Nathaniel M Schuster, Mark S Wallace, Thomas D Marcotte, Dawn C Buse, Euyhyun Lee, Lin Liu, Michelle Sexton
Objective: To assess the efficacy of cannabis for the treatment of acute migraine.
Background: Preclinical and retrospective studies suggest cannabinoids may be effective in migraine treatment. However, there have been no randomized clinical trials examining the efficacy of cannabinoids for acute migraine.
Methods: In this randomized, double-blind, placebo-controlled, crossover trial, adults with migraine treated up to four separate migraine attacks, one each with vaporized (1) 6% Δ9-tetrahydrocannabinol (THC) (THC-dominant), (2) 11% cannabidiol (CBD) (CBD-dominant), (3) 6% THC + 11% CBD, and (4) placebo cannabis flower in a randomized order. Washout period between treated migraine attacks was ≥1 week. The primary endpoint was pain relief, and secondary endpoints were pain freedom and most bothersome symptom freedom, all assessed at 2-h post-vaporization.
Results: Ninety-two participants were enrolled and randomized, and 247 migraine attacks were treated. THC + CBD was superior to placebo at achieving pain relief (67.2% vs. 46.6%, odds ratio [95% confidence interval] 2.85 [1.22, 6.65], p = 0.016), pain freedom (34.5% vs. 15.5%, 3.30 [1.24, 8.80], p = 0.017), and most bothersome symptom freedom (60.3% vs. 34.5%, 3.32 [1.45, 7.64], p = 0.005) at 2 h, as well as sustained pain freedom at 24 h and sustained most bothersome symptom freedom at 24 and 48 h. THC-dominant was superior to placebo for pain relief (68.9% vs. 46.6%, 3.14 [1.35, 7.30], p = 0.008) but not pain freedom or most bothersome symptom freedom at 2 h. CBD-dominant was not superior to placebo for pain relief, pain freedom, or most bothersome symptom freedom at 2 h. There were no serious adverse events.
Conclusion: Acute migraine treatment with 6% THC + 11% CBD was superior to placebo at 2-h post-treatment with sustained benefits at 24 and 48 h.
目的：评价大麻治疗急性偏头痛的疗效。背景：临床前和回顾性研究表明大麻素可能有效治疗偏头痛。然而，目前还没有随机临床试验检验大麻素对急性偏头痛的疗效。方法：在这项随机、双盲、安慰剂对照、交叉试验中，患有偏头痛的成年人治疗多达四次偏头痛发作，每次发作按随机顺序分别使用(1)6% Δ9-tetrahydrocannabinol (THC) （THC优势）、(2)11%大麻二酚（CBD优势）、(3)6% THC + 11% CBD和(4)安慰剂大麻花。治疗后偏头痛发作的洗脱期≥1周。主要终点是疼痛缓解，次要终点是疼痛缓解和最麻烦的症状缓解，所有这些都在蒸发后2小时进行评估。结果：92名参与者被随机纳入，247例偏头痛发作得到治疗。THC + CBD在2小时疼痛缓解（67.2% vs. 46.6%，优势比[95%置信区间]2.85 [1.22,6.65],p = 0.016）、疼痛缓解（34.5% vs. 15.5%, 3.30 [1.24, 8.80], p = 0.017）、最令人烦恼的症状缓解（60.3% vs. 34.5%, 3.32 [1.45, 7.64], p = 0.005）、24小时持续疼痛缓解和24和48小时持续最令人烦恼的症状缓解方面优于安慰剂。thc优势组在疼痛缓解方面优于安慰剂组（68.9% vs. 46.6%, 3.14 [1.35, 7.30], p = 0.008），但在2小时时疼痛缓解或最令人烦恼的症状缓解方面优于安慰剂组。在2小时时，cbd优势组在疼痛缓解、疼痛缓解或最令人烦恼的症状缓解方面并不优于安慰剂。无严重不良事件发生。结论：6% THC + 11% CBD治疗急性偏头痛在治疗后2小时优于安慰剂，并在24和48小时持续获益。
{"title":"Vaporized cannabis versus placebo for acute migraine: A randomized, double-blind, placebo-controlled crossover trial.","authors":"Nathaniel M Schuster, Mark S Wallace, Thomas D Marcotte, Dawn C Buse, Euyhyun Lee, Lin Liu, Michelle Sexton","doi":"10.1111/head.70025","DOIUrl":"10.1111/head.70025","url":null,"abstract":"<p><strong>Objective: </strong>To assess the efficacy of cannabis for the treatment of acute migraine.</p><p><strong>Background: </strong>Preclinical and retrospective studies suggest cannabinoids may be effective in migraine treatment. However, there have been no randomized clinical trials examining the efficacy of cannabinoids for acute migraine.