How are endorphins a natural remedy for anxiety? (Are endorphins sufficient to alleviate anxiety? Under which conditions?)
DOI:
https://doi.org/10.58445/rars.3235Keywords:
Anxiety, Endorphins, NeurobiologyAbstract
Generalized anxiety disorder (GAD) causes fear or anxiety responses to innocuous stimuli, exaggerated responses to concerning stimuli, affects over 300 million people globally, and is nearly twice as common in women as in men. This review discusses the underlying neurological changes, as well as the interactions between the brain,body, and sex in this complex disorder. The effects of not only societal expectations, but sex hormones, hormonal cycles, and environmental impacts are discussed. One intervention for anxiety with increasing evidence for its effectiveness is exercise, and specifically its impact on endorphins. Endorphins are opioid neuropeptides released when the body experiences stress or pain and act as the body’s natural pain relievers. Endorphins are also released during exercise. Endorphins modulate stress-related brain activity by binding to mu-opioid receptors, thereby decreasing heart rate and restlessness. Gender also must be considered when evaluating anxiety disorders due to gendered societal expectations and differences in levels of testosterone and estrogen which affect endorphin production. While males and females have similar baseline endorphin levels, the hormonal fluctuations of the menstrual cycle affect endorphins, meaning that sex differences can impact anxiety. By including multifactorial considerations in GAD, we continue to progress in understanding and improve treatment options and outcomes.
References
ABSTRACT. www.wjpps.com/wjpps_controller/abstract_id/2490. Accessed 18 Aug. 2025.
Ali, Ansam Hussein, et al. “Endorphin: Function and Mechanism of Action.” Science Archives, vol. 02, no. 01, Science Archives, 2021, pp. 09–13.
Aloisi, A. M., et al. “Sex-Related Effects on Behaviour and Beta-Endorphin of Different Intensities of Formalin Pain in Rats.” Brain Research, vol. 699, no. 2, Nov. 1995, pp. 242–249.
---. “Sex-Related Effects on Behaviour and Beta-Endorphin of Different Intensities of Formalin Pain in Rats.” Brain Research, vol. 699, no. 2, Nov. 1995, pp. 242–249.
---. “Sex-Related Effects on Behaviour and Beta-Endorphin of Different Intensities of Formalin Pain in Rats.” Brain Research, vol. 699, no. 2, Nov. 1995, pp. 242–249.
Amir, S., et al. “The Role of Endorphins in Stress: Evidence and Speculations.” Neuroscience and Biobehavioral Reviews, vol. 4, no. 1, Elsevier BV, Spring 1980, pp. 77–86.
Caballo, Vicente E., et al. “Differences in Social Anxiety between Men and Women across 18 Countries.” Personality and Individual Differences, vol. 64, no. C, Elsevier BV, July 2014, pp. 35–40.
---. “Differences in Social Anxiety between Men and Women across 18 Countries.” Personality and Individual Differences, vol. 64, no. C, Elsevier BV, July 2014, pp. 35–40.
---. “Differences in Social Anxiety between Men and Women across 18 Countries.” Personality and Individual Differences, vol. 64, no. C, Elsevier BV, July 2014, pp. 35–40.
Cavanagh, Anna, et al. “Gender Differences in Self‐reported Depression and Co‐occurring Anxiety and Stress in a Vulnerable Community Population.” Australian Psychologist, vol. 51, no. 6, Informa UK Limited, Dec. 2016, pp. 411–421.
---. “Gender Differences in Self‐reported Depression and Co‐occurring Anxiety and Stress in a Vulnerable Community Population.” Australian Psychologist, vol. 51, no. 6, Informa UK Limited, Dec. 2016, pp. 411–421.
---. “Gender Differences in Self‐reported Depression and Co‐occurring Anxiety and Stress in a Vulnerable Community Population.” Australian Psychologist, vol. 51, no. 6, Informa UK Limited, Dec. 2016, pp. 411–421.
Crowley, Nicole A., et al. “Dynorphin Controls the Gain of an Amygdalar Anxiety Circuit.” Cell Reports, vol. 14, no. 12, Elsevier BV, Mar. 2016, pp. 2774–2783.
Dbiec, Jacek, and Joseph LeDoux. The Amygdala and the Neural Pathways of Fear. Edited by Priyattam J. Shiromani, vol. 409, Humana Press, 2009, pp. 23–38.
