Addiction Medicine

The European Medicines Agency announced April 26 that its human medicines committee has recommended granting a marketing authorization for Sixmo, a long-lasting implant delivering buprenorphine as treatment for opioid use disorder (OUD).

This recommendation is a step toward making the product available to patients with OUD in the European Union, according to a press release from the EMA. Safety and efficacy of the implant were studied in three trials with a total of 628 patients. In one trial, 96.4% of patients who were treated with Sixmo responded, compared with 87.6% of patients treated with sublingual buprenorphine.

Standard treatment of OUD includes psychological and social counseling, as well as substitution opioid therapy – such as methadone or buprenorphine. The Sixmo implant involves four small rods implanted in the patient’s upper arm under local anesthetic.

The most common adverse events associated with the medicine were in keeping with the known events associated with buprenorphine – headache, constipation, and insomnia. Insertion and removal were associated with pain, severe itching, and hematoma at the implant site.

The full release can be found on the EMA website.

[email protected]

The European Medicines Agency announced April 26 that its human medicines committee has recommended granting a marketing authorization for Sixmo, a long-lasting implant delivering buprenorphine as treatment for opioid use disorder (OUD).

This recommendation is a step toward making the product available to patients with OUD in the European Union, according to a press release from the EMA. Safety and efficacy of the implant were studied in three trials with a total of 628 patients. In one trial, 96.4% of patients who were treated with Sixmo responded, compared with 87.6% of patients treated with sublingual buprenorphine.

Standard treatment of OUD includes psychological and social counseling, as well as substitution opioid therapy – such as methadone or buprenorphine. The Sixmo implant involves four small rods implanted in the patient’s upper arm under local anesthetic.

The most common adverse events associated with the medicine were in keeping with the known events associated with buprenorphine – headache, constipation, and insomnia. Insertion and removal were associated with pain, severe itching, and hematoma at the implant site.

The full release can be found on the EMA website.

[email protected]

The European Medicines Agency announced April 26 that its human medicines committee has recommended granting a marketing authorization for Sixmo, a long-lasting implant delivering buprenorphine as treatment for opioid use disorder (OUD).

This recommendation is a step toward making the product available to patients with OUD in the European Union, according to a press release from the EMA. Safety and efficacy of the implant were studied in three trials with a total of 628 patients. In one trial, 96.4% of patients who were treated with Sixmo responded, compared with 87.6% of patients treated with sublingual buprenorphine.

Standard treatment of OUD includes psychological and social counseling, as well as substitution opioid therapy – such as methadone or buprenorphine. The Sixmo implant involves four small rods implanted in the patient’s upper arm under local anesthetic.

The most common adverse events associated with the medicine were in keeping with the known events associated with buprenorphine – headache, constipation, and insomnia. Insertion and removal were associated with pain, severe itching, and hematoma at the implant site.

The full release can be found on the EMA website.

[email protected]

Rates of a potentially deadly overlap between use of nonprescribed fentanyl and use of either cocaine or methamphetamine have been increasing, a cross-sectional study of 1 million urine drug tests shows.

Leah LaRue, PharmD, of Millennium Health in San Diego, and colleagues performed the study, which sampled 1 million urine drug tests submitted by health care professionals “as part of routine care” during Jan. 1, 2013–Sept. 30, 2018. They isolated tests that were positive for either cocaine or methamphetamine – but not positive for both – and then determined how many in each group were also positive for nonprescribed fentanyl. Their analyses showed that the rate of cocaine-positive tests that also were positive for nonprescribed fentanyl increased from 0.9% in 2013 (n = 84; 95% confidence interval, 0.7%-1.1%) to 17.6% in 2018 (n = 427; 95% CI, 16.1%-19.1%), an increase of 1,850% (P less than .001). The rate of methamphetamine-positive tests that also were positive for nonprescribed fentanyl also started at 0.9% in 2013 (n = 29; 95% CI, 0.6%-1.2%) but rose to 7.9% in 2018 (n = 344; 95% CI, 7.1%-8.7%, a 798% increase (P less than .001). The study was published in JAMA Network Open.

The investigators suggested two explanations for these increases: intentional combination of drugs for “speedball effects” of combining stimulants and depressants and/or unintentional exposure on the part of users through contamination of substances. There have been increases in both cocaine-related and methamphetamine-related deaths, and the investigators of this study suspect these increases could be explained in part by overlap with opioids such as fentanyl. Part of the overdose risk inherent in these combinations is that, as the stimulant wears off, the fentanyl increasingly depresses the respiratory system, according to investigators; alternatively, opioid-naive stimulant users might be exposed to high levels of fentanyl with no opioid tolerance, which also can lead to overdose.

The study’s limitations include how samples were submitted – by health care professionals as part of routine care – and the possibility that individuals’ list of prescribed medications could have been incomplete or inaccurate such that the presence of prescribed fentanyl was counted as nonprescribed.

“The combination of nonprescribed fentanyl with cocaine or methamphetamine places an individual at increased risk of overdose,” they concluded. “Clinicians treating these individuals, and the individuals themselves, should be aware of this risk. Additionally, efforts should be made to educate the public about this risk and about overdose prevention.”

[email protected]

SOURCE: LaRue L et al. JAMA Netw Open. 2019 Apr 26. doi: 10.1001/jamanetworkopen.2019.2851.

Rates of a potentially deadly overlap between use of nonprescribed fentanyl and use of either cocaine or methamphetamine have been increasing, a cross-sectional study of 1 million urine drug tests shows.

Leah LaRue, PharmD, of Millennium Health in San Diego, and colleagues performed the study, which sampled 1 million urine drug tests submitted by health care professionals “as part of routine care” during Jan. 1, 2013–Sept. 30, 2018. They isolated tests that were positive for either cocaine or methamphetamine – but not positive for both – and then determined how many in each group were also positive for nonprescribed fentanyl. Their analyses showed that the rate of cocaine-positive tests that also were positive for nonprescribed fentanyl increased from 0.9% in 2013 (n = 84; 95% confidence interval, 0.7%-1.1%) to 17.6% in 2018 (n = 427; 95% CI, 16.1%-19.1%), an increase of 1,850% (P less than .001). The rate of methamphetamine-positive tests that also were positive for nonprescribed fentanyl also started at 0.9% in 2013 (n = 29; 95% CI, 0.6%-1.2%) but rose to 7.9% in 2018 (n = 344; 95% CI, 7.1%-8.7%, a 798% increase (P less than .001). The study was published in JAMA Network Open.

The investigators suggested two explanations for these increases: intentional combination of drugs for “speedball effects” of combining stimulants and depressants and/or unintentional exposure on the part of users through contamination of substances. There have been increases in both cocaine-related and methamphetamine-related deaths, and the investigators of this study suspect these increases could be explained in part by overlap with opioids such as fentanyl. Part of the overdose risk inherent in these combinations is that, as the stimulant wears off, the fentanyl increasingly depresses the respiratory system, according to investigators; alternatively, opioid-naive stimulant users might be exposed to high levels of fentanyl with no opioid tolerance, which also can lead to overdose.

The study’s limitations include how samples were submitted – by health care professionals as part of routine care – and the possibility that individuals’ list of prescribed medications could have been incomplete or inaccurate such that the presence of prescribed fentanyl was counted as nonprescribed.

“The combination of nonprescribed fentanyl with cocaine or methamphetamine places an individual at increased risk of overdose,” they concluded. “Clinicians treating these individuals, and the individuals themselves, should be aware of this risk. Additionally, efforts should be made to educate the public about this risk and about overdose prevention.”

[email protected]

SOURCE: LaRue L et al. JAMA Netw Open. 2019 Apr 26. doi: 10.1001/jamanetworkopen.2019.2851.

Rates of a potentially deadly overlap between use of nonprescribed fentanyl and use of either cocaine or methamphetamine have been increasing, a cross-sectional study of 1 million urine drug tests shows.

Leah LaRue, PharmD, of Millennium Health in San Diego, and colleagues performed the study, which sampled 1 million urine drug tests submitted by health care professionals “as part of routine care” during Jan. 1, 2013–Sept. 30, 2018. They isolated tests that were positive for either cocaine or methamphetamine – but not positive for both – and then determined how many in each group were also positive for nonprescribed fentanyl. Their analyses showed that the rate of cocaine-positive tests that also were positive for nonprescribed fentanyl increased from 0.9% in 2013 (n = 84; 95% confidence interval, 0.7%-1.1%) to 17.6% in 2018 (n = 427; 95% CI, 16.1%-19.1%), an increase of 1,850% (P less than .001). The rate of methamphetamine-positive tests that also were positive for nonprescribed fentanyl also started at 0.9% in 2013 (n = 29; 95% CI, 0.6%-1.2%) but rose to 7.9% in 2018 (n = 344; 95% CI, 7.1%-8.7%, a 798% increase (P less than .001). The study was published in JAMA Network Open.

The investigators suggested two explanations for these increases: intentional combination of drugs for “speedball effects” of combining stimulants and depressants and/or unintentional exposure on the part of users through contamination of substances. There have been increases in both cocaine-related and methamphetamine-related deaths, and the investigators of this study suspect these increases could be explained in part by overlap with opioids such as fentanyl. Part of the overdose risk inherent in these combinations is that, as the stimulant wears off, the fentanyl increasingly depresses the respiratory system, according to investigators; alternatively, opioid-naive stimulant users might be exposed to high levels of fentanyl with no opioid tolerance, which also can lead to overdose.

The study’s limitations include how samples were submitted – by health care professionals as part of routine care – and the possibility that individuals’ list of prescribed medications could have been incomplete or inaccurate such that the presence of prescribed fentanyl was counted as nonprescribed.

“The combination of nonprescribed fentanyl with cocaine or methamphetamine places an individual at increased risk of overdose,” they concluded. “Clinicians treating these individuals, and the individuals themselves, should be aware of this risk. Additionally, efforts should be made to educate the public about this risk and about overdose prevention.”

[email protected]

SOURCE: LaRue L et al. JAMA Netw Open. 2019 Apr 26. doi: 10.1001/jamanetworkopen.2019.2851.

Officials at the Centers for Disease Control and Prevention are warning against the misapplication of the agency’s 2016 guidelines on opioid prescribing, as well as clarifying dosage recommendations for patients starting or stopping pain medications.

In a perspective published in the New England Journal of Medicine on April 24, lead author Deborah Dowell, MD, chief medical officer for the CDC’s National Center for Injury Prevention and Control, conveyed concern that some policies and practices derived from the 2016 CDC Guideline for Prescribing Opioids for Chronic Pain are inconsistent with the recommendations and often go beyond their scope.

Misapplication examples include inappropriately applying the guideline to patients in active cancer treatment, patients experiencing acute sickle cell crises, or patients experiencing postsurgical pain, Dr. Dowell wrote.

The guideline offers guidance to clinicians treating chronic pain in adults who are already receiving opioids long-term at high dosages, she noted. It includes advice on maximizing nonopioid treatment, reviewing risks associated with continuing high-dose opioids, and collaborating with patients who agree to taper dosage, among other guidance.

Any application of the guideline’s dosage recommendation that results in hard limits or “cutting off” opioids is also an incorrect use of the recommendations, according to Dr. Dowell.

While the guideline advises clinicians to start opioids at the lowest effective dosage and avoid increasing dosage to 90 morphine milligram equivalents per day or more, that statement does not suggest discontinuation of opioids already prescribed at high dosages, according to the CDC’s clarification.

The guidance also does not apply to patients receiving or starting medication-assisted treatment for opioid use disorder.

The commentary comes after a trio of organizations raised concerns that insurers are inappropriately applying the recommendations to active cancer patients when making coverage determinations.

The American Society of Clinical Oncology, the National Comprehensive Cancer Network, and the American Society of Hematology, raised the issue in a letter to the CDC in February. In response, Dr. Dowell clarified that the recommendations are not intended to deny clinically appropriate opioid therapy to any patients who suffer chronic pain, but rather to ensure that physicians and patients consider all safe and effective treatment options.

In the perspective, Dr. Dowell wrote that the CDC is evaluating the intended and unintended impact of the 2016 opioid-prescribing guideline on clinician and patient outcomes and that the agency is committed to updating the recommendations when new evidence is available.
 

[email protected]

Officials at the Centers for Disease Control and Prevention are warning against the misapplication of the agency’s 2016 guidelines on opioid prescribing, as well as clarifying dosage recommendations for patients starting or stopping pain medications.

In a perspective published in the New England Journal of Medicine on April 24, lead author Deborah Dowell, MD, chief medical officer for the CDC’s National Center for Injury Prevention and Control, conveyed concern that some policies and practices derived from the 2016 CDC Guideline for Prescribing Opioids for Chronic Pain are inconsistent with the recommendations and often go beyond their scope.

Misapplication examples include inappropriately applying the guideline to patients in active cancer treatment, patients experiencing acute sickle cell crises, or patients experiencing postsurgical pain, Dr. Dowell wrote.

The guideline offers guidance to clinicians treating chronic pain in adults who are already receiving opioids long-term at high dosages, she noted. It includes advice on maximizing nonopioid treatment, reviewing risks associated with continuing high-dose opioids, and collaborating with patients who agree to taper dosage, among other guidance.

Any application of the guideline’s dosage recommendation that results in hard limits or “cutting off” opioids is also an incorrect use of the recommendations, according to Dr. Dowell.

While the guideline advises clinicians to start opioids at the lowest effective dosage and avoid increasing dosage to 90 morphine milligram equivalents per day or more, that statement does not suggest discontinuation of opioids already prescribed at high dosages, according to the CDC’s clarification.

The guidance also does not apply to patients receiving or starting medication-assisted treatment for opioid use disorder.

The commentary comes after a trio of organizations raised concerns that insurers are inappropriately applying the recommendations to active cancer patients when making coverage determinations.

The American Society of Clinical Oncology, the National Comprehensive Cancer Network, and the American Society of Hematology, raised the issue in a letter to the CDC in February. In response, Dr. Dowell clarified that the recommendations are not intended to deny clinically appropriate opioid therapy to any patients who suffer chronic pain, but rather to ensure that physicians and patients consider all safe and effective treatment options.

In the perspective, Dr. Dowell wrote that the CDC is evaluating the intended and unintended impact of the 2016 opioid-prescribing guideline on clinician and patient outcomes and that the agency is committed to updating the recommendations when new evidence is available.
 

[email protected]

Officials at the Centers for Disease Control and Prevention are warning against the misapplication of the agency’s 2016 guidelines on opioid prescribing, as well as clarifying dosage recommendations for patients starting or stopping pain medications.

In a perspective published in the New England Journal of Medicine on April 24, lead author Deborah Dowell, MD, chief medical officer for the CDC’s National Center for Injury Prevention and Control, conveyed concern that some policies and practices derived from the 2016 CDC Guideline for Prescribing Opioids for Chronic Pain are inconsistent with the recommendations and often go beyond their scope.

Misapplication examples include inappropriately applying the guideline to patients in active cancer treatment, patients experiencing acute sickle cell crises, or patients experiencing postsurgical pain, Dr. Dowell wrote.

The guideline offers guidance to clinicians treating chronic pain in adults who are already receiving opioids long-term at high dosages, she noted. It includes advice on maximizing nonopioid treatment, reviewing risks associated with continuing high-dose opioids, and collaborating with patients who agree to taper dosage, among other guidance.

Any application of the guideline’s dosage recommendation that results in hard limits or “cutting off” opioids is also an incorrect use of the recommendations, according to Dr. Dowell.

While the guideline advises clinicians to start opioids at the lowest effective dosage and avoid increasing dosage to 90 morphine milligram equivalents per day or more, that statement does not suggest discontinuation of opioids already prescribed at high dosages, according to the CDC’s clarification.

The guidance also does not apply to patients receiving or starting medication-assisted treatment for opioid use disorder.

The commentary comes after a trio of organizations raised concerns that insurers are inappropriately applying the recommendations to active cancer patients when making coverage determinations.

The American Society of Clinical Oncology, the National Comprehensive Cancer Network, and the American Society of Hematology, raised the issue in a letter to the CDC in February. In response, Dr. Dowell clarified that the recommendations are not intended to deny clinically appropriate opioid therapy to any patients who suffer chronic pain, but rather to ensure that physicians and patients consider all safe and effective treatment options.

In the perspective, Dr. Dowell wrote that the CDC is evaluating the intended and unintended impact of the 2016 opioid-prescribing guideline on clinician and patient outcomes and that the agency is committed to updating the recommendations when new evidence is available.
 

[email protected]

After 2 decades of steady decline in adolescent and young adult use of tobacco products, e-cigarettes have dramatically altered the landscape of substance use in youth. E-cigarette use among teens has been on the rise for years but the recent exponential increase is unprecedented. From 2017 to 2018, adolescent e-cigarette use had the largest year-to-year increase (78%, from 12% to 21%) of any individual substance or class of substances at any time during the past 2 decades of nationwide monitoring.¹ This has appropriately caught the nation’s attention. In 2016, Surgeon General Vivek H. Murthy, MD, commissioned an extensive report about electronic cigarettes, and in 2018 Surgeon General Jerome Adams, MD, MPH, issued an advisory declaring e-cigarettes a public health crisis for adolescents.²

licsiren/iStock/Getty Images

E-cigarettes have received attention as a possible boon to adult cigarette smokers seeking a less hazardous product. We can consider the use of tobacco products along a continuum from smoked tobacco, dual use (both smoked tobacco and electronic nicotine delivery), electronic nicotine delivery only, and finally, nonuse. For some adults, transitioning from smoked tobacco products to electronic delivery systems has been a step toward less overall harm from substance use, with a small minority of that population going on to achieve abstinence from all nicotine products.³ For youth and teens, the story has been the opposite. With the rapid rise of e-cigarettes, adolescents overwhelmingly have been moving in the wrong direction at each potential step along this continuum.⁴ Less than 8% of teens who use e-cigarettes indicated that smoking cessation is a factor in their use.⁵ An estimated 1.3 million U.S. teens now are dependent or at high risk for dependence upon nicotine because of e-cigarette use. Furthermore, these teens are at a fourfold higher risk of progression to cigarette use, compared with their peers.⁶

One product in particular gives us information as to why this trend has accelerated so rapidly. Juul, now the sales leader among electronic nicotine delivery systems, rose from approximately 25% to a dominant 75% of market share in just over 1 fiscal year after a social media campaign targeted toward youth and young adults. The device is shaped like an elongated flash drive, is marketed as “sleek,” “looking cool,” and being “super easy” to use. This product touts its use of nicotine salts that can deliver higher concentrations of nicotine more rapidly to mimic the experience of smoking a cigarette as closely as possible. The fruity flavors in Juul “pods” and many other devices also appeal to teens. Many youth are left misinformed, thinking they are using a relatively harmless alternative to cigarettes.

