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Gerard Moeller, MD</a></span></div></div></div><div class="max-w-full"><div class="flex flex-wrap sm:flex-nowrap items-center w-fit my-2"></div><div class="w-full flex flex-col sm:flex-row justify-between mt-2"><div class="block md:hidden "><div class="mt-2 flex items-center max-w-fit"><button title="Beyond Abstinence: Other Clinically Meaningful Endpoints for Patients With Substance Use Disorders" aria-label="facebook" class="react-share__ShareButton" style="background-color:transparent;border:none;padding:0;font:inherit;color:inherit;cursor:pointer"><svg viewBox="0 0 64 64" width="32" height="32"><circle cx="32" cy="32" r="31" fill="#3b5998"></circle><path d="M34.1,47V33.3h4.6l0.7-5.3h-5.3v-3.4c0-1.5,0.4-2.6,2.6-2.6l2.8,0v-4.8c-0.5-0.1-2.2-0.2-4.1-0.2 c-4.1,0-6.9,2.5-6.9,7V28H24v5.3h4.6V47H34.1z" fill="white"></path></svg></button><button aria-label="twitter" class="react-share__ShareButton" style="background-color:transparent;border:none;padding:0;font:inherit;color:inherit;cursor:pointer"><svg fill="#DC7633" xmlns="http://www.w3.org/2000/svg" width="32" zoomAndPan="magnify" viewBox="0 0 375 374.9999" height="32" preserveAspectRatio="xMidYMid meet" version="1.0"><defs><path d="M 7.09375 7.09375 L 367.84375 7.09375 L 367.84375 367.84375 L 7.09375 367.84375 Z M 7.09375 7.09375 " fill="#000000"></path></defs><g><path d="M 187.46875 7.09375 C 87.851562 7.09375 7.09375 87.851562 7.09375 187.46875 C 7.09375 287.085938 87.851562 367.84375 187.46875 367.84375 C 287.085938 367.84375 367.84375 287.085938 367.84375 187.46875 C 367.84375 87.851562 287.085938 7.09375 187.46875 7.09375 " fill-opacity="1" fill-rule="nonzero" fill="#000000"></path></g><g transform="translate(85, 75)"> <svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" version="1.1" height="215" width="215"><path d="M18.244 2.25h3.308l-7.227 8.26 8.502 11.24H16.17l-5.214-6.817L4.99 21.75H1.68l7.73-8.835L1.254 2.25H8.08l4.713 6.231zm-1.161 17.52h1.833L7.084 4.126H5.117z" fill="#ffffff"></path></svg> </g></svg></button><button aria-label="linkedin" class="react-share__ShareButton" style="background-color:transparent;border:none;padding:0;font:inherit;color:inherit;cursor:pointer"><svg viewBox="0 0 64 64" width="32" height="32"><circle cx="32" cy="32" r="31" fill="#007fb1"></circle><path d="M20.4,44h5.4V26.6h-5.4V44z M23.1,18c-1.7,0-3.1,1.4-3.1,3.1c0,1.7,1.4,3.1,3.1,3.1 c1.7,0,3.1-1.4,3.1-3.1C26.2,19.4,24.8,18,23.1,18z M39.5,26.2c-2.6,0-4.4,1.4-5.1,2.8h-0.1v-2.4h-5.2V44h5.4v-8.6 c0-2.3,0.4-4.5,3.2-4.5c2.8,0,2.8,2.6,2.8,4.6V44H46v-9.5C46,29.8,45,26.2,39.5,26.2z" fill="white"></path></svg></button><button title="Beyond Abstinence: Other Clinically Meaningful Endpoints for Patients With Substance Use Disorders" aria-label="pinterest" class="react-share__ShareButton" style="background-color:transparent;border:none;padding:0;font:inherit;color:inherit;cursor:pointer"><svg viewBox="0 0 64 64" width="32" height="32"><circle cx="32" cy="32" r="31" fill="#cb2128"></circle><path d="M32,16c-8.8,0-16,7.2-16,16c0,6.6,3.9,12.2,9.6,14.7c0-1.1,0-2.5,0.3-3.7 c0.3-1.3,2.1-8.7,2.1-8.7s-0.5-1-0.5-2.5c0-2.4,1.4-4.1,3.1-4.1c1.5,0,2.2,1.1,2.2,2.4c0,1.5-0.9,3.7-1.4,5.7 c-0.4,1.7,0.9,3.1,2.5,3.1c3,0,5.1-3.9,5.1-8.5c0-3.5-2.4-6.1-6.7-6.1c-4.9,0-7.9,3.6-7.9,7.7c0,1.4,0.4,2.4,1.1,3.1 c0.3,0.3,0.3,0.5,0.2,0.9c-0.1,0.3-0.3,1-0.3,1.3c-0.1,0.4-0.4,0.6-0.8,0.4c-2.2-0.9-3.3-3.4-3.3-6.1c0-4.5,3.8-10,11.4-10 c6.1,0,10.1,4.4,10.1,9.2c0,6.3-3.5,11-8.6,11c-1.7,0-3.4-0.9-3.9-2c0,0-0.9,3.7-1.1,4.4c-0.3,1.2-1,2.5-1.6,3.4 