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.

Nettle outperforms traditional treatments in clinical trials.

Below are the results from our WIND* trial, A Triple-Blind, Randomised Sham-Controlled Trial, that focused on three metrics: pain, mood, and average functionality or fitness status.

AFTER 30 Days*

100%

of users with severe low mood symptoms improved to moderate or mild low mood symptoms.

72%

of users reported clinically significant pain relief.

67%

of users reported a clinically significant improvement in their average functionality, or fitness status.

91%

of users reported Nettle was easy to integrate into their daily routine.

*Have a detailed look at our trial results here.

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. Edward Evantash

Chief Medical Officer

Edward Evantash is a highly experienced and accomplished professional in the medical field, having held various leadership positions in multiple companies. Prior to his current roles, Edward served as Medical Director and V.P. Global Medical Affairs at Hologic and held prominent positions at Tufts Medical Center.

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.

View all

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).

Read the paper

Safety of transcranial Direct Current Stimulation: Evidence Based Update 2016

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

Read the paper

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).

Read the paper

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

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

Read the paper

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

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

Read the paper

Premenstrual dysphoric disorder and changes in frontal alpha asymmetry

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

Read the paper

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

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

Read the paper

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 )

Read the paper

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)

Read the paper

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)

Read the paper

Blog

Learn more about the cycle brain connection

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

View all

November 6, 2024

The Neuroscience of Endometriosis

While traditionally viewed as a gynaecological disorder, recent research has revealed a deeper, more complex link between endometriosis and the brain.

November 6, 2024

The Neuroscience of  Perimenopause

While the clinical definition of perimenopause focuses on reproductive system changes, many of the symptoms are actually neurological, impacting mood, sleep, and cognition.

October 10, 2024

That Time of the Month

You know what we’re talking about—the days leading up to your period when you often feel low, irritable, and maybe find yourself arguing with your partner more.

August 23, 2024

The Hidden Game Changer

In recent years, a growing number of elite athletes have broken their silence about a topic long considered taboo in the world of sport - their menstrual cycles.

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...

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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.

The Cycle-Brain Connection

Three landmark studies that built Nettle

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

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

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

Real life stories from Nettle users

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

"Finally, something that worked for me."

Nettle outperforms traditional treatments in clinical trials.

100%

72%

67%

91%

Zero severe side effects reported.

Nettle Data

Historical Data

Our scientific experts

Built on verified science

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

Safety of transcranial Direct Current Stimulation: Evidence Based Update 2016

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

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

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

Premenstrual dysphoric disorder and changes in frontal alpha asymmetry

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

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

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

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

Feel Your Best in‍Every Phase