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

15 Participants Needed

Trial Summary

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.

What data supports the idea that d-Amphetamine for Cocaine Use Disorder is an effective drug?

The available research shows that sustained-release dexamphetamine, a form of d-Amphetamine, has shown positive effects in treating patients with cocaine use disorder. One study demonstrated that it helped reduce cocaine use in patients. Another study found that participants who took dextroamphetamine had better retention in the program and fewer positive drug tests compared to those who took a placebo. These findings suggest that d-Amphetamine can be an effective option for treating cocaine use disorder. ^{1 2 3 4 5}

What safety data exists for d-Amphetamine in treating 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 for cocaine-dependent patients with comorbid opioid dependence, indicating positive effects beyond just reducing cocaine use. Another study investigated its safety and efficacy for methamphetamine dependence, suggesting its potential safety in similar stimulant use disorders. Additionally, safety evaluations have been conducted in the context of ADHD treatment with mixed amphetamine salts, which are related formulations, providing further insights into the safety profile of amphetamines. ^{1 2 6 7 8}

Is the drug sustained-release d-amphetamine a promising treatment for cocaine use disorder?

Yes, sustained-release d-amphetamine is a promising treatment for cocaine use disorder. Research shows it can help reduce cocaine use and improve the health of patients with cocaine dependence. ^{2 9 10 11 12}

What is the purpose of this trial?

The objective of this protocol is to use a drug-vs-money choice task, reinforcement learning modeling and fMRI to determine the neurobehavioral and neurobiological decision-making "profile" associated with the decision to take cocaine and the reduced cocaine choice that occurs during a behavioral intervention (alternative money reinforcer) that models contingency management.

Research Team

Joshua Lile, PhD

Principal Investigator

University of Kentucky

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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+

Findings from Research

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 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 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]

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 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]

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]

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]

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]

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]

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]

References

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

Randomized controlled trial of dexamphetamine maintenance for the treatment of methamphetamine dependence. [2018]

2. England 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. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Pilot randomized controlled study of dexamphetamine substitution for amphetamine dependence. [2019]

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

Pilot randomized double blind placebo-controlled study of dexamphetamine for cocaine dependence. [2019]

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

Dextroamphetamine for cocaine-dependence treatment: a double-blind randomized clinical trial. [2019]

6. United States 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. [2019]

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

Dose effects and comparative effectiveness of extended release dexmethylphenidate and mixed amphetamine salts. [2021]

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

Effects of SHP465 mixed amphetamine salts in adults with ADHD in a simulated adult workplace environment. [2022]

9. Ireland pubmed.ncbi.nlm.nih.gov

How treatment improvement in ADHD and cocaine dependence are related to one another: A secondary analysis. [2022]

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

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

11. England pubmed.ncbi.nlm.nih.gov

Dexmethylphenidate extended-release capsules for the treatment of attention deficit hyperactivity disorder. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Dexmethylphenidate extended-release capsules for attention deficit hyperactivity disorder. [2015]