Over-the-Counter Drugs: Misuse and Safety Implications

Authors

  • Alejandro Borrego-Ruiz *

    Departamento de Psicología Social y de las Organizaciones, Universidad Nacional de Educación a Distancia (UNED), 28040 Madrid, Spain

DOI:

https://doi.org/10.55121/fds.v3i1.780

Keywords:

Over-the-Counter Drugs, OTC Medications, Misuse, Safety Implications, Public Health

Abstract

Although over-the-counter (OTC) drugs are regarded as relatively safe and effective for self-treatment, their growing prevalence and accessibility raise concerns about misuse, addiction, and adverse health consequences. This narrative review provides a current overview of OTC drugs with misuse potential and their associated safety implications. OTC drugs commonly misused include sedative antihistamines, cough mixtures, caffeine-containing products, fat burners, analgesics, laxatives, antidiarrheal medications, and decongestants, which can be harmful when improperly used, often due to recreational purposes and lack of awareness. Patterns of OTC drug misuse typically start with therapeutic use, followed by dose escalation, and are particularly concerning in vulnerable populations such as pregnant women, adolescents, children, older adults, and individuals with mental health conditions. Effective management of OTC drug use in these groups is constrained by public perception of safety, easy accessibility, insufficient oversight, limited healthcare access, and a lack of adequate professional guidance. Emerging alternatives such as probiotics and nutraceuticals offer safer options for OTC drugs, although further research is still needed to establish their effectivity and safety. Ultimately, a multifaceted, patient centered approach, incorporating pharmacological advancements, behavioral insights, and robust public health interventions, will be crucial to mitigating OTC drug misuse and improving overall health outcomes.

References

[1] Mourya, A., Mary, C., James, C., et al., 2019. A Survey on Over the Counter Drug Usage in the Community. Journal of Drug Delivery and Therapeutics. 9(2-S), 406–416. DOI: https://doi.org/10.22270/jddt.v9i2-s.2538

[2] Bowman, C., Family, H., Agius-Muscat, H., et al., 2020. Consumer Internet Purchasing of Medicines Using a Population Sample: A Mixed Methodology Approach. Research in Social and Administrative Pharmacy. 16(6), 819–827. DOI: https://doi.org/10.1016/j.sapharm.2019.09.056

[3] Algarni, M., Hadi, M.A., Yahyouche, A., et al., 2021. A Mixed-Methods Systematic Review of the Prevalence, Reasons, Associated Harms and Risk-Reduction Interventions of Over-the-Counter (OTC) Medicines Misuse, Abuse and Dependence in Adults. Journal of Pharmaceutical Policy and Practice. 14(1), 76. DOI: https://doi.org/10.1186/s40545-021-00350-7

[4] Hirose, M., Hirakawa, A., Niwa, W., et al., 2021. Acute Drug Poisoning Among Adolescents Using Over-the-Counter Drugs: Current Status. Yakugaku Zasshi. 141(12), 1389–1392. DOI: https://doi.org/10.1248/yakushi.21-00147 (in Japanese)

[5] Shimane, T., Inoura, S., Kitamura, M., et al., 2025. Prevalence of Over-the-Counter Drug Abuse and Associated Psychosocial Factors Among High School Students: A Nationwide Cross-Sectional Survey in Japan. Neuropsychopharmacology Reports. 45(2), e70030. DOI: https://doi.org/10.1002/npr2.70030

[6] Borrego-Ruiz, A., 2024. Intrinsic Motivation and Drug Consumption: A Review of Studies on Curiosity and Expansion Motives. Health and Addictions / Salud y Drogas. 24(2), 47–67. DOI: https://doi.org/10.21134/904 (in Spanish)

[7] Aschenbrenner, D.S., 2014. Overuse of Certain OTC Laxatives May Be Dangerous. American Journal of Nursing. 114(5), 25. DOI: https://doi.org/10.1097/01.NAJ.0000446776.76652.11

[8] Borron, S.W., Watts, S.H., Tull, J., et al., 2017. Intentional Misuse and Abuse of Loperamide: A New Look at a Drug With “Low Abuse Potential”. Journal of Emergency Medicine. 53(1), 73–84. DOI: https://doi.org/10.1016/j.jemermed.2017.03.018

[9] Kataveni, S., Gourishetty, R.P., Mundada, S.M., et al., 2025. Clenbuterol Abuse in Bodybuilding and Athletics: Unsupervised Use, Psychological Motivations, and Health Consequences. Cureus. 17(5), e84904. DOI: https://doi.org/10.7759/cureus.84904

[10] Schifano, F., Chiappini, S., Miuli, A., et al., 2021. Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry. 12, 657397. DOI: https://doi.org/10.3389/fpsyt.2021.657397

[11] Borrego-Ruiz, A., 2024. A Holistic Review of Fentanyl Use and Its Impact on Public Health. Current Addiction Research. 8(2), 23–33. DOI: https://doi.org/10.32739/car.2024.8.2.229

[12] Lessenger, J.E., Feinberg, S.D., 2008. Abuse of Prescription and Over-the-Counter Medications. Journal of the American Board of Family Medicine. 21(1), 45–54. DOI: https://doi.org/10.3122/jabfm.2008.01.070071

