This Week in Addiction Medicine from ASAM

Lead: Psychedelics reopen the social reward learning critical period

Lead Story:
Psychedelics reopen the social reward learning critical period 
Nature
Psychedelics have been used for millennia in both spiritual and medicinal contexts, and a number of recent clinical successes have spurred a renewed interest in developing psychedelic therapies. This study demonstrates in mice that the ability to reopen the social reward learning critical period is a shared property across psychedelic drugs. Notably, the time course of critical period reopening is proportional to the duration of acute subjective effects reported in humans. Furthermore, the ability to reinstate social reward learning in adulthood is paralleled by metaplastic restoration of oxytocin-mediated long-term depression in the nucleus accumbens. Finally, identification of differentially expressed genes in the ‘open state’ versus the ‘closed state’ provides evidence that reorganization of the extracellular matrix is a common downstream mechanism underlying psychedelic drug-mediated critical period reopening.
 
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Lead: Reduced Stress-Related Neural Network Activity Mediates the Effect of Alcohol on Cardiovascular Risk

Lead Story: 
Reduced Stress-Related Neural Network Activity Mediates the Effect of Alcohol on Cardiovascular Risk
Journal of the American College of Cardiology
Chronic stress is associated with major adverse cardiovascular events (MACE) via increased stress-related neural network activity (SNA). Light/moderate alcohol consumption (ACl/m) has been linked to lower MACE risk, but the mechanisms are unclear. This study evaluated whether the association between ACl/m and MACE is mediated by decreased SNA. Individuals enrolled in the Mass General Brigham Biobank who completed a health behavior survey were studied. A subset underwent 18F-fluorodeoxyglucose positron emission tomography, enabling assessment of SNA. Alcohol consumption was classified as none/minimal, light/moderate, or high (14 drinks/week, respectively).  ACl/m associates with reduced MACE risk, in part, by lowering the activity of a stress-related brain network known for its association with cardiovascular disease. Given alcohol’s potential health detriments, new interventions with similar effects on SNA are needed.
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Lead: Signaling-specific inhibition of the CB1 receptor for cannabis use disorder

Lead Story
Signaling-specific inhibition of the CB1 receptor for cannabis use disorder: phase 1 and phase 2a randomized trials 
Nature Medicine
Cannabis use disorder (CUD) is widespread, and there is no pharmacotherapy to facilitate its treatment. AEF0117, the first of a new pharmacological class, is a signaling-specific inhibitor of the cannabinoid receptor 1 (CB1-SSi). AEF0117 selectively inhibits a subset of intracellular effects resulting from Δ9-tetrahydrocannabinol (THC) binding without modifying behavior per se. In mice and non-human primates, AEF0117 decreased cannabinoid self-administration and THC-related behavioral impairment without producing significant adverse effects. In healthy human volunteers with CUD, AEF0117 was well tolerated and did not precipitate cannabis withdrawal. These data suggest that AEF0117 is a safe and potentially efficacious treatment for CUD.
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Lead: Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression

Lead Story: 
Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression
The New England Journal of Medicine
While electroconvulsive therapy (ECT) has been used for several years for treatment-resistant major depression, ketamine has been relatively recently approved. The authors conducted an open label, randomized, noninferiority trial with 403 patients to compare the effectiveness of ketamine to ECT. The ketamine was found to be noninferior to ECT for treatment response as reported by decrease in depressive symptoms. Further, both were associated with improved quality of life, but the ECT group did have a greater decline in memory performance. Of note, this trial excluded patients with major depression with psychosis, and previous studies have found that ketamine is inferior to ECT among those patients.
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Special Episode: Why Patients Transition Off Methadone

Special Guests:
Ashish P. Thakrar and Jarratt D. Pytell
 
Article Referenced:  
Ashish P. Thakrar, Jarratt D. Pytell, Kenneth B. Stoller, Vickie Walters, Roger D. Weiss, Geetanjali Chander, Transitioning off methadone: A qualitative study exploring why patients discontinue methadone treatment for opioid use disorder, Journal of Substance Use and Addiction Treatment, Volume 150, 2023, 209055, ISSN 2949-8759. 
 
ASAM Resources: 
2020 National Practice Guideline for the Treatment of Opioid Use Disorder 
OUD Treatment Education 
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Lead: Increasing overdose deaths among Black Americans

Lead Story
Increasing overdose deaths among Black Americans: a review of the literature
The Lancet Psychiatry
This scoping review analyzed the many and varied factors contributing to the recent rise in opioid overdose death rates among Black Americans. Differences in structural and social determinants of health; unequal access, use, and continuity of SUD and harm reduction services; variability in fentanyl exposure and risk; and changes in social and economic conditions were all found to play a role. Black Americans historically are less likely to have access to treatment services than White Americans. Work to reform the criminal legal system, expand access, address provider bias, and fund equity-improving programs need to happen to affect change.
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Lead: Practice-Based Guidelines: Buprenorphine in the Age of Fentanyl

Lead Story
The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission 
JCI Insight
Evidence suggests that the glucagon-like-peptide-1 (GLP-1) system may be involved in the neurobiology of addiction. The authors studied the impact of semaglutide, a long acting GLP-1 analogue, on alcohol use in mice and rat models and found a decrease in binge-like alcohol drinking in both mice and rats. They also found  reduced alcohol intake in rates with dependence. The proposed mechanism for this effect is modulation of central GABA neurotransmission and supports the potential role of the GLP-1 system as a potential pharmacotherapeutic target for alcohol use disorder.  
 
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Lead: Racial Inequality in Receipt of Medications for Opioid Use Disorder

Lead Story
Racial Inequality in Receipt of Medications for Opioid Use Disorder
The New England Journal of Medicine
Opioid overdose mortality has increased over the last ten years, but disproportionately among Black persons. The authors examine racial disparities in receipt of buprenorphine and naloxone after opioid use disorder (OUD) related events using Medicare data from 2016-2019. They found that Black persons were less likely to receive buprenorphine (12.7 vs 23.3%) and naloxone (14.4% vs 22.9%) than White persons within six months after the event. Further, Black persons received lower day supply of buprenorphine and were less likely to be retained on treatment. Of note, Black and White persons had similar rates of ambulatory visits in the 6 months after the event, indicating patient and provider-level barriers to access.
 
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Lead: Eat, Sleep, Console Approach or Usual Care for Neonatal Opioid Withdrawal

Lead Story: 
Eat, Sleep, Console Approach or Usual Care for Neonatal Opioid Withdrawal
The New England Journal of Medicine
This multicenter randomized controlled trial was undertaken to evaluate the the Eat, Sleep, Console Care Tool vs usual care for neonatal opioid withdrawal with the primary outcome being medically ready for hospital discharge. The Eat, Sleep, Console Care Tool relies on an assessment of withdrawal severity focused on an infant’s ability to eat, sleep, and be consoled, along with the use of nonpharmacologic interventions as first line of treatment. The Eat, Sleep, Console care approach decreased the time until infants with opioid withdrawal were medically ready for discharge by a mean of 6.7 days, and the proportion of infants receiving pharmacologic treatment by 32.5%. Hence, this approach facilitates more judicious use of medication for these infants.
 
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Special Episode: Buprenorphine Initiation and the Howard Street Method

Article Referenced:  
Noel, Marnie PharmD, BCPP; et all. The Howard Street Method: A Community Pharmacy-Led Low Dose Overlap Buprenorphine Initiation Protocol for Individuals Using Fentanyl. Journal of Addiction Medicine.
 
ASAM Resources: 
2020 National Practice Guideline for the Treatment of Opioid Use Disorder 
OUD Treatment Education 
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