Zolmitriptan for Cocaine Use Disorder

Overseen By William W Stoops, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: William Stoops

Disqualifiers: Substance use disorder, Serious physical disease, others

Compensation: Varies

Number of Visits: Unknown

Duration: At least 3 days per dose maintenance

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether zolmitriptan, a medication typically used for migraines, can reduce cocaine-related behaviors in recent cocaine users. The study compares different doses of zolmitriptan to determine if it lessens the urge to use cocaine. Participants may receive either zolmitriptan or a placebo (a pill with no active ingredient). This trial suits those who have used cocaine recently and wish to help test a potential new treatment option. As an Early Phase 1 trial, this research focuses on understanding how zolmitriptan works in people, offering participants a chance to contribute to groundbreaking research.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, if you have contraindications to cocaine or zolmitriptan, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that zolmitriptan, a medication often used for migraines, might help treat cocaine use disorder. However, studies have not yet focused on its safety for this specific use in humans.

The FDA has approved zolmitriptan for treating migraines, indicating it is generally safe for that purpose. When used for migraines, many people tolerate zolmitriptan well, though it can sometimes cause side effects like dizziness or dry mouth.

Since this trial is in an early stage, it likely focuses on understanding how safe and tolerable zolmitriptan is for people with cocaine use disorder. Researchers are closely monitoring for any side effects or reactions. If zolmitriptan eventually proves safe and effective for this new use, it could become a valuable treatment option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cocaine use disorder?

Most treatments for cocaine use disorder focus on behavioral therapies and sometimes use medications like disulfiram or naltrexone to help reduce cravings and manage withdrawal symptoms. However, Zolmitriptan is being explored as a new option because it targets serotonin receptors in the brain, which may influence the reward pathways activated by cocaine. This unique mechanism of action could potentially help reduce cocaine use by altering the brain's response to the drug. Researchers are excited about Zolmitriptan because it represents a fresh approach to treating cocaine addiction, possibly offering a new avenue for those who haven't found success with existing treatments.

What evidence suggests that zolmitriptan might be an effective treatment for cocaine use disorder?

Research suggests that zolmitriptan, a migraine medication, might help treat cocaine addiction by affecting certain brain receptors that influence serotonin, a chemical involved in cocaine's effects. Animal studies have shown that drugs like zolmitriptan can reduce behaviors linked to cocaine use, such as seeking and taking the drug. While these results are promising, they primarily come from animal studies. Recent data hint at similar effects in humans, but zolmitriptan has not yet been formally tested in people with cocaine addiction, so its effectiveness in humans remains unknown. This trial will evaluate different doses of zolmitriptan to determine its potential effectiveness in treating cocaine use disorder. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for individuals who have recently used cocaine and do not have a history of serious physical or psychiatric disorders. Participants must not have any health conditions that could interfere with the study, such as heart disease or seizures, and women must be using effective birth control.

Inclusion Criteria

Recent cocaine use

Exclusion Criteria

I do not have any serious physical or mental health conditions that would interfere with the study.

Current or past histories of substance use disorder that are deemed by the study physicians to interfere with study completion

Abnormal screening outcome (e.g., ECG, blood chemistry result) that study physicians deem clinically significant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Inpatient Admission

Participants are admitted to the inpatient unit for drug administration and monitoring

4 weeks

Daily monitoring and assessments

Treatment

Participants receive zolmitriptan or placebo and cocaine is administered acutely

At least 3 days per dose maintenance

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cocaine
• Zolmitriptan

Trial Overview The trial is testing Zolmitriptan, a migraine medication thought to reduce cocaine's addictive effects by targeting the brain's serotonin system. It compares how well Zolmitriptan works against a placebo when taken by people with Cocaine Use Disorder.

How Is the Trial Designed?

Group I: Zolmitriptan Dose 3 Experimental Treatment 2 Interventions

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 II: Zolmitriptan Dose 2 Experimental Treatment 2 Interventions

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 III: Zolmitriptan Dose 1 Experimental Treatment 1 Intervention

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 IV: Placebo Placebo Group 2 Interventions

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

Who Is Running the Clinical Trial?

