Stress is an entirely normal physiological and behavioral survival response of the body characterized by a feeling of emotional or physical tension (1). It is a concept that every individual can identify with, and has experienced in part throughout their lifetime. Stress is a useful response that enhances the ability of an individual to survive when under threat.
In this article, we’ll be exploring the underlying mechanisms behind stress, natural treatments that reduce stress, and finally, the best nootropics to directly reduce stress levels.
What Is Stress?
There are two commonly identified types of stress, the effects of which are quite different:
- Acute Stress is short-term. It may be experienced if you are running late for work, have an argument with your partner, or get in trouble with your boss. Acute stress promotes adaptation and survival.
- Chronic Stress is a long-lasting type of stress. Acute-stress can turn into chronic stress. For example, a marriage breakup, working for a toxic boss, or long-standing financial issues.
Stress disturbs an equilibrium in our body. The response is a series of changes from the sympathetic nervous system and endocrine system in an attempt to restore that balance. The primary system in stress is the hypothalamic-pituitary-adrenal (HPA) axis (2).
The body’s initial response to stress is the activation of the fight or flight response. The sympathetic nervous system is put into action and stimulates the release of catecholamine hormones (epinephrine and norepinephrine) from the adrenal glands (2). This event causes markers like an increased heart rate, increased breathing rate, and changes to blood sugar levels.
The most significant response to a stressor is the activation of the HPA axis. Information is sent to neurons in the hypothalamus, which in turn begins to synthesize corticotropin-releasing hormone (CRH) and arginine vasopressin (AV). These hormones are released into the bloodstream where they cause the release of adrenocorticotropic hormone (ACTH) from the pituitary gland. Adrenocorticotropic hormone then binds to receptors in the adrenal cortex, which causes a cascade resulting in the production of glucocorticoids (cortisol) (2). Cortisol is transported through the body where it acts to regulate the stress response by:
- Stimulating gluconeogenesis to provide glucose to the central nervous system and heart tissues.
- Promoting learning and memory processes for future stress encounters
- Aiding catabolic processes
- Maintaining blood pressure
- Regulating immune and inflammation responses
- Priming neural regions
How an individual anticipates and reacts to a stressor will determine the stress response, its duration, and how fast it is turned off. The longer it takes to adapt to stressors, the higher the risk of psychiatric, endocrine, and autoimmune diseases (3). Chronic stress results in an altered stress response profile. The brain is challenged to adjust the HPA axis in a way that is can deal with repeated stress whilst remaining responsive to new stressors (2).
Stress And Cognitive Function
When too much stress is experienced, over time, it can start to cause adverse effects on our health and behavior. Cognitively, stress can reduce the ease of mental tasks, impede memory functions, and has been related to anxiety and depression (4). Chronic stress has also been shown to produce harmful quantities of stress-related hormones that increase the risk of hypertension, immune dysfunction, cancer, and digestive disturbances (4). In fact, stress and its associated disorders are accountable for more than 70% of global illnesses (5).
There is now an evident link between stress and depression. Hormones, like corticosteroids, which are released in times of stress, regulate the rate of neurogenesis. A deficit in the growth of new neurons has been linked to an increased likelihood of depression (6). Studies are suggesting that stress hormones decrease the rates of neurogenesis (7). Stress also directly reduces the expression of brain-derived neurotrophic factor, the levels of which are thought to be directly related to mood levels.
Many interventions exist for the management of stress ranging from time management, balanced diets, humor, conflict resolution, social support, spirituality, humor, massage, and yoga. Two stress management techniques that stand out for their effectiveness in reducing stress are explored below.
Mindfulness has gained attention as an effective way of reducing stress. Originating from Buddhism traditions, mindfulness has been defined by the author Jon Kabat-Zinn from the University of Massachusetts Medical Centre and Stress Reduction Clinic as a moment-to-moment awareness (8).
