The researchers will test whether cognitively enhanced transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex can reduce craving in inpatients with cocaine use disorder. Neuroimaging before and after stimulation will establish the neural correlates of recovery and allow predictions of outcomes, which will be assessed throughout the study and one month after its completion. Results could pave the way towards development of a new self-administered intervention to reduce craving when it is needed the most, enhancing recovery real-time and in the natural environment in people with cocaine addiction as generalizable to other drugs of abuse and other disorders of self-control.

Over the past decade, the US has been affected by a re-emerging stimulant use public health crisis and alarming increases in crack/cocaine-related overdose deaths. In contrast to other types of addiction, there are no FDA approved treatments for crack/cocaine use disorder (CUD). Developing and testing evidence-based treatment options for this population, and exploring the underlying neural substrates, are therefore urgently needed. Core symptoms of addiction are craving and heightened reactivity to drug cues, attributed to impairments in prefrontal functions. This study builds upon Phase-1 and Phase-2 trials testing whether transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex can reduce craving in treatment-seeking inpatients with CUD. Participants will be randomized to receive real or sham tDCS, combined with cognitive reappraisal training of drug cues or a control condition, in a double-blind, factorial design (N=120). Craving and drug use outcomes will be assessed throughout the intervention and at one-month follow-up. Neuroimaging will be used to examine neural correlates of treatment response. Results may inform development of scalable, self-administered interventions to reduce craving and relapse risk in cocaine addiction.

Inclusion Criteria:

• Ability to understand and give informed consent
• Men and women 18-60 years of age.
• For women of childbearing potential, current use of a medically acceptable form of birth control
• DSM-5 diagnosis of stimulant use disorder with crack/cocaine as the drug of choice

Exclusion Criteria:

• Lifetime diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, bipolar I disorder, or delusional disorder as confirmed by the MINI or autism spectrum disorder as confirmed by medical history at the screening visit
• Current clinically significant or unstable medical conditions, including metabolic, endocrinological, oncological or autoimmune diseases, infectious diseases common in people with substance use disorders including Hepatitis B and C or HIV/AIDS; use of medications deemed exclusionary by the study team; or any laboratory value outside the reference range that the senior investigator team considers to be of clinical relevance
• Head trauma with loss of consciousness (>30 min)
• History of neurological or developmental disease of central origin including stroke, brain tumor or seizures, encompassing those symptoms associated with periods of drug withdrawal or abstinence
• Metal implants or devices that may be impacted by the electrical stimulation and additional MR contraindications
• Women of childbearing potential must use a medically acceptable birth control method during the study and will be asked to take a pregnancy urine test before exposure to tDCS (or MRI)

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

Immediately following publication. No end date.

Researchers who provide a methodologically sound proposal. Any purpose. Proposals should be directed to NARC@mssm.edu. To gain access, data requestors will need to sign a data access agreement.