[13] Tarasuk, J., Zhang, J., Lemyre, A., et al., 2020. National Findings From the Tracks Survey of People Who Inject Drugs in Canada, Phase 4, 2017–2019. Canada Communicable Disease Report. 46(5), 138–148. DOI: https://doi.org/10.14745/ccdr.v46i05a07

[14] van Boekel, L.C., Brouwers, E.P., van Weeghel, J., et al., 2013. Stigma Among Health Professionals Towards Patients With Substance Use Disorders and Its Consequences for Healthcare Delivery: Systematic Review. Drug and Alcohol Dependence. 131(1–2), 23–35. DOI: https://doi.org/10.1016/j.drugalcdep.2013.02.018

[15] Agnich, L.E., Stogner, J.M., Miller, B.L., et al., 2013. Purple Drank Prevalence and Characteristics of Misusers of Codeine Cough Syrup Mixtures. Addictive Behaviors. 38(9), 2445–2449. DOI: https://doi.org/10.1016/j.addbeh.2013.03.020

[16] Swatek, J.L., Marco, S.M., Midthun, K.M., 2024. Over-the-Counter Medications Encountered in the Postmortem Pediatric Population From 2010–2020. Journal of Analytical Toxicology. 48(7), 473–481. DOI: https://doi.org/10.1093/jat/bkae042

[17] Oyekan, P.J., Gorton, H.C., Copeland, C.S., 2021. Antihistamine-Related Deaths in England: Are the High Safety Profiles of Antihistamines Leading to Their Unsafe Use? British Journal of Clinical Pharmacology. 87(10), 3978–3987. DOI: https://doi.org/10.1111/bcp.14819

[18] Dinwiddie, A.T., Tanz, L.J., Bitting, J., 2022. Notes From the Field: Antihistamine Positivity and Involvement in Drug Overdose Deaths – 44 Jurisdictions, United States, 2019–2020. Morbidity and Mortality Weekly Report. 71(41), 1308–1310. DOI: https://doi.org/10.15585/mmwr.mm7141a4

[19] Gracious, B., Abe, N., Sundberg, J., 2010. The Importance of Taking a History of Over-the-Counter Medication Use: A Brief Review and Case Illustration of “PRN” Antihistamine Dependence in a Hospitalized Adolescent. Journal of Child and Adolescent Psychopharmacology. 20(6), 521–524. DOI: https://doi.org/10.1089/cap.2010.0031

[20] Borrego-Ruiz, A., 2024. A Current Overview on Adolescent Alcohol Misuse and Its Potential Negative Impacts. Alcoholism and Drug Addiction / Alkoholizm i Narkomania. 37(3), 213–240. DOI: https://doi.org/10.5114/ain.2024.149307

[21] Cada, D.J., Demaris, K., Levien, T.L., et al., 2013. Doxylamine Succinate / Pyridoxine Hydrochloride. Hospital Pharmacy. 48(9), 762–766. DOI: https://doi.org/10.1310/hpj4809-762

[22] Weathermon, R., Crabb, D.W., 1999. Alcohol and Medication Interactions. Alcohol Research and Health. 23(1), 40–54.

[23] Smith, S.M., Schroeder, K., Fahey, T., 2014. Over-the-Counter (OTC) Medications for Acute Cough in Children and Adults in Community Settings. Cochrane Database of Systematic Reviews. 2014(11), CD001831. DOI: https://doi.org/10.1002/14651858.CD001831.pub5

[24] Chiappini, S., Schifano, F., Corkery, J.M., et al., 2021. Beyond the “Purple Drank”: Study of Promethazine Abuse According to the European Medicines Agency Adverse Drug Reaction Reports. Journal of Psychopharmacology. 35(6), 681–692. DOI: https://doi.org/10.1177/0269881120959615

[25] Miuli, A., Stigliano, G., Lalli, A., et al., 2020. “Purple Drank” (Codeine and Promethazine Cough Syrup): A Systematic Review of a Social Phenomenon With Medical Implications. Journal of Psychoactive Drugs. 52(5), 453–462. DOI: https://doi.org/10.1080/02791072.2020.1797250

[26] Palamar, J.J., 2019. Use of “Lean” Among Electronic Dance Music Party Attendees. American Journal on Addictions. 28(5), 347–352. DOI: https://doi.org/10.1111/ajad.12897

[27] Peters Jr., R.J., Kelder, S.H., Markham, C.M., et al., 2003. Beliefs and Social Norms about Codeine and Promethazine Hydrochloride Cough Syrup (Cphcs) Onset and Perceived Addiction among Urban Houstonian Adolescents: An Addiction Trend in the City of Lean. Journal of Drug Education: Substance Use Research and Prevention. 33(4), 415–425. DOI: https://doi.org/10.2190/NXJ6-U60J-XTY0-09MP

[28] Ware, O.D., Garcia-Romeu, A., Zamarripa, C.A., et al., 2024. Codeine and Promethazine: Exploratory Study on “Lean” or “Sizzurp” Using National Survey Data and an Online Forum. PLOS One. 19(3), e0301024. DOI: https://doi.org/10.1371/journal.pone.0301024