Mindfulness-based strategies have proven successful in reducing stress, depression, and anxiety (9). They have been thoroughly researched for their effectiveness in both clinical and non-clinical populations from different backgrounds. A review on mindfulness-based stress reduction found that 88% of studies investigated found mindfulness-based stress reduction effective in decreasing stress in healthy populations (10). Mindfulness-based stress reduction sessions included training in body scanning, sitting meditation, and Hatha yoga.
Evidence exists to support physical activity in the maintenance of brain health. It is thought to enhance mental function, decrease the risk of neurodegeneration, and improve depression. Physical activity helps to regulate the production of neurotrophic factors, neurotransmitters, and inflammatory molecules, thus helping to achieve homeostasis.
The effect of exercise on brain function is in part due to its association with brain structure, particularly within the hippocampus. The hippocampus is the target region of the brain stress hormones. It is where exercise-induced neurogenesis and growth factor expression have been proposed as mechanisms to reduce stress.
- β-endorphins and vascular endothelial growth factor are thought to contribute to increased neurogenesis during exercise by enhancing the survival of existing neurons (6). β-endorphins, which increase during exercise, can enhance the synthesis of new neurons (13). Vascular Endothelial Growth Factor, a protein that stimulates the formation of blood vessels and brain-derived neurotrophic factor, is also increased during exercise (14).
- Exercise increases the expression of brain-derived neurotrophic factor, which is directly related to mood levels (15).
- 5-HT is also increased during exercise, which increases cell proliferation (16).
Nootropics And Stress
In the modern age, it is becoming progressively more difficult to live a healthy, balanced lifestyle. Individuals are juggling more tasks, taking on more jobs, and as a result, are often exposed to multiple stressors at the same time.
Nootropics offer a means of improving the nonspecific response to stress. Many have been used in traditional medicine as a means of calming and sedating individuals for centuries. The diverse range of applications for nootropics has seen them develop more and more attention in recent years. Many nootropics exist for stress relief.
The following takes a closer look into the more common nootropics and how they aid in reducing stress levels.
Best Nootropics To Decrease Stress
L-Theanine is a naturally occurring amino acid found almost exclusively within the leaves of the tea plant camellia sinensis. It is present in small amounts in a species of mushroom and two other species of the Camellia genus (17). Teas have been used by Asian cultures for means of relaxation for centuries and are now the second most widely consumed beverage globally after water. Theanine makes up 1-2% of the dry weight of tea leaves (18) and is thought to be found in the greatest percentage in Matcha green tea (19).
Research amongst human volunteers has demonstrated that L-theanine promotes relaxation between nearly half an hour and forty minutes after ingestion. L-theanine helps to facilitate sleep, lower the levels of excitatory chemicals, and stands out for its ability to relax the mind without causing drowsiness (18, 20). One of the mechanisms by which L-theanine achieves its relaxation effect is through its ability to enhance the production of α-brain waves (21). The generation of α-brain waves are regarded as an index of relaxation and are the same as those activated through the likes of meditation. They relax the mind without causing drowsiness (17).
A study investigating the effect of theanine supplements on eight female university students demonstrated α-waves were generated 40 minutes after ingestion of 200mg of L-theanine was dissolved in 100mL of water. The effect of the theanine was greatest in those subjects ranked as most anxious using the manifest anxiety scale method (22). The effect of L-theanine was also tested on twelve male students performing a mental arithmetic task for 20 minutes. The study results indicated there were greater sympathetic nervous system activation and heart rates during the activity with the placebo than with 200mg of L-Theanine. The exact mechanism by which L-Theanine reduced acute stress responses was unclear. Changes in the concentrations of neurotransmitters or an antagonistic role of L-Theanine against glutamic acid receptors were most likely.
