Opioid-Related Disorders

Learning Objectives

  • Identify opioids and describe how they impact the brain and behavior
  • Describe the diagnostic features, development, and risk factors of opioid use disorder, opioid intoxication, and opioid withdrawal
  • Describe sedative, hypnotic, or anxiolytic-related disorders

An opioid is one of a category of drugs that includes heroin, morphine, methadone, and codeine. Opioids have analgesic properties: that is, they decrease pain. Humans have an endogenous opioid neurotransmitter system—the body makes small quantities of opioid compounds that bind to opioid receptors reducing pain and producing euphoria. Thus, opioid drugs, which mimic this endogenous painkilling mechanism, have an extremely high potential for abuse. Natural opioids, called opiates, are derivatives of opium, which is a naturally occurring compound found in the poppy plant. There are now several synthetic versions of opiate drugs (correctly called opioids) that have very potent painkilling effects, and they are often abused. For example, the National Institute of Drug Abuse has sponsored research that suggests the misuse and abuse of the prescription pain killers hydrocodone and oxycodone are significant public health concerns (Maxwell, 2006). In 2013, the U.S. Food and Drug Administration (FDA) recommended tighter controls on their medical use.

Opioids include substances such as heroin, morphine, fentanyl, codeine, oxycodone, and hydrocodone. In the United States, a majority of heroin users begin by using prescription opioids that may also be bought illegally. Historically, heroin has been a major opioid drug of abuse (Figure 1). Heroin can be snorted, smoked, or injected intravenously. Like the stimulants described earlier, the use of heroin is associated with an initial feeling of euphoria followed by periods of agitation. Because heroin is often administered via intravenous injection, users often bear needle track marks on their arms and, like all abusers of intravenous drugs, have an increased risk for contraction of both tuberculosis and HIV.

Photograph A shows various paraphernalia spread out on a black surface. The items include a tourniquet, three syringes of varying widths, three cotton-balls, a tiny cooking vessel, a condom, a capsule of sterile water, and an alcohol swab. Photograph B shows a hand holding a spoon containing heroin tar above a small candle.

Figure 1. (a) Common paraphernalia for heroin preparation and use are shown here in a needle exchange kit. (b) Heroin is cooked on a spoon over a candle. (credit a: modification of work by Todd Huffman)

Aside from their utility as analgesic drugs, opioid-like compounds are often found in cough suppressants, anti-nausea, and anti-diarrhea medications. Given that withdrawal from a drug often involves an experience opposite to the effect of the drug, it should be no surprise that opioid withdrawal resembles a severe case of the flu. While opioid withdrawal can be extremely unpleasant, it is not life-threatening (Julien, 2005). Still, people experiencing opioid withdrawal may be given methadone to make withdrawal from the drug less difficult. Methadone is a synthetic opioid that is less euphorigenic than heroin and similar drugs. Methadone clinics help people who previously struggled with opioid addiction manage withdrawal symptoms through the use of methadone. Other drugs, including the opioid buprenorphine, have also been used to alleviate symptoms of opiate withdrawal.

Codeine is an opioid with relatively low potency. Codeine is often prescribed for minor pain, and it is available over-the-counter in some other countries. Like all opioids, codeine does have abuse potential. In fact, abuse of prescription opioid medications is becoming a major concern worldwide (Aquina, Marques-Baptista, Bridgeman, & Merlin, 2009; Casati, Sedefov, & Pfeiffer-Gerschel, 2012).

The Opioid Epidemic

The opioid epidemic, or the opioid crisis, refers to the extensive overuse of opioid drugs, both from medical prescriptions and from illegal sources. The epidemic began slowly in the United States, beginning in the late 1990s, and led to a massive increase in opioid use in recent years, contributing to over 70,000 drug overdose deaths in the United States in 2018. Fentanyl alone, being 50 times stronger than heroin and 100 times stronger than morphine, was causing about 200 overdose deaths per day in 2017.[1]

Opioids are a diverse class of moderately strong, addictive, inexpensive painkillers prescribed by doctors. In the late 1990s, pharmaceutical companies reassured the medical community that patients would not become addicted to opioid pain relievers and healthcare providers began to prescribe them at greater rates. This claim led to widespread misuse of both prescription and non-prescription opioids before it became clear that these medications could indeed be highly addictive.

