Patients in the probiotic group will take the supplement twice daily during the first seven days of chemotherapy and for seven days after each chemotherapy cycle. Researchers will collect biological samples to measure changes in the gut and vaginal microbiomes, immune function and reported symptoms. The randomized, placebo-controlled design is intended to separate effects associated with the probiotic from those of chemotherapy itself, although the release does not describe the trial’s masking procedures, primary endpoints, analysis plan or expected completion date. Researchers will also investigate associations between microbiome changes, treatment response and patient-reported outcomes, including fatigue and gastrointestinal symptoms.

The scientific rationale centers on the microbiome, the community of bacteria and other organisms living in the digestive tract. As described by Laura Chambers, DO, the clinical trial’s lead investigator and a gynecologic oncologist at the cancer center, cancer treatments can disrupt this microbial community and potentially contribute to side effects that affect how patients feel during therapy. The microbiome has roles in digesting nutrients, processing hormones, inflammation and immune function, but those general functions do not demonstrate that a particular commercial probiotic will improve chemotherapy tolerance. The trial therefore includes direct biological measurements and symptom assessments rather than relying only on changes in microbiome composition.

Probiotics and prebiotics are related but distinct interventions. Probiotics contain live microorganisms, while prebiotics are types of fiber that provide food for beneficial microbes. The Ohio State study specifically examines probiotic supplements, and the release does not report that participants will receive prebiotics. The supplements used in the trial are supplied at no cost by Pendulum Probiotics; Chambers reports no financial conflict with the manufacturer. Funding and research support come from the Ovarian Cancer Research Alliance Early Career Investigator Grant, the Doris Duke Charitable Foundation, the John Templeton Foundation and the Paul Calabresi Career Development Award for Clinical Oncology. The registered study is identified as NCT07144826. Patients interested in the trial can consult its ClinicalTrials.gov listing or contact the cancer center, and the investigators advise people receiving cancer treatment to speak with their care team before starting probiotics, prebiotics or other supplements.

Subject of Research: A randomized trial of probiotic supplementation during chemotherapy for advanced or recurrent ovarian cancer

Article Title: Can better gut health help patients with ovarian cancer tolerate chemotherapy?

Article References: Can better gut health help patients with ovarian cancer tolerate chemotherapy?. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: ovarian cancer, probiotics, gut microbiome, chemotherapy, clinical trials, placebo, treatment side effects, quality of life, immune function, cancer research, better, health

The intervention involved 84 women aged 18 to 26, with a mean age of 21.93, who were born between 1997 and 2006 and described themselves as feeling stressed or anxious. They were not diagnosed with a psychiatric condition, so the study did not evaluate a treatment for diagnosed anxiety disorder. Each morning for 28 days, participants took three capsules containing either 1.8 g of powdered Lion’s mane, 1.8 g of a blend containing 60% Lion’s mane and 40% Reishi, or placebo made from microcrystalline cellulose. The blend was standardized to 20% beta-glucans. Participants and the research team were kept unaware of treatment assignments during the study, while a separate research-centre director labelled the treatments and held the emergency code-break envelopes. A treatment-guess analysis found that participants were not significantly better at correctly identifying their assigned group than chance, including when active groups were combined and compared with placebo. Average compliance, calculated from returned capsules, was 96.7%.

The trial was preceded by a separate sort-and-rank study involving 38 women from the same target population. Participants ranked 54 statements derived from diagnostic criteria for acute stress disorder, generalized anxiety disorder, depressive disorders and attention-deficit hyperactivity disorder. Excessive anxiety and worry ranked highest, with 59.5% assigning the statement a score above +2 on the study’s 13-point scale, which represented placing an item among the 16 statements considered most important. Mental exhaustion, physical exhaustion, panic, overwhelming stress, worthlessness and low self-esteem also featured prominently. This formative phase was used to select outcome measures considered most relevant to participants, rather than leaving the trial’s targets entirely to investigators. It was a separate cohort, and its results informed measurement rather than contributing participants to the intervention comparison.

Anxiety measured by the GAD-7 was the prespecified primary outcome. Secondary measures included the anxiety subscale of the Hospital Anxiety and Depression Scale, the Perceived Stress Scale, a visual analogue scale for stress, the Chalder Fatigue Scale and Rosenberg’s Self-Esteem Scale. Participants completed full assessments at baseline and Day 28, shorter weekly questionnaires during treatment and an exploratory home assessment on Day 42, two weeks after supplementation ended. The statistical analysis used mixed models that included treatment, time, their interaction and baseline scores for the relevant outcome, with additional adjustment for baseline fruit and vegetable consumption, waist-to-hip ratio and visual analogue stress score. False-discovery-rate correction was applied across families of secondary outcomes to limit the chance of false positives. The main analysis followed the intention-to-treat population, which included participants according to their randomized assignments.

For the primary GAD-7 outcome, the researchers identified a main effect of treatment, meaning average anxiety scores differed among the three groups over the study as a whole. The mushroom blend averaged 6.49, lower than 7.76 for Lion’s mane alone, with p = 0.018 and a standardized effect size of 0.51. There was also a treatment-by-time interaction, for which p = 0.034. That interaction was most evident at the end of treatment: on Day 28, the blend group’s mean GAD-7 score was 4.16 versus 6.50 in the Lion’s mane group, with p = 0.003 and a standardized effect size of 0.94. These comparisons establish better performance than Lion’s mane alone for the primary outcome in this trial; they do not demonstrate superiority over placebo for that outcome at Day 28. The study therefore supports a treatment difference between the two active products without showing that every active product outperformed an inactive control on the primary endpoint.

Secondary results were less definitive. The treatment-by-time interaction for HADS anxiety initially met the conventional statistical threshold, at p = 0.023, but it did not remain significant after correction for multiple testing, which produced an adjusted q value of 0.072. Uncorrected post hoc comparisons favored the blend over Lion’s mane on Day 28 and over placebo on Day 42, the latter occurring two weeks after supplementation stopped. The PSS treatment interaction also fell from nominal significance, p = 0.036, to trend level after correction, again with q = 0.072. At Day 28, the blend group had a lower mean PSS score of 16.86 than both placebo, at 19.79, and Lion’s mane, at 19.35. These exploratory comparisons should not be treated as confirmatory evidence. No significant treatment effects were found for stress measured by the visual analogue scale, fatigue or self-esteem, and the trial therefore did not establish a broad pattern of supplement-specific benefits across every psychological measure.

All three groups improved over time, including the placebo group. Mean GAD-7 scores fell from 10.08 at baseline to 5.42 on Day 28 across all participants and were 6.12 on Day 42. Anxiety measured by HADS, stress measured by the PSS and visual analogue scale, and fatigue all declined, while self-esteem increased from a mean of 15.59 to 18.56 by Day 28. The broad pattern means that improvements seen within an active-treatment group cannot automatically be attributed to that supplement. The investigators identified expectancy, increased attention to wellbeing during repeated assessments, the structure of taking part in a trial and self-monitoring as possible contributors. The study measured no cortisol, inflammatory markers or other biological indicators that could help explain either supplement-specific or participatory effects. It therefore could not establish a biological pathway for the observed differences or determine whether the two mushrooms interacted in a way that produced the primary result.

Qualitative responses broadly paralleled the quantitative pattern. Participants in the Lion’s mane group more frequently reported “no change” in an analysis of their reasons for identifying their treatment, while the blend group more often reported mood improvement in exploratory comparisons. These observations were based on open-ended responses, coded independently by two researchers, and were not substitutes for the controlled questionnaire endpoints. The qualitative pattern adds context to the main result, but it came from multiple exploratory tests, and its interpretation should remain cautious. Notably, the study cannot determine whether Reishi enhanced Lion’s mane, acted independently or merely accompanied a different quantity of Lion’s mane. The Lion’s mane-only arm received 1.8 g of that mushroom, whereas the blend provided approximately 1.08 g of Lion’s mane plus 0.72 g of Reishi, and there was no Reishi-only arm. A dose-matched design would be needed to separate the contributions of the ingredients.

Safety findings were broadly reassuring but do not establish long-term safety. Participants reported 50 adverse events, involving 31 individuals. One participant discontinued because of a headache, but that person had received placebo. Statistical comparisons found no significant difference in adverse-event frequency among the three groups, including after false-discovery-rate correction. The overall pattern was consistent with good short-term tolerability in this sample, although the trial was not designed to detect rare events. Its four-week intervention also cannot address longer-term safety, optimal dose, supplement composition, bioavailability or the durability of any benefit. The intended sample of 135 was not reached because of recruitment challenges, leaving 84 participants and reducing confidence that subtler effects would have been detected. A post-hoc power calculation suggested high power for the observed primary interaction, but such retrospective calculations do not remove the uncertainty associated with an undersized trial.

The trial tested a specific Lion’s mane and Reishi blend rather than establishing that either mushroom was responsible for the primary result. Lion’s mane contains compounds such as hericenones and erinacines, while Reishi contains triterpenoids, including ganoderic acids, and polysaccharides such as beta-glucans. Preclinical research has proposed effects on nerve growth factor, brain-derived neurotrophic factor, neuroinflammation and inflammatory signaling, but the mechanisms underlying human mood effects remain unsettled, and results from earlier human studies have been inconsistent. The present trial also does not show that functional mushrooms broadly treat anxiety. Instead, it identifies a comparatively strong primary-outcome signal for one commercial blend in stressed or anxious young women without psychiatric diagnoses, while finding widespread improvement across all groups and weaker, multiplicity-adjusted evidence for other measures. Confirmatory trials would need dose-matched single-ingredient and combination arms, larger and more diverse populations, longer follow-up, biological measurements and assessment of whether the observed differences are large enough to matter outside a research setting.

Subject of Research: Four-week Lion’s mane and Reishi supplementation trial assessing anxiety, stress and wellbeing in young women.

Article Title: The effects of four-week supplementation of Lion’s mane and a Lion’s mane and Reishi blend on prioritised mood and wellbeing measures in young women

Article References: Smith, E. F., & Docherty, S. (2026). The effects of four-week supplementation of Lion’s mane and a Lion’s mane and Reishi blend on prioritised mood and wellbeing measures in young women. Frontiers in Nutrition, 13, Article 1887408. https://doi.org/10.3389/fnut.2026.1887408

Image Credits: AI Generated

DOI: 10.3389/fnut.2026.1887408

Keywords: Lion’s mane, Reishi, anxiety, young women, randomized trial, supplementation, mood, stress, placebo, wellbeing, effects, four-week

Insomnia is among the most common sleep disorders worldwide, and its consequences reach well beyond a rough morning. People with insomnia struggle to fall asleep, to stay asleep through the night, or to wake feeling genuinely refreshed, and the disorder can severely degrade quality of life. Perhaps most importantly, chronic insomnia leaves people substantially more vulnerable to developing anxiety and depression over time, making effective treatment a genuine public health priority. Existing options include cognitive behavioural therapy, which is often recommended as a first-line approach, alongside pharmacological treatments such as antidepressants and antipsychotics, but the success of these interventions varies considerably from patient to patient. It is against this backdrop of imperfect alternatives that interest in medical cannabis has surged.

In clinical settings, medical cannabis is not the same product that consumers encounter in dispensaries. Prescribed cannabis medicines typically involve controlled, laboratory-tested ratios of the two best-known cannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD), delivered in standardised forms such as tablets, sprays or oils. This standardisation is intended to give clinicians predictable doses and compositions. Anecdotal reports and marketing have long touted cannabis as a sleep aid, and the drug’s sedating reputation has made it an appealing candidate for people desperate for rest. Yet the use of medical cannabis for insomnia remains contentious among sleep researchers and clinicians, and the formal evidence base has been thin.

To resolve that uncertainty, the review team systematically assembled the available randomised evidence. The review included nine studies involving 537 adults aged 18 to 76 who were treated for insomnia. Most of the studies focused on people with primary insomnia rather than insomnia linked to other health conditions, a distinction that matters because comorbid insomnia is often harder to treat and mechanistically different. Eight of the nine trials compared regulated medical cannabis against a placebo, the gold-standard design for determining whether a treatment outperforms expectation effects. The ninth trial took a different approach, comparing medical cannabis against amitriptyline, an antidepressant with sedating properties that is sometimes used off-label for sleep.

