Learned helplessness appears alongside depression, where intense, prolonged stress can exhaust the organism. An lack of available energy often leads to psychological exhaustion and feelings of malaise. Anxiety intuitively resembles the pain response, whereas depression or apathy exist as a complete lack of engagement in the stimuli all together, but researchers found that actually ties closely with pain.
The conclusion was that helplessness after moderate stress (i.e. electric shock) resembles a state of anxiety. Anxiety can be described on a behavioural level as inhibiting the ongoing behaviour.9Nijssen A, Schelvis PR. Effect of an anti-anxiety drug in a learned helplessness experiment. Neuropsychobiology. 1987;18:195–198.
Each person shows different symptoms of learned helplessness but generally include inactivity, avoidance, procrastination, attention deficiency, and a general lack of willfulness. Those with more severe depression likewise exhibit additional symptoms of learned helplessness.10Smallheer BA, Vollman M, Dietrich MS. Learned Helplessness and Depressive Symptoms Following Myocardial Infarction. Clin Nurs Res. 2018;27:597–616.
Researchers showed that by administering a compound related to the benzodiazepine class of drugs, themselves used in the treatment of anxiety disorders, rats more readily responded to stimuli.11Nijssen A, Schelvis PR. Effect of an anti-anxiety drug in a learned helplessness experiment. Neuropsychobiology. 1987;18:195–198. This reaffirms the idea that humans, like any other animal, can recover from learned helplessness with the proper methods.
Depression and anxiety appear alongside chronic elevations of cortisol and serotonin respectively, so substances that tend to lower these may have opposite effects. Drugs that oppose the actions of serotonin include lysergic acid diethylamide (LSD) and its derivatives, as well as those classified as 5-HT3C receptor antagonists, such as ondansetron (Zofran), cyproheptadine (Periactin), mianserin and mirtazapine (Remeron).12Bétry C, Etiévant A, Oosterhof C, et al. Role of 5-HT3 Receptors in the Antidepressant Response. Pharmaceuticals (Basel). 2011;4:603–629.
Caffeine tends to lower serotonin and acts as an anti-depressant but can trigger anxiety, particularly if consumed prior to any consumption of food.
5-HT3 receptor agonists seem to counteract the effects of antidepressants in non-clinical models, whereas 5-HT3 receptor antagonists, such as ondansetron, present antidepressant-like activities.
Anti-inflammatory substances, such as niacinamide or aspirin, may have anti-anxiety effects, as they discourage the body’s fat-burning, stress-based metabolism. As they encourage the burning of sugar rather than fat, they have an anti-diabetic effect and can precipitously drop blood sugar.
It’s important to relate acute states of disease to more chronic conditions. In a stressed, low-energy state, cells become permeable and allow substances to move more freely throughout. When calcium enters into the cell, it excites and damages the cell, and such a state of chronic excitation appears in the context of neurodegenerative disease. Nicotine, among other substances, relaxes the cell, and has a similarly subjective effect to the user, protecting the body from some of the damages of stress.
Increased intracellular calcium, in association with excess nitric oxide and excitatory amino acids, is involved in several neurodegenerative diseases, including ALS, Alzheimers disease, Parkinsons disease, Huntingtons chorea, and epilepsy. Magnesium, nicotine, progesterone, and many other substances are known to protect against excitotoxic calcium overload, but there is no coherent effort in the health professions to make rational use of the available knowledge.13Ray Peat, PhD. (2009). Calcium and Disease: Hypertension, organ calcification, & shock, vs. Respiratory energy. Retrieved October 3, 2019, from http://raypeat.com/articles/articles/calcium.shtml
In a 2015 paper, Piccioto and others observed the anti-depressive effects of drugs that oppose the actions of the neurotransmitter acetylcholine.
