Microdosing for ADHD and emotion regulation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universiteit Maastricht

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03], Psychiatry and Psychology [F] - Behavior and Behavior Mechanisms [F01]

Decision date (initial)

2026-05-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

To investigate whether microdosing with a serotonergic agent (20 mcg of LSD) may improve core ADHD symptoms, emotional regulation, and sleep in adults with ADHD.

Secondary objectives 1

1. To investigate whether variation in the main treatment outcomes (core ADHD symptoms, emotion regulation, and sleep) after microdosing with a serotonergic agent (20 mcg LSD) are predicted by specific biological markers, including the genetic profile (LSD metabolism (CYP), Polygenic risk score (PRS)), the pharmacokinetic profile (PK), and brain oscillations (Theta-beta ratio (TBR)). More specifically, PK, CYP, and PRS will be investigated as potential moderators, while TBR will be included as a potential mediator.

Conditions and MedDRA coding

Attention Deficit Hyperactivity Disorder (ADHD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Ability and willingness to provide written, informed consent prior to initiation of any study-related procedures and to adhere to all study requirements.
2. Free from psychotropic medication, including ADHD medication.
3. Must be willing to refrain from taking illicit psychoactive substances during the study.
4. Must be willing to receive the study medication once every third day for 6 weeks. During three lab visits (P1, L1, L8) participants must be willing to take a taxi or public transportation home or be accompanied by a caregiver and not drive a vehicle home. During at-home administration days, participants must be willing to not drive a vehicle or use heavy equipment for 6 hours after administering the study medication.
5. Must be willing to refrain from any alcoholic drinks during the weekdays (Monday to Friday, inclusive). During the weekend, must be willing to refrain from more than 6 standard alcoholic drinks per week (1 standard drink corresponds to 0.1 L wine, 0.3 L beer, or 4 cL liquor).
6. Must be willing to refrain from 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 (EOS).
7. Understanding the procedures and the risks associated with the study
8. Age between 18 and 50 years old at screening
9. Normal weight, body mass index (weight/height2) between 18 and 28 kg/m2
10. Participants experience symptoms that meet the DSM-5 criteria for ADHD, as determined by clinical evaluation and confirmed by a structured interview (SCID-5). Participants may experience ADHD symptoms with or without comorbid disorders, including, but not limited to, emotion and sleep disorders.
11. ASRS total score ≥ 14 at screening.

Exclusion criteria 22

1. Past or present diagnosis of a primary psychotic disorder, including bipolar I or II disorder (DSM-V), or first-degree relative with a psychotic disorder
2. Previous experience of serious side effects to psychedelic drugs (anxiety or panic attacks)
3. Not willing or not able to consume alcohol in any amount (including due to religious or personal reasons), since the study medication will be dissolved in a small quantity (1 ml) of 95% Vol. ethanol.
4. Past (>12 months prior to the screening visit) or present substance addiction or dependence (determined by positive answers on the substance abuse questions in the SCID-5-SV, and the drug and alcohol consumption questions in the MDQ) except nicotine, provided consumption does not exceed (the equivalent of) 10 cigarettes per day.
5. Women of childbearing potential (WOCBP) (i.e., physiologically capable of becoming pregnant) who are unwilling or unable to use a highly effective method of contraception for the duration of the study, OR Men physiologically capable of fathering a child who are sexually active with WOCBP but are unwilling or unable to use barrier contraception (e.g., condom with or without spermicidal cream or jelly) for the duration of the study.
6. Women who are currently pregnant or lactating or plan to become pregnant or breastfeed during the study.
7. Men who plan to donate sperm during the study.
8. Somatic disorders including Central Nervous System (CNS) involvement of cancer, severe cardiovascular disease, untreated hypertension, severe liver disease, severely impaired renal function, or anything else that, in the judgement of the medical supervisor, poses too great a potential for side effects.
9. Hypertension (diastolic > 90 mmHg; systolic > 140 mmHg)
10. History of cardiac dysfunctions (arrhythmia, ischemic heart disease, etc.)
11. Any lifetime history of suicide attempt, ideation or behavior; or current (within past week prior to the screening visit) active suicidal thoughts or ideation; (as determined by positive answers on sSuicidality-related questions on the SCID-5-SV).
12. Planning to start, stop, or alter the use of any medications, supplements, or other therapeutics from the time of providing informed consent until EOS
13. Likely to require psychiatric hospitalisation during the course of the study
14. Likely to need use of any psychiatric medications with the potential to confound interpretation of study results or impact safety, at the discretion of the Investigator, in the 6 weeks following Baseline up to EOS
15. Not willing or able to stop psychotropic medication (e.g., SSRIs, ADHD medication, etc.) prior to the baseline visit through EOS.
16. Use of weight loss drugs within 21 days of screening until the end of study.
17. Planning to start, stop or alter the use of psychotherapy, massage, meditation, acupuncture, hypnosis, yoga, or other similar therapy/activity from the time of providing informed consent until EOS
18. Use of potent CYP2D6 inhibitors; moderate CYP2D6 inhibitors by Investigator discretion
19. Experience with a psychedelic drug (psilocybin, LSD, mescaline, Ayahuasca, DMT, 5-MeO-DMT) within the last 6 months prior to the screening visit
20. Participants with a positive urine drug screen at screening OR any of the lab visits
21. Any clinically significant abnormal electrocardiogram (ECG) finding (e.g., uncontrolled atrial fibrillation, ischemia) at screening, as determined by the medical supervisor (in consultation with a cardiologist, if needed).
22. Any other condition, therapy, laboratory abnormality, or other circumstance that, in the opinion of the medical supervisor, may pose additional risk to the subject from participation in the study, may interfere with the subject’s ability to comply with study procedures, may make participation in the study not in the subject’s best interest or may confound the results of the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. ADHD symptoms
2. Emotion regulation
3. Sleep

Secondary endpoints 4

1. Pharmacokinetic profile
2. Theta-beta power ratio
3. CYP2D6 functionality
4. Polygenic risk score

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universiteit Maastricht

Sponsor organisation

Universiteit Maastricht

Address

P. O. Box 616

City

Maastricht

Postcode

6200 MD

Country

Netherlands

Scientific contact point

Organisation

Universiteit Maastricht

Contact name

Kim Kuypers

Public contact point

Organisation

Universiteit Maastricht

Contact name

Kim Kuypers

Third parties 7

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications