Naltrexone for Anxiety

(SSO Trial)

Enrolling by invitation 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how naltrexone, a medication typically used to block opioid effects, might affect anxiety by testing its role in fear extinction. Researchers aim to determine if the drug can influence how people unlearn fear when reminded of supportive people in their lives. Eligible participants should be healthy adults fluent in English, with no history of mental health issues or chronic physical illnesses. Participants will receive either naltrexone or a placebo, and researchers will assess the success of the fear extinction process. As an Early Phase 1 trial, this research focuses on understanding how naltrexone works in people, offering participants a chance to contribute to groundbreaking insights.

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 there any evidence suggesting that naltrexone is likely to be safe for humans?

Research has shown that the FDA has approved naltrexone for treating opioid and alcohol dependence, confirming its safety in humans. In one study involving about 570 people using naltrexone for alcohol dependence, some reported new side effects such as anxiety (12%), joint pain (12%), and stomach pain (11%).

While these side effects are not rare, they are usually manageable. It's important to note that naltrexone can lead to more serious issues, such as the risk of opioid overdose if someone returns to using opioids. However, this risk applies only to those using opioids, not the healthy participants in this trial.

Overall, naltrexone is generally well-tolerated, especially in healthy individuals. Participants in the trial might experience some of these side effects, but serious problems are less likely in a controlled setting without opioid use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard anxiety treatments that typically involve SSRIs or benzodiazepines, naltrexone offers a novel approach by targeting opioid receptors in the brain. This mechanism is different because it may help regulate mood and stress responses in a way that traditional anxiety medications do not. Researchers are excited about naltrexone because it could potentially offer relief for anxiety with fewer side effects than conventional medications, providing a new option for those who haven't found success with existing treatments.

What evidence suggests that naltrexone might be an effective treatment for anxiety?

Research has shown that naltrexone, a medication that blocks opioid effects, can help reduce anxiety and assist in treating addiction. For instance, one study found that people with alcohol addiction and anxiety improved significantly when taking naltrexone. Other studies on opioid addiction have also noted that a long-lasting form of naltrexone helped lower anxiety symptoms. Although most research has focused on addiction, these findings suggest that naltrexone might also help manage anxiety. In this trial, participants will receive either naltrexone or a placebo to evaluate its effectiveness in reducing anxiety. Naltrexone blocks certain brain receptors, which could affect how emotions and fear are processed. ^{6 7 8 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

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]

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]

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]

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]

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 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 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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9644470/

Alcohol use disorder with comorbid anxiety disorder

After medical stabilization, the patient found significant improvement in symptoms and no return to alcohol use with a regimen of naltrexone targeting his AUD, ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3128868/

Pharmacological enhancement of naltrexone treatment for ...

Significant reduction in opioid use and improved retention in treatment have been found in several studies using depot naltrexone formulations.

3.

oregonpainguidance.org

oregonpainguidance.org/wp-content/uploads/2018/02/Anxiety-Depression-and-Insomnia-Among-Adults-With-Opioid-Dependence-Treated-With-Extended-Release-Naltrexone-vs-Buprenorphine-Naloxone.pdf

Anxiety, Depression, and Insomnia Among Adults With ...

Extended-release naltrexone hydrochloride (XR-NTX) is a promising treatment of opioid dependence,18-21 but until now, no study has focused on changes in anxiety ...

4.

academic.oup.com

academic.oup.com/alcalc/article/60/1/agae078/7903160

Comparative effects of topiramate and naltrexone on neural ...

This study compared the neural response of treatment-seeking patients with AUD on either topiramate or naltrexone during an anticipatory anxiety task.

5.

frontiersin.org

frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.1003257/full

The effects of naltrexone on retention in treatment and ...

Injectable naltrexone was significantly effective on retention in treatment (OR 1.86; 95% CI, 1.17–2.98). Conclusions: We found that naltrexone could be useful ...

6.

vivitrol.com

vivitrol.com/important-safety-information

Important Safety Information

VIVITROL can cause serious side effects, including: Risk of opioid overdose. You can accidentally overdose in two ways.

7.

samhsa.gov

samhsa.gov/substance-use/treatment/options/naltrexone

What is Naltrexone? Side Effects, Uses, Dose & Risk

Intramuscular extended release naltrexone is a medication approved by the Food and Drug Administration (FDA) to treat both opioid use ...

8.

mayoclinic.org

mayoclinic.org/drugs-supplements/naltrexone-oral-route/description/drg-20068408

Naltrexone (oral route) - Side effects & dosage

This medicine may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have ...

9.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2013/018932s017lbl.pdf

REVIA (naltrexone hydrochloride tablets USP) 50 mg Opioid ...

In an open label safety study with approximately 570 individuals with alcoholism receiving REVIA, the following new-onset adverse reactions occurred in 2% or ...

10.

vivitrolhcp.com

vivitrolhcp.com/alcohol-dependence-pivotal-study

Alcohol Dependence: VIVITROL ® Efficacy and Safety Data

Anxiety, 12%, 8%. Arthralgia, arthritis, joint stiffness, 12%, 5%. Pharyngitis, 11%, 11%. Abdominal pain, 11%, 8%. Injection site pruritus, 10%, 0%. Depression ...