{"rows":[{"id":301,"title":"Contribution of the Serotonin 5-HT2A Receptor to the Therapeutic Effect of Psilocin on Social Behavior Deficits in Mice Repeatedly Exposed to Social Defeat Stress","normalized_title":"contribution of the serotonin 5 ht2a receptor to the therapeutic effect of psilocin on social behavior deficits in mice repeatedly exposed to social defeat stress","authors":"Ibi Daisuke, Takaba Rika, Yoshida Keisuke, Kawase Ririna, Kitagawa Hiroko, Matsushita Momoko, Ito Kana, Uno Shoya, Nishimura Fumiya, Kitagaki Shinji, Hiramatsu Masayuki","abstract":"ABSTRACT Psychedelics such as psilocybin and lysergic acid diethylamide (LSD) exert hallucinogenic effects through stimulation of serotonin 5-HT2A receptors (5-HT2ARs) in the cerebral cortex. In recent years, numerous reports have demonstrated that psychedelics are effective in treating various psychiatric disorders such as major depressive disorder (MDD), treatment-resistant depression (TRD), and anxiety-related disorders. We have previously reported that administration of psilocin, the active metabolite of psilocybin, produces antidepressant-like effects in mice. Furthermore, we found that this effect is mediated by 5-HT2AR activation. Since depression and other psychiatric disorders often lead to impairments in social behavior (e.g., social avoidance), the present study examined the effects of psilocin on social avoidance behavior in mice subjected to chronic social defeat stress (CSDS), a widely used model that closely models human psychosocial stress. Mice exposed to CSDS exhibited social avoidance behavior, whereas psilocin administration before the onset of CSDS had little effect on this behavior. In contrast, psilocin administration after the completion of CSDS ameliorated social avoidance in CSDS-exposed mice. This effect was blocked by pretreatment with a 5-HT2AR antagonist, indicating that psilocin exerts its therapeutic effects through 5-HT2AR activation. Taken together, psilocin exerts therapeutic effects on social avoidance behavior after stress through activation of 5-HT2AR, but not preventive effects when administered before stress, suggesting that psilocin may promote stress resilience rather than resistance.","journal":"Neuropsychopharmacology Reports","publication_date":"2026-08-31","publication_year":2026,"doi":"10.1002/npr2.70152","pubmed_id":null,"source_url":"https://doi.org/10.1002/npr2.70152","keywords":"","substance_tags":"psilocybin,psilocin","source_name":"Crossref","date_added":"2026-07-01 06:48:03","last_checked":"2026-07-02 06:54:51","raw_json":"{\"doi\":\"10.1002/npr2.70152\",\"reference_dois\":[\"10.1016/j.cell.2020.03.020\",\"10.1001/jamapsychiatry.2020.3285\",\"10.1007/s00210‐023‐02778‐x\",\"10.3390/pharmaceutics17040411\",\"10.3389/fphar.2024.1391689\",\"10.1542/peds.2008‐1215\",\"10.1186/s12888‐023‐04681‐4\",\"10.1073/pnas.2312662120\",\"10.1016/j.bpsgos.2021.12.009\",\"10.1016/j.biopsych.2016.06.012\",\"10.1016/j.neuroscience.2021.01.029\",\"10.1016/j.neures.2022.12.015\",\"10.1038/nprot.2011.361\",\"10.1016/s0031‐9384(01)00490‐5\",\"10.1111/ejn.15812\",\"10.1016/j.neuropharm.2018.01.016\",\"10.1021/acschemneuro.9b00493\",\"10.1016/j.neuron.2007.01.008\",\"10.1016/j.bbi.2012.12.017\"],\"reference_count\":19}","topic_tags":"Depression,Anxiety,Receptor Pharmacology,Resilience,Animal Study,Treatment-Resistant Depression","study_type":"Animal Study","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published"},{"id":1944,"title":"Ethical Complexities and Best Practices in Informed Consent Processes for Psilocybin Services: A Qualitative Study","normalized_title":"ethical complexities and best practices in informed consent processes for psilocybin services a qualitative study","authors":"Chwyl Christina, Bazinet Alissa, Wilson-Poe Adrianne R., Hoffman Kim, Pertl Kellie, Wolf R. Cameron, Korthuis P. Todd, Luoma Jason B.","abstract":"","journal":"Neuroethics","publication_date":"2026-07-31","publication_year":2026,"doi":"10.1007/s12152-026-09645-5","pubmed_id":null,"source_url":"https://doi.org/10.1007/s12152-026-09645-5","keywords":"","substance_tags":"psilocybin","source_name":"Crossref","date_added":"2026-07-01 06:52:05","last_checked":"2026-07-01 11:21:33","raw_json":"{\"doi\":\"10.1007/s12152-026-09645-5\",\"reference_dois\":[\"10.4103/2231-4040.116779\",\"10.2307/3564231\",\"10.1136/medethics-2020-106070\",\"10.1080/23294515.2025.2526339\",\"10.1556/2054.2023.00267\",\"10.1089/psymed.2024.0019\",\"10.1080/02791072.2025.2454474\",\"10.1046/j.1365-2702.2003.00757.x\",\"10.1111/j.1742-9544.2010.00019.x\",\"10.1016/s2215-0366(20)30146-2\",\"10.1080/15265161.2024.2433423\",\"10.1080/15265161.2024.2433428\",\"10.1080/15265161.2025.2509929\",\"10.1038/s41386-022-01389-z\",\"10.1007/s00213-011-2358-5\",\"10.1038/s41598-021-01209-2\",\"10.1093/nc/niad017\",\"10.3390/psychoactives3030026\",\"10.1007/s12152-024-09545-6\",\"10.1016/j.newideapsych.2022.100967\",\"10.1186/s13063-020-04969-w\",\"10.1002/cncr.27397\",\"10.1001/jamapsychiatry.2024.0124\",\"10.1177/02698811241257839\",\"10.29034/ijmra.v17n1a1\",\"10.1191/1478088706qp063oa\",\"10.1177/07067437231225937\",\"10.1001/jamapsychiatry.2024.0184\",\"10.1111/nup.12475\",\"10.1016/j.brat.2015.12.009\",\"10.21203/rs.3.rs-6874539/v1\",\"10.1016/j.neuropharm.2022.109165\",\"10.1080/15265161.2024.2433418\",\"10.1080/15265161.2024.2433425\",\"10.1080/15265161.2024.2433437\",\"10.1186/s40695-021-00066-3\"],\"reference_count\":53}","topic_tags":"General","study_type":"Qualitative Study","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published"},{"id":1922,"title":"Phase 1 trial suggests benefit of psilocybin in OCD treatment","normalized_title":"phase 1 trial suggests benefit of psilocybin in ocd treatment","authors":"","abstract":"A Phase 1 trial comprising 15 patients has found that repeated high-dose administration of psilocybin was more effective than low-dose psilocybin or placebo in reducing symptoms of obsessive-compulsive disorder (OCD). Psilocybin was generally well-tolerated, with no reports of serious adverse events.","journal":"The Brown University Psychopharmacology