</p><p><strong>Methods: </strong>In this randomized, double-blind, placebo-controlled, crossover trial, adults with migraine treated up to four separate migraine attacks, one each with vaporized (1) 6% Δ9-tetrahydrocannabinol (THC) (THC-dominant), (2) 11% cannabidiol (CBD) (CBD-dominant), (3) 6% THC + 11% CBD, and (4) placebo cannabis flower in a randomized order. Washout period between treated migraine attacks was ≥1 week. The primary endpoint was pain relief, and secondary endpoints were pain freedom and most bothersome symptom freedom, all assessed at 2-h post-vaporization.</p><p><strong>Results: </strong>Ninety-two participants were enrolled and randomized, and 247 migraine attacks were treated. THC + CBD was superior to placebo at achieving pain relief (67.2% vs. 46.6%, odds ratio [95% confidence interval] 2.85 [1.22, 6.65], p = 0.016), pain freedom (34.5% vs. 15.5%, 3.30 [1.24, 8.80], p = 0.017), and most bothersome symptom freedom (60.3% vs. 34.5%, 3.32 [1.45, 7.64], p = 0.005) at 2 h, as well as sustained pain freedom at 24 h and sustained most bothersome symptom freedom at 24 and 48 h. THC-dominant was superior to placebo for pain relief (68.9% vs. 46.6%, 3.14 [1.35, 7.30], p = 0.008) but not pain freedom or most bothersome symptom freedom at 2 h. CBD-dominant was not superior to placebo for pain relief, pain freedom, or most bothersome symptom freedom at 2 h. There were no serious adverse events.</p><p><strong>Conclusion: </strong>Acute migraine treatment with 6% THC + 11% CBD was superior to placebo at 2-h post-treatment with sustained benefits at 24 and 48 h.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145862783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emmanuelle A D Schindler, Christopher H Gottschalk, Brian P Pittman, Deepak C D'Souza
<p><strong>Objective: </strong>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.</p><p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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); Χ<sup>2</sup> <sub>(2)</sub> = 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.</p><p><strong>Conclusion: </strong>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 tra
目的：本研究的目的是检查裸盖菇素作为一种脉冲治疗方案用于预防偏头痛的治疗效果和安全性，并考虑一种活性对照剂的致盲完整性。背景：在一项针对偏头痛的小型试点试验中，单次低剂量裸盖菇素被观察到具有持久的治疗效果，尽管尚未研究集束性头痛患者采用脉冲剂量方案的能力，以潜在地改善过渡性预防效果的程度和/或持续时间。此外，需要与一种充分模仿裸盖菇素急性主观效应的活性安慰剂剂进行比较，以提高盲法的完整性并测量安慰剂效应。方法：在一项探索性随机、双盲、安慰剂对照、平行组研究中，在基线时每周至少有两天偏头痛的成年人（n = 18）参加了两个间隔7天的给药疗程，在此期间，他们接受0、1或2剂量的裸盖菇素（10mg; psi）。当参与者没有接受裸盖菇素时，他们接受苯海拉明（25mg; diph）。参与者招募在2021年9月至2023年8月期间进行。主要结果测量是偏头痛频率的变化，使用从第二次服药前2周开始到第二次服药后8周持续收集的头痛日记数据。结果：在两次给药疗程结束后的2周内，组间偏头痛天数/周的基线变化无显著差异[diph-diph: -0.7(95%可信区间，-1.5至0.2)；Diph-psi: -2.0(-3.0至-1.0)；Psi-psi: -1.7(-4.1至0.7)；Χ2 (2) = 4.56, p = 0.102]，尽管与安慰剂组相比，接受一剂（dip -psi; d = 1.66）或两剂（psi-psi; d = 0.69）裸盖菇素的组有很大的效应。在8周的测量中，所有组的偏头痛频率都减少了大约50%。2周后，两组间50%有效率的差异接近显著性（diph-diph: 17%; diph-psi: 80%; psi-psi: 80%; p = 0.087）。药物置信度评级（即盲性完整性）表明苯海拉明部分取代了裸盖菇素的急性作用。未观察到裸盖菇素后偏头痛频率的变化与药物信心、急性一般药物效应或急性迷幻效应之间的相关性。未发生严重或意外的不良事件。结论：这项探索性研究发现，单剂量裸盖菇素、双剂量裸盖菇素或苯海拉明安慰剂对偏头痛频率的降低相似。虽然本研究的盲法是不完整的，但这一重要主题在研究设计和研究结果中得到了强调。裸盖菇素作为偏头痛过渡性治疗的潜力仍然存在，但需要在未来的研究中仔细规划，以区分药物和非药物作用。此外，在这些未来研究的设计和执行中纳入头痛专家是必要的，以保持裸盖菇素在头痛药物治疗中的可行性。
