This Week in Addiction Medicine from ASAM

Lead: Cannabis Use Disorder Emergency Department Visits and Hospitalizations and 5-Year Mortality

Cannabis Use Disorder Emergency Department Visits and Hospitalizations and 5-Year Mortality
JAMA Network Open
This cohort study of 11.6 million people who were studied for a median of five years investigated if individuals who have hospital-based (emergency department or hospitalization) care for a cannabis use disorder (CUD) were at increased risk of death. Researchers found that individuals with incident hospital-based care for a CUD were at a 2.8-fold increased risk of death within five years relative to the general population. These results suggest that individuals who require hospital-based care for a CUD may be at increased risk of premature death.
 
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Lead: Real-Time Assessment of Alcohol Reward, Stimulation, and Negative Affect in Individuals With and Without Alcohol Use Disorder and Depressive Disorders

Real-Time Assessment of Alcohol Reward, Stimulation, and Negative Affect in Individuals With and Without Alcohol Use Disorder and Depressive Disorders
American Journal of Psychiatry
A commonly held model of addiction posits that as addictions develop, there is progression from positive reinforcement to negative reinforcement to ameliorate withdrawal symptoms. In this study, researchers examined the subjective response to alcohol among persons with and without alcohol use disorder (AUD) and with or without comorbid depression. Regardless of the presence of comorbid depression, persons with AUD reported pleasurable effects, including stimulation and hedonic reward, after consumption of alcohol. In contrast, among those without AUD, the positive effects were less substantial. Participants did report reduction in negative affect, but the effects were relatively small. These findings suggest that positive reinforcement is sustained in the progression of AUD and the reward-sensitive stage may exist along with negative reinforcement. 
 
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Lead: Outpatient Low-Dose Initiation of Buprenorphine for People Using Fentanyl

Outpatient Low-Dose Initiation of Buprenorphine for People Using Fentanyl
JAMA Network Open
The accumulation of fentanyl in fat is likely responsible for the risk of precipitated withdrawal when buprenorphine is initiated. Low dose initiation (LDI) of buprenorphine attempts to minimize this risk. This retrospective study included 126 individuals making 175 LDI attempts in an outpatient setting. Patients chose either a 4 day or 7 day LDI protocol with buprenorphine monoproduct. Both protocols begin with buprenorphine 0.5mg, increasing to 8mg tid. Overall LDI was successful in 34% of attempts (with no difference between the protocols) and one month retention on buprenorphine was 21%. Repeated LDI attempts were less likely to be successful (second attempt aOR 0.3). Unhoused people had lower odds of success (OR 0.4). The authors conclude that people with OUD using fentanyl attempting outpatient LDI of buprenorphine had low odds of success.
 
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Lead: Association of State Cannabis Legalization With Cannabis Use Disorder and Cannabis Poisoning

Association of State Cannabis Legalization With Cannabis Use Disorder and Cannabis Poisoning
JAMA Psychiatry
This longitudinal cohort study examined the association of state-level medical and recreational cannabis laws with cannabis use disorder (CUD) and cannabis poisonings in the adult population with employer-sponsored health insurance. The study showed that from 2011 to 2021, states with legalized medical cannabis experienced 42.7% and 88.6% increases in CUD and cannabis poisoning, respectively, compared to states without legalized medical cannabis. States with legalized recreational cannabis experienced a 31.6% increase in cannabis poisoning compared to states without legalized recreational cannabis. Thus, state medical cannabis legalization was associated with increased CUD and cannabis poisonings, and state recreational cannabis legalization was associated with increased cannabis poisoning in the adult population with employer-sponsored health insurance.
 
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Lead: Current Advances in Behavioral Addictions: From Fundamental Research to Clinical Practice

Current Advances in Behavioral Addictions: From Fundamental Research to Clinical Practice
American Journal of Psychiatry
This narrative review discusses five clinically relevant and prevalent behavioral addictions that are common and often co-occur with psychiatric disorders such as depression and anxiety. Gambling disorder is the only behavioral addiction recognized as a clinical disorder in DSM-5, and Internet gaming disorder is included as a condition requiring further research. ICD-11 categorizes gambling and gaming disorders as disorders due to addictive behaviors. Additional behavioral addictions may include compulsive sexual behavior disorder, compulsive buying-shopping disorder, and problematic use of social media. Validated diagnostic instruments exist, with empirical support varying across conditions. No medications have approved indications from regulatory bodies for behavioral addictions, and cognitive-behavioral therapy has the most empirical support for efficacious treatment. Treatment optimization involving pharmacotherapy, psychotherapy, neuromodulation, and their combination warrants additional investigation.
 
