Naltrexone for Anxiety

(SSO Trial)

Recruiting at 2 trial locations

Overseen By Erica Hornstein, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of California, Los Angeles

Must not be taking: Mental health, Liver function

Disqualifiers: Pregnancy, Mental illness, Liver disease, others

Compensation: Varies

Number of Visits: 2

Duration: 1 session

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

University of California, Los Angeles researchers will recruit healthy participants (age 18-35) to participate in a study examining whether the administration of naltrexone, an opioid antagonist, eliminates the ability of social support figure reminders to enhance fear extinction--a process during which a threatening cue is learned to not predict a negative or threatening outcome (i.e., electric shock) by being repeatedly presented in the absence of that outcome. After undergoing an email screening, a telephone screening, an in lab screening, and a health screening, 60 participants will be enrolled in the study. During the experiment, 30 participants will be administered naltrexone and 30 participants will be administered placebo (both participants and experimenters will be blind to condition) before undergoing a fear extinction procedure in which threatening cues--cues that predict electric shock--will be paired with either an image of a social support figure (provided by participants) or a second threatening cue. These pairings will be presented repeatedly in the absence of shock in order for fear extinction to occur. Participants will return for a follow-up test to determine if fear extinction was successful.

Will I have to stop taking my current medications?

The trial requires that participants do not have a history of mental illness or take medications related to mental health disorders or liver function. If you are currently taking such medications, you would not be eligible to participate.

Is naltrexone safe for humans?

Naltrexone is generally considered safe for humans, but some people may experience unpleasant effects like loss of energy, stomach issues, and feelings of depression. Serious adverse events are rare, and it has been used safely in various conditions, including alcohol and opioid dependence. ^{1 2 3 4 5}

How does the drug naltrexone differ from other treatments for anxiety?

Naltrexone is unique because it is traditionally used to treat alcohol and opioid dependence by blocking the effects of these substances, and its use for anxiety is novel. Unlike typical anxiety medications, naltrexone is available in a long-acting injectable form, which can provide a steady release and potentially reduce side effects. ^{1 3 6 7 8}

What data supports the effectiveness of the drug Naltrexone for anxiety?

Research shows that Naltrexone is effective in reducing alcohol cravings and relapse rates in alcohol-dependent patients, and it may also help those with high levels of anxiety and distress. This suggests it could potentially be useful for anxiety, although direct evidence for anxiety treatment is not provided. ^{1 3 6 9 10}

Who Is on the Research Team?

Naomi Eisenberger, Ph.D.

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

Healthy adults aged 18-35 with no history of mental illness or chronic physical conditions, not pregnant, and without liver disease. Participants must be fluent in English and comfortable swallowing pills. Those with a history of substance abuse or on certain medications are excluded.

Inclusion Criteria

Healthy adults aged 18 to 35

No history of mental illness (including anxiety, depression, phobia, or any other mental health related disorder diagnosed by a mental health professional)

Fluent in English

Exclusion Criteria

Chronic physical illness (as determined by past diagnosis and/or treatment by a physician)

History of liver disease or abnormal liver function

Pregnant or planning to become pregnant during the experiment period

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Email, telephone, in-lab, and health screenings

Treatment

Participants undergo a fear extinction procedure with naltrexone or placebo administration

1 session

1 visit (in-person)

Follow-up

Participants return for a follow-up test to determine if fear extinction was successful

24 hours post-treatment

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Naltrexone
• Placebo

Trial Overview The study is testing if naltrexone blocks the positive effects of social support during fear extinction training. Half will receive naltrexone, half a placebo, before being exposed to cues associated with an electric shock alongside images of social support figures.

How Is the Trial Designed?

Group I: Naltrexone Active Control 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

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

Approved in United States as Vivitrol for:

• Alcohol dependence
• Opioid use disorder

Approved in European Union as Naltrexone for:

• Opioid dependence
• Alcohol dependence

Approved in Canada as Vivitrol for:

• Opioid use disorder
• Alcohol dependence

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

A systematic review of 49 trials found that only 14% of studies on naltrexone for alcohol dependence had high adherence assurance, which may explain the variability in treatment efficacy observed.

The study revealed a significant correlation between adherence levels and treatment outcomes, suggesting that improving adherence monitoring could enhance the effectiveness of naltrexone in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence monitoring in naltrexone pharmacotherapy trials: a systematic review. Swift, R., Oslin, DW., Alexander, M., et al.[2022]

In a 6-month trial involving 306 opioid-dependent patients, long-term treatment with naltrexone did not lead to increased levels of anxiety, depression, or craving for opioids, addressing concerns about its psychological effects.

