Clinical trial NCT05019430: Cocaine and Zolmitriptan
Official title: Behavioral Effects of Drugs (Inpatient): 42 (Cocaine and Zolmitriptan)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Cocaine Use Disorder
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2021-08-24
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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


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

Primary outcomes:
measure: Reinforcing Effects of Cocaine Following Placebo Maintenance.
timeFrame: Following at least 3 days of maintenance on placebo during inpatient admission
measure: Reinforcing Effects of Cocaine Following Zolmitriptan Dose 1 Maintenance.
timeFrame: Following at least 3 days of maintenance on zolmitriptan dose 1 during inpatient admission.
measure: Reinforcing Effects of Cocaine Following Zolmitriptan Dose 2 Maintenance.
timeFrame: Following at least 3 days of maintenance on zolmitriptan dose 2 during inpatient admission.
measure: Reinforcing Effects of Cocaine Following Zolmitriptan Dose 3 Maintenance.
timeFrame: Following at least 3 days of maintenance on zolmitriptan dose 3 during inpatient admission.
Secondary outcomes:
measure: Adjective Rating Scale-Sedative
timeFrame: 12 times over approximately 1 month inpatient admission
measure: Adjective Rating Scale-Stimulant
timeFrame: 12 times over approximately 1 month inpatient admission
measure: Drug Effect Questionnaire
timeFrame: 12 times over approximately 1 month inpatient admission
measure: Heart rate
timeFrame: Daily over approximately four week inpatient admissions
measure: Blood pressure
timeFrame: Daily over approximately 1 month inpatient admission.
measure: Temperature
timeFrame: Daily over approximately 1 month inpatient admission
measure: Side Effects
timeFrame: Daily over approximately 1 month inpatient admission
measure: Delay Discounting Task
timeFrame: 12 times over approximately 1 month inpatient admission
measure: n-back Task
timeFrame: 12 times over approximately 1 month inpatient admission
measure: Stop-Signal Task Reaction Time
timeFrame: 12 times over approximately 1 month inpatient admission
measure: Stop-Signal Task Inhibitory Failures
timeFrame: 12 times over approximately 1 month inpatient admission
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
References: