Effects of Olfactory Stimuli in Virtual Reality Cue Exposure on Craving and Attentional Bias in Alcohol Use Disorder

Sixty patients with AUD, treated in inpatient or outpatient psychiatric clinics, will be enrolled in the study. Participants will receive written and verbal information about the study, and written informed consent for participation will be obtained. A screening for eligibility will then be conducted. This will include, among other things, a history of craving and the confirmation of normosmia. Sociodemographic data, questionnaires on craving, AUD characteristics, and tendency for immersion, as well as potentially confounding variables and factors influencing physiological parameters, will be collected. Participants will then be asked to name a beverage of their choice (beer, red wine, white wine, vodka, or schnaps), which will be presented to them visually and olfactorily during the VR-CE.

Before exposure to the VR scenarios, participants will be familiarized with the VR headset. Eye tracking within the head-mounted display (HMD) will be calibrated, and participants will be allowed to acclimatize to the VR environment. Subsequently, participants will be exposed to each of the four VR-CE conditions for 5 minutes (neutral visual+no odor; neutral visual+alcohol-related odor; alcohol-related visual+no odor; and alcohol-related visual+alcohol-related odor) in randomized order. Randomization will be implemented such that the visual stimuli are presented in blocks (i.e., both neutral or both alcohol-related VR scenarios), while the olfactory stimuli (no odor vs. alcohol-related odor) are randomized within each visual block. Prior to each visual block, participants will undergo a 5-minute VR baseline session in a black virtual room with blue orientation lines, which will serve as the baseline for subjective and psychophysiological parameters.

During exposure, psychophysiological parameters and eye-tracking data will be recorded, self-reported craving will be assessed three times and sense of presence once during each VR-CE condition. After the exposure, questionnaires to assess self-reported craving, attentional bias, sense of presence, affective reaction and cybersickness will be administered.

Inclusion criteria

• age between 18-65 years
• diagnosis of alcohol dependence according to ICD-10 (F10.2)
• complete inpatient detoxification within the last three months
• history of alcohol craving
• capacity to provide written informed consent

Exclusion criteria

• substance dependences other than alcohol or nicotine
• current alcohol intoxication (tested by random breath-alcohol measurements)
• alcohol abstinence less than 7 days or on-going alcohol consumption
• severe neuropsychiatric disorder (e.g. schizophrenia-spectrum disorder, bipolar affective disorder or substantial cognitive impairment)
• severe medical conditions affecting brain or heart function that could influence the parameters under investigation
• acute suicidality or risk of harm to others
• current pharmacological treatment for alcohol dependence (e.g., benzodiazepines) or for craving (e.g., acamprosate, disulfiram, naltrexone, nalmefene)
• other medications that may have a significant influence on heart rate
• sinusitis, self-reported problems with smell, or lack of normosmia, assessed both subjectively and objectively
• limited ability to understand the study information, the consent form or the study procedures and principles