Paired-pulse rTMS Treatment for Methamphetamine Use Disorder Based on the mPFC-Cerebellum

Shanghai Mental Health Center

Status: Enrolling

Conditions: Methamphetamine Use Disorder

Treatments: Device: Paired Associative Stimulation Targeting the Cerebellar-mPFC; Device: Sham Intervention Group

Study type: Interventional

Funder types: Other

Identifiers

NCT06457230

MZhao-015

Details and patient eligibility

About

To investigate the mechanism and efficacy of a novel repetitive transcranial magnetic stimulation (rTMS) intervention model with paired medial prefrontal cortex (mPFC) -cerebellar pulses on methamphetamine use in patients and to develop a novel physiotherapeutic intervention to optimise the treatment and management of addicted patients.

Full description

Numerous studies have shown that impaired mPFC-cerebellar functional connectivity leads to impaired social preferences and behavioural flexibility and more persistent drug use in addicts. Cerebellar and mPFC paired-pulse rTMS interventions may enhance functional connectivity, effectively modulate cerebellar-prefrontal loops, reduce craving, improve cognitive flexibility, and reduce relapse risk. The aim of this project is to investigate the mechanism and efficacy of a novel paired-pulse rTMS intervention targeting the mPFC-cerebellar circuit in patients with methamphetamine use disorder, in order to develop innovative physiotherapeutic interventions and to optimize treatment and clinical management for individuals with addiction.

Prior to initiating the intervention, it was essential to determine the optimal inter-stimulus interval (ISI) for the cerebellar-mPFC paired associative stimulation. Therefore, a mechanistic study was conducted from December 2024 to June 2025 at the Chengdu Drug Rehabilitation Center in Sichuan Province before the interventional trial commenced. A mixed design was employed, contrasting single-pulse mPFC stimulation with cerebellum→mPFC cortico-cortical paired associative stimulation (ccPAS) at inter-stimulus intervals of 6 ms and 45 ms. The results revealed that individuals with methamphetamine use disorder exhibited aberrant cerebellar-mPFC circuit connectivity compared to healthy controls. Importantly, cerebellar-mPFC ccPAS with a 6-ms ISI was found to specifically modulate this inter-regional circuit dysfunction.

Therefore, based on the identified 6-ms cerebellar-mPFC stimulation interval, the current interventional study continues to implement a long-term, dual-coil combined stimulation protocol to further evaluate and establish its therapeutic efficacy.

Enrollment: 70 estimated patients

Sex: Male

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Primary substance of abuse is methamphetamine.
2. Meets the DSM-5 diagnostic criteria for severe methamphetamine use disorder (≥6 symptoms present within the past year).
3. Age: 18-60 years.
4. Education level of primary school or above, with the ability to comprehend questionnaires and behavioral tasks.
5. Normal vision and hearing; right-handed.
6. No prior participation in any TMS-related intervention therapy.

Exclusion Criteria

1. Presence of any metallic implants (e.g., dental prostheses, orthodontic braces, bone fixation plates, aneurysm clips, intrauterine devices) or implanted medical devices such as cardiac pacemakers or neurostimulators.
2. Chronic or severe somatic diseases (e.g., cardiac conditions, uncontrolled hypertension, physical disabilities).
3. Comorbid psychiatric disorders (e.g., schizophrenia, depressive disorders, anxiety disorders).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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70 participants in 2 patient groups

Sham Cerebellar Stimulation + Sham mPFC Stimulation Group

Sham Comparator group

Description:

This is the sham stimulation group. The coil will be placed vertically over the cerebellar and mPFC brain regions, allowing participants to perceive the coil's vibration and sound without receiving effective intervention. All other stimulation parameters are identical to those in the active intervention group.

Treatment:

Device: Sham Intervention Group

Cerebellar-mPFC Dual-Coil Paired-Pulse TMS Intervention Group

Experimental group

Description:

The stimulation protocol involved delivering a pulse to the cerebellum first, followed by a pulse to the mPFC after a 6ms inter-stimulus interval (ISI). This 6ms interval was determined based on findings from our prior mechanistic study.

Treatment:

Device: Paired Associative Stimulation Targeting the Cerebellar-mPFC