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

Trial Summary

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.

What data supports the idea that the drug Naltrexone for Social Connection is an effective treatment?

The available research shows that Naltrexone, particularly in its long-acting injectable form, has been effective in reducing heavy drinking and promoting abstinence in people with alcohol dependence. Studies have found that these formulations help maintain consistent drug levels in the body, which can reduce side effects and improve treatment outcomes. However, the effectiveness of Naltrexone can vary based on patient adherence to the treatment plan. While the drug is primarily used for alcohol and opioid dependence, the data suggests it can be a useful part of a treatment plan for those who are motivated and have strong support systems. ^{1 2 3 4 5}

What safety data exists for naltrexone treatment?

Naltrexone, available in oral and injectable forms (ReVia, Vivitrol, Depade), has been studied for alcohol and opioid dependence. Oral naltrexone can cause adverse events and plasma level fluctuations, while injectable forms like Vivitrol have a less severe adverse-event profile. Injectable extended-release naltrexone has been evaluated for long-term safety and efficacy in opioid dependence, with concerns about rebound overdose risk after the last dose. Preclinical studies show that naltrexone and its polymer matrix are well tolerated. Further studies are needed to fully understand the safety and efficacy of different formulations. ^{1 2 3 6 7}

Is the drug Naltrexone Hydrochloride a promising treatment for social connection?

Naltrexone Hydrochloride shows promise as it can help reduce cravings and prevent relapse in people with alcohol and opioid dependence. It has been effective in increasing the time to first relapse in some patients and has potential benefits in reducing HIV risk among opioid users. Extended-release forms improve patient compliance, making it a promising option. ^{1 2 8 9 10}

What is the purpose of this trial?

The study is a randomized, placebo-controlled design with the opioid antagonist, oral naltrexone. Following random assignment, participants will take 50mg of naltrexone or placebo once a day for 7 days. On days 1 - 7, participants complete reports of their feelings of social connection and mood in order to assess more naturalistic feelings in response to opportunities for social connection outside of the laboratory setting. Additionally, at the end of each day, they complete a physical symptoms questionnaire. On the 7th day, participants will come to the SDSU MRI scanning facility to complete tasks designed to elicit feelings of social connection in the fMRI scanner. After the scan, feelings in response to the scanner tasks will be collected.

Research Team

Tristen Inagaki, PhD

Principal Investigator

San Diego State University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

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

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

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

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

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

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

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

Naltrexone: a controversial therapy for alcohol dependence. [2022]

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

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

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

[Injectable extended-release naltrexone for opioid dependence: an open label study of long-term safety and efficacy]. [2016]

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

Review of Case Narratives from Fatal Overdoses Associated with Injectable Naltrexone for Opioid Dependence. [2019]

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

Antagonist Models for Relapse Prevention and Reducing HIV Risk. [2018]

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

Cloninger's typology and treatment outcome in alcohol-dependent subjects during pharmacotherapy with naltrexone. [2022]

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

Crystal structure of naltrexone chloride solvates with ethanol, propan-2-ol, and 2-methyl-propan-2-ol. [2020]