Goldfarb, A. H., et al. “Gender Effect on Beta-Endorphin Response to Exercise.” Medicine and Science in Sports and Exercise, vol. 30, no. 12, Ovid Technologies (Wolters Kluwer Health), Dec. 1998, pp. 1672–1676.
Goldfarb, Elizabeth V., et al. “Sex Differences in Neural Stress Responses and Correlation with Subjective Stress and Stress Regulation.” Neurobiology of Stress, vol. 11, no. 100177, Elsevier BV, Nov. 2019, p. 100177.
Hosseinzadeh Sahafi, Oveis, et al. “Shared Mechanisms of GABAergic and Opioidergic Transmission Regulate Corticolimbic Reward Systems and Cognitive Aspects of Motivational Behaviors.” Brain Sciences, vol. 13, no. 5, Multidisciplinary Digital Publishing Institute, May 2023, p. 815.
Ihalainen, Johanna K., et al. “Beyond Menstrual Dysfunction: Does Altered Endocrine Function Caused by Problematic Low Energy Availability Impair Health and Sports Performance in Female Athletes?” Sports Medicine (Auckland, N.Z.), vol. 54, no. 9, Springer Science and Business Media LLC, Sept. 2024, pp. 2267–2289.
---. “Beyond Menstrual Dysfunction: Does Altered Endocrine Function Caused by Problematic Low Energy Availability Impair Health and Sports Performance in Female Athletes?” Sports Medicine (Auckland, N.Z.), vol. 54, no. 9, Springer Science and Business Media LLC, Sept. 2024, pp. 2267–2289.
Jayakody, Kaushadh, Shalmini Gunadasa, and Christian Hosker. “Exercise for Anxiety Disorders: Systematic Review.” British Journal of Sports Medicine, vol. 48, no. 3, BMJ, Feb. 2014, pp. 187–196.
Jayakody, Kaushadh, Shalmini Gunadasa, and C. Hosker. “Exercise for Anxiety Disorders: Systematic Review.” British Journal of Sports Medicine, vol. 48, no. 3, BMJ Publishing Group Ltd and British Association of Sport and Exercise Medicine, Jan. 2013, pp. 187–196.
---. “Exercise for Anxiety Disorders: Systematic Review.” British Journal of Sports Medicine, vol. 48, no. 3, BMJ Publishing Group Ltd and British Association of Sport and Exercise Medicine, Jan. 2013, pp. 187–196.
Jayakody, Kaushadh, Shalmini Gunadasa, and Christian Hosker. “Exercise for Anxiety Disorders: Systematic Review.” British Journal of Sports Medicine, vol. 48, no. 3, BMJ, Feb. 2014, pp. 187–196.
Jetty, P. V., et al. “Neurobiology of Generalized Anxiety Disorder.” The Psychiatric Clinics of North America, vol. 24, no. 1, Mar. 2001, pp. 75–97.
Kandola, Aaron, and Brendon Stubbs. “Exercise and Anxiety.” Advances in Experimental Medicine and Biology, vol. 1228, 2020, pp. 345–352.
Keizer, H. A., and A. D. Rogol. “Physical Exercise and Menstrual Cycle Alterations. What Are the Mechanisms?” Sports Medicine (Auckland, N.Z.), vol. 10, no. 4, Oct. 1990, pp. 218–235.
Kim, Jean, and Jack Gorman. “The Psychobiology of Anxiety.” Clinical Neuroscience Research, vol. 4, no. 5–6, Elsevier BV, May 2005, pp. 335–347.
Lawther, Adam J., et al. Serotonin and the Neurobiology of Anxious States. Edited by Christian P. Müller and Kathryn A. Cunningham, vol. 31, Elsevier, 2020, pp. 505–520. Handbook of Behavioral Neuroscience.
---. Serotonin and the Neurobiology of Anxious States. Edited by Christian P. Müller and Kathryn A. Cunningham, vol. 31, Elsevier, 2020, pp. 505–520. Handbook of Behavioral Neuroscience.
LeDoux, Joseph. “The Amygdala.” Current Biology: CB, vol. 17, no. 20, Elsevier BV, Oct. 2007, pp. R868-74.
---. “The Emotional Brain, Fear, and the Amygdala.” Cellular and Molecular Neurobiology, vol. 23, no. 4–5, Oct. 2003, pp. 727–738.