E-cigarette use in youth carries many risks. Among the physical risks is exposure to harmful chemicals (even if less numerous than smoked tobacco products) such as diacetyl (a known cause of bronchiolitis obliterans, or “popcorn lung”), formaldehyde, acrolein, benzene, and metals such as nickel, tin and lead.⁷ “Safer than cigarettes” is a low bar indeed. Cognitive and emotional risks of early nicotine exposure include poor focus and attention, permanent lowering of impulse control, and a higher risk of mood and anxiety disorders.

Furthermore, nicotine is a gateway drug, with a clearly understood molecular basis for how it can potentiate the effects of later used substances, especially stimulants such as cocaine.⁸ The gateway and priming effect is compounded for youth because of ongoing brain development and plasticity during teen years. E-cigarette use also is associated with other risk behaviors including a manyfold higher likelihood of binge drinking, having multiple sexual partners in a short period of time, and using other substances such as cannabis, cocaine, methamphetamine, and heroin or nonprescribed opioids.⁹ An electronic system for vaporization also presents a risk for use of other substances. In just 1 year from 2017 to 2018, marijuana “vaping” increased by more than 50% among all ages surveyed.¹⁰

Pediatric health care providers are essential educators for both teens and parents regarding the risks of e-cigarette use. Many youth don’t know what they’re using; 66% of youth reported that the vapors they were inhaling contained only flavoring. Only 13% reported they were inhaling nicotine.¹⁰ In stark contrast to these self-reports, all Juul “pods” contain nicotine. As has been a pattern with nationwide surveys of substance use for decades, adolescent use is inversely correlated with perception of risk; 70% of 8th-12th graders do not foresee great harm in regular e-cigarette use. In addition, adolescents use substances less often when they know their parents disapprove. Parents also must be taught about the risks of e-cigarette use and can be provided with resources and taught effective strategies if they have difficulty communicating their disapproval to their children.

Age-appropriate screening in primary care settings must include specific language regarding the use of electronic cigarettes, with questions about “vaping” and “juuling.” After screening, a brief intervention includes a clear recommendation against e-cigarette use and education about the risks. Discussions with teens may be more effective with emphasis on issues that resonate with youth such as the financial cost, loss of freedom when dependence develops, and the fact that their generation is once again being targeted by the tobacco industry. Referral for further treatment, including individual and group therapy as well as family-focused interventions, should be considered for teens who use daily, use other substances regularly, or could benefit from treatment for co-occurring mental health disorders.

Electronic cigarette use should not be recommended as a smoking cessation strategy for teens.¹¹ Pediatric health care providers must advocate for regulation of these products, including increasing the legal age of purchase and banning flavoring in e-cigarettes products, Internet sales, and advertisements targeted to youth.

The rapid rise in e-cigarette use among teens is of great concern. As with all classes of substances, early initiation of nicotine drastically increases the risk of developing a substance use disorder and portends a prolonged course and greater accumulation of adverse consequences. There is an urgent need for education, prevention, and early identification of e-cigarette use to protect the current and future well-being of children and adolescents.
 

Dr. Jackson is assistant professor of psychiatry at the University of Vermont, Burlington. He said he had no relevant financial disclosures. Email Dr. Jackson at [email protected].

References

1. MMWR Morb Mortal Wkly Rep. 2018;67:1276-7.

2. e-cigarettes.surgeongeneral.gov

3. N Engl J Med 2019;380:629-37.

4. Pediatrics. 2018 Dec; 142(6):e20180486.

5. MMWR Morb Mortal Wkly Rep 2018;67:196-200.

6. JAMA Pediatr. 2017 Aug 1;171(8):788-97.

7. “Public health consequences of e-cigarettes” (Washington, DC: National Academies Press, January 2018).

8. N Engl J Med 2014;371:932-43.

9. N Engl J Med 2019;380:689-90.

10. MMWR Morb Mortal Wkly Rep. 2016 Jan 8;64(52):1403-8.

11. Pediatrics. 2019 Feb;143(2). pii: e20183652.

After 2 decades of steady decline in adolescent and young adult use of tobacco products, e-cigarettes have dramatically altered the landscape of substance use in youth. E-cigarette use among teens has been on the rise for years but the recent exponential increase is unprecedented. From 2017 to 2018, adolescent e-cigarette use had the largest year-to-year increase (78%, from 12% to 21%) of any individual substance or class of substances at any time during the past 2 decades of nationwide monitoring.¹ This has appropriately caught the nation’s attention. In 2016, Surgeon General Vivek H. Murthy, MD, commissioned an extensive report about electronic cigarettes, and in 2018 Surgeon General Jerome Adams, MD, MPH, issued an advisory declaring e-cigarettes a public health crisis for adolescents.²

licsiren/iStock/Getty Images

E-cigarettes have received attention as a possible boon to adult cigarette smokers seeking a less hazardous product. We can consider the use of tobacco products along a continuum from smoked tobacco, dual use (both smoked tobacco and electronic nicotine delivery), electronic nicotine delivery only, and finally, nonuse. For some adults, transitioning from smoked tobacco products to electronic delivery systems has been a step toward less overall harm from substance use, with a small minority of that population going on to achieve abstinence from all nicotine products.³ For youth and teens, the story has been the opposite. With the rapid rise of e-cigarettes, adolescents overwhelmingly have been moving in the wrong direction at each potential step along this continuum.⁴ Less than 8% of teens who use e-cigarettes indicated that smoking cessation is a factor in their use.⁵ An estimated 1.3 million U.S. teens now are dependent or at high risk for dependence upon nicotine because of e-cigarette use. Furthermore, these teens are at a fourfold higher risk of progression to cigarette use, compared with their peers.⁶

One product in particular gives us information as to why this trend has accelerated so rapidly. Juul, now the sales leader among electronic nicotine delivery systems, rose from approximately 25% to a dominant 75% of market share in just over 1 fiscal year after a social media campaign targeted toward youth and young adults. The device is shaped like an elongated flash drive, is marketed as “sleek,” “looking cool,” and being “super easy” to use. This product touts its use of nicotine salts that can deliver higher concentrations of nicotine more rapidly to mimic the experience of smoking a cigarette as closely as possible. The fruity flavors in Juul “pods” and many other devices also appeal to teens. Many youth are left misinformed, thinking they are using a relatively harmless alternative to cigarettes.

E-cigarette use in youth carries many risks. Among the physical risks is exposure to harmful chemicals (even if less numerous than smoked tobacco products) such as diacetyl (a known cause of bronchiolitis obliterans, or “popcorn lung”), formaldehyde, acrolein, benzene, and metals such as nickel, tin and lead.⁷ “Safer than cigarettes” is a low bar indeed. Cognitive and emotional risks of early nicotine exposure include poor focus and attention, permanent lowering of impulse control, and a higher risk of mood and anxiety disorders.

Furthermore, nicotine is a gateway drug, with a clearly understood molecular basis for how it can potentiate the effects of later used substances, especially stimulants such as cocaine.⁸ The gateway and priming effect is compounded for youth because of ongoing brain development and plasticity during teen years. E-cigarette use also is associated with other risk behaviors including a manyfold higher likelihood of binge drinking, having multiple sexual partners in a short period of time, and using other substances such as cannabis, cocaine, methamphetamine, and heroin or nonprescribed opioids.⁹ An electronic system for vaporization also presents a risk for use of other substances. In just 1 year from 2017 to 2018, marijuana “vaping” increased by more than 50% among all ages surveyed.¹⁰

Pediatric health care providers are essential educators for both teens and parents regarding the risks of e-cigarette use. Many youth don’t know what they’re using; 66% of youth reported that the vapors they were inhaling contained only flavoring. Only 13% reported they were inhaling nicotine.¹⁰ In stark contrast to these self-reports, all Juul “pods” contain nicotine. As has been a pattern with nationwide surveys of substance use for decades, adolescent use is inversely correlated with perception of risk; 70% of 8th-12th graders do not foresee great harm in regular e-cigarette use. In addition, adolescents use substances less often when they know their parents disapprove. Parents also must be taught about the risks of e-cigarette use and can be provided with resources and taught effective strategies if they have difficulty communicating their disapproval to their children.