{"title":"Comparing single- and repeat-dose psilocybin with active placebo for migraine prevention in an exploratory randomized controlled clinical trial.","authors":"Emmanuelle A D Schindler, Christopher H Gottschalk, Brian P Pittman, Deepak C D'Souza","doi":"10.1111/head.70024","DOIUrl":"https://doi.org/10.1111/head.70024","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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); Χ<sup>2</sup> <sub>(2)</sub> = 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.</p><p><strong>Conclusion: </strong>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 tra","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Pia Grant Tejada, Alexandra M Klomhaus, Rebecca Ortiz, Tristan D Tibbe, Sinifunanya E Nwaobi
Objective: We analyzed data from both a national survey and a single hospital system to determine the prevalence of migraine in individuals with autism as well as identify sociodemographic and clinical characteristics associated with migraine in individuals with autism.
Background: Few studies have examined the prevalence of migraine in autism and there are no studies examining the migraine phenotype and clinical features associated with migraine in autism.
Methods: This retrospective cohort study used two databases-the National Survey of Children's Health (NSCH) and the University of California Los Angeles hospital system electronic health record (UCLA EHR). NSCH survey data from 2018, 2019, 2020, and 2021 (data collection period for each year is June to January; e.g., NSCH 2021 period is June 2021 to January 2022; N = 50,892) were queried to identify cohorts based on responses to two survey questions identifying the presence of frequent/severe headache and autism. For UCLA cohorts, patients (12/01/1979-4/16/2023, N = 4,334,162) were queried for migraine and autism based on the International Classification of Diseases diagnosis codes. We tested the hypothesis: Headache/migraine occurs more frequently in individuals with autism versus without autism. Variables including social determinants of health (SDoH) and co-occurring illnesses were compared between autism with versus without headache/migraine.
Results: Headache and migraine prevalence was higher in individuals with autism versus those without (2021 NSCH-headache % [95% confidence interval {CI}], 7.1% [4.62-9.56] vs. 3.0% [2.62-3.19], p < 0.001 and UCLA-migraine: 3.1% [2.86-3.43] vs. 2.0% [1.97-1.99], p < 0.001). Among those with autism, the presence of headache/migraine was associated with increased odds of adverse childhood experiences such as bullying (NSCH-'Weekly/Almost daily' bullying aOR = 5.93 [2.01-17.50], p = 0.001, 'Never' reference) and being a victim of violence (NSCH-'Yes' aOR = 2.82, [1.19-6.66], p = 0.018), poor general health (NSCH-'Fair/Poor' health aOR = 9.68, [3.01-31.19], p < 0.001, 'Excellent' reference), mood disturbances, including anxiety (NSCH-'Yes' aOR = 4.50, [1.63-12.41], p = 0.004; UCLA aOR = 3.40, [2.78-4.17], p < 0.001), and depression (NSCH-'Yes' aOR = 5.70, [2.50-12.97], p < 0.001; UCLA aOR = 3.76, [3.08-4.60], p < 0.001), as well as increased rates of concussion (NSCH-'Yes' aOR = 9.05, [3.19-25.66], p < 0.001; UCLA aOR = 10.28, [6.91-15.30], p < 0.001).
Conclusions: Headache/migraine occurs at higher rates in individuals with autism and is associated with increased odds of negative SDoH and clinically relevant co-occurring illnesses. This study highlights the importance of migraine screening in individuals with autism. Future work is needed to understand the burden and impact of migraine in autism.
