Hydrocortisone-enhanced PET Scans for Cocaine Use Disorder
Recruiting in Palo Alto (17 mi)
Overseen byRajesh Narendran, MD
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Rajesh Narendran
Must not be taking: Psychotropics, Opiates, Sedatives, others
Disqualifiers: Psychiatric disorders, Opiate abuse, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial uses a special brain scan and a stress hormone injection to study how brain receptors react in people with cocaine addiction. It aims to understand why these individuals often relapse by comparing them to healthy individuals.
Will I have to stop taking my current medications?
Yes, you will need to stop taking any prescription medical or psychotropic medications to participate in this trial.
What data supports the effectiveness of the drug Hydrocortisone-enhanced PET Scans for Cocaine Use Disorder?
Research shows that cortisol, a hormone related to stress, is involved in cocaine addiction and affects craving and cognitive performance. This suggests that treatments targeting cortisol levels, like hydrocortisone, might help manage cocaine use disorder by influencing these factors.
12345Is hydrocortisone safe for use in humans?
The studies reviewed do not directly address the safety of hydrocortisone in humans for this specific treatment, but they do suggest that cortisol, a form of hydrocortisone, is involved in the body's response to cocaine. However, no specific safety concerns about hydrocortisone itself were identified in these studies.
14678How does the drug hydrocortisone differ from other treatments for cocaine use disorder?
Hydrocortisone-enhanced PET scans for cocaine use disorder are unique because they involve using hydrocortisone, a hormone that affects the stress response, to potentially alter brain activity and improve imaging results. This approach is different from standard treatments, which typically focus on behavioral therapy or medications that target neurotransmitter systems directly involved in addiction.
12459Eligibility Criteria
This trial is for men and women aged 18-55 with cocaine use disorder, without other psychiatric or addictive disorders. Participants must not be on medications, have severe illnesses, be pregnant/breastfeeding, have significant past radiation exposure, MRI-incompatible body metals, or recent abuse of various drugs including opiates and alcohol.Inclusion Criteria
No present or past DSM-5 disorders for Healthy Controls (HC)
I am between 18 and 55 years old.
Nicotine use will be quantified and controlled between groups using the Fagerstrom Test for Nicotine Dependence (Heatherton et al., 1991)
+2 more
Exclusion Criteria
I am not taking any prescription drugs or mental health medications.
No history of significant radioactivity exposure in past year from another research study or occupation that exceeds RDRC guidelines
I don't have severe illnesses like glaucoma, seizures, high blood pressure, or high cholesterol.
+3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Baseline Imaging
Participants undergo baseline PET imaging with [11C]NOP-1A
1 day
1 visit (in-person)
Hydrocortisone Challenge
Participants receive an intravenous hydrocortisone challenge and undergo PET imaging to assess NOP receptor binding
1 day
1 visit (in-person)
Follow-up
Participants are monitored for relapse over a 12-week period
12 weeks
Participant Groups
The study tests how cortisol interacts with brain receptors in people with cocaine addiction compared to healthy controls using PET scans before and after hydrocortisone administration. It aims to see if these interactions can predict relapse in cocaine users.
1Treatment groups
Experimental Treatment
Group I: PETExperimental Treatment3 Interventions
\[C-11\]NOP-1A
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of PittsburghPittsburgh, PA
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Who Is Running the Clinical Trial?
Rajesh NarendranLead Sponsor
National Institute on Drug Abuse (NIDA)Collaborator
References
Depressive symptomatology and cocaine-induced pituitary-adrenal axis activation in individuals with cocaine dependence. [2019]The hypothalamic-pituitary-adrenal (HPA) axis plays a role in cocaine dependence and major depressive disorder. The authors examined the correlation between baseline depressive symptomatology and pituitary-adrenal axis activation induced by acute cocaine challenge. Twelve patients with cocaine dependence were administered an iv bolus of cocaine (0.6 mg/kg) and their plasma was assayed for levels of adrenocorticotropic hormone (ACTH) and cortisol. Depressive symptomatology was assessed with total Hamilton rating scale for depression (HRSD) scores and its vegetative and cognitive superfactors. Cocaine produced a mean increase from baseline of 261% for ACTH and 73% for cortisol plasma levels. Changes in ACTH (r=0.69) and cortisol (r=0.59) were positively and significantly correlated with total HRSD scores and its vegetative, but not cognitive, factor symptom cluster. These results suggest that the HPA axis may be involved in affective disturbances associated with the use of cocaine. Implications of these data for the pathophysiology of cocaine dependence are discussed.