The headline result is stark in its modesty. Medical cannabis showed little to no clinically meaningful improvement in sleep quality and satisfaction, total sleep time, or daytime functioning compared with placebo. In other words, on the outcomes that matter most to patients with insomnia, how well they slept and how they functioned during the day, the drug did not demonstrate a clear advantage over an inert comparison. For a treatment whose reputation rests almost entirely on its perceived sleep benefits, this is a significant setback, and it suggests that the anecdotes driving cannabis’s popularity may not survive the scrutiny of controlled trials.

Safety signals added further concern. Participants taking medical cannabis were substantially more likely to experience mild adverse events, such as dry mouth and dizziness, than those receiving placebo. These effects are not dangerous in the way that some drug side effects can be, but they are not trivial for patients weighing whether a treatment is worth taking. Importantly, the review authors note that this safety conclusion was based on a small pool of studies, which means the true rate of adverse events remains imperfectly characterised. Even so, a treatment that shows no clear benefit while increasing the likelihood of side effects faces an unfavourable risk-benefit calculus.

There was one apparent bright spot: medical cannabis somewhat improved quality of life in the pooled analyses. But the reviewers urge heavy caution here. The certainty of this finding was rated very low, and the pooled results were compatible with anything from a slight worsening to a large improvement. That enormous range of plausible effects is a hallmark of unreliable evidence, and it means patients and clinicians cannot reasonably conclude from this dataset that cannabis genuinely enhances quality of life for people with insomnia. The finding is best read as a signal of what better-designed trials might one day examine, rather than as a positive result in its own right.

Why is the evidence so shaky? The review team graded the overall quality and certainty of the evidence as very low to low, and the reasons are instructive for anyone trying to interpret medical research headlines. The underlying studies carried a high risk of bias, meaning flaws in their design or conduct may have distorted their results. Findings were inconsistent between trials, making it hard to generalise from any single study. Sample sizes were small, with the entire review resting on 537 participants across nine trials. The studies also varied considerably in the type of cannabis product used, which limited comparability across trials, since different formulations, cannabinoid ratios and delivery methods can plausibly produce different effects. Perhaps most limiting of all, the longest study followed participants for only 12 weeks, leaving the long-term effects of cannabis treatment for insomnia essentially unknown.

There is also a representativeness problem that the reviewers highlight. The available data were heavily skewed towards younger people and women, who made up 72.66 percent of participants. As a result, the findings may not apply as well to men, to older adults, or to people with comorbid health conditions, groups that represent a large share of real-world patients seeking treatment for sleep problems. Clinicians hoping to use this evidence to guide prescribing for an older patient with multiple health issues will find that the trials simply did not include enough people like them to say anything confident. This gap between trial populations and clinical populations is a recurring weakness in cannabis research, and it is one the review makes impossible to ignore.

The authors’ conclusion is measured but firm: the evidence remains weak and uncertain, and higher-quality research is needed before medical cannabis can be recommended for insomnia. Dr Lucia Varela, lead author of the study from the University of Manitoba in Canada, emphasised that the research currently available is not sufficient to reliably answer whether medical cannabis helps people with insomnia, adding that this does not mean the treatment is ineffective, but that based on current evidence no reliable conclusions about its effectiveness can be drawn for the general population. Dr Luis Garegnani, senior author from the Universidad Hospital Italiano de Buenos Aires in Argentina, advised that rather than viewing the findings as an endorsement or a rejection of medical cannabis, clinicians and patients should recognise the uncertainty and consider individual circumstances while better evidence is generated. All authors declared no commercial or non-commercial conflicts of interest relevant to the review. For now, the message for the millions of people struggling with sleepless nights is not that cannabis cannot work, but that no one yet knows whether it does, and the only honest response to that uncertainty is more rigorous science.

