The current drug crisis, which has continued to escalate during the COVID-19 pandemic and now sur... more The current drug crisis, which has continued to escalate during the COVID-19 pandemic and now surpasses 100 000 overdose deaths annually, 1 demands solutions that cut across health care and other sectors of society. Besides the urgent need for greater implementation of effective treatments, there is a need for more widespread evidence-based prevention interventions. Especially needed are interventions that could delay youth from experimenting with drugs and help prevent the transition from occasional drug use to addiction in adolescents and young adults. Routine screening by clinicians could identify those who would benefit from early interventions.
The evolving US opioid crisis is complex and requires myriad different interventions. These inclu... more The evolving US opioid crisis is complex and requires myriad different interventions. These include reducing opioid overprescribing and curtailing the supply of illicit opioids, overdose rescue interventions, and treatment and recovery support services for those with opioid use disorders. To date, more distal primary prevention strategies that have an evidence base are underutilized. Yet, the impact of early environments on later substance use disorder risk is increasingly well understood, including knowledge of the mechanistic linkages between brain development and subsequent risk behaviors. Applying this developmental framework to prevention shows promise, and some middle-school interventions have demonstrated significant reductions in prescription opioid misuse. Reducing these risks of initial misuse of opioids may be the “ounce of prevention” that makes a substantial difference in a society now reeling from the worst drug crisis our country has seen. The challenge is to continue...
The current drug crisis, which has continued to escalate during the COVID-19 pandemic and now sur... more The current drug crisis, which has continued to escalate during the COVID-19 pandemic and now surpasses 100 000 overdose deaths annually, 1 demands solutions that cut across health care and other sectors of society. Besides the urgent need for greater implementation of effective treatments, there is a need for more widespread evidence-based prevention interventions. Especially needed are interventions that could delay youth from experimenting with drugs and help prevent the transition from occasional drug use to addiction in adolescents and young adults. Routine screening by clinicians could identify those who would benefit from early interventions.
The evolving US opioid crisis is complex and requires myriad different interventions. These inclu... more The evolving US opioid crisis is complex and requires myriad different interventions. These include reducing opioid overprescribing and curtailing the supply of illicit opioids, overdose rescue interventions, and treatment and recovery support services for those with opioid use disorders. To date, more distal primary prevention strategies that have an evidence base are underutilized. Yet, the impact of early environments on later substance use disorder risk is increasingly well understood, including knowledge of the mechanistic linkages between brain development and subsequent risk behaviors. Applying this developmental framework to prevention shows promise, and some middle-school interventions have demonstrated significant reductions in prescription opioid misuse. Reducing these risks of initial misuse of opioids may be the “ounce of prevention” that makes a substantial difference in a society now reeling from the worst drug crisis our country has seen. The challenge is to continue...
ore than 2 million Americans have an opioid use disorder (OUD), and in 2016, more than 42 000 Ame... more ore than 2 million Americans have an opioid use disorder (OUD), and in 2016, more than 42 000 Americans died of opioid overdoses. 1,2 Although in the first years of the opioid crisis, most overdose-associated deaths were caused by misuse of prescription analgesics, heroin and synthetic opioids (fentanyl and its analogues) currently account for most of the fatalities, a scenario that reflects the changing nature of the opioid crisis (Figure 1). We reviewed the pharmacology of opioids because it is relevant to their rewarding and analgesic effects that lead to their misuse, the epidemiology of the crisis and its transformations in the past 2 decades, and the interventions to treat and prevent OUD that must be implemented to overcome the current crisis and prevent it from happening again. Opioid Pharmacology Opioid drugs-prescription analgesics and illicit drugs-exert their pharmacologic effects by engaging the endogenous opioid system, where they act as agonists at the μ-opioid receptor (MOR). The agonist action at the MOR is responsible for the rewarding effects of opioids and analgesia. In the brain, these receptors are highly concentrated in regions that are part of the pain and reward networks. They are also located in regions that regulate emotions, which is why long-term opioid exposure is frequently associated with depression and anxiety. 4 In addition, MORs are located in brainstem regions that regulate breathing; there, IMPORTANCE More than 42 000 Americans died of opioid overdoses in 2016, and the fatalities continue to increase. This review analyzes the factors that triggered the opioid crisis and its further evolution, along with the interventions to manage and prevent opioid use disorder (OUD), which are fundamental for curtailing the opioid crisis. OBSERVATIONS Opioid drugs are among the most powerful analgesics but also among the most addictive. The current opioid crisis, initially triggered by overprescription of opioid analgesics, which facilitated their diversion and misuse, has now expanded to heroin and illicit synthetic opioids (fentanyl and its analogues), the potency of which further increases their addictiveness and lethality. Although there are effective medications to treat OUD (methadone hydrochloride, buprenorphine, and naltrexone hydrochloride), these medications are underused, and the risk of relapse is still high. Strategies to expand medication use and treatment retention include greater involvement of health care professionals (including psychiatrists) and approaches to address comorbidities. In particular, the high prevalence of depression and suicidality among patients with OUD, if untreated, contributes to relapse and increases the risk of overdose fatalities. Prevention interventions include screening and early detection of psychiatric disorders, which increase the risk of substance use disorders, including OUD. CONCLUSIONS AND RELEVANCE Although overprescription of opioid medications triggered the opioid crisis, improving opioid prescription practices for pain management, although important for addressing the opioid crisis, is no longer sufficient. In parallel, strategies to expand access to medication for OUD and improve treatment retention, including a more active involvement of psychiatrists who are optimally trained to address psychiatric comorbidities, are fundamental to preventing fatalities and achieving recovery. Research into new treatments for OUD, models of care for OUD management that include health care, and interventions to prevent OUD may further help resolve the opioid crisis and prevent it from happening again.
