NERVANA
Natural Nerve Analgesic
DIETARY SUPPLEMENT FORMULATED WITH
ACMELLA OLERACEA AND BOSWELLIA SERRATA
ADD-ON FOR CHRONIC AND RECURRENT PAIN
Moh. n. 149245 It. Patent number 102020000024217
STUDI CLINICI
Leggi
PAIN
“Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage.”
International Association for the Study of Pain - IASP
1
NOCICEPTIVE (Peripheral)
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Inflammation or tissues damage
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NSAIDs and opioids are effective
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Other treatments may also be
Examples
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Tendinitis
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Epicondylitis
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Osteoarthritis
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Bursitis
2
NEUROPATHIC
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Damage or disease affecting peripheral nerves and/or the central nervous system
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(hyperalgesia/allodynia)
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Drug therapies can be effective with both peripheral and central mechanisms of action: Gabapentinoids, antidepressants (tricyclics – SSRIs), anesthetics, opioids
Examples
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Low back pain
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Pudendal neuropathy
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Vestibulodynia, vulvodynia
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Neuropathic tendinitis
3
NOCIPLASTIC
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Abnormal processing of pain signals without evident tissue damage or underlying pathology.
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Neuroleptics can be effective as they modulate neurotransmitter levels involved in pain transmission.
Example
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Primary dysmenorrhea
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Pelvic pain Fibromyalgia (including fibro fog)
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Irritable bowel syndrome (IBS)
PAIN CATEGORIES
The boundaries between different types of pain are not always clear and often overlap.
That is why it is described as mixed pain, representing a combination of several pain types (nociceptive, neuropathic, and nociplastic).
Chronic pain is widely sustained by plastic changes related to the somatosensorial system: from nociceptor, to spinal cord, cortical and subcortical nuclei.
Low Back Pain
Neck pain
Tendinitis/bursitis
Osteoarticular pain
Dysmenorrhea
Vulvodynia
Pudendum neuropathy
Pelvic chronic pain
Fibromyalgia
Endometriosis
Chronic pain is approximately six times more prevalent in women than in men.
(Fillingim et al., 2009; Mogil, 2012).
Nervana is a dietary supplement that may be useful as an adjunct to pharmacological therapy prescribed by a doctor for the long-term management of chronic, nociplastic, or recurrent neuropathic pain.
STRENGTHENING SYNERGISM
SPILANTHOL
FROM ACMELLA
Spilanthol is an active compound extracted from Acmella oleracea, also known as Brazilian Jambù.
The Acmella used in Nervana® is cultivated in Sardinia to ensure the absolute absence of pesticides and full control over the supply chain.
BOSWELLIC ACIDS
FROM BOSWELLIA
Boswellia serrata, also known as frankincense (one of the gifts of the Magi), grows in India and the Himalayan region.From the trunk of the Boswellia tree, a gum resin is extracted, rich in boswellic acids, tetracyclic triterpenic acids, and polysaccharides with anti-inflammatory properties.
Spilanthol from Acmella oleracea
Mechanical nociceptive threshold in SNI (spared nerve injury) mice, measured in the ipsilateral paw to the lesion (expressed as applied force in grams), following a single injection of different doses of vehicle or Acmella oleracea.
ACMELLA PAIN RELIEF EFFECT
Boswelic acids from Boswellia serrata
Mechanical nociceptive threshold in SNI (spared nerve injury) mice, measured in the ipsilateral paw to the lesion (expressed as applied force in grams), following a single injection of different doses of vehicle or Boswellia serrata.
BOSWELLIA PAIN RELIEF EFFECT
Acmella is grown in Sardinia, to guarantee the absolute absence of pesticides and a complete control of the supply chain.
ACMELLA + BOSWELLIA = NERVANA
Synergistic effect
Dose reduction:
Acmella from 300mg/kg to 29,37mg/kg
Boswellia from 50mg/kg to 17,75mg/kg
Mechanical nociceptive threshold of the ipsilateral paw in SNI mice (expressed as applied force in grams) following a single administration of vehicle or AO + BS at increasing doses.
Additionally, the percentage of maximum possible effect (%MPE) on the mechanical nociceptive threshold of the paw ipsilateral to the lesion was measured after repeated administrations of a single dose of AO + BS (29.37 + 17.75 mg/kg), 60 minutes post-administration.
STRENGTHENING SYNERGISM
EXPONENTIAL ANALGESIA
REDUCED DOSAGES
IMPROVED SAFETY
Boccella et al. Phytotherapy Research 2023
ABSORPTION TECHNOLOGY
Optimizes the bioavailability of phytonutrients.
The boswellic acids complex is delivered through Fitosome® technology, developed by Indena, which ensures bioactivity and enhances the absorption of natural components, while maintaining the proper balance between hydrophilicity and lipophilicity.
The most important feature is not the quantity of the active ingredient consumed, but the optimization of its absorption, allowing the natural ingredients to exert their full potential benefits.
Spilanthol alkamides are formulated with cyclodextrins, cyclic oligosaccharides that facilitate the faster delivery of the compound within the body.
STRENGTHENING SYNERGISM
AND INVERSION SYNERGISM:
More active ingredients do not necessarily mean greater efficacy!
Acmella and Boswellia, when administered alone, exert an anti-allodynic effect similar to other botanicals.
The activity of a botanical extract is often due to the synergistic pharmacological activity of the active ingredients present in the phyto-complex, often described as the entourage effect.
Nervana® is exclusively made with dry extracts standardized and titrated from Acmella oleracea and Boswellia serrata, components which, when administered simultaneously, are able to develop a real strengthening of synergistic effects.
The synergism has been demonstrated by means of an isobolographic approach, which first requires the identification of the effective dose 50 (ED50) of the individual components and subsequently combines the ED50 of each component with progressively lower doses of the other.
The fixed combination that has demonstrated synergistic strengthening has been chosen for the development of the formulation.
Different active ingredients can counteract each other's effects.
This mechanism does not apply to all active ingredients or concentrations. Instead, when actives are at incorrect concentrations or co-administered with other substances, they may compete, generating the so-called inversion synergism, which in some cases can completely nullify the effects of individual components.An example is beta-hydroxybutyrate, which, when administered alone, exerts an anti-allodynic effect. However, when administered together with Acmella and/or Boswellia, it completely nullifies any activity.
POSSIBLE USES OF NERVANA®
As an add-on therapy for chronic or recurrent pain.
Nervana® may be useful as an adjunct to pharmacological therapy for chronic conditions and long-term treatments.
DYSMENORRHEA
PUDENDUM
NEUROPATHY
VULVODYNIA
FIBROMYALGIA
PELVIC
PAIN
LBP AND
NECK PAIN
CARPAL TUNNEL
SYNDROM
NATURAL NERVE ANALGESIC
ENDOMETRIOSIS
MECHANISMS OF ACTION OF
ACMELLA AND BOSWELLIA
Spilanthol (from Acmella) and boswellic acids (from Boswellia) block and interfere with both the cyclooxygenase and lipoxygenase pathways.
This mechanism is highly synergistic, as the combined action of these active ingredients is exponentially greater than the sum of their individual effects when used separately.
ANANDAMIDE:
THE FIRST DISCOVERED
ENDOCANNABINOID ETYMOLOGY:
amide, chemical family + ananda, state of bliss in Sanskrit
The endocannabinoid system is closely involved in the body's response to chronic pain, inflammation, and other immune-related processes. CB1 receptors are primarily expressed in the central nervous system, while CB2 receptors are predominantly found in the peripheral nervous system.
SPILANTHOL, by binding to FAAH (fatty acid amide hydrolase), prolongs the effect of ANANDAMIDE, the most important endogenous cannabinoid, thereby modulating pain perception.
SPILANTHOL and boswellic acids act by inhibiting the release of multiple mediators of inflammation and pain, while simultaneously promoting the activity of anandamide and the peripheral endocannabinoid system. [1,2,3,4,5,6,7]
CLINICAL TRIALS
PRECLINICAL STUDIES
CLINICAL STUDIES
Nervana in LBP
Open label multicenter study on chronic Low Back Pain (LBP) patients
STUDY COMPLETED
Abstract: The open label, multicenter, non-profit study aims to evaluate the effects of the dietary supplement named Nervana® as a support for chronic pain therapy in patients suffering from low back pain (LBP).
Materials and methods: 118 patients of both genders are enrolled, with the following characteristics: chronic pain for more than 3 months, PAIN DETECT > 12 - Numeric Rating Scale for pain (NRS) > 4. The patients' therapy is not changed, but Nervana® is added, only 2 tablets a day, for 8 weeks. The patients will be evaluated after 2, 4, and 8 weeks.
Single-center retrospective study included 33 women aged 20–35 with dysmenorrhea-related symptoms who had experienced insufficient relief from NSAIDs alone.
