Music as an Adjunct to Ketamine Therapy for Chronic Pain

NCT06994559 | Recruiting

• 1 other identifier: Music-Ketamine
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Intravenous (IV) ketamine is a treatment option for patients with chronic pain that does not respond to standard therapies, primarily working by blocking NMDA receptors in the brain. Beyond pain relief, ketamine can produce dissociative sensations, classifying it as an atypical psychedelic or mind-altering drug, and may enable patients to reprocess their pain similarly to experiences with traditional psychedelics. At the Montreal General Hospital's pain clinic, the investigators have observed patients frequently listening to music during ketamine infusions, and recent research indicates that music-especially when self-selected by patients-might provide additional pain-relieving benefits by influencing central mechanisms related to pain perception and interpretation. This intersection of music and pain relief is garnering substantial scientific interest as recent advances provide more insight into the neuroscience of music and its effects on brain regions involved in emotion, sensation, memory, and pain. This study aims to investigate the effects of music on chronic pain patients undergoing IV ketamine infusions at the Alan Edwards Pain Management Unit (AEPMU), specifically to determine whether the choice of music affects the intensity and duration of ketamine-induced pain relief. During the infusion (lasting 1 hour), patients will listen to a playlist delivered through specialized headphones, which will either consist of their own selected music (preferred music), music chosen by a music therapist, or no music at all, in a randomized order. Patients will track their pain levels throughout the infusion period and in the intervals between treatments (5 weeks) using standardized pain assessment tools. Additionally, the investigators will assess the subjective experiences of ketamine through interviews and qualitative analysis, while documenting and summarizing any adverse effects. The investigators hypothesize that listening to preferred music will enhance both the intensity and duration of pain relief from IV ketamine. To test this, the investigators will recruit patients already receiving repeated IV ketamine infusions for pain management at the AEPMU clinic. The first infusion will take place under usual conditions to establish a baseline. The infusions will occur in a dedicated room equipped with audio technology to ensure an immersive music experience.

Conditions

Chronic Pain; Chronic Noncancer Pain

Keywords

Chronic pain; Ketamine; Music

Outcome Measures

Primary Outcomes (1)

• Pain intensity

  Pain intensity assessed using a 0-10 visual rating scale anchored at 0 (absence of pain) and 10 (maximum pain imaginable). Participants will rate their average pain intensity in the previous 24 hours.

  From baseline to 24 hours after each ketamine session

Secondary Outcomes (9)

• In-session Pain intensity

  Immediately before and after each ketamine session

• In-session Pain unpleasantness

  Immediately before and after each ketamine session

• Duration of pain relief

  From baseline to the end of each condition (5 weeks) daily for one week, then weekly

• Brief Pain Inventory (pain interference)

  From baseline to the end of each condition (5 weeks)

• Brief Pain Inventory (number of pain sites)

  From baseline to the end of each condition (5 weeks)

Study Arms (6)

Preferred-Therapist-Silence

OTHER

Participants in this arm will be exposed to 1) Preferred music, 2) Therapist-selected music and 3) Silence in this order

Other: Preferred Music; Other: Therapist-selected Music; Other: Silence

Preferred-Silence-Therapist

OTHER

Participants in this arm will be exposed to 1) Preferred music, 2) Silence, and 3) Therapist-selected music, in this order

Other: Preferred Music; Other: Therapist-selected Music; Other: Silence

Therapist-Preferred-Silence

OTHER

Participants in this arm will be exposed to 1) Therapist-selected music, 2) Preferred music, 3) Silence, in this order

Other: Preferred Music; Other: Therapist-selected Music; Other: Silence

Therapist-Silence-Preferred

OTHER

Participants in this arm will be exposed to 1) Therapist-selected music, 2) Silence, and 3) Preferred music, in this order

Other: Preferred Music; Other: Therapist-selected Music; Other: Silence

Silence-Therapist-Preferred

OTHER

Participants in this arm will be exposed to 1) Silence, 2) Therapist-selected music, and 3) Preferred music, in this order

Other: Preferred Music; Other: Therapist-selected Music; Other: Silence

Silence-Preferred-Therapist

OTHER

Participants in this arm will be exposed to 1) Silence, 2) Preferred music, and 3) Therapist-selected music, in this order

Other: Preferred Music; Other: Therapist-selected Music; Other: Silence

Interventions

Preferred Music OTHER

The self-selected preferred music intervention will expose participants to music chosen based on personal tastes. Patients will be instructed to compile a playlist lasting approximately 1 hour, but preferably over 1 hour (to avoid repetition or moments without music) of their favorite music. They will be instructed to select songs that they find extremely pleasurable to listen to. Participants will be instructed to select songs that will have a higher likelihood to facilitate relaxation and introspection. This does not need to be an all-time favorite selection, but rather the music that they currently enjoy listening to the most.

Preferred-Silence-Therapist; Preferred-Therapist-Silence; Silence-Preferred-Therapist; Silence-Therapist-Preferred; Therapist-Preferred-Silence; Therapist-Silence-Preferred

Therapist-selected Music OTHER

The therapist-selected music intervention will expose participants to a curated playlist specifically designed for psychedelic treatment by expert Music Therapists, which was used in a previous study to investigate the additive hemodynamic effects of music during ketamine infusions for depression. Patients will be randomly exposed to one of 9 available playlists, all containing songs without lyrics.

