Naltrexone for Social Connection

Overseen By Tristen Inagaki, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: San Diego State University

Must not be taking: Opioid analgesics

Disqualifiers: Chronic illness, Regular medication, others

Compensation: Varies

Number of Visits: 8

Duration: 1 week

210 Participants Needed

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 treat addiction, might affect social connections and mood. Participants will take either naltrexone or a placebo (a sugar pill) daily for seven days. Throughout the trial, they will report on their feelings of social connection and mood. On the last day, they will complete tasks in an MRI scanner to observe how the brain responds to feeling connected. Ideal candidates for this trial are in good health, own a smartphone, and can provide contact information for a few close friends or family members. As an Early Phase 1 trial, this research focuses on understanding how naltrexone works in people, offering participants a unique opportunity to contribute to groundbreaking research.

Do I have to stop taking my current medications to join the trial?

Yes, you must stop taking your current medications. The trial excludes people who regularly use prescription medication.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that naltrexone is generally safe for use. It has already received approval for treating alcohol and drug addiction, indicating it has passed safety tests for these purposes. In studies, some participants experienced mild side effects like nausea or headaches. However, these side effects usually did not prevent most from continuing the treatment. This suggests that while minor discomfort may occur, the treatment is generally safe for short-term use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for enhancing social connection, like therapy or certain antidepressants, work by targeting brain chemistry related to mood and anxiety. But naltrexone, typically known for treating addiction, is being explored for its unique ability to modulate the brain's reward system, which might enhance social engagement. Researchers are excited about this treatment because it could offer a new way to improve social interaction without the prolonged timeline or side effects associated with other medications. Additionally, the short, seven-day administration period is promising for those seeking quicker results.

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

This trial will compare the effects of Naltrexone and a placebo on social connection. Research has shown that naltrexone, a drug that blocks opioids, might reduce feelings of social connection. Studies found that people taking naltrexone felt less close to friends and family compared to those taking a placebo, which contains no active drug. In one study, 71% of the measures of social connection showed a decrease with naltrexone use. While these findings might seem surprising for a study on social connection, they highlight how naltrexone can affect social interactions. ^{1 2 4 6 7}

Who Is on the Research Team?

Tristen Inagaki, PhD

Principal Investigator

San Diego State University

Are You a Good Fit for This Trial?

This trial is for English-speaking individuals in good health who are willing to share contact info of close friends, provide photos of loved ones, own a smartphone, and aren't pregnant. It's not for those with BMI over 35, metal implants, claustrophobia, regular prescription medication use, positive drug tests or excessive alcohol use.

Inclusion Criteria

I am in good health overall.

Willing to provide digital photographs of 2 close others

English fluency

Exclusion Criteria

Previous history of having difficulty taking pills

Depressive symptoms above a 9 on Patient Health Questionnaire

Self-reported chronic mental or physical illness

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants take 50mg of naltrexone or placebo once a day for 7 days and complete daily reports on social connection and mood.

1 week

7 daily reports (virtual), 1 visit (in-person)

Neuroimaging

On the 7th day, participants undergo fMRI scanning to complete tasks designed to elicit feelings of social connection.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Naltrexone Hydrochloride
• Placebo

Trial Overview The study examines the effects of naltrexone (an opioid blocker) on social connection feelings compared to a placebo. Participants take either naltrexone or placebo daily for a week and report their mood and social experiences. On the last day, they undergo an MRI scan while performing tasks that evoke social feelings.

How Is the Trial Designed?

Group I: Naltrexone Experimental Treatment 1 Intervention

50mg naltrexone HCL once daily for seven days by mouth

Group II: placebo Placebo Group 1 Intervention

sugar pill once daily for seven days by mouth

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

Approved in United States as ReVia for:

• Alcohol use disorder
• Opioid use disorder

Approved in United States as Vivitrol for:

• Alcohol use disorder
• Opioid use disorder

Approved in United States as Depade for:

• Alcohol use disorder
• Opioid use disorder

Approved in European Union as Naltrexone for:

• Alcohol dependence
• Opioid dependence

Who Is Running the Clinical Trial?

San Diego State University

Lead Sponsor

Trials

182

Recruited

119,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Injectable extended-release naltrexone, developed using biodegradable polymer microspheres, maintains stable plasma levels for about one month after a single injection, which could improve patient compliance compared to oral formulations.

Pharmacokinetic studies in rats and monkeys showed that this formulation effectively antagonizes morphine analgesia without affecting the brain's mu-opioid receptor density, indicating its potential safety and efficacy in treating alcohol and opioid dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The preclinical development of Medisorb Naltrexone, a once a month long acting injection, for the treatment of alcohol dependence. Dean, RL.[2019]

Naltrexone hydrochloride is an effective treatment for opiate addiction, particularly for patients who remain off opiates longer when they adhere to the medication, although study design challenges have made it hard to assess its efficacy fully.