Diurnal variations in plasma ACTH, cortisol and beta-endorphin levels in cocaine addicts. [2018]In order to establish possible alterations in the hypothalamic pituitary-adrenal axis and in ACTH-related opioids in cocaine addicts, plasma ACTH, cortisol and beta-endorphin levels were measured throughout the day in 9 cocaine addicts [age: 27 +/- 5 years (mean +/- SE); weight: 72 +/- 6.1 kg, duration of cocaine addiction: at least 2 years] on the day of their admission to a recovery community for drug abusers (first test) and after 15 days of abstinence (second test). Nine normal controls (age: 28 +/- 6 years; weight: 73 +/- 3.2 kg) were tested only once in a similar manner. Blood samples were taken at 06:00, 08:00, 10:00, 12:00, 18:00 and 20:00 h and served for hormonal assays. Urine samples were taken from cocaine addicts at 08:00 h on the experimental day and on the following day. Results of both urine assays were positive for cocaine catabolites, indicating cocaine administration during the day before the experimental test. From the day of their admission in the community (1st experimental day), the patients were forbidden to use cocaine. For 4 days after admission, they were treated with symptomatics to attenuate withdrawal symptoms. Thereafter, the patients underwent a washout period of pharmacological treatments for 10 days before being retested (second test). Urine samples taken at 08:00 h on this second experimental day and on the next day were negative for the presence of drug catabolites. During the first test, cocaine addicts showed higher plasma ACTH, cortisol and beta-endorphin levels than normal controls at all examined time points.(ABSTRACT TRUNCATED AT 250 WORDS)
Corticosterone circadian secretion differentially facilitates dopamine-mediated psychomotor effect of cocaine and morphine. [2019]Studies of intravenous self-administration and psychomotor effects of drugs have recently suggested that stress-induced corticosterone secretion may be an important factor determining vulnerability to drugs of abuse. In this report, we studied if basal physiological corticosterone secretion modulates sensitivity to cocaine and morphine, and if changes in the reactivity of mesolimbic dopaminergic (DA) neurons, one of the principal substrates of drug-reinforcing effects, are involved. For this purpose we determined the psychomotor effects of these drugs in animals in which corticosterone secretion was suppressed by adrenalectomy and in adrenalectomized animals submitted to different corticosterone replacement therapies designed to mimic (1) only the diurnal levels of the hormone, obtained by the subcutaneous implantation of 50 mg corticosterone pellets; (2) only the nocturnal levels, obtained by adding corticosterone (50 micrograms/ml) to the drinking solution during the dark period; and (3) the entire circadian fluctuation, obtained by combining the two previous treatments. Locomotor response to cocaine and morphine was studied after both systemic and central injections, into the nucleus accumbens for cocaine and into the ventral tegmental area for morphine. These sites were chosen because stimulant effects of cocaine and morphine injected in these structures are dopamine dependent. Our results show that suppression of corticosterone by adrenalectomy reduced the locomotor response to cocaine and morphine, injected both systemically and centrally. The reinstatement of diurnal levels of corticosterone totally reversed adrenalectomy's effects on the behavioral response to cocaine, whereas the reestablishment of the entire corticosterone circadian fluctuation (diurnal plus nocturnal levels) was necessary to reverse the response to morphine.(ABSTRACT TRUNCATED AT 250 WORDS)
Quantitative medial temporal lobe brain morphology and hypothalamic-pituitary-adrenal axis function in cocaine dependence: a preliminary report. [2019]Preclinical and clinical studies have shown that cocaine increases plasma adrenocorticotropin hormone (ACTH) and cortisol. Chronic elevation of plasma cortisol exerts direct toxic effects upon hippocampal neurons and exacerbates hippocampal damage resulting from ischemia and seizures. The authors tested for evidence of hippocampal damage in patients with chronic cocaine dependence. Medial temporal lobe and total brain volumes were quantified using magnetic resonance imaging (MRI) in 27 patients with cocaine dependence and 16 healthy subjects. Basal and ovine corticotropin releasing hormone (oCRH) stimulated ACTH and cortisol levels were also examined in a subset of 8 healthy and 9 cocaine dependent subjects after 21 days of abstinence. No evidence for decreased hippocampal or total brain volume in cocaine dependence was observed. Similarly, basal and oCRH stimulated ACTH and cortisol levels in cocaine dependent patients did not differ from those in healthy subjects.