Though aggressive opioid prescription practices played the biggest role in creating the epidemic, the popularity of illegal substances such as potent heroin and illicit fentanyl have become an increasingly large factor. It has been suggested that decreased supply of prescription opioids caused by opioid prescribing reforms turned people who were already addicted to opioids towards illegal substances.[2]

In 2015, approximately 50% of drug overdoses were not the result of an opioid product from a prescription, though most abusers’ first exposure had still been by lawful prescription.[3] By 2018, another study suggested that 75% of opioid abusers started their opioid use by taking drugs which had been obtained in a way other than by legitimate prescription.[4]

Those addicted to opioids, both legal and illegal, are increasingly young, white, and female, with 1.2 million women addicted compared to 0.9 million men in 2015. While men have higher rates of opioid abuse on the whole and are more likely to visit the emergency room or die from an overdose, heroin deaths among women increased at more than twice the rate than among men from 1995 to 2015.[5]

The populations of rural areas of the country have been the hardest hit. Teen abuse of opioids has been noticeably increasing since 2006, using prescription drugs more than any illicit drug except marijuana and more than cocaine, heroin, and methamphetamine combined. The crisis has also changed moral, social, and cultural resistance to street drug alternatives such as heroin.

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Opioid-Related Disorders

Opioid use disorder (OUD) is a substance use disorder relating to the use of an opioid. Any such disorder causes significant impairment or distress. Signs of the disorder include a strong desire to use opioids, increased tolerance to opioids, difficulty fulfilling obligations, trouble reducing use, and withdrawal symptoms with discontinuation. Opioid withdrawal symptoms may include nausea, muscle aches, diarrhea, trouble sleeping, agitation, and a low mood. Addiction and dependence are components of a substance use disorder. Complications may include opioid overdose, suicide, HIV/AIDS, hepatitis C, and problems at school, work, or home.

If a person is appropriately taking opioids for a medical condition, issues of tolerance and withdrawal do not apply.

Epidemiology

Opioid use disorders affect over 16 million people worldwide, over 2.1 million in the United States, and there are over 120,000 deaths worldwide annually attributed to opioids.

Over 16 million people worldwide are opioid-dependent and would meet the criteria for opioid use disorder, three million in the United States alone. Opioid use disorder results in over 120,000 and 47,000 deaths per year worldwide and in the United States, respectively. Opioid-related death is the most lethal drug epidemic in American history. According to the CDC, the age-adjusted drug poisoning death rate involving opioid analgesics increased to 7.0 per 100,000 in 2015. Substance abuse is widespread, with over 20 million suffering from substance use disorder, including alcohol, methamphetamines, and opioids. Nearly 10% of the United States population over the age of 12 has used an illicit drug in the prior month. Of the 20 million Americans with substance abuse, two million are using prescription opioid pain medications, and 500 thousand use heroin. Recreational use of opioids was at its highest in 2010 and has gradually decreased as the opioid epidemic has gained attention in the United States. Up to 50% of patients on chronic opioid therapy meet the criteria for opioid use disorder.

The prevalence of opioid use and dependency varies by age and gender. Men are more likely to use opioids, become dependent on various opioids, and account for the majority of opioid-related overdoses, although women are prescribed opioids more often than men, and in recent years, women are abusing opioids in record numbers. Studies show that overdose deaths from synthetic opioids in women between ages 30 and 64 have increased 1643%. In 2017, the age‐adjusted death rate from drug overdoses involving opioids (per 100,000) was 6.1 for men and 4.2 for women.[6]

Deaths due to opioid use tend to skew at older ages with overdoses from opioids highest among individuals between the ages of 40 and 50. Yet, heroin overdoses peak between the ages of 20 and 30. The peak age of treatment for opioid use disorder is between 20- and 35-year-olds. Patients diagnosed with an opioid-use disorder are more likely to encounter legal problems related to their drug use if they have previous criminal records and high impulsivity.

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This video explains the struggles of opioid use and how it may lead to a disorder.

You can view the transcript for “Signs of Opioid Use Disorder” here (opens in new window).

Etiology

The etiology of opiate use disorder is multifaceted. Dependence and substance abuse is a product of biological, environmental, genetic, and psychosocial factors. Opioids, including prescription analgesics, derive from the poppy plant. Clinicians prescribe various opioids to control pain, decrease cough, or relieve diarrhea. Opioid-use disorders occur in individuals from all educational and socioeconomic backgrounds. There is a biological base of addiction. Patients can be deficient in neurotransmitters, such as dopamine, making them more likely to seek external sources of endorphins. In an attempt to self-correct this deficit, some individuals may turn to opioids. Separately, a patient with first-degree relatives who have a substance abuse disorder is more likely to develop an opiate use disorder. There is an estimated 50% heritability for opioid use disorder.

