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

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This study aims to identify the neural, behavioral, and pharmacological mechanisms promoting diminished expression of drug-related memories in human drug addiction. In this fMRI study with a within-subjects placebo-controlled double-blind cross-over design, oral methylphenidate (20 mg) or placebo will be administered to individuals with cocaine use disorders (CUD) to peak during the retrieval of a drug-cue memory before extinction; in addition to fMRI activations, skin conductance responses (SCR, acquired simultaneously) will serve as the psychophysiological indicators of memory modification. Assessments of interference with the return of drug-cue memories via SCR and craving will be conducted the day following MRI. This pharmocologically-enhanced behavioral approach to decreasing drug memories and craving in iCUD could ultimately be used to develop effective cue-exposure therapies for drug addiction. Procedures include MRI, blood draw, questionnaires and interviews, skin conductance response measures, and behavioral tasks.

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.

What evidence supports the effectiveness of methylphenidate as a drug for treating cocaine use disorder?

Research shows that methylphenidate is effective in reducing ADHD symptoms in both children and adults, and a study found it improved ADHD symptoms in adults with cocaine dependence without worsening cocaine use. However, the study's small size means these results are preliminary. ^{1 2 3 4 5}

Is methylphenidate generally safe for humans?

Methylphenidate, used in various forms like Concerta and Ritalin, is generally considered safe for treating ADHD in both adults and children, with most side effects being mild and resolving quickly. However, some reports indicate it can cause psychiatric reactions like hallucinations in children, so monitoring is important. ^{1 6 7 8 9}

How is the drug methylphenidate unique in treating cocaine use disorder?

Methylphenidate is unique because it is primarily used to treat ADHD by improving focus and reducing impulsivity, and it is being explored for cocaine use disorder due to its potential to manage ADHD symptoms in individuals with cocaine dependence without worsening cocaine use. ^{1 2 3 6 7}

Research Team

Rita Z Goldstein, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

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.

I am between 26 and 50 years old.

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

Exclusion Criteria

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

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

I have had a head injury that made me lose consciousness.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. Switzerland 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. [2018]

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

Double-blind placebo-controlled trial of methylphenidate in the treatment of adult ADHD patients with comorbid cocaine dependence. [2019]

3. New Zealand 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. [2019]

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

Review of new compounds available in Australia for the treatment of attention-deficit hyperactivity disorder. [2017]

5. New Zealand pubmed.ncbi.nlm.nih.gov

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

6. United States 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. [2022]

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

The safety and efficacy of methylphenidate and dexmethylphenidate in adults with attention deficit/hyperactivity disorder. [2021]

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

Hallucinations and other psychotic symptoms associated with the use of attention-deficit/hyperactivity disorder drugs in children. [2009]

9. France pubmed.ncbi.nlm.nih.gov

[Utilization of methylphenidate(Ritalin) in France]. [2013]