Craigo

Advancements in Intranasal Delivery of Drugs for Cluster Headache Treatment using Cubosome-Based Nanocarriers: A Review Preeti Chaudhary, Kirtan Vimal Shah, Darshan Rajendra Bodas, Sanjana Prasad Deshmukh, Akash Milind Solanki Published in Research Journal of Pharmacy and Technology on December 1, 2025 Link: https://doi.org/10.52711/0974-360X.2025.00887 Abstract: Cluster headaches (CH) represent a debilitating neurological disorder characterized by severe, recurrent attacks of pain, often leading to significant impairment in quality of life. Traditional treatments often face issues like delayed onset of action, systemic side effects, and challenges in achieving optimal drug concentrations at the target site. Intranasal drug delivery has emerged as a promising alternative for the management of cluster headaches due to its potential for rapid absorption and direct access to the central nervous system. Among the novel strategies under investigation, cubosome-based nanocarriers have gained significant attention due to their unique structural properties, biocompatibility, and ability to encapsulate a wide range of therapeutic agents. This review highlights recent advancements in intranasal delivery systems, focusing on cubosome-based nanocarriers for the treatment of cluster headaches. It explores the physicochemical characteristics of cubosomes that make them ideal for intranasal administration, including their high surface area, mucoadhesive properties, and ability to enhance drug stability and bioavailability. The review also examines the potential of cubosome-encapsulated verapamil, a calcium channel blocker, as a promising candidate for rapid and effective cluster headache relief. Furthermore, it addresses the challenges and future perspectives in the development and clinical translation of cubosome-based intranasal therapies. By synthesizing current research findings, this review aims to provide insights into the potential of cubosome-based nanocarriers as a transformative approach in the treatment of cluster headaches, paving the way for more effective, patient-friendly therapeutic options.

HNY and right on Jon, exactly - CH is pretty much a stress-test for Helsinki and CIOMS. I can only imagine the complexities of designing CH studies that advance knowledge but always place the well-being of the study participant first, let alone sitting on the ethics committees that have to review and approve them. Check out the below, part 33. World Medical Association Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects https://jamanetwork.com/journals/jama/fullarticle/1760318 And the Council for International Organizations of Medical Sciences, guideline 5. https://www.ncbi.nlm.nih.gov/books/NBK614415/ I saw a few posts on socials in recent weeks venting that there isn't enough research on CH and I get it but I also want to acknowledge that like the lead author of this study, we have some amazing researchers in our corner and I am so thankful for that as well as excited to see what happens in 2026. I feel we saw some real advancement in our understanding in 2025. Thank-you for bringing up this very relevant point.

Thank-you to the researchers. The study was exploratory and only had 18 participants split into three groups so the lack of statistical power is the likely reason for the discrepancy where the single-dose group showed a large effect size against placebo yet the primary outcome for the trial failed to reach statistical significance. And the single dose group reported greater improvement than the two dose group... could be just simply random variability again due to the small sample. Diphenhydramine was used to mimic the effects of psilocybin yet they found it only "partially substituted" for them, do they mean the participants may have been able to distinguish the active from placebo and potentially biased the self-reported headache diary results? i.e. expectation bias. Given the placebo performed unexpectedly well, should we be asking if diphenhydramine has therapeutic potential for migraine? Batch has previously said the neuropeptides involved in migraine and CH such as CGRP, PACAP, SP etc can trigger mast cell degranulation, histamine release and a self-sustaining feedback loop hence the early recommendation to take Benadryl (diphenhydramine) or more recently the full monty supplements with the D3 regimen for CH. Looking forward to larger trials. Welcome to read the study at link above or interact with it in NotebookLM (AI) below. https://notebooklm.google.com/notebook/94236d69-1463-4b24-93a4-a3870f7e9701?authuser=1