When patients diagnosed with opioid use disorder are exposed to an environment that includes opioid use, they may be more likely to develop substance abuse disorder. Environmental influence on opioid use may be secondary to peer relationships or be from a physician’s prescription for a previous injury. Patients with a history of depression, post-traumatic stress disorder (PTSD), or anxiety are more likely to suffer from substance abuse, as well as patients with histories of childhood trauma and abuse. Opioid dependence includes physical or psychological dependence or both. The majority of opioids in use are prescribed, but many are obtained illegally. According to the CDC, there were more than 191 million opioid prescriptions prescribed from 2012 to 2017.

Genetics may also play a role in the development of opioid use disorder. Mu, delta, and kappa are the three different principal receptors for opioids. Mu acts in the brain by decreasing the release of neurotransmitters. Research has demonstrated a genetic basis in the treatment of pain for opioid use disorder. There are no specific pharmacogenomic dosing recommendations, as there is no clear evidence connecting genotype to drug effect, toxicity, or dependence.

Treatment

Individuals with an opioid use disorder are often treated with opioid replacement therapy using methadone or buprenorphine. Being on such treatment reduces the risk of death. Additionally, individuals 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 goal of therapy is to minimize drug-use relapse. The combination of education, motivational enhancement, and self-help groups helps patients change how they think about the ways that opioids affect their lives. Group therapy helps maintain self-control and restraint for patients with substance abuse disorder. Group therapy is cost-effective in comparison to individualized therapy in the treatment of substance abuse.

CBT is most effective if combined with medications; however, there are mixed results on its effectiveness. Education about dealing with pain syndromes and minimizing opioid use can help build rapport and create realistic treatment goals. There is also the need to warn patients to avoid misuse of other drugs, which enhance the effects of opioids such as benzodiazepines, to help prevent overdose. Opioid replacement, maintenance, or substitution therapy involves replacing an opioid with a longer-acting but less euphoric and addicting opioid. The commonly used drugs are buprenorphine and methadone prescribed and given under medical supervision.

Methadone, an oral mu agonist, has been widely used and studied worldwide, and methadone maintenance is a well-established approach in treating opioid use disorder. The advantages of methadone treatment include blocking euphoric effects, decreasing narcotic craving, and reducing the transmission of infectious diseases. Methadone maintenance is non-sedating and is medically safe, provided there is no concomitant use of other prescription or illicit drugs. The maintenance phase begins approximately six weeks after the initiation of therapy. The length of the maintenance phase can last years to an entire lifetime. Tapering off methadone can take weeks or months, depending on the patient’s opioid dependence.

An alternative oral, long-acting opioid is buprenorphine for maintenance therapy. Buprenorphine treatment reduces morbidity and mortality. The recommended for buprenorphine is the minimum treatment of 12 months, although, as with methadone, risks of relapse and overdose increase following discontinuation of buprenorphine.

Key Takeaways: Opioid Use Disorder

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Sedative-Hypnotic- or Anxiolytic-Related Disorders

Just as with the opioid use disorders and others we have learned about thus far, another category of drug use that may lead to mental illness or addiction include sedative, hypnotic, or anxiolytic-related drugs. The DSM-5 categorizes these as either sedative, hypnotic, or anxiolytic use disorder; sedative, hypnotic, or anxiolytic intoxication; sedative, hypnotic, or anxiolytic withdrawal; or another sedative-, hypnotic-, or anxiolytic-induced mental disorder. Hypnotic (from Greek Hypnos, sleep), or soporific drugs, commonly known as sleeping pills, are a class of psychoactive drugs whose primary function is to induce sleep and for the treatment of insomnia (sleeplessness), or for surgical anesthesia. This group is related to sedatives. Whereas the term sedative describes drugs that serve to calm or relieve anxiety, the term hypnotic generally describes drugs whose main purpose is to initiate, sustain, or lengthen sleep. Because these two functions frequently overlap, and because drugs in this class generally produce dose-dependent effects (ranging from anxiolysis to loss of consciousness), they are often referred to collectively as sedative-hypnotic drugs. Anxiolytic drugs are those used to reduce and treat anxiety, such as benzodiazepines like Xanax or Valium.

