Open-Label Psilocybin Study in Transdiagnostic Population

Inclusion Criteria: 1. At least one psychiatric symptom causing functional impairment over the past 30 days as established by a trained rater on the DIAMOND (at least "mild" impairment) and/or the WHODAS-2.0 12-item (a raw score of \>16) - assessment instruments indexing health and disability. 2. English fluency - able to understand the process of consent and the risk and benefits associated with the study, and able to provide written (signed and dated) informed consent form. 3. Agree to set up safe transportation after leaving the site following the dosing session. Acceptable arrangements include: arranging for a friend/family member to drive them home, pick them up and escort them home; if the participant is unable to arrange for a friend/family member to escort them home, the study staff will arrange private transportation and follow up with the participant to ensure that they arrived at their destination. 4. Must be able to identify a physician/treater that can be contacted to further assure that it is safe for the subject to participate and agree to sign a medical release for the investigators to communicate directly with this outside provider to confirm treatment and medical history via phone and/or email. 5. Ability to orally ingest pills for psilocybin dosing visit. 6. Must provide an adult contact (relative, spouse, close friend or other caregiver) who is willing and able to be reached by the PI and/or study personnel in the event of an emergency, and who can provide transportation for study visits if necessary and independently comment on any changes in the participant's mood or behavior after the administration of psilocybin. Be medically stable (no medical issues based on physical exam, labs and medical evaluation) as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an ECG, and routine blood and urinalysis laboratory tests (see section 6.3.4 for labs). Must also demonstrate decisional capacity based on clinical assessment ensuring the participant can understand, appreciate, and reason through the study's purpose, procedures, and associated risks, as well as tolerate the potential effects of the study medication. 7. Be psychologically stable: Concurrent psychotherapy is allowed if the type and frequency of the therapy has been stable for at least one month prior to screening and is expected to remain stable during participation in the study (up to 4-weeks post-dosing). 8. If participant is of childbearing potential, must agree to use adequate birth control and not attempt to become pregnant during study up to 4 weeks post dosing session (see Section 6.3.3). If participant is of childbearing potential, must have a negative urine pregnancy test at study entry and prior to the dosing session. Participants who are FOCBP must not plan to become pregnant or donate eggs, starting at least 1 month before receiving the trial intervention and for at least 1 week after the final follow-up visit. A FOCBP is defined as a female who is considered fertile following menarche and until becoming postmenopausal, unless permanently sterile (see below). Females in the following categories are not considered FOCBP: * Premenarchal. * Premenopausal with 1 of the following: 1. Documented hysterectomy or bilateral salpingectomy/tubal occlusion/oophorectomy. 2. Postmenopausal. * A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. * Females receiving hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use 1 of the nonhormonal, highly effective contraception methods if they wish to continue their HRT during the trial. Exclusion Criteria: Psychiatric Exclusion Criteria: 1. Personal history of a primary psychotic disorder (e.g., schizophrenia, delusional disorder, schizoaffective disorder) or Bipolar I disorder, or at least one first-degree relative with a diagnosis of primary psychotic disorder (e.g., schizophrenia, delusional disorder, schizoaffective disorder) or Bipolar I disorder. 2. Active suicidal intent or suicidal or non-suicidal self-injurious behaviors, as defined by a "yes" response to question 4 on C-SSRS within the past 6 months at screening or prior to dosing (Active Suicidal Ideation with Some Intent to Act, with or without Specific Plan). 3. Use of a classic psychedelic (i.e., LSD, psilocybin, DMT, mescaline) within the 3 months prior to enrollment (not including microdosing). 4. Use of ketamine within the past month at Screening. 