Comparing single- and repeat-dose psilocybin with active placebo for migraine prevention in an exploratory randomized controlled clinical trial Emmanuelle A D Schindler, Christopher H Gottschalk, Brian P Pittman, Deepak C D'Souza Published in Headache on December 29, 2025 Link: https://headachejournal.onlinelibrary.wiley.com/doi/10.1111/head.70024 Abstract: Objective: The goals of this study were to examine the therapeutic effects and safety of psilocybin given as a pulsed regimen for the prevention of migraine and to consider the blinding integrity of an active control agent. Background: The administration of a single low dose of psilocybin was observed to have lasting therapeutic effects in one small pilot trial in migraine, although the ability of a pulse dose regimen, as practiced by patients with cluster headache, to potentially improve magnitude and/or duration of transitional preventive effects has not been studied. Furthermore, comparison to an active placebo agent that adequately mimics the acute subjective effects of psilocybin is required to improve blinding integrity and measure placebo effects. Methods: In an exploratory randomized, double-blind, placebo-controlled, parallel group study, adults with migraine having at least two weekly migraine days at baseline (n = 18) participated in two drug administration sessions separated by 7 days during which they received zero, one, or two doses of psilocybin (10 mg; psi). Whenever participants did not receive psilocybin, they received diphenhydramine (25 mg; diph). Participant recruitment took place between September 2021 and August 2023. The primary outcome measure was a change in migraine frequency using headache diary data collected starting 2 weeks before and continuing through 8 weeks after the second drug session. Results: In the 2 weeks after completion of the two drug administration sessions, the change from baseline in migraine days/week was not significantly different among groups [diph-diph: -0.7 (95% confidence interval, -1.5 to 0.2); diph-psi: -2.0 (-3.0 to -1.0); psi-psi: -1.7 (-4.1 to 0.7); Χ2 (2) = 4.56, p = 0.102], despite large effect sizes against the placebo group in the those receiving one (diph-psi; d = 1.66) or two (psi-psi; d = 0.69) doses of psilocybin. Similar reductions in migraine frequency approximating 50% were seen in all groups over the 8 weeks measured. The difference in 50% response rate among groups over 2 weeks, however, approached significance (diph-diph: 17%; diph-psi: 80%; psi-psi: 80%; p = 0.087). Drug confidence ratings (i.e., blinding integrity) suggested that diphenhydramine partially substituted for the acute effects of psilocybin. No correlations were observed between changes in migraine frequency after psilocybin and drug confidence, acute general drug effects, or acute psychedelic effects. No serious or unexpected adverse events occurred. Conclusion: This exploratory study found similar reductions in migraine frequency with single-dose psilocybin, a two-dose pulse of psilocybin, or diphenhydramine placebo. Whereas blinding was incomplete in this study, this important topic is highlighted in the study design and findings. The potential for psilocybin to serve as a transitional treatment in migraine remains but will require careful planning in future studies to separate drug and non-drug effects. Furthermore, the inclusion of headache specialists in the design and execution of these future studies is necessary to preserve the viability of psilocybin treatment in headache medicine.

As I said in my other post, I’m pleased to have you here - whilst sorry you are in a bout, you have a good vibe that I resonate with. Yes! I have thought more than once about most of your suggestions and I love it - whether there is an out of the box solution or something custom, there is an old world charm about the forums here that I really do appreciate but understand if it was a little more in line with the times like integrated into an app it might be able to add more value, whether support, social connections, helping more people, fellowship etc. Someone from the awesome admin team might be able to give an update on any behind the scenes improvements that are in the pipeline. I’m sure I read somewhere there were some website things in the works. Good on you for offering your skills man, that’s what I just love about this community, people are too good.

Do you guys say this as you slurp another piece of fermented shark from the tin? Hehe. I really love that saying though, I will remember that! Sorry to hear about your bout with pneumonia, glad you are on the mend from that - hopefully the steroids and I suspect antibiotics didn't mess you around too much. A couple of years ago I had a real bad run with a recurrent bacterial infection that used 5 rounds of antibiotics before my doctor presented a biologic which I had said absolutely not in a million years - saw a functional doc, got it under control but low and behold that was the one year I fell from cluster free remission whilst maintaining the target vitamin D3 range - opened my eyes to a few different topics including microbiome - sorry to say I don't know that the fermented shark packs a probiotic punch like kim chi though. You also mentioned in another post about foraging up there in Iceland for medicine, I suspect your varieties would be quite different to what's found in more warmer climates. It's the same in New Zealand, we have mystical magical varieties down under, one example being Psilocybe weraroa, they look like little blue testicles and pack a heck of a punch. Happy to see you here on the forums - I recently landed here earlier in the year, good bunch of folk here and we all seem to love cats. I feel like this is the more appropriate place to share recent research. So... I sign off by saying Happy new year and thank-you for the old one!

