A Field-Wide Review and Analysis of Study Materials Used in Psilocybin Trials: Assessment of Two Decades of Research
Yaden, David B; Graziosi, Marianna; Owen, Alexa M; Agin-Liebes, Gabrielle; Aaronson, Scott T; Allen, Katja Ehrmann; Barrett, Frederick S; Bogenschutz, Michael P; Carhart-Harris, Robin; Ching, Terence H W; Cosimano, Mary P; Danforth, Alicia; Davis, Alan K; Garcia-Romeu, Albert; Griffiths, Roland; Grob, Charles S; Gründer, Gerhard; Gukasyan, Natalie; Heinzerling, Keith G; Hendricks, Peter S; Holze, Friederike; Horton, David M; Johnson, Matthew W; Kelmendi, Benjamin; Knatz Peck, Stephanie; Koslowski, Michael; Liechti, Matthias E; Mertens, Lea J; Moreno, Francisco A; Nayak, Sandeep M; Nicholas, Christopher R; Preller, Katrin H; Rieser, Nathalie M; Ross, Stephen; Sergi, Karina; Sloshower, Jordan; Smigielski, Lukasz; Stenbæk, Dea Siggaard; Vollenweider, Franz X; Weiss, Brandon; Wolff, Max; Yaden, Mary Elizabeth
INTRODUCTION/UNASSIGNED:Serotonergic psychedelics, serotonin 2A receptor agonists such as psilocybin that can result in substantially altered states of consciousness, are used in recreational and research settings. The safety of psychedelic experiences in research settings is supported by controlled physical environments, presence of clinical and medical staff to address emergent issues, screening for personal and family history of potential contraindications, and psychoeducational preparation with psychological support. Research settings typically provide psychoeducation to participants verbally and in writing (e.g., informed consent), and such documents and conversations can provide safety-related information-but may also introduce a wide range of expectancies. Such expectancies might involve the specific character of the acute subjective effects of psychedelics, possible side effects, and anticipated outcomes. METHODS/UNASSIGNED:To better understand the content of this psychoeducation, we gathered study materials from many psilocybin studies conducted in the past two decades in healthy and therapeutic populations. We conducted a reflexive thematic analysis to better understand these documents. RESULTS/UNASSIGNED:While these documents varied substantially between studies, we identified themes intended to lower levels of risk and optimize therapeutic effects from psychedelic treatments. The most frequently coded themes related to (1) biological and physical safety, (2) psychological safety and well-being, (3) aspects of setting, and (4) potential for expectancies. Prioritizing biological and psychological safety was evident in the materials from all sites. Furthermore, we identify potential contributors to expectancy unrelated to safety and suggest that these extrapharmacological elements be studied systematically in future research. CONCLUSIONS/UNASSIGNED:Ideally, future research should strive to maximize safety while attempting to minimize extraneous expectancies.
