LAAM produced long-lasting effects, which allowed the person receiving treatment to visit a clinic only three times per week, as opposed to daily as with methadone.

The brain reward circuitry is rooted in these networks, interacting between the mesolimbic and prefrontal cortex; these systems link motivation, anti-stress, incentive salience, and wellbeing.

[71][72] The differences in the genetic regions encoding the dopamine receptors for each individual may help to elucidate part of the risk for opioid addiction and general substance abuse.

In a study of 530 Han Chinese heroin-addicted individuals from a Methadone Maintenance Treatment Program, those with the specific genetic variation showed higher mean heroin consumption by around double those without the SNP.

[74] Chronic intake of opioids such as heroin may cause long-term effects in the orbitofrontal area (OFC), which is essential for regulating reward-related behaviors, emotional responses, and anxiety.

[77][58][78] Increased brain-derived neurotrophic factor (BDNF) signaling in the ventral tegmental area (VTA) has been shown to mediate opioid-induced withdrawal symptoms via downregulation of insulin receptor substrate 2 (IRS2), protein kinase B (AKT), and mechanistic target of rapamycin complex 2 (mTORC2).

Awareness campaigns, community outreach programs, and school-based education initiatives can help people make informed decisions about opioid use and recognize the signs of addiction early on.

[89] Large U.S. retail pharmacy chains are implementing protocols, guidelines, and initiatives to take back unused opioids, providing naloxone kits, and being vigilant about suspicious prescriptions.

[102][104] Other risk factors for overdose mortality related to opioids at the individual level include clinical factors such as cardiovascular disease, comorbid mental disorders and psychological stress (e.g., depression), a history of substance use disorders, economic and community distress (e.g., low education, high unemployment), and characteristics such as male sex and middle age.

[18] It reports a lack of clinical evidence that "abuse-deterrent" opioids (e.g., OxyContin), as labeled by the U.S. Food and Drug Administration, are effective for OUD risk mitigation.

[18] While receiving opioid therapy, patients should be periodically evaluated for opioid-related complications and clinicians should review state prescription drug monitoring program systems.

Withdrawal management alone is strongly discouraged, because of its association with elevated risks of HIV and hepatitis C transmission, high rates of overdose deaths, and nearly universal relapse.

[113] Buprenorphine/naloxone is usually preferred over methadone because of its safety profile, which is considered significantly better, primarily with regard to its risk of overdose[114] and effects on the heart (QTc prolongation).

[113][120] In some countries (not the U.S. or Australia),[113] regulations enforce a limited time for people on ORT programs that conclude when a stable economic and psychosocial situation is achieved.

[113] Medical (improper diluents, non-sterile injecting equipment), psychosocial (mental health, relationships), and legal (arrest and imprisonment) issues that can arise from the use of illegal opioids are concurrently eliminated or reduced.

[7] ORT has proved to be the most effective treatment for improving the health and living condition of people experiencing illegal opiate use or dependence, including mortality reduction[113][122][7] and overall societal costs, such as the economic loss from drug-related crime and healthcare expenditure.

[113] A review of UK hospital policies found that local guidelines delayed access to substitute opioids, for instance by requiring lab tests to demonstrate recent use or input from specialist drug teams before prescribing.

[123][124] ORT is endorsed by the World Health Organization, United Nations Office on Drugs and Crime and UNAIDS as effective at reducing injection, lowering risk for HIV/AIDS, and promoting adherence to antiretroviral therapy.

[131] While methadone is a widely prescribed form of OAT, it often requires more frequent clinical visits compared to buprenorphine/naloxone, which also has a better safety profile and lower risk of respiratory depression and overdose.

[155] Compared to methadone, it consistently results in improved birth weight and gestational age, though these findings should be interpreted with caution due to potential biases.

[163] Contingency Management Therapy (CMT) employs similar principles as operant behavioral conditioning, such as using incentives to reach certain goals (e.g., verified abstinence, usually in the form of urine drug testing).

The medical community has looked to novel technologies and traditional alternative medicines for new ways to approach the issues of continued cravings and impaired executive functioning.

While consensus on their efficacy has not been reached, a number of reviews have shown promising results for the use of non-invasive brain stimulation (NIBS) for reducing cravings in OUD.

Used for three to five days of continuous treatment, NET delivers alternating current via surface electrodes placed trans-cranially at the base of the skull on each side of the head.

[179][180][181] Some evidence suggests the possibility that opioid use disorders occur due to genetic or other chemical mechanisms that may be difficult to identify or change, such as dysregulation of brain circuitry involving reward and volition.

[197][198] The current, fourth wave, which began in 2016, has been characterized by polysubstance overdose due to synthetic opioids like fentanyl mixed with stimulants such as methamphetamine or cocaine.

[204] With respect to race, the discrepancy in deaths is thought to be due to an interplay between physician prescribing and lack of access to healthcare and certain prescription drugs.

[211] Among the middle class, means of acquiring funds include elder financial abuse and international dealers noticing a lack of enforcement in their transaction scams throughout the Caribbean.

[213] Since March 2020, as a result of the COVID-19 pandemic, buprenorphine may be dispensed via telemedicine in the U.S.[214][215] In October 2021, New York Governor Kathy Hochul signed legislation to combat the opioid crisis.

[224] One JAMA review by Gomes et al. showed that estimated years of life loss (YLL) due to opioid toxicity in the U.S. increased by 276%.