[29] Borrego-Ruiz, A., 2025. Ethnic-Cultural Bullying Among Adolescents: Key Insights From Global Evidence. Cultural Conflict and Integration. 2(1), 10–25. DOI: https://doi.org/10.55121/cci.v2i1.553

[30] Qiu, Y.W., Lv, X.F., Jiang, G.H., et al., 2017. Larger Corpus Callosum and Reduced Orbitofrontal Cortex Homotopic Connectivity in Codeine Cough Syrup-Dependent Male Adolescents and Young Adults. European Radiology. 27(3), 1161–1168. DOI: https://doi.org/10.1007/s00330-016-4465-5

[31] Bates, M.L.S., Trujillo, K.A., 2021. Use and Abuse of Dissociative and Psychedelic Drugs in Adolescence. Pharmacology, Biochemistry, and Behavior. 203, 173129. DOI: https://doi.org/10.1016/j.pbb.2021.173129

[32] Karami, S., Major, J.M., Calderon, S., et al., 2018. Trends in Dextromethorphan Cough and Cold Products: 2000–2015 National Poison Data System Intentional Abuse Exposure Calls. Clinical Toxicology. 56(7), 656–663. DOI: https://doi.org/10.1080/15563650.2017.1416124

[33] McClure, E.W., Daniels, R.N., 2023. Classics in Chemical Neuroscience: Dextromethorphan (DXM). ACS Chemical Neuroscience. 14(12), 2256–2270. DOI: https://doi.org/10.1021/acschemneuro.3c00088

[34] Schwartz, R.H., 2005. Adolescent Abuse of Dextromethorphan. Clinical Pediatrics. 44(7), 565–568. DOI: https://doi.org/10.1177/000992280504400702

[35] Qiu, Y.W., Lv, X.F., Jiang, G.H., et al., 2017. Potential Gray Matter Unpruned in Adolescents and Young Adults Dependent on Dextromethorphan-Containing Cough Syrups: Evidence From Cortical and Subcortical Study. Brain Imaging and Behavior. 11(5), 1470–1478. DOI: https://doi.org/10.1007/s11682-016-9628-0

[36] Fallata, G., Alhumaidan, O., Alkhunein, S., et al., 2025. Caffeine Consumption and Exposure in Saudi Arabia: A Cross-Sectional Analysis. Frontiers in Nutrition. 12, 1556001. DOI: https://doi.org/10.3389/fnut.2025.1556001

[37] Iglseder, B., 2018. Doping for the Brain. Zeitschrift für Gerontologie und Geriatrie. 51(2), 143–148. DOI: https://doi.org/10.1007/s00391-017-1351-y

[38] Sharif, S., Guirguis, A., Fergus, S., et al., 2021. The Use and Impact of Cognitive Enhancers Among University Students: A Systematic Review. Brain Sciences. 11(3), 355. DOI: https://doi.org/10.3390/brainsci11030355

[39] Brunton, G., Khouja, C., Raine, G., et al., 2019. Caffeinated Energy Drink Use and Reported Effects in Young People: A Rapid Overview of Systematic Reviews. EPPI-Centre, Social Science Research Unit, UCL Institute of Education: London, UK. Available from: https://eppi.ioe.ac.uk/CMS/Portals/0/PDF%20reviews%20and%20summaries/Caffeinated%20energy%20drink%20use%20and%20reported%20effects%20in%20young%20people%20CED1.pdf

[40] Al Ghali, R.M., Al Shaibi, H., Al Majed, H., et al., 2017. Caffeine Consumption Among Zayed University Students in Dubai, United Arab Emirates: A Cross-Sectional Study. Arab Journal of Nutrition and Exercise. 1, 131. DOI: https://doi.org/10.18502/ajne.v1i3.1230

[41] Soós, R., Gyebrovszki, Á., Tóth, Á., et al., 2021. Effects of Caffeine and Caffeinated Beverages in Children, Adolescents and Young Adults: Short Review. International Journal of Environmental Research and Public Health. 18(23), 12389. DOI: https://doi.org/10.3390/ijerph182312389

[42] Wegmann Düring, S., Botfeldt Møller-Pedersen, T., Hovmand, O.R., 2025. Psychotic Symptoms Following Consumption of Energy Drinks: A Systematic Review. Nordic Journal of Psychiatry. 79(5), 325–332. DOI: https://doi.org/10.1080/08039488.2025.2499593

[43] Stephanos, K., Hayes, B.D., 2025. Caffeine Overdose Resulting in Seizure-Like Activity and Rhabdomyolysis in a Child: A Case Report. Journal of Emergency Medicine. 75, 323–326. DOI: https://doi.org/10.1016/j.jemermed.2025.03.006

[44] Holloway, F.A., Michaelis, R.C., Huerta, P.L., 1985. Caffeine–Phenylethylamine Combinations Mimic the Amphetamine Discriminative Cue. Life Sciences. 36(8), 723–730. DOI: https://doi.org/10.1016/0024-3205(85)90191-2

[45] Melones-Peña, N., Gómez-Gómez, B., Gracia-Lor, E., 2025. How Much Consumed Caffeine Is Actually Absorbed? Bioaccessibility and Bioavailability in Energy Drinks, Infusions and Soft Drinks. Food Chemistry. 492, 145626. DOI: https://doi.org/10.1016/j.foodchem.2025.145626