Salivary Cortisol Levels Are Associated with Craving and Cognitive Performance in Cocaine-Abstinent Subjects: A Pilot Study. [2020]Cortisol is a glucocorticoid hormone secreted by the adrenal cortex upon the activation of the hypothalamic-pituitary-adrenal (HPA) axis. Assessment of cortisol in saliva has emerged as a reliable way of evaluating HPA function. We examined the relationships between salivary cortisol levels with both craving and cognitive performance, as a possible biomarker of cocaine addiction. Cognitive performance (attention, declarative and working memory, executive functions and recognition of emotions) was assessed in 14 abstinent cocaine-dependent subjects in outpatient treatment and 13 control participants. Three salivary samples were collected at home by all the participants in the morning, afternoon and at bedtime. Patients showed higher levels of cortisol in the morning, as well as higher area under the curve with respect to the ground (AUCg). Regarding cognitive performance, cocaine-abstinent subjects showed worse performance in attention (d2 test), verbal memory (Spanish Complementary Verbal Learning Test, TAVEC) and executive tests (Tower of Hanoi and phonological fluency test) with respect to the control group. Morning cortisol levels and the AUCg index were negatively associated with the age of onset of drug consumption and the AUCg index was also positively associated with craving in our patients' group. Moreover, morning cortisol levels, as well as the AUCg index, were negatively associated with verbal memory performance. Therefore, our pilot study suggests that salivary cortisol measurements could be a good avenue to predict craving level, as well as cognitive status, especially the declarative memory domain.
Metyrapone and cocaine: a double-blind, placebo-controlled drug interaction study. [2013]Pre-clinical research suggests that suppression of adrenocorticosteroid synthesis might decrease susceptibility to stress-induced relapse. Metyrapone effectively suppresses cortisol synthesis and thus might have promise as a cocaine dependence treatment. The present inpatient study evaluated the interaction of metyrapone and cocaine to assess the safety of conducting an outpatient trial. Twelve nontreatment-seeking cocaine-dependent individuals completed this double-blind, placebo-controlled, crossover study with two factors: medication (750 mg of metyrapone vs. placebo) and infusion (40 mg of cocaine vs. saline). Safety measures included vital signs, adverse events, and electrocardiogram. Efficacy measures included visual analog scale (VAS) ratings of craving and drug effect. Neuroendocrine measures included cortisol and ACTH. As predicted, metyrapone was well tolerated and did not exacerbate cocaine's physiological effects. Also as predicted, metyrapone did not significantly alter cocaine's subjective effects. The results of the present study suggest that metyrapone at the dose studied can likely be used safely in an outpatient study with active cocaine users.
Cocaine effects on pulsatile secretion of ACTH in men. [2018]The effects of cocaine on pulsatile secretion of adrenocorticotropic hormone (ACTH) in men were studied under controlled clinical research ward conditions. Eight men with a Diagnostic and Statistical Manual of the American Psychiatric Association Version III, revised, diagnosis of concurrent cocaine and opioid dependence provided their informed consent for participation in this study. After an overnight fast, a challenge dose of cocaine (30 mg i.v.) or placebo was administered under single-blind conditions in a randomized order on 2 study days. Blood samples were collected at 2-min intervals for 76 min during base line and for an additional 76 min after i.v. administration of the challenge dose. Peak plasma cocaine levels of 313.8 +/- 46.5 ng/ml were detected within 2 min after cocaine administration. The cluster analysis program originally described by Veldhuis and Johnson (1986) was used to characterize ACTH pulsatile secretion (Iranmanesh et al., 1990). Acute cocaine administration (30 mg i.v.) significantly increased ACTH mean peak amplitude (P
Effects of cocaine on pulsatile activity of hypothalamic-pituitary-adrenal axis in male rhesus monkeys: neuroendocrine and behavioral correlates. [2018]Cocaine stimulates the hypothalamic-pituitary-adrenal (HPA) axis in rodents and in humans. This study examined the acute effects of cocaine (0.4 and 0.8 mg/kg) and saline placebo on pulsatile adrenocorticotropic hormone (ACTH) and cortisol release in seven male rhesus monkeys. Pulsatile ACTH and cortisol release were evaluated with an intensive (2-min) venous blood sampling procedure and cluster analysis. In addition, the behavioral responses to cocaine were analyzed to assess the relationship between HPA axis activation and behavior. Although analysis of group data revealed significant (P .05; N.S.). Base-line cortisol, but not ACTH, levels were higher (P
Effects of cortisol and cocaine on plasma prolactin and growth hormone levels in cocaine-dependent volunteers. [2013]In rodents, corticosterone (cortisol in humans) facilitates cocaine self-administration purportedly via enhancement of dopaminergic activity in the brain. This study sought to assess central dopaminergic effects of cortisol in humans and to compare them to those of cocaine. Twelve cocaine-dependent individuals received an intravenous bolus of cortisol (0.5 and 0.2 mg/kg; n=6 for each dose) and cocaine (0.2 mg/kg) in a double-blind randomized placebo-controlled and counterbalanced fashion. Their plasma was assayed over the next 120 min for prolactin and growth hormone (GH), which are two neuroendocrine indices of dopaminergic function. Cortisol injections produced significant increases in GH, while cocaine resulted in significant decreases in prolactin. Placebo administration was associated with gradual declines in prolactin, but the levels at the 90- and 120-min time points were significantly lower after cocaine than after placebo infusion. These different neuroendocrine response profiles point to important differences between dopaminergic effects of cortisol and cocaine.