Music listening group is a music therapy intervention where participants partake in music listening in groups. The sessions will be conducted by an appropriately qualified music therapist.

Treatment as usual as provided locally, which may include pharmacological and/or non-pharmacological interventions (e.g. mindfulness-based intervention, structured physical activity).

This scale is a patient-reported short screening tool that can be used repeatedly. It consists of 11 questions, including 9 ranging from 0-4 and 2 from 0-2, producing a DUDIT sum score of 0-40. In addition, a DUDIT-C sum score of the first 4 items can range from 0-16. Higher scores indicate higher substance use severity. A score of 0 indicates self-reported abstinence, scores ≥ 7 indicate heavy use.

This scale is a patient-reported short screening tool that can be used repeatedly. It consists of 10 questions, each ranging from 0-4, producing an AUDIT sum score of 0-40. In addition, an AUDIT-C sum score of the first 3 items can range from 0-12. Higher scores indicate higher substance use severity. A score of 0 indicates self-reported alcohol abstinence, scores ≥ 3/4 (women/men) indicate alcohol misuse.

EQ-5D is a patient-reported scale with 5 items plus a visual analogue scale (VAS).

The 5-item scale ranges from "less than 0" (worse than death; depending on country-specific weights) to 1 (best). The VAS provides a global one-item rating of current perceived health ranging from 0 (worst possible) to 100 (best possible health).

MADRS is a clinician-administered ten-item interview measuring symptoms of depression. The scale assesses severity of depressive symptoms (rating symptoms on a 7-point scale). Scores range from 0-6, with a maximum score of 60. A higher score indicates more severe depression.

Clinicians will judge whether a participant is still participating, has decided to withdraw from the study, or contact has been lost. Importantly, participants will not be regarded as withdrawn if they decide to withdraw from interventions or from some assessment procedures.

We will ask participants to describe any adverse events, and clinicians will then rate whether these were serious or non-serious and related or non-related.

Patients' participation in the study ends after two years. From public records that are unaffected by loss of contact, employment will be monitored until 10 years after randomisation.

Patients' participation in the study ends after two years. From electronic health records unaffected by loss of contact, hospitalisation will be monitored until 10 years after randomisation.

Patients' participation in the study ends after two years. From public records that are unaffected by loss of contact, criminal record will be monitored until 10 years after randomisation.

Patients' participation in the study ends after two years. From public records that are unaffected by loss of contact, survival will be monitored until 10 years after randomisation.

The ICR is a patient-reported scale that assesses overall motivation to change, including readiness to change. It has 3 items and is rated on a 10-point Likert scale, and total scores range from 0 to 30. Higher scores indicate higher motivation to change.

The Craving Scale is a 3-item patient-reported scale. Scores range from 0-9. High scores indicate higher cravings.

The IOS is a patient-reported single-item visual scale of closeness. scores range from 1-7, with higher score indicating higher social connectedness.

A more comprehensive patient-reported scale than the brief ICR mentioned above. URICA has 32 items and measures the extent to which individuals identify with different stages of change (precontemplation, contemplation, action, maintenance). Each subscale consists of eight items using 5-point Likert scales ranging from 1 to 5 (resulting in scores ranging from 8 to 40). Subscale scores can be used to trace changes in attitudes related to the specific stages of change. The subscales are combined arithmetically (Contemplation + Action + Maintenance - Precontemplation) to yield a Readiness to Change score, with a possible range of 16-80 and higher scores indicating greater readiness for change.

SHAPS is a patient-reported scale with 14 items. It measures the capacity to derive pleasure from four different hedonic experiences: interest/pastimes, social interaction, sensory experience and food/drink. Scores range from 0-4. Higher scores represent higher anhedonia level and a lower hedonic tone.

The SCI has 8 questions covering various sleep aspects such as: sleep onset delay, night-time awakenings, extent of the problem and its effect on daytime activities, mood and relations. Responses are scored from 0 (poor state) to 4 (no/minor problems). A total score of ≤ 16 indicates probable insomnia. Maxmimum score is 32.

Objective measures of substance use will be assessed through hair testing. Three strands of hair as thick as a matchstick will be collected from the occiput as close to the scalp as possible. The 3 cm most proximal to the scalp will be analysed. The levels of substance use will be quantitatively determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a protocol deriving the maximum amount of high-quality valid information from the smallest amount of hair.

Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) will be used as potential functional biomarkers of individual substance use burden of the brain. NfL and GFAP analysis: Serum will be collected in silica tubes. After 30min clotting time, the samples will be centrifuged with 1500g for 15min at room temperature. Storage temperature will be -80°C. NfL and GFAP concentrations will be measured in triplicates using simple-plex assays (ProteinSimple, CA, USA) on Ella microfluidic system (BioTechne, MN, USA).

The selected CANTAB tasks:

1. Rapid Visual Information Processing (RVP):

   This task focuses on sustained attention.

2. Spatial Working Memory (SWM):

   This task mainly assesses visuospatial working memory.

3. Paired Associates Learning (PAL):

   This task measures visuospatial declarative learning and memory.

4. Intra-Dimensional/Extra-Dimensional Set-Shifting (ID/ED):

This test covers rule acquisition and reversal, featuring visual discrimination and attentional set-shifting analogous to the Wisconsin Card Sorting Task.

COSIMO will measure cognitive empathy and mental perspective taking. Performance will be assessed as number of correct answers.

The shortened version of TCIA will be used to measure creative imagery abilities. Participants will be asked to view simple graphite images, generate transformation ideas and draw their favorite idea on paper with no time limit, with the possibility of elaborating or changing the selected image. They will also be asked to write what their drawing represents.

The level of creative imagery will be measured by scoring the drawings according to three characteristics: vividness, originality, and transformative ability.

1. Morphometric analysis (MRI-Voxel Based Morphometry, VBM):

   This analysis permits statistical estimation of whole-brain voxel-level local changes in volume.

2. Cortical folding and cortical thickness:

   Geometrical representations for the cortical surfaces of each patient will be reconstructed and compared based on 3d/T1-images.

3. Diffusion Tensor Imaging (MRI-DTI) analysis:

   DTI will provide precise indices related to tissue white-matter integrity and microstructure reorganization.

4. DRI fiber tracking:

Tracking and reconstruction of white-matter tracks allow to study the larger scale patterns of connectivity and differences in the major association paths in the brain.