Ignite Creation Date:
2024-06-16 @ 11:49 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06430580
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-15
First Post:
2024-05-13
Brief Title:
Cannabinoids and Biological Reactivity to Stress
Sponsor:
Auburn University
Organization:
Auburn University
Study Overview
Official Title:
Cannabinoids and Biological Reactivity to Stress
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
COBRAS
Brief Summary:
The goal of this study is to test the impact of two drugs that produce temporary stress-like symptoms both in isolation and together on cannabis use motivation in individuals with Cannabis Use Disorder The main questions it will answer are
1 How do different forms of stress affect cannabis use motivation
2 How do different forms of stress affect the bodys natural cannabinoids
Researchers will compare a placebo to both drugs in isolation as well as together across four separate lab visits
Participants will
1 Complete a clinical screening interview by phone or in-person and visit the lab for a medical screening and if eligible
a Visit the lab four times where they will i Take one of four drug combinations ii Complete an interview questionnaires and computerized tasks iii Have their brain activity recorded with an EEG cap iv Provide three blood samples
1 How do different forms of stress affect cannabis use motivation
2 How do different forms of stress affect the bodys natural cannabinoids
Researchers will compare a placebo to both drugs in isolation as well as together across four separate lab visits
Participants will
1 Complete a clinical screening interview by phone or in-person and visit the lab for a medical screening and if eligible
a Visit the lab four times where they will i Take one of four drug combinations ii Complete an interview questionnaires and computerized tasks iii Have their brain activity recorded with an EEG cap iv Provide three blood samples
Detailed Description:
The prevalence of daily cannabis use and cannabis use disorder CUD has increased in the United States over the past two decades Unfortunately psychosocial treatments produce minimal long-term abstinence rates and no FDA-approved medications for CUD exist Thus identifying novel CUD treatment targets is an increasingly urgent public health need
Stress-elicited cannabis use motivation has been implicated in worse CUD outcomes but a mechanistic understanding of how acute stress increases cannabis use motivation in CUD is limited Prior work has demonstrated that acute psychosocial stress enhancement of subsequent cannabis cue incentive salience as indexed by the late positive potential neural measure of approach-motivated attention recorded using electroencephalography EEG was associated with worse CUD severity and intervention response independent of subjective craving Moreover hypothalamic pituitary adrenal HPA-axis rather than noradrenergic or subjective reactivity to the psychosocial stressor was associated with subsequent potentiation of the cannabis cue-elicited late positive potential These studies suggest that non-genomic rapid glucocorticoid effects may be a contributing mechanism in stress amplification of neural drug-cue reactivity but their correlational designs preclude causal inference Further psychosocial stressors are unable to isolate HPA-axis vs noradrenergic components of stress reactivity
To isolate HPA-axis activation and test causality pharmacological manipulations common in animal models but rare in human studies will be used to produce separate and co-operative glucocorticoid 20mg hydrocortisone and noradrenergic 54mg yohimbine activation The investigators will employ a 2x2 randomized placebo-controlled double-blind crossover design in 36 participants with severe CUD The primary aim is to test the causal potentiating effect of glucocorticoids on drug-cue reactivity and drug use motivation and further determine if the effect depends on co-occurring noradrenergic stimulation Preclinical work indicates that glucocorticoids can potentiate reward motivation via mobilization of endocannabinoid activity primary target of cannabis Thus as an exploratory aim the investigators will obtain plasma samples to test the impact of pharmacological stress on circulating endocannabinoids 2-AG AEA and their mediating role in glucocorticoid potentiation of drug-cue reactivity and drug use motivation This project represents a highly novel integration of a rigorous pharmacological challenge design with biological markers of drug-cue incentive salience and endocannabinoid system activity If hypotheses are confirmed one causal mechanism through which stress increases neural cannabis cue reactivity will be known which has immediate implications for testing experimental therapeutics The long-term goal is to understand how a stress-related mechanism predictive of worse CUD phenotype is generated and can be blocked in CUD Development of this model will provide a valid efficient and relative to other neuroimaging methods low-cost approach to screen candidate medications and optimize psychosocial drug cue exposure therapies
Stress-elicited cannabis use motivation has been implicated in worse CUD outcomes but a mechanistic understanding of how acute stress increases cannabis use motivation in CUD is limited Prior work has demonstrated that acute psychosocial stress enhancement of subsequent cannabis cue incentive salience as indexed by the late positive potential neural measure of approach-motivated attention recorded using electroencephalography EEG was associated with worse CUD severity and intervention response independent of subjective craving Moreover hypothalamic pituitary adrenal HPA-axis rather than noradrenergic or subjective reactivity to the psychosocial stressor was associated with subsequent potentiation of the cannabis cue-elicited late positive potential These studies suggest that non-genomic rapid glucocorticoid effects may be a contributing mechanism in stress amplification of neural drug-cue reactivity but their correlational designs preclude causal inference Further psychosocial stressors are unable to isolate HPA-axis vs noradrenergic components of stress reactivity
To isolate HPA-axis activation and test causality pharmacological manipulations common in animal models but rare in human studies will be used to produce separate and co-operative glucocorticoid 20mg hydrocortisone and noradrenergic 54mg yohimbine activation The investigators will employ a 2x2 randomized placebo-controlled double-blind crossover design in 36 participants with severe CUD The primary aim is to test the causal potentiating effect of glucocorticoids on drug-cue reactivity and drug use motivation and further determine if the effect depends on co-occurring noradrenergic stimulation Preclinical work indicates that glucocorticoids can potentiate reward motivation via mobilization of endocannabinoid activity primary target of cannabis Thus as an exploratory aim the investigators will obtain plasma samples to test the impact of pharmacological stress on circulating endocannabinoids 2-AG AEA and their mediating role in glucocorticoid potentiation of drug-cue reactivity and drug use motivation This project represents a highly novel integration of a rigorous pharmacological challenge design with biological markers of drug-cue incentive salience and endocannabinoid system activity If hypotheses are confirmed one causal mechanism through which stress increases neural cannabis cue reactivity will be known which has immediate implications for testing experimental therapeutics The long-term goal is to understand how a stress-related mechanism predictive of worse CUD phenotype is generated and can be blocked in CUD Development of this model will provide a valid efficient and relative to other neuroimaging methods low-cost approach to screen candidate medications and optimize psychosocial drug cue exposure therapies
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R21DA058780-01A1 | NIH | None | httpsreporternihgovquickSearchR21DA058780-01A1 |