William Stoops

Lead Sponsor

Trials

9

Recruited

240+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Cocaine addiction treatment involves managing both physical and psychological withdrawal symptoms, particularly intense cravings, and various medications have been explored based on cocaine's effects on neurotransmitters.

The review highlights different pharmacotherapeutic strategies for treating cocaine dependence, especially in patients also maintained on methadone, while discussing future research directions and the limitations of current pharmacotherapy options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapeutic interventions for cocaine abuse: present practices and future directions. Crosby, RD., Halikas, JA., Carlson, G.[2013]

Chronic treatment with kappa opioid agonists EKC and U50,488 significantly reduced cocaine self-administration in rhesus monkeys over a 10-day period, indicating their potential as treatments for cocaine dependence.

While both drugs effectively decreased cocaine use, they also caused side effects like sedation and vomiting, with EKC showing fewer adverse effects than U50,488, which could complicate their therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of kappa opioids on cocaine self-administration by rhesus monkeys. Negus, SS., Mello, NK., Portoghese, PS., et al.[2016]

The study of RTI-336, a dopamine transporter inhibitor, involved 22 healthy adult males and demonstrated excellent safety and tolerability at doses up to 20 mg, with only mild and transient side effects observed.

Pharmacokinetic analysis showed that RTI-336 was well-absorbed, with peak plasma concentrations occurring around 4 hours post-dose and a consistent half-life of approximately 17 hours, indicating a favorable profile for potential use in treating cocaine dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Double-Blind, Placebo-Controlled Trial Demonstrating the Safety, Tolerability, and Pharmacokinetics of Single, Escalating Oral Doses of RTI-336. Carroll, FI., Kosten, TR., Buda, JJ., et al.[2020]

A survey of 332 regular cocaine users in São Paulo revealed that adverse reactions to cocaine are very common, with symptoms like hot flushes (84%), uncontrollable shaking (76%), and feeling ill (75%) being frequently reported.

The study found that more severe adverse reactions, such as convulsions (18%) and passing out (21%), were linked to factors like higher dependence on cocaine and the use of tranquilizers, highlighting the need for preventive strategies to mitigate these potentially fatal effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors associated with adverse reactions to cocaine among a sample of long-term, high-dose users in São Paulo, Brazil. Ferri, CP., Dunn, J., Gossop, M., et al.[2019]

In a study involving 8 volunteers with histories of cocaine and heroin abuse, the combination of cocaine and hydromorphone produced effects that were sometimes greater than either drug alone, indicating a potential for enhanced effects when used together.

Oral naltrexone effectively blocked the effects of hydromorphone but did not affect the physiological or subjective effects of cocaine, suggesting that while naltrexone may not be useful for treating cocaine abuse alone, it could help patients with both cocaine and heroin dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of naltrexone on response to intravenous cocaine, hydromorphone and their combination in humans. Walsh, SL., Sullivan, JT., Preston, KL., et al.[2013]

The CURB study is a multi-site, double-blind, placebo-controlled trial involving 300 participants to evaluate the safety and efficacy of sublingual buprenorphine (BUP) combined with extended-release injectable naltrexone (XR-NTX) for treating cocaine dependence in individuals with a history of opioid use disorders.

The study aims to determine if BUP can effectively reduce cocaine use while XR-NTX prevents the development of physical dependence on BUP, with participants receiving cognitive behavioral therapy alongside their medication regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cocaine use reduction with buprenorphine (CURB): rationale, design, and methodology. Mooney, LJ., Nielsen, S., Saxon, A., et al.[2021]

Dexmedetomidine significantly reduced seizure activity and lethality in a mouse model of acute cocaine toxicity, with only 12% of treated mice experiencing lethality compared to 72% in the control group.

While moxonidine and alpha-methyldopa also reduced seizure activity, they were less effective in preventing cocaine-induced lethality, highlighting dexmedetomidine as a promising treatment option for cocaine toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparison of Dexmedetomidine, Moxonidine and Alpha-Methyldopa Effects on Acute, Lethal Cocaine Toxicity. Seyit, M., Erdur, B., Kortunay, S., et al.[2020]

Flupenthixol decanoate, administered as an infrequent intramuscular injection, was well tolerated in a preliminary trial with 10 outpatient crack cocaine smokers and showed a significant reduction in cocaine craving and use.

