2026 ECNP Congress

PS04-4199

Effects of repeated low-dose LSD on neuropsychological functioning in adults with ADHD: A randomized placebo-controlled study

Eline Haijen-Bongers — P. Hurks, J. Schepers, P. Vizeli, J. Santos de Jesus, L. Mueller, Y. Schmid, M. Liechti, K. Kuypers · Maastricht University, Neuropsychology & Psychopharmacology, Maastricht, Netherlands

2026 ECNP Congress

Rationale

Attention-deficit hyperactivity disorder (ADHD) is characterized by substantial heterogeneity in symptoms and cognitive functioning. According to the Triple Pathway Model [1], this variability may arise from impairments in inhibition, motivation, and temporal processing. These neuropsychological domains are closely linked to functional outcomes and are known to be sensitive to pharmacological interventions. Repeated low-dose administration of psychedelics is being explored as a potential treatment for ADHD [2], but controlled evidence for clinical improvement beyond the placebo effect remains limited [3]. So far, no study has investigated the effects of repeated low doses of a psychedelic on neuropsychological functioning in adults with ADHD.

Objectives

This study investigated performance across neuropsychological domains relevant to ADHD, including attention, inhibition, motivational processing, and temporal processing, before and after a six-week biweekly low-dose lysergic acid diethylamide (LSD) treatment (20 μg) in adults with ADHD. Based on prior findings, we expected improvements in attention and temporal processing and explored whether baseline ADHD symptoms and domain-specific performance predicted treatment outcomes after six weeks, given the heterogeneity of ADHD.

Methods

A double-blind, placebo-controlled, parallel-group design was used. Behavioral task performance was assessed at baseline and after six weeks of treatment, prior to administration of the final dose, to assess cumulative effects outside the acute drug state. Five neuropsychological performance tasks were administered: the Psychomotor Vigilance Task (sustained attention), the Stop-Signal Task (inhibition), the Delay Discounting Task (motivational processing), the Time Production Task, and the Time Reproduction Task (temporal processing). Fifty-three patients were randomized to LSD (n = 27) or placebo (n = 26), and 46 completed the study. Age was included as a covariate given its established association with neuropsychological functioning. This study is based on data from a previously published trial that focused on clinical symptoms [3], whereas the present analyses examine neuropsychological outcomes.

Results

An effect of the LSD treatment was observed on a temporal processing measure (Time Reproduction Task), indicated by a reduced under-reproduction of long (30 and 45 seconds) time intervals following LSD treatment compared to placebo. No differential effects between groups were detected on other neuropsychological tasks, although small changes over time were observed in both groups. Exploratory analyses indicated that baseline performance differentially predicted outcomes related to inhibition and time reproduction across groups, whereas baseline ADHD symptoms were unrelated to treatment outcomes after six weeks.

Conclusions

These findings do not support broad cumulative effects of low-dose LSD treatment on neuropsychological functioning in adults with ADHD. The observed effect on temporal processing appears to be domain- and task-specific and should be interpreted cautiously, particularly given the absence of corresponding effects in other domains and the lack of clinical improvement in the parent trial [3]. Future research should examine the robustness of this finding and clarify whether low-dose LSD effects are more pronounced under acute conditions or vary across subgroups of individuals with ADHD.

Registry: ClinicalTrials.gov, TRN: NCT05200936, Registration date: 21 December 2021.

References

  1. Sonuga-Barke, et al. (2010). Beyond the dual pathway model: evidence for the dissociation of timing, inhibitory, and delay-related impairments in attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry, 49(4), 345-355.
  2. Haijen, et al. (2022). Microdosing with psychedelics to self-medicate for ADHD symptoms in adults: A prospective naturalistic study. Neuroscience Applied, 1, 101012.
  3. Mueller, et al. (2025). Safety and Efficacy of Repeated Low-Dose LSD for ADHD Treatment in Adults: A Randomized Clinical Trial. JAMA Psychiatry.