Assessing of Behavioral Risk and Response to Electromagnetic and Psychedelic Therapies

NCT07745569 | Not Yet Recruiting Phase 2 DMC FDA Drug FDA Device

• 2 other identifiers: 25-535HT9425-25-1-0954
• Study Type: interventional
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief Summary

PRE-EMPT will assemble a cohort of 150 participants from three populations (low risk, intermediate risk, and high risk for self-harm). We will obtain clinical assessments, structural and functional MRI utilizing tasks pioneered by our team to assess cognitive control (CC) and emotion regulation (ER), and peripheral circular RNA (circRNA) levels to characterize the molecular brain states associated with behavioral risk. The clinical, imaging, and transcriptomic data will be fused and jointly analyzed to increase the accuracy of our risk prediction models. PRE-EMPT in three separate Aims will then prospectively assess three promising and innovative interventions for their potential to reduce suicidal ideation and alter activity in key neural networks: 1) neurofeedback (NF) using real-time fMRI with simultaneous electroencephalography (EEG), 2) a form of transcranial magnetic stimulation (TMS) called accelerated intermittent theta burst stimulation (aiTBS) with dose optimization through electric field modeling; and 3) psilocybin assisted therapy (PSI), with flexible dosing plan to maximize the depth of psychedelic experience. These therapies were chosen based on our team's prior work in all three interventions demonstrating rapid action and large effects.

Conditions

PTSD; Major Depression; PTSD - Post Traumatic Stress Disorder; Suicidality

Keywords

TMS; Transcranial magnetic stimulation; neuromodulation; psilocybin; neurofeedback

Outcome Measures

Primary Outcomes (1)

• Neurofeedback

  Aim 1 will recruit a low risk to intermediate risk populations, i.e., low-to-moderate levels of depression or anxiety/PTSD with occasional suicidal ideation, up to significant depression and anxiety with chronic suicidal ideation). Following baseline assessment with the universal assessment battery, participants will be randomized to active or sham group and undergo real-time fMRI neurofeedback studies occurring across two visits.

  From enrollment through post-treatment visit about 6-8 weeks.

Secondary Outcomes (1)

• TMS

  From enrollment through post-treatment visit about 6-8 weeks.

Other Outcomes (2)

• Psilocybin

  From enrollment through post-treatment visit about 6-8 weeks.

• Predictive model

  From enrollment through post-treatment visit about 6-8 weeks.

Study Arms (3)

Arm 1: Neurofeedback

SHAM COMPARATOR

You will undergo 2 sessions of neurofeedback treatment, with an interval of 1-2 weeks between sessions up to a month maximum. Neurofeedback training and treatment in this study is performed inside an MRI scanner while wearing a cap to measure brain waves (EEG). You will be lying comfortably inside an MRI machine for 1 hour while your brain activity is being scanned. You will see a screen with a thermometer-style red bar, which will represent activity of a specific region of your brain (the amygdala), involved in emotion experience in the active condition. For those assigned to the sham condition, the red bar will not represent brain activity and will move randomly. By controlling the height of the red bar in real time, you will be able to try to regulate activity of that brain region. By controlling the neurofeedback signal, you may learn to enhance your brain activity associated with happy future thoughts.

Behavioral: Neurofeedback

Arm 2: TMS

ACTIVE COMPARATOR

The day before you begin the rTMS treatments, you will be asked to come in for a short visit to determine the level of stimulation that is right for you. You will then receive up to 100 rTMS treatments, given five days a week for 10 days. For the first 50 treatments, you will receive real stimulation to the left side of your brain. After 50 treatments to the left side, depending on how it affects you, you may qualify to receive 50 more treatments to the right side of your brain. You might feel a slight twitch in your hand. A camera will track your head movements during the procedure. Most people experience tapping or twitching on their scalp during rTMS. The stimulation will last 10 minutes, followed by 30 minutes of rest before another session.

Device: Transcranial Magnetic Stimulation

Arm 3: Psilocybin

ACTIVE COMPARATOR

You may receive 2 psilocybin assisted therapy treatments, given once a week, for 2 weeks. Preparation Sessions: Before the first psilocybin session, you will meet with the study therapist and physician for 1-2 preparation meetings, to answer questions and make sure you understand the sequence of events during the intervention. Psilocybin Session: You will lie on a comfortable couch, receive the medication and be guided through the psychedelic experience with the two trained study staff, while being medically monitored, for approximately 8 hours. If needed, you may receive medications to treat side effects like high blood pressure, or anxiety. You will need to have a trusted person to take you home and stay with you for the night after each psilocybin session. Integration Session: The next day after each psilocybin session, you will meet with the therapist again and talk about your experience. Depending on what you experienced in the first week, the dose may be increased.