[46] Lee, S.J., Na, Y., Lee, K.W., 2025. Association Between the Consumption of Sugar-Sweetened Beverages and High-Caffeine Drinks and Self-Reported Mental Health Conditions Among Korean Adolescents. Nutrients. 17(16), 2652. DOI: https://doi.org/10.3390/nu17162652

[47] Dobrek, L., 2025. The Review on Adverse Effects of Energy Drinks and Their Potential Drug Interactions. Nutrients. 17(15), 2435. DOI: https://doi.org/10.3390/nu17152435

[48] Jeukendrup, A.E., Randell, R., 2011. Fat Burners: Nutrition Supplements That Increase Fat Metabolism. Obesity Reviews. 12(10), 841–851. DOI: https://doi.org/10.1111/j.1467-789X.2011.00908.x

[49] Clark, J.E., Welch, S., 2021. Comparing Effectiveness of Fat Burners and Thermogenic Supplements to Diet and Exercise for Weight Loss and Cardiometabolic Health: Systematic Review and Meta-Analysis. Nutrition and Health. 27(4), 445–459. DOI: https://doi.org/10.1177/0260106020982362

[50] Jakopin, Ž., 2019. Risks Associated With Fat Burners: A Toxicological Perspective. Food and Chemical Toxicology. 123, 205–224. DOI: https://doi.org/10.1016/j.fct.2018.10.051

[51] Yellapu, R.K., Mittal, V., Grewal, P., et al., 2011. Acute Liver Failure Caused by “Fat Burners” and Dietary Supplements: A Case Report and Literature Review. Canadian Journal of Gastroenterology. 25(3), 157–160. DOI: https://doi.org/10.1155/2011/174978

[52] Lilley, L.J., Wiseman, M., Sadowski, B., 2025. Drug-Induced Liver Injury With Novel Fat Burner AlbutarexV2 in an Active Duty Sailor. Military Medicine. usaf175. DOI: https://doi.org/10.1093/milmed/usaf175

[53] Sousa, D., Carmo, H., Roque Bravo, et al., 2020. Diet Aid or Aid to Die: An Update on 2,4-Dinitrophenol (2,4-DNP) Use as a Weight-Loss Product. Archives of Toxicology. 94(4), 1071–1083. DOI: https://doi.org/10.1007/s00204-020-02675-9

[54] Turnock, L.A., Hearne, E., Germain, J., et al., 2025. Off-Label GLP-1 Weight-Loss Medicine Use Among Online Bodybuilders: Folk Pharmacology, Risk and Harm Reduction. International Journal of Drug Policy. 142, 104854. DOI: https://doi.org/10.1016/j.drugpo.2025.104854

[55] Gholami, F., Antonio, J., Iranpour, M., et al., 2024. Does Green Tea Catechin Enhance Weight-Loss Effect of Exercise Training in Overweight and Obese Individuals? A Systematic Review and Meta-Analysis of Randomized Trials. Journal of the International Society of Sports Nutrition. 21(1), 2411029. DOI: https://doi.org/10.1080/15502783.2024.2411029

[56] Witkoś, J., Hartman-Petrycka, M., Błażejewski, G., 2025. The Effect of Over-the-Counter Analgesics on Changes to the Sensory Sensitivity of Patients Treated With Transcutaneous Electrical Nerve Stimulation. Scientific Reports. 15(1), 29638. DOI: https://doi.org/10.1038/s41598-025-14588-7

[57] Sadik, D., St-Onge, J.F., St-Onge, F., et al., 2025. Rubber Band Ligation: A New Treatment Option for External Hemorrhoids. Cureus. 17(8), e89701. DOI: https://doi.org/10.7759/cureus.89701

[58] Burlacu, R., Bourdin, V., Blin, P., et al., 2025. Over-the-Counter Non-Steroidal Anti-Inflammatory Medications: Focus on the Management of Acute Pain. Therapie. 80(4), 449–468. DOI: https://doi.org/10.1016/j.therap.2024.10.061 (in French)

[59] Singh, D.S., Pflugmacher, S., 2025. Ecotoxicological Assessments of Over-the-Counter NSAID (Diclofenac, Ibuprofen, Aspirin) and Antipyretic (Acetaminophen) Pharmaceuticals: A Review of Their Toxicity Effects on Aquatic Crustaceans. Integrated Environmental Assessment and Management. vjaf082. DOI: https://doi.org/10.1093/inteam/vjaf082

[60] Wang, R., Xuan, D.D., Xuan, J., et al., 2025. The Economic Burden of Patients With Diabetic Peripheral Neuropathic Pain Based on a Real-World Study in China. ClinicoEconomics and Outcomes Research. 17, 437–446. DOI: https://doi.org/10.2147/CEOR.S501243

[61] Qnais, E., Barakat, M., Alnajjar, R., et al., 2025. Awareness, Attitudes, and Practices Regarding OTC Drugs in Circassian and Chechen Communities in Jordan: A Cross-Sectional Study. Patient Preference and Adherence. 19, 1661–1672. DOI: https://doi.org/10.2147/PPA.S525522