c1.4,0.4,3,0.7,4.5,0.7c8.8,0,16-7.2,16-16C48,23.2,40.8,16,32,16z" fill="white"></path></svg></button><button aria-label="email" class="react-share__ShareButton" style="background-color:transparent;border:none;padding:0;font:inherit;color:inherit;cursor:pointer"><svg viewBox="0 0 64 64" width="32" height="32"><circle cx="32" cy="32" r="31" fill="#7f7f7f"></circle><path d="M17,22v20h30V22H17z M41.1,25L32,32.1L22.9,25H41.1z M20,39V26.6l12,9.3l12-9.3V39H20z" fill="white"></path></svg></button><a class="print-wrap flex justify-center items-center cursor-pointer"><svg id="print" xmlns="http://www.w3.org/2000/svg" width="24" height="24" fill="currentColor" class="print bi bi-printer" viewBox="0 0 16 16"> <path d="M2.5 8a.5.5 0 1 0 0-1 .5.5 0 0 0 0 1z"></path> <path d="M5 1a2 2 0 0 0-2 2v2H2a2 2 0 0 0-2 2v3a2 2 0 0 0 2 2h1v1a2 2 0 0 0 2 2h6a2 2 0 0 0 2-2v-1h1a2 2 0 0 0 2-2V7a2 2 0 0 0-2-2h-1V3a2 2 0 0 0-2-2H5zM4 3a1 1 0 0 1 1-1h6a1 1 0 0 1 1 1v2H4V3zm1 5a2 2 0 0 0-2 2v1H2a1 1 0 0 1-1-1V7a1 1 0 0 1 1-1h12a1 1 0 0 1 1 1v3a1 1 0 0 1-1 1h-1v-1a2 2 0 0 0-2-2H5zm7 2v3a1 1 0 0 1-1 1H5a1 1 0 0 1-1-1v-3a1 1 0 0 1 1-1h6a1 1 0 0 1 1 1z"></path></svg></a></div><style> .print-wrap { width: 32px; height: 32px; background: #7F7F7F; border-radius: 100%; } .print { background: #7F7F7F; color: white; padding: 2px; border-radius: 100%; } </style></div></div></div></div><div class=" lg:w-full flex flex-col lg:flex-row lg:items-center lg:justify-end"><div class="related-landing sm:w-auto md:max-w-fit lg:w-[auto] md:text-center my-2 md:my-0 undefined"><a class="" href="/conferences/acnp"><div class="mt-6"><span class="text-primary text-sm">Conferences</span><span class="mx-1 text-sm">|</span><span class="text-sm text-blue-700 underline">ACNP</span></div></a></div></div><div class="w-full flex flex-col px-4 py-4 border-t border-b border-solid border-gray-400 my-4 "><h3 class="text-primary text-xl font-semibold">Key Takeaways</h3><ul class="list-disc px-8"><li class="py-2 "> Complete abstinence is not the only meaningful endpoint for substance use disorder patients; reduction in use can save lives. </li><li class="py-2 "> The session explores alternative endpoints like impulsivity, compulsive behaviors, and craving in clinical trials. </li><li class="py-2 hidden"> Dr. F. Gerard Moeller emphasizes the need for diverse endpoints to improve treatment efficacy for substance use disorders.</li></ul><span class="text-xs font-bold text-primary underline cursor-pointer mt-2 ml-4">SHOW MORE</span></div><p class="py-2 mb-2 text-sm italic text-gray-600">While complete abstinence is a good goal, what other clinically meaningful endpoints are there for patients with substance use disorders? Learn more in this ACNP 2024 Annual Meeting session!</p><div class="py-2"><div class="blockText_blockContent__TbCXh"><div class="relative"><div class="brightcove-fluid" autoplay=""></div></div><p class="pb-2">F. Gerard Moeller, MD, shares more on his session "<a rel="nofollow noreferrer noopener" target="_blank" href="https://acnp.societyconference.com/user/server/submission_pdf.php">Novel Non-Abstinence Endpoints/Measures for Clinical Trials in Substance use Disorders</a>" at the <a rel="nofollow noreferrer noopener" target="_blank" href="https://acnp.org/annual-meeting/">American College of Neuropsychopharmacology (ACNP) Annual Meeting</a>. </p><p class="pb-2">His take home message: Complete abstinence is not the only clinically meaningful endpoint for patient with substance use disorders. A reduction of use in fentanyl, for example, good result in saving lives. </p><p class="pb-2">The varied presenters of this session cover reduction in use, impulsivity, compulsive behaviors, craving, and more. </p><p class="pb-2"><em>Are you attending this year's ACNP meeting? Let us know at <a rel="nofollow" target="_self" href="mailto:PTEditor@MMHGroup.com">PTEditor@MMHGroup.com</a>!