PMCID:12060849
PMID: 40351554
ISSN: 2831-4433
CID: 5843892
Genomics yields biological and phenotypic insights into bipolar disorder
O'Connell, Kevin S; Koromina, Maria; van der Veen, Tracey; Boltz, Toni; David, Friederike S; Yang, Jessica Mei Kay; Lin, Keng-Han; Wang, Xin; Coleman, Jonathan R I; Mitchell, Brittany L; McGrouther, Caroline C; Rangan, Aaditya V; Lind, Penelope A; Koch, Elise; Harder, Arvid; Parker, Nadine; Bendl, Jaroslav; Adorjan, Kristina; Agerbo, Esben; Albani, Diego; Alemany, Silvia; Alliey-Rodriguez, Ney; Als, Thomas D; Andlauer, Till F M; Antoniou, Anastasia; Ask, Helga; Bass, Nicholas; Bauer, Michael; Beins, Eva C; Bigdeli, Tim B; Pedersen, Carsten Bøcker; Boks, Marco P; Børte, Sigrid; Bosch, Rosa; Brum, Murielle; Brumpton, Ben M; Brunkhorst-Kanaan, Nathalie; Budde, Monika; Bybjerg-Grauholm, Jonas; Byerley, William; Cabana-Domínguez, Judit; Cairns, Murray J; Carpiniello, Bernardo; Casas, Miquel; Cervantes, Pablo; Chatzinakos, Chris; Chen, Hsi-Chung; Clarence, Tereza; Clarke, Toni-Kim; Claus, Isabelle; Coombes, Brandon; Corfield, Elizabeth C; Cruceanu, Cristiana; Cuellar-Barboza, Alfredo; Czerski, Piotr M; Dafnas, Konstantinos; Dale, Anders M; Dalkner, Nina; Degenhardt, Franziska; DePaulo, J Raymond; Djurovic, Srdjan; Drange, Ole Kristian; Escott-Price, Valentina; Fanous, Ayman H; Fellendorf, Frederike T; Ferrier, I Nicol; Forty, Liz; Frank, Josef; Frei, Oleksandr; Freimer, Nelson B; Fullard, John F; Garnham, Julie; Gizer, Ian R; Gordon, Scott D; Gordon-Smith, Katherine; Greenwood, Tiffany A; Grove, Jakob; Guzman-Parra, José; Ha, Tae Hyon; Hahn, Tim; Haraldsson, Magnus; Hautzinger, Martin; Havdahl, Alexandra; Heilbronner, Urs; Hellgren, Dennis; Herms, Stefan; Hickie, Ian B; Hoffmann, Per; Holmans, Peter A; Huang, Ming-Chyi; Ikeda, Masashi; Jamain, Stéphane; Johnson, Jessica S; Jonsson, Lina; Kalman, Janos L; Kamatani, Yoichiro; Kennedy, James L; Kim, Euitae; Kim, Jaeyoung; Kittel-Schneider, Sarah; Knowles, James A; Kogevinas, Manolis; Kranz, Thorsten M; Krebs, Kristi; Kushner, Steven A; Lavebratt, Catharina; Lawrence, Jacob; Leber, Markus; Lee, Heon-Jeong; Liao, Calwing; Lucae, Susanne; Lundberg, Martin; MacIntyre, Donald J; Maier, Wolfgang; Maihofer, Adam X; Malaspina, Dolores; Manchia, Mirko; Maratou, Eirini; Martinsson, Lina; Mattheisen, Manuel; McGregor, Nathaniel W; McInnis, Melvin G; McKay, James D; Medeiros, Helena; Meyer-Lindenberg, Andreas; Millischer, Vincent; Morris, Derek W; Moutsatsou, Paraskevi; Mühleisen, Thomas W; O'Donovan, Claire; Olsen, Catherine M; Panagiotaropoulou, Georgia; Papiol, Sergi; Pardiñas, Antonio F; Park, Hye Youn; Perry, Amy; Pfennig, Andrea; Pisanu, Claudia; Potash, James B; Quested, Digby; Rapaport, Mark H; Regeer, Eline J; Rice, John P; Rivera, Margarita; Schulte, Eva C; Senner, Fanny; Shadrin, Alexey; Shilling, Paul D; Sigurdsson, Engilbert; Sindermann, Lisa; Sirignano, Lea; Siskind, Dan; Slaney, Claire; Sloofman, Laura G; Smeland, Olav B; Smith, Daniel J; Sobell, Janet L; Soler Artigas, Maria; Stein, Dan J; Stein, Frederike; Su, Mei-Hsin; Sung, Heejong; Świątkowska, Beata; Terao, Chikashi; Tesfaye, Markos; Tesli, Martin; Thorgeirsson, Thorgeir E; Thorp, Jackson G; Toma, Claudio; Tondo, Leonardo; Tooney, Paul A; Tsai, Shih-Jen; Tsermpini, Evangelia Eirini; Vawter, Marquis P; Vedder, Helmut; Vreeker, Annabel; Walters, James T R; Winsvold, Bendik S; Witt, Stephanie H; Won, Hong-Hee; Ye, Robert; Young, Allan