Update","publication_date":"2026-07-31","publication_year":2026,"doi":"10.1002/pu.31474","pubmed_id":null,"source_url":"https://doi.org/10.1002/pu.31474","keywords":"","substance_tags":"psilocybin","source_name":"Crossref","date_added":"2026-07-01 06:49:23","last_checked":"2026-07-02 06:54:51","raw_json":"{\"doi\":\"10.1002/pu.31474\",\"reference_dois\":[],\"reference_count\":0}","topic_tags":"OCD,Clinical Trial,Adverse Events","study_type":"Clinical Trial","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published"},{"id":3812,"title":"Past-Year Psilocybin and Alcohol Co-Use: Associations With Mental Health Symptoms","normalized_title":"past year psilocybin and alcohol co use associations with mental health symptoms","authors":"Hummel Haley M., Obrochta Alexia N., Kerr David C. R., Cservenka Anita","abstract":"Interest has grown in the effects of psilocybin on mental health, but little is known about its naturalistic use alongside alcohol and its relationship to depression and/or anxiety symptoms. Data from the nationally-representative 2024 National Survey Investigating Hallucinogenic Trends of participants who did ( n = 1234) or did not ( n = 1607) report past-year psilocybin and alcohol co-use were compared on depressive and anxiety symptoms and poor mental health days. Weighted regressions adjusted for age, sex, survey collection period, race, ethnicity, and past-year cannabis and other psychedelic use. Individuals with psilocybin and alcohol co-use had fewer depressive symptoms ( B (SE) = −.57(.28), β = −.04, p =.043) than those who used alcohol without psilocybin, suggesting potential benefits of psilocybin in individuals with co-use. After removing cannabis and other psychedelic use covariates, psilocybin use was also related to lower anxiety symptoms. However, given the observational and self-report study design, causal inferences cannot be made. Thus, longitudinal and experimental studies are needed.","journal":"Journal of Drug Issues","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1177/00220426261466154","pubmed_id":null,"source_url":"https://doi.org/10.1177/00220426261466154","keywords":"","substance_tags":"psilocybin","source_name":"Crossref","date_added":"2026-07-02 06:54:51","last_checked":"2026-07-02 06:54:51","raw_json":"{\"doi\":\"10.1177/00220426261466154\",\"reference_dois\":[\"10.52965/001c.127794\",\"10.2196/15830\",\"10.1001/jamahealthforum.2025.4011\",\"10.1007/s11469-023-01163-2\",\"10.1111/acer.14518\",\"10.1111/adb.13229\",\"10.15288/jsa.1993.54.326\",\"10.1037/1040-3590.6.2.117\",\"10.1080/09687637.2023.2236291\",\"10.20944/preprints202506.1536.v1\",\"10.1097/01.alc.0000081617.37539.d6\",\"10.3389/fpsyt.2019.00955\",\"10.1016/j.psychres.2020.112749\",\"10.1016/j.jad.2023.01.108\",\"10.15288/jsad.23-00312\",\"10.1016/j.dscb.2025.100286\",\"10.1080/02791072.2022.2044096\",\"10.15288/jsa.2001.62.190\",\"10.1001/jamapsychiatry.2025.3038\",\"10.1556/2054.2023.00243\",\"10.1007/s00213-011-2236-1\",\"10.1016/j.biopsych.2014.04.010\",\"10.1046/j.1525-1497.2001.016009606.x\",\"10.1016/j.drugpo.2024.104507\",\"10.1177/02698811241292956\",\"10.3390/molecules26102948\",\"10.1016/0306-4603(96)00042-1\",\"10.1136/bmj-2023-078084\",\"10.3389/fpsyt.2024.1429373\",\"10.3389/fpsyt.2023.1199642\",\"10.1038/s41429-020-0311-8\",\"10.1073/pnas.1524187113\",\"10.1111/add.13757\",\"10.1176/appi.ajp.2019.19010035\",\"10.7326/annals-24-03145\",\"10.3389/fpsyg.2021.729425\",\"10.1038/s44220-026-00630-8\",\"10.1001/archinte.166.10.1092\",\"10.1080/02791072.2022.2039815\",\"10.1038/nrn2884\",\"10.1146/annurev-psych-040422-045007\"],\"reference_count\":50}","topic_tags":"Depression,Anxiety,Observational Study","study_type":"Observational Study","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published"},{"id":3811,"title":"Investigating the impact of serotonergic psychedelic drugs, MDMA and ketamine on social cognition in psychiatric disorders: A scoping review.","normalized_title":"investigating the impact of serotonergic psychedelic drugs mdma and ketamine on social cognition in psychiatric disorders a scoping review","authors":"Smith SA, Mohammad H, Lee LHN, Dennett L, Smith S, Burback L, Winkler O, Greenshaw A, Jetly R, Kennedy SH, Bhat V, Swainson J, Vermetten E, Cao B, Li XM, Zhang Y","abstract":"Interest in psychedelic drugs has increased rapidly because of their potential therapeutic role in psychiatric disorders. Impairments in the sociocognitive skills needed to build and maintain social relationships are prominent features of many psychiatric and neurodevelopmental disorders. Emerging evidence suggests that compounds such as 3,4-methylenedioxymethamphetamine (MDMA), lysergic acid diethylamide (LSD), and psilocybin may influence these impairments. This review aimed to determine whether psychedelic drugs may modulate social cognition in individuals with psychiatric or neurodevelopmental disorders associated with cognitive impairment. A search of the MEDLINE, PsycINFO, EMBASE, and Scopus databases was conducted. Twenty studies were identified that evaluated the effects of ketamine, MDMA, psilocybin, LSD, and ayahuasca in depressive disorders, anxiety disorders, autism spectrum disorder (ASD), and post-traumatic stress disorder (PTSD). Findings included neural activation patterns suggesting that ketamine and psilocybin may modulate processes relevant to social perception, particularly facial emotion processing, in depressive disorders. Positive findings were also reported for MDMA in participants with PTSD, including improvements in self-reported psychosocial functioning, self-awareness, and self-compassion. Current evidence suggests that psychedelic drugs may modulate processes relevant to social cognition in psychiatric disorders, although direct evidence of improved social-cognitive functioning remains limited. Not applicable.","journal":"Psychopharmacology","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1007/s00213-026-07110-y","pubmed_id":"42380668","source_url":"https://pubmed.ncbi.nlm.nih.gov/42380668/","keywords":"Psychedelic drugs, Psychiatry, Scoping review, Social cognition","substance_tags":"psilocybin","source_name":"PubMed","date_added":"2026-07-01 13:00:05","last_checked":"2026-07-02 06:54:10","raw_json":"{\"pubmed_id\":\"42380668\"}","topic_tags":"Depression,Anxiety,PTSD,Emotional