The First "Hit" to the Endocannabinoid System? Associations Between Prenatal Cannabis Exposure and Frontolimbic White Matter Pathways in Children

Journal: Biological Psychiatry Global Open Science, 2024, doi: 10.1016/j.bpsgos.2023.09.005

Authors: Julia M. Evanski, Clara G. Zundel, Samantha L. Baglot, Shreya Desai, Leah C. Gowatch, Samantha L. Ely, … Hilary A. Marusak


Background: Cannabis is the most used federally illicit substance among pregnant people in the United States. However, emerging preclinical data show that a significant portion of cannabis constituents, such as Δ9-tetrahydrocannabinol and its bioactive metabolites, readily cross the placenta and accumulate in the fetal brain, disrupting neurodevelopment. Recent research using the Adolescent Brain Cognitive Development (ABCD) Study cohort has linked prenatal cannabis exposure (PCE) to greater neurobehavioral problems and lower total gray and white matter volume in children. Here, we examined the impact of PCE on frontolimbic white matter pathways that are critical for cognitive- and emotion-related functioning, show a high density of cannabinoid receptors, and are susceptible to cannabis exposure during other periods of rapid neurodevelopment (e.g., adolescence).

Methods: This study included 11,530 children (mean ± SD age = 118.99 ± 7.49 months; 47% female) from the ABCD Study cohort. Linear mixed-effects models were used to examine the effects of caregiver-reported PCE on fractional anisotropy of 10 frontolimbic pathways (5 per hemisphere).

Results: PCE was associated with lower fractional anisotropy of the right (β = -0.005, p < .001) and left (β = -0.003, p = .007) fornix, and these results remained significant after adjusting for a variety of covariates, multiple comparisons, fractional anisotropy of all fibers, and using a quality-control cohort only.

Conclusions: In sum, we demonstrated small, yet reliable, effects of PCE on white matter integrity during childhood, particularly in the fornix, which plays a crucial role in emotion- and memory-related processes. Future studies are needed to understand the impacts of small changes in brain structure or function on neurodevelopment and risk of neurobehavioral problems.

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Alcohol Use Disorder Treatment: Problems and Solutions

Journal: Annual Review of Pharmacology and Toxicology, 2024, doi: 10.1146/annurev-pharmtox-031323-115847

Author: George F. Koob


Alcohol use disorder (AUD) afflicts over 29 million individuals and causes more than 140,000 deaths annually in the United States. A heuristic framework for AUD includes a three-stage cycle-binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation-that provides a starting point for exploring the heterogeneity of AUD with regard to treatment. Effective behavioral health treatments and US Food and Drug Administration-approved medications are available but greatly underutilized, creating a major treatment gap. This review outlines challenges that face the alcohol field in closing this treatment gap and offers solutions, including broadening end points for the approval of medications for the treatment of AUD; increasing the uptake of screening, brief intervention, and referral to treatment; addressing stigma; implementing a heuristic definition of recovery; engaging early treatment; and educating health-care professionals and the public about challenges that are associated with alcohol misuse. Additionally, this review focuses on broadening potential targets for the development of medications for AUD by utilizing the three-stage heuristic model of addiction that outlines domains of dysfunction in AUD and the mediating neurobiology of AUD.

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Characteristics and Engagement among English-Language Online Forums for Addiction Recovery Available in the US

Journal: Internet Interventions, 2024, doi: 10.1016/j.invent.2024.100708

Authors: Jason B. Colditz, Lily H. Hsiao, Brandon G. Bergman, David W. Best, Eric G. Hulsey, Jaime E. Sidani, Bruce L. Rollman, & Kevin L. Kraemer


In developing public resources for the Networks Enhancing Addiction Recovery – Forum Activity Roadmap (NEAR-FAR), we completed a systematic observational study of English-language online forums related to recovery from alcohol or other drug addiction in late 2021. Among 207 identified forums, the majority were classified as “general addiction” or alcohol-focused, though classifications related to other substances were common on websites hosting multiple forums. Commonly used social media platforms such as Reddit, Facebook, or Quora offered easily accessible venues for individuals seeking online support related to a variety of substances. Forums were related to established recovery programs such as 12-step and SMART Recovery as well as other nonprofit and for-profit recovery programs, and to community forums without formal recovery programming. Among 148 forums with any observed user activity, the median time between unique user engagements was 27 days (inter-quartile range: 2-74). Among 98 forums with past-month posting activity, we found a median of <10 posts per week (inter-quartile range: 1-78). This study compares three metrics of observed forum activity (posts per week, responses per post, time between unique user engagements) and operationalizes forum characteristics that may potentiate opportunities for enhanced engagement and social support in addiction recovery.