The treatment led to a remarkable 260% increase in the average time participants stayed in treatment, suggesting its potential efficacy in managing cocaine withdrawal and dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outpatient treatment of 'crack' cocaine smoking with flupenthixol decanoate. A preliminary report. Gawin, FH., Allen, D., Humblestone, B.[2019]

In a study involving 65 crack-cocaine dependent patients, modafinil did not show significant benefits when added to cognitive behavioral therapy (CBT), as it did not improve treatment retention or reduce cocaine use overall.

However, patients who adhered to modafinil treatment for at least 8 weeks experienced greater reductions in cocaine use, suggesting that optimizing adherence could enhance the effectiveness of modafinil in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modafinil in the treatment of crack-cocaine dependence in the Netherlands: Results of an open-label randomised controlled feasibility trial. Nuijten, M., Blanken, P., van den Brink, W., et al.[2018]

Mixed kappa/mu-opioid agonists, such as MCL-101 and (-)cyclorphan, significantly reduced cocaine self-administration in rhesus monkeys, indicating their potential efficacy in treating cocaine addiction.

These mixed agonists produced fewer side effects compared to the kappa-selective agonist enadoline, suggesting they may be safer options for therapeutic use without affecting the discriminative stimulus effects of cocaine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of mixed-action kappa/mu opioids on cocaine self-administration and cocaine discrimination by rhesus monkeys. Bowen, CA., Negus, SS., Zong, R., et al.[2015]

In a study involving 13 experienced opiate and cocaine users, cyclazocine showed only modest effects as a kappa-opioid agonist and did not significantly alter the response to cocaine, suggesting limited efficacy in reducing cocaine's effects.

Despite the modest effects, participants exhibited lower responses to cocaine after four days of cyclazocine pretreatment, indicating potential for kappa-opioid drugs in diminishing acute cocaine effects, although results were not strongly conclusive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclazocine: comparison to hydromorphone and interaction with cocaine. Preston, KL., Umbricht, A., Schroeder, JR., et al.[2019]

In a study with rhesus monkeys, low-efficacy mu-opioid agonists like nalbuphine and butorphanol significantly reduced cocaine self-administration more effectively than high-efficacy agonists like fentanyl and morphine, suggesting a potential for safer treatment options.

The low-efficacy agonists produced fewer negative side effects on food-maintained responding, indicating they may be better suited for managing cocaine use without blocking the positive effects of cocaine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of mu-opioid agonists on cocaine- and food-maintained responding and cocaine discrimination in rhesus monkeys: role of mu-agonist efficacy. Negus, SS., Mello, NK.[2019]

Citations

1. nature.com nature.com/articles/s41398-020-00956-6

Preclinical support for the therapeutic potential of ... These findings suggest that zolmitriptan has potential for repurposing as a treatment for cocaine use disorders.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05019430?tab=results

Study Results | NCT05019430 | Cocaine and Zolmitriptan These trials gather additional information about a drug's safety, efficacy, or optimal use. Phase Not Applicable. Describes trials without ...

3. withpower.com withpower.com/trial/early-phase-1-9-2021-677f0

Zolmitriptan for Cocaine Use Disorder · Info for Participants The available research does not provide any data supporting the effectiveness of Zolmitriptan for treating Cocaine Use Disorder. Instead, the studies focus on ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05019430

Study Details | NCT05019430 | Cocaine and Zolmitriptan These trials gather additional information about a drug's safety, efficacy, or optimal use. Phase Not Applicable. Describes trials without FDA-defined phases ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5570061/

Preclinical Evidence That 5-HT1B Receptor Agonists Show ... 5-HT1B receptor agonists enhance cocaine intake during daily self-administration sessions but decrease cocaine intake when tested after prolonged abstinence ...

6. researchgate.net researchgate.net/publication/343403694_Preclinical_support_for_the_therapeutic_potential_of_zolmitriptan_as_a_treatment_for_cocaine_use_disorders

(PDF) Preclinical support for the therapeutic potential of ... These findings suggest that zolmitriptan has potential for repurposing as a treatment for cocaine use disorders.