The goal of this clinical trial is to learn about the effects of the combination of ketamine and realtime functional magnetic resonance imaging (fMRI) neurofeedback training on the treatment of individuals with alcohol use disorder (AUD). The main questions the investigators aim to answer are:
* Can the investigators observe a positive, significant therapeutic effect by comparing changes in alcohol use via i) mean alcohol use per day, ii) heavy drinking days one month after the last treatment intervention? * Are changes in glutamatergic neurotransmission in the nucleus accumbens related to cue-induced cravings in individuals with AUD? * Is there a significant, ketamine-dependent change in glutamate levels in the nucleus accumbens?
Participants will be given ketamine or placebo and real-time fMRI neurofeedback (rt-fMRI NFT) or sham rt-fMRI NFT.
The investigators will compare three intervention groups to investigate the effects of the stand-alone effects as well as potential synergies between the combination of pharmacological and non-pharmacological intervention.
Informed Consent as documented by signature
In- and outpatients aged 18 to 65 years of all sexes.
DSM-IV diagnosis of alcohol use disorder (mild - severe).
Motivation to reduce or stop alcohol use
History of DSM-IV severe drug dependence other than alcohol (except for caffeine or nicotine) and any opiod use disorder within two months prior to enrolment.
Hallucinogen and ketamine use 3 months prior to study participation (including regular microdosing).
Alcohol withdrawal symptoms at any of the treatment visits (V2 and V3) (CIWA-Ar Scale >9).
Current or lifetime psychotic disorders
Parallel
Ketamine
DrugA single dose of ketamine 0.8 mg ketamine (i.v.) per kilogram bodyweight
Real-time fMRI Neurofeedback Training
BehavioralParticipants will undergo a closed-loop rt-fMRI paradigm over 25 minutes. Participants will be instructed to use strategies to downregulate cue-induced cravings. The Intensity of cues will adjust based on the participants neural activity in response to cues. This dynamic feedback mechanism allows for personalized training aimed at improving the participant's ability to manage cravings.
Placebo
DrugSingle dose of placebo (0.9% NaCl infusion)
Sham Neurofeedback Training/ Ketamine
BehavioralParticipants get a real time neurofeedback based on a control regions' activity, which serves as a sham region and receive 0.8 mg ketamine (i.v.) per kilogram bodyweight. The use of sham-NFT allows for a rigorous assessment of the specific effects of combined rt-fMRI NFT and ketamine by controlling for non-specific factors such as expectancy effects or the therapeutic context.
Change in mean alcohol use per day
Change in mean alcohol use per day. Alcohol use is measured via a combination of the digital app and the Timeline Follow-Back Questionnaire.
Change in heavy drinking days
Change in heavy drinking days. Defined as five or more standard units of alcohol in a day for a man and four or more standard units of alcohol in a day for a woman. Alcohol use is measured via a combination of the digital app and the Timeline Follow-Back Questionnaire.
Changes in glutamat levels during craving
Changes in glutamatergic signalling in the NAcc measured via Magnetic Resonance Spectroscopy (MRS) during craving vs neutral cue exposure.
Changes in Brain Derived Neurotrophic Factor
Treatment-induced changes in neuroplasticity assessed using the brain derived neurotrophic factor (BDNF) through blood analysis.
Individual variations in ketamine pharmacokinetics
Changes in ketamine plasma concentrations and its metabolites measured via blood samples taken.
Predictive value of baseline rs-fMRI for treatment response
Predictive value of rs-fMRI for treatment response assessed via the two primary outcomes
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Dr. med. Marcus Herdener
Lead sponsor
Psychiatric University Hospital, Zurich
Sponsor institution
University of Zurich
Collaborator