{"title":"Migraine prevalence and phenotype in autism: A retrospective cohort study using a US National Health Survey and large academic health system electronic health record.","authors":"Maria Pia Grant Tejada, Alexandra M Klomhaus, Rebecca Ortiz, Tristan D Tibbe, Sinifunanya E Nwaobi","doi":"10.1111/head.70035","DOIUrl":"https://doi.org/10.1111/head.70035","url":null,"abstract":"<p><strong>Objective: </strong>We analyzed data from both a national survey and a single hospital system to determine the prevalence of migraine in individuals with autism as well as identify sociodemographic and clinical characteristics associated with migraine in individuals with autism.</p><p><strong>Background: </strong>Few studies have examined the prevalence of migraine in autism and there are no studies examining the migraine phenotype and clinical features associated with migraine in autism.</p><p><strong>Methods: </strong>This retrospective cohort study used two databases-the National Survey of Children's Health (NSCH) and the University of California Los Angeles hospital system electronic health record (UCLA EHR). NSCH survey data from 2018, 2019, 2020, and 2021 (data collection period for each year is June to January; e.g., NSCH 2021 period is June 2021 to January 2022; N = 50,892) were queried to identify cohorts based on responses to two survey questions identifying the presence of frequent/severe headache and autism. For UCLA cohorts, patients (12/01/1979-4/16/2023, N = 4,334,162) were queried for migraine and autism based on the International Classification of Diseases diagnosis codes. We tested the hypothesis: Headache/migraine occurs more frequently in individuals with autism versus without autism. Variables including social determinants of health (SDoH) and co-occurring illnesses were compared between autism with versus without headache/migraine.</p><p><strong>Results: </strong>Headache and migraine prevalence was higher in individuals with autism versus those without (2021 NSCH-headache % [95% confidence interval {CI}], 7.1% [4.62-9.56] vs. 3.0% [2.62-3.19], p < 0.001 and UCLA-migraine: 3.1% [2.86-3.43] vs. 2.0% [1.97-1.99], p < 0.001). Among those with autism, the presence of headache/migraine was associated with increased odds of adverse childhood experiences such as bullying (NSCH-'Weekly/Almost daily' bullying aOR = 5.93 [2.01-17.50], p = 0.001, 'Never' reference) and being a victim of violence (NSCH-'Yes' aOR = 2.82, [1.19-6.66], p = 0.018), poor general health (NSCH-'Fair/Poor' health aOR = 9.68, [3.01-31.19], p < 0.001, 'Excellent' reference), mood disturbances, including anxiety (NSCH-'Yes' aOR = 4.50, [1.63-12.41], p = 0.004; UCLA aOR = 3.40, [2.78-4.17], p < 0.001), and depression (NSCH-'Yes' aOR = 5.70, [2.50-12.97], p < 0.001; UCLA aOR = 3.76, [3.08-4.60], p < 0.001), as well as increased rates of concussion (NSCH-'Yes' aOR = 9.05, [3.19-25.66], p < 0.001; UCLA aOR = 10.28, [6.91-15.30], p < 0.001).</p><p><strong>Conclusions: </strong>Headache/migraine occurs at higher rates in individuals with autism and is associated with increased odds of negative SDoH and clinically relevant co-occurring illnesses. This study highlights the importance of migraine screening in individuals with autism. Future work is needed to understand the burden and impact of migraine in autism.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"What's in the pipeline for pediatric headache treatment?","authors":"Amy A Gelfand, Christina L Szperka","doi":"10.1111/head.70037","DOIUrl":"https://doi.org/10.1111/head.70037","url":null,"abstract":"","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Benoit Gerard, Hubert Praudel, Michel Lanteri-Minet, Elise Van Obberghen, Fanny Rocher-Moreau, Johanna Rousset, Ulysse Jacquier, Sylvie Leroy, Margot Delin
Background: Eptinezumab is an anti-calcitonin gene-related peptide monoclonal antibody used for migraine prevention. During clinical trials, hypersensitivity to eptinezumab was described without a clear underlying mechanism. To determine if the reaction was immunoglobulin E-mediated, the team of Nice University Hospital (Nice, France) performed the eptinzeumab skin tests. A 10-step desensitization protocol has been proposed to manage these reactions.
Findings: Two patients presenting with immediate hypersensitivity reactions underwent the eptinezumab skin test. Neither skin test was positive, suggesting a non-immunoglobulin E-mediated mechanism. The patients then completed the desensitization protocol successfully.
Conclusion: This hospital-based 10-step desensitization protocol appears safe and effective.