ore than 2 million Americans have an opioid use disorder (OUD), and in 2016, more than 42 000 Ame... more ore than 2 million Americans have an opioid use disorder (OUD), and in 2016, more than 42 000 Americans died of opioid overdoses. 1,2 Although in the first years of the opioid crisis, most overdose-associated deaths were caused by misuse of prescription analgesics, heroin and synthetic opioids (fentanyl and its analogues) currently account for most of the fatalities, a scenario that reflects the changing nature of the opioid crisis (Figure 1). We reviewed the pharmacology of opioids because it is relevant to their rewarding and analgesic effects that lead to their misuse, the epidemiology of the crisis and its transformations in the past 2 decades, and the interventions to treat and prevent OUD that must be implemented to overcome the current crisis and prevent it from happening again. Opioid Pharmacology Opioid drugs-prescription analgesics and illicit drugs-exert their pharmacologic effects by engaging the endogenous opioid system, where they act as agonists at the μ-opioid receptor (MOR). The agonist action at the MOR is responsible for the rewarding effects of opioids and analgesia. In the brain, these receptors are highly concentrated in regions that are part of the pain and reward networks. They are also located in regions that regulate emotions, which is why long-term opioid exposure is frequently associated with depression and anxiety. 4 In addition, MORs are located in brainstem regions that regulate breathing; there, IMPORTANCE More than 42 000 Americans died of opioid overdoses in 2016, and the fatalities continue to increase. This review analyzes the factors that triggered the opioid crisis and its further evolution, along with the interventions to manage and prevent opioid use disorder (OUD), which are fundamental for curtailing the opioid crisis. OBSERVATIONS Opioid drugs are among the most powerful analgesics but also among the most addictive. The current opioid crisis, initially triggered by overprescription of opioid analgesics, which facilitated their diversion and misuse, has now expanded to heroin and illicit synthetic opioids (fentanyl and its analogues), the potency of which further increases their addictiveness and lethality. Although there are effective medications to treat OUD (methadone hydrochloride, buprenorphine, and naltrexone hydrochloride), these medications are underused, and the risk of relapse is still high. Strategies to expand medication use and treatment retention include greater involvement of health care professionals (including psychiatrists) and approaches to address comorbidities. In particular, the high prevalence of depression and suicidality among patients with OUD, if untreated, contributes to relapse and increases the risk of overdose fatalities. Prevention interventions include screening and early detection of psychiatric disorders, which increase the risk of substance use disorders, including OUD. CONCLUSIONS AND RELEVANCE Although overprescription of opioid medications triggered the opioid crisis, improving opioid prescription practices for pain management, although important for addressing the opioid crisis, is no longer sufficient. In parallel, strategies to expand access to medication for OUD and improve treatment retention, including a more active involvement of psychiatrists who are optimally trained to address psychiatric comorbidities, are fundamental to preventing fatalities and achieving recovery. Research into new treatments for OUD, models of care for OUD management that include health care, and interventions to prevent OUD may further help resolve the opioid crisis and prevent it from happening again.
In 2016, 42249 Americans fatally overdosed on an opioid (1). Although prescribing of opioid analg... more In 2016, 42249 Americans fatally overdosed on an opioid (1). Although prescribing of opioid analgesics has declined thanks to greater awareness and new guidelines, increasing numbers of individuals are initiating opioid use with heroin, and nearly half of the fatal opioid overdoses in 2016 involved fentanyl and synthetic analogues. Expanding access to medications for opioid use disorder (OUD) is essential if we are to reverse these trends. The opioid agonist methadone, the partial agonist buprenorphine, and the antagonist naltrexone in its extended-release formulation have been repeatedly shown to reduce opioid use and its health consequences, including overdose, compared with behavioral therapy alone or no treatment (24). Methadone and buprenorphine (the oldest and most thoroughly studied medications) have also been shown to improve social functioning; reduce other medical complications associated with OUD, such as infectious disease transmission; and reduce criminality. Despite this evidence, fewer than half of persons with an OUD receive medication for it, and the average treatment lasts less than 6 months. The study by Larochelle and colleagues (5) (which is, to our knowledge, the first prospective cohort study of patients enrolled from an emergency department who had had a nonfatal opioid overdose) further solidifies the evidence of the benefits of methadone and buprenorphine in preventing opioid-related deaths. The authors looked at mortality and medication-assisted treatment (MAT) use or nonuse among 17568 opioid overdose survivors over 12 months after overdose. Both methadone and buprenorphine were associated with significant reductions in opioid-related and all-cause mortality (5). No association was found for treatment with naltrexone, although this might reflect the limited number of participants who received it. This study also highlights the gross underuse of these effective medications. All persons in the study population had a history of overdose, which is a recognized risk factor for future overdoses. However, just 30% (n = 5273) received any medication for OUD in the year after overdose: 11% received methadone for a median of 5 months, 17% buprenorphine for a median of 4 months, and 6% naltrexone for a median of 1 month (these tallies were not mutually exclusive because 5% of the sample received more than 1 medication). This number is consistent with the OUD treatment gap shown by national data. According to the Treatment Episode Data Set maintained by the Substance Abuse and Mental Health Services Administration, 37% of patients treated in specialty facilities for a heroin use disorder and 31% for a nonheroin OUD had treatment plans that included MAT in 2015 (6). The number is also consistent with the low treatment retention rates reported in the Treatment Episode Data Set: Approximately 50% of patients who start MAT for OUD interrupt it within the first 6 months. This highlights the need for interventions to facilitate treatment retention. Larochelle and colleagues' results are also alarming because, although participants met criteria for OUD and had had an overdose, many were subsequently given prescriptions for opioids (34%) or benzodiazepines (26%) in the 12 months after the overdose. This indicates that guidelines cautioning against prescription opioids and their co-use with benzodiazepines are not being followed. Overall, the findings identify major deficiencies in OUD treatment, including underuse of MAT and a fracture in the engagement of health care on how to manage OUD. Stigma is a root reason for both. Despite increased integration of the opioid treatment system with the rest of health care (thanks to health