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Science, not promises

The human brain is an enigma. As neuroscientists, we are in awe of its capabilities to help us lead healthier lives. Our research is a testament to our dedication to helping you both understand and unlock your brain's full potential.

DISCLAIMER

Throughout our communications, we use the word women to include all people experiencing menstrual-related issues, including but not limited to all people assigned female at birth.

The Cycle-Brain Connection

We now know that throughout a woman's menstrual cycle, hormonal fluctuations significantly impact the brain's structure, function, and plasticity. During the follicular phase, rising oestrogen levels enhance cognitive abilities, particularly in verbal and social domains. At ovulation, both oestrogen and testosterone peak, boosting performance and libido. The luteal phase sees an increase in progesterone and a decline in oestrogen, often triggering premenstrual syndrome (PMS) symptoms, which may necessitate additional support.

Recent research underscores the impact of hormones on the brain: oestrogen is linked to enhanced neuronal plasticity, as well as a boost in the neurotransmitter serotonin. Progesterone, on the other hand, influences amygdala reactivity, which can affect anxiety and mood. It also impacts levels of gamma-aminobutyric acid (GABA), a neurotransmitter that generally has a calming effect but can be associated with mood imbalances. Although not all mechanisms are fully understood, this emerging research is crucial for understanding that dynamic changes do occur in the brain across different menstrual cycle phases.

It was clinical research exploring the connection between the menstrual cycle and the brain that made us ask ourselves: why aren’t we addressing menstrual symptoms at the level of the brain?

Three landmark studies that built Nettle

Nettle is founded on over 30 years of clinical research into its underlying technology transcranial direct current stimulation (tDCS) in the areas of chronic pain and depression treatment. In 2020, our research collaborators applied this technology to address menstrual symptoms related to pain and mood. Since then, we have conducted our own clinical trials, which examine the impact of targeted tDCS on both pain and mood symptoms.

L Dutra et al, International Journal of Women's Health (2020)

Modulating Anxiety and Functional Capacity with Anodal tDCS Over the Left Dorsolateral Prefrontal Cortex in Primary Dysmenorrhea

The purpose of this trial was to examine the impact of transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex (DLPFC) on anxiety and functionality in patients with primary dysmenorrhea. The study demonstrated significant improvement in mood for 84% of users, concluding that tDCS appears to be an effective therapeutic approach for improving anxiety and functionality in women with primary dysmenorrhea.

R Pegado, et al., Pain Medicine (December, 2020)

Effects of Transcranial Direct Current Stimulation for Treatment of Primary Dysmenorrhea: Preliminary Results of a Randomized Sham-Controlled Trial

The purpose of this trial was to explore the impact of transcranial direct current stimulation (tDCS) targeting the motor cortex (M1) on pain, mood, and physical performance in patients with primary dysmenorrhea (PDM). Over the course of one week, non-invasive brain stimulation (tDCS) reduced pain symptoms in 89% of participants, offering preliminary evidence of tDCS's potential in managing menstrual pain.

E Radytė et al., Preprint (February, 2024)

Modelling and Preliminary Clinical Validation of Home-based Menstrual Neuromodulation Therapy

Our study with Nettle measured the impact of brain stimulation on both pain and mood symptoms by targeting both the M1 and DLPFC during the five sessions our users underwent. In just one month’s use Nettle, results showed a 53% reduction in pain, a 34% improvement in mood, and an 11% improvement in function. This lays the groundwork for further research into Nettle, particularly  over a three-month period, during which we anticipate further  improvements in symptoms due to neuroplasticity effects.

Real life stories from Nettle users

Nettle was built with the participation of over 100 women in clinical and usability trials. Hear their stories in their own words.

Meet Divya*

"I feel a lot more in control, after just one month."

One of Nettle's first users, Divya experienced severe mood fluctuations before her period. A few years ago, she recognised that her symptoms resembled depression and sought treatment, but traditional methods were less effective than she had hoped. Since using Nettle, she reports a significant calming of the chaos she used to experience.

Meet Abby*

"Finally, something that worked for me."