{"title":"First successful protocol for desensitization to eptinezumab.","authors":"Benoit Gerard, Hubert Praudel, Michel Lanteri-Minet, Elise Van Obberghen, Fanny Rocher-Moreau, Johanna Rousset, Ulysse Jacquier, Sylvie Leroy, Margot Delin","doi":"10.1111/head.70000","DOIUrl":"https://doi.org/10.1111/head.70000","url":null,"abstract":"<p><strong>Background: </strong>Eptinezumab is an anti-calcitonin gene-related peptide monoclonal antibody used for migraine prevention. During clinical trials, hypersensitivity to eptinezumab was described without a clear underlying mechanism. To determine if the reaction was immunoglobulin E-mediated, the team of Nice University Hospital (Nice, France) performed the eptinzeumab skin tests. A 10-step desensitization protocol has been proposed to manage these reactions.</p><p><strong>Findings: </strong>Two patients presenting with immediate hypersensitivity reactions underwent the eptinezumab skin test. Neither skin test was positive, suggesting a non-immunoglobulin E-mediated mechanism. The patients then completed the desensitization protocol successfully.</p><p><strong>Conclusion: </strong>This hospital-based 10-step desensitization protocol appears safe and effective.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Migraine is a disorder of function: No evidence for structural alterations within the central nervous system in migraine.","authors":"Jan Mehnert, Adrian Scutelnic","doi":"10.1111/head.70010","DOIUrl":"https://doi.org/10.1111/head.70010","url":null,"abstract":"","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Keshet Pardo, Maor Mermelstein, Gal Tsur, Shlomit Yust-Katz
Background: Patients with obesity often experience stigma in healthcare, which may lead to underdiagnosis or undertreatment. In the context of pain management, and migraine specifically, patients with obesity are more likely to receive both opioid and non-opioid analgesics. However, little is known about their use of preventive treatments.
Methods: We conducted a large retrospective cohort study using propensity score matching for sex and age, utilizing data from the Clalit Health Services database in Israel. The study compared newly diagnosed patients with migraine with and without obesity, identified between June 2020 and June 2023. The comparison focused on prescriptions for migraine-specific acute medication (triptans) and preventive migraine treatments.
Results: Our final analysis included 11,934 patients with migraine and obesity and 11,934 without obesity. Patients with obesity were more likely to have cardiovascular risk factors and psychiatric comorbidities. Patients with obesity were also more likely to receive acute treatment with triptans (adjusted odds ratio [aOR] 1.17, 95% confidence interval [CI] [1.11-1.23]), and preventive treatments such as topiramate (aOR 1.66, 95% CI [1.38-1.99]), gabapentinoids (aOR 1.30, 95% CI [1.13-1.50]), and duloxetine (aOR 1.42, 95% CI [1.18-1.70]), adjusting for comorbidities.
Conclusion: Our findings do not support the notion that patient with migraine and obesity are undertreated; instead, they show a modest increase in prescriptions for acute and some of the preventive medications.
{"title":"Do patients with migraine and obesity receive different treatments? Insights from real-world data.","authors":"Keshet Pardo, Maor Mermelstein, Gal Tsur, Shlomit Yust-Katz","doi":"10.1111/head.70011","DOIUrl":"https://doi.org/10.1111/head.70011","url":null,"abstract":"<p><strong>Background: </strong>Patients with obesity often experience stigma in healthcare, which may lead to underdiagnosis or undertreatment. In the context of pain management, and migraine specifically, patients with obesity are more likely to receive both opioid and non-opioid analgesics. However, little is known about their use of preventive treatments.</p><p><strong>Methods: </strong>We conducted a large retrospective cohort study using propensity score matching for sex and age, utilizing data from the Clalit Health Services database in Israel. The study compared newly diagnosed patients with migraine with and without obesity, identified between June 2020 and June 2023. The comparison focused on prescriptions for migraine-specific acute medication (triptans) and preventive migraine treatments.</p><p><strong>Results: </strong>Our final analysis included 11,934 patients with migraine and obesity and 11,934 without obesity. Patients with obesity were more likely to have cardiovascular risk factors and psychiatric comorbidities. Patients with obesity were also more likely to receive acute treatment with triptans (adjusted odds ratio [aOR] 1.17, 95% confidence interval [CI] [1.11-1.23]), and preventive treatments such as topiramate (aOR 1.66, 95% CI [1.38-1.99]), gabapentinoids (aOR 1.30, 95% CI [1.13-1.50]), and duloxetine (aOR 1.42, 95% CI [1.18-1.70]), adjusting for comorbidities.</p><p><strong>Conclusion: </strong>Our findings do not support the notion that patient with migraine and obesity are undertreated; instead, they show a modest increase in prescriptions for acute and some of the preventive medications.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145756231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eric A Kaiser, Audrey Cavanah, Geoffrey K Aguirre, Frances E Jensen