</em></p><p class="pb-2"><strong>Dr Moeller</strong> <em>is a professor in the Department of Pharmacology and Toxicology at Virginia Commonwealth University. </em></p></div></div><div class="flex items-center lg:w-3/4 mb-4 pb-12"></div><div class="jsx-19ede9f0a5a45918 py-4 relative bg-primary md:px-8 -ml-6 xs:ml-0 w-screen xs:w-auto"><div class="jsx-19ede9f0a5a45918 px-4 sm:px-0"><div class="flex justify-between items-center py-1 space-x-4 border-0 select-none sm:border-b border-secondary"><div class="text-3xl text-white text-lg sm:text-3xl">Related Videos</div></div></div><div style="scroll-snap-type:none" class="jsx-19ede9f0a5a45918 flex items-start overflow-x-auto space-x-4 py-4 relative mx-auto w-full pl-4"><a id="" class="w-[200px] h-fit space-y-3 flex-none select-none no-underline" style="scroll-snap-align:center;text-decoration:none" 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Gerard Moeller, MD, shares more on his session \"Novel Non-Abstinence Endpoints/Measures for Clinical Trials in Substance use Disorders\" at the American College of Neuropsychopharmacology (ACNP) Annual Meeting. \n\nHis take home message: Complete abstinence is not the only clinically meaningful endpoint for patient with substance use disorders. A reduction of use in fentanyl, for example, good result in saving lives. \n\nThe varied presenters of this session cover reduction in use, impulsivity, compulsive behaviors, craving, and more. \n\nAre you attending this year's ACNP meeting? Let us know at PTEditor@MMHGroup.com!\n\nDr Moeller is a professor in the Department of Pharmacology and Toxicology at Virginia Commonwealth University. ","description":"While complete abstinence is a good goal, what other clinically meaningful endpoints are there for patients with substance use disorders? Learn more in this ACNP 2024 Annual Meeting session!","author":[{"@type":"Person","name":"F. Gerard Moeller, MD"}]}</script></div></div><div class="flex-none w-[300px] z-[9999] relative hidden md:block"><div style="top:5rem" class="sticky custom-spacing"><div class="collapse-container " style="overflow:hidden;max-height:900px;transition:max-height .4s ease-in-out"></div></div></div></div><div id="div-gpt-ad-pixel" style="width:1px;height:1px" class=""></div><noscript><iframe src="https://www.googletagmanager.com/ns.html?id=GTM-5V9L5PL" height="0" width="0" style="display:none;visibility:hidden"></iframe></noscript><div id="footerOuterWrap" class="w-full bg-primary flex flex-col items-center justify-center"><div class="container w-[1340px]"><div id="footerInnerWrap" class="bg-primary w-full py-12"><div class="py-4 pl-4 flex flex-row items-center"><div class="flex flex-row flex-wrap w-[55%] h-full"><div class="w-[33%] p-1 my-0 cursor-pointer text-footer-text-color hover:text-footer-text-color/80 hover:underline"><a class="text-md" target="_self" href="/about">About</a></div><div 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So there's definitely a need for rapid reacting antidepressant with potential for improvement in suicidality,” Upadhyaya told ","_key":"8d6099669fff0"},{"_type":"span","marks":["em"],"text":"Psychiatric Times ","_key":"8d6099669fff1"},{"_type":"span","marks":[],"text":"in an interview.","_key":"8d6099669fff2"}],"_type":"block"},{"style":"normal","_key":"66081d8802e5","markDefs":[],"children":[{"_type":"span","marks":[],"text":"The