Another review in pediatric migraine just published. Here we start to see an intervention with probiotics to modulate the microbiome. Let's see what happens in 2026 with this evolving area of research. Targeting the microbiome in pediatric migraine: gastrointestinal manifestations and the therapeutic role of Bifidobacterium longum Pi-Chuan Fan, Huey-Huey Chua, Chia-Ray Lin, Tzu-Hsuan Lai, Lih-Chu Chiou, Wang-Tso Lee Gut Microbes on December 27, 2025 https://doi.org/10.1080/19490976.2025.2606487 Abstract: Migraine is a disabling neurological disorder that often begins in childhood or adolescence and is frequently accompanied by gastrointestinal (GI) symptoms. However, the microbiota signatures and gut–brain interactions underlying pediatric migraine, particularly in the presence of GI disorder, remain poorly defined. This study aimed to explore the clinical and microbial features of pediatric migraine, as well as the therapeutic potential of probiotics. We prospectively enrolled 126 pediatric migraine patients (ages 6–19) with or without GI disorder and 50 age-matched healthy controls. Fecal microbiota was profiled using 16S rRNA sequencing. Patients with migraine were stratified based on Rome IV-defined GI disorders and evaluated for headache characteristics, PedMIDAS scores (disability assessment), plasma calcitonin gene related peptide (CGRP, thought as a key biomarker of migraine), cytokines, and fecal calprotectin. Probiotic effects were tested in both young (3–4 weeks) and adult capsaicin-induced migraine rat models, and an exploratory pilot study involving 23 pediatric migraine patients. Compared to controls, migraine patients exhibited distinct gut microbiota with reduced Bifidobacterium longum. and elevated Bacteroides. GI disorders were present in 46.8% of migraine patients and were associated with significantly higher rates of abdominal pain (50% vs. 13%, p <0.001), greater migraine-related disability (PedMIDAS: 60 ± 13.2 vs. 29 ± 7.0, p = 0.042), elevated fecal calprotectin, and enrichment of Streptococcus gallolyticus. In contrast, Faecalibacterium prausnitzii, positively correlated with B. longum, was linked to milder symptoms and shorter disease duration in migraine patients without GI disorder. In animal models, B. longum attenuated trigeminal activation in both young and adult rats. An exploratory pilot study showed B. longum supplementation led to reductions in headache days, intensity, and frequency. These findings reveal distinct gut microbial signatures in pediatric migraine, and identify B. longum as a promising microbiota-targeted therapeutic strategy. Our work highlights the therapeutic potential of modifying the gut–brain axis in childhood migraine.

Thanks CHfather – I don’t recall Batch’s earlier advice either, likely before my time. We’re talking roughly 200–500mg calcium in a multi vitamin and most probably consume at least that daily through a standard diet. Check out this ask the Doctor post from Havard, although the patient was taking a different class of calcium channel blocker I suspect the answer would be the same. While high doses of intravenous calcium are sometimes used to reverse an overdose of a calcium-channel blocker, the 600 milligrams of calcium in your daily supplement isn't enough to interfere with the drug's ability to lower blood pressure. In fact, oral calcium supplementation has been shown to lower blood pressure slightly in some people. So you can continue to take both without risking your bones or raising your blood pressure. https://www.health.harvard.edu/blood-pressure/do-calcium-supplements-interfere-with-calcium-channel-blockers As for vitamin D3, this study by Holick and colleagues looked at supplementation with 10,000iu D3 (amongst other doses) and found no change in serum calcium (albeit an increase in 25(OH)D and decrease in PTH). You could see an increase in calcium labs maintaining 80-120ng/mL however if maintained within normal reference my understanding is that you are good. https://www.nature.com/articles/s41598-019-53864-1 You could jump on one of the Facebook or Reddit groups and ask the question there, I know a couple of chronic warriors that take both verapamil and the regimen together and are doing well. One comment about verapamil that stuck with me was that many warriors find the immediate release vs the sustained release works better for CH prophylaxis - why I am not sure but thought to add. Happy holidays all.

Hi all. I used the search function to see if this had been shared on the forums already, I couldn't find anything. Australian headache researcher Dr Faraidoon Haghdoost has obtained funding for a clinical trial into the potential for psilocybin to prevent disabling cluster headache, funded through the Novel Treatments and Management Strategies for Chronic Pain stream of the Australian Medical Research Future Fund (MRFF). The trial is called the ‘Psilocybin Efficacy and Acceptability on Cluster Headache Episodes’ PEACE Study. Faraidoon has put a request out to any Australian Cluster Headache warriors that would be prepared to talk about their journey with the disease to help raise awareness, I quote from his recent post on Big Head Pain on Facebook. If you are a CH warrior in Australia or know someone that is whom may be willing to have a chat with Faraidoon about getting involved, please reach out to him at the links below. Seeking a Person with Cluster Headache for a Media Interview (Plus Big Publication News!) I’m excited to share that our manuscript, “Patient Perspectives on Research Gaps in Cluster Headache”, has been accepted for publication in Headache journal! This work is deeply rooted in patient experience, and we’re thrilled to see it moving into the academic and clinical space. As part of sharing this milestone, we’re organising media interviews to discuss the findings and raise awareness of cluster headache. We are looking for someone living with cluster headache in Australia who would be willing to join one of these interviews - including sharing their name, photo, and personal experience, if comfortable. Your voice could make a real difference in helping the broader community understand the condition. If you’re interested - or would like more information before deciding - please comment below or message me privately. We’d be very happy to include someone from our community in these interviews. Thank you all for your ongoing support and for continuing to strengthen this community. More about the study: https://www.georgeinstitute.org/news-and-media/news/hope-for-cluster-headache-community-as-psilocybin-trial-funded Big Head Pain Facebook group: https://www.facebook.com/groups/3085334835045020 Email: faraidoonhaghdoost@gmail.com