Several pharmacological studies have confirmed that nicotinic blockers (antagonists or partial agonists) can alleviate depression-like behaviors in mice, either alone or in combination with monoaminergic drugs.14Picciotto MR, Lewis AS, van Schalkwyk GI, et al. Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states. Neuropharmacology. 2015;96:235–243. 15Andreasen JT, Olsen GM, Wiborg O, et al. Antidepressant-like effects of nicotinic acetylcholine receptor antagonists, but not agonists, in the mouse forced swim and mouse tail suspension tests. J. Psychopharmacol. (Oxford). 2009;23:797–804. 16Andreasen JT, Olsen GM, Wiborg O, et al. Antidepressant-like effects of nicotinic acetylcholine receptor antagonists, but not agonists, in the mouse forced swim and mouse tail suspension tests. J. Psychopharmacol. (Oxford). 2009;23:797–804. 17Bacher I, Wu B, Shytle DR, et al. Mecamylamine – a nicotinic acetylcholine receptor antagonist with potential for the treatment of neuropsychiatric disorders. Expert Opin Pharmacother. 2009;10:2709–2721. 18Mineur YS, Eibl C, Young G, et al. Cytisine-based nicotinic partial agonists as novel antidepressant compounds. J. Pharmacol. Exp. Ther. 2009;329:377–386. 19Mineur YS, Einstein EB, Seymour PA, et al. α4β2 nicotinic acetylcholine receptor partial agonists with low intrinsic efficacy have antidepressant-like properties. Behav Pharmacol. 2011;22:291–299. 20Rollema H, Guanowsky V, Mineur YS, et al. Varenicline has antidepressant-like activity in the forced swim test and augments sertraline’s effect. Eur. J. Pharmacol. 2009;605:114–116.
Through its inhibition of histone deacetylases (HDAC), nicotine protects the brain and can support its recovery from stress. HDAC inhibitors have been shown to counter some of the toxic effects of acetylcholine on the brain’s nerves. Consuming one HDAC inhibitor decreases nicotine craving, and theoretically, the HDAC inhibitor vitamin B3 as niacinamide can aid in smoking cessation.
Some brain receptors increase anxiety, such as β2 subunit containing nicotinic ACh receptors (β2*nAChRs.) Nicotine opposes β2*nAChRs in smaller amounts, but larger amounts of nicotine actually increases the number of β2*nAChRs, which can result in greater anxiety, eventually increasing anxiety past baseline levels.
As hinted in the former study, drugs that promote the actions of the neurotransmitter GABA can reverse a state of anxiety. Such substances include, once again, niacinamide, as well as the amino acids L-theanine,21Nathan, P. J., Lu, K., Gray, M., & Oliver, C. (2006). The neuropharmacology of L-theanine(N-ethyl-L-glutamine): A possible neuroprotective and cognitive enhancing agent. Journal of Herbal Pharmacotherapy, 6(2), 21–30. L-theanine (N-ethyl-L-glutamine) or theanine is a major amino acid uniquely found in green tea. L-theanine has been historically reported as a relaxing agent, prompting scientific research on its pharmacology. Animal neurochemistry studies suggest that L-theanine increases brain serotonin, dopamine, GABA levels and has micromolar affinities for AMPA, Kainate and NMDA receptors. In addition has been shown to exert neuroprotective effects in animal models possibly through its antagonistic effects on group 1 metabotrophic glutamate receptors. Behavioural studies in animals suggest improvement in learning and memory. Overall, L-theanine displays a neuropharmacology suggestive of a possible neuroprotective and cognitive enhancing agent and warrants further investigation in animals and humans.taurine,22Jia F, Yue M, Chandra D, et al. Taurine Is a Potent Activator of Extrasynaptic GABAA Receptors in the Thalamus. J. Neurosci. 2008;28:106–115. and glycine. Hormones that have GABA-like effects include the androgens, as well as progesterone. According to Dr. Ray Peat, in an estrogen-dominant person, a supplement of progesterone temporarily relieves the suppressive effects of estrogen upon the thyroid and may trigger a thyroid storm.23Shomon M. An Interview With Dr. Raymond Peat: A Renowned Nutritional Counselor Offers His Thoughts About Thyroid Disease [Internet]. 2000 [cited 2019 Oct 2]. Available from: 24http://www.thyroid-info.com/articles/ray-peat.htm.
Occasionally, a person with a goiter will temporarily become hyperthyroid as the gland releases its colloid stores in a corrective process.25Shomon, M. (n.d.). An Interview With Dr. Raymond Peat: A Renowned Nutritional Counselor Offers His Thoughts About Thyroid Disease. Retrieved October 2, 2019, from http://www.thyroid-info.com/articles/ray-peat.htm
Administering a thyroid supplement can assist in lowering anxiety if the pulse if below around 80 BPM as an average throughout the day with an average temperature below 98.6 degrees Fahrenheit. Either with or without a thyroid supplement, inhaling and exhaling into a closed system (such as a brown paper bag) will raise blood CO2 levels, which will further dilate and relax blood vessels, lower blood pressure and attenuate anxiety.
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