Outstanding Natural Ingredients for Mental Wellness

Mental Wellness Support: Pharmactive Style.

While modern medicine often focuses on mental illness, we should investigate improving our mental wellness.  Taking an active role in supporting and enhancing our mental wellness will allow us to respond better when “times are challenging.” We focus on our mental or cognitive functions and emotions when we talk about mental wellness.  These all boil down to three interconnected areas; occasional stress, sleep, and cognitive function.  Interconnection can be seen in these brief examples:

  • People may have issues with sleep, yet occasional stress is why they are having trouble sleeping.[i]
  • A person may have occasional stress due to a lack of sleep.[ii]
  • A person may struggle with cognitive function, not realizing that it is worry (occasional stress[iii]) or sleep problems[iv] causing them not to remember something.

Poor mental wellness isn’t just bad for mental health because it can impact all aspects of our lives.  Areas such as cardiovascular health[v], immune health[vi], weight control[vii], elevated blood sugar[viii], pain management[ix], relationships[x], difficulties at work, home, and school are just the tip of the iceberg.

Pharmactive to the Rescue.

As we will see, Pharmactive provides formulators and R&D experts with one key ingredient (affron®), which has compelling science for two of the three areas of concern for mental wellness: Stress and Sleep.  In addition, affron® can provide an indirect pathway to cognitive health.  This blog will also discuss some of the best ingredients to combine with affron® to achieve a unique and cutting-edge finished product.  Remember that the science behind affron® is all you need to provide a compelling finished product, yet combining it with other clinically proven ingredients with differing mechanisms of action will take your product to another level and make it stand out.  Let’s help others get their mental wellness back on track.

Affron® and Occasional Stress.

affron® is a patented and clinically substantiated ingredient of saffron (Crocus sativus L.).   To date, there are eight clinical trials completed and more pending, which cover a wide array of health benefits, and bioavailability.  With regards to mood, just 28mg of affron® daily (lowest clinically proven dose of any saffron ingredient) provided clinically proven effects of:

  • Alleviating occasional stress, frustration, and tension in adults[xi]
  • Helped children (12-16 years of age) maintain a positive mood and alleviate occasional stress, frustration, and tension.[xii]
  • Improve psychological symptoms (low mood and occasional stress) in perimenopausal women (32-33% reduction)[xiii]

Combination Suggestions: affron®and Sleep.

There are several published clinical studies done with affron® and sleep.  The first study evaluated the effects of taking 14 mg of affron® twice daily and showed significant improvements in Insomnia Severity Index (ISI), Restorative Sleep Questionnaire (RSQ), and the Pittsburgh Sleep Diary (PSD).  A second study[xvi] also looked at a 14 mg twice per day dose and showed improvements in Pittsburgh Sleep Quality Index (PSQI).  The results showed substantial improvements in the daytime function of people claiming to be poor sleepers.  The third and most recent study[xvii] evaluated the small dose of just 14mg taken one hour before bedtime and its impact on sleep.  The results showed a low amount of just 14mg taken 1 hour before sleep significantly improves sleep quality.  This same study unlocked a new mechanism of action as it was noted that melatonin production increased with this dosing schedule.  This latest study opens the door for easy formulating with a much lower dose making it easier to formulate with a unique delivery method such as stick-packs, films, gummies, or a small beverage.

Combination Suggestions: Cognitive.

While affron® does not have any studies showing a direct impact on cognitive health and function, we can extrapolate a potential benefit due to its effects on stress and sleep.  Sleep deprivation is linked to adverse changes in cognitive performance, impaired attention, working memory, and decision making.[xx]  Like sleep, occasional stress has also been shown to harm cognitive health, primarily decision making, slower learning, and memory.[xxi]  When looking to formulate a cutting-edge cognitive health product, three excellent clinically proven ingredients come to mind:  Sage (SibeliusTM: Sage) (Salvia officinalis L.),  Bacopa (Synapsa®)  (Bacopa monnieri), and Green oat (Neuravena®) (Avena sativa).  Studies with Sage have shown improvement in secondary memory, recognition, recall, accuracy, and attention speed.[xxii]  Studies with Bacopa improve measures of verbal learning, memory, and retention,[xxiii] while studies with green oat extract showed cognitive improvements and multitasking.[xxiv]  When looking to create an “outside the box” formulation for cognitive health, the low dose and clinical substantiation of affron® would yield a powerful combination.