care reform), policy and infrastructural factors continue to impede MAT uptake. Treatment facilities often lack medical personnel who can prescribe medications; even if staff at opioid treatment programs are able to dispense methadone, they may not be waivered to prescribe buprenorphine. In addition, insurers may not cover all forms of MAT, and when they do, coverage is usually subjected to limits on duration that lessen treatment effectiveness. Receiving an agonist medication for maintenance is pharmacodynamically distinct from sustaining an addiction to prescription analgesics or illicit opioids (7), yet misperceptions that methadone and buprenorphine substitute a new addiction for an old one persist. Where maintenance medications are used, they are often prescribed for too short a time or at too low a dose. According to the Substance Abuse and Mental Health Services Administration, nearly half of patients receiving buprenorphine in opioid treatment facilities receive 90 days or fewer of continuous treatment with this medication (8), indicating that many providers are not following evidence-based practices. Several strategies might increase MAT delivery to those at risk for opioid overdose, including initiating buprenorphine therapy in the emergency department for…
In 2016, 42249 Americans fatally overdosed on an opioid (1). Although prescribing of opioid analg... more In 2016, 42249 Americans fatally overdosed on an opioid (1). Although prescribing of opioid analgesics has declined thanks to greater awareness and new guidelines, increasing numbers of individuals are initiating opioid use with heroin, and nearly half of the fatal opioid overdoses in 2016 involved fentanyl and synthetic analogues. Expanding access to medications for opioid use disorder (OUD) is essential if we are to reverse these trends. The opioid agonist methadone, the partial agonist buprenorphine, and the antagonist naltrexone in its extended-release formulation have been repeatedly shown to reduce opioid use and its health consequences, including overdose, compared with behavioral therapy alone or no treatment (24). Methadone and buprenorphine (the oldest and most thoroughly studied medications) have also been shown to improve social functioning; reduce other medical complications associated with OUD, such as infectious disease transmission; and reduce criminality. Despite this evidence, fewer than half of persons with an OUD receive medication for it, and the average treatment lasts less than 6 months. The study by Larochelle and colleagues (5) (which is, to our knowledge, the first prospective cohort study of patients enrolled from an emergency department who had had a nonfatal opioid overdose) further solidifies the evidence of the benefits of methadone and buprenorphine in preventing opioid-related deaths. The authors looked at mortality and medication-assisted treatment (MAT) use or nonuse among 17568 opioid overdose survivors over 12 months after overdose. Both methadone and buprenorphine were associated with significant reductions in opioid-related and all-cause mortality (5). No association was found for treatment with naltrexone, although this might reflect the limited number of participants who received it. This study also highlights the gross underuse of these effective medications. All persons in the study population had a history of overdose, which is a recognized risk factor for future overdoses. However, just 30% (n = 5273) received any medication for OUD in the year after overdose: 11% received methadone for a median of 5 months, 17% buprenorphine for a median of 4 months, and 6% naltrexone for a median of 1 month (these tallies were not mutually exclusive because 5% of the sample received more than 1 medication). This number is consistent with the OUD treatment gap shown by national data. According to the Treatment Episode Data Set maintained by the Substance Abuse and Mental Health Services Administration, 37% of patients treated in specialty facilities for a heroin use disorder and 31% for a nonheroin OUD had treatment plans that included MAT in 2015 (6). The number is also consistent with the low treatment retention rates reported in the Treatment Episode Data Set: Approximately 50% of patients who start MAT for OUD interrupt it within the first 6 months. This highlights the need for interventions to facilitate treatment retention. Larochelle and colleagues' results are also alarming because, although participants met criteria for OUD and had had an overdose, many were subsequently given prescriptions for opioids (34%) or benzodiazepines (26%) in the 12 months after the overdose. This indicates that guidelines cautioning against prescription opioids and their co-use with benzodiazepines are not being followed. Overall, the findings identify major deficiencies in OUD treatment, including underuse of MAT and a fracture in the engagement of health care on how to manage OUD. Stigma is a root reason for both. Despite increased integration of the opioid treatment system with the rest of health care (thanks to health care reform), policy and infrastructural factors continue to impede MAT uptake. Treatment facilities often lack medical personnel who can prescribe medications; even if staff at opioid treatment programs are able to dispense methadone, they may not be waivered to prescribe buprenorphine. In addition, insurers may not cover all forms of MAT, and when they do, coverage is usually subjected to limits on duration that lessen treatment effectiveness. Receiving an agonist medication for maintenance is pharmacodynamically distinct from sustaining an addiction to prescription analgesics or illicit opioids (7), yet misperceptions that methadone and buprenorphine substitute a new addiction for an old one persist. Where maintenance medications are used, they are often prescribed for too short a time or at too low a dose. According to the Substance Abuse and Mental Health Services Administration, nearly half of patients receiving buprenorphine in opioid treatment facilities receive 90 days or fewer of continuous treatment with this medication (8), indicating that many providers are not following evidence-based practices. Several strategies might increase MAT delivery to those at risk for opioid overdose, including initiating buprenorphine therapy in the emergency department for…
Developmental cognitive neuroscience, Jan 10, 2017
Adolescence is a time of dramatic changes in brain structure and function, and the adolescent bra... more Adolescence is a time of dramatic changes in brain structure and function, and the adolescent brain is highly susceptible to being altered by experiences like substance use. However, there is much we have yet to learn about how these experiences influence brain development, how they promote or interfere with later health outcomes, or even what healthy brain development looks like. A large longitudinal study beginning in early adolescence could help us understand the normal variability in adolescent brain and cognitive development and tease apart the many factors that influence it. Recent advances in neuroimaging, informatics, and genetics technologies have made it feasible to conduct a study of sufficient size and scope to answer many outstanding questions. At the same time, several Institutes across the NIH recognized the value of collaborating in such a project because of its ability to address the role of biological, environmental, and behavioral factors like gender, pubertal hor...