Processing,Review Article","study_type":"Review Article","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published"},{"id":3662,"title":"Efficacy in Relapse Prevention: Psilocybin in Alcohol Use Disorder With Depressive Symptoms","normalized_title":"efficacy in relapse prevention psilocybin in alcohol use disorder with depressive symptoms","authors":"Centre Hospitalier Universitaire de Nīmes","abstract":"Up to 40% of individuals with alcohol use disorder (AUD) experience depression, which increases the risk of early relapse. Depression can cause relapse to occur 3 times faster in individuals with AUD who experience depressive symptoms at discharge. No treatments have been approved for individuals with both AUD and depression. Psilocybin, a psychedelic, shows promising results in treating both depression and addiction. It may be particularly effective for preventing relapse in people with AUD who also have depressive symptoms after detoxification, offering quicker action than traditional antidepressants. The Psilocybin Alcohol Depression (PAD) pilot study, launched in February 2024, has provided critical insights for avoiding methodological flaws and demonstrated that psilocybin-assisted psychotherapy (PAP) is both feasible and acceptable. Preliminary efficacy analyses were conducted: at 12 weeks, the 25 mg group showed significantly greater reductions in drinking days (p = 0.038) and craving frequency (p = 0.045). Relapse rates were 35% in the 25 mg group and 50% in the control group (HR = 0.52 \\[0.16-1.65\\]). In the ERPPAD trial, the study authors will compare high-dose PAP with low-dose PAP in preventing relapse in individuals with AUD and depressive symptoms. The hypothesis is that high-dose PAP will be more effective than low-dose in preventing relapse over 6 months.","journal":"ClinicalTrials.gov","publication_date":"2026-06-30","publication_year":2026,"doi":null,"pubmed_id":null,"source_url":"https://clinicaltrials.gov/study/NCT07638553","keywords":"Alcohol Use Disorder, Depressive Sympotoms, Psilocybin, Psilocybin (high dose), Psilocybin (low dose), RECRUITING","substance_tags":"psilocybin","source_name":"ClinicalTrials.gov","date_added":"2026-07-01 11:04:28","last_checked":"2026-07-02 06:57:00","raw_json":"{\"nct_id\":\"NCT07638553\",\"overall_status\":\"RECRUITING\",\"phase\":[\"PHASE3\"]}","topic_tags":"Depression,Addiction,Safety","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"clinical trial"},{"id":3547,"title":"A Phase 2, Open-Label Study Investigating the Safety and Efficacy of Psilocybin-Assisted Therapy for Sexual Assault-Related Posttraumatic Stress Disorder (PTSD)","normalized_title":"a phase 2 open label study investigating the safety and efficacy of psilocybin assisted therapy for sexual assault related posttraumatic stress disorder ptsd","authors":"Sunstone Medical","abstract":"A Phase 2, Open-Label Study to explore the efficacy, safety, and tolerability of psilocybin-assisted therapy in women with sexual assault-related Posttraumatic Stress Disorder (PTSD).","journal":"ClinicalTrials.gov","publication_date":"2026-06-30","publication_year":2026,"doi":null,"pubmed_id":null,"source_url":"https://clinicaltrials.gov/study/NCT06902974","keywords":"Post Traumatic Stress Disorder, PTSD, Psilocybin 25 mg, Psilocybin-assisted therapy, RECRUITING","substance_tags":"psilocybin","source_name":"ClinicalTrials.gov","date_added":"2026-07-01 11:04:28","last_checked":"2026-07-02 06:57:00","raw_json":"{\"nct_id\":\"NCT06902974\",\"overall_status\":\"RECRUITING\",\"phase\":[\"PHASE2\"]}","topic_tags":"PTSD,Clinical Trial,Safety","study_type":"Clinical Trial","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"clinical trial"},{"id":3002,"title":"Modeled Long-Term Effects of Psilocybin on Dynamic Activity and Effective Connectivity of Fronto-Striatal-Thalamic Circuits","normalized_title":"modeled long term effects of psilocybin on dynamic activity and effective connectivity of fronto striatal thalamic circuits","authors":"Pasquini Lorenzo, Vohryzek Jakub, Escrichs Anira, Perl Yonatan Sanz, Ponce-Alvarez Adrian, Idesis Sebastian, Girn Manesh, Roseman Leor, Mitchell Jennifer M., Gazzaley Adam, Kringelbach Morten, Nutt David J., Lyons Taylor, Carhart-Harris Robin L., Deco Gustavo","abstract":"ABSTRACT Psilocybin has been shown to induce fast and sustained symptoms improvements across various psychiatric conditions, yet its long-term mechanisms of action are not fully understood. Initial evidence suggests that longitudinal functional and structural brain changes implicate fronto-striatal-thalamic (FST) circuitry, a broad system involved in goal-directed behavior and motivational states. Here, we performed secondary analyses and applied computational modeling to resting-state fMRI data from a within-subject longitudinal psilocybin trial in psychedelic-naïve healthy volunteers. We first showed that dynamic FST activity increased 4 weeks after a full dose of psilocybin. We then proceeded to mechanistically account for these changes by providing tentative model-based support that reductions in the structure-function coupling contribute to increased dynamic FST activity postpsilocybin. Finally, we used computational approaches to show that psilocybin induces longitudinal increases in bottom-up and reduced top-down modulation of FST circuits. We then used publicly available receptor maps to show that cortical reductions in top-down modulation are linked to regional 5-HT2A receptor availability, while increased information outflow via subcortical and limbic regions relates to local D2 receptor availability. Together, these findings suggest that increased FST flexibility weeks after a high dose of psilocybin is linked to serotonergic-mediated decreases in top-down information flow and dopaminergic-mediated increases in bottom-up information flow. This long-term functional re-organization of FST circuits may represent a common mechanism contributing to the potential clinical efficacy of psilocybin across various neuropsychiatric disorders including substance abuse, major depression, and anorexia nervosa.","journal":"Human Brain