Preferred-Silence-Therapist; Preferred-Therapist-Silence; Silence-Preferred-Therapist; Silence-Therapist-Preferred; Therapist-Preferred-Silence; Therapist-Silence-Preferred

Silence OTHER

The silence intervention will expose patients to the same therapeutic procedures, in the same room and context, and with the same noise-cancelling headphones. The purpose is to cancel any potentially perturbing background noise, as no music will be played.

Preferred-Silence-Therapist; Preferred-Therapist-Silence; Silence-Preferred-Therapist; Silence-Therapist-Preferred; Therapist-Preferred-Silence; Therapist-Silence-Preferred

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of chronic (3 months) pain of noncancerous origin, including chronic primary and secondary pain conditions, irrespective of its mechanistic contributors (nociceptive, neuropathic, or nociplastic), and of moderate to severe intensity (rated ≥ 4 in a 0-10 scale);
• Participants must have been prescribed IV ketamine treatment at the AEPMU, based on their treating clinician's assessment and judgment;
• Prior their participation in the study, all Participants must have undergone at least one ketamine IV session in the AEPMU clinical setting, which was well tolerated and did not reveal any important adverse effects, and which is expected to be repeated;
• Be able to use an electronic device (e.g., computer, tablet, smartphone) to complete questionnaires and diaries. For patients who may not possess such a device, a smartphone will be loaned for the duration of the study;
• No contraindication for intravenous ketamine treatment, including: poorly controlled cardiovascular disease, pregnancy or current or past history of psychosis, moderate to severe hepatic disease, elevated intracranial or extraocular pressure, and current or past history of substance abuse;
• Abstention from consuming grapefruit juice on the day of the ketamine infusions as it may alter the metabolism of ketamine;

You may not qualify if:

• Low tolerability or ineffectiveness of previous intravenous treatment or ketamine infusions;
• Current diagnosis or treatment for cancer;
• Significant hearing impairment not improved with hearing aids and/or sound amplification or unwillingness to listen to music during treatment;
• Known intellectual disability or autism spectrum disorder;
• Known risk factors for intracranial hemorrhage, including previous significant trauma, known aneurysm, or previous neurosurgery;
• Evidence of clinically relevant disease, e.g., renal or hepatic impairment, significant coronary artery disease (myocardial infarct within a year prior to initial randomization), cerebrovascular disease, viral hepatitis B or C, acquired immunodeficiency syndrome or history of seizure disorder;
• Prior or current (i.e., past-year) history of substance use disorder (except for caffeine or nicotine use disorder) as defined by DSM-5 criteria;
• Acute psychotic or suicidal ideation symptoms, as judged by the referring clinician.

Sponsors & Collaborators

• McGill University: lead
• McGill University Health Centre/Research Institute of the McGill University Health Centre: collaborator

Study Sites (1)

Montreal General Hospital

Montreal, Quebec, H3G 1A4, Canada

RECRUITING

Related Publications (6)

• Sorensen J, Bengtsson A, Backman E, Henriksson KG, Bengtsson M. Pain analysis in patients with fibromyalgia. Effects of intravenous morphine, lidocaine, and ketamine. Scand J Rheumatol. 1995;24(6):360-5. doi: 10.3109/03009749509095181.

  PMID: 8610220 BACKGROUND

• Olofsen E, Kamp J, Henthorn TK, van Velzen M, Niesters M, Sarton E, Dahan A. Ketamine Psychedelic and Antinociceptive Effects Are Connected. Anesthesiology. 2022 May 1;136(5):792-801. doi: 10.1097/ALN.0000000000004176.

  PMID: 35188952 BACKGROUND

• Lunde SJ, Vuust P, Garza-Villarreal EA, Vase L. Music-induced analgesia: how does music relieve pain? Pain. 2019 May;160(5):989-993. doi: 10.1097/j.pain.0000000000001452. No abstract available.

  PMID: 30507782 BACKGROUND

• Greenway KT, Garel N, Goyette N, Turecki G, Richard-Devantoy S. Adjunctive music improves the tolerability of intravenous ketamine for bipolar depression. Int Clin Psychopharmacol. 2021 Jul 1;36(4):218-220. doi: 10.1097/YIC.0000000000000363.

  PMID: 33902087 BACKGROUND

• Greenway KT, Garel N, Dinh-Williams LL, Beaulieu S, Turecki G, Rej S, Richard-Devantoy S. Music as an Intervention to Improve the Hemodynamic Response of Ketamine in Depression: A Randomized Clinical Trial. JAMA Netw Open. 2024 Feb 5;7(2):e2354719. doi: 10.1001/jamanetworkopen.2023.54719.

  PMID: 38315489 BACKGROUND

• Garza-Villarreal EA, Pando V, Vuust P, Parsons C. Music-Induced Analgesia in Chronic Pain Conditions: A Systematic Review and Meta-Analysis. Pain Physician. 2017 Nov;20(7):597-610.

  PMID: 29149141 BACKGROUND

MeSH Terms

Conditions

Chronic Pain

Interventions

SIR1 protein, S cerevisiae

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Mark A Ware, MD

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

• Mathieu Roy, PhD

  McGill University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark A Ware, MD

CONTACT

1-5149348222; mark.ware@mcgill.ca

Carlos Gevers-Montoro, PhD

CONTACT

carlos.geversmontoro@mcgill.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 20, 2025
• First Posted: May 29, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: IPD will be share upon reasonable request
• Access Criteria: IPD will be share upon reasonable request

Locations

CA (1)