History
The Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5) defines opioid use disorder as a problematic pattern of opioid use leading to clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period: [3]
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Taking larger amounts of opioids or taking opioids over a longer period than was intended
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Experiencing a persistent desire for the opioid or engaging in unsuccessful efforts to cut down or control opioid use.
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Spending a great deal of time in activities necessary to obtain, use, or recover from the effects of the opioid.
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Craving, or a strong desire or urge to use opioids.
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Using opioids in a fashion that results in a failure to fulfill major role obligations at work, school, or home.
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Continuing to use opioids despite experiencing persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of opioids.
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Giving up or reducing important social, occupational, or recreational activities because of opioid use.
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Continuing to use opioids in situations in which it is physically hazardous.
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Continuing to use opioids despite knowledge of having persistent or recurrent physical or psychological problems that are likely to have been caused or exacerbated by the substance.
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Tolerance, as defined by either a need for markedly increased amounts of opioids to achieve intoxications or desired effect, or a markedly diminished effect with continued use of the same amount of an opioid.
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Withdrawal, as manifested by either the characteristic opioid withdrawal syndrome, or taking opioids to relieve or avoid withdrawal symptoms.
Tolerance and withdrawal criteria are not considered to be met for individuals taking opioids solely under appropriate medical supervision.
Opioid use disorder can be classified by severity as mild, moderate, or severe.
Tolerance
Tolerance is the need for increasing doses of medication to achieve the initial effect of the drug. Tolerance to the analgesic and euphoriant effects and unwanted adverse effects, such as respiratory depression, sedation, and nausea, may develop. However, little tolerance develops to constipation and meiosis. Opioid tolerance usually does not develop in patients with cancer who are being treated for pain; the need for increasing doses in those patients typically is due to an increasing level of pain. No consistent relationship between intrinsic efficacy and tolerance exists.
Withdrawal
Continuous administration of opioids leads to physical dependence, the emergence of withdrawal symptoms during abstinence. Physical dependence is expected after 2-10 days of continuous use when the drug is stopped abruptly. The onset and duration of withdrawal varies with the drug used. For example, meperidine withdrawal symptoms peak in 8-12 hours and last for 4-5 days. Heroin withdrawal symptoms usually peak within 36-72 hours and may last for 7-14 days. Symptoms of opioid withdrawal include the following:
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Autonomic symptoms - Diarrhea, rhinorrhea, diaphoresis, lacrimation, shivering, nausea, emesis, piloerection (the phrase stopping "cold turkey" refers to piloerection, or "gooseflesh")
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Central nervous system arousal - Sleeplessness, restlessness, tremors
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Pain - Abdominal cramping, bone pains, and diffuse muscle aching
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Craving - For the medication
Addiction
The phenomenon of addiction is seen in a variable number of patients using drugs. Addiction is characterized as a psychological and behavioral syndrome in which the following features are observed:
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Drug craving
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Compulsive use
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Strong tendency to relapse after withdrawal
Addiction must be defined by the observation of maladaptive behaviors, such as adverse consequences due to drug use, loss of control over drug use, and preoccupation with obtaining opioids, rather than pharmacological phenomenon of physiologic dependence, tolerance, and dose escalation. Do not use the term addiction to describe patients who are merely physically dependent. Also, keep in mind that undertreatment in patients with pain may result in a pseudoaddiction, and opioid-seeking behavior may be mistaken for addiction.
Long-acting medications, such as methadone and sustained-release morphine, tend to have slower onset of action, and the rush or high experienced with more rapid-onset medications is not as prominent. Thus, the longer-acting opioids are less likely to be abused.
Physical
Dependence
Mental status effects include depression with any or all of its symptoms, such as sleep disturbances, lack of interest, selflessness, suicidal ideation, and poor coping skills.
Physiological effects: Because tolerance to many of the actions of the opioids develops, it is not likely for even a careful observer to notice the effects of opioids. Small-sized pupils may be the only observation because only very mild tolerance develops for miosis. Inflamed nasal mucosa may be seen if heroin is snorted.
Withdrawal
Mental status effects include purposive behaviors, such as complaints and manipulations directed at getting more drugs, or anxiety.
Physiologic effects include autonomic signs (eg, tachycardia, high blood pressure, fever, piloerection [goose flesh], mydriasis, and lacrimation, CNS arousal (irritability), and yawning.
In milder abstinence syndrome, clinical features may be limited to dysphoria, craving, yawning, lacrimation, rhinorrhea, and restlessness. In moderate-to-severe cases, piloerection, mydriasis, increased BP and pulse, and GI symptoms are seen as well.
Intoxication
Mental status effects include euphoria, sedation, decreased anxiety, a sense of tranquility, and indifference to pain produced by mild-to-moderate intoxication. Severe intoxication can lead to delirium and coma.