<p><strong>Objective: </strong>The aim of this study was to determine the photoreceptor basis of light avoidance in mice and assess the effect of CGRP sensitization on this behavior.</p><p><strong>Background: </strong>Prior studies have suggested that photophobia is mediated by a subset of retinal ganglion cells (RGCs) that contain melanopsin, making them intrinsically photosensitive (ipRGCs). These cells also receive extrinsic input from cones, which can also mediate light sensitivity. Here, we examined how spectral targeting of melanopsin or specific cone types in mice produces light avoidance and whether sensitizing mice with calcitonin gene-related peptide (CGRP) amplifies the avoidance response to ipRGC stimulation.</p><p><strong>Methods: </strong>Light avoidance behavior was measured in a two-zone chamber illuminated by narrow-band light-emitting diodes (LEDs) targeting photopic opsins: 365 nm (ultraviolet [UV]; rodent S-cone), 460 nm (blue; melanopsin), and 630 nm (red; human L-cone). In a non-targeted assay, we assessed the degree of light avoidance in wild-type (WT) C57BL/6J mice to varying contrasts (0.05 to 1.00) of the blue and red LEDs. In a targeted assay, mice were exposed to zones with differing relative contrast levels (0.50, 0.75, or 1.00) for the targeted photoreceptor(s). This was assessed in transgenic mice with: (1) human L-cone cone knock-in (HLCKI) or (2) adult-onset ablation of M1 ipRGCs (Opn4<sup>aDTA</sup>). Mice were studied without intervention or following chronic intermittent administration of CGRP with either peripheral CGRP or vehicle (Veh) administration every-other-day for 9 days. A primary measure (mean +/- SEM) was the asymptote value (AV) of chamber preference.</p><p><strong>Results: </strong>WT mice showed greater light avoidance with increasing light contrast. HLCKI mice avoided zones with high melanopsin (1.00: 0.52 ± 0.08; n = 18) and L-cone (1.00: 0.30 ± 0.11; n = 15) stimulation but showed a preference for the zone with higher S-cone (1.00: -0.35 ± 0.06; n = 16) stimulation. These effects were contrast-dependent. The addition of S-cone stimulation reduced the aversive effect of melanopsin (0.10 ± 0.12; n = 14) or L-cone (-0.19 ± 0.10; n = 15) contrast. Ablation of ipRGCs in HLCKI x Opn4<sup>aDTA</sup> mice eliminated both avoidance of melanopsin stimulation and the preference for S-cone stimulation, as compared to controls. Nine days of chronic intermittent administration of CGRP led to significantly increased avoidance of melanopsin stimulation (0.58 ± 0.08, n = 21) as compared to Veh administration (0.26 ± 0.09, n = 22) (F (1, 41) = 5.70, p = 0.022).</p><p><strong>Conclusions: </strong>Our findings support a key role for the ipRGCs in the production of photophobia. This aversive response to light stems from integrated ipRGC signals that combine excitatory intrinsic melanopsin and extrinsic L-cone inputs and are opposed by extrinsic, inhibitory S-cone input. Chronic elevation of CGRP levels in migraine
{"title":"Amplifying and ameliorating light avoidance in mice with photoreceptor targeting and calcitonin gene-related peptide sensitization.","authors":"Eric A Kaiser, Audrey Cavanah, Geoffrey K Aguirre, Frances E Jensen","doi":"10.1111/head.70018","DOIUrl":"10.1111/head.70018","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to determine the photoreceptor basis of light avoidance in mice and assess the effect of CGRP sensitization on this behavior.</p><p><strong>Background: </strong>Prior studies have suggested that photophobia is mediated by a subset of retinal ganglion cells (RGCs) that contain melanopsin, making them intrinsically photosensitive (ipRGCs). These cells also receive extrinsic input from cones, which can also mediate light sensitivity. Here, we examined how spectral targeting of melanopsin or specific cone types in mice produces light avoidance and whether sensitizing mice with calcitonin gene-related peptide (CGRP) amplifies the avoidance response to ipRGC stimulation.