Eric M. Wargo

Bio: Eric M. Wargo is an academic researcher from National Institute on Drug Abuse. The author has contributed to research in topics: Methadone & Heroin. The author has an hindex of 8, co-authored 10 publications receiving 682 citations.

Prevention and Treatment of Opioid Misuse and Addiction: A Review.

Abstract: 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.

The Risks of Marijuana Use During Pregnancy.

Abstract: Currently, 29 states and Washington, DC, have passed laws to legalize medical marijuana. Although evidence for the effectiveness of marijuana or its extracts for most medical indications is limited and in many cases completely lacking, there are a handful of exceptions. For example, there is increasing evidence for the efficacy of marijuana in treating some forms of pain and spasticity, and 2 cannabinoid medications (dronabinol and nabilone) are approved by the US Food and Drug Administration for alleviating nausea induced by cancer chemotherapy. A systematic review and meta-analysis by Whiting et al1 found evidence, although of low quality, for the effectiveness of cannabinoid drugs in the latter indication. The antinausea effects of tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana, are mediated by the interactions of THC with type 1 cannabinoid (CB1) receptors in the dorsal vagal complex. Cannabidiol, another cannabinoid in marijuana, exerts antiemetic properties through other mechanisms. Nausea is a medically approved indication for marijuana in all states where medical use of this drug has been legalized. However, some sources on the internet are touting marijuana as a solution for the nausea that commonly accompanies pregnancy, including the severe condition hyperemesis gravidarum. Although research on the prevalence of marijuana use by pregnant women is

Promising roles for pharmacists in addressing the U.S. opioid crisis.

Abstract: Overdoses of prescription or illicit opioids claimed the lives of 116 Americans each day in 2016, and the crisis continues to escalate. As healthcare systems evolve to address the crisis, the potential of pharmacists to make a positive difference is significant. In addition to utilizing available prescription drug monitoring programs to help prevent diversion of opioids, practicing pharmacists can be alert for signs of opioid misuse by patients (e.g., multiple prescriptions from different physicians) as well as inappropriate prescribing or hazardous drug combinations that physicians may not be aware of (e.g., opioid analgesics combined with benzodiazepines). They can also supply patients with information on risks of opioids, proper storage and disposal of medications, and the harms (and illegality) of sharing medications with other people. Increasingly, pharmacies are sites of distribution of the opioid antagonist naloxone, which has been shown to save lives when made available to opioid users and their families or other potential bystanders to an overdose; and pharmacists can provide guidance about its use and even legal protections for bystanders to an overdose that customers may not be aware of. Pharmacists can also recommend addiction treatment to patients and be a resource for information on addiction treatment options in the community. As addiction treatment becomes more integrated with general healthcare, pharmacies are also increasingly dispensing medications like buprenorphine and, in the future, possibly methadone. Pharmacists in private research labs and at universities are helping to develop the next generation of addiction treatments and safer, non-addictive pain medications; they can also play a role in implementation research to enhance the delivery of addiction interventions and medications in pharmacy settings. Meanwhile, pharmacists in educational settings can promote improved education about the neurobiology and management of pain and its links to opioid misuse and addiction.

Overdose Prevention Through Medical Treatment of Opioid Use Disorders

Abstract: In their article, Larochelle and colleagues provided convincing evidence of the benefits of methadone and buprenorphine in preventing opioid-related deaths in patients with a history of nonfatal op...