5. History of regular and frequent use of a classic psychedelic (more than 10 times per year) in a structured, intentional setting over the past 10 years. Structured use refers to participation in organized retreats, ceremonies, or church services. Microdosing is not included. 6. History of Other Hallucinogen Use Disorder. 7. History of intolerance to drugs known significantly to alter perception (i.e., psilocybin, LSD, salvinorium A, mescaline). 8. Patients taking 5-hydroxytryptophan or St. John's Wort 9. A positive breathalyzer test 10. A positive urine toxicology screening, which detects the standard panel of five drugs (marijuana, cocaine, opioids/opiates, amphetamines, and phencyclidine (PCP)), as well as benzodiazepines, 3,4-methylenedioxymethamphetamine (MDMA). If a participant tests positive for any of these substances, the PI may request a retest during the screening phase. The exceptions to the exclusion are prescribed opioid pain medication and benzodiazepines, or over-the-counter non-narcotic pain medication. If a participant is prescribed benzodiazepines, the participant will be asked to refrain from taking on the day of the psilocybin dosing session. Additionally, participants will not be excluded from the study based on the use of cannabis. However, they will be instructed to refrain from use of cannabis on the day before, day of, and day following the drug administration session. Participants whose primary clinical presenting issue is substance use-related will not be excluded based on a positive test at screening but will be expected to adhere to the dosing day drug test produces (outlined in section 6.3.6). 11. Changes to psychotropic medication and/or dosages within the past 3 months. 12. Current or recent (within 2 weeks of enrollment) prescription of MAOI, Lithium, and/or methadone use. 13. Has a psychiatric condition that precludes the establishment of therapeutic rapport as evidenced by long-term patterns of unstable relationships, a history of significant stress- related paranoia, or identity disturbances. 14. Use of any other investigational drugs within 30 days prior to Screening. 15. Allergy to gelatin. General Medical/Laboratory Exclusion Criteria: 1. Hypertension at screening is defined as: systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg, on the lowest of three measurements. 2. History of cardiovascular disease, including but not limited to clinically significant coronary artery disease, cardiac hypertrophy, cardiac ischemia, congestive heart failure, myocardial infarction, angina pectoris, coronary artery bypass graft or artificial heart valve, stroke, transient ischemic attack, or any clinically significant arrhythmia. 3. Any clinically significant abnormal electrocardiogram (ECG) finding, such as findings suggestive of ischemia or infarct, complete bundle branch block, atrial fibrillation or other symptomatic arrhythmias, or predominantly non-sinus rhythm, at Screening. 4. Resting QT interval with Fridericia's correction (QTcF) ≥ 450 msec (male) or ≥ 470 msec a. (female) at Screening, or inability to determine QTcF interval. 5. Presence of risk factors for torsades de pointes, including: long QT syndrome, uncontrolled hypokalemia or hypomagnesemia, history of cardiac failure, history of clinically significant/symptomatic bradycardia, family history of idiopathic sudden death or congenital long QT syndrome, or concomitant use of a torsadogenic medication. 6. Moderate-to-severe hepatic impairment, defined as a Child-Pugh score ≥ 5, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2 x the upper limit of normal (ULN), or bilirubin \> 1.5 x ULN, unless this is attributable to Gilbert's syndrome 7. Use of vasoconstrictive medications (i.e. sumatriptan, pseudoephedrine, midodrine) within 5 half-lives of test days and use of steroids or certain other immunomodulatory agents (i.e. azathioprine) in the past 2 weeks. 8. Moderate-to-severe renal impairment, defined as an estimated glomerular filtration rate of \< 50 mL/min/1.73 m2 at Screening 9. Uncontrolled diabetes with an HbA1c \> 8 10. Significant uncontrolled hypothyroidism (thyroid stimulating hormone \[TSH\] \< 0.8 x lower limit of normal) with the exception of stably treated hypothyroidism and uncontrolled hyperthyroidism (thyroid stimulating hormone \[TSH\] \< 0.8 x \> 1.5 x upper Any other condition, disorder or finding which in the opinion of the investigator would adversely impact participant safety or the ability of the participant to complete the study, including compliance with all study requirements and procedures.