[62] Rorat, M.J., Szymański, W., Zińczuk, A., 2025. To Use or Not to Use: Safety of Selected Painkillers in Patients With Chronic Liver Diseases. Clinical and Experimental Hepatology. 11(2), 113–120. DOI: https://doi.org/10.5114/ceh.2025.151745

[63] Huang, C., Keller, M., Yang, S., 2025. Pain Self-Management Strategies for Hidradenitis Suppurativa Patients: An In-Person Survey Study. Journal of Cutaneous Medicine and Surgery. 29(3), 259–262. DOI: https://doi.org/10.1177/12034754241308245

[64] Lacy, B.E., Shea, E.P., Manuel, M., et al., 2021. Lessons Learned: Chronic Idiopathic Constipation Patient Experiences With Over-the-Counter Medications. PLOS One. 16(1), e0243318. DOI: https://doi.org/10.1371/journal.pone.0243318

[65] McCormick, D., 2019. Managing Costs and Care for Chronic Idiopathic Constipation. American Journal of Managed Care. 25(4S), S63–S69.

[66] Rao, S.S.C., Brenner, D.M., 2021. Efficacy and Safety of Over-the-Counter Therapies for Chronic Constipation: An Updated Systematic Review. American Journal of Gastroenterology. 116(6), 1156–1181. DOI: https://doi.org/10.14309/ajg.0000000000001222

[67] Rao, S.S.C., Brenner, D.M., 2022. Evidence-Based Treatment Recommendations for OTC Management of Chronic Constipation. Journal of the American Association of Nurse Practitioners. 34(9), 1041–1044. DOI: https://doi.org/10.1097/JXX.0000000000000760

[68] Lombardi, N., Crescioli, G., Maggini, V., et al., 2022. Adverse Events Related to Herbal Dietary Supplements and Over-the-Counter Medications Containing Laxatives: A 10-Year Update From the Italian Phytovigilance and Pharmacovigilance Systems. Annali dell’Istituto Superiore di Sanità. 58(2), 131–138. DOI: https://doi.org/10.4415/ANN_22_02_09

[69] Noergaard, M., Traerup Andersen, J., Jimenez-Solem, E., et al., 2019. Long Term Treatment With Stimulant Laxatives—Clinical Evidence for Effectiveness and Safety? Scandinavian Journal of Gastroenterology. 54(1), 27–34. DOI: https://doi.org/10.1080/00365521.2018.1563806

[70] Talukdar, M.I.A., Ahamad, I., Iqbal, S., et al., 2021. Fabrication of Metal Incorporated Polymer Composite: An Excellent Antibacterial Agent. Journal of Molecular Structure. 1225, 129091. DOI: https://doi.org/10.1016/j.molstruc.2020.129091

[71] Talukdar, M.I.A., Akram, M.K., Singh, T., et al., 2019. In-Situ Modification of Castor Oil With Divalent Metal Ions Like Zn (II), Cu (II), Co (II) and Ba (II) and Their Comparative Antioxidant Study by In-Vitro Methods. Food Chemistry. 284, 213–218. DOI: https://doi.org/10.1016/j.foodchem.2019.01.033

[72] Horn, J.R., Mantione, M.M., Johanson, J.F., 2012. OTC Polyethylene Glycol 3350 and Pharmacists’ Role in Managing Constipation. Journal of the American Pharmacists Association. 52(3), 372–380. DOI: https://doi.org/10.1331/JAPhA.2012.10161

[73] Palkar, P., Kothari, D., 2018. Bradycardia and Syncope in a Patient Presenting With Loperamide Abuse. Cureus. 10(5), e2599. DOI: https://doi.org/10.7759/cureus.2599

[74] Donnelly, S.C., 2020. Recreational Drug Use of Over-the-Counter (OTC) Medication: Loperamide and the Opiate Epidemic. QJM: An International Journal of Medicine. 113(1), 1. DOI: https://doi.org/10.1093/qjmed/hcz315

[75] Schifano, F., Chiappini, S., 2018. Is There Such a Thing as a “Lope” Dope? Analysis of Loperamide-Related European Medicines Agency (EMA) Pharmacovigilance Database Reports. PLOS One. 13(10), e0204443. DOI: https://doi.org/10.1371/journal.pone.0204443

[76] Aschenbrenner, D.S., 2018. FDA to Minimize Abuse Potential of OTC Antidiarrheal. American Journal of Nursing. 118(6), 25–26. DOI: https://doi.org/10.1097/01.NAJ.0000534847.35384.10

[77] Sapra, A., Bhandari, P., Gupta, S., et al., 2019. A Rising Concern of Loperamide Abuse: A Case Report on Resulting Cardiac Complications. Cureus. 11(12), e6314. DOI: https://doi.org/10.7759/cureus.6314

[78] Rawala, M.S., Gulati, R., Rizvi, S., 2020. Cardiac Dysrhythmia Associated With Opioid Toxicity. Cureus. 12(5), e8243. DOI: https://doi.org/10.7759/cureus.8243

[79] Fletcher, P., Steffen, R., DuPont, H., 1995. Benefit/Risk Considerations With Respect to OTC-Descheduling of Loperamide. Arzneimittel-Forschung. 45(5), 608–613.