phase 2 study focused on evaluating the safety, tolerability, and preliminary efficacy of SPN-820 in a cohort of adults (N=40) with MDD who had not achieved sufficient symptom control with their current FDA-approved treatments, he said. Specifically, the study looked at every 3 day dosing; the agent was administered on day 1, 4, and 7.","_key":"1f09b40e6b770"}],"_type":"block"},{"_type":"block","style":"normal","_key":"bfbbf561936e","markDefs":[],"children":[{"_key":"748aefa410c40","_type":"span","marks":[],"text":"“We found that the drug was very well tolerated,” he said. “It had no serious or severe adverse event.” Almost 40% of the patients had no adverse events, he said, but he acknowledged that it meant approximately 60% of the patients did experience adverse events. The most common adverse events were headache (20.0%), nausea (20.0%), somnolence (15.0%), and dizziness (10.0%).1 However, there was no study discontinuation due to adverse events."}]},{"children":[{"_type":"span","marks":[],"text":"In considering efficacy, Upadhyaya and colleagues looked at MADRS, HAM-D 6, and CGIS scores. “What we found is a very rapid improvement in HAM-D 6 scores in 2 hours…and after each subsequent dose we saw slightly better improvement,” he told ","_key":"66a71c2d41840"},{"marks":["em"],"text":"Psychiatric Times. ","_key":"66a71c2d41841","_type":"span"},{"_type":"span","marks":[],"text":"Improvement was also seen with MADRS scores. They also saw reduced suicide ideation.","_key":"66a71c2d41842"}],"_type":"block","style":"normal","_key":"808bb1175601","markDefs":[]},{"style":"normal","_key":"bb656eae6f32","markDefs":[],"children":[{"_type":"span","marks":[],"text":"SPN-820 is a small molecule that can be taken orally, Upadhyaya said, with participants in this study taking capsules. It is a novel, first in class novel mechanism of action, he added. “The agent works intracellularly to increase mTORC1 activity, which then, in the presence of BDNF, leads to increased protein synthesis related to synaptogenesis,” he explained. ”So it increases the number of synapses, dendritic spines, and the connection that strengthens the synaptic connections that is thought to be involved in the rapid antidepressant effect.”","_key":"b18e3d50d4cc0"}],"_type":"block"},{"children":[{"_type":"span","marks":[],"text":"","_key":"40dfd96b91a90"}],"_type":"block","style":"normal","_key":"d0be412d4a25","markDefs":[]},{"children":[{"_type":"span","marks":[],"text":"Unlike other rapidly acting antidepressants, SPN-820 may ultimately have similar mechanisms of action, he added, but the other agents worked indirectly by the activity on NMDA receptor or 5HT receptors. “We bypass that and go straight intracellularly and improve mTORC1 activity,” Upadhyaya explained. “Because of that, we don’t expect any abuse potential with this product.” Similarly, other rapidly acting antidepressants, both on the market and under investigation, may result in dissociative symptoms, but this trial did not find any evidence of such.","_key":"b67ff67036e50"}],"_type":"block","style":"normal","_key":"a05fdfc8b788","markDefs":[]},{"_key":"093991601e41","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"9bccc18284100"}],"_type":"block","style":"normal"},{"_type":"block","style":"normal","_key":"bbabdc09fd6c","markDefs":[{"href":"https://one.psychiatrictimes.com/subscribe/","_key":"991ebaf3480f","_type":"link"}],"children":[{"_key":"4217fc5be9260","_type":"span","marks":["em"],"text":"For more information from Dr Upadhyaya on SPN-820 as well as highlights from other sessions and posters, "},{"_type":"span","marks":["em","991ebaf3480f"],"text":"subscribe to the Psychiatric Times e-newsletter","_key":"4217fc5be9261"},{"text":".