[{"id":847,"title":"OCD, TRPA1s, AND THE VAGAL FEAR PATHWAY.","sha":"74ec27b32cf62e4025f328208bac3597","user_id":null,"state":"published","body":"As mentioned in articles in NPBR.1. and JBI.2., the crucial stage in MAOI and St John' s Wort OCD cures I have repeatedly found to be strong TRPA1 receptor activation by radicals, resulting in gut serotonin and CCK release. Matsuo et al.3. have pointed out that the TRPA1 vagal/trigeminal innate fear pathway, demonstrated in animals, is conserved in humans, including the vagal solitary tract nucleus path to the midbrain parabrachial nucleus. Vagal activation of this fear pathway leads to hypometabolism in brain areas due to suppression of pyruvate dehydrogenase activity by phosphorylation.\r\nOCD cure, as detailed earlier, appears to relate to disruption of vagal afferent feedback, and resulting reversal of brain hypometabolism in crucial areas could provide increased \"neural noise\", bringing back the ability to \"drown\" persistent thoughts and to \"mind wander\" i.e activation of the default mode network. This hypothesis is testable, given current research into new TRPA1 agonists.\r\n.1. Neurology,Psychiatry and Brain Research 5(4):181, 8(4):185, 10(4):149.\r\n.2. Journal of Brief Ideas. \"Oxidative stress, MAOIs and OCD\". \"OCD, St John's Wort and iron\".\"OCD, radicals and TRPA1 receptors.\"\r\n.3. Matsuo et al. Nature Communications. 2021 12(1):2074. / (bioRxiv posted May 19, 2020).    ","created_at":"2021-04-20T05:16:01.376Z","updated_at":"2021-05-21T06:01:19.734Z","zenodo_id":4775135,"doi":"https://doi.org/10.5281/zenodo.4775135","subject":null,"tags":["ocd","trpa1","vagal fear pathway."],"vote_count":0,"view_count":1,"score":0.1,"deleted":false,"muted":false,"tweeted":false,"attachment_file_name":null,"attachment_content_type":null,"attachment_file_size":null,"attachment_updated_at":null},{"id":612,"title":"\"OCD, radicals and TRPA1 receptors\".","sha":"d4dfa1a905c32f84b3c55fdc97b78fab","user_id":null,"state":"published","body":"Further to NPBR .1. and Journal of Brief Ideas papers on \"Oxidative stress, MAOIs and OCD\" and \"OCD, St John's Wort and Iron\", this paper concerns TRPA1 human gut receptors which respond to oxidative stress. The 1,2,3- and 1,2,4- benzenetriols are responsible for much of the gut release from coffee of radicals which act at TRPA1 receptors, resulting in serotonin release. However, a number of natural products are strong agonists at TRPA1 receptors notably cinnamaldehyde. On St John's Wort,(5 x 333mg whole herb equivalent per day),as on MAOIs, adding cinnamaldehyde produces the same post-serotonin release patterns (e.g alternating auricle high blood flow) observed when taking new batches of serotonin releasing coffees (the 1,2,4 benzenetriol is quickly oxidized in air to an inactive, insoluble form). Small true cinnamon bark quills have been found to work best,(cinnamaldehyde is quickly oxidized to TRPA1-inactive cinnamic acid in the human stomach), and daily cinnamaldehyde addition this way to St John's Wort has improved the OCD cure. The cinnamaldehyde TRPA1 agonist effect adds to the peripheral serotonin release which alters vagal systems, likely resulting in a resetting of the brain's default mode system, which is influenced by vagal stimulation via, significantly, the auricle .2., in treatment for depression, for example.\r\n\r\n1. Neurology,Psychiatry and Brain Research 5(4):181, 8(4):185, 10(4):149.\r\n2. Biological Psychiatry (2016) Vol. 79(4):266-273.","created_at":"2019-07-21T15:35:34.280Z","updated_at":"2019-11-14T00:46:22.604Z","zenodo_id":3445538,"doi":"https://doi.org/10.5281/zenodo.3445538","subject":null,"tags":["ocd","radicals","trpa1","vagus","auricle"],"vote_count":1,"view_count":1,"score":1.1,"deleted":false,"muted":false,"tweeted":false,"attachment_file_name":null,"attachment_content_type":null,"attachment_file_size":null,"attachment_updated_at":null},{"id":1234,"title":"Antidepressants, the gut microbiota, TRPA1 receptors and self-cooling.","sha":"5479cf237932e4c70ad63b1322598599","user_id":null,"state":"published","body":"Enhanced efflux pump expression and intracellular production of reactive oxygen species in gut bacteria has been\r\nobserved following exposure for sixty days to several antidepressants, at clinically relevant concentrations.1. This pattern has been shown to be associated with increased microbiota antibiotic resistance, but from another point of view this chronic effect of antidepressant use may over time increase radical levels in the aerobic (small) intestine by altering the gut microbiota, leading to OCD-curative radical action at gut TRPA1 receptors, releasing serotonin from enterochromaffin cells,(linked to anxiety modulation.2.), as outlined previously.3. \r\nThe peripheral release of serotonin and CCK due to gut TRPA1 activation causes blood flow changes repeatedly seen just prior to the onset of cure-points on MAOI treatment, most strikingly alternating hot, high blood flow red ears (followed by bilateral). This may relate to a reinstatement of more effective self-cooling systems, as possible defects of self-cooling systems and raised temperatures are positively correlated with depression severity in a large-scale recent study.4. The complex role of the vagus in metabolic regulation, and the need for vagal change in OCD cure referred to in earlier papers make this pattern understandable.5.\r\n\r\n.1.ProcNatlAcadSciUSA.2023.Jan31;120(5):e2208344120.\r\n.2.Nature.2023.Apr;616(7955):137-142.\r\n.3.Neurology,Psychiatry,andBrainResearch5(4):181,8(4):185,10(4):149.Journal of Brief Ideas.\"Oxidative stress,\r\n    MAOIs and OCD\",\"OCD,radicals and TRPA1 receptors\".\r\n.4.Nature.Scientific Reports.2024.5 Feb.\r\n.5.AnnalsofNYAcademyofSciences.2019.1454(1):42-55.      \r\n\r\n","created_at":"2024-06-17T06:53:13.205Z","updated_at":"2024-09-30T07:53:33.890Z","zenodo_id":12660254,"doi":"https://doi.org/10.5281/zenodo.12660254","subject":null,"tags":["antidepressants","ocd","gut microbiota","trpa1","self-cooling"],"vote_count":1,"view_count":1,"score":1.1,"deleted":false,"muted":false,"tweeted":false,"attachment_file_name":null,"attachment_content_type":null,"attachment_file_size":null,"attachment_updated_at":null}]