Feasibility of Integrating Olfactory Stimuli Into Virtual Reality Cue Exposure for Patients With Alcohol Dependence

Alcohol dependence (AD) is a prevalent and burdensome clinical condition with high relapse rates. A central risk factor for relapse is craving for alcohol, which can be evoked by both real-world and virtual cues in immersive Virtual Reality (VR). In addition to visual and auditory stimuli, olfactory stimuli are increasingly recognized as important for creating realistic, multisensory VR environments. However, no systematic investigation has yet examined how olfactory stimuli embedded in VR-based Cue Exposure (VR-CE) influence cue-elicited craving. As part of the OLFA-VR (Effects of Olfactory Stimuli in Virtual Reality Cue Exposure on Craving in Alcohol Dependence) research project, the present feasibility study aims to evaluate the feasibility, tolerability and acceptability of implementing olfactory stimuli into VR-CE.

In addition, this study not only examines the general feasibility of alcohol-related olfactory stimuli in VR-CE but also explores which specific alcohol-related olfactory stimuli prove to be feasible.

The investigators hypothesize that implementing olfactory stimuli into VR-CE will be feasible and tolerable for patients with AD, with no preventable serious side effects caused by VR-CE. The investigators also hypothesize that VR-CE will induce craving in most patients.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Dependence
• Intervention / Treatment: Device: VR Cue-Exposure Including Olfactory Stimuli

Detailed Description

Twenty patients with alcohol dependence (AD), treated in an inpatient or outpatient psychiatric clinic, will be included in the study. Participants will receive written and verbal information about the study and informed consent for participation will be obtained. A screening for eligibility will then be conducted. Sociodemographic data will be collected, and screening for harmful alcohol use (Alcohol Use Disorders Identification Test, AUDIT) and assessment of AD severity (Alcohol Dependence Scale, ADS) will be performed.

Participants will be exposed to two types of Virtual Reality (VR) scenarios combined with corresponding olfactory stimuli: a neutral VR scenario with neutral visual and olfactory stimuli (rose), and an alcohol-related VR scenario with alcohol-related visual and olfactory stimuli (beer, white wine, red wine, vodka, schnaps). The VR-CE protocol comprises one exposure to the neutral VR-CE followed by five alcohol-related VR-CEs. The five alcohol-related VR-CEs will be presented in a randomized order, each pairing a visual stimuli with the corresponding olfactory stimuli for a specific beverage.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nadja Ruckser, M.Sc.; Phone Number: +49 30 838 67876; Email: nadja.ruckser@charite.de

Study Locations

• Germany
  • State of Berlin
    • Berlin, State of Berlin, Germany, 10115
      • Recruiting
      • Psychiatric University Hospital Charité at St. Hedwig Hospital

Participation Criteria

Eligibility Criteria

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

Study Population

Patients with alcohol dependence treated in inpatient or outpatient psychiatric clinic

Description

Inclusion Criteria:

• age: 18-65 years
• diagnosis of alcohol dependence according to ICD-10 (F10.2)
• history of alcohol craving
• able to provide written informed consent

Exclusion Criteria:

• hyposmia
• dependence on substances other than alcohol and nicotine
• current alcohol intoxication (randomly tested by measurement of breath alcohol concentration)
• unable to understand the study information, consent form or principles of the study
• abstinence for less than 7 days or ongoing consumption of alcohol
• severe neuropsychiatric disorder (e.g. schizophrenia spectrum disorders, bipolar affective disorder) or substantial cognitive impairment
• serious illnesses affecting brain or heart function that influence physiological study parameters
• acute suicidality (or acute endangerment of others)
• concurrent pharmacological treatment targeting AUD (e.g. benzodiazepines) or craving (e.g. acamprosate, disulfiram, naltrexone, nalmefene) and further medication significantly influencing heart rate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Olfactory VR; neutral and alcohol-related olfactory and visual stimuli in a Virtual Reality Cue Exposure	Device: VR Cue-Exposure Including Olfactory Stimuli; Virtual Reality Cue Exposure (NCT05861843, NCT06333457)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of Integrating Olfactory Stimuli Into Virtual Reality Cue Exposure	Questions regarding olfactory stimuli identification, olfactory perception of intensity (0=imperceptible-100=intensely perceptible), realism (0=unrealistic-100=realistic) and congruence with visual stimuli (0=incongruous-100=congruous), higher scores reflect higher feasibility; dropout	Day 1, after each Virtual Reality Cue Exposure (VR-CE): questions regarding olfactory stimuli identification, olfactory perception of intensity, realism and congruence Day 1, after completion of all VR-CEs and assessments: dropout
Tolerability of Integrating Olfactory Stimuli Into Virtual Reality Cue Exposure	Questions regarding tolerability of the technology and olfactory stimuli (0=unpleasant-100=pleasant), higher scores reflect higher tolerability Emotional side effects: Self-Assessment Manikin (SAM; valence, arousal and dominance, range -8 to 8 in steps of 2; -8=happy/tense/submissive feeling, 0=neither happy/tense/submissive nor unhappy/calm/submissive, 8=unhappy/calm/submissive) and Positive and Negative Affect Schedule (PANAS; positive affect: range 10-50, higher score reflects higher levels of positive affect; negative affect: range 10-50, lower score reflects lower levels of negative affect) Physical side effects (cybersickness): Fast Motion Sickness Scale (FMS; range 0-20, higher score reflects higher levels of cybersickness) and Simulator Sickness Questionnaire (SSQ; total score, range 0-48, higher score reflects more sickness; nausea factor, 0-27 range, higher score reflects more nausea; oculomotor factor, range 0-21, higher score reflects more oculomotor problems)	Day 1, before the start of the Virtual Reality Cue Exposures (VR-CE): SAM, PANAS, FMS, SSQ Day 1, after each VR-CE: questions regarding tolerability, SAM, FMS Day 1, after completion of all VR-CEs: SAM, PANAS, FMS, SSQ
Acceptability of Integrating Olfactory Stimuli Into Virtual Reality Cue Exposure	Question regarding technical functionality User experience: User Experience Questionnaire (UEQ; pragmatic quality, hedonic quality and overall scale: range -3 to +3, -3=most negative, 0=neutral, +3=most positive answer) Semi-structured interview including overall impression, perceived usefulness of the integration of olfactory stimuli into Virtual Reality Cue Exposure (VR-CE), perceived willingness to use, open-ended feedback	Day 1, after each VR-CE: question regarding technical functionality Day 1, after completion of all VR-CEs: UEQ, semi-structured interview

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of Initial Clinical Efficacy of Integrating Olfactory Stimuli Into Virtual Reality Cue Exposure	Craving: Visual Analogue Scale (VAS; range 0-10, higher score represents higher levels of craving) Semi-structured interview including perceived craving Presence: Visual Analogue Scale (VAS; range 0-10, higher score represents higher levels of presence)	Day 1, before the start of the Virtual Reality Cue Exposures (VR-CE), after each VR-CE and after completion of all VR-CEs: VAS craving and presence Day 1, after completion of all VR-CE: Semi-structured interview

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Investigators: Principal Investigator: Alva Lütt, Dr. med., Psychiatrische Universitätsklinik der Charité im St. Hedwig Krankenhaus, 10115 Berlin, Germany; Principal Investigator: Stefan Gutwinski, Prof. Dr. med., Psychiatrische Universitätsklinik der Charité im St. Hedwig Krankenhaus, 10115 Berlin, Germany

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2026
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: January 20, 2026
• First Submitted That Met QC Criteria: January 28, 2026
• First Posted (Actual): February 5, 2026

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Alcohol Dependence, Virtual Reality Cue Exposure, Olfactory
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Sensation Disorders; Olfaction Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Anosmia; Alcoholism
• Other Study ID Numbers: EA1/269/24_feasibility

Drug and device information, study documents

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