LUCID-201-001: A Double-Blind, Single Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Lucid-201 in Healthy Male and Female Volunteers and Patients with Depressive Symptoms on a selective-serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI)

Exclusion Criteria41

• Known history or presence of any clinically significant hepatic, renal/genitourinary, gastrointestinal, cardiovascular, cerebrovascular, pulmonary, endocrine, immunological, musculoskeletal, neurological, psychiatric, dermatological or hematological disease or condition unless determined as not clinically significant by the PI/Sub-Investigator.
• Clinically significant history or presence of any clinically significant gastrointestinal pathology (e.g., chronic diarrhea, inflammatory bowel disease), unresolved gastrointestinal symptoms (e.g., diarrhea, vomiting), or other conditions known to interfere with the absorption, distribution, metabolism or excretion of the drug experienced within seven days prior to first trial drug administration, as determined by the PI/Sub-Investigator.
• History of seizures, including once off for both the participant and their first-degree relatives with history of seizures, history of head trauma with the exception of fully resolved minor concussions (no hospitalization or loss of consciousness), history of neurosurgery, or first-degree relatives with idiopathic generalized epilepsy or other congenital epilepsies.
• Presence of any clinically significant illness within 30 days prior to first dosing, as determined by the PI/Sub-Investigator.
• Presence of any significant physical or organ abnormality as determined by the PI/Sub-Investigator.
• A positive test result for human immunodeficiency virus (HIV), chronic Hepatitis B surface antigen, or Hepatitis C.
• A positive test result for drugs with abuse potential (amphetamines, methamphetamines, methadone, barbiturates, benzodiazepines, cocaine, opiates, methylenedioxymethamphetamine, phencyclidine, tetrahydrocannabinol), alcohol (via breathalyzer test), and/or cotinine.
• Positive pregnancy test for female participants.
• Known history or presence of:
• a. Hypersensitivity or idiosyncratic reaction to psilocybin, psilocin and/or related substances and/or excipients;
• b. Clinically significant food allergies;
• c. Presence of any dietary restrictions unless deemed by the PI/Sub-I as “Not Clinically Significant;”
• d. Severe allergic reactions (e.g., anaphylactic reactions, angioedema).
• a. Current or past history of schizophrenia spectrum, psychotic disorder (unless due to a medical condition), or bipolar I or II disorder.
• b. Current or past history within the last two years of alcohol or drug dependence (excluding caffeine and nicotine).
• c. Current or past history within the last five years of major depressive disorder, obsessive-compulsive disorder, panic disorder, anorexia nervosa, or bulimia nervosa.
• d. Have a first-degree relative with schizophrenia spectrum, psychotic disorder (unless substance-induced or due to a medical condition), or bipolar I or II disorder.
• e. Has a psychiatric condition judged to be incompatible with establishment of rapport or safe exposure to psilocin.
• f. Suicidal ideation or active suicidality, based on C-SSRS results.
• Intolerance to and/or difficulty with blood sampling through venipuncture.
• Use of psychedelics (e.g., psilocybin or ‘magic mushrooms,’ LSD, mescaline, DMT, ayahuasca) in the past two years or more than five times in lifetime.
• Individuals who have donated, in the days prior to first trial drug administration:
• a. >400 mL of blood in the previous 30 days;
• b. 500 mL or more in the previous 56 days.
• Donation of plasma by plasmapheresis within 7 days prior to trial drug administration.
• Individuals who have participated in another clinical trial or who received an investigational drug within 30 days prior to trial drug administration.
• Use of any enzyme-modifying drugs and/or other products, including strong inhibitors of cytochrome P450 (CYP) enzymes (e.g., cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (e.g., barbiturates, carbamazepine, glucocorticoids, phenytoin, St. John´s Wort, and rifampicin) in the previous 30 days before trial drug administration.
• Use of any prescription medication within 14 days prior to trial drug administration (except for accepted methods of contraception). The use of topical drugs (without significant systemic absorption) may be deemed acceptable by the PI/Sub-Investigator.
• Use of over-the-counter medications (including oral multivitamins, herbal and/or dietary supplements) within seven days prior to trial drug administration (except for accepted methods of contraception). The use of topical drugs (without significant systemic absorption) may be deemed acceptable by the PI/Sub-Investigator.
• Consumption of food or beverages containing grapefruit and/or pomelo within 10 days prior to trial drug administration.
• Consumption of food or beverages containing caffeine/methylxanthines, poppy seeds and/or alcohol within 48 hr before dosing (includes coffee and tea).
• Individuals having undergone any major surgery within three months prior to the start of the trial, unless deemed not clinically significant by PI/Sub-Investigator.
• Have any other conditions that, in the opinion of the Investigator or Sponsor, would make the participant unsuitable for inclusion, or could interfere with the participant participating in or completing the trial.
• Difficulty with swallowing tablets or capsules.
• Have had a new tattoo or body piercing within 30 days prior to trial drug administration.
• In the opinion of the Investigator, the participant is not suitable for the trial.
• Criterion 4 has been changed to the following:
• Presence of any clinically significant illness – except for depressive disorders – within 30 days prior to first dosing, as determined by the PI/Sub-Investigator.
• Criterion 10 has been changed to the following:
• One additional criterion has been added:
• Presence of severe depressive symptoms (as measured by the Hamilton-Depression Rating Scale (HAM-D), scores greater than or equal to 24).