Zolmitriptan for Cocaine Use Disorder

Recruiting in Palo Alto (17 mi)

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Waitlist Available

Sponsor: William Stoops

Trial Summary

What is the purpose of this trial?

This trial is testing zolmitriptan, a migraine medication, to see if it can help people who use cocaine. The medication works by affecting certain brain receptors to reduce the desire for cocaine. The goal is to find out if this treatment can be effective in humans as it has shown promise in animal studies. Zolmitriptan has been used successfully for treating migraines.

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.

What data supports the idea that Zolmitriptan for Cocaine Use Disorder is an effective drug?

The available research does not provide any data supporting the effectiveness of Zolmitriptan for treating Cocaine Use Disorder. Instead, the studies focus on other drugs, such as kappa-opioid agonists and mu-opioid agonists, which have shown some potential in reducing cocaine use. For example, kappa-opioid agonists like cyclazocine and mixed kappa/mu agonists have been studied for their ability to reduce cocaine self-administration in animals. However, these studies do not mention Zolmitriptan as a treatment for Cocaine Use Disorder. ^{1 2 3 4 5}

What safety data exists for using Zolmitriptan to treat Cocaine Use Disorder?

The provided research does not contain specific safety data on the use of Zolmitriptan (Zomig) for treating Cocaine Use Disorder. The studies focus on other substances and their effects on cocaine toxicity or dependence, such as dexmedetomidine, moxonidine, alpha-methyldopa, cyclazocine, and kappa-opioid agonists. Therefore, no direct safety data for Zolmitriptan in this context is available from the given research. ^{1 4 6 7 8}

Is the drug Zolmitriptan a promising treatment for Cocaine Use Disorder?

The provided research articles do not mention Zolmitriptan as a treatment for Cocaine Use Disorder. Therefore, there is no evidence from these articles to suggest that Zolmitriptan is a promising treatment for this condition. ^{8 9 10 11 12}

Research Team

Eligibility Criteria

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

Treatment Details

Interventions

• Cocaine (Stimulant)
• Zolmitriptan (5-HT1b Agonist)

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.

Participant Groups

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+

Dr. Nora Volkow

National Institute on Drug Abuse (NIDA)

Chief Executive Officer since 2003

MD from National Autonomous University of Mexico

Dr. Nora Volkow

National Institute on Drug Abuse (NIDA)

Chief Medical Officer since 2003

MD from National Autonomous University of Mexico

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Effects of mixed-action kappa/mu opioids on cocaine self-administration and cocaine discrimination by rhesus monkeys. [2015]

2. United States 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. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Effects of naltrexone on response to intravenous cocaine, hydromorphone and their combination in humans. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Cyclazocine: comparison to hydromorphone and interaction with cocaine. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Effects of kappa opioids on cocaine self-administration by rhesus monkeys. [2016]

6. England 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. [2019]

7. Estonia pubmed.ncbi.nlm.nih.gov

A Comparison of Dexmedetomidine, Moxonidine and Alpha-Methyldopa Effects on Acute, Lethal Cocaine Toxicity. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Pharmacotherapeutic interventions for cocaine abuse: present practices and future directions. [2013]

9. United States pubmed.ncbi.nlm.nih.gov

Outpatient treatment of 'crack' cocaine smoking with flupenthixol decanoate. A preliminary report. [2019]

10. Switzerland 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. [2020]

11. United States 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. [2018]

12. United States pubmed.ncbi.nlm.nih.gov

Cocaine use reduction with buprenorphine (CURB): rationale, design, and methodology. [2021]