One of our early usability trial participants, Abby struggled with debilitating period pains and anxiety for as long as she can remember. She tried birth control and over-the-counter painkillers but found that the former worsened her condition, while the latter provided only temporary relief.

* Real testimonies from real users, their names have been changed to protect their privacy.
Our science validates that Nettle is a safe and highly effective alternative, offering numerous advantages over traditional treatments.

Below are the results from our clinical trial, a Triple-Blind, Randomised Sham-Controlled Trial, that focused on three metrics: pain, mood, and function or the ability to perform everyday tasks. In just one month’s of use each symptom improved by:

53%

Pain

The average reduction in menstrual pain was 53%. This decrease continued over time, suggesting that the most significant reduction could be expected after 3 months of consistent use. Remarkably, over 44% of women reported minimal period pain (rated under 2 out of 10) after just one month of using Nettle. For comparison, painkillers typically only reduce pain by 45-53% on average¹, and it's estimated that at least 18% of women obtain no relief from NSAIDs².

34%

Mood

During the PMS period, the average symptoms of low mood improved by 34%. Impressively, 100% of users with extremely severe low mood symptoms (PANAS score above 25) reported a shift to moderate or mild symptoms after just one month of using Nettle. Furthermore, the relief from low mood symptoms extended for an additional month after discontinuation of Nettle, indicating potential long-term improvements with continued use.

11%

Function

The average functionality, or fitness status, improved by 11%. This improvement is primarily attributed to reductions in pain and anxiety, as well as enhancements in mood, which collectively lead to increased activity levels. These benefits were directly associated with the use of Nettle and tended to diminish during the follow-up period, suggesting they are not directly brain-based effects but rather secondary effects of improvements in overall brain health and plasticity.

Zero severe side effects reported.

While Nettle may take time to reach it’s full effect (most users will feel its full effect after 3 months of consistent use), this natural approach is proven to not only yield longer-term results but also come with zero severe side effects.

Nettle Data

In real-life data with our early users the most commonly reported side effect was mild tingling during sessions which subsided shortly after.

Historical Data

A 2020 study that is a review of over 2,000 tDCS sessions found side effects to be mild, transient and well-tolerated.

Meet

Our scientific experts

Dr. Sanjula Dhillon Singh
Neurosurgeon

Neurosurgeon focused on global public health. Also the founder of the podcast called ‘Science with Sanjula’ where she interviews world-leading scientists about big issues in global healthcare. She is helping Samphire translate our science into public impact.

Professor Maria Theresa Micussi
Women’s Health Researcher

Researcher from Universidade Federal do Rio Grande do Norte focused on neglected women's health conditions. Responsible for running Samphire's clinical trials.

Professor Rodrigo Pegado
Chronic Pain Expert

World-leading chronic pain researcher from Universidade Federal do Rio Grande do Norte. He was the first person in the world to publish a paper on the topic of tDCS to treat pain in dysmenorrhea (menstrual pain).

Dr. Marie Christine Nizzi
Psychologist and Researcher

Pyschologist and world-leading researcher on innovative clinical interventions. Currently the president of Harvard Alumni for Mental Health and is responsible for developing Samphire's cognitive science-based interventions.

Professor David Silbersweig
Professor of Neuropsychiatry

Professor of Neuropsychiatry at Harvard and global PMDD neuroanatomy expert. He worked on one of the first pieces of research that showed that PMDD is a neurobiological condition, which laid the foundation for PMDD being recognised by the International Classification of Diseases.

Dr. Shazia Malik
Chief Medical Advisor

A highly qualified and experienced Consultant Obstetrician and Gynaecologist, with subspecialty accreditation in Reproductive Medicine and Surgery. She brings invaluable expertise in chronic gynaecological conditions like endometriosis and PCOS, and is supporting our clinical efforts to advance medical research in the UK.

Built on verified science

Nettle was built on over 30 years of research in the fields of chronic pain and depression management. Have a look at some of the key papers that validate our technology.

Transcranial direct current stimulation to reduce chronic pelvic pain in endometriosis: Phase II Randomized Controlled Clinical Trial

S Mechsner, et al., Pain Medicine (March, 2023).

