Methylphenidate for Cocaine Use Disorder

Overseen By Kathryn Drury, B.M.

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Icahn School of Medicine at Mount Sinai

Disqualifiers: Schizophrenia, Neurological disease, Cardiovascular, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day per session

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether methylphenidate, a medication commonly used for ADHD, can reduce drug-related memories and cravings in individuals with cocaine use disorder. Participants will receive either methylphenidate or a placebo during memory recall sessions to determine its effect on cravings and memory of drug cues. If successful, this approach could lead to improved addiction therapies. This trial suits those struggling with cocaine use and seeking new treatment options. As an Early Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking addiction therapy development.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that methylphenidate, the treatment under study, is generally safe. In a controlled lab study, researchers administered it with cocaine without major issues. However, methylphenidate can sometimes cause side effects, including stomach problems, heart-related issues, and, in rare cases, mental health problems like hallucinations.

Despite these risks, many studies have not found a significant increase in serious heart problems in people using methylphenidate for conditions like ADHD. As this is an early-phase trial, researchers focus on understanding the treatment's safety in humans, continuously gathering and checking safety information.

Participants in clinical trials like this one help researchers learn more about the safety and effectiveness of treatments like methylphenidate for different conditions. ^{1 2 3 4 5}

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

Methylphenidate is unique because it targets dopamine and norepinephrine pathways in the brain, which play crucial roles in addiction mechanisms. Most treatments for cocaine use disorder focus on behavioral therapies and medications like disulfiram or topiramate, which don't directly address these pathways. Methylphenidate, commonly known for treating ADHD, may help reduce cocaine cravings and improve attention and impulse control, offering a new angle in managing this condition. Researchers are excited because it could provide a pharmacological option that directly influences the brain's reward system, potentially leading to more effective treatment outcomes.

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

Research suggests that methylphenidate, one of the treatments in this trial, might help with cocaine use disorder (CUD) by altering how the brain remembers drug-related experiences. Some studies have used it safely with cocaine, showing no major side effects. However, evidence of its effectiveness in treating CUD remains limited and uncertain. Methylphenidate could potentially reduce cravings by changing the brain's response to drug cues. More research is needed to confirm these early findings. Participants in this trial will receive either methylphenidate followed by a placebo or a placebo followed by methylphenidate to evaluate its potential benefits. ^{1 3 6 7 8}

Who Is on the Research Team?

Rita Z Goldstein, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for men and women aged 26-50 with a diagnosis of cocaine use disorder (CUD) who can give informed consent. It's not suitable for those with metal implants, schizophrenia, developmental disorders like autism, cardiovascular diseases including high blood pressure, other serious medical conditions or infectious diseases such as Hepatitis B/C or HIV/AIDS.

Inclusion Criteria

I understand the study and agree to participate.

DSM-V diagnosis for CUD or otherwise problematic cocaine use as clinically determined

I am between 26 and 50 years old.

Exclusion Criteria

I have a history of brain-related neurological disease, including seizures.

Metal implants or other MR contraindications

I have been diagnosed with schizophrenia or a developmental disorder like autism.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 20 mg of methylphenidate or a placebo in a cross-over design to assess the impact on drug-cue memory retrieval

1 day per session

2 visits (in-person)

Follow-up

Participants are monitored for changes in skin conductance responses and craving 24 hours after each neuroimaging session

24 hours after each session

What Are the Treatments Tested in This Trial?

Interventions

• Memory reconsolidation
• Methylphenidate
• Placebo

Trial Overview

The study tests if Methylphenidate affects the way people with CUD remember drug-related cues. Participants will take either Methylphenidate or a placebo in a controlled environment while undergoing an MRI scan to observe brain activity and skin conductance responses that indicate memory modification.

How Is the Trial Designed?

Group I: Methylphenidate then Placebo Experimental Treatment 3 Interventions

20 mg of methylphenidate then matching placebo pill.

Group II: Placebo then Methylphenidate Placebo Group 3 Interventions

Matching placebo pill then 20 mg of methylphenidate.

Methylphenidate is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Methylphenidate for:

• Attention Deficit Hyperactivity Disorder (ADHD)
• Narcolepsy

Approved in Canada as Methylphenidate for:

• Attention Deficit Hyperactivity Disorder (ADHD)
• Narcolepsy

Approved in European Union as Methylphenidate for:

• Attention Deficit Hyperactivity Disorder (ADHD)
• Narcolepsy

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Controlled-delivery methylphenidate (methylphenidate CD) is effective and well-tolerated for treating ADHD in children aged 6 and older, showing superior control of symptoms compared to osmotic release methylphenidate during a typical school day.