Wrap Up.

As we can see, affron® provides companies with one ingredient that directly addresses two of the three areas of mental wellness and health.  The low daily dose and ease of use in formulating with unique delivery methods add to the attractive nature of this fantastic ingredient.  When combined with other ingredients with differing mechanisms of action, we open the door to creating a product that stands above the rest.

David Foreman

The Herbal Pharmacist



[i] Kim EJ, Dimsdale JE.  The effect of psychosocial stress on sleep: a review of polysomnographic evidence.  Behav Sleep Med. 2007;5(4):256-278.  doi:10.1080/15402000701557383

[ii] Choi DW, Chun SY, Lee SA, Han KT, Park EC.  Association between Sleep Duration and Perceived Stress: Salaried Worker in Circumstances of High Workload.  Int J Environ Res Public Health.  2018;15(4):796.  Published 2018 Apr 19.  doi:10.3390/ijerph15040796

[iii] Scott SB, Graham-Engeland JE, Engeland CG, et al. The Effects of Stress on Cognitive Aging, Physiology, and Emotion (ESCAPE) Project.  BMC Psychiatry.  2015;15:146.  Published 2015 Jul 3.  doi:10.1186/s12888-015-0497-7

[iv] Xu W, Tan C, Zou J, et al.,  Sleep problems and risk of all-cause cognitive decline or dementia: an updated systematic review and meta-analysis Journal of Neurology, Neurosurgery & Psychiatry 2020;91:236-244

[v] Dimsdale JE.  Psychological stress and cardiovascular disease.  J Am Coll Cardiol.  2008;51(13):1237-1246. doi:10.1016/j.jacc.2007.12.024

[vi] Segerstrom SC, Miller GE. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry.  Psychol Bull.  2004;130(4):601-630.  doi:10.1037/0033-2909.130.4.601

[vii] Block JP, He Y, Zaslavsky AM, Ding L, Ayanian JZ. Psychosocial stress and change in weight among US adults.  Am J Epidemiol.  2009;170(2):181-192.  doi:10.1093/aje/kwp104

[viii] Surwit RS, Schneider MS, Feinglos MN. Stress and diabetes mellitus. Diabetes Care. 1992 Oct;15(10):1413-22. doi: 10.2337/diacare.15.10.1413. PMID: 1425110.

[ix] Ahmad AH, Zakaria R. Pain in Times of Stress. Malays J Med Sci. 2015;22(Spec Issue):52-61.

[x] Lau KKH, Randall AK, Duran ND, Tao C. Examining the Effects of Couples’ Real-Time Stress and Coping Processes on Interaction Quality: Language Use as a Mediator.  Front Psychol.  2019;9:2598.  Published 2019 Jan 15.  doi:10.3389/fpsyg.2018.02598

[xi] Kell G, Rao A, Beccaria G, Clayton P, Inarejos-García AM, Prodanov M. affron® a novel saffron extract (Crocus sativus L.) improves mood in healthy adults over four weeks in a double-blind, parallel, randomized, placebo-controlled clinical trial.  Complement Ther Med. 2017 Aug;33:58-64.  doi: 10.1016/j.ctim.2017.06.001. Epub 2017 Jun 13.  PMID: 28735826.

[xii] Lopresti AL, Drummond PD, Inarejos-García AM, Prodanov M. affron®, a standardized extract from saffron (Crocus sativus L.) for the treatment of youth anxiety and depressive symptoms: A randomised, double-blind, placebo-controlled study.  J Affect Disord.  2018 May;232:349-357.  doi: 10.1016/j.jad.2018.02.070. Epub 2018 Feb 26.  PMID: 29510352.