Age-appropriate screening in primary care settings must include specific language regarding the use of electronic cigarettes, with questions about “vaping” and “juuling.” After screening, a brief intervention includes a clear recommendation against e-cigarette use and education about the risks. Discussions with teens may be more effective with emphasis on issues that resonate with youth such as the financial cost, loss of freedom when dependence develops, and the fact that their generation is once again being targeted by the tobacco industry. Referral for further treatment, including individual and group therapy as well as family-focused interventions, should be considered for teens who use daily, use other substances regularly, or could benefit from treatment for co-occurring mental health disorders.

Electronic cigarette use should not be recommended as a smoking cessation strategy for teens.¹¹ Pediatric health care providers must advocate for regulation of these products, including increasing the legal age of purchase and banning flavoring in e-cigarettes products, Internet sales, and advertisements targeted to youth.

The rapid rise in e-cigarette use among teens is of great concern. As with all classes of substances, early initiation of nicotine drastically increases the risk of developing a substance use disorder and portends a prolonged course and greater accumulation of adverse consequences. There is an urgent need for education, prevention, and early identification of e-cigarette use to protect the current and future well-being of children and adolescents.
 

Dr. Jackson is assistant professor of psychiatry at the University of Vermont, Burlington. He said he had no relevant financial disclosures. Email Dr. Jackson at [email protected].

References

1. MMWR Morb Mortal Wkly Rep. 2018;67:1276-7.

2. e-cigarettes.surgeongeneral.gov

3. N Engl J Med 2019;380:629-37.

4. Pediatrics. 2018 Dec; 142(6):e20180486.

5. MMWR Morb Mortal Wkly Rep 2018;67:196-200.

6. JAMA Pediatr. 2017 Aug 1;171(8):788-97.

7. “Public health consequences of e-cigarettes” (Washington, DC: National Academies Press, January 2018).

8. N Engl J Med 2014;371:932-43.

9. N Engl J Med 2019;380:689-90.

10. MMWR Morb Mortal Wkly Rep. 2016 Jan 8;64(52):1403-8.

11. Pediatrics. 2019 Feb;143(2). pii: e20183652.

After 2 decades of steady decline in adolescent and young adult use of tobacco products, e-cigarettes have dramatically altered the landscape of substance use in youth. E-cigarette use among teens has been on the rise for years but the recent exponential increase is unprecedented. From 2017 to 2018, adolescent e-cigarette use had the largest year-to-year increase (78%, from 12% to 21%) of any individual substance or class of substances at any time during the past 2 decades of nationwide monitoring.¹ This has appropriately caught the nation’s attention. In 2016, Surgeon General Vivek H. Murthy, MD, commissioned an extensive report about electronic cigarettes, and in 2018 Surgeon General Jerome Adams, MD, MPH, issued an advisory declaring e-cigarettes a public health crisis for adolescents.²

licsiren/iStock/Getty Images

E-cigarettes have received attention as a possible boon to adult cigarette smokers seeking a less hazardous product. We can consider the use of tobacco products along a continuum from smoked tobacco, dual use (both smoked tobacco and electronic nicotine delivery), electronic nicotine delivery only, and finally, nonuse. For some adults, transitioning from smoked tobacco products to electronic delivery systems has been a step toward less overall harm from substance use, with a small minority of that population going on to achieve abstinence from all nicotine products.³ For youth and teens, the story has been the opposite. With the rapid rise of e-cigarettes, adolescents overwhelmingly have been moving in the wrong direction at each potential step along this continuum.⁴ Less than 8% of teens who use e-cigarettes indicated that smoking cessation is a factor in their use.⁵ An estimated 1.3 million U.S. teens now are dependent or at high risk for dependence upon nicotine because of e-cigarette use. Furthermore, these teens are at a fourfold higher risk of progression to cigarette use, compared with their peers.⁶

One product in particular gives us information as to why this trend has accelerated so rapidly. Juul, now the sales leader among electronic nicotine delivery systems, rose from approximately 25% to a dominant 75% of market share in just over 1 fiscal year after a social media campaign targeted toward youth and young adults. The device is shaped like an elongated flash drive, is marketed as “sleek,” “looking cool,” and being “super easy” to use. This product touts its use of nicotine salts that can deliver higher concentrations of nicotine more rapidly to mimic the experience of smoking a cigarette as closely as possible. The fruity flavors in Juul “pods” and many other devices also appeal to teens. Many youth are left misinformed, thinking they are using a relatively harmless alternative to cigarettes.

E-cigarette use in youth carries many risks. Among the physical risks is exposure to harmful chemicals (even if less numerous than smoked tobacco products) such as diacetyl (a known cause of bronchiolitis obliterans, or “popcorn lung”), formaldehyde, acrolein, benzene, and metals such as nickel, tin and lead.⁷ “Safer than cigarettes” is a low bar indeed. Cognitive and emotional risks of early nicotine exposure include poor focus and attention, permanent lowering of impulse control, and a higher risk of mood and anxiety disorders.

Furthermore, nicotine is a gateway drug, with a clearly understood molecular basis for how it can potentiate the effects of later used substances, especially stimulants such as cocaine.⁸ The gateway and priming effect is compounded for youth because of ongoing brain development and plasticity during teen years. E-cigarette use also is associated with other risk behaviors including a manyfold higher likelihood of binge drinking, having multiple sexual partners in a short period of time, and using other substances such as cannabis, cocaine, methamphetamine, and heroin or nonprescribed opioids.⁹ An electronic system for vaporization also presents a risk for use of other substances. In just 1 year from 2017 to 2018, marijuana “vaping” increased by more than 50% among all ages surveyed.¹⁰

Pediatric health care providers are essential educators for both teens and parents regarding the risks of e-cigarette use. Many youth don’t know what they’re using; 66% of youth reported that the vapors they were inhaling contained only flavoring. Only 13% reported they were inhaling nicotine.¹⁰ In stark contrast to these self-reports, all Juul “pods” contain nicotine. As has been a pattern with nationwide surveys of substance use for decades, adolescent use is inversely correlated with perception of risk; 70% of 8th-12th graders do not foresee great harm in regular e-cigarette use. In addition, adolescents use substances less often when they know their parents disapprove. Parents also must be taught about the risks of e-cigarette use and can be provided with resources and taught effective strategies if they have difficulty communicating their disapproval to their children.

Age-appropriate screening in primary care settings must include specific language regarding the use of electronic cigarettes, with questions about “vaping” and “juuling.” After screening, a brief intervention includes a clear recommendation against e-cigarette use and education about the risks. Discussions with teens may be more effective with emphasis on issues that resonate with youth such as the financial cost, loss of freedom when dependence develops, and the fact that their generation is once again being targeted by the tobacco industry. Referral for further treatment, including individual and group therapy as well as family-focused interventions, should be considered for teens who use daily, use other substances regularly, or could benefit from treatment for co-occurring mental health disorders.

Electronic cigarette use should not be recommended as a smoking cessation strategy for teens.¹¹ Pediatric health care providers must advocate for regulation of these products, including increasing the legal age of purchase and banning flavoring in e-cigarettes products, Internet sales, and advertisements targeted to youth.

The rapid rise in e-cigarette use among teens is of great concern. As with all classes of substances, early initiation of nicotine drastically increases the risk of developing a substance use disorder and portends a prolonged course and greater accumulation of adverse consequences. There is an urgent need for education, prevention, and early identification of e-cigarette use to protect the current and future well-being of children and adolescents.
 

Dr. Jackson is assistant professor of psychiatry at the University of Vermont, Burlington. He said he had no relevant financial disclosures. Email Dr. Jackson at [email protected].

References

1. MMWR Morb Mortal Wkly Rep. 2018;67:1276-7.

2. e-cigarettes.surgeongeneral.gov

3. N Engl J Med 2019;380:629-37.

4. Pediatrics. 2018 Dec; 142(6):e20180486.

5. MMWR Morb Mortal Wkly Rep 2018;67:196-200.

6. JAMA Pediatr. 2017 Aug 1;171(8):788-97.

7. “Public health consequences of e-cigarettes” (Washington, DC: National Academies Press, January 2018).

8. N Engl J Med 2014;371:932-43.

9. N Engl J Med 2019;380:689-90.

10. MMWR Morb Mortal Wkly Rep. 2016 Jan 8;64(52):1403-8.

11. Pediatrics. 2019 Feb;143(2). pii: e20183652.

The Food and Drug Administration on April 19 approved the first generic naloxone hydrochloride nasal spray (Narcan) as treatment for stopping or reversing an opioid overdose.