Mapping","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1002/hbm.70596","pubmed_id":null,"source_url":"https://doi.org/10.1002/hbm.70596","keywords":"","substance_tags":"psilocybin","source_name":"Crossref","date_added":"2026-07-01 11:03:06","last_checked":"2026-07-02 06:54:51","raw_json":"{\"doi\":\"10.1002/hbm.70596\",\"reference_dois\":[\"10.1146/annurev.neuro.9.1.357\",\"10.1016/j.bpsc.2022.04.003\",\"10.1016/j.jneumeth.2013.10.018\",\"10.1523/jneurosci.2830‐16.2016\",\"10.1001/jamapsychiatry.2022.2096\",\"10.1016/j.neuroimage.2017.03.045\",\"10.1016/j.celrep.2018.05.022.psychedelics\",\"10.1056/nejmoa2032994\",\"10.1016/s2215‐0366(16)30065‐7\",\"10.1073/pnas.1119598109\",\"10.1124/pr.118.017160\",\"10.1111/adb.12013\",\"10.1001/jamapsychiatry.2020.3285\",\"10.1038/s41591‐022‐01744‐z\",\"10.1016/j.celrep.2021.109836\",\"10.1016/j.cub.2018.07.083\",\"10.1073/pnas.1905534116\",\"10.1103/physreve.108.064410\",\"10.1038/s42003-022-03505-7\",\"10.1038/s41562-020-01003-6\",\"10.1016/j.nicl.2017.08.006\",\"10.1093/brain/awab406\",\"10.1038/s41398‐021‐01706‐y\",\"10.1073/pnas.2002509117\",\"10.1093/cercor/bhac064\",\"10.1101/306951\",\"10.1101/2025.04.22.650037\",\"10.1056/nejmoa2206443\",\"10.1016/j.neuroimage.2022.119671\",\"10.1016/j.nicl.2022.103233\",\"10.3109/00952990.2016.1170135\",\"10.1016/j.conb.2010.01.007\",\"10.1073/pnas.1921475117\",\"10.1016/j.celrep.2020.108128\",\"10.1126/sciadv.ade6049\",\"10.1038/s42003‐021‐02537‐9\",\"10.1038/s42003‐022‐03330‐y\",\"10.1038/s41467‐026‐71962‐3\",\"10.1016/j.euroneuro.2021.06.001\",\"10.1177/02698811211026454\",\"10.1038/s41586‐023‐06204‐3\",\"10.1124/pr.115.011478\",\"10.1073/pnas.1809298115\",\"10.1080/02791072.2017.1312643\",\"10.1177/0269881120909409\",\"10.1073/pnas.1815129116\",\"10.1371/journal.pcbi.1009139\",\"10.1016/j.neuron.2012.03.037\",\"10.1038/s41586‐024‐07624‐5\",\"10.1038/s41467‐019‐08934‐3\",\"10.1016/j.biopsych.2022.07.013\",\"10.1186/1477‐7525‐5‐63\",\"10.1006/nimg.2001.0978\",\"10.1126/science.adf0435\",\"10.1038/s41583‐020‐0367‐2\",\"10.1016/s0893‐133x(98)00108‐0\"],\"reference_count\":56}","topic_tags":"Depression,Eating Disorders,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Healthy Volunteers","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published"},{"id":1939,"title":"Psilocybin shows mixed results for patients with treatment-resistant depression","normalized_title":"psilocybin shows mixed results for patients with treatment resistant depression","authors":"","abstract":"Patients with treatment-resistant depression who received psilocybin-assisted psychotherapy showed clinically meaningful improvement in depressive symptoms relative to placebo, a Phase 2b trial has found. However, the study did not show a significant effect on the primary outcome of treatment response 6 weeks after the first of two doses of psilocybin. Study results were published online March 18, 2026 in JAMA Psychiatry.","journal":"The Brown University Psychopharmacology Update","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1002/pu.31461","pubmed_id":null,"source_url":"https://doi.org/10.1002/pu.31461","keywords":"","substance_tags":"psilocybin","source_name":"Crossref","date_added":"2026-07-01 06:49:23","last_checked":"2026-07-01 11:21:33","raw_json":"{\"doi\":\"10.1002/pu.31461\",\"reference_dois\":[],\"reference_count\":0}","topic_tags":"Depression,Clinical Trial,Treatment-Resistant Depression","study_type":"Clinical Trial","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published"},{"id":1938,"title":"Single-dose psilocybin with CBT more effective than nicotine patch for smoking cessation","normalized_title":"single dose psilocybin with cbt more effective than nicotine patch for smoking cessation","authors":"","abstract":"","journal":"The Brown University Psychopharmacology Update","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1002/pu.31467","pubmed_id":null,"source_url":"https://doi.org/10.1002/pu.31467","keywords":"","substance_tags":"psilocybin","source_name":"Crossref","date_added":"2026-07-01 06:49:23","last_checked":"2026-07-01 11:21:33","raw_json":"{\"doi\":\"10.1002/pu.31467\",\"reference_dois\":[],\"reference_count\":0}","topic_tags":"Addiction","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published"},{"id":1920,"title":"Revealing shortcomings in the assessment of psilocybin effects on OCD-related symptoms in preclinical and clinical studies: A systematic review","normalized_title":"revealing shortcomings in the assessment of psilocybin effects on ocd related symptoms in preclinical and clinical studies a systematic review","authors":"Jalalian-Javadpour Marzieh, Yekta Batool Ghorbani, Reyhani Niloufar, Hajizamani Shadi, Azizi Ali, Azad Najma Khoshrooz, Mohammadi Hamidreza, Vaseghi Salar","abstract":"","journal":"Journal of Affective Disorders Reports","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1016/j.jadr.2026.101098","pubmed_id":null,"source_url":"https://doi.org/10.1016/j.jadr.2026.101098","keywords":"","substance_tags":"psilocybin","source_name":"Crossref","date_added":"2026-07-01 06:49:23","last_checked":"2026-07-02 06:54:51","raw_json":"{\"doi\":\"10.1016/j.jadr.2026.101098\",\"reference_dois\":[\"10.1007/s00213-024-06566-0\",\"10.1080/15622975.2016.1190867\",\"10.1038/s41598-020-59282-y\",\"10.1177/0269881114565144\",\"10.1038/s41380-024-02786-0\",\"10.1007/s00213-022-06286-3\",\"10.1016/s2215-0366(16)30065-7\",\"10.1097/j.pbj.0000000000000128\",\"10.3389/fpsyt.2025.1726818\",\"10.1093/ijnp/pyae057\",\"10.1001/jamapsychiatry.2020.3285\",\"10.1176/appi.ajp.2013.13040574\",\"10.1016/j.pnpbp.2005.11.005\",\"10.1016/j.neuropharm.2025.110648\",\"10.1016/j.neuropharm.2024.110202\",\"10.1037/bne0000579\",\"10.1001/archgenpsychiatry.2010.116\",\"10.3389/fpsyt.2023.1221131\",\"10.1073/pnas.2022489118\",\"10.3389/fphar.2021.640241\",\"10.1097/fbp.0000000000000757\",\"10.1192/bjo.2023.535\",\"10.1002/(sici)1096-9861(20000214)417:3<337::aid-cne7>3.0.co;2-o\",\"10.1097/fbp.0000000000000813\",\"10.1177/0269881120959614\",\"10.2139/ssrn.6218466\",\"10.1007/s00210-023-02843-5\",\"10.1016/j.heliyon.2022.e12135\",\"10.1038/s41380-023-02280-z\",\"10.1007/s00213-024-06644-3\",\"10.1371/journal.pone.0063972\",\"10.1586/