</p><p><strong>Methods: </strong>Light avoidance behavior was measured in a two-zone chamber illuminated by narrow-band light-emitting diodes (LEDs) targeting photopic opsins: 365 nm (ultraviolet [UV]; rodent S-cone), 460 nm (blue; melanopsin), and 630 nm (red; human L-cone). In a non-targeted assay, we assessed the degree of light avoidance in wild-type (WT) C57BL/6J mice to varying contrasts (0.05 to 1.00) of the blue and red LEDs. In a targeted assay, mice were exposed to zones with differing relative contrast levels (0.50, 0.75, or 1.00) for the targeted photoreceptor(s). This was assessed in transgenic mice with: (1) human L-cone cone knock-in (HLCKI) or (2) adult-onset ablation of M1 ipRGCs (Opn4<sup>aDTA</sup>). Mice were studied without intervention or following chronic intermittent administration of CGRP with either peripheral CGRP or vehicle (Veh) administration every-other-day for 9 days. A primary measure (mean +/- SEM) was the asymptote value (AV) of chamber preference.</p><p><strong>Results: </strong>WT mice showed greater light avoidance with increasing light contrast. HLCKI mice avoided zones with high melanopsin (1.00: 0.52 ± 0.08; n = 18) and L-cone (1.00: 0.30 ± 0.11; n = 15) stimulation but showed a preference for the zone with higher S-cone (1.00: -0.35 ± 0.06; n = 16) stimulation. These effects were contrast-dependent. The addition of S-cone stimulation reduced the aversive effect of melanopsin (0.10 ± 0.12; n = 14) or L-cone (-0.19 ± 0.10; n = 15) contrast. Ablation of ipRGCs in HLCKI x Opn4<sup>aDTA</sup> mice eliminated both avoidance of melanopsin stimulation and the preference for S-cone stimulation, as compared to controls. Nine days of chronic intermittent administration of CGRP led to significantly increased avoidance of melanopsin stimulation (0.58 ± 0.08, n = 21) as compared to Veh administration (0.26 ± 0.09, n = 22) (F (1, 41) = 5.70, p = 0.022).</p><p><strong>Conclusions: </strong>Our findings support a key role for the ipRGCs in the production of photophobia. This aversive response to light stems from integrated ipRGC signals that combine excitatory intrinsic melanopsin and extrinsic L-cone inputs and are opposed by extrinsic, inhibitory S-cone input. Chronic elevation of CGRP levels in migraine","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145756199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rising together: Building the next generation of reviewers in headache medicine.","authors":"Nan Cheng, Risako Shirane, Patricia A Olson","doi":"10.1111/head.70022","DOIUrl":"https://doi.org/10.1111/head.70022","url":null,"abstract":"","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145756238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrew M Blumenfeld, Larry Charleston, Deena Kuruvilla, Belinda Savage-Edwards, Richard B Lipton, Ritu Singh, Patricia Jacob, Nicole A Lawrence, Cuiwei Wang, Hope L O'Brien
<p><strong>Objective: </strong>Examine treatment responses to and safety of onabotulinumtoxinA for the preventive treatment of chronic migraine (CM) among diverse racial groups.</p><p><strong>Background: </strong>Evidence suggests there are differences in headache treatment patterns, symptom profiles, and burden based on race. However, limited data are available describing the response to preventive migraine treatments among these groups.</p><p><strong>Methods: </strong>The Chronic Migraine OnabotulinuMtoxinA Prolonged Efficacy open Label (COMPEL) trial was a single-arm, open-label, multicenter, prospective study (January 23, 2012-November 16, 2015) that enrolled adults of various races with CM to receive onabotulinumtoxinA 155 U every 12 weeks over 108 weeks. These analyses assessed White, Asian (primarily Republic of Korea residents), and Black/African American subgroups based on self-report. Pacific Islander/American Indian/Alaska Native and Hispanic/Latinx subgroups were not analyzed separately because of the small sample sizes and potential overlap with predefined racial categories (e.g., Hispanic/Latinx White) for the latter. Analyses of baseline demographics and clinical characteristics, including headache features, across the subgroups were performed. Change from baseline in the number of monthly headache days (MHDs), including proportions with ≥50% reduction in MHDs, and change from baseline scores on the 6-item Headache Impact Test (HIT-6), Migraine Disability Assessment (MIDAS) absenteeism, presenteeism, and total scores, and Migraine-Specific Quality of Life questionnaire version 2.1 (MSQ v2.1) Role Function-Restrictive (RFR), Emotional Function (EF), and Role Function-Preventive (RFP) domains were evaluated for each subgroup.