\n\n","_key":"4217fc5be9262","_type":"span","marks":["em"]},{"text":"Reference","_key":"709138391104","_type":"span","marks":["strong"]}]},{"markDefs":[],"children":[{"text":"1. 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Mizrahi and Blasco noted they also found significant associations between synaptic density and neurite density index (NDI), suggesting potential microstructural abnormalities in grey matter.","_key":"9c40993c35b60"}],"_type":"block","style":"normal","_key":"f1238c632cb3"},{"style":"normal","_key":"06720d58321a","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"c1a6ac835b180"}],"_type":"block"},{"markDefs":[],"children":[{"_key":"fada0acdf5e30","_type":"span","marks":[],"text":"In an exclusive video interview with "},{"_key":"fada0acdf5e31","_type":"span","marks":["em"],"text":"Psychiatric Times"},{"_type":"span","marks":[],"text":", Mizrahi and Blasco emphasized the clinical relevance of these findings. “In these clinical groups, compared to healthy volunteers, there was a reduction in synaptic density levels,” Blasco said. They explained that the study provided critical evidence that negative symptoms in psychosis—such as reduced motivation and interest in social engagement—are tied to disruptions in brain connectivity. “This ability that we have to connect with others and to be engaged in society really seems to be related to how our brain connects within itself,” Mizrahi said.","_key":"fada0acdf5e32"}],"_type":"block","style":"normal","_key":"d0c288bce984"},{"_key":"54119143899c","markDefs":[],"children":[{"_type":"span","marks":[],"text":"","_key":"0a5123ee7dea0"}],"_type":"block","style":"normal"},{"_type":"block","style":"normal","_key":"12af1411df80","markDefs":[],"children":[{"_type":"span","marks":[],"text":"Mizrahi also highlighted the impact of cannabis on synaptic density and the importance of further longitudinal studies to explore this relationship. The findings underscore the need for continued investigation into synaptic dysfunction as a key mechanism in psychosis and CHR states, with implications for targeted interventions.","_key":"8a1e402be5a20"}]},{"_key":"9c514d6be6ad","markDefs":[],"children":[{"_key":"22b7d05d255f0","_type":"span","marks":[],"text":"Mizrahi added that these results contribute to a growing understanding of how early synaptic changes influence psychosis onset and progression, paving the way for more precise diagnostics and treatment strategies.\n\nBeyond their findings, Mizrahi and Blasco praised the ACNP conference for its forward-thinking focus and commitment to translational research. For instance, Mizrahi was intrigued by discussions on the role of glia in schizophrenia, \"instead of just looking at the standard mechanism of action for antipsychotics... the next frontier is to actually start to understand the brain and see whether we can actually prevent disease.”"}],"_type":"block","style":"normal"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"Blasco was also impressed with the networking opportunities. “This is the first time that I’m coming as a PhD student,” she said. “It’s a great opportunity to share and network... and also to learn from the best scientists on how to develop a career in science.”\n\n","_key":"8adfc9a092b60"},{"_type":"span","marks":["strong"],"text":"Reference\n","_key":"180e06e15500"},{"_type":"span","marks":[],"text":"1. Blasco M Belen. Synaptic Density in Early Stages of Psychosis and Clinical High Risk: A Link with Negative Symptoms. Presented at: The 63rd Annual Meeting of the American College of Neuropsychopharmacology. Phoenix, Arizona; December 8 - 12, 2024. 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The study involved participants aged 18 to 65 with moderate to severe AUD, who were administered suvorexant or placebo over four weeks. Results indicated a significant reduction in unexpected threat reactivity and overall alcohol consumption, without affecting predicted threat. The findings highlight the potential of orexin antagonism as a promising target for stress-related drinking and AUD.","audioUrl":"https://s3.us-east-1.amazonaws.com/ai-generated-audios/www.psychiatrictimes.com/1c309372-5c9d-421f-b4b3-9ae006517049_1733809157704.72493c88-2750-4fee-90eb-e1d495e83101.mp3","gptTakeaways":"• Orexin antagonism, using suvorexant, may reduce stress reactivity and drinking severity in individuals with moderate to severe AUD.\n\n• The study involved participants aged 18 to 65, randomly assigned to suvorexant or placebo, with good adherence and tolerance reported.\n\n• Suvorexant showed a 40.2% reduction in unexpected threat reactivity and reduced overall drinking, without affecting predicted threat.\n\n• The research underscores the potential of orexin antagonism as a promising target for stress-related drinking and AUD.","taxonomyMapping":[{"_id":"pst_taxonomy_336_psychopharmacology","_createdAt":"2020-03-26T06:11:21Z","_rev":"4roekEga8ZReQAdH6zkAp9","cmeType":"per","parent":{"isMainTopic":true,"_createdAt":"2020-03-26T06:11:21Z","name":"Topics","_updatedAt":"2023-03-31T19:15:59Z","_rev":"uvXJooXtzvjNOyx50HTt8m","_type":"taxonomy","_id":"pst_taxonomy_53202_clinical","identifier":"topics","parent":null},"pixelTrackingCode":null,"_type":"taxonomy","name":"Psychopharmacology","_updatedAt":"2023-03-31T19:23:25Z","identifier":"topics/psychopharmacology","perKeywordMapping":["Psychiatry","Neurology","New Drugs"]},{"_rev":"BmvClBuXMtNlljYu6nhdr9","_type":"taxonomy","_id":"pst_taxonomy_394_substanceusedisorder","_updatedAt":"2020-06-10T19:45:36Z","name":"Substance Use Disorder","identifier":"topics/substance-use-disorder","parent":{"_createdAt":"2020-03-26T06:11:21Z","_rev":"xx0Ames3576JN2Whgbhxu6","_type":"taxonomy","name":"Addiction \u0026 Substance Use","_id":"pst_taxonomy_254_addictionsubstanceuse","parent":{"_rev":"uvXJooXtzvjNOyx50HTt8m","_type":"taxonomy","name":"Topics","_id":"pst_taxonomy_53202_clinical","_updatedAt":"2023-03-31T19:15:59Z","identifier":"topics","isMainTopic":true,"_createdAt":"2020-03-26T06:11:21Z"},"cmeType":"per","identifier":"topics/addiction-suds-compulsive","perKeywordMapping":["Psychiatry","Neurology"],"_updatedAt":"2024-04-24T15:55:14Z"},"_createdAt":"2020-03-26T06:11:21Z","pixelTrackingCode":null}],"contentCategory":{"_updatedAt":"2020-02-25T09:35:56Z","_createdAt":"2020-02-06T09:15:47Z","_rev":"snQqhhB4O8T5bi1viURsgs","_type":"contentCategory","name":"Articles","_id":"8bdaa7fc-960a-4b57-b076-75fdce3741bb"},"documentGroup":{"_rev":"ejz6Pq3OnBuSEtH3SjPWK8","_type":"documentGroup","_id":"a943f457-0edc-4360-ab7c-f44c2a035d27","_updatedAt":"2024-02-02T21:28:12Z","identifier":{"current":"conferences/acnp","_type":"slug"},"_createdAt":"2024-02-02T21:28:12Z","pixelTrackingCode":null,"name":"ACNP","parent":{"_updatedAt":"2021-10-07T14:43:42Z","identifier":{"_type":"slug","current":"conferences"},"parent":null,"_createdAt":"2020-03-26T06:12:02Z","_rev":"wprjukSzaYWKhfPX4FSqef","_type":"documentGroup","name":"Conferences","_id":"pst_documentGroup_53201_conferences"}},"factCheckAuthorMapping":null,"documentGroupMapping":null,"body":[{"disableTextWrap":false,"_type":"figure","alt":"Aleksey/Adobestock","hotspot":{"y":0.5,"height":1,"_type":"sanity.imageHotspot","width":0.7505827150144779,"x":0.624708642492761},"imgcaption":[{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"Aleksey/Adobestock","_key":"4b7708bfcd21"}],"_type":"block","style":"normal","_key":"c67ab2fbfd74"}],"widthP":20,"crop":{"top":0,"left":0.24941728498552201,"bottom":0,"_type":"sanity.imageCrop","right":0},"alignment":"left","asset":{"_ref":"image-611b2b90b3e538d72b83d1d6f16ed1035cc5f30a-1346x886-jpg","_type":"reference"},"disableLightBox":true,"_key":"a37b45f7b58a"},{"children":[{"_type":"span","marks":["strong"],"text":"CONFERENCE REPORTER","_key":"0ac7b4b1c871"}],"_type":"block","style":"normal","_key":"2cda02ab9b00","markDefs":[]},{"children":[{"_key":"387dfbef42ba0","_type":"span","marks":[],"text":"Orexin may prove to be another tool to address alcohol disorder, according to research presented at the 63rd Annual Meeting of the American College of Neuropsychopharmacology."},{"_type":"span","marks":["sup"],"text":"1","_key":"4eb941065ba4"}],"_type":"block","style":"normal","_key":"d6387b6cfd85","markDefs":[]},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"Stephanie Gorka, PhD, shared highlights from her research (NCT05656534) on orexin antagonism and its role in alcohol use disorder (AUD), specifically in reducing stress reactivity and subsequent drinking severity.","_key":"d362ed758a0c0"},{"text":"2","_key":"41124d704314","_type":"span","marks":["sup"]},{"_type":"span","marks":[],"text":" In addition to investigating the psychopharmacology of suvorexant for this use, Gorka and her team were interested in exploring which types of patients with moderate to severe AUD would benefit from orexin antagonism in modifying brain-behavior stress targets. Gorka, associate professor in the Department of Psychiatry \u0026 Behavioral Health Institute for Behavioral Medicine Research at the Ohio State University College of Medicine, launched the first Promising Targets Oral Session at the meeting.","_key":"5eb77493f5fe"}],"_type":"block","style":"normal","_key":"a103c7906cb5"},{"children":[{"_type":"span","marks":[],"text":"Study participants were aged 18 to 65 years, were in general medical good health, and met the ","_key":"5224b604058c0"},{"_type":"span","marks":["em"],"text":"DSM-5","_key":"5224b604058c1"},{"_type":"span","marks":[],"text":" criteria for current moderate to severe AUD. Individuals were randomly assigned to the active treatment group (10 mg oral suvorexant) or placebo. The active treatment and placebo arms were matched in age, biological sex, race/ethnicity, and total score on the Alcohol Use Disorders Identification Test (AUDIT).","_key":"5224b604058c2"}],"_type":"block","style":"normal","_key":"26307a6f6507","markDefs":[]},{"style":"normal","_key":"a9afddde99f9","markDefs":[],"children":[{"marks":[],"text":"Treatments were administered as a drug challenge and then self-administered nightly for 4 weeks. The team used a No Threat-Predictable Threat-Unpredictable Threat task at baseline, after treatment administration, and after the 4 weeks of treatment; startle eyeblink potentiation was used as a measure. Smartphones monitored daily medication adherence, subjective stress levels, alcohol consumption, and any adverse events.","_key":"69c739f5060f0","_type":"span"}],"_type":"block"},{"children":[{"_type":"span","marks":[],"text":"Adherence