[xiii] Lopresti AL, Smith SJ.   The Effects of a Saffron Extract (affron®) on Menopausal Symptoms in Women during Perimenopause: A Randomised, Double-Blind, Placebo-Controlled Study.   J Menopausal Med. 2021;27:e8.   https://doi.org/10.6118/jmm.21002

[xiv] Chandrasekhar K, Kapoor J, Anishetty S. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults.  Indian J Psychol Med. 2012;34(3):255-262.  doi:10.4103/0253-7176.106022

[xv] Terburg D, Syal S, Rosenberger LA, Heany S, Phillips N, Gericke N, Stein DJ, van Honk J. Acute effects of Sceletium tortuosum (Zembrin), a dual 5-HT reuptake and PDE4 inhibitor, in the human amygdala and its connection to the hypothalamus.  Neuropsychopharmacology.  2013 Dec;38(13):2708-16. doi: 10.1038/npp.2013.183. Epub 2013 Aug 1.  PMID: 23903032; PMCID: PMC3828542.

[xvi] Nishide A, Fujita T, Shoyama Y, et al., Sleep Enhancement by Saffron Extract affron® in Randomized Clinical Trial, Japanese Pharmacology and Therapeutics, Volume 46, No. 8 2018  http://www.balansprodukter.com/balans/files/Viva_Affron_Sleep.pdf

[xvii] Lopresti A, Smith S, Drummond P, An investigation into an evening intake of a saffron extract (affron®) on sleep quality, cortisol, and melatonin concentrations in adults with poor sleep: a randomised, double-blind, placebo-controlled, multi-dose study, Sleep Medicine, Volume 86, 2021, Pages 7-18,

[xviii] Adib-Hajbaghery M, Mousavi SN.  The effects of chamomile extract on sleep quality among elderly people: A clinical trial.  Complement Ther Med. 2017 Dec;35:109-114.  doi: 10.1016/j.ctim.2017.09.010. Epub 2017 Oct 13.  PMID: 29154054.

[xix] Kim HJ, Kim J, Lee S, et al. A Double-Blind, Randomized, Placebo-Controlled Crossover Clinical Study of the Effects of Alpha-s1 Casein Hydrolysate on Sleep Disturbance.  Nutrients.  2019;11(7):1466.  Published 2019 Jun 27.  doi:10.3390/nu11071466

[xx] Alhola P, Polo-Kantola P. Sleep deprivation: Impact on cognitive performance.  Neuropsychiatr Dis Treat.  2007;3(5):553-67.  PMID: 19300585; PMCID: PMC2656292.

[xxi] McManus E, Talmi D, Haroon H,  Muhlert N, The Effects of Psychosocial Stress on Memory and Cognitive Ability: A Meta-Analysis medRxiv 2020.11.30.20240705; doi:https://doi.org/10.1101/2020.11.30.20240705

[xxii] Scholey, Andrew B., et al. “An Extract of Salvia (Sage) with Anticholinesterase Properties Improves Memory and Attention in Healthy Older Volunteers.” Psychopharmacology, vol. 198, no. 1, 2008, pp. 127–139., doi:10.1007/s00213-008-1101-3.

[xxiii] Morgan A, Stevens J.  Does Bacopa monnieri improve memory performance in older persons?  Results of a randomized, placebo-controlled, double-blind trial.  J Altern Complement Med 2010;16:753-9.

[xxiv] Kennedy DO, Jackson PA, Forster J, Khan J, Grothe T, Perrinjaquet-Moccetti T, Haskell-Ramsay CF.  Acute effects of a wild green-oat (Avena sativa) extract on cognitive function in middle-aged adults: A double-blind, placebo-controlled, within-subjects trial.  Nutr Neurosci.  2017 Feb;20(2):135-151. doi: 10.1080/1028415X.2015.1101304. Epub 2015 Nov 30.  PMID: 26618715.


Pharmactive Biotech Products S.L.U does not sell or distribute (SibeliusTM: Sage) (Salvia officinalis L.),  Bacopa (Synapsa®)  (Bacopa monnieri), and Green oat (Neuravena®) (Avena sativa).

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Pharmactive Biotech Products, S.L. is a privately-owned Spanish company that develops, and manufactures differentiated natural ingredients supported by scientific evidence. Pharmactive makes these innovative ingredients available to other companies in the Nutraceutical, Pharmaceutical and Veterinary Industries for marketing/distribution.

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