14737175.9.2.255\",\"10.1192/bjo.2025.10895\",\"10.3389/fphar.2024.1391412\",\"10.1080/02791072.2020.1849879\",\"10.1016/j.celrep.2018.05.022\",\"10.3389/fpsyt.2022.1040217\",\"10.1177/02698811241269751\",\"10.1038/s41386-019-0324-9\",\"10.1177/02698811231205692\",\"10.1271/bbb.90095\",\"10.3114/fuse.2024.14.14\",\"10.1177/0269881119895520\",\"10.1177/02698811261424214\",\"10.4088/jcp.v67n1110\",\"10.1007/s00210-025-03912-7\",\"10.1016/j.pharmthera.2003.11.002\",\"10.1016/j.bbr.2020.113093\",\"10.1038/nrn3746\",\"10.1136/pgmj.57.671.543\",\"10.1016/j.comppsych.2025.152619\",\"10.1038/s41380-019-0431-3\",\"10.3389/fnbeh.2014.00180\",\"10.3390/ijms22020835\",\"10.1017/s1461145701002401\",\"10.1038/s41386-024-01794-6\",\"10.32598/bcn.2021.1920.2\",\"10.1016/j.neuron.2021.06.008\",\"10.1016/j.biopsych.2011.06.023\",\"10.1038/s41398-023-02456-9\",\"10.1038/s41572-019-0102-3\",\"10.1503/jpn.150012\",\"10.1007/s00228-024-03680-y\",\"10.1016/j.euroneuro.2013.12.006\",\"10.1016/j.jpsychires.2025.11.021\",\"10.1016/j.pnpbp.2024.111243\",\"10.1080/02791072.2014.963754\",\"10.1002/(sici)1098-2396(199709)27:1<79::aid-syn8>3.0.co;2-a\",\"10.1136/gpsych-2023-101208\",\"10.1177/02698811241249436\"],\"reference_count\":78}","topic_tags":"OCD,Systematic Review,Review Article,Animal Study","study_type":"Systematic Review","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published"},{"id":171,"title":"Blinding Integrity in Psychedelic Randomized Clinical Trials: A Systematic Review.","normalized_title":"blinding integrity in psychedelic randomized clinical trials a systematic review","authors":"Orsini DK, Wong S, Di Luch S, Chan B, Vasudeva S, Lovell GFM, Le GH, Jones BDM, Chisamore N, Mollica A, Johnson DE, Kaczmarek ES, Goel A, Burke MJ, Mansur R, McIntyre RS, Husain MI, Rosenblat JD","abstract":"Psychedelic drugs possess acute psychoactive effects that can compromise blinding integrity in randomized clinical trials (RCTs). Functional unblinding, when participants or raters correctly identify treatment allocation based on subjective effects, may bias outcomes through expectancy effects, challenging the validity of efficacy estimates and regulatory acceptance. To systematically quantify the prevalence of blinding integrity assessment and the extent of functional unblinding in psychedelic RCTs for psychiatric disorders. A systematic review was conducted in accordance with PRISMA guidelines across OVID, MEDLINE, Embase, and APA PsycINFO (January 1, 2020, to December 11, 2025), supplemented by manual searches of 3 prior reviews for studies prior to January 2020. Eligible studies included all RCTs investigating psychedelics as psychiatric interventions. Data extracted included blinding integrity assessment methods and results for participants and raters. Of 112 RCTs (11 psilocybin, 17 lysergic acid diethylamide [LSD], 78 ketamine, 11 3,4-methylenedioxymethamphetamine [MDMA], 2 ayahuasca, 2 N,N-dimethyltryptamine [DMT], and 1 noribogaine), only 29.5% (n = 33) evaluated blinding integrity, yet 57.1% (n = 64) cited blinding as a limitation. Functional unblinding was substantial: psilocybin, LSD, and ayahuasca studies frequently reported blinding failure values of more than 90% among participants and raters, inert placebo-controlled MDMA trials exceeded 85%, and ketamine trials rarely assessed blinding (17.9%) but showed improved preservation with midazolam vs saline controls. No control strategy consistently achieved ideal blinding. This first evaluation of blinding integrity in psychedelic RCTs indicates functional unblinding is pervasive among participants and raters raising concerns about the validity of efficacy findings. Few trials assess blinding or expectancy, highlighting the need for standardized, validated measures and innovative designs to separate true pharmacological effects from expectancy-driven responses.","journal":"JAMA psychiatry","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1001/jamapsychiatry.2026.0255","pubmed_id":"41984443","source_url":"https://pubmed.ncbi.nlm.nih.gov/41984443/","keywords":"","substance_tags":"psilocybin","source_name":"PubMed","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-02 06:54:10","raw_json":"{\"pubmed_id\":\"41984443\"}","topic_tags":"Clinical Trial,Randomized Controlled Trial,Systematic Review,Review Article","study_type":"Randomized Controlled Trial","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published"},{"id":107,"title":"Implementing psilocybin-assisted therapy in palliative care settings: A survey of stakeholders.","normalized_title":"implementing psilocybin assisted therapy in palliative care settings a survey of stakeholders","authors":"Plourde L, Chang SL, Nguyen O, Garel N, Farzin H, Stephan JF, Fallu JS, Dorval M, P3A Research Group","abstract":"While the adoption of psilocybin-assisted therapy for existential distress offers promising support for patients with life-threatening illnesses, implementing this intervention into palliative care settings presents significant real-world challenges. To examine palliative care stakeholders' knowledge and attitudes regarding psilocybin-assisted therapy, and identify barriers and facilitators to its implementation. We conducted a cross-sectional online survey between April 15 and December 18, 2024. The survey assessed perceived knowledge, attitudes, and perceived barriers and facilitators to the effective integration of psilocybin-assisted therapy into palliative care settings. One hundred and twenty-one adults involved in palliative care (physicians, other healthcare professionals, caregivers, and managers) were recruited from Canada's four most populous provinces: Québec, Ontario, Alberta, and British Columbia. Forty-three percent of stakeholders reported having good knowledge of psilocybin's potential benefits and risks. Attitudes towards psilocybin-assisted therapy were predominantly non-favourable (61%), yet varied across occupational groups ( Translating the potential of psilocybin-assisted therapy for existential distress from clinical trials into palliative care settings requires careful consideration and collaboration with stakeholders. Given the significant divergence in perspectives