The Role of Potassium Channels in Working Memory Impairments of Chronic Cocaine Users (POTCHICUD)

Randomised, Double-Blind, Placebo-Controlled, Crossover Study Investigating the Role of Potassium Channels in Working Memory Impairments of Chronic Cocaine Users

The study aims to address the neurobiological basis of cognitive impairments in chronic cocaine users by investigating the potential impact of an acute potassium channel blockade on working memory performance and other cognitive functions.

Study Overview

• Status: Not yet recruiting
• Conditions: Cognitive Impairments; Cocaine Use Disorder (CUD)
• Intervention / Treatment: Drug: 4-aminopyridine (4-AP); Drug: Placebo

Detailed Description

Chronic cocaine use is associated with impairments in cognitive functions, particularly in working memory, which are thought to contribute to the persistence of addictive behaviors and high relapse rates. Despite the clinical relevance of these cognitive deficits, the underlying neuropharmacological mechanisms remain insufficiently understood.

Preclinical and clinical evidence suggests that potassium channels may play an important role in the regulation of neuronal excitability and cognitive processes, including working memory. However, their contribution to cognitive impairments in individuals with cocaine use disorder has not yet been systematically investigated in humans.

The present study aims to investigate the role of potassium channel modulation in working memory performance in individuals with chronic cocaine use. The study addresses the following key research questions: (1) Does modulation of potassium channels influence working memory performance in individuals with chronic cocaine use? and (2) How are potential effects related to behavioral responses observed during the experimental sessions?

To address these questions, a randomized, controlled, cross-over study will be conducted in participants with a history of chronic cocaine use. Participants will complete a series of neurocognitive tasks assessing working memory and related cognitive domains under controlled experimental conditions. Blood samples will be collected at multiple time points to quantify substance levels and to support the interpretation of behavioral findings. The results of this study may contribute to a better understanding of the neurobiological mechanisms underlying cognitive impairments in cocaine use and inform future research on cognitive dysfunction in substance use disorders.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Prof. Dr. rer. nat. Boris B. Quednow, Dr. rer. nat.; Phone Number: +41 58 384 27 77; Email: quednow@bli.uzh.ch
• Study Contact Backup: Name: Laura V Schurek, M. Sc.; Phone Number: +41 58 384 26 16; Email: studie-potchicud@bli.uzh.ch

Study Locations

• Switzerland
  • Canton of Zurich
    • Zurich, Canton of Zurich, Switzerland, 8008
      • University Hospital of Psychiatry Zurich
      • Contact: Prof. Dr. rer. nat. Boris B. Quednow, Dr. rer. nat.; Phone Number: +41 58 384 27 77; Email: quednow@bli.uzh.ch
      • Contact: Laura V. Schurek, M. Sc.; Phone Number: +41 58 384 26 16; Email: studie-potchicud@bli.uzh.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Current diagnosis of mild, moderate, or severe CoUD according to DSM-5
• Minimum cocaine use of 1g/month in the last three months
• Cocaine as the primary drug of consumption
• Willingness to abstain from cocaine use at least 72 hours before prior to each study visit
• Ability to read, understand and provide written informed consent
• To be sufficiently fluent in German
• Age between 20 and 50 years
• Body mass index (BMI) between 19 and 30 kg/m2
• If applicable: luteal phase of the menstrual cycle
• For individuals with childbearing potential: use of contraceptive measures

Exclusion Criteria:

