This Week in Addiction Medicine from ASAM

Lead Story: Adolescents’ and Young Adults’ Perceptions of Risks and Benefits Differ by Type of Cannabis Products

Adolescents’ and young adults’ perceptions of risks and benefits differ by type of cannabis products
Addictive Behaviors
Cannabis use patterns among adolescents and young adults (AYAs) have changed recently, with increasing use of non-combustible cannabis products. This survey of 433 California AYAs compared a variety of perceived risks and benefits corresponding to short-term and long-term use of combustible, blunt, vaporized, and edible cannabis, and between "ever" and "never" users. Combustible cannabis and blunts were perceived to have greater risks and benefits than vaporized/edible cannabis. The most common perceived risks were “get into trouble” and “become addicted.” The most common benefits were “feel high or buzzed” and “feel less anxious.” Ever cannabis users perceived less risks and greater benefits than never users.
 
Electronic cigarette use among adults in 14 countries: A cross-sectional study
eClinicalMedicine
Using 2015-2018 Global Adult Tobacco Survey (GATS) data, prevalence of e-cigarette use and variations by sociodemographic characteristics was examined in 14 countries. Given the progress towards a tobacco-free generation, continued surveillance of e-cigarette use is essential to developing, sustaining, and strengthening tobacco control at the country level. Approximately 18.3 million adults used e-cigarettes across these countries; higher use was observed in certain countries among men, young adults, urban residents, adults with higher education levels, and higher wealth index. Continued monitoring of e-cigarette use is critical for developing interventions and policies to prevent tobacco initiation and enhance cessation support.
 
Assessment of Community-Level Vulnerability and Access to Medications for Opioid Use Disorder
JAMA Network Open
This cross-sectional study examined the association of community vulnerability to disasters and pandemics with geographic access to each of the three Medications for Opioid Use Disorder (MOUDs) and whether this association differs by urban, suburban, or rural classification. All zip code tabulation areas (ZCTAs) within the continental U.S. were included. Median drive time to the nearest treatment location was greatest for methadone (35 [16-60] minutes) and shortest for buprenorphine (16 [0-30] minutes; P 

Lead Story: Defining Recovery From Alcohol Use Disorder: Development of an NIAAA Research Definition

Show Notes:
 
Defining Recovery From Alcohol Use Disorder: Development of an NIAAA Research Definition 
The American Journal of Psychiatry 
The authors present a newly developed National Institute on Alcohol Abuse and Alcoholism (NIAAA) definition of recovery from the DSM-5 diagnosis of alcohol use disorder (AUD). This definition views recovery as a process of behavioral change and an outcome, incorporating two key components of recovery: remission from DSM-5 AUD and cessation from heavy drinking, a non-abstinent recovery outcome. It also emphasizes the importance of biopsychosocial functioning and quality of life in enhancing outcomes. By adopting a uniform definition, researchers and health care professionals can more precisely operationalize and measure recovery-related processes.  
 
Benzodiazepine-Involved Overdose Deaths in the USA: 2000–2019 
Journal of General Internal Medicine 
Overdose deaths involving benzodiazepines and opioids are well studied and characterized. In this study, the authors examine all benzodiazepine-involved overdose deaths to better understand the pattern of use and overdoses between 2010 and 2019. While opioids were involved in 83.5% of all benzodiazepine related overdoses, antidepressants (18.8%), alcohol (16.3%), cocaine (13.4%) and psychostimulants (7.3%) were also frequently involved. Only 9% of benzodiazepine overdose deaths did not co-involve another substance. In addition, a larger proportion of deaths with benzodiazepine alone were due to suicide (36.2%) compared to those involving opioids (8.5%). Any interventions to reduce overdose deaths involving benzodiazepines need to consider co-involved substances and the role of suicide.   
Differences in clinical features associated with cannabis intoxication in presentations to European emergency departments according to patient age and sex 
Clinical Toxicology 
Using presentations in the Euro-DEN Plus dataset from 2014 to 2019, this study investigated whether clinical features associated with acute cannabis intoxication in patients presenting to Emergency Departments for medical assistance differ according to patient age and sex. The most frequent clinical features in patients younger than 20 years were vomiting, reduced consciousness, and headache; and less frequently acute psychosis. Patients older than 49 years more often had hypotension and less frequently vomiting, anxiety, agitation, and reduced consciousness. Males more frequently presented with hypertension, psychosis, chest pain, and seizures. 
  
