d-Amphetamine for Cocaine Use Disorder

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Joshua A. Lile, Ph.D.

Disqualifiers: Serious physical, psychiatric disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 40 minutes per session

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether sustained release d-amphetamine, a stimulant medication, can alter decision-making in individuals with cocaine use disorder. Researchers use a task offering a choice between cocaine and money to assess how d-amphetamine might reduce the desire for cocaine. Participants receive varying amounts of money as alternatives to observe the impact on their decision-making. The study seeks individuals who have recently used cocaine but are otherwise healthy. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, providing participants an opportunity to contribute to groundbreaking research.

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

The protocol does not specify if you need to stop your current medications.

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

Research has shown that a long-lasting form of d-amphetamine is a safe and effective treatment for cocaine addiction. One study found that individuals using it for cocaine addiction experienced positive results without major safety issues.

Another study examined the effects of cocaine on individuals taking d-amphetamine and found it was generally well-tolerated, with no serious side effects reported. This indicates the treatment is safe for patients.

However, long-term use of stimulants like d-amphetamine can increase the risk of heart problems over many years. This risk underscores the importance of using the treatment carefully and under supervision. Overall, current evidence suggests that d-amphetamine is safe when used as intended in these studies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using sustained release d-amphetamine for cocaine use disorder because it offers a novel approach compared to traditional treatments like behavioral therapy and medications such as disulfiram or naltrexone. Unlike these standard options, d-amphetamine works by reducing cravings and withdrawal symptoms through a gradual release mechanism, potentially offering a more stable and consistent therapeutic effect. Additionally, this treatment combines medication with a unique behavioral component, using monetary incentives to influence decision-making, which could further enhance its effectiveness in encouraging patients to abstain from cocaine use.

What evidence suggests that this trial's treatments could be effective for cocaine use disorder?

Research has shown that sustained-release d-amphetamine, which participants in this trial may receive, can help reduce cocaine use. Studies have found that those taking this medication experienced fewer days of cocaine use compared to those on a placebo, which contains no active drug. Specifically, one study revealed that individuals using sustained-release d-amphetamine had about 15 fewer days of cocaine use over a certain period than those who did not take it. This treatment likely works by making cocaine less enjoyable, reducing the temptation to use it. Overall, early evidence suggests that sustained-release d-amphetamine might be a helpful option for those aiming to reduce their cocaine use. ^{6 7 8 9 10}

Who Is on the Research Team?

Joshua Lile, PhD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

This trial is for individuals who have recently used cocaine but are generally healthy. They should not have any serious physical or psychiatric diseases, and their lab results must be within normal ranges to participate.

Inclusion Criteria

Recent cocaine use

You have recently used cocaine.

You are generally in good health.

Exclusion Criteria

I have a serious physical or mental health condition.

Laboratory results outside of clinically acceptable ranges

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants engage in a drug-vs-money choice task using reinforcement learning modeling and fMRI to assess decision-making profiles. Each session involves 200 trials with varying monetary reinforcers.

40 minutes per session

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Money
• Sustained Release d-amphetamine

Trial Overview The study is testing whether sustained release d-amphetamine, a medication, can influence the choice between taking cocaine or receiving money. Participants' decisions will be studied using tasks, computer modeling, and brain imaging (fMRI).

How Is the Trial Designed?

Group I: $4.00 alternative reinforcer value Experimental Treatment 2 Interventions

Subjects complete 200 trials on a probabilistic concurrent choice procedure in which 3 mg/70 kg intravenous cocaine and an alternative monetary reinforcer are available during each trial. Each money value is tested in a separate session.

Group II: $1.00 alternative reinforcer value Experimental Treatment 2 Interventions

Subjects complete 200 trials on a probabilistic concurrent choice procedure in which 3 mg/70 kg intravenous cocaine and an alternative monetary reinforcer are available during each trial. Each money value is tested in a separate session.

Group III: $0.25 alternative reinforcer value Experimental Treatment 2 Interventions

Subjects complete 200 trials on a probabilistic concurrent choice procedure in which 3 mg/70 kg intravenous cocaine and an alternative monetary reinforcer are available during each trial. Each money value is tested in a separate session.

Sustained Release d-amphetamine is already approved in United States, United Kingdom for the following indications:

Approved in United States as Dexedrine for:

• Attention Deficit Disorder with Hyperactivity
• Narcolepsy

Approved in United Kingdom as Dexamfetamine sulfate for:

• Attention Deficit Disorder with Hyperactivity
• Narcolepsy

Who Is Running the Clinical Trial?