across the treatment groups was good, she reported, and the agent appeared to be well tolerated. Gorka noted there were no moderate or severe adverse events reported. In addition, mild adverse events were similarly reported in both the placebo and drug treatment groups.","_key":"66da571a8f910"}],"_type":"block","style":"normal","_key":"9fb4f7eecefa","markDefs":[]},{"children":[{"_key":"6e6e3bc1baad0","_type":"span","marks":[],"text":"Gorka et al found suvorexant was beneficial for the unexpected threat reactivity both after the initial dose and again after 4 weeks of treatment. Specifically, they found the agent was associated with a 40.2% reduction in unexpected threat reactivity. It also resulted in an overall reduction of drinking for these participants. However, the drug did not have an impact on predicted threat."}],"_type":"block","style":"normal","_key":"d04a1fdc3eab","markDefs":[]},{"_type":"block","style":"normal","_key":"d7823218324e","markDefs":[],"children":[{"_type":"span","marks":[],"text":"Because suvorexant is FDA-approved for sleep issues, the researchers also considered the impact of sleep in the study. The participants were all relatively good sleepers to start, getting 7 to 8 hours per night, Gorka told attendees, and not much changed with drug initiation. Gorka et al concluded any changes in sleep did not account for changes in startle and subjective stress.","_key":"6a853cd1bf430"}]},{"_type":"block","style":"normal","_key":"433f9203e1e5","markDefs":[],"children":[{"_type":"span","marks":[],"text":"The research has greater implications, Gorka explained, as 12% of US adults meet criteria for AUD and alcohol related mortality has doubled in the past 20 years. Meanwhile, there are only a handful of medications that address AUD, and about half of those receiving these medications relapse, she told attendees.","_key":"7c58a70b35610"}]},{"style":"normal","_key":"d2c0af643191","markDefs":[],"children":[{"_type":"span","marks":[],"text":"Produced in the hypothalamus, orexins are associated with wakefulness, arousal, energy metabolism, and stress, Gorka said. She was intrigued because orexin receptor 1 and orexin receptor 2 are distributed throughout the brain and in networks involved in stress, fear, and anxiety. She and her team hypothesized orexin antagonism may be effective in disrupting AUD’s negative reinforcement cycle. ","_key":"6858ab2fc8d70"}],"_type":"block"},{"markDefs":[],"children":[{"_type":"span","marks":[],"text":"“These results extend our initial findings that SUV [suvorexant]selectively and effectively reduces objective reactivity to U-threat [unexpected threat] in humans,” explained Gorka. “These results have significant clinical implications and further highlight the role and importance of the orexin system as a promising target for stress-related drinking and AUD.”1","_key":"7eb16930b064"}],"_type":"block","style":"normal","_key":"d829e06758b7"},{"children":[{"_type":"span","marks":[],"text":"Based on these findings, Gorka said the next step would be a large scale randomized controlled trial to further investigate the relationship and for whom this treatment works.","_key":"bae9805887a5"}],"_type":"block","style":"normal","_key":"2441e651b778","markDefs":[]},{"markDefs":[],"children":[{"_type":"span","marks":["strong"],"text":"References","_key":"335f30c4bce90"}],"_type":"block","style":"normal","_key":"8abffc741154"},{"style":"normal","_key":"ba138fdd9049","markDefs":[],"children":[{"_type":"span","marks":[],"text":"1. 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