Animal studies have shown theanine to elicit a neurochemical effect on the brain with significant increases to the concentrations of serotonin and dopamine, the ‘feel-good’ hormones (23). It is thought to decrease serotonin synthesis but increase degradation and release leading to altered concentrations (24). Further animal studies suggest L-theanine contributes to the formation of gamma-aminobutyric acid (GABA). GABA blocks the release of dopamine and serotonin, and so promotes relaxation and calmness (19).
2. Valeriana Officinalis
Valeriana officinalis (Valerian), a plant native to Europe and Asia has been identified for its sedative and anxiety-reducing properties. The essential oils of the plants are recognized for increasing the release of GABA as well as inhibiting the breakdown of GABA (25).
The theory by which Valerian exerts its sedative effect is that it acts as a nervous system depressant (26). When compared to four weeks of treatment of diazepam (a hypnotic, anxiolytic, and skeletal muscle relaxant), Valerian resulted in a significant reduction in anxiety symptoms (27). It has also significantly improved sleep quality in those with insufficient sleep after two weeks of administration at bedtime (28).
Valeriana officinalis has up to 150 compounds (29); therefore, similar to most herbal compounds, its actions are variable.
3. Bacopa Monnieri
Bacopa Monnieri is an ancient herb from Indian descent that has been used in the treatment of memory decline, fatigue, pain, fevers, inflammation and epilepsy for centuries. Animal and human studies support the use of B. monnieri for the treatment of stress and anxiety.
The most active ingredient within B. monnieri is a bacoside. Bacosides cross the brain-blood barrier and affect brain health through their improvement of neural signaling. Studies have shown B. monnieri intake to reduce subjective anxiety levels. A randomized, double-blind placebo-controlled study in 46 healthy volunteers found participants taking 300mg of B. monnieri extract for 12 weeks had significantly reduced measures of anxiety (30).
The precise mechanism by which B. monnieri enhances cognitive function is not entirely clear. Potential mechanisms are that:
- The active bacosides act on the calcium channels of the smooth muscle cells, which results in vasodilation. This causes increases blood flow to the brain. The additional oxygen and glucose available in the blood may maintain brain function in times of stress (31).
- B. monnieri increases the levels of several neurotransmitters, including serotonin, acetylcholine, GABA, and glutamate. With these neurotransmitters in higher circulation, neuronal activity is increased (32).
Bacopa monnieri has, in some individuals, been recognized for causing nausea, gastrointestinal disturbances and altered motility (33) at doses of 300mg once daily over 12 weeks. Despite these minor gastrointestinal effects, the extract was found to be safe and tolerable with no significant abnormalities caused.
L-Tyrosine is a non-essential amino acid that is used by the body to make proteins. It is ingested from dietary sources, including casein, a milk protein, and some types of meat and red wine (34). Tyrosine is the precursor to a family of neurotransmitters that impact mood. Its levels are tightly controlled by the body. When too little tyrosine is consumed, the body metabolically produces tyrosine, when too much tyrosine is produced, it is broken down to other compounds (34). Consequently, supplementation of tyrosine has yielded mixed results.
A double-blind, randomized crossover study of eight male soccer players found supplementation with 250mL L-tyrosine at 5 hours, and 1-hour pre-exercise testing significantly increased responses of vigilance and reduced mental effort compared to a placebo (35). Others have found tyrosine to result in no mood state improvements (36).
Tyrosine is thought to prevent the depletion of catecholamine neurotransmitters norepinephrine and dopamine, often seen during stress. Maintaining norepinephrine levels in the hypothalamus means the release of corticosteroids (stress hormones) is suppressed (34). These results suggest that supplemental tyrosine can protect against the adverse effects of stress. Tyrosine has also proved successful in improving performance on memory and tracking tasks and reducing diastolic blood pressure (37).
Phenibut, also named β-phenyl-γ-aminobutyric acid, has been used widely in Russian clinical practice to relieve tension, anxiety, and fear since its introduction in the 1960s. It is used to improve sleep in individuals suffering psychologically, and as a pre- and post-operative medicine. Phenibut also has been used as an anti-depressant substance in those with the likes of post-traumatic stress disorder.