between clinical and non-clinical groups, tailored interprofessional education could help build shared understanding and support effective implementation. Being conducted in Canada, transferability to different regulatory frameworks may be limited.","journal":"Palliative medicine","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1177/02692163261446141","pubmed_id":"42154482","source_url":"https://pubmed.ncbi.nlm.nih.gov/42154482/","keywords":"attitude of health personnel, hallucinogens, palliative care, psilocybin, surveys and questionnaires","substance_tags":"psilocybin","source_name":"PubMed","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-02 06:54:10","raw_json":"{\"pubmed_id\":\"42154482\"}","topic_tags":"End-of-Life Distress,Clinical Trial,Observational Study,Safety","study_type":"Clinical Trial","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published"},{"id":58,"title":"MFCC-DFT mapping of ligand recognition at the 5-HT receptor: energetic analysis of the interactions between serotonin, psychedelics, and antipsychotics.","normalized_title":"mfcc dft mapping of ligand recognition at the 5 ht receptor energetic analysis of the interactions between serotonin psychedelics and antipsychotics","authors":"Junior WSC, Bezerra KS, Matias EGC, Oliveira JIN, Fulco UL","abstract":"Mental disorders represent a major global health problem, with depression being one of the most prevalent and disabling conditions worldwide. Growing evidence suggests that the serotonergic system, particularly the 5-HT receptor, plays an important role in modulating mood and cognitive processes, constituting a key pharmacological target for several psychoactive compounds. In this study, we investigated the molecular interaction profile between the 5-HT receptor and four pharmacologically relevant ligands, serotonin (5-HT), psilocybin/psilocin (PSILO), lysergic acid diethylamide (LSD), and lumateperone (LMTP). Interaction energies were evaluated using the molecular fragmentation with conjugated caps (MFCC) method combined with density functional theory (DFT) calculations. Crystallographic structures were used as initial models, and residue-level interaction energies were calculated to identify the amino acids that contribute most to ligand stabilization at the receptor binding site. The results reveal that the complexes exhibit total interaction energies ranging from -35.38 to -71.98 kcal mol under dielectric conditions representative of the protein environment. Key residues such as Asp155, Phe339, Leu229, and Val366 were identified as the main contributors to ligand stabilization in the studied systems, highlighting their role as structural anchors within the orthosteric binding pocket. Energy decomposition further revealed distinct interaction patterns associated with different regions of the ligand. Therefore, this study provides a detailed energetic characterization of ligand recognition in the 5-HT receptor and offers details that may contribute to the rational design of new serotonergic agents with potential for therapeutic applications.","journal":"Physical chemistry chemical physics: PCCP","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1039/d6cp00943c","pubmed_id":"42300394","source_url":"https://pubmed.ncbi.nlm.nih.gov/42300394/","keywords":"","substance_tags":"psilocybin,psilocin","source_name":"PubMed","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-02 06:54:10","raw_json":"{\"pubmed_id\":\"42300394\"}","topic_tags":"Depression,Receptor Pharmacology,Drug Interactions","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published"},{"id":21,"title":"Chemistry/structural biology of psychedelic drugs and their receptor(s).","normalized_title":"chemistry structural biology of psychedelic drugs and their receptor s","authors":"Gumpper RH, Nichols DE","abstract":"This brief review highlights some of the structure-activity relationships of classic serotonergic psychedelics. In particular, we discuss structural features of three chemotypes: phenethylamines, ergolines and certain tryptamines, which possess psychedelic activity in humans. Where they are known, we point out the underlying molecular mechanisms utilized by each of the three chemotypes of psychedelic molecules. With a focus on the 5-HT receptor subtype, a G-protein coupled receptor known to be the primary target of psychedelics, we refer to several X-ray and cryoEM structures, with a variety of ligands bound, to illustrate the underlying atomistic basis for some of the known pharmacological observations of psychedelic drug actions. LINKED ARTICLES: This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.","journal":"British journal of pharmacology","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1111/bph.17361","pubmed_id":"39354889","source_url":"https://pubmed.ncbi.nlm.nih.gov/39354889/","keywords":"5-HT2A agonists, 5-HT2A receptor, LSD, Psychedelic chemotypes, crystal structures, docking, ergolines, phenethylamines, psilocybin, structural biology, structure-activity relationships, therapeutic potential, tryptamines","substance_tags":"psilocybin","source_name":"PubMed","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-02 06:54:10","raw_json":"{\"pubmed_id\":\"39354889\"}","topic_tags":"Mechanism of Action,Receptor Pharmacology,Review Article","study_type":"Review Article","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published"},{"id":20,"title":"Psilocybin as a novel treatment for chronic pain.","normalized_title":"psilocybin as a novel treatment for chronic pain","authors":"Askey T, Lasrado R, Maiarú M, Stephens GJ","abstract":"Psychedelic drugs are under active consideration for clinical use and have generated significant interest for their potential as anti-nociceptive treatments for chronic pain, and for addressing conditions like depression, frequently co-morbid with pain. This review primarily explores the utility of preclinical animal models in investigating the potential of psilocybin as an anti-nociceptive agent. Initial studies involving psilocybin in animal models of neuropathic and inflammatory pain are summarised, alongside areas where further research is needed. The potential mechanisms of