Physiological effects include the following:
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Respiratory depression (may occur while the patient maintains consciousness)
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Alterations in temperature regulations
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Hypovolemia (true as well as relative), leading to hypotension
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Miosis
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Needle marks or soft tissue infection
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Increase sphincter tone (can lead to urinary retention)
Addiction
The physical examination provides little information to add in the diagnosis of addiction. However, symptoms of opioid withdrawal or track marks are often suggestive of addiction.
Constipation is a common occurrence due to almost continuous use of narcotics.
Causes
Opioid dependence is considered a biopsychosocial disorder. Pharmacological, social, genetic, and psychodynamic factors interact to influence abuse behaviors associated with drugs. However, pharmacological factors can be especially prominent, more so than in other types of drug use disorders.
Pharmacological factors
Opioids are strongly reinforcing agents because of the euphoric effects and reported ability to reduce anxiety, increase self esteem, and help coping with daily problems. Most opioids associated with abuse and dependence are mu-agonists, such as heroin, morphine, hydrocodone, oxycodone, and meperidine. Some partial mu-agonists, such as buprenorphine, or some that have no mu-agonism, such as pentazocine, also can possess reinforcing properties. Rapid development of physical dependence and a protracted abstinence syndrome are unique to opioid use and can make abstinence difficult.
Of note, more than half of persons taking 90 days of opioid therapy over a 6-month period remain on opioids years later. Opioid continuation was strongly associated with prior opioid exposure, daily opioid doses of 120 mg or more of morphine equivalent per day, and possible misuse; however the data from which these associations did not include clinical measures of pain or disease severity. [24]
Kratom
Kratom (Mitragyna speciosa) is a psychoactive plant in the coffee family native to Southeast Asia. [25] Its use in the United States has grown over the past decade and it is estimated that millions of people take it regularly. [26] Controversy exists regarding whether kratom has any acceptable medicinal use and its safety.
The ongoing debate in the United States regarding kratom and its growing use originates from reports of kratom-related deaths, seizures, liver failure, psychosis, and concern of its addictive properties. [27] Proponents of kratom describe the botanical product and its history of being sold as a dietary supplement in Southeast Asia to manage pain, boost energy, and as a method to avoid opioid use and relieve opioid withdrawal symptoms. Recently, recreational use of kratom has been described. [28]
In 2016, the DEA announced its intention to designate kratom as a Schedule 1 controlled substance (ie, a substance with high potential for abuse and no currently accepted medical use). [29] Criticism of the DEA’s announcement came from those using kratom. Researchers also expressed concern regarding expensive and time-consuming regulations required to obtain Schedule I substances. Instead, the DEA withdrew the scheduling, and announced they would gather further scientific evidence. Kratom is currently listed as a "drug of concern" within the DEA’s Drugs of Abuse resource guide 2017 edition. [30]
Studies in rodents suggest alkaloids in kratom bind to opioid receptors and elicit antinociceptive properties, but with less respiratory depression than typical opioids. [31]
FDA scientists analyzed the chemical structures of the 25 most common compounds in kratom utilizing a computational model. Their conclusion was that all of the compounds share structural characteristics with controlled opioid analgesics, such as morphine derivatives. Additionally, the FDA found the compounds in kratom bind strongly to mu-opioid receptors, comparable to opioid drugs. [32]
At the time of this writing, a handful of states (ie, Alabama, Arkansas, Indiana, Tennessee, Vermont, Wisconsin) and several cities (ie, Denver, San Diego, Sarasota, and Washington DC) have banned or limited kratom sales. Legislation is being considered in other states (eg, Illinois). [33]
Social factors
Easy drug availability and acceptable social attitudes make experimentation easy. A high rate of drug use is seen in areas of the city with poor parental functioning and higher crime and unemployment rates. Except for the association between higher exposure to the drug and higher rates of addiction, the precise role of social factors in creating dependent and addictive behaviors is uncertain.
Psychological factors
Ego defects in certain patients are postulated to form the basis of drug use. Opioids are theorized to help the ego in managing painful effects such as anxiety, guilt, and anger. Behavioral theory postulates that basic reward-punishment mechanisms perpetuate addictive behavior.
Preexisting mental health diagnoses appear to increase the risk for long-term use of opioids among adolescents and young adults with chronic pain. [34]
Genetic factors
Genetic epidemiologic studies suggest a high degree of heritable vulnerability for opioid dependence. [35] Gene polymorphisms for dopamine receptors/transporters, opioid receptors, serotonin receptors/transporters, proenkephalin, and catechol-O-methyltransferase (COMT) all appear to be associated with vulnerability to opioid dependence. Future interventions for opioid dependence may include medications identified through genetic research.
