Clearmind’s Phase I/IIa program for CMND-100 in alcohol use disorder has cleared an early safety gate: after dosing the first cohort (n=6; Yale n=4, Johns Hopkins n=2), an unblinded DSMB review recommended the study continue, and a new site at Tel Aviv Sourasky Medical Center has opened and enrolled its first patient. The FDA-cleared trial is evaluating single and multiple oral doses of CMND-100, a non-hallucinogenic, MEAI-based candidate, for safety, tolerability, pharmacokinetics, and preliminary efficacy.
The core development is threefold: initial dosing completed with top-line signals the company characterizes as positive, an external safety body authorizing progression without modification, and geographic expansion to accelerate recruitment and diversify the dataset. The study is already running at Yale, Johns Hopkins, and Hadassah; adding Tel Aviv Sourasky increases patient flow and adds operational redundancy—important in a disorder with episodic engagement and historically high screen fail and dropout rates.
Strategically, Clearmind is trying to carve a differentiated path within the “psychedelic-adjacent” AUD space by advancing a non-hallucinogenic mechanism that avoids the psychotherapy-heavy infrastructure classic psychedelics require. That choice is as much about trial execution as it is about clinical positioning. If CMND-100 maintains a benign safety profile at ascending doses, sponsors and sites can operate with standard outpatient workflows rather than the monitored dosing sessions, specialized training, and potential REMS considerations associated with hallucinogens. The site mix—two high-credibility U.S. academic centers plus Israeli hospitals with strong internal medicine and psychiatry capabilities—also signals a bid for cross-border regulatory relevance and a faster enrollment cadence than a purely U.S. footprint might allow.
For sites, the operational load skews toward conventional early-phase work: PK sampling, sequenced dose escalation, and frequent patient-reported outcomes for craving and consumption, rather than intensive psychotherapy delivery. That can widen the pool of participating centers and staff, supporting throughput without specialized psychotherapeutic capacity. CROs will need to manage harmonization across U.S.-Israel regulatory and data standards, especially around alcohol consumption endpoints, electronic diaries, and potential biomarker use. For sponsors and investors, the tension is familiar: early green lights from DSMBs are necessary but not sufficient; the program’s value will ride on whether reductions in craving translate into accepted regulatory endpoints such as percent heavy drinking days, no heavy drinking days, or sustained abstinence. Regulators have been clear that subjective craving alone will not carry an approval in AUD, and placebo response can be substantial in behavioral measures.
What matters next is dose-escalation continuity and the first look at objective consumption metrics alongside safety and PK. Clarity on the magnitude of effect—absolute and relative changes in heavy drinking days, responder analyses, and durability over multiple weeks—will determine whether the Phase IIa can pivot to a randomized, adequately powered proof-of-concept rather than remain a signal-finding exercise. Watch for the incorporation of adherence and consumption verification tools such as transdermal alcohol monitoring or remote breath testing to de-risk self-report bias, as well as any interaction data with common concomitant medications used in AUD and comorbid anxiety/depression. The non-hallucinogenic posture could streamline both development and commercialization if efficacy holds, but the bar remains reduction in harmful drinking behavior. Without clear, quantified outcomes beyond safety, the program’s momentum will hinge on the next cohort readouts and the design discipline of the impending placebo-controlled expansion.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