Safety of transcranial Direct Current Stimulation: Evidence Based Update 2016

M Bikson, et al., Brain Stimulation ( 2016 ).

Development and testing of a novel IoT consumer tDCS device for the treatment of primary dysmenorrhea

E Radyte, et al., Brain Stimulation Journal (January, 2023).

Depression, anxiety, stress, and dysmenorrhea: a protocol for a systematic review

AH Pakpour et al., Systematic Reviews (March, 2020).

Altered cognitive control network mediates the association between long-term pain and anxiety symptoms in primary dysmenorrhea

Z Yu et al., NeuroReport (January, 2024).

Premenstrual dysphoric disorder and changes in frontal alpha asymmetry

E Baehr et al., International Journal of Psychophysiology (2004).

Modelling and Preliminary Clinical Validation of Home-based Menstrual Neuromodulation Therapy

E Radytė et al., Preprint (February, 2024)

Evidence-Based Guidelines and Secondary Meta-Analysis for the Use of Transcranial Direct Current Stimulation in Neurological and Psychiatric Disorders

F Fregni, et al., International Journal of Neuropsychopharmacology ( April, 2021 )

Effects of Transcranial Direct Current Stimulation for Treatment of Primary Dysmenorrhea: Preliminary Results of a Randomized Sham-Controlled Trial

R Pegado, et al., Pain Medicine (December, 2020)

Modulating Anxiety and Functional Capacity with Anodal tDCS Over the Left Dorsolateral Prefrontal Cortex in Primary Dysmenorrhea

L Dutra et al, International Journal of Women's Health (2020)

Join our waitlist to get early access to Nettle

Nettle launches summer 2024. Waitlist members will receive early access to our releases and exclusive offers. Keep an eye on our newsletter for the latest updates on our clinical trials and neuroscience content.

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Blog

Learn more about the cycle brain connection.

Explore our blog where we break down neuroscience, menstrual health, and the cycle-brain connection.

March 20, 2024

The Menstrual Pain-Brain Connection

Pain is not just a symptom. It's a complex experience deeply influenced by biological, psychological, and social factors. Pain is also notoriously difficult to measure - and...
February 26, 2024

Neuroplasticity as a tool for optimising menstrual health

For centuries, the prevailing belief was that the adult brain was immutable to change. The concept of neuroplasticity—the brain's ability to change functionally or structurally...
November 16, 2023

Will Neuroimaging Revolutionise the Diagnosis of PMDD?

Despite its impact, it takes an average of 20 years for women to be accurately diagnosed with PMDD. The diagnosis is fraught with unique challenges, which include...
October 30, 2023

Periods, Productivity, and the Path to Progress

The statistics are glaring: menstrual symptoms undeniably influence productivity. However, while these numbers are revealing, capturing the full spectrum of menstrual symptoms...
October 17, 2023

The Problem with Painkillers: They Weren't Made for Women

Over 90% of women continue to grapple with menstrual cramps using an unevolved, 1980s-era solution: over-the-counter (OTC) painkillers. This makes even less sense when you look...
September 29, 2023

Women with severe PMS and PMDD experience depression-like symptoms every month

An increasing number of clinical studies are examining the brain in relation to the menstrual cycle, with a particular focus on women with severe PMS symptoms or Premenstrual...
Blog

Learn more about the cycle brain connection.

Explore our blog where we break down neuroscience, menstrual health, and the cycle-brain connection.

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11 Jan 2022
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11 Jan 2022
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Women with severe PMS and PMDD experience depression-like symptoms every month

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11 Jan 2022
5 min read
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The Problem with Painkillers: They Weren't Made for Women

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11 Jan 2022
5 min read
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Periods, Productivity, and the Path to Progress

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11 Jan 2022
5 min read
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Will Neuroimaging Revolutionise the Diagnosis of PMDD?

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11 Jan 2022
5 min read
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Neuroplasticity as a tool for optimising menstrual health

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11 Jan 2022
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The Menstrual Pain-Brain Connection

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11 Jan 2022
5 min read