Developmental cognitive neuroscience, Jan 10, 2017
Adolescence is a time of dramatic changes in brain structure and function, and the adolescent bra... more Adolescence is a time of dramatic changes in brain structure and function, and the adolescent brain is highly susceptible to being altered by experiences like substance use. However, there is much we have yet to learn about how these experiences influence brain development, how they promote or interfere with later health outcomes, or even what healthy brain development looks like. A large longitudinal study beginning in early adolescence could help us understand the normal variability in adolescent brain and cognitive development and tease apart the many factors that influence it. Recent advances in neuroimaging, informatics, and genetics technologies have made it feasible to conduct a study of sufficient size and scope to answer many outstanding questions. At the same time, several Institutes across the NIH recognized the value of collaborating in such a project because of its ability to address the role of biological, environmental, and behavioral factors like gender, pubertal hor...
Science needs to drive our thinking as we navigate a new legislative environment in which many Am... more Science needs to drive our thinking as we navigate a new legislative environment in which many Americans have access to marijuana for therapeutic or recreational use. With the responsibility to fund, conduct, and make use of the research on marijuana, and understand the impacts of new policies, comes the obligation of not thinking in simplistic, black-and-white terms about this substance. The drug's unique harms include neurodevelopmental impacts that may be long lasting or permanent, yet some evidence suggests the drug may benefit people with certain medical conditions (e.g., chronic pain). Marijuana use is also entangled with other substance use and should not be considered in isolation. Finally, policy options are not limited to the extremes of prohibition vs. full commercialization; a spectrum of intermediate options can and should be considered and evaluated as states create new policies around this drug.
Adolescence, as every teenager, parent, and youth professional knows, is a time of risks. With gr... more Adolescence, as every teenager, parent, and youth professional knows, is a time of risks. With greater freedom and independence, young people face new choices involving automobiles, addictive substances, and sexuality-frequently in combination. Poor choices about these risks can have terrible consequences for individuals, families, and society as a whole. The statistics are frightening, but they are not unknown to young people. For decades, adolescents have been bombarded by facts about the risks they face. Yet efforts to scare young decision makers with numbers and percentages have met with limited success (Reyna & Farley, 2006). There is even evidence that some risk-awareness-raising programs, such as DARE, actually increase the behaviors they are designed to prevent (see Lilienfeld, 2007). To reduce adolescent risk taking, a different approach is needed: one that recognizes how adolescents reason.
Prescription opioid abuse and addiction, along with consequences such as overdose death and incre... more Prescription opioid abuse and addiction, along with consequences such as overdose death and increasing transition to heroin use, constitute a devastating public health problem in the United States. Increasingly it is clear that overprescription of these medications over the past two decades has been a major upstream driver of the opioid abuse epidemic. This commentary considers the factors that have led to overprescription of opioids by clinicians, discusses recent evidence casting doubt on the efficacy of opioids for treating chronic pain, and describes the ongoing efforts by federal and community stakeholders to address this epidemic. For example, supporting prescription drug monitoring programs and improved clinician training in pain management to help reduce the supply of opioids, increasing dissemination of evidence-based primary prevention programs to reduce demand for opioids, and expanding access to effective opioid agonist therapies and antagonist medications for both treat...
The “biomechanoids” of the Swiss painter H. R. Giger (1940–2014) depict the sadomasochistic bonda... more The “biomechanoids” of the Swiss painter H. R. Giger (1940–2014) depict the sadomasochistic bondage of humans and machines. Although Giger’s art has commonly been interpreted in psychoanalytic terms as representing some past trauma connected with origins and birth, I argue that it also encodes a distinctly gnostic warning about the trajectory of consciousness in relation to technology, a “fall of spirit into matter” that may lie ahead of our species rather than behind. With the help of the endosymbiosis theory of biologist Lynn Margulis, I decode the dark warning transmission in Giger’s work, especially the iconic “Space Jockey” Giger designed for Ridley Scott’s 1979 blockbuster Alien—a fossilized star pilot fused to its ship. As a vision of the more disturbing possibilities of cyborgs or human-machine symbionts, the Space Jockey contrasts sharply with optimistic dreams of Singularities and “spiritual machines.” It suggests a posthuman future in which distinctly nonspiritual machine...
