Researchers at the University of California, San Francisco (UCSF) have initiated a first-in-human Phase I clinical trial to evaluate whether repeated low-intensity focused ultrasound can safely reduce persistent auditory hallucinations in individuals with schizophrenia. Led by UCSF psychiatry professor Karuna Subramaniam, the study began enrollment in late October 2026 in California, according to the Focused Ultrasound Foundation. The research aims to determine if non-invasive sound waves directed at deep brain structures can offer relief for patients whose symptoms do not fully respond to standard antipsychotic medications.

How the UCSF Focused Ultrasound Trial Works

The UCSF trial investigates a non-invasive wearable device developed by Attune Neurosciences that delivers low-intensity focused ultrasound (LIFU) through the skull. According to Medical Xpress, the technology targets the caudate, a deep brain region located within the striatum that researchers hypothesize plays a critical role in generating auditory hallucinations.

The Phase I protocol plans to enroll up to 12 participants experiencing persistent auditory hallucinations. The study uses a within-participant crossover design, meaning each volunteer serves as their own comparison group. Participants are scheduled to undergo five daily active ultrasound sessions and five sham comparison sessions, with the two treatment periods separated by a washout period to allow any immediate effects to clear.

During the sham sessions, the wearable device delivers unfocused sonication. This method puts out the same overall amount of ultrasound energy and mimics the physical sensation of the procedure without concentrating the acoustic energy on the caudate. This structure helps scientists distinguish the specific physiological effects of targeted deep-brain stimulation from placebo or nonspecific clinical responses. Before and after the treatment phases, investigators will use resting-state functional magnetic resonance imaging (fMRI) to measure changes in neural connectivity involving the caudate, while also monitoring mood, psychiatric symptoms, tolerability, and side effects.

Evaluating Early Claims and Predecessor Data

Because the UCSF trial is a Phase I investigation, its primary scientific objective is establishing basic safety and procedural feasibility rather than proving clinical cure or broad efficacy. A sample size of up to 12 individuals is designed to detect immediate tolerability issues and observe preliminary biomarkers, not to support broad medical conclusions for the wider patient population.

Differences in how preliminary observations are framed have already emerged in coverage of the launch. According to Medical Xpress, the study is strictly an early-stage evaluation of repeated LIFU sessions focusing on safety and feasibility, while TechnologyTimes characterizes the project as building on a three-person predecessor pilot and claims in its headline that the wearable device silenced voices in all three initial patients. Clinical researchers emphasize that secondary reports of preliminary pilot responses do not substitute for peer-reviewed, controlled outcome data from the newly launched trial.

Parallel Research: NYU Langone Studies Ultrasound for Delusions

The UCSF launch coincides with separate, newly published research exploring ultrasound neuromodulation for a different dimension of psychosis. According to DPA International, researchers at NYU Langone Health recently tested transcranial ultrasound stimulation in 10 individuals diagnosed with schizophrenia or schizoaffective disorder whose symptoms persisted despite medication.

Published in the journal npj Acoustics, the NYU Langone study focused on reducing delusions rather than auditory hallucinations, targeting a different deep brain structure called the globus pallidus internus. Guided by MRI scans, researchers administered a single 10-minute session where gentle sound waves were switched on and off every 30 seconds. Each of the 10 participants received both the real stimulation and a pretend treatment separated by a one-week interval under double-blind conditions.

The NYU team observed a modest reduction in delusion severity lasting up to a week following the active 10-minute session, with average patient scores on a delusion severity scale dropping by 1.2 points. By contrast, average scores increased by 0.4 points following the pretend session. Side effects in the NYU cohort—which included temporary fatigue, mild headaches, and brief symptom fluctuations—were mild and resolved quickly. While both the NYU and UCSF initiatives highlight growing psychiatric interest in acoustic brain stimulation, the two trials involve distinct brain targets, stimulation schedules, and primary symptoms.

Frequently Asked Questions

What safety and tolerability findings will the UCSF trial monitor?

Researchers will systematically track adverse events, physical comfort, mood changes, and overall psychiatric symptom stability across the five daily active sessions and five sham sessions, alongside pre- and post-treatment fMRI brain scans to assess structural and functional safety.

How does the study separate real ultrasound effects from the placebo effect?

Every participant receives both active focused ultrasound and a sham condition separated by a washout period. The sham condition delivers unfocused ultrasound energy so the physical experience remains identical without concentrating sound waves on the caudate.

Are early reports of reduced hallucinations proven clinical outcomes?

No. While secondary reporting has referenced symptom reductions in a small three-person preliminary pilot, those observations are not confirmed, peer-reviewed efficacy outcomes. Larger, randomized trials will be required after Phase I safety testing before the device can be considered a validated therapy.

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