• Presence or history of severe neurological disorders or head injuries
• Current diagnosis of an acute or chronic infectious disease
• If applicable: pregnancy and breastfeeding
• Lifetime history of any epileptic seizures
• Lifetime diagnosis of a cardiovascular disease, specifically arrhythmia and long QT syndrome
• Clinically significant laboratory or ECG abnormality that could be a safety issue in the study
• Lifetime diagnosis of liver or kidney disease including moderate or severe renal impairment (creatinine clearance < 50 ml/min)
• Known hypersensitivity or allergy to 4-aminopyridine
• Use of potassium channel blockers within the last 3 months
• Use of psychotropic medication within the last 7 days
• Use of inhibitors of the organic cation transporter 2 (OCT2), such as cimetidine
• Lifetime diagnosis of schizophrenia, bipolar disorder, obsessive-compulsive disorder, or autism spectrum disorder according to DSM-5
• Diagnosis of a current episode of depression
• Current diagnosis of a moderate or severe substance use disorder other than CoUD according than DSM-5
• Daily cannabis consumption in the past three months
• (E-Cigarette) Fagerström Test of Nicotine Dependence Score > 5 (strong nicotine dependence)
• Inability to follow the procedures of the study, e.g., due to language problems
• Being related to or in any form dependent on the investigator
• Prior participation (less than two years ago) in a study investigating working memory using the n-back task, the SWM, PAL, RVP, or LNST
• Participation in another study with investigational drugs within the 30 days preceding and during the present study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence AB; Participants receive fampridine (A) in one experimental session and placebo (B) in the other, in the order A then B.	Drug: 4-aminopyridine (4-AP); Two doses of fampridine administered during one of the two experimental test sessions.; Drug: Placebo; Matching placebo administered during one of the two experimental test sessions.
Experimental: Sequence BA; Participants receive placebo (B) in one experimental session and fampridine (A) in the other, in the order B then A.	Drug: 4-aminopyridine (4-AP); Two doses of fampridine administered during one of the two experimental test sessions.; Drug: Placebo; Matching placebo administered during one of the two experimental test sessions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global Working Memory Performance	Working memory performance will be assessed using a cognitive test battery covering different domains of working memory, including visuo-spatial (Spatial Working Memory [SWM], total errors; Paired Associates Learning [PAL], first trial memory score) and verbal-numeric components (Letter Number Sequencing Task [LNST], total score; Letter N-Back Task, discrimination index d'). Individual test scores will be standardized (z-transformation) and combined into a global working memory score according to Vonmoos et al (2013).	Baseline and during both experimental sessions

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP)	Neurofilament light chain (NfL), a marker of axonal integrity, and glial fibrillary acidic protein (GFAP), a marker of microglia activation, levels will be analysed to assess potential drug challenge-related brain structural remodelling or to predict the effect of potassium challenge blockade.	Baseline and during both experimental sessions
Plasma concentration	Plasma concentration of the study drug	During both experimental sessions
Heart rate variability	Heart rate variability is recorded during the test sessions to measure the level of stress and to investigate whether the physiological strain of the test is reduced when taking the study drug.	During both experimental sessions
Subjective ratings of current mood and craving	Subjective ratings of current mood (affective state, stress) and craving, pre- and post-cue exposure. Current affective state will be assessed using the Positive and Negative Affect Schedule (PANAS; positive affect range: 10-50, negative affect range: 10-50) and visual analog scales (VAS; range 0-100, with higher scores indicating greater levels) of affective state and stress burden. Current cocaine craving will be assessed using the Cocaine Craving Questionnaire-Brief (CCQ-Brief; total score range: 10-70, with higher scores representing worse outcomes) and visual analog scales (VAS; range 0-100, with higher scores indicating greater levels) of craving intensity, distinguishing between wanting, needing and having the urge for cocaine.	Baseline and during both experimental sessions
Adverse effects of the study drug	Potential adverse effects of the study drug will be assessed using the List of Complaints and visual analog scales (VAS; range 0-100, with higher scores indicating greater levels) of perceived effects of the substance, dizziness, drowsiness, nausea and impaired concentration.	During both experimental sessions

Collaborators and Investigators

• Sponsor: Boris Quednow
• Collaborators: University of Zurich

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: April 8, 2026
• First Submitted That Met QC Criteria: April 8, 2026
• First Posted (Actual): April 16, 2026

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: working memory; cocaine use disorder; cognitive impairments; 4-aminopyridine; fampridine; potassium channels
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Amines; Aminopyridines; 4-Aminopyridine
• Other Study ID Numbers: 2025-01432

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