[80] Langer, B., Kunow, C., 2019. Medication Dispensing, Additional Therapeutic Recommendations, and Pricing Practices for Acute Diarrhoea by Community Pharmacies in Germany: A Simulated Patient Study. Pharmacy Practice. 17(3), 1579. DOI: https://doi.org/10.18549/PharmPract.2019.3.1579

[81] Podwojniak, A.C., Chen, K., Pullinger, B., et al., 2025. Severe Nasal Spray Oxymetazoline Use Disorder – A Case Report. Journal of Addictive Diseases. 1–5. DOI: https://doi.org/10.1080/10550887.2024.2430072

[82] Tuncay Tanriverdi, S., Gokce, E.H., Sušanj, I., et al., 2024. Comprehensive Evaluation of Xylometazoline Hydrochloride Formulations: Ex-Vivo and In-Vitro Studies. European Journal of Pharmaceutics and Biopharmaceutics. 203, 114466. DOI: https://doi.org/10.1016/j.ejpb.2024.114466

[83] Wojas, O., Krzych-Fałta, E., Furmańczyk, K., et al., 2019. The Use of Nasal Over-the-Counter Agents in the Evaluated Polish Population: The Underrated Role of the Pharmacist in Patient Education on Medical Treatment in Patients With Allergic Rhinitis. Postepy Dermatologii i Alergologii. 36(5), 524–530. DOI: https://doi.org/10.5114/ada.2019.84289

[84] Banaś, B.P., Brzeźniakiewicz-Janus, K., Majdanik, S., et al., 2024. Hemorrhagic Stroke Caused by Xylometazoline Poisoning. Journal of Forensic Sciences. 69(1), 359–364. DOI: https://doi.org/10.1111/1556-4029.15416

[85] Barkholtz, H.M., Hadzima, R., Miles, A., 2023. Pharmacology of R-(-)-Methamphetamine in Humans: A Systematic Review of the Literature. ACS Pharmacology and Translational Science. 6(7), 914–924. DOI: https://doi.org/10.1021/acsptsci.3c00019

[86] Goraya, M.H.N., Inayat, F., Taj, S., et al., 2023. Acute Ischemic Colitis Associated With Oral Decongestant Use: A Systematic Review. Journal of Clinical and Translational Research. 9(3), 195–205.

[87] Gelotte, C.K., 2018. An Open-Label, Randomized, Four-Treatment Crossover Study Evaluating the Effects of Salt Form, Acetaminophen, and Food on the Pharmacokinetics of Phenylephrine. Regulatory Toxicology and Pharmacology. 95, 333–338. DOI: https://doi.org/10.1016/j.yrtph.2018.04.008

[88] Hatton, R.C., Hendeles, L., 2022. Why Is Oral Phenylephrine on the Market After Compelling Evidence of Its Ineffectiveness as a Decongestant? Annals of Pharmacotherapy. 56(11), 1275–1278. DOI: https://doi.org/10.1177/10600280221081526

[89] Aschenbrenner, D.S., 2021. Abuse or Misuse of OTC Decongestant Produces Serious Adverse Effects. American Journal of Nursing. 121(7), 24. DOI: https://doi.org/10.1097/01.NAJ.0000758484.08733.6f

[90] McCoul, E.D., 2021. Contemporary Role and Regulation of Over-the-Counter Sinonasal Medications. Otolaryngology–Head and Neck Surgery. 165(1), 7–13. DOI: https://doi.org/10.1177/0194599820969177

[91] Carr, W.W., Yawn, B.P., 2017. Management of Allergic Rhinitis in the Era of Effective Over-the-Counter Treatments. Postgraduate Medicine. 129(6), 572–580. DOI: https://doi.org/10.1080/00325481.2017.1333384

[92] McDonnell, J., Weller, K., Pien, L.C., 2020. Safety of Intranasal Steroids: An Updated Perspective. Current Allergy and Asthma Reports. 20(11), 69. DOI: https://doi.org/10.1007/s11882-020-00960-2

[93] Bridgeman, M.B., 2017. Overcoming Barriers to Intranasal Corticosteroid Use in Patients With Uncontrolled Allergic Rhinitis. Integrated Pharmacy Research and Practice. 6, 109–119. DOI: https://doi.org/10.2147/IPRP.S129544

[94] Koob, G.F., Volkow, N.D., 2010. Neurocircuitry of Addiction. Neuropsychopharmacology. 35(1), 217–238. DOI: https://doi.org/10.1038/npp.2009.110

[95] Volkow, N.D., Morales, M., 2015. The Brain on Drugs: From Reward to Addiction. Cell. 162(4), 712–725. DOI: https://doi.org/10.1016/j.cell.2015.07.046

[96] Borrego-Ruiz, A., Borrego, J.J., 2025. Pharmacogenomic and Pharmacomicrobiomic Aspects of Drugs of Abuse. Genes. 16(4), 403. DOI: https://doi.org/10.3390/genes16040403

[97] Borrego-Ruiz, A., Borrego, J.J., 2025. The Bidirectional Interplay Between Substances of Abuse and Gut Microbiome Homeostasis. Life. 15(6), 834. DOI: https://doi.org/10.3390/life15060834

