A growing body of evidence suggests a wide range of brain areas including medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex (DLPFC) and other subcortical regions, such as anterior cingulate cortex (ACC) are critical for regulating cognitive control over decisions and involving in drug related cue processing. Previous studies have demonstrated that transcranial magnetic stimulation (rTMS) over dorsolateral prefrontal cortex reduces craving for meth dependences. Specifically, the H7 coil induces a magnetic field can target mPFC and ACC. In this study, the investigators investigated whether repeated dTMS intervention of medial prefrontal and cingulate cortices in methamphetamine addiction could reduce the subjective craving and improve the cognitive abilities.

The study will be conducted at the drug rehabilitation center in China. The whole procedure includes enrollment, pre-intervention evaluation, intervention (for 3 weeks, 5 times a week, 15 times in total), post-intervention evaluation and one month follow up evaluation.

In enrollment session, participants are recruited according to inclusion criteria.

In the pre-intervention evaluation, firstly, participants need complete a questionnaire to assess their demographic information, drug addiction history and drug abstinence. And then are assigned to either 10Hz group or sham group according to the counterbalance of their basic demographic and drug use information. Then, participants need complete craving, cognitive ability and electroencephalogram (EEG) assessment. For craving assessing, participants are shown a video of methamphetamine usage for 5 minutes, and then rated on the visual analogue scale (0 means completely undesired and 100 means extremely wanting) to report their craving for methamphetamine. For cognitive ability and EEG signal assessing, the whole process is conducted on the computer according to instructions.

In the intervention session, dTMS was administered using a TMS stimulator (Magstim, U.K.) equipped with a unique H-shaped coil design. The H-coil version used in this study was the H7 (Brainsway, Jerusalem, Israel). When placed 4-5 cm anterior to the foot motor cortex and used at 100% of the leg resting motor threshold (RMT), the H7 coil stimulates the dorsal mPFC and ACC bilaterally. A participant's RMT was determined before the first treatment and at the beginning of each week by ascertaining the coil position that elicited the minimal involuntary contractions of the feet (three of six attempts). The 10Hz group received 10 Hz dTMS at 100% of RMT, with 3-second pulse and 17-second intervals, for a total of 50 trains and 1500 pulses per session. The sham group received treatment with identical technical parameters, which induced scalp sensations but without penetration of the electric field into the brain.

Post-intervention evaluation and one month follow up evaluation are the same as in pre-intervention evaluation.

To ensure study quality, some measures are taken as bellow:

Researchers and drug rehabilitation staff will work together in whole process and the data will be converted into electronic versions once finishing each evaluation.

In the intervention, patients, operators, and raters were blind to treatment condition. Each patient is assigned a magnetic card that determined the coil (real or sham) in the helmet and raters are not present while treatments are administered.

After each treatment times, any side effect from participant's report are recorded to assure the safety and feasibility.

Statistical analyses are performed using SPSS 21.0. The principal statistical analysis is performed using repeated-measures analysis of variance and regression analysis. All missing data will be recorded and marked.

Inclusion Criteria:

• Methamphetamine dependents
• middle school degree or above

Exclusion Criteria:

• Have contraindications to rTMS (head trauma, epilepsy or history of epilepsy, metal implant etc.)
• psychiatric illnesses
• intellectual impairment (IQ<90)

share all IPD that underlie results in a publication

Within twelve months after the trial complete

share to health care personnel, patients and the general public.