反差系列

This Week in the ASAM Weekly

Although not well-known, subliminal menthol has been around since the 1950s. It’s a level of menthol added to cigarettes that is too low to be perceived by taste, but just high enough to enhance other flavors of tobacco, reduce harshness, and facilitate smoking. What is troubling is that although many countries have banned the use of menthol, many of these bans apply only to “characterizing flavors,” which subliminal menthol is not (). 

Even completely banning menthol still leaves loopholes to be exploited. WS-3 is an odorless, synthetic agent that has a similar cooling effect as menthol by acting upon the same receptor (TRPM8). An opinion article from  argues that such bans should instead target the downstream concern, such as a “cooling effect” that enhances smoking, rather than the whack-a-mole approach of targeting specific chemicals. It’s important to get this right, because cigarette smoking continues to be a significant cause of morbidity, mortality, and rising health care costs in the US ().

In a way, these articles underscore the importance of thoughtfully applying scientific evidence. For example, anecdotal reports have created hype around the use of semaglutides in alcohol use disorders, but a retrospective observational study is now providing real-world evidence of a therapeutic benefit. Yet the authors are clear in stating that it is “insufficient to justify…off-label [use] to treat AUD”- randomized clinical trials are needed for that (). Similarly, Dr. Nora Volkow, director of the National Institute on Drug Abuse (NIDA) and also one of the above study’s authors, cautioned a Senate subcommittee on the hype around psychedelic medicine as it was “being offered to a wide variety of patients without sufficient evidence.” While she equated this to believing in “fairy tales,” she also recognized the incredible promise to come from further research ().

It shouldn’t be so shocking then, as some have reported (), that the FDA advisory panel has recommended against the use of MDMA in the treatment of PTSD. The panel cited several concerns: strength and integrity of the scientific research, risks to patients, and the influence of therapy in evaluating a medication, just to name a few (). In addition, this shouldn’t be viewed as an all-out rejection of psychedelic medicine; rather, it’s an advisory panel concluding that for a particular treatment “more research is needed.” How much more is what we should focus on.

Thanks for reading,

Nicholas Athanasiou, MD, MBA, DFASAM
Editor in Chief

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

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Lead Story

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Nature Communications

In this retrospective cohort study of patients receiving medication for treatment of obesity, the authors evaluated the association of semaglutide with incidence and recurrence of alcohol use disorder (AUD). In the cohort, patients received semaglutide or non-GLP1RA medications, including naltrexone and topiramate. In matched cohort analysis, patients who received semaglutide had much lower rates of incident AUD (HR=0.5) compared to those receiving non-GLP1RA medications; in sub-analysis comparing semaglutide to naltrexone/topiramate, they also had lower incident AUD (HR=0.44). Among those with a history of AUD, semaglutide was also associated with lower recurrence of AUD (HR=0.44) overall and in sub-analysis (HR=0.25). These findings support the potential benefit of semaglutide for AUD in a real-world population and need for randomized clinical trials. 

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Research and Science

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Journal of Psychiatry and Neuroscience

This study used MRI to measure thickness of brain cortical gray matter in 95 patients with ketamine use disorder (KUD) and 169 drug-free controls. Patients with KUD had significant psychiatric symptoms, including psychotic symptoms (72%), depressive symptoms (62%), memory impairment (47%), and irritability (33%). Patients with KUD also had widespread reductions in cortical thickness compared to controls. The most severe reductions were found in the frontal and parietal lobes. Estimated lifetime ketamine consumption correlated with reduced cortical thickness in some regions; however, age of onset of ketamine use showed no correlations. The authors note the need for greater understanding of the mechanism of cortical thickness reduction in KUD.

Drug and Alcohol Dependence

Researchers searched for and reviewed articles concerning digital health interventions for women with OUD. The majority (12) of the 17 articles concerned the peripartum period. The most common intervention was telemedicine; also included were wireless overdose response buttons, telephone motivational interviewing, and a smartphone-based relapse prevention system. A wide variety of outcomes were measured such as retention in treatment, appointments kept, and urine drug screens. One study provided smartphones to address the barrier of digital inequality. Interpersonal violence was addressed in a study by selecting a code word during in-person visits that could then be used during virtual visits to signal the patient was in an unsafe environment. The wireless overdose buttons were also used to signal gender-based violence. The authors call for more studies covering the postpartum period which carries a high risk for overdose and death.

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JAMA Network Open

This study examined the association of smoking with health care expenditures among US adults with chronic lower respiratory disease. A cross-sectional methodology utilized 13,017 adults with chronic lower respiratory disease in 2020. A weighted 31.3% and 31.2% of those aged 35 to 64 years were current and former smokers, respectively, with annual smoking attributable health care expenditures (SAHEs) of $13.6 billion, or $2,752 per current smoker and $1,083 per former smoker. Among those 65 years or older, a weighted 19.2% were current smokers and 54.3% were former smokers, with annual SAHEs of $5.3 billion, or $1,704 per current smoker and $682 per former smoker. The high SAHEs found in this study suggest the importance of targeted cessation interventions for this population.

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JAMA Health Forum

While the opioid overdose epidemic is well recognized, we understand little about the friends, families, and acquaintances who mourn those losses. This cross-sectional study sought to better understand this group and found that an estimated 82.7 million US adults experienced a personal loss, with 48.9 million experiencing the loss of a family member or close friend. Those with lower income were more likely to experience a loss, but otherwise loss was similar across all demographics, including age, sex, race, education, political affiliation, and geographic region. Those who had experienced a loss were more likely to recognize addiction policies as important, and the authors suggest that since loss occurs across all demographics and political affiliations, there is an opportunity to mobilize people to affect policy.

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Psychological Medicine

This study included 11,363 residents of Ontario, Canada, initially between ages 12 and 24 who had completed the Canadian Community Health Survey between 2009 and 2012. They were followed until 2018 for an endpoint of new onset psychotic disorder. Past year cannabis use was reported by 23% of respondents and 1.2% used health services for psychotic disorders during the follow-up. In younger respondents, 12-19 years, cannabis use was highly associated with a psychotic disorder during follow-up (aHR=11.2). This was not true for older respondents, 20-33 years, (aHR=1.3). The authors note that the risk they found is greater than in previous studies and attribute this to the increased potency of cannabis since the earlier studies. They conclude these results support the theory that adolescence is a vulnerable time to use cannabis.

Drug and Alcohol Dependence

This study sought to understand the reasons that tobacco companies use non-perceptible (subliminal) levels of menthol. Researchers used previously secret internal tobacco company documents dated 1955 to 2012 in the Truth Tobacco Industry Documents archive on menthol at subliminal levels. Beginning in at least the 1950s, tobacco companies used subliminal menthol to compensate the flavor loss caused by filters, reduce smoke harshness, reduce dryness, and increase smoke coolness. Varying menthol concentrations were considered to help convert people who smoke non-menthol to menthol brands, possibly because people who smoke menthol have more difficulty quitting than people who smoke non-menthol cigarettes.

Computers in Biology and Medicine

While buprenorphine is an effective treatment for opioid use disorder (OUD), some patients discontinue treatment early with increased risk of relapse and overdose. This study used claims data and machine learning (ML) models to assess factors that may predict early discontinuation of buprenorphine. The authors identified a few important predictors, including age, initial days of supply and early medication adherence. They suggest using ML models in clinical practice could help identify patients at risk of earlydiscontinuation and allow providers to personalize treatment to improve patient retention in long-term treatment.

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