In clinical trials lasting 3 weeks, methylphenidate CD was found to be more effective than a placebo and equally effective as immediate-release methylphenidate, making it a strong option for managing ADHD symptoms during school hours.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on methylphenidate controlled-delivery capsules (Equasym XL, Metadate CD) in the treatment of children and adolescents with attention-deficit hyperactivity disorder. Anderson, VR., Keating, GM.[2019]

Controlled-delivery methylphenidate (methylphenidate CD) is effective and well tolerated for treating ADHD in children aged 6 and older, showing superior control of symptoms compared to osmotic release methylphenidate during a typical school day.

In clinical trials lasting 3 weeks, methylphenidate CD was found to be more effective than a placebo and equally effective as immediate-release methylphenidate, making it a strong option for managing ADHD symptoms during school hours.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methylphenidate controlled-delivery capsules (EquasymXL, Metadate CD): a review of its use in the treatment of children and adolescents with attention-deficit hyperactivity disorder. Anderson, VR., Keating, GM.[2018]

In a 7-week study involving 226 adults with ADHD, OROS methylphenidate significantly improved ADHD symptoms compared to placebo, as shown by lower scores on the Adult ADHD Investigator Symptom Report Scale.

The treatment was well tolerated, with no serious adverse events reported, and a higher percentage of participants on OROS methylphenidate were classified as responders compared to those on placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of OROS methylphenidate in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, double-blind, parallel group, dose-escalation study. Adler, LA., Zimmerman, B., Starr, HL., et al.[2022]

Dexmethylphenidate, a chirally pure form of methylphenidate, has been shown to effectively manage ADHD in children at half the dose of traditional Ritalin, based on clinical trials involving 684 children.

The drug works by inhibiting the reuptake of norepinephrine and dopamine, and has been found to be well tolerated, with ongoing research to further understand its therapeutic action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmethylphenidate--Novartis/Celgene. Focalin, D-MPH, D-methylphenidate hydrochloride, D-methylphenidate, dexmethylphenidate, dexmethylphenidate hydrochloride. [2018]

Methylphenidate and dexmethylphenidate are effective and safe treatments for adults with ADHD, supported by a review of clinical trials, although the evidence is less extensive compared to children and adolescents.

Higher doses of these medications are linked to improved treatment responses, but there are moderate safety concerns, highlighting the importance of individualized treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of methylphenidate and dexmethylphenidate in adults with attention deficit/hyperactivity disorder. Sopko, MA., Caberwal, H., Chavez, B.[2021]

A review of the French Pharmacovigilance database revealed 21 reported adverse drug reactions related to methylphenidate, with 16 cases suspected to be linked to the medication; these were mostly mild and resolved quickly.

The findings indicate that there is no evidence of methylphenidate misuse or overuse among the 1300 to 4000 children treated in France, supporting the need for continued strict prescription regulations to prevent potential misuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Utilization of methylphenidate(Ritalin) in France]. Frances, C., Hoizey, G., Millart, H., et al.[2013]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4476488/

Clinical potential of methylphenidate in the treatment of ...

Controlled laboratory studies have shown that MPH can be safely administered in combination with cocaine without relevant clinical consequences.

2.

frontiersin.org

frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1508732/full

Methylphenidate abuse and misuse in patients affected ...

The misuse of methylphenidate is associated with substantial risks, including addiction, adverse health outcomes, and broader public health concerns. While it ...

3.

jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2779686

Comparison of Treatments for Cocaine Use Disorder ...

The findings suggest that contingency management programs may be beneficial for the treatment of cocaine use disorder among adults who actively use cocaine.

4.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0376871606002778

Double-blind comparison of methylphenidate and placebo

In 48 cocaine-dependent adults with ADHD (Schubiner et al., 2002), methylphenidate (MPH) was more effective in treating ADHD symptoms based on clinician ...

5.

researchgate.net

researchgate.net/publication/396867015_Methylphenidate_for_the_Treatment_of_Cocaine_Use_Disorder_A_Systematic_Review_and_Meta-analysis

Methylphenidate for the Treatment of Cocaine Use Disorder

Conclusions Evidence on the efficacy of MPH for the treatment of CUD is still limited and inconclusive. However, there might be a rationale for ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12443935/

Current insights into the safety and adverse effects of ...

Additionally, MPH has the potential for misuse, abuse, and dependence, particularly due to its dopaminergic effects, which can contribute to ...

7.

fda.gov

fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-safety-review-update-medications-used-treat-attention

Safety Review Update of Medications used to treat ADHD

Study findings reported no evidence of increased risk of serious cardiovascular effects among children and young people who use ADHD medications.

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S0149763419302350

Neurological and psychiatric adverse effects of long-term ...

We aimed to map current evidence regarding neurological and psychiatric outcomes, adverse or beneficial, of long-term MPH (> 1 year) treatment in ADHD.