Increased global integration in the brain after psilocybin therapy for depression 
Nature Medicine 
Two clinical trials assessed the subacute impact of psilocybin on brain function in treatment resistant depression. In both trials, the antidepressant response to psilocybin was rapid, sustained, and correlated with decreases in fMRI brain network modularity, implying that psilocybin’s antidepressant action may depend on a global increase in brain network integration. Network cartography analyses indicated that 5-HT2A receptor-rich higher-order functional networks became more functionally interconnected and flexible after psilocybin treatment. Consistent efficacy-related brain changes, correlating with robust antidepressant effects across two studies, suggest an antidepressant mechanism for psilocybin therapy: global increases in brain network integration. 
 
Non–prescribed buprenorphine preceding treatment intake and clinical outcomes for opioid use disorder 
Journal of Substance Abuse Treatment 
In this study, data were obtained from a large, multi-site, multi-state office-based opioid treatment (OBOT) network. Individuals (n=971) were randomly selected from a pool of 18,513 initiating buprenorphine care. At treatment entry, 60% tested positive for buprenorphine (TPB), and 73% of these were taking non-prescribed buprenorphine. The TPB group was less likely to test positive for opiates at treatment entry (25% vs. 53%) and continued to be less likely to test positive for opiates during the first several months of treatment. The TPB group was less likely to discontinue treatment (hazard ratio 0.52). There were no significant differences comparing those prescribed with non-prescribed use, in the TPB group. They suggest that use of “diverted” buprenorphine is a marker of patient motivation for treatment and conclude that “concerns regarding buprenorphine diversion due to misuse may be misplaced.”  
  
What are the implications of the steady 40 year rise in US fatal overdoses?: Introduction to a special section 
International Journal of Drug Policy 
While overdose deaths due to opioids is understood to be the driver of current increase in overdose deaths and a well-recognized epidemic, in a series of recent studies it was demonstrated that overdose deaths have been steadily increasing over the last 40 years.  In this editorial, the authors discuss various commentaries responding to these studies and highlight various perspectives on these data. While much of the focus in recent years has been on opioid overdose deaths and access to medication assisted treatment, interventions may be needed to address broader factors associated with substance use, including both supply and demand side factors. In addition, data at more local levels may be useful in predicting substance use epidemics at more local levels for intervention. 
  
The Effectiveness of Exercise as an Adjunct Intervention to Improve Quality of Life and Mood in Substance Use Disorder: A Systematic Review 
Substance Use and Misuse 
This review examined 42 papers (2531 individuals) regarding the effect of exercise on quality of life, depression, and anxiety during treatment of substance use disorder. The majority, 22 studies, took place in an inpatient rehabilitation setting. They examined a broad range of exercise modalities: aerobic, resistance, flexibility, tai chi, yoga, high intensity interval training, and increasing step count. The results support a beneficial impact of exercise on quality of life, depression, and anxiety. There was a dose response effect with greater benefit with increased number of sessions per week and over 12 weeks of program duration, however, some improvement was seen following a single session. The modality of exercise was less important and simply increasing daily step count was beneficial.   
 
Addressing the substance use treatment gap in Africa using digital screening and brief interventions 
The Lancet Psychiatry 
Services and staffing for substance use treatment and prevention are scarce throughout many parts of Africa. One treatment option is a self-administered digital substance use screening and brief intervention (SBI). This literature search noted a paucity of research investigating the feasibility of SBIs in Africa. Such an SBI has the potential to increase access to care and decrease intervention delivery costs. Given the rapid increase in internet penetration rates, and smartphone usage across the continent, as well as limited access to treatment, there is an urgent need to explore the utility of this treatment tool across the continent. 

Lead Story: Association of Medication Treatment for Opioid Use Disorder With Suicide Mortality

Show Notes:
 
 
Association of Medication Treatment for Opioid Use Disorder With Suicide Mortality
The American Journal of Psychiatry 
This study evaluated whether medications for opioid use disorders (MOUD) are associated with reduced risk of suicide mortality and compared different agents. Data were collected for 61,633 veterans (93% male) receiving MOUD. Approximately half received buprenorphine and a quarter received methadone or naltrexone (oral or extended-release).  The hazard ratio (HR) for suicide mortality while on MOUD was 0.45 and for all-cause mortality, it was 0.34. Stopping MOUD increased the risk for suicide (HR = 1.47) and all-cause mortality (HR = 1.14). Buprenorphine reduced suicide mortality (HR = 0.34) whereas naltrexone did not (HR = 1.28). Buprenorphine reduced all-cause mortality (HR = 0.27) to a greater extent than naltrexone (HR = 0.64), while results with methadone were less clear. Overall, MOUD produced dramatic reductions in both suicide and all-cause mortality with the effect most pronounced for buprenorphine. Naltrexone, however, did not reduce suicide mortality.   
 