The range for normal depends on the country and the lab. Quest offers a range of 30-100ng/mL however the specific regimen you may read about here and on other platforms for CH prophylaxis targets a vitamin D blood level of 80-100ng/mL for episodic, the upper limit for Quests range for normal and slightly above that for chronic CH. Enjoy the watch and hopefully a pain free holidays ahead.

Appreciate your feedback and thank-you for your kind words snafu!

Hi all. Here is a 10 minute explainer video utilizing AI to generate some pixar characters of myself and Pete Batcheller to offer an introduction and "flight briefing" of the Vitamin D Regimen, a patient led preventative treatment protocol for Cluster Headache. For more information on the regimen I know there is plenty on information in the forums here and the guides, interviews and other Vitamin D videos can be found over at www.vitamindregimen.com

"The pilot ‘Psilocybin Efficacy and Acceptability on Cluster Headache Episodes’ (PEACE) pilot trial will assess whether 10 mg of psilocybin once a week for four weeks compared to placebo can prevent cluster headache attacks. The study builds on early patient reports and small-scale trials that indicate its potential benefits." So that's 1g dried cubensis give or take (0.8 - 1.2g) depending potency every 7 days for 4 weeks, in sort parallels the community busting protocol. I hope they are able to recruit the numbers. I had recently read one of his articles on migraine: Migraine management: Non-pharmacological points for patients and health care professionals He is also the recipient of the 2025 Peter Goadsby Award for Best Scientific Oral Abstract presentation at the Australian and New Zealand Headache Society Annual Scientific Meeting in Sydney on 30–31 August. His presentation, “Gaps in Research and Management of Cluster Headache Through Patient Perspectives,” underscored the need to listen to patient voices and address the gaps that remain in both clinical care and research.

A new clinical trial in Australia has funding approved to test psilocybin as a preventive treatment for cluster headache. The PEACE Trial (Psilocybin Efficacy and Acceptability on Cluster headache Episodes), led by Faraidoon Haghdoost and supported by the The George Institute for Global Health and the University of New South Wales under the Medical Research Future Fund (MRFF), aims to evaluate whether weekly low-dose psilocybin can safely reduce the frequency or severity of cluster attacks. There is also a survey on Faraidoon's page assessing the cluster headache research gaps based on the patients perspectives. https://www.faraidoonhaghdoost.com/post/cluster-headache-trial-got-funded-in-australia https://www.georgeinstitute.org/news-and-media/news/hope-for-cluster-headache-community-as-psilocybin-trial-funded

Greetings and sorry they are back - it sucks. My one fall from remission whilst using the D3 regimen saw me find o2 and the cluster o2 kit for the first time - I was getting o2 slap backs but as Bejeeber said that’s not bad to have several hours in between nocturnal attacks, I was aborting in 6 minutes or so and getting a slap back an hour later. An amazing advocate in our community Pete McCormick suggested to try staying on the oxygen for the same amount of time it took to abort the attack but at a lower flow rate, when I did that I found an immediate improvement back to my normal 2-3 attacks per night, aborted and back to bed in around the 15-20 minute mark which was an amazing improvement on previous abortives. I only needed the o2 setup for a total of four days before higher levels of vitamin D3 put me back into remission, thank God. Can’t add much about caffeine suffice to say some warriors use a strong black coffee rather than energy drinks and report it works, if concerned / wary about energy drinks, I know I am. I’d just straight hit up the oxygen upon waking rather than caffeine and save a strong black coffee or otherwise for shadows during the day. All that being said and in lieu of challenges obtaining Emgality, is the vitamin D3 regimen an option for you as another tool to add in the kit?