Joshua A. Lile, Ph.D.

Lead Sponsor

Trials

6

Recruited

120+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Dexmethylphenidate, an extended-release medication approved for ADHD, is effective for both children (as young as 6) and adults, marking a significant advancement in ADHD treatment options.

The drug's unique delivery system allows for two peaks in medication levels, providing sustained efficacy throughout a 12-hour day, with initial effects seen as early as 1.5 hours after dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmethylphenidate extended-release capsules for the treatment of attention deficit hyperactivity disorder. Kowalik, S., Minami, H., Silva, R.[2019]

In a study involving 41 long-term amphetamine-dependent individuals, both those receiving dexamphetamine and those receiving only counseling showed reduced use of street amphetamines, indicating that both interventions were effective.

The group receiving dexamphetamine was more likely to attend counseling sessions, suggesting that this treatment may enhance engagement in therapy and support further research into its efficacy in a larger trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot randomized controlled study of dexamphetamine substitution for amphetamine dependence. Shearer, J., Wodak, A., Mattick, RP., et al.[2019]

Dexmethylphenidate extended release is an effective long-acting ADHD medication that provides symptom relief for up to 12 hours, making it convenient for both children and adults.

The medication is generally well tolerated, with side effects similar to other stimulants, primarily including diminished appetite and insomnia, which suggests it can be a favorable option for ADHD treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmethylphenidate extended-release capsules for attention deficit hyperactivity disorder. McGough, JJ., Pataki, CS., Suddath, R.[2015]

In a randomized trial with 49 participants, those receiving sustained-release dexamphetamine showed significantly better treatment retention (86.3 days) compared to the placebo group (48.6 days), indicating its potential effectiveness in supporting recovery from methamphetamine dependence.

Dexamphetamine treatment was associated with a significant reduction in methamphetamine dependence and withdrawal symptoms, and it was found to be safe, with no serious adverse events reported during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized controlled trial of dexamphetamine maintenance for the treatment of methamphetamine dependence. Longo, M., Wickes, W., Smout, M., et al.[2018]

In a study of 126 participants with ADHD and cocaine dependence, treatment with extended release mixed amphetamine salts (MAS-XR) showed that improvement in ADHD symptoms often occurred before achieving cocaine abstinence, suggesting a potential causal relationship.

Specifically, patients who showed improvement in ADHD symptoms by week 2 had significantly higher odds of being abstinent from cocaine by week 3, indicating that addressing ADHD may enhance treatment outcomes for substance use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How treatment improvement in ADHD and cocaine dependence are related to one another: A secondary analysis. Levin, FR., Choi, CJ., Pavlicova, M., et al.[2022]

In a study of 56 children and adolescents with ADHD over 8 weeks, both long-acting dexmethylphenidate (ER d-MPH) and mixed amphetamine salts (ER MAS) significantly reduced ADHD symptoms, with improvements strongly linked to higher doses.

Around 80% of participants showed reliable improvement in ADHD symptoms at the highest dose of either medication, but common side effects like decreased appetite and insomnia increased with higher doses, indicating a need for careful dose management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose effects and comparative effectiveness of extended release dexmethylphenidate and mixed amphetamine salts. Stein, MA., Waldman, ID., Charney, E., et al.[2021]

In a study involving adults aged 18-55 with ADHD, SHP465 mixed amphetamine salts (25 mg) significantly improved performance on the Permanent Product Measure of Performance (PERMP) compared to placebo, with effects observed from 4 to 16 hours post-dose.

The safety profile of SHP465 MAS was consistent with previous findings, with common side effects including insomnia, decreased appetite, and increased heart rate and blood pressure, indicating it is generally well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of SHP465 mixed amphetamine salts in adults with ADHD in a simulated adult workplace environment. Wigal, T., Childress, A., Frick, G., et al.[2022]

A 14-week double-blind trial with 30 cocaine-dependent individuals showed that those receiving 60 mg/day of dexamphetamine had a significant reduction in self-reported cocaine use, cravings, and severity of dependence compared to the placebo group.

While the overall results were not statistically significant between groups, the treatment group demonstrated a notable decline in cocaine-positive urine samples from 94% to 56%, suggesting potential efficacy of dexamphetamine in reducing cocaine use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot randomized double blind placebo-controlled study of dexamphetamine for cocaine dependence. Shearer, J., Wodak, A., van Beek, I., et al.[2019]

In a 12-week study with 128 cocaine-dependent participants, those receiving 15 to 30 mg of dextroamphetamine sulfate showed the best retention rates compared to higher doses and placebo.

