The Role of Neuroactive Steroids in Stress, Drug Craving and Drug Use in Cocaine Use Disorders

Early Phase 1

Completed

Brief Summary: To use pregnenolone (PREG; 300; 500mg) daily versus placebo (PLA) as a probe to assess the role of neuroactive steroids in individuals with cocaine use disorder (CUD).

Detailed Description: This experimental study aims to examine the effects of PREG on a) repeated cocaine craving, mood and neurobiological reactivity to brief, guided imagery exposure to stress, drug cues and neutral situations in the laboratory and b) daily cocaine intake, craving, cognition and mood in men and women with CUD; and c) sex differences in all of these outcomes. The study's hypothesis is that PREG vs PLA will dose-specifically decrease stress-induced and drug-cue induced cocaine craving, improve mood and cognitive performance, and normalize hypothalamic pituitary adrenal (HPA) axis response to stress and drug-cue imagery, and reduce cocaine intake and craving in daily life in individuals with CUD.

Recruitment & Eligibility

Inclusion Criteria

Male or female individuals, ages 18 to 60.
Subjects must meet current DSM-V criteria for cocaine use disorder; documented positive urine toxicology screen for cocaine at intake or collateral information from family members, significant others, room-mates etc., on recent use.
Subject has voluntarily given informed consent and signed the informed consent document.
Able to read English and complete study evaluations.

Exclusion Criteria

Women who are pregnant, or nursing or are of childbearing potential and not practicing an effective means of birth control.
Meet current criteria for use disorder on another psychoactive substance, such as, heroin, amphetamines, hallucinogens/PCP, excluding alcohol and nicotine.
Any current use of opiates or past history of opiate use disorder.
Current use of any psychoactive drugs, including anxiolytics, antidepressants, naltrexone or antabuse.
Any psychotic disorder or current Axis I psychiatric symptoms requiring specific attention, including need for psychiatric medications for current major depression and anxiety disorders.
Significant underlying medical conditions such as cerebral, renal, thyroid or cardiac pathology which in the opinion of study physician would preclude patient from fully cooperating or be of potential harm during the course of the study.
Abstinent from cocaine for more than two weeks prior to admission.
Hypotensive individuals with sitting blood pressure below 90/50 mmHG.

Arm && Interventions

Group	Intervention	Description
PREG 300	Pregnenolone (PREG)	Eligible participants will be randomly assigned to PREG 300 mg/day over 8 weeks with a) an inpatient-outpatient option where they will be admitted to the Clinical Neuroscience Research Unit (CNRU) at the Connecticut Mental Health Center (CMHC) for first two weeks and then outpatient at Yale Stress Center (YSC) for the remaining 6 weeks, or b) an outpatient option where they will participate in the entire study outpatient at YSC.
patients receiving placebo	Placebos	Eligible participants will be randomly assigned to a placebo (PLA) treatment over 8 weeks with a) an inpatient-outpatient option where they will be admitted to the Clinical Neuroscience Research Unit (CNRU) at the Connecticut Mental Health Center (CMHC) for the first two weeks and then transition to outpatient at Yale Stress Center (YSC) for the remaining 6 weeks, or b) an outpatient only option where they will participate in the entire study outpatient at YSC.
PREG 500	Pregnenolone (PREG)	Eligible participants will be randomly assigned to PREG 500 mg/day over 8 weeks with a) an inpatient-outpatient option where they will be admitted to the Clinical Neuroscience Research Unit (CNRU) at the Connecticut Mental Health Center (CMHC) for first two weeks and then outpatient at Yale Stress Center (YSC) for the remaining 6 weeks, or b) an outpatient option where they will participate in the entire study outpatient at YSC.

Primary Outcome Measures

Name	Time	Method
Craving Change in Stress and Cue Relative to Neutral	Experiment during treatment week 2	Cocaine craving assessed in a laboratory experiment with exposure to stress, cocaine cue and neutral control condition in those receiving PREG (300mg; 500mg) vs Placebo. Cocaine craving was assessed using the Cocaine Craving Questionnaire (CCQ), a brief 10-item self-report craving scale that ranges in mean score from 1 to 7, where a higher score indicates higher craving. Data presented here is craving change in stress relative to neutral and craving change in cue relative to neutral, where the possible range in mean change score is -6 to +6.

Secondary Outcome Measures

Name	Time	Method
Anxiety Change in Stress and Cue Relative to Neutral	Experiment during treatment week 2	Anxiety assessed in laboratory experiment with exposure to stress, cocaine cue and neutral control condition in participants receiving PREG (300mg; 500mg) vs. Placebo treatment. Anxiety was assessed using a 10-point visual analog scale (VAS) in which 0="not at all" and 10="extremely high", with the mean score ranging from 0 to 10, and where higher score means higher anxiety. Data presented here is anxiety change in stress relative to neutral and anxiety change in cue relative to neutral, where the possible range in mean change score is -10 to +10.
Cortisol Level Change in Stress and Cue Relative to Neutral	Experiment during treatment week 2	Plasma was collected at each laboratory session to measure cortisol level and assess change in cortisol response to stress and cocaine cue relative neutral imagery condition exposure. Data presented here are change in cortisol level (mg/dl) in stress relative to neutral condition and cue relative to neutral condition.
Pregnenolone Concentration	between weeks 2-3 of treatment	Blood plasma concentration of pregnenolone in two doses of PREG (300mg; 500mg), and matching placebo, assessed over a 24 hour period.