Subject of Research: Medical cannabis as a treatment for insomnia

Article Title: Insufficient evidence to back medical cannabis for insomnia

Article References: Insufficient evidence to back medical cannabis for insomnia. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: medical cannabis, insomnia, Cochrane review, sleep quality, THC, CBD, systematic review, placebo, evidence quality, sleep disorders, clinical trials, daytime functioning

An international team led by Stefan Zielen of Goethe University Frankfurt has now reported the results of the TIPP trial, the first study to evaluate a full year of tiotropium treatment as an add-on to inhaled corticosteroids in children aged one to five with severe, partially controlled or uncontrolled preschool asthma. The trial was investigator-initiated and funded by the German Federal Ministry of Education and Research, with Boehringer Ingelheim supplying medication but having no role in design, analysis, or reporting. Published in eClinicalMedicine, the phase III, multicentre, randomised, double-blind, placebo-controlled study enrolled children at twelve German hospitals and one specialised practice. To qualify, each child must have experienced at least one severe exacerbation requiring hospitalisation or at least two courses of systemic corticosteroids in the preceding two years, and their asthma had to remain partly controlled or uncontrolled despite at least four weeks of inhaled corticosteroid therapy, according to Global Initiative for Asthma criteria.

The design was deliberately conservative. Children received two puffs of 1.25 micrograms of tiotropium, a total daily dose of 2.5 micrograms, delivered by Respimat soft-mist inhaler with a spacer and mask, or an identical placebo, once daily for 52 weeks. The dose was chosen from earlier paediatric data showing that both 2.5 and 5 micrograms were well tolerated in this age range, with the lower dose preferred for prolonged use. Of 100 children screened, 86 were randomised, 44 to tiotropium plus inhaled corticosteroids and 42 to placebo plus inhaled corticosteroids. Randomisation used permuted blocks stratified by site, generated independently at the Interdisciplinary Centre for Clinical Trials in Mainz, and everyone involved—families, clinicians, and analysts—remained blinded throughout. Caregivers logged symptoms daily through a purpose-built smartphone diary, and visits at weeks 6, 16, 28, 40, and 52 tracked height, weight, spirometry in children old enough to cooperate, and a battery of immunological markers including total IgE, eosinophil counts, and allergen-specific IgE.

The cohort itself tells a story of how severe preschool asthma really is. The children, with a mean age of 3.3 years, had experienced a median of 3.5 severe exacerbations in the year before enrolment. Eighty-six percent reported daytime symptoms, 78 percent suffered nocturnal awakenings, and 65 percent met the definition of uncontrolled asthma despite a heavy background of controller medication: 52 percent were already on inhaled corticosteroids plus a long-acting beta agonist, and another 14 percent were on that combination plus a leukotriene receptor antagonist. Bronchitis, cough, and respiratory infections dominated the symptom landscape, as they do in real-world clinics. Recruitment, however, proved punishing. The original plan called for 204 children, later revised to 152, but pandemic-era reductions in acute presentations, a brutal influenza and respiratory syncytial virus season in late 2022, and Germany’s high standard of fully insured routine care left the team with 100 screened patients. The authors candidly attribute part of the shortfall to inconsistent nomenclature—many of these children are labelled with recurrent obstructive bronchitis rather than asthma and are treated in family practices rather than specialist centres.

The primary result was unambiguous in its null finding. Time to first severe exacerbation—defined as hospitalisation, at least three days of systemic steroids, or one day of rectal prednisolone—was statistically indistinguishable between groups, with a hazard ratio of 0.99 and a confidence interval spanning unity. A model for recurrent severe exacerbations reached the same conclusion. The secondary endpoints followed suit: severe exacerbations per patient-year (0.8 versus 1.1), hospitalisations, systemic steroid rescue, salbutamol use, symptom-free days, physician visits, missed daycare days, antibiotic prescriptions, lung function, and biomarker-based subgroups all failed to separate the treatments. Younger children, aged one to three, fared worse than four-to-five-year-olds regardless of treatment, with a significantly higher rate of mild exacerbations—an age effect, the authors stress, not a treatment interaction.