Another review on this subject published a few days back.. A review on gut microbiota and migraine severity: a complex relationship Noha M. Gamil, Rana M. Ghorab, Reham Z. Elsadawy, Nada M. Khadrawy, Mohamed Abdelhamid, Khalid A. Ismael, Omar A. Mohamed, Mohamed M. Ata, Habiba T. Jalal, Joumana E. Zeidan, Reem T. Rashed & Riham A. El-Shiekh Springer Nature Inflammopharmacology Published: 27 November 2025 https://pubmed.ncbi.nlm.nih.gov/41298977/ The gut-brain axis plays a vital role in migraine pathophysiology. Studies highlight reciprocal interactions between the central nervous system and the gastrointestinal tract. Previous research suggests that factors such as gut microbiota profiles, inflammatory mediators, neuropeptides, serotonin pathways, stress hormones, and nutritional substances influence this interaction. The pathophysiology of migraine has been linked to changes in the gut-brain axis, which affects migraine severity and frequency. Additionally, dietary approaches, including the ketogenic diet, vitamin D supplementation, omega-3 intake, probiotics, and weight loss plans, have shown promising effects in reducing migraine symptoms by positively impacting the gut microbiota and the gut-brain axis. Understanding these connections could lead to novel therapeutic strategies for effectively managing migraines. It is worth noting that research highlights several innovative treatments for migraine, such as Zelirex and Cevimide, implantable devices like Cefaly and Revilion, and new effective routes of administration for Sumatriptan. Finally, patients’ perspectives and concerns were thoroughly discussed, with a focus on future directions in the migraine-gut axis research.

Notebook LM Audio Summary Podcast Generation (AI generated). Cluster_Headaches_Solved_Dual-Target_Neuromodulation.m4a

Update of Seven Cases of Refractory Cluster Headache Treated with Combined Occipital Nerve and Sphenopalatine Ganglion Stimulation with Good Mean Outcome in a Long Term Follow Up Juan Carlos Mario Andreani, Fabián Piedimonte, Osvaldo Bruera, Marco Lisicki, Diego Bashkansky Published Vol. 19 in NeuroTarget 2025 Link: https://doi.org/10.47924/neurotarget2025549 Abstract: Cluster headache (CH) is an extremely debilitating and often difficult-to-treat headache disorder characterized by recurrent attacks of excruciating pain associated with cranial autonomic symptoms. Several invasive neuromodulation procedures have been evaluated in the past, but the combination of these procedures to maximize response has not been studied in groups of patients. This presentation aims to describe an update on the evolution of cases based on a recent publication of ours. This single-center, retrospective, observational study included seven patients (3F/4M) suffering from CCH, according to the diagnostic criteria of the current International Classification of Headache Disorders, and considered refractory based on the Consensus Statement of the European Headache Federation. Between February 2010 and March 2021, these patients underwent implantation of electrodes for SPG and greater occipital nerve (GON) stimulation ipsilateral to the side of the pain. The mean follow-up time was 6.38 years ± 3.6. Six out of the seven patients (86%) experienced good-to-excellent initial pain relief, defined as ≥50% reduction in VAS scores compared to baseline, with marked improvement in attack severity and functional impact. Almost complete remission of symptoms was achieved in most cases. Multiple techniques have been proposed to control CH symptoms. Here we report, for the first time, that combined invasive SPG and GON neurostimulation significantly and enduringly improves CCH symptoms in a series of refractory patients. The relatively low number and severity of complications suggest a favorable risk-benefit profile. Synergistic invasive SPG-GON stimulation appears to be a relatively safe and promising alternative for effective and long-lasting control of CCH.

Notebook LM Audio Summary Podcast Generation (AI generated). Cluster_Headache_Restlessness_Explained_By_Brain_Scan.m4a