action, including targeting serotonergic pathways through the activation of 5-HT receptors at both spinal and central levels, as well as neuroplastic actions that improve functional connectivity in brain regions involved in chronic pain, are considered. Current clinical aspects and the translational potential of psilocybin from animal models to chronic pain patients are reviewed. Also discussed is psilocybin's profile as an ideal anti-nociceptive agent, with a wide range of effects against chronic pain and its associated inflammatory or emotional components. LINKED ARTICLES: This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.","journal":"British journal of pharmacology","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1111/bph.17420","pubmed_id":"39614355","source_url":"https://pubmed.ncbi.nlm.nih.gov/39614355/","keywords":"neuropathic pain, neuroplasticity, nociplastic pain, psilocybin, psychedelic drugs, serotonergic signalling","substance_tags":"psilocybin","source_name":"PubMed","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-02 06:54:10","raw_json":"{\"pubmed_id\":\"39614355\"}","topic_tags":"Depression,Chronic Pain,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Emotional Processing,Review Article,Animal Study,Inflammation","study_type":"Review Article","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published"},{"id":19,"title":"The Australia story: Current status and future challenges for the clinical applications of psychedelics.","normalized_title":"the australia story current status and future challenges for the clinical applications of psychedelics","authors":"Nutt DJ, Hunt P, Schlag AK, Fitzgerald P","abstract":"The past decade has seen a huge increase in clinical research with psychedelic drugs and 3,4-methylenedioxymethamphetamine (MDMA), which have revealed great potential for treating mental health conditions. Given this progress in research, as well as the current unmet clinical need of millions of patients, in 2023, the Australian Therapeutic Goods Administration (TGA) approved the use of psilocybin for treatment-resistant depression and MDMA for PTSD to take effect from 1 July 2023. The campaign for TGA approval was led by a coalition comprising the Australian charity Mind Medicine Australia with support from Professor David Nutt, Drug Science, Professor Arthur Christopolous, Professor Chris Langmead (both from Monash University) and from large numbers of clinical, academic and patient groups. Under the rescheduling, current prescribing rights are limited to psychiatrists who have become authorised prescribers under the TGA's Authorised Prescriber Scheme, and psilocybin can only be used for treatment resistant depression and MDMA can only be used for PTSD. This paper reviews the background for this decision, its implications for approvals in other jurisdictions, as well as for the development pathways for other psychedelic drugs. LINKED ARTICLES: This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.","journal":"British journal of pharmacology","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1111/bph.17398","pubmed_id":"39701143","source_url":"https://pubmed.ncbi.nlm.nih.gov/39701143/","keywords":"3,4-methylenedioxymethamphetamine (MDMA), Australia, psilocybin, psychedelics, therapeutic goods administration (TGA)","substance_tags":"psilocybin","source_name":"PubMed","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-02 06:54:10","raw_json":"{\"pubmed_id\":\"39701143\"}","topic_tags":"Depression,PTSD,Mechanism of Action,Review Article,Treatment-Resistant Depression","study_type":"Review Article","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published"},{"id":18,"title":"Neuropsychopharmacology of hallucinogenic and non-hallucinogenic 5-HT receptor agonists.","normalized_title":"neuropsychopharmacology of hallucinogenic and non hallucinogenic 5 ht receptor agonists","authors":"Sharp T, Ippolito A","abstract":"Psychedelic drugs such as LSD and psilocin were once relegated to the fringes of medical research because of their association with counterculture movements and a perceived concern about harm through recreational use, and their consequent legal prohibition in the early 1970s. However, these drugs are now experiencing a renaissance in the field of psychiatry based on increasing evidence that they can produce long-lasting improvements in health across a wide variety of mental illnesses, including major depression, addictions and anxiety disorders. These drugs interact with many different 5-HT receptor subtypes but the powerful psychedelic experience, which (depending on set and setting) includes profound alterations in perception, mood and cognition, accompanied by vivid hallucinations, is now widely considered mediated by an agonist action at 5-HT receptors. However, the link between the psychedelic experience, 5-HT receptor agonism and therapeutic effects is currently uncertain. Indeed, recent research has revealed a new class of 5-HT receptor agonists which appear to retain the therapeutic potential of psychedelics drugs without inducing disorienting hallucinatory experiences. Biased signalling, partial agonism and non-selectivity at the 5-HT receptor are amongst the possible explanations for the differential properties of these drugs, whereas increased neuroplasticity offers a likely account of their common therapeutic effects. This article explores the neuropsychopharmacological properties of hallucinogenic and non-hallucinogenic 5-HT receptor agonists in the context of their promise as novel drug treatments in psychiatry. LINKED ARTICLES: This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.","journal":"British journal of pharmacology","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1111/bph.70050","pubmed_id":"40405723","source_url":"https://pubmed.ncbi.nlm.nih.gov/40405723/","keywords":"5-HT, 5-HT2A receptor, antidepressant, hallucinogens, psychedelics, serotonin","substance_tags":"psilocin","source_name":"PubMed","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-02 06:54:10","raw_json":"{\"pubmed_id\":\"40405723\"}","topic_tags":"Depression,Anxiety,Addiction,Neuroplasticity,Pharmacology,Receptor