Safety and Efficacy of Low Dose MM120 for ADHD Proof of Concept Trial

Safety and Efficacy of Repeated Low Dose d-Lysergic Acid Diethylamide (LSD) D-tartrate (MM120) as Treatment for ADHD in Adults: a Multi-center, Randomized, Double-blind, Placebo-controlled Phase 2a Proof of Concept Trial

This study measures the safety and efficacy of repeated low dose MM120 as treatment for ADHD in adults: a multi-center, randomized, double-blind, placebo-controlled

Study Overview

• Status: Completed
• Conditions: ADHD; Attention Deficit Disorder
• Intervention / Treatment: Other: Placebo; Drug: MM120

Detailed Description

This study is a multi-center, randomized, double-blind, placebo-controlled Phase 2a study of low dose MM120 (20 μg) compared with a placebo administered for 6 weeks (twice a week on a 3/4-day schedule).

Low dose MM120 (20 μg) is about 20% of the dose typically consumed for recreational psychedelic purposes.

There will be a 1:1 randomization, double-blind, to MM120 or placebo with the aim to reach 26 evaluable patients in each of the 2 arms at Week 6.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands
    • Maastricht University
• Switzerland
  • Basel, Switzerland
    • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female outpatients ≥ 18 and ≤ 65 years of age at Screening
• Patients with the diagnosis of Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) ADHD, as determined by clinical evaluation and confirmed by structured interview (MINI).
• Adequate organ function.
• Able to understand the study procedures and understand risks associated with the study, and sign written informed consent to participate in the study.
• Must be willing to refrain from more than 6 standard alcoholic drinks a week, more than 10 cigarettes a day, and more than 2 cups of coffee a day throughout the study treatment period (6 weeks) and until the last study visit is complete.

Exclusion Criteria:

