Opioid use disorder


Opioid use disorder is a substance use disorder characterized by cravings for opioids, continued use despite physical and/or psychological deterioration, increased tolerance with use, and withdrawal symptoms after discontinuing opioids. Opioid withdrawal symptoms include nausea, muscle aches, diarrhea, trouble sleeping, agitation, and a low mood. Addiction and dependence are important components of opioid use disorder.
Risk factors include a history of opioid misuse, current opioid misuse, young age, socioeconomic status, race, untreated psychiatric disorders, and environments that promote misuse. Complications may include opioid overdose, suicide, HIV/AIDS, hepatitis C, and problems meeting social or professional responsibilities. Diagnosis may be based on criteria by the American Psychiatric Association in the DSM-5.
Opioids include substances such as heroin, morphine, fentanyl, codeine, dihydrocodeine, oxycodone, hydrocodone and tramadol. A useful standard for the relative strength of different opioids is morphine milligram equivalents. It is recommended for clinicians to refer to daily MMEs when prescribing opioids to decrease the risk of misuse and adverse effects. Long-term opioid use occurs in about 4% of people following their use for trauma or surgery-related pain. In the United States, most heroin users begin by using prescription opioids that may also be bought illegally.
People with opioid use disorder are often treated with opioid replacement therapy using methadone or buprenorphine. Such treatment reduces the risk of death. Additionally, they may benefit from cognitive behavioral therapy, other forms of support from mental health professionals such as individual or group therapy, twelve-step programs, and other peer support programs. The medication naltrexone may also be useful to prevent relapse. Naloxone is useful for treating an opioid overdose and giving those at risk naloxone to take home is beneficial.
This disorder is much more prevalent than first realized. In 2020, the CDC estimated that nearly 3 million people in the U.S. were living with OUD and more than 65,000 people died by opioid overdose, of whom more than 15,000 overdosed on heroin. In 2022, the U.S. reported 81,806 deaths caused by opioid-related overdoses. Canada reported 32,632 opioid-related deaths between January 2016 and June 2022'''.'''

Signs and symptoms

Opioid intoxication

Signs and symptoms of opioid intoxication include:
Signs and symptoms of opioid overdose include, but are not limited to:
Opioid withdrawal can occur with a sudden decrease in, or cessation of, opioids after prolonged use. Onset of withdrawal depends on the half-life of the opioid that was used last. With heroin this typically occurs five hours after use. With methadone, it may take two days.
The length of time that major symptoms occur also depends on the opioid used. For heroin withdrawal, symptoms are typically greatest at two to four days and can last up to two weeks. Less significant symptoms may remain longer, in which case the withdrawal is known as post-acute-withdrawal syndrome.
Treatment of withdrawal may include methadone and buprenorphine. Medications for nausea or diarrhea may also be used.

Cause

Opioid use disorder can develop for many reasons, including systemic failures such as pervasive marketing strategies, over-prescribing, and self-medication. Scoring systems have been derived to assess the likelihood of opiate addiction in chronic pain patients. Healthcare practitioners have long been aware that despite the effective use of opioids for managing pain, empirical evidence supporting long-term opioid use is minimal. Many studies of patients with chronic pain have failed to show any sustained improvement in their pain or ability to function with long-term opioid use.
A 2024 literature review suggests that adverse childhood experiences are significantly associated with opioid use disorder later in life. ACEs include witnessing violence, experiencing abuse and neglect, and growing up with a family member with a mental health or substance abuse problem.

Mechanism

Addiction

is a chronic brain disorder characterized by compulsive drug use despite adverse consequences. Addiction involves the overstimulation of the brain's mesocorticolimbic reward circuit, essential for motivating behaviors linked to survival and reproductive fitness, like seeking food and sex. This reward system encourages associative learning and goal-directed behavior. In addiction, substances overactivate this circuit, causing compulsive behavior due to changes in brain synapses.
In the brain's mesolimbic region, Nucleus Accumbens accepts releases of dopamine triggered by the neurotransmitters. 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.
The incentive-sensitization theory differentiates between "wanting" and "liking". This explains the addictive potential of non-pleasurable substances and the persistence of opioid addiction despite tolerance to their euphoric effects. Addiction surpasses mere avoidance of withdrawal, involving cues and stress that reactivate reward-driven behaviors. This is thought to be an important reason detoxification alone is unsuccessful 90% of the time.
Overexpression of the gene transcription factor ΔFosB in the nucleus accumbens plays a crucial role in the development of an addiction to opioids and other addictive drugs by sensitizing drug reward and amplifying compulsive drug-seeking behavior. Like other addictive drugs, overuse of opioids leads to increased ΔFosB expression in the nucleus accumbens.
Opioids affect dopamine neurotransmission in the nucleus accumbens via the disinhibition of dopaminergic pathways as a result of inhibiting the GABA-based projections to the ventral tegmental area from the rostromedial tegmental nucleus, which negatively modulates dopamine neurotransmission. In other words, opioids inhibit the projections from the RMTg to the VTA, which in turn disinhibits the dopaminergic pathways that project from the VTA to the nucleus accumbens and elsewhere in the brain.
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. Studies of the D2 Dopamine Receptor, in particular, have shown some promising results. One specific SNP is at the TaqI RFLP. In a 2014 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. This study helps to show the contribution of dopamine receptors to substance addiction and more specifically to opioid abuse.
Neuroimaging has shown functional and structural alterations in the brain. Chronic intake of opioids such as heroin may cause long-term effects in the orbitofrontal area, which is essential for regulating reward-related behaviors, emotional responses, and anxiety. Moreover, neuroimaging and neuropsychological studies demonstrate dysregulation of circuits associated with emotion, stress and high impulsivity.

Dependence

Opioid dependence can occur as physical dependence, psychological dependence, or both. Drug dependence is an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus. Dependence is a component of a substance use disorder. Opioid dependence can manifest as physical dependence, psychological dependence, or both.
Increased brain-derived neurotrophic factor signaling in the ventral tegmental area has been shown to mediate opioid-induced withdrawal symptoms via downregulation of insulin receptor substrate 2, protein kinase B, and mechanistic target of rapamycin complex 2. As a result of downregulated signaling through these proteins, opiates cause VTA neuronal hyperexcitability and shrinkage. It has been shown that when an opiate-naive person begins using opiates in concentrations that induce euphoria, BDNF signaling increases in the VTA.
Upregulation of the cyclic adenosine monophosphate signal transduction pathway by cAMP response element binding protein, a gene transcription factor, in the nucleus accumbens is a common mechanism of psychological dependence among several classes of drugs of abuse. Upregulation of the same pathway in the locus coeruleus is also a mechanism responsible for certain aspects of opioid-induced physical dependence.
A scale was developed to compare the harm and dependence liability of 20 drugs. The scale uses a rating of zero to three to rate physical dependence, psychological dependence, and pleasure to create a mean score for dependence. Selected results can be seen in the chart below. Heroin and morphine both scored highest, at 3.0.
DrugMeanPleasurePsychological dependencePhysical dependence
Heroin/Morphine3.003.03.03.0
Cocaine2.393.02.81.3
Alcohol1.932.31.91.6
Benzodiazepines1.831.72.11.8
Tobacco2.212.32.61.8