“In the wake of the opioid crisis, a number of efforts are underway to make this emergency overdose reversal treatment more readily available and more accessible,” said Douglas Throckmorton, MD, deputy center director for regulatory programs in the FDA’s Center for Drug Evaluation and Research, in a press release. “In addition to this approval of the first generic naloxone nasal spray, moving forward, we will prioritize our review of generic drug applications for naloxone.”

The agency said the naloxone nasal spray does not need assembly and can be used by anyone, regardless of medical training. The drug is administered by spraying naloxone into one nostril while a patient is lying on his or her back and can be repeated. If the spray is administered quickly after the overdose begins, the effect of the opioid will be countered, often within minutes. However, patients should still seek immediate medical attention.

The FDA cautioned that, when used on a patient with an opioid dependence, naloxone can cause severe opioid withdrawal, characterized by symptoms such as body aches, diarrhea, tachycardia, fever, runny nose, sneezing, goose bumps, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure.

Find the full press release on the FDA website.

[email protected]

The Food and Drug Administration on April 19 approved the first generic naloxone hydrochloride nasal spray (Narcan) as treatment for stopping or reversing an opioid overdose.

“In the wake of the opioid crisis, a number of efforts are underway to make this emergency overdose reversal treatment more readily available and more accessible,” said Douglas Throckmorton, MD, deputy center director for regulatory programs in the FDA’s Center for Drug Evaluation and Research, in a press release. “In addition to this approval of the first generic naloxone nasal spray, moving forward, we will prioritize our review of generic drug applications for naloxone.”

The agency said the naloxone nasal spray does not need assembly and can be used by anyone, regardless of medical training. The drug is administered by spraying naloxone into one nostril while a patient is lying on his or her back and can be repeated. If the spray is administered quickly after the overdose begins, the effect of the opioid will be countered, often within minutes. However, patients should still seek immediate medical attention.

The FDA cautioned that, when used on a patient with an opioid dependence, naloxone can cause severe opioid withdrawal, characterized by symptoms such as body aches, diarrhea, tachycardia, fever, runny nose, sneezing, goose bumps, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure.

Find the full press release on the FDA website.

[email protected]

The Food and Drug Administration on April 19 approved the first generic naloxone hydrochloride nasal spray (Narcan) as treatment for stopping or reversing an opioid overdose.

“In the wake of the opioid crisis, a number of efforts are underway to make this emergency overdose reversal treatment more readily available and more accessible,” said Douglas Throckmorton, MD, deputy center director for regulatory programs in the FDA’s Center for Drug Evaluation and Research, in a press release. “In addition to this approval of the first generic naloxone nasal spray, moving forward, we will prioritize our review of generic drug applications for naloxone.”

The agency said the naloxone nasal spray does not need assembly and can be used by anyone, regardless of medical training. The drug is administered by spraying naloxone into one nostril while a patient is lying on his or her back and can be repeated. If the spray is administered quickly after the overdose begins, the effect of the opioid will be countered, often within minutes. However, patients should still seek immediate medical attention.

The FDA cautioned that, when used on a patient with an opioid dependence, naloxone can cause severe opioid withdrawal, characterized by symptoms such as body aches, diarrhea, tachycardia, fever, runny nose, sneezing, goose bumps, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure.

Find the full press release on the FDA website.

[email protected]

The Food and Drug Administration is making changes to opioid analgesic labeling to give better information to clinicians on how to properly taper patients dependent on opioid use, according to Douglas Throckmorton, MD, deputy director for regulatory programs in the FDA’s Center for Drug Evaluation and Research.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA has recently received reports that patients physically dependent on opioid pain medicines who are taken off their medication too quickly have experienced serious adverse events, such as withdrawal symptoms, uncontrolled pain, and suicide. Both the FDA and the Centers for Disease Control and Prevention offer guidelines on how to properly taper opioids, Dr. Throckmorton said, but more needs to be done to ensure that patients are being provided with the correct advice and care.

The changes to the labels will include expanded information to health care clinicians and are intended to be used when both the clinician and patient have agreed to reduce the opioid dosage. When this is discussed, factors that should be considered include the dose of the drug, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient.

Other actions the FDA is pursuing to combat opioid use disorder include working with the National Academies of Sciences, Engineering, and Medicine on guidelines for the proper opioid analgesic prescribing for acute pain resulting from specific conditions or procedures, and advancing policies that make immediate-release opioid formulations available in fixed-quantity packaging for 1 or 2 days.

“The FDA remains committed to addressing the opioid crisis on all fronts, with a significant focus on decreasing unnecessary exposure to opioids and preventing new addiction; supporting the treatment of those with opioid use disorder; fostering the development of novel pain treatment therapies and opioids more resistant to abuse and misuse; and taking action against those involved in the illegal importation and sale of opioids,” Dr. Throckmorton said.

Find the full statement by Dr. Throckmorton on the FDA website.

[email protected]

The Food and Drug Administration is making changes to opioid analgesic labeling to give better information to clinicians on how to properly taper patients dependent on opioid use, according to Douglas Throckmorton, MD, deputy director for regulatory programs in the FDA’s Center for Drug Evaluation and Research.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA has recently received reports that patients physically dependent on opioid pain medicines who are taken off their medication too quickly have experienced serious adverse events, such as withdrawal symptoms, uncontrolled pain, and suicide. Both the FDA and the Centers for Disease Control and Prevention offer guidelines on how to properly taper opioids, Dr. Throckmorton said, but more needs to be done to ensure that patients are being provided with the correct advice and care.

The changes to the labels will include expanded information to health care clinicians and are intended to be used when both the clinician and patient have agreed to reduce the opioid dosage. When this is discussed, factors that should be considered include the dose of the drug, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient.

Other actions the FDA is pursuing to combat opioid use disorder include working with the National Academies of Sciences, Engineering, and Medicine on guidelines for the proper opioid analgesic prescribing for acute pain resulting from specific conditions or procedures, and advancing policies that make immediate-release opioid formulations available in fixed-quantity packaging for 1 or 2 days.

“The FDA remains committed to addressing the opioid crisis on all fronts, with a significant focus on decreasing unnecessary exposure to opioids and preventing new addiction; supporting the treatment of those with opioid use disorder; fostering the development of novel pain treatment therapies and opioids more resistant to abuse and misuse; and taking action against those involved in the illegal importation and sale of opioids,” Dr. Throckmorton said.

Find the full statement by Dr. Throckmorton on the FDA website.

[email protected]

The Food and Drug Administration is making changes to opioid analgesic labeling to give better information to clinicians on how to properly taper patients dependent on opioid use, according to Douglas Throckmorton, MD, deputy director for regulatory programs in the FDA’s Center for Drug Evaluation and Research.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA has recently received reports that patients physically dependent on opioid pain medicines who are taken off their medication too quickly have experienced serious adverse events, such as withdrawal symptoms, uncontrolled pain, and suicide. Both the FDA and the Centers for Disease Control and Prevention offer guidelines on how to properly taper opioids, Dr. Throckmorton said, but more needs to be done to ensure that patients are being provided with the correct advice and care.

The changes to the labels will include expanded information to health care clinicians and are intended to be used when both the clinician and patient have agreed to reduce the opioid dosage. When this is discussed, factors that should be considered include the dose of the drug, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient.

Other actions the FDA is pursuing to combat opioid use disorder include working with the National Academies of Sciences, Engineering, and Medicine on guidelines for the proper opioid analgesic prescribing for acute pain resulting from specific conditions or procedures, and advancing policies that make immediate-release opioid formulations available in fixed-quantity packaging for 1 or 2 days.

“The FDA remains committed to addressing the opioid crisis on all fronts, with a significant focus on decreasing unnecessary exposure to opioids and preventing new addiction; supporting the treatment of those with opioid use disorder; fostering the development of novel pain treatment therapies and opioids more resistant to abuse and misuse; and taking action against those involved in the illegal importation and sale of opioids,” Dr. Throckmorton said.

Find the full statement by Dr. Throckmorton on the FDA website.

[email protected]

MILWAUKEE – Congress has allocated a half billion dollars annually to the National Institutes of Health for a program that seeks to end America’s opioid crisis. The agency is putting in place over two-dozen projects spanning basic and translational research, clinical trials, and implementation of new strategies to address pain and fight addiction.

The Helping to End Addiction Long-term (HEAL) initiative has over $850 million in total obligated for fiscal year 2019, said Walter Koroshetz, MD, speaking at the scientific meeting of the American Pain Society. This represents carryover from 2018, a planning year for the initiative, along with the 2019 $500 million annual supplement to the NIH’s base appropriation.

In 2018, NIH and other federal agencies successfully convinced Congress that funding a coordinated use of resources was necessary to overcome the country’s dual opioid and chronic pain crises. “Luck happens to the prepared,” said Dr. Koroshetz, director of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Md., adding that many hours went into putting together a national pain strategy that is multidisciplinary and multi-layered, and involves multiple players.

The two aims of research under the initiative are to improve treatments for misuse and addiction, and to enhance pain management. Focusing on this latter aim, Dr. Koroshetz said that the initiative has several research priorities to enhance pain management.