• Past or present diagnosis of a primary psychotic disorder or first degree relative with a psychotic disorder.
• Past or present bipolar disorder (DSM-5).
• Any lifetime history of suicide attempt.
• Once Informed Consent form is signed, not willing or able to stop any prescription or non-prescription ADHD medications.
• Use of investigational medication/treatment in the past 30 days.
• Patients with a positive urine drug screen with the exception of THC or its metabolites.
• Pregnant or nursing females.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm 1- Placebo; A total of 26 patients will receive a placebo identical in appearance to the investigational medicinal product (IMP) administered orally twice weekly (e.g., Tuesday/Friday) for 6 weeks.	Other: Placebo; A treatment which is designed to have no therapeutic value.
Experimental: Arm 2- MM120; A total of 26 patients will receive 20 μg of MM120 administered orally twice weekly for 6 weeks.	Drug: MM120; MM120 is a psychedelic drug that can cause intensified thoughts, emotions, and sensory perception. At sufficiently high dosages MM120 manifests primarily visual, as well as auditory, hallucinations.; Other Names: MM-120; DT120; lysergide tartrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Adult Attention-Deficit/Hyperactivity Disorder (ADHD) Symptoms	The Adult ADHD investigator symptom rating scale (AISRS) total score consists of 18 items from the original Attention-deficit/hyperactivity Disorder Rating Scale (ADHD-RS). The ADHD-RS includes 9 items that address symptoms of inattention, and 9 items that address symptoms of impulsivity and hyperactivity. Each item is rated from 0 to 3. The AISRS total score can range from 0 to 54. A higher score corresponds to a worse severity of ADHD.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Adult Attention-Deficit/Hyperactivity Disorder (ADHD) Investigator Symptom Rating Scale (AISRS) Symptoms	The Adult ADHD investigator symptom rating scale (AISRS) total score consists of 18 items from the original Attention-deficit/hyperactivity Disorder Rating Scale (ADHD-RS). The ADHD-RS includes 9 items that address symptoms of inattention, and 9 items that address symptoms of impulsivity and hyperactivity. Each item is rated from 0 to 3. The AISRS total score can range from 0 to 54. A higher score corresponds to a worse severity of ADHD.	Week 2
Number of Patients Who Experience a Decrease in the Clinical Global Impressions Scale (CGI-S)	The Clinical Global Impression - Severity (CGI-S) was used to assess the subject's current severity of illness at the time of the assessment relative to the clinician's past experience with patients who have the same diagnosis. The CGI-S comprises 1 Investigator-completed (or trained rater-completed) item with 7 possible ratings (1-7 points), where a higher score indicates more severe illness.	Baseline, Week 2, Week 6, Week 10
Change From Baseline in in Clinical Global Impressions Scale (CGI-S)	The Clinical Global Impression - Severity (CGI-S) was used to assess the subject's current severity of illness at the time of the assessment relative to the clinician's past experience with patients who have the same diagnosis. The CGI-S comprises 1 Investigator-completed (or trained rater-completed) item with 7 possible ratings (1-7 points), where a higher score indicates more severe illness.	Baseline, Week 2, Week 6
Adult Attention-deficit/Hyperactivity Disorder Self-reporting Rating Scale (ASRS)	The Adult Attention-Deficit/Hyperactivity Disorder Self-Reporting Rating Scale (ASRS) is composed of 18 questions, and uses a scale that ranges from 0-4 based on the individuals mark in either the "never, rarely, sometimes, often, very often" column for a possible total score of 72. A higher score corresponds to a worse severity of ADHD.	6 weeks
Change From Baseline in Connors' Adult ADHD Rating Scale (CAARS)	The Connors' Adult ADHD Rating Scale (CAARS) Self-Report Long Form is a 66-item measure of ADHD symptom. Responses are scored on a 4-point scale, where 0 = not at all, 1 = just a little, 2 = pretty much, and 3 = very much. Item scores are summed to three main scores which are then transformed using population-derived age- and sex-adjusted norm values to a T-score. A T-score < 60 indicates no ADHD. A T-score of 60-64 indicates borderline ADHD. A T-score of > 64 indicates ADHD.	6 weeks
5 Dimensions of Altered States of Consciousness Questionnaire (5D-ASC) Scores	The 5 dimensions of altered states of consciousness (5D-ASC) scale is a visual analog scale (VAS) consisting of 94 items each scored on a 0-100mm VAS extrapolated to 100% scale for quantitative evaluation. These 94 items are categorized into five dimensions: oceanic boundlessness (min:0, max:2700), anxious ego dissolution (min:0, max:2100), visionary destructuralization (min:0, max:1800), auditory alterations (min:0, max:1600), and vigilance reduction (min:0, max:1200). The total score is the sum of all questions and can range from 0 to 9400. Higher scores = more alteration in state of consciousness.	6 weeks
Mystical Experience Questionnaire 30 Items (MEQ30)	The Mystical Experience Questionnaire 30 item (MEQ30) is a 30-item questionnaire rated on a six-point scale. The scale has been used to assess mystical experiences in studies using psilocybin and LSD. Higher scores = greater mystical experiences. The total score is expressed as a percentage of the maximum possible score (0 to 100%).	6 weeks
Summary of Drug Effects Visual Analog Scale (VAS)	A series of single item visual Analog Scales (VAS) are used repeatedly 0 -6 hours after drug administration: The following 9 items were used in VAS (0-100 mm): "any drug effect", "good drug effect", bad drug effect", "drug liking", "fear", nausea", "alteration of vision", "alteration of sense of time", and "the boundaries between myself and my surroundings seem to blur". VAS scores range from 0 = no effect to 100 = strong effect. The scores for each item are extrapolated to a 100% scale and presented for each time point of assessment.	6 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Outcomes	Maximum Plasma Concentration [Cmax] of MM-120 in the blood at Week 1 Day 1	0.5, 1, 2, 3, 4, 6 hours post-dose
Pharmacokinetic Parameters (Cmax)	Maximum concentration (Cmax)	0.5, 1, 2, 3, 4, 6 hours post-dose
Pharmacokinetic Parameters (Tmax and t1/2)	Time to maximum concentration (Tmax), half life (t1/2)	0.5, 1, 2, 3, 4, 6 hours post-dose
Pharmacokinetic Parameters (AUC0-inf and AUC0-6h)	Area under the concentration curve from time 0 to infinity (AUC0-inf), Area under the concentration curve from time 0 to 6 hour (AUC0-6h)	0.5, 1, 2, 3, 4, 6 hours post-dose

Collaborators and Investigators

• Sponsor: Definium Therapeutics US, Inc.
• Investigators: Principal Investigator: Matthias Liechti, University Hospital, Basel, Switzerland; Principal Investigator: Kim Kuypers, Maastricht University

Publications and helpful links

General Publications

• Mueller L, Santos de Jesus J, Schmid Y, Muller F, Becker A, Klaiber A, Straumann I, Luethi D, Haijen ECHM, Hurks PPM, Kuypers KPC, Liechti ME. Safety and Efficacy of Repeated Low-Dose LSD for ADHD Treatment in Adults: A Randomized Clinical Trial. JAMA Psychiatry. 2025 Jun 1;82(6):555-562. doi: 10.1001/jamapsychiatry.2025.0044.

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2021
• Primary Completion (Actual): November 6, 2023
• Study Completion (Actual): December 4, 2023

Study Registration Dates

• First Submitted: December 21, 2021
• First Submitted That Met QC Criteria: January 7, 2022
• First Posted (Actual): January 21, 2022

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Attention Deficit and Disruptive Behavior Disorders; Attention Deficit Disorder with Hyperactivity
• Other Study ID Numbers: MMED007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No