Between 2014 and 2024, 363 clinical trials on ketamine were registered. Most trials addressed FDA-approved uses: anesthesia (22%), pain management (28%), and esketamine for treatment-resistant depression (29%). Trials for treatment-resistant depression have reached phase III and IV. Combinations with electroconvulsive therapy, psychotherapy, virtual reality, or transcranial magnetic stimulation are common. Sub-anesthetic doses may offer new treatments for neuropsychiatric conditions involving glutamate excitotoxicity and oxidative stress, such as major depression, schizophrenia, and bipolar disorder. The number of ketamine studies is expected to grow, and new variants may be approved for additional indications.
The clinical trial landscape for ayahuasca and DMT expanded rapidly after 2020-2021, dominated by early-stage development. Most trials are phase I, primarily sponsored by academic or hospital institutions, and focus on DMT-only administration. Eligibility criteria are conservative, enrolling medically and psychiatrically healthy adults with extensive cardiovascular and psychiatric exclusions. Primary outcomes prioritize acute safety, physiological monitoring, and characterization of subjective altered-states, while disorder-specific symptom endpoints are less common. Publications from depression-focused trials provide preliminary evidence of potential clinical effects, but the field remains constrained by a limited number of indication-specific programs beyond depression.