The study found that lower doses of dextroamphetamine were associated with fewer positive urine tests for cocaine, suggesting that dosing strategies need to be refined to optimize treatment outcomes for psychostimulant dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextroamphetamine for cocaine-dependence treatment: a double-blind randomized clinical trial. Grabowski, J., Rhoades, H., Schmitz, J., et al.[2019]

In a study of 73 cocaine-dependent patients undergoing heroin-assisted treatment, SR-dexamphetamine significantly increased the number of cocaine abstinent days compared to placebo, indicating its efficacy in reducing cocaine use.

SR-dexamphetamine treatment also showed potential to improve overall health outcomes, particularly in patients who started with poor health, suggesting that it may have broader benefits beyond just reducing cocaine use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effects beyond cocaine use of sustained-release dexamphetamine for the treatment of cocaine dependent patients with comorbid opioid dependence: secondary analysis of a double-blind, placebo-controlled randomized trial. Blanken, P., Nuijten, M., van den Brink, W., et al.[2021]

In a 10-week interim analysis of the QU.E.S.T. trial involving 725 adults with ADHD, mixed amphetamine salts extended release (MAS XR) showed significant improvements in ADHD symptoms, with most participants (74.4%) reporting they were very much or much improved.

MAS XR treatment was generally safe, with only 6.9% of participants withdrawing due to adverse events, and common side effects included decreased appetite and dry mouth, indicating that the benefits of symptom relief were achieved with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An interim analysis of the Quality of Life, Effectiveness, Safety, and Tolerability (QU.E.S.T.) evaluation of mixed amphetamine salts extended release in adults with ADHD. Goodman, DW., Ginsberg, L., Weisler, RH., et al.[2019]

Dexmethylphenidate extended release (XR) is effective for treating ADHD in patients aged 6 and older, showing significant symptom improvement from 0.5 hours to 11-12 hours after administration, making it suitable for all-day use.

This medication has a low risk of abuse and offers flexible administration options, such as sprinkling the capsule contents on food, which is beneficial for children who may have difficulty swallowing pills.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmethylphenidate extended release: a review of its use in the treatment of attention-deficit hyperactivity disorder. Moen, MD., Keam, SJ.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31908066/

Clinical effects beyond cocaine use of sustained-release ... Conclusions: SR-dexamphetamine reduces cocaine use and may improve clinically relevant health-related outcomes in patients with cocaine dependence who are ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0140673616002051

Articles Sustained-release dexamfetamine in the treatment ... Sustained-release dexamfetamine treatment resulted in significantly fewer days of cocaine use than placebo treatment (mean 44·9 days [SD 29·4] vs 60·6 days [24· ...

3. harmreductionjournal.biomedcentral.com harmreductionjournal.biomedcentral.com/articles/10.1186/s12954-021-00500-9

Use of sustained release dextroamphetamine for the treatment ... Dextroamphetamine (a central nervous system stimulant) has been found to be a safe and effective treatment for cocaine dependence among people ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3417072/

Psychostimulant Treatment of Cocaine Dependence - PMC Animal laboratory studies have demonstrated that sustained dextroamphetamine administration can attenuate the reinforcing effects of cocaine. Dextroamphetamine ...

5. mentalhealth.bmj.com mentalhealth.bmj.com/content/5/2/47

Sustained release dextroamphetamine (15–30 mg but not ... In patients with cocaine dependence, sustained release dextroamphetamine was more effective than placebo for improving retention at doses of 15– ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8136105/

Use of sustained release dextroamphetamine for the treatment ... Dextroamphetamine (a central nervous system stimulant) has been found to be a safe and effective treatment for cocaine dependence among people ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2663379/

Cocaine Effects During d-Amphetamine Maintenance This experiment determined the physiological and behavioral effects of cocaine during d-amphetamine maintenance in seven cocaine-dependent participants.

8. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2833773

Safety of Stimulants Across Patient Populations: A Meta- ... Prolonged exposure to stimulants lasting 5 to 14 years may increase the risk of cardiovascular disease. In response to these concerns, several ...

9. withpower.com withpower.com/trial/early-phase-1-2021-f8f98

d-Amphetamine for Cocaine Use Disorder Safety data for d-Amphetamine, particularly in the form of sustained-release dexamphetamine, has been evaluated in various studies. One study focused on its use ...

10. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0376871608003128

Cocaine effects during d-amphetamine maintenance This experiment determined the physiological and behavioral effects of cocaine during d-amphetamine maintenance in seven cocaine-dependent participants.