Hydrocortisone-enhanced PET Scans for Cocaine Use Disorder

Overseen By Rajesh Narendran, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Rajesh Narendran

Must not be taking: Psychotropics, Opiates, Sedatives, others

Disqualifiers: Psychiatric disorders, Opiate abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

80 Participants Needed

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. ^{1 2 3 4 5}

Is 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. ^{2 3 6 7 8}

How 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. ^{1 2 3 4 9}

Research Team

Rajesh Narendran, MD

Principal Investigator

University of Pittsburgh

Eligibility 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)

Nicotine use will be quantified and controlled between groups using the Fagerstrom Test for Nicotine Dependence (Heatherton et al., 1991)

Fulfil DSM-5 criteria for cocaine use disorder

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.

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

Treatment Details

Interventions

• [C-11]NOP-1A
• Hydrocortisone

Trial Overview 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.

Participant Groups

Group I: PET Experimental Treatment 3 Interventions

\[C-11\]NOP-1A

Who Is Running the Clinical Trial?

Rajesh Narendran

Lead Sponsor

Trials

4

Recruited

180+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

In a study of 14 abstinent cocaine-dependent individuals and 13 control participants, higher morning salivary cortisol levels were found in cocaine users, indicating altered HPA axis function that may relate to addiction.

The study suggests that salivary cortisol levels could serve as a biomarker for predicting craving and cognitive performance, particularly in verbal memory, highlighting potential avenues for treatment and assessment in cocaine addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salivary Cortisol Levels Are Associated with Craving and Cognitive Performance in Cocaine-Abstinent Subjects: A Pilot Study. Sampedro-Piquero, P., Vicario, S., Pérez-Rivas, A., et al.[2020]

In a study involving 27 patients with cocaine dependence and 16 healthy controls, no significant differences in hippocampal or total brain volumes were found, suggesting that chronic cocaine use may not lead to structural brain damage in these areas.

Additionally, levels of ACTH and cortisol, both at baseline and after stimulation, were similar between cocaine-dependent individuals and healthy subjects, indicating that cocaine dependence may not alter the hypothalamic-pituitary-adrenal (HPA) axis response in the short term after abstinence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative medial temporal lobe brain morphology and hypothalamic-pituitary-adrenal axis function in cocaine dependence: a preliminary report. Jacobsen, LK., Giedd, JN., Kreek, MJ., et al.[2019]

In a study of 12 patients with cocaine dependence, an acute cocaine challenge significantly increased levels of adrenocorticotropic hormone (ACTH) by 261% and cortisol by 73%, indicating strong activation of the hypothalamic-pituitary-adrenal (HPA) axis.

There was a significant positive correlation between the increases in ACTH and cortisol levels and the severity of depressive symptoms, particularly in vegetative symptoms, suggesting that the HPA axis may play a role in the mood disturbances associated with cocaine use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Depressive symptomatology and cocaine-induced pituitary-adrenal axis activation in individuals with cocaine dependence. Elman, I., Breiter, HC., Gollub, RL., et al.[2019]

Cocaine addicts exhibited significantly higher levels of plasma ACTH, cortisol, and beta-endorphin compared to normal controls, indicating alterations in their hypothalamic-pituitary-adrenal (HPA) axis at the time of admission.

After 15 days of abstinence, cocaine addicts showed normalized levels of these hormones, suggesting that abstinence can lead to recovery of HPA axis function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diurnal variations in plasma ACTH, cortisol and beta-endorphin levels in cocaine addicts. Vescovi, PP., Coiro, V., Volpi, R., et al.[2018]

Suppressing corticosterone secretion through adrenalectomy decreased the locomotor response to both cocaine and morphine in animals, indicating that basal corticosterone levels play a crucial role in drug sensitivity.

Restoring diurnal levels of corticosterone fully reversed the effects of adrenalectomy on cocaine response, while a complete circadian fluctuation of corticosterone was necessary to restore the response to morphine, highlighting the importance of hormonal timing in drug effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticosterone circadian secretion differentially facilitates dopamine-mediated psychomotor effect of cocaine and morphine. Marinelli, M., Piazza, PV., Deroche, V., et al.[2019]

In a study involving 12 cocaine-dependent individuals, metyrapone was found to be well tolerated and did not worsen the physiological effects of cocaine, indicating its safety for potential outpatient use.

Metyrapone did not significantly change the subjective effects of cocaine, suggesting that while it may help in reducing stress-induced relapse, it does not interfere with the immediate drug experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metyrapone and cocaine: a double-blind, placebo-controlled drug interaction study. Winhusen, T., Somoza, E., Harrer, JM., et al.[2013]

In a study involving 8 men with concurrent cocaine and opioid dependence, a single intravenous dose of cocaine (30 mg) significantly increased various measures of adrenocorticotropic hormone (ACTH) secretion, indicating a strong physiological response to cocaine.

The findings suggest that cocaine may stimulate the release of corticotropin-releasing factor, which enhances the amplitude of ACTH pulses without changing their frequency, highlighting a specific mechanism of action related to hormone regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cocaine effects on pulsatile secretion of ACTH in men. Teoh, SK., Sarnyai, Z., Mendelson, JH., et al.[2018]

Cocaine administration (0.8 mg/kg) significantly increased the amplitude of pulsatile adrenocorticotropic hormone (ACTH) and cortisol release in male rhesus monkeys that exhibited behavioral stimulation, indicating a link between HPA axis activation and behavioral response.

However, not all monkeys responded similarly; those classified as low responders showed decreased ACTH peak amplitude and no change in cortisol release, suggesting individual differences in response to cocaine that were not related to plasma cocaine levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of cocaine on pulsatile activity of hypothalamic-pituitary-adrenal axis in male rhesus monkeys: neuroendocrine and behavioral correlates. Sarnyai, Z., Mello, NK., Mendelson, JH., et al.[2018]

In a study involving 12 cocaine-dependent individuals, cortisol administration led to significant increases in growth hormone (GH), indicating enhanced dopaminergic activity, while cocaine resulted in decreased prolactin levels, suggesting different effects on the dopaminergic system.

The contrasting neuroendocrine responses to cortisol and cocaine highlight important differences in their mechanisms of action, with cortisol potentially facilitating dopaminergic activity while cocaine appears to suppress it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of cortisol and cocaine on plasma prolactin and growth hormone levels in cocaine-dependent volunteers. Elman, I., Lukas, SE.[2013]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Salivary Cortisol Levels Are Associated with Craving and Cognitive Performance in Cocaine-Abstinent Subjects: A Pilot Study. [2020]

2. Ireland pubmed.ncbi.nlm.nih.gov

Quantitative medial temporal lobe brain morphology and hypothalamic-pituitary-adrenal axis function in cocaine dependence: a preliminary report. [2019]

3. Ireland pubmed.ncbi.nlm.nih.gov

Depressive symptomatology and cocaine-induced pituitary-adrenal axis activation in individuals with cocaine dependence. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Diurnal variations in plasma ACTH, cortisol and beta-endorphin levels in cocaine addicts. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Corticosterone circadian secretion differentially facilitates dopamine-mediated psychomotor effect of cocaine and morphine. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Metyrapone and cocaine: a double-blind, placebo-controlled drug interaction study. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Cocaine effects on pulsatile secretion of ACTH in men. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Effects of cocaine on pulsatile activity of hypothalamic-pituitary-adrenal axis in male rhesus monkeys: neuroendocrine and behavioral correlates. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Effects of cortisol and cocaine on plasma prolactin and growth hormone levels in cocaine-dependent volunteers. [2013]