The drug is considered very safe, with common side effects being gastrointestinal irritation and minor increases in blood pressure, and it is recommended that patients be detoxified and opiate-free for 2-5 days before starting treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of naltrexone, a long-acting opiate antagonist. Crabtree, BL.[2013]

In a 1-year open-label extension study involving 114 patients, injectable extended-release naltrexone (XR-NTX) demonstrated long-term efficacy, with 50.9% of participants remaining abstinent from opioids throughout the study.

The treatment was generally safe, with only 21.1% of patients reporting adverse events and no severe adverse events noted, although 16.7% experienced elevated liver function tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Injectable extended-release naltrexone for opioid dependence: an open label study of long-term safety and efficacy]. Krupitsky, EM., Nunes, EV., Ling, W., et al.[2016]

Naltrexone HCL (ReVia) can be an effective addition to treatment for alcohol dependence in individuals who are motivated to change their drinking habits.

The use of naltrexone is controversial as it contrasts with the abstinence-focused approach of Alcoholics Anonymous and many medical treatment programs, highlighting the need for nurses to understand this debate to better advocate for their patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone: a controversial therapy for alcohol dependence. Freed, PE., York, LN.[2022]

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]

Naltrexone, an opiate receptor antagonist, is effective in delaying the time to first relapse in heavy drinking, particularly in alcohol-dependent patients with an early age of onset of drinking problems (Cloninger Type II).

Recent studies suggest that naltrexone's effectiveness varies among different patient subgroups, indicating that targeting specific groups, like those with Cloninger Type II, may enhance pharmacological relapse prevention strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cloninger's typology and treatment outcome in alcohol-dependent subjects during pharmacotherapy with naltrexone. Kiefer, F., Jiménez-Arriero, MA., Klein, O., et al.[2022]

Naltrexone is an effective opioid receptor antagonist used to prevent relapse in individuals dependent on opioids and alcohol, highlighting its role in addiction treatment.

The study identifies three solvated forms of naltrexone chloride with ethanol and other alcohols, which can aid in the unambiguous identification of naltrexone in pharmaceutical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crystal structure of naltrexone chloride solvates with ethanol, propan-2-ol, and 2-methyl-propan-2-ol. Menze, AR., Sinnott, JP., Nazarenko, AY.[2020]

A review of 263 cases related to Vivitrol (extended-release naltrexone) found that 84.6% of fatal overdoses occurred within two months after the last injection, highlighting a critical period for overdose risk.

The study suggests that there may be a link between Vivitrol discontinuation and increased overdose risk, indicating the need for further investigation and monitoring during this time frame.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of Case Narratives from Fatal Overdoses Associated with Injectable Naltrexone for Opioid Dependence. Saucier, R., Wolfe, D., Dasgupta, N.[2019]

Naltrexone is an opioid antagonist that effectively blocks the effects of opioids without causing physical dependence, but it must be administered after detoxification from opioids to avoid withdrawal symptoms.

Recent studies in Russia showed improved patient compliance with oral naltrexone, leading to reduced HIV risk among those in treatment, which contributed to the FDA's approval of extended-release injectable naltrexone as a promising option for preventing relapse in opioid dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antagonist Models for Relapse Prevention and Reducing HIV Risk. Woody, GE., Krupitsky, E., Zvartau, E.[2018]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7021584/

Opioids and social bonding: Effect of naltrexone on feelings of ... In support of hypotheses, naltrexone (vs. placebo) reduced feelings of social connection toward the close others (e.g., family, friends, romantic partners).

2. academic.oup.com academic.oup.com/scan/article/11/5/728/1753497

Opioids and social bonding: naltrexone reduces feelings of ... Results demonstrated that naltrexone (vs placebo) reduced feelings of connection both in the laboratory and in daily reports.

3. nature.com nature.com/articles/s41398-024-03088-3

Endogenous mu-opioid modulation of social connection in ... In total, 12/17 outcomes (71%) showed a negative effect of naltrexone on social connectedness, while the remaining 5/17 (29%) indicated a ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4958027/

Naltrexone alters the processing of social and emotional ... We tested the effects of a nonspecific opioid antagonist, naltrexone (NTX), on social processing in humans. NTX is used to treat alcohol and opiate dependence, ...

5. ikonrecoverycenters.org ikonrecoverycenters.org/5-key-findings-on-vivitrol-long-term-efficacy/

5 Key Findings on Vivitrol Long-Term Efficacy Vivitrol, a once-monthly injectable medication containing naltrexone, is used to treat opioid and alcohol use disorders by reducing cravings ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05007561?term=NALTREXONE&rank=5

Understanding How Opioids Affect the Experiential and ... The study is a randomized, placebo-controlled design with the opioid antagonist, oral naltrexone . Following random assignment, participants will take 50mg of ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0149763420306898

A mu-opioid feedback model of human social behavior Blocking the mu-opioid system with naltrexone resulted in an attentional bias to emotional faces and an increased identification of the emotional expressions ...