This Week in the ASAM Weekly

If you’ll be at ASAM’s 55th Annual Conference this week, we’ve got several publications to keep you busy while you travel, in-between presentations, or while you’re waiting to meet old (or new!) friends and colleagues. We’ve even got several that make good conversation starters.

First, the publications included under “Learn More” are brief but thought-provoking. Although opioid withdrawal syndrome was characterized in the 1940s and withdrawal treatments are used for more patients per year than any other form of OUD treatment, we still lack a clear consensus on how to define and address it (Lancet Psychiatry). Principles of primary care medicine such as a medication-first approach supported by behavioral interventions, specialty referral, and active listening position the field well to treat a chronic illness like opioid use disorder, creating the opportunity to increase treatment access (Journal of General Internal Medicine).

Professor Nutt et al briefly review the last 70 years of psychedelic research, focusing on recent research developments and emerging neuroscience as well as future (Journal of Studies on Alcohol and Drugs), while indirectly demonstrating the significance of set, setting, and suggestibility. A Letter to the Canadian Medical Association Journal raises concern about recommendation 13 from the recently published Canadian guideline on AUD, which discouraged the use of SSRI’s for comorbid anxiety and depression.

Canada is ahead of the US with regards to cannabis legalization, so there is much we can learn from their experience. Increases in cannabis use and heavy cannabis use continue a preexisting trend, the illicit cannabis market is shrinking, use of processed cannabis products is increasing, but public education seems to be working (International Journal of Drug Policy).

Finally, our lead publication adds to the important research from Japan on methamphetamine use and psychosis. Scientists identified epigenetic changes that may account for the long-term biological changes related to methamphetamine dependence; these results are similar to what has been found with other neuropsychiatric disorders, such as schizophrenia (Addiction Biology).

Hope to see you in Dallas.

Nicholas Athanasiou, MD, MBA, DFASAM
Editor in Chief

with Co-Editors: Brandon Aden, MD, MPH, FASAM, Jack Woodside, MD, John A. Fromson, MD

Lead Story

Epigenome-wide association study on methamphetamine dependence 🔓

Addiction Biology

The authors of this study postulate that some of the biologic changes resulting from methamphetamine use may be associated with epigenetic changes from DNA methylation. Such associations have been seen in schizophrenia, mood disorder, obsessive-compulsive disorder, and Parkinson’s disease. Subjects with methamphetamine dependence (n=24) as well as age and sex matched controls had an epigenome-wide analysis of DNA methylation and identification of sites where methylation differed between subjects with methamphetamine dependence and controls. Thirteen regions with differential methylation were found. Of particular interest was hypomethylation of the CNOT1 and PUM1 genes leading to alterations in mRNA metabolism similar to those seen in bipolar disorder and schizophrenia. These changes relate to symptoms in common such as psychosis. The authors conclude that symptoms seen in methamphetamine dependency may result from genetic changes similar to those in other psychiatric disorders.

Research and Science

How have cannabis use and related indicators changed since legalization of cannabis for non-medical purposes? Results of the Canadian Cannabis Survey 2018–2022 🔓

International Journal of Drug Policy

Cannabis use for non-medical purposes was legalized and regulated in Canada through the Cannabis Act in October 2018. This study examined trends in use of cannabis for non-medical purposes and related indicators from pre- to post-legalization in Canada (2018–2022). Past 12-month cannabis consumption increased among Canadians from 22% in 2018 to 27% in 2022. Similarly, daily/almost daily (DAD) consumption increased from 5% in 2018 to 7% in 2022. Consumption of dried flower, hash/kief, and concentrates/extracts (e.g., wax, shatter, budder) decreased since 2018, whereas consumption of edibles, beverages, and vape pens/cartridges increased. Legal purchasing increased from 4% in 2018 to 69% in 2022, while accessing cannabis through social and illegal sources decreased over time. The legal market is increasingly displacing the illicit cannabis market in Canada.

Prison Buprenorphine Implementation and Postrelease Opioid Use Disorder Outcomes 🔓

JAMA Network Open

This cohort study involved 15,225 adults incarcerated and released from prisons in Massachusetts. When buprenorphine treatment began to be offered during incarceration (previously only naltrexone was available), postrelease buprenorphine receipt in the community increased, accompanied by a smaller decrease in naltrexone receipt. When stratified by sex, there was also a small decrease in postrelease all-cause mortality in the male cohort (and a decrease in postrelease opioid overdose in the female cohort that was not statistically significant). These results suggest that offering buprenorphine during incarceration might improve treatment receipt during the critical postrelease period.