The current drug crisis, which has continued to escalate during the COVID-19 pandemic and now sur... more The current drug crisis, which has continued to escalate during the COVID-19 pandemic and now surpasses 100 000 overdose deaths annually, 1 demands solutions that cut across health care and other sectors of society. Besides the urgent need for greater implementation of effective treatments, there is a need for more widespread evidence-based prevention interventions. Especially needed are interventions that could delay youth from experimenting with drugs and help prevent the transition from occasional drug use to addiction in adolescents and young adults. Routine screening by clinicians could identify those who would benefit from early interventions.
The evolving US opioid crisis is complex and requires myriad different interventions. These inclu... more The evolving US opioid crisis is complex and requires myriad different interventions. These include reducing opioid overprescribing and curtailing the supply of illicit opioids, overdose rescue interventions, and treatment and recovery support services for those with opioid use disorders. To date, more distal primary prevention strategies that have an evidence base are underutilized. Yet, the impact of early environments on later substance use disorder risk is increasingly well understood, including knowledge of the mechanistic linkages between brain development and subsequent risk behaviors. Applying this developmental framework to prevention shows promise, and some middle-school interventions have demonstrated significant reductions in prescription opioid misuse. Reducing these risks of initial misuse of opioids may be the “ounce of prevention” that makes a substantial difference in a society now reeling from the worst drug crisis our country has seen. The challenge is to continue...
The current drug crisis, which has continued to escalate during the COVID-19 pandemic and now sur... more The current drug crisis, which has continued to escalate during the COVID-19 pandemic and now surpasses 100 000 overdose deaths annually, 1 demands solutions that cut across health care and other sectors of society. Besides the urgent need for greater implementation of effective treatments, there is a need for more widespread evidence-based prevention interventions. Especially needed are interventions that could delay youth from experimenting with drugs and help prevent the transition from occasional drug use to addiction in adolescents and young adults. Routine screening by clinicians could identify those who would benefit from early interventions.
The evolving US opioid crisis is complex and requires myriad different interventions. These inclu... more The evolving US opioid crisis is complex and requires myriad different interventions. These include reducing opioid overprescribing and curtailing the supply of illicit opioids, overdose rescue interventions, and treatment and recovery support services for those with opioid use disorders. To date, more distal primary prevention strategies that have an evidence base are underutilized. Yet, the impact of early environments on later substance use disorder risk is increasingly well understood, including knowledge of the mechanistic linkages between brain development and subsequent risk behaviors. Applying this developmental framework to prevention shows promise, and some middle-school interventions have demonstrated significant reductions in prescription opioid misuse. Reducing these risks of initial misuse of opioids may be the “ounce of prevention” that makes a substantial difference in a society now reeling from the worst drug crisis our country has seen. The challenge is to continue...
ore than 2 million Americans have an opioid use disorder (OUD), and in 2016, more than 42 000 Ame... more ore than 2 million Americans have an opioid use disorder (OUD), and in 2016, more than 42 000 Americans died of opioid overdoses. 1,2 Although in the first years of the opioid crisis, most overdose-associated deaths were caused by misuse of prescription analgesics, heroin and synthetic opioids (fentanyl and its analogues) currently account for most of the fatalities, a scenario that reflects the changing nature of the opioid crisis (Figure 1). We reviewed the pharmacology of opioids because it is relevant to their rewarding and analgesic effects that lead to their misuse, the epidemiology of the crisis and its transformations in the past 2 decades, and the interventions to treat and prevent OUD that must be implemented to overcome the current crisis and prevent it from happening again. Opioid Pharmacology Opioid drugs-prescription analgesics and illicit drugs-exert their pharmacologic effects by engaging the endogenous opioid system, where they act as agonists at the μ-opioid receptor (MOR). The agonist action at the MOR is responsible for the rewarding effects of opioids and analgesia. In the brain, these receptors are highly concentrated in regions that are part of the pain and reward networks. They are also located in regions that regulate emotions, which is why long-term opioid exposure is frequently associated with depression and anxiety. 4 In addition, MORs are located in brainstem regions that regulate breathing; there, IMPORTANCE More than 42 000 Americans died of opioid overdoses in 2016, and the fatalities continue to increase. This review analyzes the factors that triggered the opioid crisis and its further evolution, along with the interventions to manage and prevent opioid use disorder (OUD), which are fundamental for curtailing the opioid crisis. OBSERVATIONS Opioid drugs are among the most powerful analgesics but also among the most addictive. The current opioid crisis, initially triggered by overprescription of opioid analgesics, which facilitated their diversion and misuse, has now expanded to heroin and illicit synthetic opioids (fentanyl and its analogues), the potency of which further increases their addictiveness and lethality. Although there are effective medications to treat OUD (methadone hydrochloride, buprenorphine, and naltrexone hydrochloride), these medications are underused, and the risk of relapse is still high. Strategies to expand medication use and treatment retention include greater involvement of health care professionals (including psychiatrists) and approaches to address comorbidities. In particular, the high prevalence of depression and suicidality among patients with OUD, if untreated, contributes to relapse and increases the risk of overdose fatalities. Prevention interventions include screening and early detection of psychiatric disorders, which increase the risk of substance use disorders, including OUD. CONCLUSIONS AND RELEVANCE Although overprescription of opioid medications triggered the opioid crisis, improving opioid prescription practices for pain management, although important for addressing the opioid crisis, is no longer sufficient. In parallel, strategies to expand access to medication for OUD and improve treatment retention, including a more active involvement of psychiatrists who are optimally trained to address psychiatric comorbidities, are fundamental to preventing fatalities and achieving recovery. Research into new treatments for OUD, models of care for OUD management that include health care, and interventions to prevent OUD may further help resolve the opioid crisis and prevent it from happening again.