</p><p><strong>Results: </strong>Of 716 enrolled participants, 582 (81.3%) were White, 89 (12.4%) were Asian, 41 (5.7%) were Black/African American, and 4 (0.6%) were Pacific Islander/American Indian/Alaska Native. Withdrawal from the study occurred for 50.5% of the White subgroup, 32.6% of the Asian subgroup, and 48.8% of the Black/African American subgroup. The most common reasons for study discontinuation were participant withdrawal of granted consent (12.8%) and lost to follow-up (11.5%). After treatment with onabotulinumtoxinA 155 U every 12 weeks, all subgroups demonstrated significant reductions from baseline in MHDs at all time points to week 108 (all p < 0.001) and 60.3%-73.3% experienced ≥50% reduction from baseline in MHDs at week 108. Each analyzed subgroup demonstrated significant reductions from baseline to week 108 in HIT-6 total (all p < 0.001), MIDAS total (White, p < 0.001; Asian, p < 0.001; Black/African American, p = 0.0062), MIDAS absenteeism (White, p < 0.001; Asian, p < 0.001; Black/African American, p = 0.002), MIDAS presenteeism (all p < 0.001), MSQ v2.1 RFR (all p < 0.001), MSQ v2.1 EF (White, p < 0.001; Asian, p < 0.001; Black/African American, p = 0.009), and MSQ v2.1 RFP (all p < 0.00
{"title":"OnabotulinumtoxinA treatment among diverse racial groups: Post hoc analysis of the phase 4 Chronic migraine OnabotulinuMtoxinA Prolonged Efficacy open-Label (COMPEL) trial.","authors":"Andrew M Blumenfeld, Larry Charleston, Deena Kuruvilla, Belinda Savage-Edwards, Richard B Lipton, Ritu Singh, Patricia Jacob, Nicole A Lawrence, Cuiwei Wang, Hope L O'Brien","doi":"10.1111/head.70007","DOIUrl":"https://doi.org/10.1111/head.70007","url":null,"abstract":"<p><strong>Objective: </strong>Examine treatment responses to and safety of onabotulinumtoxinA for the preventive treatment of chronic migraine (CM) among diverse racial groups.</p><p><strong>Background: </strong>Evidence suggests there are differences in headache treatment patterns, symptom profiles, and burden based on race. However, limited data are available describing the response to preventive migraine treatments among these groups.</p><p><strong>Methods: </strong>The Chronic Migraine OnabotulinuMtoxinA Prolonged Efficacy open Label (COMPEL) trial was a single-arm, open-label, multicenter, prospective study (January 23, 2012-November 16, 2015) that enrolled adults of various races with CM to receive onabotulinumtoxinA 155 U every 12 weeks over 108 weeks. These analyses assessed White, Asian (primarily Republic of Korea residents), and Black/African American subgroups based on self-report. Pacific Islander/American Indian/Alaska Native and Hispanic/Latinx subgroups were not analyzed separately because of the small sample sizes and potential overlap with predefined racial categories (e.g., Hispanic/Latinx White) for the latter. Analyses of baseline demographics and clinical characteristics, including headache features, across the subgroups were performed. Change from baseline in the number of monthly headache days (MHDs), including proportions with ≥50% reduction in MHDs, and change from baseline scores on the 6-item Headache Impact Test (HIT-6), Migraine Disability Assessment (MIDAS) absenteeism, presenteeism, and total scores, and Migraine-Specific Quality of Life questionnaire version 2.1 (MSQ v2.1) Role Function-Restrictive (RFR), Emotional Function (EF), and Role Function-Preventive (RFP) domains were evaluated for each subgroup.</p><p><strong>Results: </strong>Of 716 enrolled participants, 582 (81.3%) were White, 89 (12.4%) were Asian, 41 (5.7%) were Black/African American, and 4 (0.6%) were Pacific Islander/American Indian/Alaska Native. Withdrawal from the study occurred for 50.5% of the White subgroup, 32.6% of the Asian subgroup, and 48.8% of the Black/African American subgroup. The most common reasons for study discontinuation were participant withdrawal of granted consent (12.8%) and lost to follow-up (11.5%). After treatment with onabotulinumtoxinA 155 U every 12 weeks, all subgroups demonstrated significant reductions from baseline in MHDs at all time points to week 108 (all p < 0.001) and 60.3%-73.3% experienced ≥50% reduction from baseline in MHDs at week 108. Each analyzed subgroup demonstrated significant reductions from baseline to week 108 in HIT-6 total (all p < 0.001), MIDAS total (White, p < 0.001; Asian, p < 0.001; Black/African American, p = 0.0062), MIDAS absenteeism (White, p < 0.001; Asian, p < 0.001; Black/African American, p = 0.002), MIDAS presenteeism (all p < 0.001), MSQ v2.1 RFR (all p < 0.001), MSQ v2.1 EF (White, p < 0.001; Asian, p < 0.001; Black/African American, p = 0.009), and MSQ v2.1 RFP (all p < 0.00","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145756266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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