Phenibut is a modified version of the gamma-aminobutyric acid (GABA) molecules. GABA is the major inhibitory or ‘downer’ neurotransmitter in most areas of the central nervous system. It promotes feelings of relaxation and calmness. Low GABA levels have been linked to more severe depression and anxiety (38). Phenibut, as a GABA-mimetic, has been investigated for its ability to affect cognition and behavior in the way GABA would.
Penibut has a phenyl ring incorporated in its structure, which improves the entry of the molecule into the brain (39). Phenibut increases the release of GABA from nerve endings (40) and activates GABAB receptors (41).
Phenibut is a nootropic for which research remains mostly within animal studies. Little is known about the toxicology of the substance. Phenibut increases levels of dopamine and the activation of dopamine’s pathways. This is thought to give rise to the sedative and calming effects of the drug (42).
6. Rhodiola Rosea
Rhodiola Rosea is a plant that grows in arctic regions throughout the US, Canada, Europe and some regions of Asia. Once again, its use dates back through the centuries of traditional medicine. Rhodiola Rosea contains several active compounds that elicit multiple effects, including antioxidant, anticarcinogenic, cognitive blunting, and neuroendocrine properties.
The active compounds in Rhodiola Rosea are rosavins, salidrosides, and tyrosyl. They are thought to promote the release of key neurotransmitters that relieve stress, including serotonin, dopamine, and norepinephrine (43). Rhodiola Rosea has also worked to improve the ability of precursors to cross the blood-brain barrier, thus improving their effectiveness (44). It has been used successfully to act against fatigue, irritability, headaches, and poor appetite in doses of 50mg three times daily (44, 45, 46).
Ginseng comes from the roots of several species of plants in the genus Panax. Though there are many varieties, Asian and American ginseng have been used in traditional medicine for centuries. Asian ginseng is recognized for its potential to act as an anti-hypoxia to stress (47). American ginseng has been shown to improve heart and blood circulatory functioning (48), therefore increasing the levels of oxygen and glucose available for the brain.
Ginseng contains active compounds called ginsenosides, which are believed responsible for the potential pharmacological effects of Ginseng. Trials in healthy young adults have found Ginseng in doses of 200 or 400mg to improve feelings of mental fatigue (49). It has also proven effective in reducing mental clarity through reaction times (50) and immediate word recall (51). Research investigating the effects of ginseng have conflicting results, potentially due to the variance of total ginsenosides between species and growing environments.
The effect of Ginseng on stress reduction is likely due once again, to the neuroprotective properties of the plants. Ginsenoside metabolites from the Ginseng plants are thought to antagonize the nicotinic acetylcholine receptors (52). The reduced activity of these receptors is thought to suppress the release of stress hormones from the adrenal glands (32).
Furthermore, when stress hormones circulate in the long-term, neurogenesis is reduced in the hippocampus, which can influence memory function (53). Ginseng works by intercepting the elevation of stress hormones, therefore, allowing neurogenesis to occur as normal. Other potential mechanisms, including ginsenosides activating the estrogen receptors, also exist; however, the studies are limited.
The estrogenic effects of ginseng bare potential risk of adverse effects for particular types of breast cancer, endometriosis, and other hormone-affected conditions. These incidents are rare and have only been identified in isolated cases, most often when Ginseng is taken in combination products (54).
Stress is an unavoidable part of daily life, yet its levels are a key determinant of long-term health. To maintain a well-balanced approach to stress relief, lifestyle factors such as exercise, a good diet, and mindfulness strategies can be supplemented with the nootropics detailed in this article and others.
A common trend of the supported nootropics is their contribution to maintaining balanced neurotransmitter levels, normalizing cortisol levels, regulating circulation, and supporting neurogenesis.
There are many approaches to stress relief available; finding a solution that will work for you to support healthy stress responses is key.