Guanfacine to Improve Substance Use Outcomes in Women

This study proposes to extend previous Phase I experimental work to address the following specific aims: (1) assess GUA's target engagement of drug craving and cognitive flexibility in a laboratory challenge session and in a 10-week outpatient clinical study, (2) demonstrate target validation by showing that reduced drug craving and improved cognitive flexibility will predict lower drug use outcomes during the 10-week clinical trial in SUD women, and finally, (3) evaluate data replication and scalability of GUA target effects across two clinical sites (Yale and SUNY-Stony Brook).

Inclusion criteria

• 100 treatment seeking women
• Ages 18-70 years
• Body mass index (BMI) of 18-35
• Meet current DSM-V criteria for co-occurring SUDs, with primary DSM-V cocaine or primary DSM-V opioid use disorder AND co-occurring cannabis or alcohol or nicotine use disorders;
• Positive drug urine toxicology screens for primary addictive disorder during a 2-week intake assessment period
• Good health as verified by screening examination
• Able to read English and complete study evaluations
• Able to provide informed written and verbal consent

Exclusion criteria

• Meet criteria for physiological dependence on alcohol requiring medical detoxification
• Regular use of anti-hypertensives, anti-arrythmics, antiretroviral medications, and medications that would interact with Guanfacine and be contraindicated as per study physician;
• Psychotic or otherwise severely psychiatrically disabled (i.e., suicidal, homicidal, current mania)
• Significant underlying medical conditions which in the opinion of study physician would preclude patient from fully cooperating or be of potential harm during the course of the study; Specifically hepatic and renal impairment as per liver enzymes at 3X the normal limit, or BUN>50mg or BUN:Cr > 10:1.
• Hypotensive women with sitting blood pressure below 100/50 mmHG
• Women who are pregnant, nursing or refuse to use a reliable form of birth control
• EKG evidence at baseline screening of any clinically significant conduction abnormalities, including a Bazlett's QT c>470 msec for women.