Uncovering the neurological substrates underlying restlessness in cluster headache - A functional MRI study Shu-Ting Chen, Chia-Chun Chiang, Yung-Lin Chen, Shin-Yi Tseng, Mei-Chun Chen, Chi-ieong David Lau & Jr-Wei Wu Published in The Journal of Headache and Pain on November 25, 2025 Link: https://doi.org/10.1186/s10194-025-02209-7 Abstract: Restlessness or agitation is one of the core symptoms of cluster headache (CH). However, the neurological substrate underlying this phenomenon has not been thoroughly analyzed. Whether they are attributed to the core aggression circuit or other CH-related structures remains unclear. The aim of this study is to use functional neuroimaging to elucidate the underlying mechanism of restlessness or agitation in CH. We prospectively recruited consecutive patients with CH from the Headache Clinic of Taipei Veterans General Hospital between Jan 2022 and July 2025. Patients who consistently reported either the presence or absence of restlessness during CH attacks were enrolled and categorized into two groups: restlessness and non-restlessness. All enrolled patients underwent a functional magnetic resonance imaging (fMRI) scan. In the restlessness group, patients were required to exhibit restlessness during the fMRI scan, whereas those in the non-restlessness group showed no restlessness at the time of scanning. In this study, 32 regions of interest (ROIs) relevant to CH pathophysiology and the core aggression circuit were selected. To identify restlessness-related networks, ROI-to-ROI functional connectivity was compared between the restlessness and non-restlessness groups. To investigate downstream network for restlessness, ROI-to-voxel analyses were conducted using a general linear model, with ROIs showing significant differences in the initial ROI-to-ROI analysis as seeds. Multiple comparisons were corrected using both the false discovery rate (FDR) and family-wise error (FWE) methods. A total of 24 patients with CH were recruited and categorized into two groups: restlessness (N = 14) and non-restlessness (N = 10). The ROI-to-ROI functional connectivity analysis of CH patients with restlessness revealed a significant connection between the non-pain side locus coeruleus (LC) and the pain-side substantia nigra pars compacta (SNpc), which survived FDR correction (p-FDR = 0.016). Seed-based general linear model analysis further revealed decreased connectivity between the pain-side SNpc and pain-side superior frontal gyrus, which survived FWE correction (p = 0.037). However, there were no significant cortical connectivity from the LC survived the FDR correction. Our fMRI findings suggest that the neurological substrates of restlessness in CH involve the LC and SNpc rather than the core aggression network. Weakened connectivity from the SNpc to the superior frontal cortex may represent the downstream pathway contributing to restlessness in CH.

Notebook LLM Audio Summary Podcast Generation (AI generated). Leaky_Gut_Causes_Chronic_Migraines_and_Pain.m4a