First, the biological basis for chronic pain needs to be understood in order to formulate effective therapies and interventions. “We need to understand the transition from acute to chronic pain,” he commented. “We need to see if we can learn about the risk factors for developing chronic pain; if we get really lucky, we might identify some biological markers” that identify who is at risk for this transition “in a high-risk acute pain situation.”

Next, a key request of industry and academia will be development of more drugs that avoid the dual-target program of opioids, which affect reward circuitry along with pain circuitry. “Drugs affecting the pain circuit and the reward circuit will always result in addiction” potential, said Dr. Koroshetz. “We’re still using drugs for pain from the poppy plant that were discovered 8,000 years ago.”

The hope with the HEAL initiative is to bring together academic centers with patient populations and research capabilities with industry, to accelerate moving nonaddictive treatments through to phase 3 trials.

[email protected]

MILWAUKEE – Congress has allocated a half billion dollars annually to the National Institutes of Health for a program that seeks to end America’s opioid crisis. The agency is putting in place over two-dozen projects spanning basic and translational research, clinical trials, and implementation of new strategies to address pain and fight addiction.

The Helping to End Addiction Long-term (HEAL) initiative has over $850 million in total obligated for fiscal year 2019, said Walter Koroshetz, MD, speaking at the scientific meeting of the American Pain Society. This represents carryover from 2018, a planning year for the initiative, along with the 2019 $500 million annual supplement to the NIH’s base appropriation.

In 2018, NIH and other federal agencies successfully convinced Congress that funding a coordinated use of resources was necessary to overcome the country’s dual opioid and chronic pain crises. “Luck happens to the prepared,” said Dr. Koroshetz, director of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Md., adding that many hours went into putting together a national pain strategy that is multidisciplinary and multi-layered, and involves multiple players.

The two aims of research under the initiative are to improve treatments for misuse and addiction, and to enhance pain management. Focusing on this latter aim, Dr. Koroshetz said that the initiative has several research priorities to enhance pain management.

First, the biological basis for chronic pain needs to be understood in order to formulate effective therapies and interventions. “We need to understand the transition from acute to chronic pain,” he commented. “We need to see if we can learn about the risk factors for developing chronic pain; if we get really lucky, we might identify some biological markers” that identify who is at risk for this transition “in a high-risk acute pain situation.”

Next, a key request of industry and academia will be development of more drugs that avoid the dual-target program of opioids, which affect reward circuitry along with pain circuitry. “Drugs affecting the pain circuit and the reward circuit will always result in addiction” potential, said Dr. Koroshetz. “We’re still using drugs for pain from the poppy plant that were discovered 8,000 years ago.”

The hope with the HEAL initiative is to bring together academic centers with patient populations and research capabilities with industry, to accelerate moving nonaddictive treatments through to phase 3 trials.

[email protected]

MILWAUKEE – Congress has allocated a half billion dollars annually to the National Institutes of Health for a program that seeks to end America’s opioid crisis. The agency is putting in place over two-dozen projects spanning basic and translational research, clinical trials, and implementation of new strategies to address pain and fight addiction.

The Helping to End Addiction Long-term (HEAL) initiative has over $850 million in total obligated for fiscal year 2019, said Walter Koroshetz, MD, speaking at the scientific meeting of the American Pain Society. This represents carryover from 2018, a planning year for the initiative, along with the 2019 $500 million annual supplement to the NIH’s base appropriation.

In 2018, NIH and other federal agencies successfully convinced Congress that funding a coordinated use of resources was necessary to overcome the country’s dual opioid and chronic pain crises. “Luck happens to the prepared,” said Dr. Koroshetz, director of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Md., adding that many hours went into putting together a national pain strategy that is multidisciplinary and multi-layered, and involves multiple players.

The two aims of research under the initiative are to improve treatments for misuse and addiction, and to enhance pain management. Focusing on this latter aim, Dr. Koroshetz said that the initiative has several research priorities to enhance pain management.

First, the biological basis for chronic pain needs to be understood in order to formulate effective therapies and interventions. “We need to understand the transition from acute to chronic pain,” he commented. “We need to see if we can learn about the risk factors for developing chronic pain; if we get really lucky, we might identify some biological markers” that identify who is at risk for this transition “in a high-risk acute pain situation.”

Next, a key request of industry and academia will be development of more drugs that avoid the dual-target program of opioids, which affect reward circuitry along with pain circuitry. “Drugs affecting the pain circuit and the reward circuit will always result in addiction” potential, said Dr. Koroshetz. “We’re still using drugs for pain from the poppy plant that were discovered 8,000 years ago.”

The hope with the HEAL initiative is to bring together academic centers with patient populations and research capabilities with industry, to accelerate moving nonaddictive treatments through to phase 3 trials.

[email protected]

Habitual use of opioids “rewires” the brain’s reward system. In the study, researchers will be testing ANS-6637 (Amygdala Neurosciences), a drug that may inhibit the dopamine surge of opioid use, without affecting the levels of dopamine needed for normal brain function.

The phase 1 trial will enroll up to 50 healthy adults aged 18 to 65 years. On the first day of the 10-day study, they will receive a single dose of midazolam, chosen to act as a template for liver metabolism. After a drug-free day 2, on days 3 through 7 they will receive 600 mg/d of ANS-6637. On day 8, the participants will be given the 2 drugs together to determine how the investigational drug affects midazolam levels, which also will help the researchers understand how ANS-6637 is processed in the body. The volunteers will return for a final outpatient visit after 1 week.

At present, few pharmacologic interventions target opioid-related cravings, says researcher Henry Masur, MD, chief of the Clinical Center’s Critical Care Medicine Department. If proven effective, the researchers say, ANS-6637 could be part of a comprehensive package of services, including harm reduction, opioid agonist therapy, and behavioral interventions.

The study is funded through NIH’s Helping to End Addiction Long-Term (HEAL) Initiative, an “aggressive, trans-agency effort to speed scientific solutions” to the opioid crisis.

Habitual use of opioids “rewires” the brain’s reward system. In the study, researchers will be testing ANS-6637 (Amygdala Neurosciences), a drug that may inhibit the dopamine surge of opioid use, without affecting the levels of dopamine needed for normal brain function.

The phase 1 trial will enroll up to 50 healthy adults aged 18 to 65 years. On the first day of the 10-day study, they will receive a single dose of midazolam, chosen to act as a template for liver metabolism. After a drug-free day 2, on days 3 through 7 they will receive 600 mg/d of ANS-6637. On day 8, the participants will be given the 2 drugs together to determine how the investigational drug affects midazolam levels, which also will help the researchers understand how ANS-6637 is processed in the body. The volunteers will return for a final outpatient visit after 1 week.

At present, few pharmacologic interventions target opioid-related cravings, says researcher Henry Masur, MD, chief of the Clinical Center’s Critical Care Medicine Department. If proven effective, the researchers say, ANS-6637 could be part of a comprehensive package of services, including harm reduction, opioid agonist therapy, and behavioral interventions.

The study is funded through NIH’s Helping to End Addiction Long-Term (HEAL) Initiative, an “aggressive, trans-agency effort to speed scientific solutions” to the opioid crisis.

Habitual use of opioids “rewires” the brain’s reward system. In the study, researchers will be testing ANS-6637 (Amygdala Neurosciences), a drug that may inhibit the dopamine surge of opioid use, without affecting the levels of dopamine needed for normal brain function.

The phase 1 trial will enroll up to 50 healthy adults aged 18 to 65 years. On the first day of the 10-day study, they will receive a single dose of midazolam, chosen to act as a template for liver metabolism. After a drug-free day 2, on days 3 through 7 they will receive 600 mg/d of ANS-6637. On day 8, the participants will be given the 2 drugs together to determine how the investigational drug affects midazolam levels, which also will help the researchers understand how ANS-6637 is processed in the body. The volunteers will return for a final outpatient visit after 1 week.

At present, few pharmacologic interventions target opioid-related cravings, says researcher Henry Masur, MD, chief of the Clinical Center’s Critical Care Medicine Department. If proven effective, the researchers say, ANS-6637 could be part of a comprehensive package of services, including harm reduction, opioid agonist therapy, and behavioral interventions.

The study is funded through NIH’s Helping to End Addiction Long-Term (HEAL) Initiative, an “aggressive, trans-agency effort to speed scientific solutions” to the opioid crisis.

Most people who could benefit from FDA-approved medications for opioid use disorder do not receive them, and access to those treatments is not equitable, according to a new consensus study report from the National Academies of Sciences, Engineering, and Medicine.

“Methadone, buprenorphine, and extended-release naltrexone are safe and highly effective medications that are already approved by the U.S. Food and Drug Administration to treat OUD,” the report said. “These medications save lives, but the majority of people with OUD in the United States receive no treatment at all.”

