Cocaine and Zolmitriptan

NCT ID: NCT05019430

Last Updated: 2025-08-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-15
• Study Completion Date: 2025-01-09

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

Conditions

Cocaine Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Placebo

Subjects will be maintained on oral placebo. Cocaine will be administered acutely during placebo maintenance. Placebo will be administered acutely during placebo maintenance.

Group Type: PLACEBO_COMPARATOR

Cocaine

Intervention Type: DRUG

The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and zolmitriptan.

Placebo oral capsule

Intervention Type: DRUG

The pharmacodynamic effects of placebo will be determined.

Zolmitriptan Dose 1

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.

Group Type: EXPERIMENTAL

Cocaine

Intervention Type: DRUG

The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and zolmitriptan.

Zolmitriptan Dose 2

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.

Group Type: EXPERIMENTAL

Cocaine

Intervention Type: DRUG

The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and zolmitriptan.

Zolmitriptan

Intervention Type: DRUG

The pharmacodynamic effects of zolmitriptan maintenance will be determined.

Zolmitriptan Dose 3

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.

Group Type: EXPERIMENTAL

Cocaine

Intervention Type: DRUG

The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and zolmitriptan.

Zolmitriptan

Intervention Type: DRUG

The pharmacodynamic effects of zolmitriptan maintenance will be determined.

Interventions

Cocaine

The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and zolmitriptan.

Intervention Type: DRUG

Placebo oral capsule

The pharmacodynamic effects of placebo will be determined.

Intervention Type: DRUG

Zolmitriptan

The pharmacodynamic effects of zolmitriptan maintenance will be determined.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Recent cocaine use

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

William Stoops

OTHER

Sponsor Role: lead

Responsible Party

William Stoops

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

University of Kentucky

Lexington, Kentucky, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R01DA052203

Identifier Type: NIH

Identifier Source: secondary_id

View Link

BED In 42

Identifier Type: -

Identifier Source: org_study_id