Patients who remained in treatment experienced a gradual reduction in symptoms of anhedonia, depression, anxiety, and craving within the first 1-2 months, suggesting that naltrexone can be safely used without exacerbating these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Anhedonia, depression, anxiety, and craving in opioid dependent patients stabilized on oral naltrexone or naltrexone implant]. Krupitsky, EM., Zvartau, EE., Blokhina, EA., et al.[2019]

A systematic review of 29 randomized placebo-controlled trials involving 5997 alcohol-dependent patients found that naltrexone significantly reduces heavy drinking in 70% of the studies, highlighting its efficacy in this area.

However, naltrexone showed less effectiveness in promoting abstinence, with only 36% of trials demonstrating an advantage over placebo, suggesting that its primary benefit lies in reducing excessive drinking rather than achieving complete sobriety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The status of naltrexone in the treatment of alcohol dependence: specific effects on heavy drinking. Pettinati, HM., O'Brien, CP., Rabinowitz, AR., et al.[2013]

In a 12-week clinical trial with 202 alcohol-dependent patients, naltrexone significantly reduced the relapse rate to heavy drinking (7.9% for naltrexone vs. 18.8% for placebo), indicating its efficacy in treating alcoholism.

Naltrexone was well-tolerated with low rates of adverse events, such as abdominal pain and headache, and it did not negatively affect liver function or biochemical markers of heavy drinking, demonstrating its safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled study of naltrexone in the treatment of alcohol-dependence disorder: results from a multicenter clinical trial. Guardia, J., Caso, C., Arias, F., et al.[2013]

In a study involving ten opiate-free volunteers, naltrexone was administered over three weeks, leading to three participants dropping out due to unpleasant side effects, while the remaining seven experienced tolerable but still aversive effects.

A separate group of ten subjects receiving single doses of naltrexone also reported significant aversive reactions, including loss of energy, gastrointestinal issues, and mental depression, which may hinder the drug's acceptance as a treatment for opiate dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aversive effects of naltrexone in subjects not dependent on opiates. Hollister, LE., Johnson, K., Boukhabza, D., et al.[2019]

In a Phase I trial with 36 healthy participants, long-acting injectable depot naltrexone was found to be well tolerated, with mild adverse events reported by 36.67% of subjects, and no serious treatment-related adverse events occurred.

The pharmacokinetics showed that naltrexone maintained a constant plasma concentration for at least 30 days after a single injection, indicating its potential for effective long-term treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of injectable, depot naltrexone for the relapse prevention treatment of opioid dependence. Xuyi, W., Juelu, W., Xiaojun, X., et al.[2016]

Injectable formulations of naltrexone, such as Vivitrex/Vivitrol and Naltrel, show promise in treating alcohol dependence with potentially fewer side effects compared to oral naltrexone, which has limitations like a small treatment effect size and plasma level fluctuations.

Vivitrex/Vivitrol has been effective in reducing heavy drinking in alcohol-dependent males, while Naltrel has been shown to promote abstinence and reduce relapse rates, indicating that these depot formulations may offer improved therapeutic options for alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone long-acting formulation in the treatment of alcohol dependence. Johnson, BA.[2021]

Citations

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

Adherence monitoring in naltrexone pharmacotherapy trials: a systematic review. [2022]

2. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Anhedonia, depression, anxiety, and craving in opioid dependent patients stabilized on oral naltrexone or naltrexone implant]. [2019]

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

The status of naltrexone in the treatment of alcohol dependence: specific effects on heavy drinking. [2013]

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

A double-blind, placebo-controlled study of naltrexone in the treatment of alcohol-dependence disorder: results from a multicenter clinical trial. [2013]

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

Naltrexone in the treatment of alcoholism: predicting response to naltrexone. [2013]

6. Ireland pubmed.ncbi.nlm.nih.gov

Aversive effects of naltrexone in subjects not dependent on opiates. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Phase I study of injectable, depot naltrexone for the relapse prevention treatment of opioid dependence. [2016]

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

Serious adverse events reported in placebo randomised controlled trials of oral naltrexone: a systematic review and meta-analysis. [2023]

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

Naltrexone long-acting formulation in the treatment of alcohol dependence. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Follow-up after a six-month maintenance period on naltrexone versus placebo in heroin addicts. [2019]