The report, called “Medications for Opioid Use Disorder Save Lives,” said a critical factor in addressing the crisis is “confronting the major barriers” to using those medications. It also said additional research will be needed to address opioid use disorder among subpopulations in the United States, such as adolescents, older adults, people with comorbidities, racial and ethnic groups, and people with low socioeconomic status. The National Academies’ report was sponsored by NIDA and SAMHSA.

A few weeks before the release of National Academies report, the National Academy of Medicine (NAM) held a webinar providing details on its Action Collaborative on Countering the U.S. Opioid Epidemic. The collaborative, a partnership of public and private stakeholders, aims to address the opioid crisis through a multidisciplinary, cross-sector effort.

The collaborative is represented by federal agencies, state and local governments, health care systems, provider groups, nonprofits, payers, industry, academia, patient organizations, and communities across about 55 organizations, according to Victor J. Dzau, MD, chair of the Action Collaborative and current NAM president. Over a 2-year period, the collaborative’s goal is to accelerate progress in overcoming the opioid crisis by recognizing the challenges, research gaps, and needs of organizations involved in the crisis and “elevate and accelerate evidence-based, multisectoral, and interprofessional solutions,” he said.

“This is not a problem that can be solved by a single sector. It is truly a whole of society problem,” said Adm. Brett P. Giroir, MD, assistant secretary for health at the U.S. Department of Health and Human Services, said during the webinar. “And the only way that we are going to be able to begin making inroads to reverse the trends of this crisis is if we work together.” Dr. Giroir also serves as cochair of the steering committee for the collaborative.

In its overview of the collaborative, the NAM outlined four working groups developed through a series of surveys and planning meetings that would identify the resources that currently exist to combat the opioid epidemic and determine which resources still need to be developed. In the Health Professional Education and Training Working Group, for example, the objective is to examine what is being taught to health professionals about acute and chronic pain management at an accreditation, certification, and regulatory level to develop educational tools based around knowledge gaps in those areas and analyze how the new resources are affecting health professions after they have been adopted, said Steve Singer, PhD, vice president of education and outreach at the Accreditation Council for Graduate Medical Education and colead of the working group.“Our goal is really to provide guidance and resources across the continuum of health professions and education with an interprofessional – and patient-informed view,” he said.

The Opioid Prescribing Guidelines and Evidence Standards Working Group plans to address the disparities in prescribing and tapering guidelines for acute and chronic pain as well as identify where pain management guidelines in different specialties “cannot be justified,” based on available evidence.

“Further, we think it’s really important to not just have guidelines that will sit on a shelf, but we also want to think about how we can support implementation of these guidelines into practice ... ” said Helen Burstin, MD, MPH, executive vice president and CEO for the Council of Medical Specialty Societies and colead of the working group.

Alonzo L. Plough, PhD, MPH, vice president of research-evaluation-learning at the Robert Wood Johnson Foundation and colead of the Prevention, Treatment, and Recovery Services Working Group, explained that the goal of his group is to identify the “essential elements and components” and best practices of prevention, treatment, and recovery for OUD. He noted that, although the working group will not be able to reach all patient populations affected by OUD, it has discussed targeting vulnerable high-risk populations, such as those involved in the criminal justice system, homeless veterans, mothers, and children.

“This is an ecosystem that requires great concentration and effort to make sure that there are integrated approaches throughout the continuum that work for patients and clients from different walks of life, and I think that our overall guidance is how we can recognize and use evidence to find those approaches and build on them for guidance,” he said.

The Research, Data, and Metrics Needs Working Group is tasked with collaborating with the other groups to obtain currently available information and identify what barriers exist to greater transparency, sharing and interoperability of data as well as what gaps in research currently exist that would further the collaborative’s mission, said Kelly J. Clark, MD, MBA, of the ASAM. “It is simply critical for us to utilize the data that’s out there, to pool it into more actionable information – and then to act on it,” Dr. Clark said.

The NAM is seeking new organizations interested in joining the collaborative as a network organization, which would receive updates and provide input on the collaborative but would not be a part of the working groups.

The first public meeting of the Action Collaborative on Countering the U.S. Opioid Epidemic will take place on April 30, 2019, in Washington.

Most people who could benefit from FDA-approved medications for opioid use disorder do not receive them, and access to those treatments is not equitable, according to a new consensus study report from the National Academies of Sciences, Engineering, and Medicine.

“Methadone, buprenorphine, and extended-release naltrexone are safe and highly effective medications that are already approved by the U.S. Food and Drug Administration to treat OUD,” the report said. “These medications save lives, but the majority of people with OUD in the United States receive no treatment at all.”

The report, called “Medications for Opioid Use Disorder Save Lives,” said a critical factor in addressing the crisis is “confronting the major barriers” to using those medications. It also said additional research will be needed to address opioid use disorder among subpopulations in the United States, such as adolescents, older adults, people with comorbidities, racial and ethnic groups, and people with low socioeconomic status. The National Academies’ report was sponsored by NIDA and SAMHSA.

A few weeks before the release of National Academies report, the National Academy of Medicine (NAM) held a webinar providing details on its Action Collaborative on Countering the U.S. Opioid Epidemic. The collaborative, a partnership of public and private stakeholders, aims to address the opioid crisis through a multidisciplinary, cross-sector effort.

The collaborative is represented by federal agencies, state and local governments, health care systems, provider groups, nonprofits, payers, industry, academia, patient organizations, and communities across about 55 organizations, according to Victor J. Dzau, MD, chair of the Action Collaborative and current NAM president. Over a 2-year period, the collaborative’s goal is to accelerate progress in overcoming the opioid crisis by recognizing the challenges, research gaps, and needs of organizations involved in the crisis and “elevate and accelerate evidence-based, multisectoral, and interprofessional solutions,” he said.

“This is not a problem that can be solved by a single sector. It is truly a whole of society problem,” said Adm. Brett P. Giroir, MD, assistant secretary for health at the U.S. Department of Health and Human Services, said during the webinar. “And the only way that we are going to be able to begin making inroads to reverse the trends of this crisis is if we work together.” Dr. Giroir also serves as cochair of the steering committee for the collaborative.

In its overview of the collaborative, the NAM outlined four working groups developed through a series of surveys and planning meetings that would identify the resources that currently exist to combat the opioid epidemic and determine which resources still need to be developed. In the Health Professional Education and Training Working Group, for example, the objective is to examine what is being taught to health professionals about acute and chronic pain management at an accreditation, certification, and regulatory level to develop educational tools based around knowledge gaps in those areas and analyze how the new resources are affecting health professions after they have been adopted, said Steve Singer, PhD, vice president of education and outreach at the Accreditation Council for Graduate Medical Education and colead of the working group.“Our goal is really to provide guidance and resources across the continuum of health professions and education with an interprofessional – and patient-informed view,” he said.

The Opioid Prescribing Guidelines and Evidence Standards Working Group plans to address the disparities in prescribing and tapering guidelines for acute and chronic pain as well as identify where pain management guidelines in different specialties “cannot be justified,” based on available evidence.

“Further, we think it’s really important to not just have guidelines that will sit on a shelf, but we also want to think about how we can support implementation of these guidelines into practice ... ” said Helen Burstin, MD, MPH, executive vice president and CEO for the Council of Medical Specialty Societies and colead of the working group.

Alonzo L. Plough, PhD, MPH, vice president of research-evaluation-learning at the Robert Wood Johnson Foundation and colead of the Prevention, Treatment, and Recovery Services Working Group, explained that the goal of his group is to identify the “essential elements and components” and best practices of prevention, treatment, and recovery for OUD. He noted that, although the working group will not be able to reach all patient populations affected by OUD, it has discussed targeting vulnerable high-risk populations, such as those involved in the criminal justice system, homeless veterans, mothers, and children.

“This is an ecosystem that requires great concentration and effort to make sure that there are integrated approaches throughout the continuum that work for patients and clients from different walks of life, and I think that our overall guidance is how we can recognize and use evidence to find those approaches and build on them for guidance,” he said.

The Research, Data, and Metrics Needs Working Group is tasked with collaborating with the other groups to obtain currently available information and identify what barriers exist to greater transparency, sharing and interoperability of data as well as what gaps in research currently exist that would further the collaborative’s mission, said Kelly J. Clark, MD, MBA, of the ASAM. “It is simply critical for us to utilize the data that’s out there, to pool it into more actionable information – and then to act on it,” Dr. Clark said.

The NAM is seeking new organizations interested in joining the collaborative as a network organization, which would receive updates and provide input on the collaborative but would not be a part of the working groups.

The first public meeting of the Action Collaborative on Countering the U.S. Opioid Epidemic will take place on April 30, 2019, in Washington.

Most people who could benefit from FDA-approved medications for opioid use disorder do not receive them, and access to those treatments is not equitable, according to a new consensus study report from the National Academies of Sciences, Engineering, and Medicine.

“Methadone, buprenorphine, and extended-release naltrexone are safe and highly effective medications that are already approved by the U.S. Food and Drug Administration to treat OUD,” the report said. “These medications save lives, but the majority of people with OUD in the United States receive no treatment at all.”