[98] Yene, F., Bantie, B., Yilma, T., et al., 2025. Non-Prescribed Drug Use and Its Associated Factors Among Pregnant Women in Southwest Ethiopia. Scientific Reports. 15(1), 22851. DOI: https://doi.org/10.1038/s41598-024-80247-y

[99] Thiruchelvam, K., Uwajima, E., Selan, S.M.G., et al., 2025. Prevalence of Over-the-Counter Medication Use in Pregnancy: A Systematic Review and Meta-Analysis. Discover Public Health. 22, 278. DOI: https://doi.org/10.1186/s12982-025-00656-w

[100] Ma, C., Zhang, H., 2025. A Cross-Sectional Study on Self-Medication With Over-the-Counter Drugs Among Adolescents: An Analysis of Current Practices. Frontiers in Public Health. 13, 1560299. DOI: https://doi.org/10.3389/fpubh.2025.1560299

[101] Abraham, O., Chmielinski, J., 2018. Adolescents’ Misuse of Over-the-Counter Medications: The Need for Pharmacist-Led Intervention. Innovations in Pharmacy. 9(3), 1–7. DOI: https://doi.org/10.24926/iip.v9i3.979

[102] Karami, S., Ventura, C.A.I., Pinnow, E., et al., 2025. Trends in US Pediatric Unintentional Nonprescription Cold and Cough, Analgesic and Antipyretic Drug Exposure Cases Amid the COVID-19 Pandemic. Clinical Drug Investigation. 45(7), 401–416. DOI: https://doi.org/10.1007/s40261-025-01444-9

[103] Summerlin, J., Eiland, L.S., 2025. The Use and Safety of Cough and Cold Medications in the Pediatric Population. Journal of Pediatric Pharmacology and Therapeutics. 30(1), 17–26.

[104] Bentley, S., Downs, L., Oliver, S., et al., 2024. Over-the-Counter Analgesic-Related Exposure and Toxicity in Pediatrics. Journal of the American Pharmacists Association. 64(6), 102218. DOI: https://doi.org/10.1016/j.japh.2024.102218

[105] Purser, G.L., Munroe, L., Zayed, C., 2025. Over-the-Counter Cough Medicine and Prescription Drug Misuse Among Adolescents and Young Adults. Health and Social Work. 50(2), 111–120. DOI: https://doi.org/10.1093/hsw/hlaf004

[106] Aydın Aksoy, E., Güçiz Doğan, B., Yalçın, S.S., 2024. Nutrient Supplements for Young Children and Mothers’ Self-Medication With Over-the-Counter Drugs During the COVID-19 Pandemic. Nutrients. 16(23), 4182. DOI: https://doi.org/10.3390/nu16234182

[107] Gilson, A.M., Chladek, J.S., Stone, J.A., et al., 2025. Older Adult Misuse of Over-the-Counter Medications: Effectiveness of a Novel Pharmacy-Based Intervention to Improve Patient Safety. Journal of Patient Safety. 21(1), 38–47. DOI: https://doi.org/10.1097/PTS.0000000000001288

[108] Sheikh-Taha, M., Dimassi, H., 2018. Use of Over-the-Counter Products in Older Cardiovascular Patients Admitted to a Tertiary Care Center in USA. BMC Geriatrics. 18(1), 301. DOI: https://doi.org/10.1186/s12877-018-0989-7

[109] Stone, J.A., Lester, C.A., Aboneh, E.A., et al., 2017. A Preliminary Examination of Over-the-Counter Medication Misuse Rates in Older Adults. Research in Social and Administrative Pharmacy. 13(1), 187–192. DOI: https://doi.org/10.1016/j.sapharm.2016.01.004

[110] Mosca, A., Chiappini, S., Mancusi, G., et al., 2025. Over-the-Counter Psychosis: A Systematic Review of the Misuse of Antihistamines, Cough Medicines, and Decongestants and the Risk of Developing Psychosis. Current Neuropharmacology. 23(8), 956–973. DOI: https://doi.org/10.2174/011570159X344365250114064248

[111] Bareis, N., Edlund, M., Ringeisen, H., et al., 2025. Characterizing Schizophrenia Spectrum Disorders: Results of the U.S. Mental and Substance Use Disorders Prevalence Study. Psychiatric Services. 76(1), 2–12. DOI: https://doi.org/10.1176/appi.ps.20240138

[112] Rodan, S.C., Maguire, S., Meez, N., et al., 2025. Prescription and Nonprescription Drug Use Among People With Eating Disorders. JAMA Network Open. 8(7), e2522406. DOI: https://doi.org/10.1001/jamanetworkopen.2025.22406

[113] Boniol, M., Kunjumen, T., Nair, T.S., et al., 2022. The Global Health Workforce Stock and Distribution in 2020 and 2030: A Threat to Equity and “Universal” Health Coverage? BMJ Global Health. 7(6), e009316. DOI: https://doi.org/10.1136/bmjgh-2022-009316

[114] Michaeli, D.T., Michaeli, J.C., Albers, S., et al., 2024. The Healthcare Workforce Shortage of Nurses and Physicians: Practice, Theory, Evidence, and Ways Forward. Policy, Politics and Nursing Practice. 25(4), 216–227. DOI: https://doi.org/10.1177/15271544241286083