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ASAM Weekly Special Episode: Dr. David Fiellin & Dr. Eric Strain sit down to discuss the concept of Treatment Refractory Addiction

Host Dr. Nick Athanasiou is joined by Dr. David Fiellin and Dr. Eric Strain to discuss the concept of Treatment Refractory Addiction.  Why does the field of addiction medicine need this term, how is it defined and how the current treatment system aligns with the idea? Listen to the full interview to learn more!
 
Treatment Failure Versus Failed Treatments: The Risks of Embracing Treatment Refractory Addiction [Dr. David Fiellin]
The Concept of Treatment-Refractory Addiction: A Call to the Field [Dr. Eric Strain]
The Concept of Treatment-Refractory Addiction: Implications for Addiction Treatment Systems and Research [Dr. Edward Nunes & Dr. Thomas McLellan]
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Lead: Review of Evidence on Alcohol and Health

Review of Evidence on Alcohol and Health
National Academies of Sciences, Engineering, and Medicine
To inform the next edition of the Dietary Guidelines for Americans (DGA), Congress tasked the National Academies with convening an expert committee to independently review the evidence on the relationship between moderate alcohol consumption and eight health outcomes including obesity, cancer, and cardiovascular disease. This controversial report found that a pattern of moderate drinking was associated with 18 percent fewer cardiovascular disease deaths, a 16 percent lower risk of all-cause mortality, and a 10 percent heightened risk of breast cancer for women.
 
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Lead: The impact of schizophrenia genetic load and heavy cannabis use on the risk of psychotic disorder in the EU-GEI case-control and UK Biobank studies

The impact of schizophrenia genetic load and heavy cannabis use on the risk of psychotic disorder in the EU-GEI case-control and UK Biobank studies
Psychological Medicine
Using data from the EU-GEI case-control study and UK Biobank, researchers examined the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS), on risk for psychosis. Schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use. It was associated with lifetime and daily cannabis use without psychosis, but the effect was substantially reduced when cannabis use disorder (CUD) PRS was included in the model. Regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS. Regular use of high-potency cannabis remains a strong predictor of psychotic disorder, independent of schizophrenia PRS. Schizophrenia PRS does not seem to be associated with heavy cannabis use. These are important findings, at a time of increasing use and potency of cannabis worldwide. 
 
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Lead: Prevalence of pharmacotherapy for attention-deficit/hyperactivity disorder and prescription stimulant misuse: A national study of US college students

Prevalence of pharmacotherapy for attention-deficit/hyperactivity disorder and prescription stimulant misuse: A national study of US college students
Addiction
This is an observational study using cross-sectional data from the American College Health Association–National College Health Assessment III. It measured the association between university-level prevalence of attention deficit/hyperactivity disorder (ADHD) medication treatment and prevalence of prescription stimulant misuse (PSM) among college students.  Among university students in the United States, there appears to be a positive association between attending universities with a greater prevalence of ADHD medication treatment and risk of prescription stimulant misuse (PSM). This study provides further support for the possibility that ADHD medication treatment prevalence is a risk factor for PSM.
 
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Lead: Xylazine Pharmacokinetics in Patients Testing Positive for Fentanyl and Xylazine

Xylazine Pharmacokinetics in Patients Testing Positive for Fentanyl and Xylazine 
Clinical Chemistry
This study of xylazine pharmacokinetics used plasma samples from 28 patients who had urine screens positive for xylazine and fentanyl. The patients were being treated for skin lesions, most commonly, then shortness of breath or opioid overdose. At least two subsequent plasma samples were analyzed for xylazine and xylazine metabolites by LC-MS/MS. The median terminal half-life for xylazine in plasma was 12 hours (range 6-21 hours). Animal studies show xylazine to be extensively metabolized, with little unchanged xylazine eliminated in urine. The two most abundant metabolites were oxo-x and sulfone-x, which did not have a window of detection longer than xylazine. Researchers had no information as to the timing or route of xylazine ingestion or if additional xylazine was consumed during the study period. These factors could affect the accuracy of the results.
 
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