In lieu of a recent article I wrote exploring the literature that may support dysbiosis in cluster headache (check general board), a number of parallels were cautiously drawn from emerging migraine literature, which I thought worth sharing in one place here on the migraine board. These recent studies explore the emerging role of dysbiosis as a causative factor in migraine pathogenesis, exploring potential links via the gut-brain axis, microbial imbalance and therapeutic interventions like probiotics or faecal microbiota transplantation (FMT). Whilst I don’t suffer from migraine myself, having read this body of work, if I did I think it would be a fair and reasonable question to be asking: “Do I have dysbiosis, and if so, what can I do about it?” None of the papers below explore the role of optimised nutrition in detail, nor do they touch on two of my favourite patient-led protocols that are known to reshape the gastrointestinal environment and microbiome - high-dose vitamin D and psilocybin - but the door remains open for those avenues to be investigated (and hopefully discussed here). Happy reading – welcome your comment and you’ll find a NotebookLM audio summary generation below if you’d rather listen to a podcast rather than read studies. I have offered the links to the articles and a short generated summary snippet - any of the articles are behind a paywall and you’d like me to shoot you off a copy please reach out via DM. Gut microbiota dysbiosis enhances migraine-like pain via TNFα upregulation Published January 2020 https://doi.org/10.1007/s12035-019-01721-7 Yuanyuan Tang, Sufang Liu, Hui Shu, Lora Yanagisawa, Feng Tao Key finding: Antibiotic-induced dysbiosis and germ-free status markedly worsen nitroglycerin-triggered migraine-like pain in mice through TNFα-mediated trigeminal sensitisation; probiotics reverse the effect. The association between migraine and gut microbiota: a systematic review Published April 2023 https://doi.org/10.1007/s13760-025-02779-y Alon Gorenshtein, Kamel Shihada, Liron Leibovitch, Tom Liba, Avner Goren Key finding: Consistent reduction in anti-inflammatory genera (especially Faecalibacterium) and increased Veillonella in migraineurs; overall picture of dysbiosis and reduced diversity. A causal effect of gut microbiota in the development of migraine Published July 2023 https://doi.org/10.1186/s10194-023-01609-x Qiang He, Wenjing Wang, Yang Xiong, Chuanyuan Tao, Lu Ma, Junpeng Ma, Chao You, and The International Headache Genetics Consortium Key finding: Mendelian randomisation evidence of causal links from multiple bacterial taxa (including Bifidobacteriaceae) to migraine, migraine with aura, and migraine without aura. Making migraine easier to stomach: the role of the gut–brain–immune axis in headache disorders Published 2023 https://doi.org/10.1111/ene.15934 Marissa Sgro, Jason Ray, Emma Foster, Richelle Mychasiuk Key finding: Narrative review emphasising that a diverse, healthy microbiome is required for optimal brain health and that dietary manipulation is a logical therapeutic lever. Migraine as a Disease Associated with Dysbiosis and Possible Therapy with Fecal Microbiota Transplantation Published 14 August 2023 https://doi.org/10.3390/microorganisms11082083 Ágnes Kappéter, Dávid Sipos, Adorján Varga, Szabolcs Vigvári, Bernadett Halda-Kiss, Zoltán Péterfi Key finding: Explicitly proposes fecal microbiota transplantation as a future therapeutic option for migraine on the basis of restored serotonin signalling and reduced neuroinflammation. Linking Migraine to Gut Dysbiosis and Chronic Non-Communicable Diseases Published 11 October 2023 https://doi.org/10.3390/nu15204327 Manuela Di Lauro, Cristina Guerriero, Kevin Cornali, Maria Albanese, Micaela Costacurta, Nicola Biagio Mercuri, Nicola Di Daniele, Annalisa Noce Key finding: Places gut dysbiosis at the centre of a bidirectional relationship between migraine and cardiometabolic disorders; advocates nutritional and lifestyle approaches to restore eubiosis. Lipopolysaccharide, VE-cadherin, HMGB1, and HIF-1α levels are elevated in the systemic circulation in chronic migraine patients with medication overuse headache: evidence of leaky gut and inflammation Published 2024 https://doi.org/10.1186/s10194-024-01730-5 Doga Vuralli, Merve Ceren Akgor, Hale Gok Dagidir, Ozlem Gulbahar, Meltem Yalinay, Hayrunnisa Bolay Key finding: First human evidence of raised circulating LPS and leaky-gut markers in chronic migraine + medication-overuse headache, directly implicating intestinal hyperpermeability. The Brain, the Eating Plate, and the Gut Microbiome: Partners in Migraine Pathogenesis Published 11 July 2024 https://doi.org/10.3390/nu16142222 Parisa Gazerani, Laura Papetti, Turgay Dalkara, Calli Leighann Cook, Caitlin Webster, Jinbing Bai Key finding: Strong call for personalised dietary and pre/probiotic interventions; highlights bidirectional influence between diet, microbiome, and migraine susceptibility. Oral and Gut Dysbiosis in Migraine: Oral Microbial Signatures as Biomarkers of Migraine Published 2025 https://doi.org/10.1212/NXI.0000000000200437 Soomi Cho, Yeonjae Jung, Hyun-Seok Oh, Jungyon Yum, Seungwon Song, JaeWook Jeong, Woo-Seok Ha, Kyung Min Kim, Won-Joo Kim, Min Kyung Chu Key finding: Oral dysbiosis is even more pronounced than gut dysbiosis in migraine; specific oral microbial clusters predict migraine status with high accuracy and correlate with headache frequency. Unravelling the gut–brain connection: a systematic review of migraine and the gut microbiome Published 3 April 2025 https://doi.org/10.1186/s10194-025-02039-7 Caroline W Mugo, Ella Church, Richard D Horniblow, Susan P Mollan, Hannah Botfield, Lisa J Hill, Alexandra J Sinclair, Olivia Grech Key finding: Synbiotic and combined probiotic–synbiotic regimens consistently reduce attack frequency, severity, duration, and analgesic consumption in randomised trials. Gut microbiota, probiotics, and migraine: a clinical review and meta-analysis Published 12 September 2025 https://doi.org/10.22514/jofph.2025.043 Olga Grodzka, Izabela Domitrz Key finding: Meta-analysis of RCTs confirms probiotics significantly lower migraine frequency; effect on severity approaches significance despite limited trials.

Two useful tools I wanted to share for anyone here who keenly follows research on cluster headaches, migraine or anything for that matter. The first is Harzing’s Publish or Perish. It is a free citation analysis program that lets you easily search scientific literature across a range of journal sources. Link: https://harzing.com/resources/publish-or-perish The second that I am really loving at the moment is Google’s NotebookLM. It allows you to upload papers, PDFs, and links, then ask structured questions and generate summaries, comparisons and notes directly from your sources. For anyone trying to understand mechanisms, track themes across papers or just stay organised while reading, it is extremely handy. Link: https://notebooklm.google Both tools make it easier for patients who like to follow the science closely to evaluate studies and stay on top of emerging research. If anyone wants a quick explanation of how to use either tool for cluster headache-related topics, I am happy to share examples. The last tool - bonus lol, I went looking for something to match CHFathers cat picture in a recent AI post - found another Google tool. An experimental tool for visual exploration: you input images for subject, scene, style and the system remixes them into new visuals - here's what I got for my new CH Forums profile pic - I am here to stay now! https://labs.google/fx/tools/whisk

