• 21 to 65 years old

• Fluent in English

• Have given written informed consent

• Have at least a high-school level of education or equivalent (e.g. GED).

• Have a baseline GRID-HAMD score ≥ 16

• Have a confirmed DSM-5 diagnosis of Major Depressive Disorder and currently experiencing a major depressive episode

• Have a confirmed DSM-5 diagnosis of Alcohol Use Disorder

• Have undergone some form of therapy for MDD or AUD in the past, but are not interested in initiating standard pharmacotherapies for major depressive disorder or alcohol use disorder (e.g. selective serotonin reuptake inhibitor, disulfiram, naloxone, etc.)

• Be judged by study team clinicians to be at low risk for suicidality

• Average of at least 4 non-drinking day/month in the past 90 days, or a score of less than 4 on the PAWWS scale

• Have at least 2 heavy drinking days per month in the past 90 days

• Concurrent psychotherapy or pharmacotherapy with SSRIs, SNRIs, and/or bupropion 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

• 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 and urinalysis laboratory tests

• 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 the mornings of drug session days. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on session days

• Agree to refrain from using any psychoactive drugs, including nicotine, within 24 hours of each drug administration. The exception is caffeine

• Agree not to take any as needed medications on the mornings of drug sessions

• Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration

• Agree to use effective methods of contraception during the study (females)

• Agree that for one week before each drug session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the study investigators. Exceptions will be evaluated by the study investigators and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals

• Have limited lifetime use of hallucinogens (the following criteria are preferred: no use in the past 5 years; total hallucinogen use less than 10 times)

• Proof of COVID-19 vaccination