ore than 2 million Americans have an opioid use disorder (OUD), and in 2016, more than 42 000 Ame... more ore than 2 million Americans have an opioid use disorder (OUD), and in 2016, more than 42 000 Americans died of opioid overdoses. 1,2 Although in the first years of the opioid crisis, most overdose-associated deaths were caused by misuse of prescription analgesics, heroin and synthetic opioids (fentanyl and its analogues) currently account for most of the fatalities, a scenario that reflects the changing nature of the opioid crisis (Figure 1). We reviewed the pharmacology of opioids because it is relevant to their rewarding and analgesic effects that lead to their misuse, the epidemiology of the crisis and its transformations in the past 2 decades, and the interventions to treat and prevent OUD that must be implemented to overcome the current crisis and prevent it from happening again. Opioid Pharmacology Opioid drugs-prescription analgesics and illicit drugs-exert their pharmacologic effects by engaging the endogenous opioid system, where they act as agonists at the μ-opioid receptor (MOR). The agonist action at the MOR is responsible for the rewarding effects of opioids and analgesia. In the brain, these receptors are highly concentrated in regions that are part of the pain and reward networks. They are also located in regions that regulate emotions, which is why long-term opioid exposure is frequently associated with depression and anxiety. 4 In addition, MORs are located in brainstem regions that regulate breathing; there, IMPORTANCE More than 42 000 Americans died of opioid overdoses in 2016, and the fatalities continue to increase. This review analyzes the factors that triggered the opioid crisis and its further evolution, along with the interventions to manage and prevent opioid use disorder (OUD), which are fundamental for curtailing the opioid crisis. OBSERVATIONS Opioid drugs are among the most powerful analgesics but also among the most addictive. The current opioid crisis, initially triggered by overprescription of opioid analgesics, which facilitated their diversion and misuse, has now expanded to heroin and illicit synthetic opioids (fentanyl and its analogues), the potency of which further increases their addictiveness and lethality. Although there are effective medications to treat OUD (methadone hydrochloride, buprenorphine, and naltrexone hydrochloride), these medications are underused, and the risk of relapse is still high. Strategies to expand medication use and treatment retention include greater involvement of health care professionals (including psychiatrists) and approaches to address comorbidities. In particular, the high prevalence of depression and suicidality among patients with OUD, if untreated, contributes to relapse and increases the risk of overdose fatalities. Prevention interventions include screening and early detection of psychiatric disorders, which increase the risk of substance use disorders, including OUD. CONCLUSIONS AND RELEVANCE Although overprescription of opioid medications triggered the opioid crisis, improving opioid prescription practices for pain management, although important for addressing the opioid crisis, is no longer sufficient. In parallel, strategies to expand access to medication for OUD and improve treatment retention, including a more active involvement of psychiatrists who are optimally trained to address psychiatric comorbidities, are fundamental to preventing fatalities and achieving recovery. Research into new treatments for OUD, models of care for OUD management that include health care, and interventions to prevent OUD may further help resolve the opioid crisis and prevent it from happening again.
In 2016, 42249 Americans fatally overdosed on an opioid (1). Although prescribing of opioid analg... more In 2016, 42249 Americans fatally overdosed on an opioid (1). Although prescribing of opioid analgesics has declined thanks to greater awareness and new guidelines, increasing numbers of individuals are initiating opioid use with heroin, and nearly half of the fatal opioid overdoses in 2016 involved fentanyl and synthetic analogues. Expanding access to medications for opioid use disorder (OUD) is essential if we are to reverse these trends. The opioid agonist methadone, the partial agonist buprenorphine, and the antagonist naltrexone in its extended-release formulation have been repeatedly shown to reduce opioid use and its health consequences, including overdose, compared with behavioral therapy alone or no treatment (24). Methadone and buprenorphine (the oldest and most thoroughly studied medications) have also been shown to improve social functioning; reduce other medical complications associated with OUD, such as infectious disease transmission; and reduce criminality. Despite this evidence, fewer than half of persons with an OUD receive medication for it, and the average treatment lasts less than 6 months. The study by Larochelle and colleagues (5) (which is, to our knowledge, the first prospective cohort study of patients enrolled from an emergency department who had had a nonfatal opioid overdose) further solidifies the evidence of the benefits of methadone and buprenorphine in preventing opioid-related deaths. The authors looked at mortality and medication-assisted treatment (MAT) use or nonuse among 17568 opioid overdose survivors over 12 months after overdose. Both methadone and buprenorphine were associated with significant reductions in opioid-related and all-cause mortality (5). No association was found for treatment with naltrexone, although this might reflect the limited number of participants who received it. This study also highlights the gross underuse of these effective medications. All persons in the study population had a history of overdose, which is a recognized risk factor for future overdoses. However, just 30% (n = 5273) received any medication for OUD in the year after overdose: 11% received methadone for a median of 5 months, 17% buprenorphine for a median of 4 months, and 6% naltrexone for a median of 1 month (these tallies were not mutually exclusive because 5% of the sample received more than 1 medication). This number is consistent with the OUD treatment gap shown by national data. According to the Treatment Episode Data Set maintained by the Substance Abuse and Mental Health Services Administration, 37% of patients treated in specialty facilities for a heroin use disorder and 31% for a nonheroin OUD had treatment plans that included MAT in 2015 (6). The number is also consistent with the low treatment retention rates reported in the Treatment Episode Data Set: Approximately 50% of patients who start MAT for OUD interrupt it within the first 6 months. This highlights the need for interventions to facilitate treatment retention. Larochelle and colleagues' results are also alarming because, although participants met criteria for OUD and had had an overdose, many were subsequently given prescriptions for opioids (34%) or benzodiazepines (26%) in the 12 months after the overdose. This indicates that guidelines cautioning against prescription opioids and their co-use with benzodiazepines are not being followed. Overall, the findings identify major deficiencies in OUD treatment, including underuse of MAT and a fracture in the engagement of health care on how to manage OUD. Stigma is a root reason for both. Despite increased integration of the opioid treatment system with the rest of health care (thanks to health