Cocaine and Zolmitriptan
- Conditions
- Cocaine Use Disorder
- Interventions
- Registration Number
- NCT05019430
- Lead Sponsor
- William Stoops
- Brief Summary
Cocaine potently inhibits the reuptake of serotonin (5-HT). Increased synaptic 5-HT resulting from this reuptake inhibition activates multiple 5-HT receptor subtypes. Some of these receptor subtypes have been implicated in the abuse-related effects of cocaine, including its primary reinforcing effects (i.e., cocaine taking behavior). 5-HT1b receptors, which are autoreceptors on 5-HT nerve endings that regulate 5-HT release and heteroreceptors that also mediate other neurotransmitter release, play a particularly important role in cocaine effects, likely because they are highly expressed in the mesocorticolimbic system. The 5-HT1b system displays profound dysregulation during both active cocaine use and abstinence. Initial preclinical research showed that selective 5-HT1b agonists enhanced the reinforcing and locomotor effects of cocaine during ongoing cocaine administration, but subsequent research showed that these agents robustly attenuated reinstatement of cocaine- and cue-primed cocaine seeking behavior. These findings have been replicated in rigorously conducted studies using multiple schedules of reinforcement and negative sucrose reinforcement controls across laboratories. Notably, though, these preclinical studies used compounds not approved for use in humans, hindering translation. Recently published data show that zolmitriptan, a commercially available selective 5-HT1b agonist migraine medication, also selectively attenuates the reinforcing and other abuse-related effects of cocaine, regardless of stage of use (i.e., ongoing or extinguished cocaine self-administration).
Although a robust preclinical literature supports the premise that 5-HT1b activation reduces a number of cocaine-associated behaviors (e.g., self-administration, cocaine seeking), this area remains unstudied in humans. The overarching goal of this project is to advance these promising preclinical findings, specifically those with zolmitriptan, to a clinical population, thereby demonstrating that the 5-HT1b system plays a key role in the effects of cocaine in humans
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
- Recent cocaine use
- Abnormal screening outcome (e.g., ECG, blood chemistry result) that study physicians deem clinically significant
- Current or past histories of substance use disorder that are deemed by the study physicians to interfere with study completion
- History of serious physical disease, current physical disease, impaired cardiovascular functioning, chronic obstructive pulmonary disease, history of seizure or current or past histories of serious psychiatric disorder that in the opinion of the study physician would interfere with study participation will be excluded from participation
- Females not currently using effective birth control
- Contraindications to cocaine or zolmitriptan
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Placebo Placebo oral capsule Subjects will be maintained on oral placebo. Cocaine will be administered acutely during placebo maintenance. Placebo will be administered acutely during placebo maintenance. Zolmitriptan Dose 2 Zolmitriptan Subjects will be maintained on oral zolmitriptan dose 2. Cocaine will be administered acutely during zolmitriptan dose 2 maintenance. Placebo will be administered acutely during zolmitriptan dose 2 maintenance. Placebo Cocaine Subjects will be maintained on oral placebo. Cocaine will be administered acutely during placebo maintenance. Placebo will be administered acutely during placebo maintenance. Zolmitriptan Dose 1 Cocaine Subjects will be maintained on oral zolmitriptan dose 1. Cocaine will be administered acutely during zolmitriptan dose 1 maintenance. Placebo will be administered acutely during zolmitriptan dose 1 maintenance. Zolmitriptan Dose 2 Cocaine Subjects will be maintained on oral zolmitriptan dose 2. Cocaine will be administered acutely during zolmitriptan dose 2 maintenance. Placebo will be administered acutely during zolmitriptan dose 2 maintenance. Zolmitriptan Dose 3 Cocaine Subjects will be maintained on oral zolmitriptan dose 3. Cocaine will be administered acutely during zolmitriptan dose 3 maintenance. Placebo will be administered acutely during zolmitriptan dose 3 maintenance. Zolmitriptan Dose 3 Zolmitriptan Subjects will be maintained on oral zolmitriptan dose 3. Cocaine will be administered acutely during zolmitriptan dose 3 maintenance. Placebo will be administered acutely during zolmitriptan dose 3 maintenance.
- Primary Outcome Measures
Name Time Method Reinforcing Effects of Cocaine Following Zolmitriptan Dose 3 Maintenance. Following at least 3 days of maintenance on zolmitriptan dose 3 during inpatient admission. Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement.
Reinforcing Effects of Cocaine Following Placebo Maintenance. Following at least 3 days of maintenance on placebo during inpatient admission Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement.
Reinforcing Effects of Cocaine Following Zolmitriptan Dose 1 Maintenance. Following at least 3 days of maintenance on zolmitriptan dose 1 during inpatient admission. Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement.
Reinforcing Effects of Cocaine Following Zolmitriptan Dose 2 Maintenance. Following at least 3 days of maintenance on zolmitriptan dose 2 during inpatient admission. Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement.
- Secondary Outcome Measures
Name Time Method Temperature Daily over approximately 1 month inpatient admission Degrees fahrenheit. Measured daily during inpatient admission.
Adjective Rating Scale-Sedative 12 times over approximately 1 month inpatient admission Subjects will complete the adjective rating scale during 12 sessions while they are admitted to our inpatient unit. Responses to 16 items are summed (total score=0-64; Higher values=more sedation) to calculate scores on a sedative subscale.
Adjective Rating Scale-Stimulant 12 times over approximately 1 month inpatient admission Subjects will complete the adjective rating scale during 12 sessions while they are admitted to our inpatient unit. Responses to 16 items are summed (total score=0-64; Higher values=more sedation) to calculate scores on a stimulant subscale.
Heart rate Daily over approximately four week inpatient admissions Beats per minute. Measured daily during inpatient admission.
Blood pressure Daily over approximately 1 month inpatient admission. mmHg. Measured daily during inpatient admission.
Drug Effect Questionnaire 12 times over approximately 1 month inpatient admission Subjects will complete the drug effect questionnaire during 12 sessions while they are admitted to our inpatient unit. The items (total scores=0-100; Higher scores=greater drug effect) on this scale categorize the constellation of drug effects endorsed by subjects.
Side Effects Daily over approximately 1 month inpatient admission Subjects will complete a side effects questionnaire daily while they reside on the inpatient unit. Side Effects questions will query subjects about common effects of centrally active medications.
n-back Task 12 times over approximately 1 month inpatient admission Subjects will complete the n-back task during 12 sessions while they are admitted to our inpatient unit. Percentage of correct responses will be the outcome.
Delay Discounting Task 12 times over approximately 1 month inpatient admission Subjects will complete the delay discounting task during 12 sessions while they are admitted to our inpatient unit. Responses will be used to calculate discounting slope (i.e., K).
Stop-Signal Task Inhibitory Failures 12 times over approximately 1 month inpatient admission Subjects will complete the stop-signal task during 12 sessions while they are admitted to our inpatient unit. Proportion of inhibitory failures will be the outcome variable.
Stop-Signal Task Reaction Time 12 times over approximately 1 month inpatient admission Subjects will complete the stop-signal task during 12 sessions while they are admitted to our inpatient unit. Reaction time in milliseconds and proportion of inhibitory failures will be the outcome variables.
Trial Locations
- Locations (1)
University of Kentucky
🇺🇸Lexington, Kentucky, United States