H; Zandi, Peter P; Zillich, Lea; ,; Adolfsson, Rolf; Alda, Martin; Alfredsson, Lars; Backlund, Lena; Baune, Bernhard T; Bellivier, Frank; Bengesser, Susanne; Berrettini, Wade H; Biernacka, Joanna M; Boehnke, Michael; Børglum, Anders D; Breen, Gerome; Carr, Vaughan J; Catts, Stanley; Cichon, Sven; Corvin, Aiden; Craddock, Nicholas; Dannlowski, Udo; Dikeos, Dimitris; Etain, Bruno; Ferentinos, Panagiotis; Frye, Mark; Fullerton, Janice M; Gawlik, Micha; Gershon, Elliot S; Goes, Fernando S; Green, Melissa J; Grigoroiu-Serbanescu, Maria; Hauser, Joanna; Henskens, Frans A; Hjerling-Leffler, Jens; Hougaard, David M; Hveem, Kristian; Iwata, Nakao; Jones, Ian; Jones, Lisa A; Kahn, René S; Kelsoe, John R; Kircher, Tilo; Kirov, George; Kuo, Po-Hsiu; Landén, Mikael; Leboyer, Marion; Li, Qingqin S; Lissowska, Jolanta; Lochner, Christine; Loughland, Carmel; Luykx, Jurjen J; Martin, Nicholas G; Mathews, Carol A; Mayoral, Fermin; McElroy, Susan L; McIntosh, Andrew M; McMahon, Francis J; Medland, Sarah E; Melle, Ingrid; Milani, Lili; Mitchell, Philip B; Morken, Gunnar; Mors, Ole; Mortensen, Preben Bo; Müller-Myhsok, Bertram; Myers, Richard M; Myung, Woojae; Neale, Benjamin M; Nievergelt, Caroline M; Nordentoft, Merete; Nöthen, Markus M; Nurnberger, John I; O'Donovan, Michael C; Oedegaard, Ketil J; Olsson, Tomas; Owen, Michael J; Paciga, Sara A; Pantelis, Christos; Pato, Carlos N; Pato, Michele T; Patrinos, George P; Pawlak, Joanna M; Ramos-Quiroga, Josep Antoni; Reif, Andreas; Reininghaus, Eva Z; Ribasés, Marta; Rietschel, Marcella; Ripke, Stephan; Rouleau, Guy A; Roussos, Panos; Saito, Takeo; Schall, Ulrich; Schalling, Martin; Schofield, Peter R; Schulze, Thomas G; Scott, Laura J; Scott, Rodney J; Serretti, Alessandro; Smoller, Jordan W; Squassina, Alessio; Stahl, Eli A; Stefansson, Hreinn; Stefansson, Kari; Stordal, Eystein; Streit, Fabian; Sullivan, Patrick F; Turecki, Gustavo; Vaaler, Arne E; Vieta, Eduard; Vincent, John B; Waldman, Irwin D; Weickert, Cynthia S; Weickert, Thomas W; Werge, Thomas; Whiteman, David C; Zwart, John-Anker; Edenberg, Howard J; McQuillin, Andrew; Forstner, Andreas J; Mullins, Niamh; Di Florio, Arianna; Ophoff, Roel A; Andreassen, Ole A; ,
Bipolar disorder is a leading contributor to the global burden of disease1. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown2. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.8 million controls), combining clinical, community and self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-analysis, a fourfold increase over previous findings3, and identified an ancestry-specific association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes in the aetiology of bipolar disorder. Genes prioritized through fine-mapping were enriched for ultra-rare damaging missense and protein-truncating variations in cases with bipolar disorder4, highlighting convergence of common and rare variant signals. We report differences in the genetic architecture of bipolar disorder depending on the source of patient ascertainment and on bipolar disorder subtype (type I or type II). Several analyses implicate specific cell types in the pathophysiology of bipolar disorder, including GABAergic interneurons and medium spiny neurons. Together, these analyses provide additional insights into the genetic architecture and biological underpinnings of bipolar disorder.
PMID: 39843750
ISSN: 1476-4687
CID: 5778012