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This Week in the ASAM Weekly

Dr. Nora Volkow, director of the National Institute on Drug Abuse, recently advocated for broadening access to methadone treatment for OUD (). While some politicians or trade groups may frame this as radical, such leading-expert opinion is based on scientific evidence and an appreciation for a rapidly evolving addiction crisis. As the lead article demonstrates, the increasing co-use of stimulants and opioids has significantly increased the risk for overdose death, and the possible reasons tell only part of the story: discontinuation of opioid agonist treatment, lack of similar medications for stimulants, potency of illicit drug supply, etc…(). 

Scientific and political innovation will help us catch up to the crisis. A promising vaccine demonstrated efficacy in both male and female rats to several physiological properties of fentanyl without blocking effects of other opioids (). Future direction in depression treatment may involve a better understanding of the opioid system ().And Italy has developed a system of wastewater-based epidemiology that could better prepare us for future trends in the use of major and new psychoactive substances ().

Dr. Volkow has also been advocating to update the institute’s name to the National Institute of Drugs and Addiction. Such choice words will speak volumes and such action will inspire others, but such change may take an act of Congress (). 

Thanks for reading,

Nicholas Athanasiou, MD, MBA, DFASAM
Editor in Chief

with Co-Editors: Brandon Aden, MD, Debra R. Newman, PA-C, MSPAS, MPH, Jack Woodside, MD, John A. Fromson, MD

Lead Story

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BMC Public Health

The authors note a dramatic increase in the use of methamphetamine in people with OUD and an increased presence of a stimulant in opioid toxicity deaths. A random sample of 20% of persons in the overdose registry of the Province of British Columbia, Canada, was selected for years 2010 to 2018. Persons who used opioids, stimulants, or both (n=7460) were identified by ICD codes and fatal overdose events determined from coroners’ data. People using both opioids and stimulants had twice the risk of fatal overdose compared to those using opioids only (HR=2.02, p<0.001). People using stimulants alone had a similar risk of fatal overdose to those using opioids alone (HR=1.05, p=0.76). The authors note that while concern has been directed toward the opioid crisis, people who use stimulants have a similar risk of fatal overdose. They call for increased support for people who use stimulants. 

Research and Science 

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The Lancet Psychiatry

This retrospective cohort study investigated the risk of all-cause death and years lost following hospitalization in people with a previous hospitalization for a substance use disorder (SUD). Using Czech national health registries, individuals with a SUD had an increased risk of death due to any cause after the onset of 26 out of 28 physical health conditions, in comparison to those without a SUD. Individuals with SUDs had substantial years lost after the onset of physical health conditions; in most cases, considerably larger losses than those without SUDs. 

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Pharmaceutics

Fentanyl (FEN) is a potent synthetic opioid associated with increasing incidence of opioid use disorder (OUD) and fatal opioid overdose. Vaccine immunotherapy for FEN-associated disorders may be a viable therapeutic strategy. In this study, immunized male and female rats produced significant levels of anti-FEN antibodies that were highly effective at neutralizing FEN–induced antinociception in the tail flick assay and hot plate assays. The vaccine also decreased FEN brain levels following drug administration. Immunization blocked FEN-induced, but not morphine-induced, rate-disrupting effects on schedule-controlled responding. Cross-reactivity assays showed anti-FEN antibodies bound to FEN and sufentanil but not to morphine, methadone, buprenorphine, or oxycodone. These data support further clinical development of this vaccine to address OUD in humans.

Substance Use and Misuse

While opioid use disorder (OUD) among adolescents has increased, they are less likely to access treatment, particularly medications for opioid use disorders (MOUD). In this paper, the authors interviewed prescribers and non-prescribers who attended a learning series focused on treatment of adolescents to assess perceptions on providing MOUD to adolescents. While prescribers were overwhelmingly supportive of providing MOUD to adolescents, including those under the age 18, non-prescribers were less likely to support MOUD for adolescents, particularly those under 18. Major barriers reported were lack of training and experience and increases in social work and mental health services were needed to increase access. 

Learn More

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Journal of Addiction Medicine

In this commentary, the authors propose take-home naloxone (THN) and overdose education at all federally-qualified opioid treatment programs (OTPs). Broadening the reach, patients enrolled at an OTP can educate their social network about its benefits. Should mandating THN at OTPs be successful, the practice could be considered for anyone leaving a federal correctional facility with a diagnosis of an OUD. From a public health perspective, THN may also encourage people who misuse opioids, including those who have been reversed by naloxone, to engage in treatment.

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La Clinica Terapeutica

Drug use epidemiology has been based on questionnaires where accuracy is subject to sampling bias and subjects’ truthfulness. This letter describes the use of wastewater screening for drug metabolites used in 33 cities in Italy to monitor the epidemiology of drug use. Results are expressed as doses per 1000 inhabitants based on the size of a typical dose and knowledge of its metabolism. Results show trends of increase or decrease in the use of specific substances over time. Also, the mix of substances differs from city to city. In addition, 69 new psychoactive substances were identified. They conclude that this is a valuable tool for tracking patterns of drug use and trafficking.  

Addictive Behaviors

While operant conditioning is a well-studied etiology of excessive gambling, the authors argue that a more complex motivation exists. Current models do not account for people’s perceptions of contingency and the relationship between their behavior and outcomes. In addition, people can modify schedules of rewards to which they are exposed, particularly on slot machines, by choosing the number of lines and amounts of bets. There are short and long-term schedule-based rewards that may influence behavior. Finally, there is a potential role for negative reinforcement, specifically regret or anticipated regret about not placing a bet. Research is needed to better understand this complex behavior and to inform future interventions and policies. 

Biological Psychiatry

This commentary examines the findings of Carazo-Arias et al.* As antidepressant treatments evolve, it is likely that the opioid systems will become one of the core modulatory systems to target, either directly using mu opioid receptors (MORs), delta opioid receptors (DORs), kappa opioid receptors (KOR), or indirectly via SSRIs or tricyclic antidepressants. Depression can undoubtedly have many different etiologies and will require different pharmacotherapies. Future research will need to assess if fluoxetine efficacy always requires endogenous opioid systems for alleviating negative affective states.

*. Biol Psychiatry 2022

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