Research and Science 
Fetal Exposure to Cannabis and Childhood Metabolic Outcomes: The Healthy Start Study 
The Journal of Clinical Endocrinology & Metabolism
This study investigated whether fetal exposure to cannabis is associated with increased adiposity and markers of impaired glucose homeostasis in early childhood. Approximately 15% of mothers had detectable levels of any cannabinoid at ~27 weeks’ gestation, indicating fetal exposure to cannabis. Fetal exposure to cannabis was associated with increased adiposity and fasting glucose in early childhood. This study further supports discouraging women from using any cannabis while pregnant or breastfeeding to minimize adverse health effects on the offspring.
 
Trends in seizures of powders and pills containing illicit fentanyl in the United States, 2018 through 2021 
Drug and Alcohol Dependence
Fentanyl continues to be a leading cause of overdose in the United States and is increasingly found in counterfeit prescription pills. This study examines trends in pills containing fentanyl using the national seizure data from High Intensity Drug Trafficking Areas between January 2018 and December 2021. There was a significant increase in both fentanyl-containing powder seizures (424 to 1539) and pill seizures (68 to 635) during the study period. In addition, the proportion of seizures that were pills increased (13.8% to 29.2%) and the number of pills seized increased (42,202 to 2,089,186). While the presence of fentanyl in heroin supply is more widely known, its presence in pills poses a potential risk that is not as widely disseminated, resulting in the need for public education. 
 
Beliefs and Characteristics Associated With Believing Nicotine Causes Cancer: A Descriptive Analysis to Inform Corrective Message Content and Priority Audiences
Nicotine and Tobacco Research
In this study, authors examine cigarette smokers’ perceptions about harm from tobacco, specifically nicotine as the source of harm. The authors found that a significant proportion of smokers (61.2%) believed that nicotine was the source of cancer risk or were not sure. This belief was more common among non-Hispanic Black and Hispanic smokers as well as those with low incomes. Smokers with high school or higher education were less likely to believe nicotine was the source of the risk. In addition, those who had used a non-combustible tobacco product, including electronic cigarettes, were less likely to have this perception. The misperception about the risk of nicotine may impact smokers’ behavior, and switching to less harmful products and education is needed to correct this commonly held belief.  
 
Effect of Medical Marijuana Card Ownership on Pain, Insomnia, and Affective Disorder Symptoms in Adults
JAMA Network Open
This randomized clinical trial involving 186 participants examined the risks and benefits of obtaining a medical marijuana card for adults who seek medical marijuana for pain, insomnia, and anxiety or depressive symptoms. Immediate acquisition of a medical marijuana card increased the incidence and severity of cannabis use disorder (CUD) and resulted in no significant improvement in pain, anxiety, or depressive symptoms, but improved self-reported sleep quality. Findings suggest the need for further investigation into the benefits of medical marijuana card ownership for insomnia symptoms and the risk of CUD, particularly for those with anxiety or depressive symptoms.
 
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Burst Suppression Electroencephalography (EEG) Pattern with Coma and Loss of Brain Stem Reflexes Following a Baclofen Overdose with Subsequent Full Recovery
 American Journal of Case Reports
Baclofen toxicity can present both clinically and with EEG abnormalities consistent with anoxic brain injury, suggesting an inevitable progression to brain death. This is a case report of a middle-aged woman found unresponsive who presented with apnea, loss of rudimentary neurologic findings on physical exam, burst suppression EEG findings, and a prolonged comatose state for nearly 48 h, followed by rapid resolution of symptoms secondary to a supratherapeutic baclofen ingestion. When provided with appropriate supportive care and prolonged observation, improvement with full neurologic recovery is often seen despite the initial grim clinical picture.
 
Against Our Instincts: Decriminalization of Buprenorphine
Journal of the American Board of Family Medicine
In this commentary the authors make a case for the decriminalization of the possession of buprenorphine. The authors cite the dramatic reduction in mortality (by 2/3 in one meta-analysis) with buprenorphine treatment. According to data from Tennessee, buprenorphine has little risk of overdose when used alone. A meta-analysis indicated that diverted buprenorphine was used for therapeutic rather than recreational purposes. Many have difficulty accessing buprenorphine due to a lack of providers and economic barriers, and the authors note that when a Vermont county decided not to prosecute possession of buprenorphine (along with other measures to increase access) the overdose rate reduced by 50% while increasing in the rest of the state. The authors conclude that the benefits of decriminalizing buprenorphine possession outweigh the risks.