care reform), policy and infrastructural factors continue to impede MAT uptake. Treatment facilities often lack medical personnel who can prescribe medications; even if staff at opioid treatment programs are able to dispense methadone, they may not be waivered to prescribe buprenorphine. In addition, insurers may not cover all forms of MAT, and when they do, coverage is usually subjected to limits on duration that lessen treatment effectiveness. Receiving an agonist medication for maintenance is pharmacodynamically distinct from sustaining an addiction to prescription analgesics or illicit opioids (7), yet misperceptions that methadone and buprenorphine substitute a new addiction for an old one persist. Where maintenance medications are used, they are often prescribed for too short a time or at too low a dose. According to the Substance Abuse and Mental Health Services Administration, nearly half of patients receiving buprenorphine in opioid treatment facilities receive 90 days or fewer of continuous treatment with this medication (8), indicating that many providers are not following evidence-based practices. Several strategies might increase MAT delivery to those at risk for opioid overdose, including initiating buprenorphine therapy in the emergency department for…
In 2016, 42249 Americans fatally overdosed on an opioid (1). Although prescribing of opioid analg... more In 2016, 42249 Americans fatally overdosed on an opioid (1). Although prescribing of opioid analgesics has declined thanks to greater awareness and new guidelines, increasing numbers of individuals are initiating opioid use with heroin, and nearly half of the fatal opioid overdoses in 2016 involved fentanyl and synthetic analogues. Expanding access to medications for opioid use disorder (OUD) is essential if we are to reverse these trends. The opioid agonist methadone, the partial agonist buprenorphine, and the antagonist naltrexone in its extended-release formulation have been repeatedly shown to reduce opioid use and its health consequences, including overdose, compared with behavioral therapy alone or no treatment (24). Methadone and buprenorphine (the oldest and most thoroughly studied medications) have also been shown to improve social functioning; reduce other medical complications associated with OUD, such as infectious disease transmission; and reduce criminality. Despite this evidence, fewer than half of persons with an OUD receive medication for it, and the average treatment lasts less than 6 months. The study by Larochelle and colleagues (5) (which is, to our knowledge, the first prospective cohort study of patients enrolled from an emergency department who had had a nonfatal opioid overdose) further solidifies the evidence of the benefits of methadone and buprenorphine in preventing opioid-related deaths. The authors looked at mortality and medication-assisted treatment (MAT) use or nonuse among 17568 opioid overdose survivors over 12 months after overdose. Both methadone and buprenorphine were associated with significant reductions in opioid-related and all-cause mortality (5). No association was found for treatment with naltrexone, although this might reflect the limited number of participants who received it. This study also highlights the gross underuse of these effective medications. All persons in the study population had a history of overdose, which is a recognized risk factor for future overdoses. However, just 30% (n = 5273) received any medication for OUD in the year after overdose: 11% received methadone for a median of 5 months, 17% buprenorphine for a median of 4 months, and 6% naltrexone for a median of 1 month (these tallies were not mutually exclusive because 5% of the sample received more than 1 medication). This number is consistent with the OUD treatment gap shown by national data. According to the Treatment Episode Data Set maintained by the Substance Abuse and Mental Health Services Administration, 37% of patients treated in specialty facilities for a heroin use disorder and 31% for a nonheroin OUD had treatment plans that included MAT in 2015 (6). The number is also consistent with the low treatment retention rates reported in the Treatment Episode Data Set: Approximately 50% of patients who start MAT for OUD interrupt it within the first 6 months. This highlights the need for interventions to facilitate treatment retention. Larochelle and colleagues' results are also alarming because, although participants met criteria for OUD and had had an overdose, many were subsequently given prescriptions for opioids (34%) or benzodiazepines (26%) in the 12 months after the overdose. This indicates that guidelines cautioning against prescription opioids and their co-use with benzodiazepines are not being followed. Overall, the findings identify major deficiencies in OUD treatment, including underuse of MAT and a fracture in the engagement of health care on how to manage OUD. Stigma is a root reason for both. Despite increased integration of the opioid treatment system with the rest of health care (thanks to health care reform), policy and infrastructural factors continue to impede MAT uptake. Treatment facilities often lack medical personnel who can prescribe medications; even if staff at opioid treatment programs are able to dispense methadone, they may not be waivered to prescribe buprenorphine. In addition, insurers may not cover all forms of MAT, and when they do, coverage is usually subjected to limits on duration that lessen treatment effectiveness. Receiving an agonist medication for maintenance is pharmacodynamically distinct from sustaining an addiction to prescription analgesics or illicit opioids (7), yet misperceptions that methadone and buprenorphine substitute a new addiction for an old one persist. Where maintenance medications are used, they are often prescribed for too short a time or at too low a dose. According to the Substance Abuse and Mental Health Services Administration, nearly half of patients receiving buprenorphine in opioid treatment facilities receive 90 days or fewer of continuous treatment with this medication (8), indicating that many providers are not following evidence-based practices. Several strategies might increase MAT delivery to those at risk for opioid overdose, including initiating buprenorphine therapy in the emergency department for…
Developmental cognitive neuroscience, Jan 10, 2017
Adolescence is a time of dramatic changes in brain structure and function, and the adolescent bra... more Adolescence is a time of dramatic changes in brain structure and function, and the adolescent brain is highly susceptible to being altered by experiences like substance use. However, there is much we have yet to learn about how these experiences influence brain development, how they promote or interfere with later health outcomes, or even what healthy brain development looks like. A large longitudinal study beginning in early adolescence could help us understand the normal variability in adolescent brain and cognitive development and tease apart the many factors that influence it. Recent advances in neuroimaging, informatics, and genetics technologies have made it feasible to conduct a study of sufficient size and scope to answer many outstanding questions. At the same time, several Institutes across the NIH recognized the value of collaborating in such a project because of its ability to address the role of biological, environmental, and behavioral factors like gender, pubertal hor...
