ASAM Weekly for February 14, 2023

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ASAM Weekly for February 14, 2023

This Week in the ASAM Weekly

Studies have shown a strong relationship between cannabis use and psychosis, some going as far as supporting a causal relationship. However, a remarkably large study examining national insurance databases for psychosis-related claims compared all states based on medical, recreational, and retail cannabis policies and found that, in general, the policies were not associated with increased psychosis-related outcomes (JAMA Network). Such studies do lead to further questions, but as Dr. Torrey explicitly points out, our ability to find answers is hindered by the missing data on rates of schizophrenia in America (Psychiatric Times).

Similarly, a twin study demonstrated that recreational cannabis policies compared across two states lead to increased cannabis use but not a wide range of other psychosocial problems, including further substance use disorders (Psychological Medicine). This is relevant for the gateway-drug hypothesis (Neuroscience News) but should not distract us from the important work of setting up guardrails around cannabis use (Politico).

At times, psychedelics seem to be jumping the guardrails imposed on other therapeutics (Medpage Today), while heading down a path of normalization and spiritualization. From micro-dosing mom groups (Washington Post) to psychedelic churches (Santa Fe New Mexican), we must have ways to help people safely. Future research into “nonpsychedelic psychedelics” may help us find them (NEJM).

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

State Cannabis Legalization and Psychosis-Related Health Care Utilization 🔓

JAMA Network

Psychosis has long been considered a potential consequence of cannabis use. In this retrospective cohort study, the association of state cannabis legalization with psychosis-related health care claims among some 63,680,589 privately insured individuals were investigated. There were 7,503,907 psychosis-related diagnoses and 20,799,285 prescriptions filled for antipsychotics over the study period. State medical and recreational cannabis policies were not found to be associated with a statistically significant increase in rates of psychosis-related health outcomes.

2023 Addiction Medicine Research Priorities Listening Session

The National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Drug Abuse (NIDA), and Agency for Healthcare Research and Quality (AHRQ) have requested input from addiction medicine specialists on how to improve the clinical relevance of their addiction medicine research portfolios.

Please provide input on their questions below and add any questions or comments you may have at the end of the form. We will also discuss these questions at the "Bridging the Gap between Science and Clinical Practice in Addiction Medicine" session during the ASAM 2023 Annual Conference.

If you have any questions, please email Ray Denny, PhD, Associate Director of Science, at rdenny@asam.org. Thank you!

Provide Input

Research and Science

Recreational cannabis legalization has had limited effects on a wide range of adult psychiatric and psychosocial outcomes 🔓

Psychological Medicine

This longitudinal twin-cohort study examined the potential causal effect of recreational cannabis legalization on substance use, substance use disorder (SUD), and psychosocial outcomes. The twin living in a recreational state used cannabis more frequently and had fewer alcohol use disorder (AUD) symptoms than the co-twin living in a non-recreational state with legalization resulting in a 0.11 standard deviation increase in cannabis frequency. Changes in negative outcomes as a result of legalization were not found. Future research might consider what patterns of consumption pose the most risk.

The trajectory of two negative symptom dimensions in first-episode psychosis and the role of cannabis use: A 10-year follow-up study🔓

Schizophrenia Research

This study investigated the trajectories of diminished expression and apathy over 10 years and the effects of baseline and persistent cannabis use on the development of diminished expression and apathy during follow-up, while controlling other potential sources and predictors of secondary negative symptoms. Both cannabis use at baseline and persistent cannabis use after a first episode of psychosis were associated with more severe symptoms of diminished expression. The results imply a causal relationship between cannabis use and diminished expression and suggest that measures to reduce cannabis use both before and after psychosis onset may reduce expressive negative symptoms.

Cost-effectiveness of office-based buprenorphine treatment for opioid use disorder

Drug and Alcohol Dependence

This study draws on medical research to estimate variables such as overdose rates in and out of treatment, rates of treatment discontinuation and reentry, relapse rates in and out of treatment, and healthcare and criminal justice costs. For 100,000 persons with opioid use disorder (OUD) treated with buprenorphine, 9350 overdoses (900 fatal) would be prevented over 5 years. This would yield 1.07 additional quality adjusted life years (QALY) per person with a healthcare cost of $17,000. Assuming buprenorphine treatment was half as effective and twice as expensive that figure becomes $25,500/QALY, which is less than the US GDP per capita. When savings of criminal justice costs are also considered, buprenorphine treatment is highly cost effective.

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Reconsidering “dissociation” as a predictor of antidepressant efficacy for esketamine

Psychopharmacology

While the dissociative effect of ketamine has been considered a side effect historically, there has been some suggestion that it may be related to the therapeutic anti-depressant effects. In this study, the authors conducted a pooled secondary analysis of the TRANSFORM-1 and TRANSFORM-2 trials for esketamine use for treatment-resistant depression to examine the relationship between its dissociative effect and anti-depressant effects. In their analysis they did not find a clinically significant association (negative or positive) between experience of dissociation and the antidepressant effects of the medication.

The Inflammatory Signals Associated with Psychosis: Impact of Comorbid Drug Abuse🔓

Biomedicines

The authors conducted a literature review to examine the potential relationship between immune-inflammatory changes and psychosis and substance use. In their review, the authors note there are multiple neuroinflammatory markers that have been linked to psychotic disorders including cytokines, chemokines, endocannabinoids, and others. Many of these same markers are found in patients with substance use disorders (SUD). The authors suggest these findings compliment the neurodevelopmental model of psychosis and SUD and suggest an inflammatory process may be involved in early abnormal neurodevelopment with subsequent inflammatory events precipitating symptoms. While the authors note that further research is needed, this may have implications for the prevention, diagnosis, and treatment of these disorders.

Novel role of AMPK in cocaine reinforcement via regulating CRTC1🔓

Translational Psychiatry

Repeated cocaine exposure causes compensatory neuroadaptations in neurons in the nucleus accumbens (NAc), a region that mediates reinforcing effects of drugs. This study employed a cocaine self-administration model in rats to investigate the effect of adenosine monophosphate-activated protein kinase (AMPK) and its target cyclic adenosine monophosphate response element binding protein-regulated transcriptional co-activator 1 (CRTC1) on cocaine reinforcement and the motivation for cocaine. The results indicate that AMPK in the NAc shell (NAcsh) is critical for cocaine reinforcement, possibly via the regulation of CRTC1 signaling. These findings may help reveal potential therapeutic targets and have important implications for the treatment of cocaine use disorder and relapse.

Translational Challenges in Psychedelic Medicine

The New England Journal of Medicine

The author notes that psychedelic agents show activity at the serotonin 2A receptor (5-HT2A). A recent research paper reports on the synthesis of 17 compounds that have 5-HT2A receptor activity. Two of these showed no psychedelic activity in rodents (indicated by head-twitch) but did show positive effects on rodent measures of anxiety and depression. However, rodent to human translational research has yielded little in psychiatric drugs in recent decades. Psychedelic research in humans involves controlled environments and cortical activity corresponds to psychedelic effect and therapeutic response. These (and other) features of human research could be incorporated into, and benefit, animal research.