Pharmacology","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published"},{"id":17,"title":"Psychedelics, entactogens and psychoplastogens for depression and related disorders.","normalized_title":"psychedelics entactogens and psychoplastogens for depression and related disorders","authors":"Hoyer D","abstract":"Currently, the most actively investigated rapidly acting antidepressants, anxiolytics and/or anti PTSD agents, include psychedelics e.g. psilocybin, LSD, N,N-dimethyltryptamine, ayahuasca; non-hallucinogenic entactogens, e.g. MDMA; psychoplastogens which rapidly promote neuroplasticity, e.g. ibogaine, ketamine and esketamine; and other atypicals e.g. dextromorphan/bupropion, esmethadone. Late-stage clinical trials support psychedelics and/or MDMA-assisted psychotherapy as rapidly acting treatments for major depressive disorder (MDD), treatment-resistant depression (TRD), PTSD or generalised anxiety disorders (GAD). Psilocybin, MDMA and LSD were granted FDA breakthrough status for TRD/MDD, PTSD and GAD, respectively, although FDA recently rejected the new drug application of MDMA in PTSD. Most of these drugs target the 5-HT and monoamine systems. Classical psychedelics act as 5-HT receptor agonists, although LSD, DMT and psilocybin target other 5-HT and/or dopamine receptors. Psychedelic-dependent 5-HT receptor agonism also has profound anti-(neuro)inflammatory effects. Advanced imaging studies suggest that brain 5-HT levels are reduced in depression. Functional magnetic resonance studies show that neural networks (cortico thalamic, salience, default mode) are profoundly impaired in depression. Such network defects are corrected upon psychedelic/entactogen treatment, offering a unique opportunity to serve as biomarkers for depression, anxiety and PTSD precision medicine trials. Psychedelics and entactogens target common end pathways, namely neuroplasticity/synaptogenesis, either directly via monoamine or glutamate receptors and/or indirectly, via BDNF and mTORC1 pathways. Together, these findings strongly support a biological basis for MDD, GAD, PTSD and related conditions, which can be considered as mixed biochemical, neurological and neuroimmune disorders, and are profoundly modified by psychedelics, entactogens and the newly developed psychoplastogens. LINKED ARTICLES: This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.","journal":"British journal of pharmacology","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1111/bph.70088","pubmed_id":"40518133","source_url":"https://pubmed.ncbi.nlm.nih.gov/40518133/","keywords":"5-HT (serotonin), Brain-derived neurotrophic factor (BDNF), Empathogens, Entactogens, LSD (lysergic acid diethylamide), MDMA (3,4-methylenedioxy methamphetamine), Post-traumatic stress disorders (PTSD), Psychedelics, Psychoplastogens, Treatment resistant depression (TRD)","substance_tags":"psilocybin","source_name":"PubMed","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-02 06:54:10","raw_json":"{\"pubmed_id\":\"40518133\"}","topic_tags":"Depression,Anxiety,PTSD,Neuroplasticity,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Biomarkers,Aging,Clinical Trial,Treatment-Resistant Depression,Inflammation,Immune Function","study_type":"Clinical Trial","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published"},{"id":16,"title":"Evidence that 5-HT receptor signalling efficacy and not biased agonism differentiates serotonergic psychedelic from non-psychedelic drugs.","normalized_title":"evidence that 5 ht receptor signalling efficacy and not biased agonism differentiates serotonergic psychedelic from non psychedelic drugs","authors":"Ippolito A, Vasudevan S, Hurley S, Gilmour G, Westhorpe F, Churchill G, Sharp T","abstract":"Serotonergic psychedelic drugs are under investigation as therapies for various psychiatric disorders, including major depression. Although serotonergic psychedelic drugs are 5-HT receptor agonists, some such agonists are not psychedelic, potentially due to differences in 5-HT receptor ligand bias or signalling efficacy. Here, we investigated 5-HT receptor signalling properties of selected psychedelic and non-psychedelic drugs. G-coupled (Ca and IP) and β-arrestin2 signalling effects of six psychedelic drugs (psilocin, 5-MeO-DMT, LSD, mescaline, 25B-NBOMe and DOI) and three non-psychedelic drugs (lisuride, TBG and IHCH-7079) were characterised using SH-SY5Y cells expressing human 5-HT receptors. Ligand bias and signalling efficacy were measured using concentration-responses curves, compared with 5-HT. The generality of findings was tested using rat C6 cells which express endogenous 5-HT receptors. In SH-SY5Y cells, all psychedelic drugs were partial agonists at both 5-HT receptor signalling pathways and none showed significant ligand bias. In comparison, the non-psychedelic drugs were not distinguishable from psychedelic drugs in terms of ligand bias properties but exhibited the lowest 5-HT receptor signalling efficacy of all drugs tested. The latter result was confirmed in C6 cells. In summary, all psychedelic drugs tested were unbiased, partial 5-HT receptor agonists. Importantly, the non-psychedelic drugs lisuride, TBG and IHCH-7079 were discriminated from psychedelic drugs, not through ligand bias but rather by low efficacy. Therefore, low 5-HT receptor signalling efficacy may explain why some 5-HT receptor agonists are not psychedelic, although a larger panel of drugs should be tested to confirm this idea. This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.","journal":"British journal of pharmacology","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1111/bph.70109","pubmed_id":"40545270","source_url":"https://pubmed.ncbi.nlm.nih.gov/40545270/","keywords":"5-HT, 5-HT2A receptor, Gq and β-arrestin2 signalling, biased agonism, psychedelic, serotonin","substance_tags":"psilocin","source_name":"PubMed","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-02 06:54:10","raw_json":"{\"pubmed_id\":\"40545270\"}","topic_tags":"Depression,Mechanism of Action,Receptor Pharmacology,Animal Study","study_type":"Animal Study","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published"}],"total":2751,"page":1,"per_page":20,"pages":138}