It is also important to understand the paradoxical effects of some sedative drugs. Serious complications can occur in conjunction with the use of sedatives, creating the opposite effect as to that intended. Malcolm Lader at the Institute of Psychiatry in London estimates the incidence of these adverse reactions at about 5%, even in short-term use of the drugs.[7] The paradoxical reactions may consist of depression, with or without suicidal tendencies, phobias, aggressiveness, violent behavior, and symptoms sometimes misdiagnosed as psychosis. However, psychosis is more commonly related to benzodiazepine withdrawal syndrome.

Hypnotic drugs are regularly prescribed for insomnia and other sleep disorders, with over 95% of insomnia patients being prescribed hypnotics in some countries. Many hypnotic drugs are habit-forming and, due to many factors known to disturb the human sleep pattern, a physician may instead recommend changes in the environment before and during sleep, better sleep hygiene, the avoidance of caffeine or other stimulating substances, or behavioral interventions such as CBT for insomnia (CBT-I) before prescribing medication for sleep. When prescribed, hypnotic medication should be used for the shortest period of time necessary.

Among individuals with sleep disorders, 13.7% are taking or prescribed nonbenzodiazepines, while 10.8% are taking benzodiazepines, as of 2010, in the USA. Early classes of drugs, such as barbituates, have fallen out of use in most practices but are still prescribed for some patients. In children, prescribing hypnotics is not yet acceptable unless used to treat night terrors or sleepwalking.

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In this video, psychiatrist Anna Lembke talks about the difficulties some of her patients have in stopping their dependence on benzodiazepines.

You can view the transcript for “Benzodiazepine Withdrawal Difficulties: Stanford Psychiatrist Anna Lembke, M.D.” here (opens in new window).

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Glossary

anxiolytic: drugs used to reduce and treat anxiety

codeine: opiate with relatively low potency often prescribed for minor pain

hypnotic: describes drugs whose main purpose is to initiate, sustain, or lengthen sleep

methadone: synthetic opioid that is less euphorogenic than heroin and similar drugs; used to manage withdrawal symptoms in opiate users

methadone clinic: uses methadone to treat withdrawal symptoms in opiate users

methamphetamine: type of amphetamine that can be made from pseudoephedrine, an over-the-counter drug; widely manufactured and abused

opiate/opioid: one of a category of drugs that has strong analgesic properties; opiates are produced from the resin of the opium poppy; includes heroin, morphine, methadone, and codeine

sedative: drugs that serve to calm or relieve anxiety

  1. Fentanyl As A Dark Web Profit Center, From Chinese Labs To U.S. Streets", KUAR, NPR Radio News, Sept. 4, 2019 ↵
  2. Prescription Opioid Data". Centers for Disease Control and Prevention (CDC). Retrieved November 2, 2018. ↵
  3. Shipton EA, Shipton EE, Shipton AJ (June 2018). "A Review of the Opioid Epidemic: What Do We Do About It?". Pain and Therapy. 7 (1): 23–36. ↵
  4. Pergolizzi JV, LeQuang JA, Taylor R, Raffa RB (January 2018). "Going beyond prescription pain relievers to understand the opioid epidemic: the role of illicit fentanyl, new psychoactive substances, and street heroin". Postgraduate Medicine. 130 (1): 1–8. ↵
  5. Barbosa‐Leiker, Celestina, Aimee N. C. Campbell, R. Kathryn McHugh, Constance Guille, and Shelly F. Greenfield. “Opioid Use Disorder in Women and the Implications for Treatment.” Psychiatric Research and Clinical Practice, October 13, 2020, n/a-n/a. https://doi.org/10.1176/appi.prcp.20190051. ↵
  6. Barbosa‐Leiker, Celestina, Aimee N. C. Campbell, R. Kathryn McHugh, Constance Guille, and Shelly F. Greenfield. “Opioid Use Disorder in Women and the Implications for Treatment.” Psychiatric Research and Clinical Practice, October 13, 2020, n/a-n/a. https://doi.org/10.1176/appi.prcp.20190051. ↵
  7. Lader M, Morton S (1991). "Benzodiazepine Problems". British Journal of Addiction. 86 (7): 823–828. doi:10.1111/j.1360-0443.1991.tb01831.x. PMID 1680514. ↵