Transcranial Magnetic Stimulation Used to Both Measure Cortical Excitability and Explore Methamphetamine Cue Craving

Specific Primary Aims include:

Aim # 1. The investigators explore the feasibility of using the TMS to investigate the cortical excitability and to inhibit meth cue craving in meth dependent population. The investigators anticipate that meth elevates cortical excitability measured by motor threshold, causes changes of cortical silent period, and RC. The investigators also anticipate that paired pulse measures (short-interval intracortical inhibition, short-interval intracortical facilitation and long-interval intracortical inhibition) will be different from healthy control, which are more directly linked to glutamatergic cortical facilitation and GABAergic inhibition, respectively.

Aim # 2. Given the change of the cortical excitability in meth users, the investigators will use inhibiting TMS (1 Hz) over medial prefrontal cortex to study whether TMS can be used to reduce cue craving. The investigators hypothesize that repetitive TMS reduce meth cue craving in meth dependent population compared with sham rTMS.


Eligibility Criteria:
Inclusion Criteria:

1. Be volunteers who are dependent on meth and not currently seeking treatment. They must not have received substance abuse treatment within the previous 30 days.
2. Be male or female of any race or ethnic group, between the ages of 18 and 50 years.
3. Meet DSM IV criteria for meth dependence as determined by the MINI International Neuropsychiatric Interview (MINI).
4. Currently be using meth by smoked, oral, or intravenous routes of administration, used meth for a minimum of 2 years and a minimum of an average of 3 times a week in the 30 days prior to screening.
5. Be in stable mental and physical health.
6. If female, test non-pregnant and use adequate birth control. All female subjects will have urine pregnancy tests in all three phases of the study.
7. Be capable of providing written informed consent to participate in this study.
8. Be able to comply with protocol requirements and be likely to complete all study procedures.
9. Live within a 50 mile radius of our research program, have reliable transportation, and have a stable residence for at least the 30 days prior to starting the study.
10. Be willing to abstain from alcohol, marijuana and CNS acting prescription and OTC medications for the 2 week screening and hospitalization phases.
11. Have a positive urine for meth within 72 hours of admission to the hospital phase of the study and have at least one other positive urine for meth during the screening phase.
12. Be right-handed.

Exclusion Criteria:

1. Have current dependence, defined by DSM IV criteria, on any psychoactive substances other than meth, nicotine, or caffeine.
2. Have a history and/or test positive for significant hepatic, renal, endocrine, cardiac, or inflammatory diseases, as well as stroke, seizures, migraine, serious head trauma, or other neurological disorders that might interfere with stability during the study or the acquisition of accurate fMRI scans.
3. If female, have intentions to become pregnant during the study.
4. Have been required by the courts to obtain treatment for meth or some other substance dependence.
5. Be seeking treatment for meth or other substance dependence.
6. Have a medical history or condition considered by the investigators to place the subject at increased risk (implanted ferrous materials or devices) or to decrease the likelihood of study completion.
7. Be anticipating elective surgery or hospitalization within 8 weeks of signing the informed consent agreement.
8. Be on medications in the last 30 days that may alter CNS function or alter fMRI results. Examples of such medications include but are not limited to the following: psychotropics, CNS active anti-hypertensives, steroids, anticonvulsants, antihistamines and CNS OTCs.
9. Have a life time history of major Axis I disorders such as: BPAD, Schizophrenia, PTSD, or Dementia, or have a current history of Major Depression or suicide attempt within 12 months
10. Have a self report of \>21 standard alcohol drinks per week in any week in the 30 days prior to screening or a Carbohydrate Deficient Transferrin \>3.0%.
11. Be unwilling to use a patch and cease smoking cigarettes for the eight days in the hospital.