Two exploratory signals flickered at the margins. Caregivers using the electronic diary reported fewer night-time awakenings in the tiotropium group, a median of 5 percent of nights versus 9 percent, a nominally significant difference the authors insist requires confirmation in adequately powered trials with multiplicity control. And in a post-hoc analysis, the median time to first exacerbation of any severity was longer with tiotropium, 61 days versus 35 days, yielding a nominal hazard ratio of 0.60—yet the corresponding log-rank test was not significant, and the investigators rightly decline to claim efficacy from exploratory statistics. Spirometry, restricted to the minority of children aged four and older who could perform acceptable manoeuvres, showed a numerical average FEV1 gain of 131 millilitres at week 24 in the tiotropium arm, a clinically relevant magnitude echoing findings in older children, but the difference did not reach statistical significance in the small subgroup.

What the trial did deliver was reassurance on safety. Eighty-three of the 86 children experienced at least one adverse event, a total of 847, ranging from nasopharyngitis and bronchitis to pneumonia—unsurprising in a cohort of wheezing toddlers followed through a full year of respiratory-virus seasons. Crucially, the distribution was balanced, and if anything favoured tiotropium: upper respiratory infections and pneumonia were both more frequent in the placebo group, and none of the severe adverse events were judged causally related to the study drug. No new safety signals emerged, consistent with the established tolerability profile of tiotropium in paediatric populations. For a medication acting on muscarinic receptors in very young airways, this absence of harm carries genuine weight, even in the absence of demonstrated benefit.

The authors place their null result in context with an honest accounting of limitations. The trial was substantially underpowered relative to its original ambition; the sample size calculation assumed 90 percent of placebo children would suffer a severe exacerbation within a year against 75 percent on tiotropium, and the smaller-than-planned cohort eroded precision for the primary endpoint and especially for secondary and subgroup analyses. No correction for multiple testing was applied, so the nominally significant secondary findings must be read as exploratory. Preschool asthma is phenotypically heterogeneous, and heterogeneous background therapy may have diluted any true treatment effect. Lung function data were confined to a small, older subset, and the sample was far too small to detect rare adverse events. Still, the investigators argue that adequately powered studies, not dismissal, are the appropriate response to these data.

For clinicians and families, the practical message is measured. Tiotropium cannot currently be recommended as routine add-on therapy for preschool children with partially controlled or uncontrolled asthma on inhaled corticosteroids; the evidence is simply insufficient to support that step. But neither has it been excluded as potentially helpful in a suitably selected subgroup. The trial underscores a broader and uncomfortable truth: children under five with severe asthma remain one of the most under-evidenced populations in respiratory medicine, where diagnostic inconsistency, licensing gaps, and recruitment difficulties converge to leave treatment decisions resting on extrapolation from older children. TIPP, despite its underpowered outcome, has mapped that terrain carefully—establishing feasibility of a year-long placebo-controlled inhaler trial in toddlers, confirming safety, and defining the exacerbation-prone phenotype that future studies must target. Until adequately powered trials arrive, the standard armamentarium of inhaled corticosteroids, careful trigger management, and vigilant exacerbation planning remains the best available defence for these smallest patients.

Subject of Research: A phase III randomised trial of tiotropium add-on therapy for preschool children with partial or uncontrolled asthma

Article Title: Efficacy and safety of tiotropium in partial and uncontrolled preschool asthma (TIPP): a phase III, multicentre, randomised, double-blind, placebo-controlled trial

Article References: Zielen, S., Wollscheid, N., Nickolay, T., Grimmel, C., Scheele, D., Sattler, F., Prenzel, F., Lorenz, M., Schaub, B., Lex, C., Stieglitz, F., Trischler, J., Donath, H., Lau, S., Hamelmann, E., Vogelberg, C., Gerstlauer, M., Grychtol, R., Schubert, R., … Wosniok, J. (2026). Efficacy and safety of tiotropium in partial and uncontrolled preschool asthma (TIPP): a phase III, multicentre, randomised, double-blind, placebo-controlled trial. eClinicalMedicine, 99, Article 104172. https://doi.org/10.1016/j.eclinm.2026.104172

Image Credits: AI Generated

DOI: 10.1016/j.eclinm.2026.104172

Keywords: preschool asthma, tiotropium, long-acting muscarinic antagonist, inhaled corticosteroids, severe exacerbations, phase III trial, Respimat, paediatric pulmonology, randomised controlled trial, asthma control, placebo, drug safety