Review Article: Neurobiologic Advances from the Brain Disease Model of Addiction

Abstract: This article reviews scientific advances in the prevention and treatment of substance-use disorder and related developments in public policy. In the past two decades, research has increasingly supported the view that addiction is a disease of the brain. Although the brain disease model of addiction has yielded effective preventive measures, treatment interventions, and public health policies to address substance-use disorders, the underlying concept of substance abuse as a brain disease continues to be questioned, perhaps because the aberrant, impulsive, and compulsive behaviors that are characteristic of addiction have not been clearly tied to neurobiology. Here we review recent advances in the neurobiology of addiction to clarify the link between addiction and brain function and to broaden the understanding of addiction as a brain disease. We review findings on the desensitization of reward circuits, which dampens the ability to feel pleasure and the motivation to pursue everyday activities; the increasing strength of conditioned responses and stress reactivity, which results in increased cravings for alcohol and other drugs and negative emotions when these cravings are not sated; and the weakening of the brain regions involved in executive functions such as decision making, inhibitory control, and self-regulation that leads to repeated relapse. We also review the ways in which social environments, developmental stages, and genetics are intimately linked to and influence vulnerability and recovery. We conclude that neuroscience continues to support the brain disease model of addiction. Neuroscience research in this area not only offers new opportunities for the prevention and treatment of substance addictions and related behavioral addictions (e.g., to food, sex, and gambling) but may also improve our understanding of the fundamental biologic processes involved in voluntary behavioral control. In the United States, 8 to 10% of people 12 years of age or older, or 20 to 22 million people, are addicted to alcohol or other drugs. 1 The abuse of tobacco, alcohol, and illicit drugs in the United States exacts more than $700 billion annually in costs related to crime, lost work productivity, and health care. 2-4 After centuries of efforts to reduce addiction and its related costs by punishing addictive behaviors failed to produce adequate results, recent basic and clinical research has provided clear evidence that addiction might be better considered and treated as an acquired disease of the brain (see Box 1 for definitions of substance-use disorder and addiction). Research guided by the brain disease model of addiction has led to the development of more effective methods of prevention and treatment and to more informed public health policies. Notable examples include the Mental Health Parity and Addiction Equity Act of 2008, which requires medical insurance plans to provide the same coverage for substance-use disorders and other mental illnesses that is provided for other illnesses, 5 and the proposed bipartisan Senate legislation that From the National Institute on Drug Abuse (N.D.V.) and the National Institute of Alcohol Abuse and Alcoholism (G.F.K.) — both in Bethesda, MD; and the Treatment Research Institute, Philadelphia (A.T.M.). Address reprint requests to Dr. Volkow at the National Institute on Drug Abuse, 6001 Executive Bld., Rm. 5274, Bethesda, MD 20892, or at nvolkow@ nida . nih . gov.

Reproducible brain-wide association studies require thousands of individuals

Abstract: Magnetic resonance imaging (MRI) has transformed our understanding of the human brain through well-replicated mapping of abilities to specific structures (for example, lesion studies) and functions1-3 (for example, task functional MRI (fMRI)). Mental health research and care have yet to realize similar advances from MRI. A primary challenge has been replicating associations between inter-individual differences in brain structure or function and complex cognitive or mental health phenotypes (brain-wide association studies (BWAS)). Such BWAS have typically relied on sample sizes appropriate for classical brain mapping4 (the median neuroimaging study sample size is about 25), but potentially too small for capturing reproducible brain-behavioural phenotype associations5,6. Here we used three of the largest neuroimaging datasets currently available-with a total sample size of around 50,000 individuals-to quantify BWAS effect sizes and reproducibility as a function of sample size. BWAS associations were smaller than previously thought, resulting in statistically underpowered studies, inflated effect sizes and replication failures at typical sample sizes. As sample sizes grew into the thousands, replication rates began to improve and effect size inflation decreased. More robust BWAS effects were detected for functional MRI (versus structural), cognitive tests (versus mental health questionnaires) and multivariate methods (versus univariate). Smaller than expected brain-phenotype associations and variability across population subsamples can explain widespread BWAS replication failures. In contrast to non-BWAS approaches with larger effects (for example, lesions, interventions and within-person), BWAS reproducibility requires samples with thousands of individuals.

Reproducible brain-wide association studies require thousands of individuals

Abstract: Magnetic resonance imaging (MRI) has transformed our understanding of the human brain through well-replicated mapping of abilities to specific structures (for example, lesion studies) and functions1-3 (for example, task functional MRI (fMRI)). Mental health research and care have yet to realize similar advances from MRI. A primary challenge has been replicating associations between inter-individual differences in brain structure or function and complex cognitive or mental health phenotypes (brain-wide association studies (BWAS)). Such BWAS have typically relied on sample sizes appropriate for classical brain mapping4 (the median neuroimaging study sample size is about 25), but potentially too small for capturing reproducible brain-behavioural phenotype associations5,6. Here we used three of the largest neuroimaging datasets currently available-with a total sample size of around 50,000 individuals-to quantify BWAS effect sizes and reproducibility as a function of sample size. BWAS associations were smaller than previously thought, resulting in statistically underpowered studies, inflated effect sizes and replication failures at typical sample sizes. As sample sizes grew into the thousands, replication rates began to improve and effect size inflation decreased. More robust BWAS effects were detected for functional MRI (versus structural), cognitive tests (versus mental health questionnaires) and multivariate methods (versus univariate). Smaller than expected brain-phenotype associations and variability across population subsamples can explain widespread BWAS replication failures. In contrast to non-BWAS approaches with larger effects (for example, lesions, interventions and within-person), BWAS reproducibility requires samples with thousands of individuals.