What is the mechanism of action of this treatment?

Common treatments for alcoholism include naltrexone, disulfiram, acamprosate, and gabapentin. Naltrexone works by blocking opioid receptors, reducing the rewarding effects of alcohol and decreasing cravings. Disulfiram inhibits the enzyme acetaldehyde dehydrogenase, causing unpleasant symptoms when alcohol is consumed, thus deterring drinking. Acamprosate modulates glutamate neurotransmission, helping to restore the balance of neurotransmitters disrupted by chronic alcohol use. Gabapentin, an anticonvulsant, is thought to reduce alcohol cravings and withdrawal symptoms by modulating GABA and glutamate systems. These mechanisms are crucial as they target different aspects of alcohol dependence, offering multiple pathways to support recovery. Tolcapone, a COMT inhibitor, is being studied for its potential to affect alcohol response and decision-making, which could provide another therapeutic avenue by influencing dopamine metabolism.

What side effects are associated with this type of intervention?

Naltrexone, a common treatment for alcohol dependence, is generally well-tolerated but can cause side effects such as abdominal pain and headache. Elevated liver enzymes have been observed, particularly in patients taking concurrent analgesics. Other side effects may include nausea, which is common during the initial week of treatment. While tolcapone (a COMT inhibitor) is not specifically mentioned for alcoholism treatment, it is important to monitor liver function due to potential hepatotoxicity, a concern shared with naltrexone.

What prior FDA approvals exist?

The FDA has approved several medications for the treatment of alcoholism, including disulfiram, naltrexone, and acamprosate. Disulfiram works by causing unpleasant effects when alcohol is consumed, while naltrexone reduces the rewarding effects of alcohol, and acamprosate helps maintain abstinence by stabilizing chemical balance in the brain. While Tolcapone, a COMT inhibitor, is being studied for its effects on alcohol response and decision-making, it is not yet approved for the treatment of alcoholism. Current FDA-approved treatments focus on different mechanisms such as aversion, reward reduction, and chemical stabilization.

What other types of research exist?

Promising novel alternatives to Tolcapone for alcoholism treatment in 2024 may include medications targeting different pathways such as naltrexone (an opioid receptor antagonist), acamprosate (which modulates glutamatergic neurotransmission), and newer agents like baclofen (a GABA-B receptor agonist) and varenicline (a partial nicotinic receptor agonist). Additionally, emerging treatments involving neuromodulation and personalized medicine approaches based on genetic profiles are also being explored.

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Tolcapone for Alcoholism and ADHD

Phase 2

Recruiting

Led By Joseph P Schacht, PhD

Research Sponsored by University of Colorado, Denver

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age 21-65.

Currently not taking any medication for AUD or ADHD.

Must not have

Females of childbearing potential who are pregnant (by plasma HCG), nursing, or who are not using a reliable form of contraception

Current DSM-5 psychotic, mood, anxiety, obsessive-compulsive, trauma-related, or eating disorder, as assessed by SCID-5

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 30 minutes after laboratory alcohol administration on day 1 of each medication period. each medication period is 8 days long.

Summary

This trial tests tolcapone to see if it helps people with both alcohol use issues and attention problems. The study focuses on people with both AUD and ADHD. Tolcapone works by affecting brain chemicals related to mood and behavior. Initially used for Parkinson's disease, tolcapone might be considered for ADHD treatment.

Who is the study for?

This trial is for adults aged 21-65 who meet the criteria for both Alcohol Use Disorder (AUD) and Attention-Deficit/Hyperactivity Disorder (ADHD), but are not currently seeking treatment or taking medication for these conditions. Participants must live within 50 miles of the study site, be able to understand consent forms, and not have any severe medical issues or metal in their body.

What is being tested?

The study tests if tolcapone, a drug that affects brain chemistry, changes how people with AUD/ADHD respond to alcohol, make decisions, react to alcohol cues in the brain, control impulses and focus attention compared to a placebo. It also looks at whether it affects their drinking habits.

What are the potential side effects?

Tolcapone can cause liver problems which will be monitored closely. Other possible side effects include diarrhea, nausea, sleepiness or trouble sleeping. Some people might experience confusion or hallucinations.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 21 and 65 years old.

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I am not on medication for alcohol use disorder or ADHD.

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I am not on medication for alcohol use disorder or ADHD.

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I am between 21 and 65 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not pregnant, nursing, and I use reliable contraception.

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I have been diagnosed with a mental health disorder like schizophrenia, depression, or an eating disorder.

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I am not having thoughts of harming myself or others.

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I have or had liver disease, or my liver tests are higher than normal.

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I am currently taking medication for mental health issues.

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I have had a neurological disease or head injury that caused me to be unconscious for more than 2 minutes.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 30 minutes after laboratory alcohol administration on day 1 of each medication period. each medication period is 8 days long.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~30 minutes after laboratory alcohol administration on day 1 of each medication period. each medication period is 8 days long.

This trial's timeline: 3 weeks for screening, Varies for treatment, and 30 minutes after laboratory alcohol administration on day 1 of each medication period. each medication period is 8 days long. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in alcohol cue-elicited brain activation (fMRI) between medication periods

Change in alcohol-induced stimulation between medication periods

Change in cognitive-control-associated brain activation (fMRI) between medication periods

+3 more

Trial Design

2Treatment groups

Experimental Treatment

Group I: Tolcapone then PlaceboExperimental Treatment2 Interventions

Participants in this arm will receive tolcapone during the first medication period (1 capsule containing 200 mg tolcapone on study days 1 and 2; 3 capsules containing a total of 600 mg tolcapone on study days 3-8), and placebo during the second medication period (1 capsule on study days 1 and 2; 3 capsules on study days 3-8).

Group II: Placebo then TolcaponeExperimental Treatment2 Interventions

Participants in this arm will receive placebo during the first medication period (1 capsule on study days 1 and 2; 3 capsules on study days 3-8), and tolcapone during the second medication period (1 capsule containing 200 mg tolcapone on study days 1 and 2; 3 capsules containing a total of 600 mg tolcapone on study days 3-8).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Placebo

1995

Completed Phase 3

~2670

Tolcapone

2014

Completed Phase 2

~630

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for alcoholism include naltrexone, disulfiram, acamprosate, and gabapentin. Naltrexone works by blocking opioid receptors, reducing the rewarding effects of alcohol and decreasing cravings. Disulfiram inhibits the enzyme acetaldehyde dehydrogenase, causing unpleasant symptoms when alcohol is consumed, thus deterring drinking. Acamprosate modulates glutamate neurotransmission, helping to restore the balance of neurotransmitters disrupted by chronic alcohol use. Gabapentin, an anticonvulsant, is thought to reduce alcohol cravings and withdrawal symptoms by modulating GABA and glutamate systems. These mechanisms are crucial as they target different aspects of alcohol dependence, offering multiple pathways to support recovery. Tolcapone, a COMT inhibitor, is being studied for its potential to affect alcohol response and decision-making, which could provide another therapeutic avenue by influencing dopamine metabolism.