The report, called “Medications for Opioid Use Disorder Save Lives,” said a critical factor in addressing the crisis is “confronting the major barriers” to using those medications. It also said additional research will be needed to address opioid use disorder among subpopulations in the United States, such as adolescents, older adults, people with comorbidities, racial and ethnic groups, and people with low socioeconomic status. The National Academies’ report was sponsored by NIDA and SAMHSA.

A few weeks before the release of National Academies report, the National Academy of Medicine (NAM) held a webinar providing details on its Action Collaborative on Countering the U.S. Opioid Epidemic. The collaborative, a partnership of public and private stakeholders, aims to address the opioid crisis through a multidisciplinary, cross-sector effort.

The collaborative is represented by federal agencies, state and local governments, health care systems, provider groups, nonprofits, payers, industry, academia, patient organizations, and communities across about 55 organizations, according to Victor J. Dzau, MD, chair of the Action Collaborative and current NAM president. Over a 2-year period, the collaborative’s goal is to accelerate progress in overcoming the opioid crisis by recognizing the challenges, research gaps, and needs of organizations involved in the crisis and “elevate and accelerate evidence-based, multisectoral, and interprofessional solutions,” he said.

“This is not a problem that can be solved by a single sector. It is truly a whole of society problem,” said Adm. Brett P. Giroir, MD, assistant secretary for health at the U.S. Department of Health and Human Services, said during the webinar. “And the only way that we are going to be able to begin making inroads to reverse the trends of this crisis is if we work together.” Dr. Giroir also serves as cochair of the steering committee for the collaborative.

In its overview of the collaborative, the NAM outlined four working groups developed through a series of surveys and planning meetings that would identify the resources that currently exist to combat the opioid epidemic and determine which resources still need to be developed. In the Health Professional Education and Training Working Group, for example, the objective is to examine what is being taught to health professionals about acute and chronic pain management at an accreditation, certification, and regulatory level to develop educational tools based around knowledge gaps in those areas and analyze how the new resources are affecting health professions after they have been adopted, said Steve Singer, PhD, vice president of education and outreach at the Accreditation Council for Graduate Medical Education and colead of the working group.“Our goal is really to provide guidance and resources across the continuum of health professions and education with an interprofessional – and patient-informed view,” he said.

The Opioid Prescribing Guidelines and Evidence Standards Working Group plans to address the disparities in prescribing and tapering guidelines for acute and chronic pain as well as identify where pain management guidelines in different specialties “cannot be justified,” based on available evidence.

“Further, we think it’s really important to not just have guidelines that will sit on a shelf, but we also want to think about how we can support implementation of these guidelines into practice ... ” said Helen Burstin, MD, MPH, executive vice president and CEO for the Council of Medical Specialty Societies and colead of the working group.

Alonzo L. Plough, PhD, MPH, vice president of research-evaluation-learning at the Robert Wood Johnson Foundation and colead of the Prevention, Treatment, and Recovery Services Working Group, explained that the goal of his group is to identify the “essential elements and components” and best practices of prevention, treatment, and recovery for OUD. He noted that, although the working group will not be able to reach all patient populations affected by OUD, it has discussed targeting vulnerable high-risk populations, such as those involved in the criminal justice system, homeless veterans, mothers, and children.

“This is an ecosystem that requires great concentration and effort to make sure that there are integrated approaches throughout the continuum that work for patients and clients from different walks of life, and I think that our overall guidance is how we can recognize and use evidence to find those approaches and build on them for guidance,” he said.

The Research, Data, and Metrics Needs Working Group is tasked with collaborating with the other groups to obtain currently available information and identify what barriers exist to greater transparency, sharing and interoperability of data as well as what gaps in research currently exist that would further the collaborative’s mission, said Kelly J. Clark, MD, MBA, of the ASAM. “It is simply critical for us to utilize the data that’s out there, to pool it into more actionable information – and then to act on it,” Dr. Clark said.

The NAM is seeking new organizations interested in joining the collaborative as a network organization, which would receive updates and provide input on the collaborative but would not be a part of the working groups.

The first public meeting of the Action Collaborative on Countering the U.S. Opioid Epidemic will take place on April 30, 2019, in Washington.

The findings could lead the way to understanding the brain’s intake and output of energy in good health and bad and the part that alcohol plays.

In previous studies, the researchers have shown that alcohol significantly affects brain glucose metabolism, a measure of energy use, as well as regional brain activity, assessed through changes in blood oxygenation. But regional differences in glucose metabolism are hard to interpret, they say. In a study with healthy volunteers, they used brain imaging techniques to help quantify “match and mismatch” in energy consumption and expenditure across the brain—what they termed power and cost.

The researchers assessed power by observing to what extent brain regions are active and use energy, and cost by observing how brain regions expended energy. They found that different brain regions that serve distinct functions have “notably different power and different cost.”

Next, they tested a group of light drinkers and heavy drinkers and found both acute and chronic exposure to alcohol affected power and cost. In heavy drinkers, the researchers say, they saw less regional power, for example, in the thalamus, the sensory gateway, and frontal cortex. The researchers interpreted the decreases in power as reflecting the toxic effects of long-term exposure to alcohol on the brain cells.

They also found power dropped in the visual regions during acute alcohol exposure, which was related to disruption of visual processing. Visual regions also had the most significant drops in cost of activity during intoxication. That is consistent with the reliance of those regions on alternative energy sources, such as acetate (a byproduct of alcohol metabolism), the researchers say.

Their approach for characterizing brain energetic patterns related to alcohol use could be useful in other ways, the researchers say. “Studying energetic signatures of brain regions in different neuropsychiatric diseases is an important future direction,” said co-lead investigator Dr. Ehsan Schokri-Kojori. “The measures of power and cost may provide new multimodal biomarkers.”

The findings could lead the way to understanding the brain’s intake and output of energy in good health and bad and the part that alcohol plays.

In previous studies, the researchers have shown that alcohol significantly affects brain glucose metabolism, a measure of energy use, as well as regional brain activity, assessed through changes in blood oxygenation. But regional differences in glucose metabolism are hard to interpret, they say. In a study with healthy volunteers, they used brain imaging techniques to help quantify “match and mismatch” in energy consumption and expenditure across the brain—what they termed power and cost.

The researchers assessed power by observing to what extent brain regions are active and use energy, and cost by observing how brain regions expended energy. They found that different brain regions that serve distinct functions have “notably different power and different cost.”

Next, they tested a group of light drinkers and heavy drinkers and found both acute and chronic exposure to alcohol affected power and cost. In heavy drinkers, the researchers say, they saw less regional power, for example, in the thalamus, the sensory gateway, and frontal cortex. The researchers interpreted the decreases in power as reflecting the toxic effects of long-term exposure to alcohol on the brain cells.

They also found power dropped in the visual regions during acute alcohol exposure, which was related to disruption of visual processing. Visual regions also had the most significant drops in cost of activity during intoxication. That is consistent with the reliance of those regions on alternative energy sources, such as acetate (a byproduct of alcohol metabolism), the researchers say.

Their approach for characterizing brain energetic patterns related to alcohol use could be useful in other ways, the researchers say. “Studying energetic signatures of brain regions in different neuropsychiatric diseases is an important future direction,” said co-lead investigator Dr. Ehsan Schokri-Kojori. “The measures of power and cost may provide new multimodal biomarkers.”

The findings could lead the way to understanding the brain’s intake and output of energy in good health and bad and the part that alcohol plays.

In previous studies, the researchers have shown that alcohol significantly affects brain glucose metabolism, a measure of energy use, as well as regional brain activity, assessed through changes in blood oxygenation. But regional differences in glucose metabolism are hard to interpret, they say. In a study with healthy volunteers, they used brain imaging techniques to help quantify “match and mismatch” in energy consumption and expenditure across the brain—what they termed power and cost.

The researchers assessed power by observing to what extent brain regions are active and use energy, and cost by observing how brain regions expended energy. They found that different brain regions that serve distinct functions have “notably different power and different cost.”

Next, they tested a group of light drinkers and heavy drinkers and found both acute and chronic exposure to alcohol affected power and cost. In heavy drinkers, the researchers say, they saw less regional power, for example, in the thalamus, the sensory gateway, and frontal cortex. The researchers interpreted the decreases in power as reflecting the toxic effects of long-term exposure to alcohol on the brain cells.

They also found power dropped in the visual regions during acute alcohol exposure, which was related to disruption of visual processing. Visual regions also had the most significant drops in cost of activity during intoxication. That is consistent with the reliance of those regions on alternative energy sources, such as acetate (a byproduct of alcohol metabolism), the researchers say.

Their approach for characterizing brain energetic patterns related to alcohol use could be useful in other ways, the researchers say. “Studying energetic signatures of brain regions in different neuropsychiatric diseases is an important future direction,” said co-lead investigator Dr. Ehsan Schokri-Kojori. “The measures of power and cost may provide new multimodal biomarkers.”