A non-hallucinogenic LSD analog with therapeutic potential for mood disorders
Summary: Hallucinations limit widespread therapeutic use of psychedelics as rapidly acting antidepressants. Here we profiled the non-hallucinogenic lysergic acid diethylamide (LSD) analog 2-bromo-LSD (2-Br-LSD) at more than 33 aminergic G protein-coupled receptors (GPCRs). 2-Br-LSD shows partial ago...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723002140 |
| _version_ | 1811158427157659648 |
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| author | Vern Lewis Emma M. Bonniwell Janelle K. Lanham Abdi Ghaffari Hooshmand Sheshbaradaran Andrew B. Cao Maggie M. Calkins Mario Alberto Bautista-Carro Emily Arsenault Andre Telfer Fatimeh-Frouh Taghavi-Abkuh Nicholas J. Malcolm Fatema El Sayegh Alfonso Abizaid Yasmin Schmid Kathleen Morton Adam L. Halberstadt Argel Aguilar-Valles John D. McCorvy |
| author_facet | Vern Lewis Emma M. Bonniwell Janelle K. Lanham Abdi Ghaffari Hooshmand Sheshbaradaran Andrew B. Cao Maggie M. Calkins Mario Alberto Bautista-Carro Emily Arsenault Andre Telfer Fatimeh-Frouh Taghavi-Abkuh Nicholas J. Malcolm Fatema El Sayegh Alfonso Abizaid Yasmin Schmid Kathleen Morton Adam L. Halberstadt Argel Aguilar-Valles John D. McCorvy |
| author_sort | Vern Lewis |
| collection | DOAJ |
| description | Summary: Hallucinations limit widespread therapeutic use of psychedelics as rapidly acting antidepressants. Here we profiled the non-hallucinogenic lysergic acid diethylamide (LSD) analog 2-bromo-LSD (2-Br-LSD) at more than 33 aminergic G protein-coupled receptors (GPCRs). 2-Br-LSD shows partial agonism at several aminergic GPCRs, including 5-HT2A, and does not induce the head-twitch response (HTR) in mice, supporting its classification as a non-hallucinogenic 5-HT2A partial agonist. Unlike LSD, 2-Br-LSD lacks 5-HT2B agonism, an effect linked to cardiac valvulopathy. Additionally, 2-Br-LSD produces weak 5-HT2A β-arrestin recruitment and internalization in vitro and does not induce tolerance in vivo after repeated administration. 2-Br-LSD induces dendritogenesis and spinogenesis in cultured rat cortical neurons and increases active coping behavior in mice, an effect blocked by the 5-HT2A-selective antagonist volinanserin (M100907). 2-Br-LSD also reverses the behavioral effects of chronic stress. Overall, 2-Br-LSD has an improved pharmacological profile compared with LSD and may have profound therapeutic value for mood disorders and other indications. |
| first_indexed | 2024-04-10T05:23:18Z |
| format | Article |
| id | doaj.art-2c21b545191b4d11912819fd72041816 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-10T05:23:18Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-2c21b545191b4d11912819fd720418162023-03-08T04:14:04ZengElsevierCell Reports2211-12472023-03-01423112203A non-hallucinogenic LSD analog with therapeutic potential for mood disordersVern Lewis0Emma M. Bonniwell1Janelle K. Lanham2Abdi Ghaffari3Hooshmand Sheshbaradaran4Andrew B. Cao5Maggie M. Calkins6Mario Alberto Bautista-Carro7Emily Arsenault8Andre Telfer9Fatimeh-Frouh Taghavi-Abkuh10Nicholas J. Malcolm11Fatema El Sayegh12Alfonso Abizaid13Yasmin Schmid14Kathleen Morton15Adam L. Halberstadt16Argel Aguilar-Valles17John D. McCorvy18Department of Neuroscience, Carleton University, Ottawa, ON K1S 5B6, CanadaDepartment of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USABetterLife Pharma Inc., Vancouver, BC V6H 1A6, CanadaBetterLife Pharma Inc., Vancouver, BC V6H 1A6, CanadaDepartment of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Neuroscience, Carleton University, Ottawa, ON K1S 5B6, CanadaDepartment of Neuroscience, Carleton University, Ottawa, ON K1S 5B6, CanadaDepartment of Neuroscience, Carleton University, Ottawa, ON K1S 5B6, CanadaDepartment of Neuroscience, Carleton University, Ottawa, ON K1S 5B6, CanadaDepartment of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Neuroscience, Carleton University, Ottawa, ON K1S 5B6, CanadaDepartment of Neuroscience, Carleton University, Ottawa, ON K1S 5B6, CanadaDepartment of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USADepartment of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USADepartment of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Corresponding authorDepartment of Neuroscience, Carleton University, Ottawa, ON K1S 5B6, Canada; Corresponding authorDepartment of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Corresponding authorSummary: Hallucinations limit widespread therapeutic use of psychedelics as rapidly acting antidepressants. Here we profiled the non-hallucinogenic lysergic acid diethylamide (LSD) analog 2-bromo-LSD (2-Br-LSD) at more than 33 aminergic G protein-coupled receptors (GPCRs). 2-Br-LSD shows partial agonism at several aminergic GPCRs, including 5-HT2A, and does not induce the head-twitch response (HTR) in mice, supporting its classification as a non-hallucinogenic 5-HT2A partial agonist. Unlike LSD, 2-Br-LSD lacks 5-HT2B agonism, an effect linked to cardiac valvulopathy. Additionally, 2-Br-LSD produces weak 5-HT2A β-arrestin recruitment and internalization in vitro and does not induce tolerance in vivo after repeated administration. 2-Br-LSD induces dendritogenesis and spinogenesis in cultured rat cortical neurons and increases active coping behavior in mice, an effect blocked by the 5-HT2A-selective antagonist volinanserin (M100907). 2-Br-LSD also reverses the behavioral effects of chronic stress. Overall, 2-Br-LSD has an improved pharmacological profile compared with LSD and may have profound therapeutic value for mood disorders and other indications.http://www.sciencedirect.com/science/article/pii/S2211124723002140CP: NeuroscienceCP: Molecular biology |
| spellingShingle | Vern Lewis Emma M. Bonniwell Janelle K. Lanham Abdi Ghaffari Hooshmand Sheshbaradaran Andrew B. Cao Maggie M. Calkins Mario Alberto Bautista-Carro Emily Arsenault Andre Telfer Fatimeh-Frouh Taghavi-Abkuh Nicholas J. Malcolm Fatema El Sayegh Alfonso Abizaid Yasmin Schmid Kathleen Morton Adam L. Halberstadt Argel Aguilar-Valles John D. McCorvy A non-hallucinogenic LSD analog with therapeutic potential for mood disorders Cell Reports CP: Neuroscience CP: Molecular biology |
| title | A non-hallucinogenic LSD analog with therapeutic potential for mood disorders |
| title_full | A non-hallucinogenic LSD analog with therapeutic potential for mood disorders |
| title_fullStr | A non-hallucinogenic LSD analog with therapeutic potential for mood disorders |
| title_full_unstemmed | A non-hallucinogenic LSD analog with therapeutic potential for mood disorders |
| title_short | A non-hallucinogenic LSD analog with therapeutic potential for mood disorders |
| title_sort | non hallucinogenic lsd analog with therapeutic potential for mood disorders |
| topic | CP: Neuroscience CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723002140 |
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