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Pathways to Opioid Use and Implications for Prevention: Voices of Young Adults in Recovery

Journal: Substance Abuse Treatment, Prevention and Policy, 2024, doi: 10.1186/s13011-023-00584-5

Authors: Parissa J. Ballard, Taylor J. Arnold, Elena M. Vidrascu, Guadalupe C. Hernandez, Emily Ozer, Mark Wolfson, … Stephanie S. Daniel


Background: Opioid use remains a major public health issue, especially among young adults. Despite investment in harm reduction and supply-side strategies such as reducing overprescribing and safe medication disposal, little is known about demand-side issues, such as reasons for use and pathways to opioid use. Adolescents and young adults who struggle with opioid use disorder (OUD) are multifaceted individuals with varied individual histories, experiences, challenges, skills, relationships, and lives.

Methods: To inform the development of prevention strategies that hold promise for addressing opioid use, this study employs brief structured surveys and semi-structured in-depth interviews with 30 young adults (ages 18-29; 19 female, 23 White, 16 from Suburban areas) in recovery from OUD. For survey data, we used descriptive statistics to summarize the means and variance of retrospectively reported risk and protective factors associated with opioid use. For in-depth interview data, we used a combination of thematic analysis and codebook approaches to generate common themes and experiences shared by participants.

Results: Surveys revealed that the most endorsed risk factors pertained to emotions (emotional neglect and emotional abuse) followed by sexual abuse, physical abuse, and physical neglect. Themes generated from qualitative analyses reveal challenging experiences during adolescence, such as unaddressed mental health, social, and emotional needs, which were often reported as reasons for opioid initiation and use. Through surveys and interviews, we also identified positive assets, such as skills and social relationships that were present for many participants during adolescence.

Conclusion: Implications include the need for universal prevention strategies that include emotion-focused interventions and supports alongside current harm reduction and environmental strategies to regulate prescriptions; the potential utility of more emotion-focused items being included on screening tools; and more voices of young people in recovery.

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Estimating the Ratio of Fatal to Non-Fatal Overdoses Involving all Drugs, all Opioids, Synthetic Opioids, Heroin or Stimulants, USA, 2010-2020

Journal: Injury Prevention, 2024, doi: 10.1136/ip-2023-045091

Authors: Shannon M. Casillas, Cassandra M. Pickens, Lauren J. Tanz, & Alana M. Vivolo-Kantor


Introduction: US drug overdose deaths are at historic levels. For every fatal drug overdose, there are many more non-fatal; however, minimal nationally representative data exist on trends in the ratio of fatal to non-fatal drug overdoses and how this differs by drug type.

Methods: Data from the Centers for Disease Control and Prevention’s National Vital Statistics System were used to assess the number of fatal overdoses; data from the Healthcare Cost and Utilization Project Nationwide Emergency Department Sample database were used to estimate the number of non-fatal overdoses treated in emergency departments. Counts of fatal and non-fatal overdoses by drug type (all drug, all opioid, synthetic opioid, heroin, stimulant, and opioid and stimulant polysubstance) were calculated from 2010 to 2020 (for non-fatal synthetic opioid-involved overdoses, from 2016 to 2020 only). Trends in overdose counts and the ratio of fatal to non-fatal overdoses were assessed.

Results: On average, counts of fatal overdoses increased quarterly among all drug types, and non-fatal overdoses increased among most drug types. Over the 11-year period, the greatest average quarterly percent change (AQPC) in fatal overdose counts was among synthetic opioid-involved overdoses (AQPC: 7.1%; 95% CI: 6.0 to 8.2) and for non-fatal overdoses was among heroin-involved overdoses (AQPC: 4.3%; 95% CI: 3.9 to 4.8). During 2010‒2020, there was approximately 1 fatal overdose per 15 non-fatal. The ratio of fatal to non-fatal drug overdoses increased among every drug type except heroin; ratio increases were driven by greater relative increases in fatal overdoses compared with non-fatal.

Conclusions: Assessment of the ratio of fatal to non-fatal drug overdoses can be used to understand the lethality of different drugs and inform response and prevention efforts.

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