Developmental cognitive neuroscience, Jan 10, 2017
Adolescence is a time of dramatic changes in brain structure and function, and the adolescent bra... more Adolescence is a time of dramatic changes in brain structure and function, and the adolescent brain is highly susceptible to being altered by experiences like substance use. However, there is much we have yet to learn about how these experiences influence brain development, how they promote or interfere with later health outcomes, or even what healthy brain development looks like. A large longitudinal study beginning in early adolescence could help us understand the normal variability in adolescent brain and cognitive development and tease apart the many factors that influence it. Recent advances in neuroimaging, informatics, and genetics technologies have made it feasible to conduct a study of sufficient size and scope to answer many outstanding questions. At the same time, several Institutes across the NIH recognized the value of collaborating in such a project because of its ability to address the role of biological, environmental, and behavioral factors like gender, pubertal hor...
Science needs to drive our thinking as we navigate a new legislative environment in which many Am... more Science needs to drive our thinking as we navigate a new legislative environment in which many Americans have access to marijuana for therapeutic or recreational use. With the responsibility to fund, conduct, and make use of the research on marijuana, and understand the impacts of new policies, comes the obligation of not thinking in simplistic, black-and-white terms about this substance. The drug's unique harms include neurodevelopmental impacts that may be long lasting or permanent, yet some evidence suggests the drug may benefit people with certain medical conditions (e.g., chronic pain). Marijuana use is also entangled with other substance use and should not be considered in isolation. Finally, policy options are not limited to the extremes of prohibition vs. full commercialization; a spectrum of intermediate options can and should be considered and evaluated as states create new policies around this drug.
Adolescence, as every teenager, parent, and youth professional knows, is a time of risks. With gr... more Adolescence, as every teenager, parent, and youth professional knows, is a time of risks. With greater freedom and independence, young people face new choices involving automobiles, addictive substances, and sexuality-frequently in combination. Poor choices about these risks can have terrible consequences for individuals, families, and society as a whole. The statistics are frightening, but they are not unknown to young people. For decades, adolescents have been bombarded by facts about the risks they face. Yet efforts to scare young decision makers with numbers and percentages have met with limited success (Reyna & Farley, 2006). There is even evidence that some risk-awareness-raising programs, such as DARE, actually increase the behaviors they are designed to prevent (see Lilienfeld, 2007). To reduce adolescent risk taking, a different approach is needed: one that recognizes how adolescents reason.
Prescription opioid abuse and addiction, along with consequences such as overdose death and incre... more Prescription opioid abuse and addiction, along with consequences such as overdose death and increasing transition to heroin use, constitute a devastating public health problem in the United States. Increasingly it is clear that overprescription of these medications over the past two decades has been a major upstream driver of the opioid abuse epidemic. This commentary considers the factors that have led to overprescription of opioids by clinicians, discusses recent evidence casting doubt on the efficacy of opioids for treating chronic pain, and describes the ongoing efforts by federal and community stakeholders to address this epidemic. For example, supporting prescription drug monitoring programs and improved clinician training in pain management to help reduce the supply of opioids, increasing dissemination of evidence-based primary prevention programs to reduce demand for opioids, and expanding access to effective opioid agonist therapies and antagonist medications for both treat...
The “biomechanoids” of the Swiss painter H. R. Giger (1940–2014) depict the sadomasochistic bonda... more The “biomechanoids” of the Swiss painter H. R. Giger (1940–2014) depict the sadomasochistic bondage of humans and machines. Although Giger’s art has commonly been interpreted in psychoanalytic terms as representing some past trauma connected with origins and birth, I argue that it also encodes a distinctly gnostic warning about the trajectory of consciousness in relation to technology, a “fall of spirit into matter” that may lie ahead of our species rather than behind. With the help of the endosymbiosis theory of biologist Lynn Margulis, I decode the dark warning transmission in Giger’s work, especially the iconic “Space Jockey” Giger designed for Ridley Scott’s 1979 blockbuster Alien—a fossilized star pilot fused to its ship. As a vision of the more disturbing possibilities of cyborgs or human-machine symbionts, the Space Jockey contrasts sharply with optimistic dreams of Singularities and “spiritual machines.” It suggests a posthuman future in which distinctly nonspiritual machine...
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