Hey Kevin. To my knowledge there is no specific migraine busting protocol. FunTimes offered a solid reply to your earlier post on the general board and the key information regarding the process is on the following page. https://clusterbusters.org/resource/alternative-treatments/#busting You might find the Yale psilocybin migraine study useful to look at as the dose they used somewhat correlates to the Cluster Busters range, if I am correct They gave 0.143 mg/kg of pure psilocybin and when you apply a conversion factor for Psilocybe cubensis potency (roughly 0.8 percent psilocybin by dry weight with variance as to strain, when it was picked and even which part of the fruit) that works out to the same content found in about 1.5 g of dried cubensis - give or take, maybe a little less. The key difference is that the study used one single dose followed by a two-week observation period whereas cluster warriors traditionally repeat doses every five to seven days. https://www.sciencedirect.com/science/article/pii/S187874792301214X My personal thoughts - start a bit lower than the typical 1.5g dried cubensis mushroom to get accustomed to the feeling, I quite enjoy the euphoria and introspection and find it doesn’t last too long before I’m hungry and tired. For what it’s worth a quick scour of the literature found the most recent paper with title including "migraine" "psilocybin" - a case report of a single male migraineur in his 30s whom used psilocybin alongside otc pain relief at 1.2g dried as an acute treatment with greater reported efficacy than pain relief alone. https://pmc.ncbi.nlm.nih.gov/articles/PMC10561985/ You may find another popular treatment option used by members of the CH community worth a look-in whilst you are here, the Vitamin D3 Anti-Inflammatory Regimen. You’ll find the information here or collated by myself and Pete Batcheller over at www.vitamindregimen.com I would say that given a sensible approach and applying the protocols as per the guides, IMHO both of these patient led avenues are generally safe and worth investigating - in any event a walk down the unknown path can cause a bit of anxiety so good luck as you navigate - I remember being nervous as heck in 2015 when I started the D3 regimen against my Doctors best recommendations and yet 8 days later things took a turn for me, I cried like baby, hugged wifey and got my life back - 10 years later I think there is still a part of me that is in disbelief that it actually worked and I only wish that could be the same for everyone. Whilst I have had success with D3, I found a penchant in the hobby of mycology, I have a wonderful big laminar flow hood that takes up our spare room and all the mycological tools to grow wild and wonderful varieties from "cubes" to turkey tails and beyond - and have done so over the years with great success, it is a fascinating and wildly fulfilling hobby with lots of highs (no pun intended) and lows of the process. It isn't a fast thing either and after weeks, sometimes months of cultivation to have a fruiting body appear overnight is awesome or to awake one morning after the same period to find dreaded trichoderma has destroyed all your hard work is devastating! Still, well worth it for the journey and knowledge learned! Were there any specific questions you wanted answers to, I’m sure we will do our best to help. Best wishes to you. Cheers, Craig.

Hi Nut cluster. I’m clearly not female (I missed the social cues upon joining the forum regarding using a cat as my profile picture), I don’t have much to add regarding estrogen but I have always been intrigued with vitamin D biology during pregnancy and your post captured my interest so please excuse me if this is a little off topic but wanted to share. Cholecalciferol / vitamin D3 is converted via hydroxylation into the blood storage form calcifediol which is then further converted into its hormonal form, calcitriol, mostly (but not exclusively) by the kidneys. The blood level of calcitriol is maintained in a strict range to maintain calcium homeostasis and is regulated by parathyroid hormone. During pregnancy the levels of calcitriol, the hormonal form, increases by double or triple to levels you’d see in granulomatous disease or intoxication but without hypercalcemia. The body deliberately raises both calcitriol and binding proteins in order to support placental development, immuno-regulation and fetal skeletal growth. The levels then fall back into normal range 2-6 weeks postpartum. There is still much we don’t understand about this intriguing process. It’s interesting that many female warriors report skipping cycles during pregnancy and to also consider why they return postpartum (and perhaps also why MS relapse may occur postpartum), and although tempting to speculate it may have something to do with the increase in calcitriol and its immuno-modulatory properties, probably an oversimplification - the body is just so complex. Dr. Hollis & Dr. Wagner have a combined century or so of research looking at vitamin D and reproductive outcomes, this was a great talk from last year although can’t recall if they cover the specifics of the points above.