SUBMITTED
Abstract: NSAIDs provide relief for dysmenorrhea but have limited efficacy and potential side effects. This retrospective study evaluates the effectiveness of Nervana® as an adjunct therapy for dysmenorrhea symptom management in women with an inadequate response to NSAIDs.
Methods: Participants received Nervana® in addition to NSAIDs over three menstrual cycles. The primary outcome was the reduction in pain intensity, measured by the Numeric Rating Scale (NRS). Secondary outcomes included changes in NSAID consumption.
Nervana in DYSMENORRHEA- PMS
Nervana in VULVODYNIA
Synergy Between Acmella + Boswellia and Transcutaneous Electrical Nerve Stimulation (TENS) in Patients with Vestibulodynia: A Double-Blind, Randomized, Placebo-Controlled Trial
TRIAL FINISHED
Abstract:The research hypothesis of this study is to prospectively assess the efficacy of an oral supplement containing Acmella and Boswellia (Nervana®) in patients with vestibulodynia undergoing TENS therapy as part of a multimodal and synergistic treatment strategy.
Methods: Eighty women were randomly assigned to receive either oral Nervana® or a placebo, twice daily for 60 days. All patients underwent TENS therapy following a self-administered home-based protocol.
BIBLIOGRAPHY
[1] Petrangolini, G., et al. "Targeting Cannabinoid Receptors and Fatty Acid Amide Hydrolase: An Innovative Food-Grade Delivery System of Zingiber officinale and Acmella oleracea Extracts as Natural Adjuvant in Pain Management." J Nutr Food Sci 10 (2019): 766. [2] Poeckel, D. and O. Werz, Boswellic acids: biological actions and molecular targets. Curr Med Chem, 2006. 13(28): p. 3359-69. [3] Safayhi, H., et al., Boswellic acids: novel, specific, nonredox inhibitors of 5-lipoxygenase. J Pharmacol Exp Ther, 1992. 261(3): p. 1143-6 [4] Werz, O., et al., Nonredox 5-lipoxygenase inhibitors require glutathione peroxidase for efficient inhibition of 5-lipoxygenase activity. Mol Pharmacol, 1998. 54(2): p. 445-51. [5] Tausch, L., et al., Identification of human cathepsin G as a functional target of boswellic acids from the anti-inflammatory remedy frankincense. J Immunol, 2009. 183(5): p. 3433-42. [6] Safayhi, H., et al., Inhibition by boswellic acids of human leukocyte elastase. J Pharmacol Exp Ther, 1997. 281(1): p. 460-3. [7] Syrovets, T., et al., Acetyl-boswellic acids inhibit lipopolysaccharide-mediated TNF-alpha induction in monocytes by direct interaction with IkappaB kinases. J Immunol, 2005. 174(1): p. 498-506.
NERVANA®
Dietary supplement formulated with Acmella oleracea and Boswellia serrata
Supports joint function and counteracts localized tension states*
The gastro-protected formulation of NERVANA® allows the tablet to pass through the stomach without causing adverse effects, ensuring that the active ingredients reach the intestine unchanged, where they exert their action.
The two natural compounds are specifically studied and formulated to optimize their absorption, which would otherwise be negligible in standard formulations. Boswellia is incorporated into a Phytosome® (Indena), a phospholipid complex that enhances its bioavailability, while Acmella is formulated with cyclodextrins, cyclic oligosaccharides that facilitate faster delivery of the compound into the body.
The formulation of NERVANA® is designed to ensure the absence of adverse effects.
* (EFSA authorized claim)
Daily dose and method of administration:
Take 1 tablet twice daily (morning and evening), preferably on an empty stomach.
NERVANA®
Gynecological cream formulated with Acmella oleracea, Boswellia serrata, and CBD
Soothing, moisturizing and regenerating intimate cream
Thanks to its patented and synergistic combination of Acmella, Boswellia, and CBD, this formula provides fast and effective soothing action for the intimate area, ensuring deep hydration—particularly beneficial for sensitive, damaged, or dehydrated skin.
CBD, in combination with Evening Primrose Oil, helps minimizing skin inflammation, alleviating irritation and redness while maintaining mucosal elasticity and reducing dryness and discomfort.
Directions for use:
Apply a small amount of product (1-2 pumps) directly to the vulvar area, gently massaging until fully absorbed.Apply Nervana® Gynecological Cream twice daily (morning and evening) or as needed.For long-lasting relief, if applying only once a day, it is recommended to use it in the evening before bedtime.