Morilak, David A., et al. “Role of Brain Norepinephrine in the Behavioral Response to Stress.” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 29, no. 8, Elsevier BV, Dec. 2005, pp. 1214–1224.
Moylan, S., H. A. Eyre, et al. “Exercising the Worry Away: How Inflammation, Oxidative and Nitrogen Stress Mediates the Beneficial Effect of Physical Activity on Anxiety Disorder Symptoms and Behaviours.” Neuroscience and Biobehavioral Reviews, vol. 37, no. 4, Elsevier BV, May 2013, pp. 573–584.
Moylan, S., M. Maes, et al. “The Neuroprogressive Nature of Major Depressive Disorder: Pathways to Disease Evolution and Resistance, and Therapeutic Implications.” Molecular Psychiatry, vol. 18, no. 5, Springer Science and Business Media LLC, May 2013, pp. 595–606.
Naukkarinen, Hannu, et al. “Deramciclane in the Treatment of Generalized Anxiety Disorder: A Placebo-Controlled, Double-Blind, Dose-Finding Study.” European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, vol. 15, no. 6, Elsevier BV, Dec. 2005, pp. 617–623.
(PDF) Neurobiological Mechanisms of Human Anxiety. www.researchgate.net/publication/313166562_Neurobiological_mechanisms_of_human_anxiety.
Puryear, Corey B., et al. “Opioid Receptor Modulation of Neural Circuits in Depression: What Can Be Learned from Preclinical Data?” Neuroscience and Biobehavioral Reviews, vol. 108, Elsevier BV, Jan. 2020, pp. 658–678.
Reeves, Kaitlin C., et al. “Opioid Receptor-Mediated Regulation of Neurotransmission in the Brain.” Frontiers in Molecular Neuroscience, vol. 15, June 2022, p. 919773.
Ressler, Kerry J. “Amygdala Activity, Fear, and Anxiety: Modulation by Stress.” Biological Psychiatry, vol. 67, no. 12, June 2010, pp. 1117–1119.
---. “Amygdala Activity, Fear, and Anxiety: Modulation by Stress.” Biological Psychiatry, vol. 67, no. 12, June 2010, pp. 1117–1119.
Sharp, Jessica L., et al. “Sex Differences in Opioid Receptor Mediated Effects: Role of Androgens.” Neuroscience and Biobehavioral Reviews, vol. 134, no. 104522, Elsevier BV, Mar. 2022, p. 104522.
Shrihari, T. G. “Beta Endorphins - Holistic Therapeutic Approach to Cancer.” Annals of Ibadan Postgraduate Medicine, vol. 17, no. 2, Ann Ib Postgrad Med, Dec. 2019, pp. 111–114.
Simmons, Alan, et al. “Anxiety Vulnerability Is Associated with Altered Anterior Cingulate Response to an Affective Appraisal Task.” Neuroreport, vol. 19, no. 10, Ovid Technologies (Wolters Kluwer Health), July 2008, pp. 1033–1037.
Stein, Murray B. “Neurobiology of Generalized Anxiety Disorder.” The Journal of Clinical Psychiatry, vol. 70 Suppl 2, J Clin Psychiatry, 2009, pp. 15–19.
Weiser, M. J., and R. J. Handa. “Estrogen Impairs Glucocorticoid Dependent Negative Feedback on the Hypothalamic-Pituitary-Adrenal Axis via Estrogen Receptor Alpha within the Hypothalamus.” Neuroscience, vol. 159, no. 2, Mar. 2009, pp. 883–895.
Zhang, Changqing. Role of Beta-Endorphin in Control of Stress and Cancer Progression in Fetal Alcohol Exposed Rats. 2013, https://doi.org/10.7282/T3XS5SG3.
---. Role of Beta-Endorphin in Control of Stress and Cancer Progression in Fetal Alcohol Exposed Rats. 2013, https://doi.org/10.7282/T3XS5SG3.
www.researchgate.net/profile/Tg-Shrihari-2/publication/325336833_BETA_-_Endorphins_-_A_Novel_Natural_Holistic_Healer/links/6003b1ed45851553a04c685b/BETA-Endorphins-A-Novel-Natural-Holistic-Healer.pdf. Accessed 18 Aug. 2025.
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