The Effectiveness of combined Cognitive Behavioural Therapy and Heart Rate Variability Biofeedback Compared to Treatment-As-Usual on Physiological Stress Reactivity and Resting-State Functional Connectivity in Methamphetamine Use Disorder Patients in Indonesia: Protocol for a Randomized Controlled Trial

Methamphetamine is a stimulant with high use rates in North America and East and South-East Asia, including Indonesia. Its use can disrupt stress regulation and brain connectivity, increasing the risk of relapse. Cognitive Behavioral Therapy (CBT) is an effective approach for relapse prevention in methamphetamine use disorder (MUD), but it does not directly target physiological stress responses. Heart rate variability biofeedback (HRV-BF), using a “Stress Eraser” device, can support stress regulation. This two-arm randomized controlled trial will assess the effectiveness of CBT combined with HRV-BF, alongside TAU, in reducing psychophysiological stress reactivity (primary outcome), as measured by heart rate variability (HRV) at three months post-baseline. Secondary outcomes include resting-state brain connectivity, perceived stress, depression, anxiety, quality of life, and craving. Participants will be recruited from an inpatient facility of the National Narcotics Board of Indonesia if they are ≥18 years old and meet MUD criteria via the Addiction Severity Index and urine test. The CBT-HRV-BF group will receive 12 CBT sessions with integrated HRV-BF and between-session practice. TAU follows a Therapeutic Community approach with counselling, family support, psychoeducation, and spiritual sessions, but does not include CBT or HRV-BF. Outcomes will be assessed at baseline, post-intervention, and six-month follow-up. This is the first randomized controlled trial to investigate the effectiveness of combined CBT and HRV-BF, in addition to TAU, for adult MUD patients in Indonesia.