Drug: Psilocybin (drug)

Interventions

Psilocybin (drug) DRUG

In this intervention, open-label flexible-dosing of psilocybin assisted therapy in intermediate and high-risk patients will be delivered to reduce suicidal ideation and identify mediators of response. The study team will deliver two separate psilocybin sessions accompanied by preparation and integration therapy. Factors such as dose, depression severity, serotonergic use, and depth of mystical experiences will be correlated with suicidality reduction.

Arm 3: Psilocybin

Neurofeedback BEHAVIORAL

This intervention will deliver active or sham real-time fMRI neurofeedback occurring across two visits to a low-to-intermediate risk population, i.e., low-to-severe levels of depression or anxiety/PTSD identified by clinical scales, with suicidal ideation present but no intent or plan.

Arm 1: Neurofeedback

Transcranial Magnetic Stimulation DEVICE

This intervention will deliver open-label aiTBS, an efficient FDA-cleared form of rTMS for major depressive disorder to patients with intermediate/high risk (i.e., significant depression and anxiety; chronic suicidal ideation). The study team will conduct modeling of the electric field intensity and distribution for each participant, and provide proof of concept for an electric-field informed dosing strategy that engages brain networks.

Also known as: TMS

Arm 2: TMS

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old
• Have been on a stable psychiatric medication regimen for at least four weeks prior to study participation.
• Formal diagnosis of major depressive disorder or post-traumatic stress disorder by a mental health professional.
• Must be under the care of a medical provider (ex: primary care, therapist, psychiatrist, psychiatric nurse practitioner) for mental health treatment who can provide contact information and written confirmation that they will be willing and able to care for participant during their entire involvement in the study.

You may not qualify if:

• A prior history of other central nervous system disease or any history of seizures;
• history of psychotic disorders (e.g., schizophrenia, schizoaffective disorder, bipolar disorder type I);
• history of current or recent (within one year) substance/alcohol use disorder, with the exception of tobacco use disorder;
• meet criteria for Very High risk of suicide, or require inpatient hospital-level care for psychiatric reasons at time of consent, to reduce exacerbation of risk of harm to self during study;
• presence of any implanted metal or electrical device (e.g. pacemaker);
• recent medical hospitalization (within three weeks);
• any condition that would prevent the participant from completing the protocol, such as significant agitation;
• appointment of a legal representative or treatment guardian;
• any ongoing litigation related to a health condition;
• any other contraindication to exposure to strong magnetic fields or MRI, such as severe claustrophobia;
• pregnancy or lactation;
• a family history of schizophrenia or schizoaffective disorder (first or second degree relatives), or bipolar disorder type 1 (first degree relatives), to reduce risk of exacerbation of an undiagnosed psychotic condition;
• other medical conditions that would preclude safe participation in the trial (e.g., decompensated heart failure);
• starting or planning to start psychotherapy or changing the frequency or intensity of existing psychotherapy during the trial (current psychotherapy can be continued provided the frequency and intensity has been stable for ≥2 months prior to screening);
• membership in a vulnerable population (minors, prisoners);

Sponsors & Collaborators

• University of New Mexico: lead
• United States Department of Defense: collaborator
• The Mind Research Network: collaborator

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Combat Disorders; Depressive Disorder, Major; Suicidal Ideation

Interventions

Transcranial Magnetic Stimulation; Psilocybin; Pharmaceutical Preparations; Neurofeedback

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Depressive Disorder; Mood Disorders; Suicide; Self-Injurious Behavior; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Biofeedback, Psychology; Mind-Body Therapies; Complementary Therapies; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Feedback, Psychological

Study Officials

• Davin Quinn, MD

  University of New Mexico

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Crystal A Garcia

CONTACT

505-272-9552; crabaca@salud.unm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2026
• First Posted: August 4, 2026
• Study Start: August 31, 2026
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2030
• Last Updated: August 4, 2026

Record last verified: 2026-07