This clinical trial studies if **GATE-251** can help treat major depressive disorder (MDD), a severe form of depression. It also looks at how safe GATE-251 is. Participants will take GATE-251 or a placebo (a pill with no medicine) once a week for 6 weeks. During this time, they will visit the clinic weekly to see if their depression improves. This is a **Phase 2** study, which means that the main goal is to find out if the treatment works and if it's safe. The study will last up to 98 days for each person, including time for initial checks, the treatment period, and follow-up visits. - **Commitment:** Weekly clinic visits for 6 weeks. - **Eligibility:** Adults 18-64 with specific depression, anxiety, and insomnia scores. - **Risks:** Possible side effects from GATE-251, like any new medication. Participants must not have certain health conditions or take specific medications. They must agree to not use certain substances, like alcohol or cannabis, during the trial. If you are interested, you should discuss with your doctor to see if this study is right for you.