Methamphetamine (MA) is a psychostimulant drug with high abuse potential. MA can be smoked, snorted, injected or ingested orally to produce a release of high levels of dopamine into the brain and reduction of dopamine uptake. Its use results in feelings of pleasure, increased energy, and greater alertness lasting up to 12 hours. In 2010, the National Survey on Drug Use and Health reported that 353,000 Americans aged 12 or older reported being current MA users. Over the past decade MA use rates have fluctuated with current use rates on the decline; however, importantly, even though overall use rates are declining, use rates among males and females are approaching equal proportions. This use rate pattern is unlike other drugs of abuse, which typically demonstrate males using more than females. In some states, more females than males consider MA as their drug of choice. Namely, in a 2010 report in the state of Utah, more females were diagnosed with MA as a primary substance of abuse than males upon admission to treatment.

Depression and MA use are highly comorbid. The relationship between MA use and depression is likely bidirectional, with MA use causing changes in mood and being used as a self-medicating behavior to reduce symptoms of depression. Several studies have shown that depression rates are higher in MA-using females compared to their male counterparts. It is likely that neurobiological and psychosocial mechanisms contribute to increased incidence of depressive symptoms in females.

No clear treatment model exists to suggest how the comorbidity of depression and MA use is best managed. In studies of antidepressants for treatment of MA withdrawal and dependence, findings have suggested that antidepressants are ineffective for treating depressive symptoms.

Creatine is an organic acid occurring naturally in vertebrates, where it takes part in energy homeostasis in tissues with fluctuating energy demands. Exogenous creatine has been shown to increase brain concentrations of PCr. Neuroimaging studies of creatine have shown increased brain phosphocreatine (PCr) content with creatine administration. Therefore, we hypothesize that oral creatine administration will increase PCr levels and reduce depressive symptoms in a sample of depressed female MA users. This hypothesis will be tested by a within subjects design by giving depressed MA using females oral creatine for eight weeks and measuring PCr pre- and post-treatment with magnetic resonance spectroscopy. Moreover, depressive symptoms will be measured by administration of the Hamilton Depression Rating Scale twice weekly during the course of creatine treatment.

Inclusion Criteria:

1. Female gender, ages 18-64 years inclusive
2. Diagnosis of MA dependence or abuse within the past 12 months, with MA preferred drug of abuse, identified by the SCID-I-RV
3. Current diagnosis of Major Depressive Disorder identified by the SCID-I-RV
4. Current HAM-D17 score of > 15

Exclusion Criteria:

1. Diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder, identified by the SCID-I-RV
2. History of or current diagnosis of renal disease, such as chronic renal failure, acute renal failure or end stage renal disease
3. Diabetes type I or II
4. Colitis or diverticulitis
5. Seizure disorder
6. Current serious suicide risk identified by the Columbia Severity Suicide Rating Severity
7. Current treatment with an antipsychotic, mood stabilizer, or antidepressant
8. Positive HIV test
9. Active Hepatitis C
10. Contraindication to magnetic resonance scan