psilocybin), excipients, and HPMC (hydroxypropyl methyl cellulose) capsules.

Eligibility Criteria:
Inclusion Criteria:

* Male or female, 19 to 65 years of age
* Must be a first responder, any work status (Employed full-time or part-time, Off-work, Retired, Volunteer)
* Fluent in English
* Able to understand the informed consent form, study procedures and willing to participate in study
* Clinically diagnosed with a mental health condition such as:

  1. Depression
  2. Chronic anxiety
  3. Obsessive-compulsive disorder
  4. PTSD
  5. Unresolved grief
  6. Adjustment Disorder
  7. Acute Stress Disorder
* Stable dose of medications for the last three months, with no changes anticipated for the duration of the study
* Medical clearance by the Investigator (MD) prior to study enrollment
* Willing and able to attend two in-person sessions throughout the 12-week program, in addition to remote sessions
* Concurrent therapy is allowed if the type and frequency of the therapy has been stable for at least two months prior to screening and is expected to remain stable during participation in the study.
* Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on Week 10. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on Week 10.
* Agree that for one week before the drug sessions, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement (specifically SAM-e, 5-HTP, L-tryptophan, St John's Wort) except when approved by the study Investigator. Exceptions will be evaluated by the Investigator and may include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals.
* Agree to refrain from consuming alcohol within two days prior to the Week 10 visit.
* Agree not to take any "as needed" medications on the morning of the Week 10 visit.
* Agree to use of highly effective methods of contraception during the study (females)
* Normal body mass index (BMI 18.5-24.9)

Exclusion Criteria:

* Current or past history of schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), bipolar disorder, delusional disorder, dissociative disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder, anorexia nervosa, bulimia nervosa or substance abuse, as assessed by medical history
* Presence of active psychotic symptoms
* Currently diagnosed psychotic disorder in first-degree relatives, not including psychotic disorders secondary to an apparent medical reason, e.g. brain injury, dementia, or lesions of the brain, as assessed by medical history.
* Diagnosis of dementia or delirium
* Risk of suicide as determined by the Investigator
* Significantly intrusive PTSD as determined by the Investigator
* Extreme emotional lability can be disruptive to the group milieu and is a relative exclusion criterion
* Uncontrolled cardiopulmonary disease, cardiovascular disease, or hypertension
* Any other clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, vascular or any other major concurrent illness that, in the opinion of the Investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if he/she takes part in the study
* Psychoactive substance use (MDMA, psilocybin, LSD) within the previous two months.
* If female and of child-bearing potential: pregnant, suspected or planning to become pregnant during the study
* Participation in another clinical trial (currently or within the last 30 days)
* Current use of rifamycins (rifampin, rifabutin, rifapentine), anticonvulsants (carbamazepine, phenytoin, phenobarbital), nevirapine, efavirenz, taxol, dexamethasone); cytochrome P450 Inhibitors - including all HIV protease inhibitors, verapamil, diltiazem, itraconazole, ketoconazole, erythromycin, clarithromycin, azithromycin, and troleandomycin; ergot alkaloids, pimozide, midazolam, triazolam, lovastatin, simvastatin, fentanyl, warfarin, metoprolol, propranolol, buspirone, tramadol, selegiline, sumatriptan.
* Current use of inhibitors of UGT1A9 and 1A10, monoamine oxidase inhibitors (MAOIs), Tricyclic antidepressants, aldehyde dehydrogenase inhibitors (ALDHs) and alcohol dehydrogenase inhibitors (ADHs).