Patients' Perspectives on Discontinuing Buprenorphine for the Treatment of Opioid Use Disorder

Journal of Addiction Medicine

Medication for opioid use disorder (MOUD), including buprenorphine, is known to reduce morbidity and mortality, but many patients discontinue buprenorphine within the first year. In this qualitative study, the authors interviewed patients who had discontinued treatment to understand why. Reported reasons included logistical hurdles, such as beliefs about high hurdles to return to care after missing appointments or frequency of visits required. Rule violations were also a reported issue, including requirement for abstinence from other substances. Medication effects were also a barrier, including attributed adverse effects and ineffective control of pain. A final reported reason was the desire to return to opioid use, in one case to self-manage psychological issues. Addressing some of these factors could improve retention.

Learn More

Addressing Opioid Use Disorder in Primary Care: Revisiting Core Primary Care Principles to Confidently Initiate Treatment 🔓

Journal of General Internal Medicine

Efforts have been made to increase access to medication for opioid use disorder (OUD), particularly in primary care settings. The authors note the history of primary care and principles used to manage other complicated chronic medical conditions also apply to OUD. First, just as under the medication-first principle providers would swiftly initiate medication for severe hypertension, they should initiate medications for patients with OUD. The second principle of supporting medication with behavior interventions and referral to specialist when needed, also aptly applies. The third principle, utilizing patient narratives to inform care, is an important component of treating patients with OUD. The authors advocate for primary care providers to embrace these principles and initiate OUD treatment when opportunities occur.

A perspective on psychedelics as treatments for addictions: Past, Present, and Future

Journal of Studies on Alcohol and Drugs

This Perspectives piece gives a brief overview on the last 70 years of psychedelic research in relation to the treatment of mental illness with a particular focus on addictions. It then reviews work in the 1950s/60s that started following the discovery of LSD and recent research developments related to neuroscience, the rise of MDMA use in psychotherapy, and the emergence of ketamine as a treatment for mental illnesses. Brain mechanisms of these therapeutic effects are also highlighted. The current status of research and future challenges in the field are reviewed. Work with botanically derived psychedelics should learn and benefit from the extensive knowledge available from Indigenous groups who have used psychedelics for spiritual purposes. With ketamine as perhaps the most widely accepted and used substance in this category, a framework for research and transition to clinical practice is available.

Establishing a research agenda for the study and assessment of opioid withdrawal

The Lancet Psychiatry

The authors of this article call for increased research on opioid withdrawal. They note that withdrawal is frequently cited as a reason that people continue to use opioids. They also see considerable inconsistency between the many opiate withdrawal scales. For example, the authors note that insomnia is not part of 60% of the most used scales. Few scales have had psychometric analysis to establish validity. The authors outline nine areas of research, including: how do withdrawal symptoms differ for different opioids, how other substances (methamphetamine, xylazine) affect withdrawal, research on precipitated withdrawal and its treatment, study of protracted withdrawal, and development of biomarkers for opioid withdrawal severity. The authors conclude that improving treatment of opioid withdrawal will improve treatment of opioid use disorder.

Navigating the nuances of the Canadian guideline’s stance on selective serotonin reuptake inhibitors in concurrent alcohol use disorder and mood or anxiety disorders 🔓

Canadian Medical Association Journal

This letter was written in response to the recently published Canadian guideline for treatment of alcohol use disorder (AUD). The guideline states that SSRIs should not be used to treat depression and anxiety in the context of AUD, citing a lack of quality evidence supporting their use, the fact that depression symptoms reduce rapidly with abstinence, and evidence that SSRIs may worsen drinking outcomes. The authors feel the studies cited for increased drinking with SSRIs are not convincing due to small sample sizes and conflicting results. For example, a small sertraline trial found worse drinking outcomes in early-onset AUD but improved outcomes in late-onset AUD. The guideline cautions that it is not referring to “severe psychiatric conditions.” The letter’s authors suggest that SSRIs be continued for patients who have benefited from them with monitoring for additional benefit or harm.

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