[115] Barakat, M., Sallam, M., 2025. Pharmacy Workforce: A Systematic Review of Key Drivers of Pharmacists’ Satisfaction and Retention. Journal of Pharmaceutical Policy and Practice. 18(1), 2470848. DOI: https://doi.org/10.1080/20523211.2025.2470848

[116] Barrett, R., Aldamkhi, H., 2021. An Evaluation of the Knowledge and Perceptions of Pharmacy Staff and Pre-Registration Students of E-Cigarettes Use: A Systematic Review. Tobacco Use Insights. 14. DOI: https://doi.org/10.1177/1179173X211016867

[117] Risvoll, H., Musial, F., Halvorsen, K.H., et al., 2019. Pharmacy Employees’ Involvement in Safeguarding Persons With Dementia Who Use Dietary Supplements: Results From a Survey of Norwegian Pharmacies. BMC Complementary and Alternative Medicine. 19(1), 179. DOI: https://doi.org/10.1186/s12906-019-2587-4

[118] Persson, A., Troein, M., Lundin, S., et al., 2022. Swedish Community Pharmacy Employees’ Knowledge and Experience of Substandard and Falsified Medical Products: A Cross-Sectional Descriptive Survey. International Journal of Pharmacy Practice. 30(5), 414–419. DOI: https://doi.org/10.1093/ijpp/riac059

[119] Alanazi, S., Dekhaela, S., Obaidy, S., et al., 2023. Assessment of Employee Engagement in Pharmaceutical Care Service at King Abdulaziz Medical City – Central Region (KAMC): A Cross-Sectional Study. Saudi Pharmaceutical Journal. 31(5), 765–772. DOI: https://doi.org/10.1016/j.jsps.2023.03.017

[120] Simons, G., Ismail, N., Sandhu, K., et al., 2022. The Potential Role of Community Pharmacy Staff in Reducing Patient Delay in Consulting With Symptoms of Rheumatoid Arthritis: A Qualitative Study. BMC Rheumatology. 6(1), 50. DOI: https://doi.org/10.1186/s41927-022-00280-0

[121] De Tran, V., Pham, T.T., Le, T.H., et al., 2024. Workplace Wellbeing in Community Pharmacy Practice: A Cross-Sectional Study in Can Tho, Vietnam. AIMS Public Health. 11(1), 258–272. DOI: https://doi.org/10.3934/publichealth.2024013

[122] Marupuru, S., Axon, D.R., Campbell, P., et al., 2020. Exploring Performance Predictors Among Employees in a Pharmacist-Led Medication Management Center. Journal of the American Pharmacists Association. 60(6), 809–817. DOI: https://doi.org/10.1016/j.japh.2020.04.009

[123] Sánchez-Sánchez, E., Fernández-Cerezo, F.L., Díaz-Jimenez, J., et al., 2021. Consumption of Over-the-Counter Drugs: Prevalence and Type of Drugs. International Journal of Environmental Research and Public Health. 18(11), 5530. DOI: https://doi.org/10.3390/ijerph18115530

[124] Hailu, A.D., Workneh, B.D., Kahissay, M.H., 2021. Influence of Pharmaceutical Marketing Mix Strategies on Physicians’ Prescribing Behaviors in Public and Private Hospitals, Dessie, Ethiopia: A Mixed Study Design. BMC Public Health. 21(1), 65. DOI: https://doi.org/10.1186/s12889-020-10063-2

[125] Groves, P.M., Thompson, R.F., 1970. Habituation: A Dual-Process Theory. Psychological Review. 77(5), 419–450. DOI: https://doi.org/10.1037/h0029810

[126] Oinas, J.P., Wazaify, M., Laaksonen, R., 2024. Preventing the Abuse and Misuse of Over-the-Counter Medicines: A Survey of Community Pharmacists in Finland. Substance Use and Misuse. 59(3), 411–420. DOI: https://doi.org/10.1080/10826084.2023.2275564

[127] Algarni, M., Jalal, Z., Hadi, M.A., et al., 2022. Community Pharmacists’ Views and Experiences Toward Over-the-Counter Medicines Misuse and Abuse in Saudi Arabia: A Qualitative Study. Frontiers in Pharmacology. 13, 997342. DOI: https://doi.org/10.3389/fphar.2022.997342

[128] Dressel, A., Schneider, R., DeNomie, M., et al., 2018. Assessing Health Promotion Interventions: Limitations of Traditional Research Methods in Community-Based Studies. Health Promotion Practice. 19(4), 573–580. DOI: https://doi.org/10.1177/1524839917725489

[129] Iyamu, I., Gómez-Ramírez, O., Xu, A.X., et al., 2022. Challenges in the Development of Digital Public Health Interventions and Mapped Solutions: Findings From a Scoping Review. Digital Health. 8. DOI: https://doi.org/10.1177/20552076221102255

[130] Weber, P., Birkholz, L., Straub, R., et al., 2024. The Limitations and Potentials of Evaluating Economic Aspects of Community-Based Health Promotion: A Critical Review. Applied Health Economics and Health Policy. 22(2), 165–179. DOI: https://doi.org/10.1007/s40258-023-00864-y

[131] Kemm, J., 2006. The Limitations of “Evidence-Based” Public Health. Journal of Evaluation in Clinical Practice. 12(3), 319–324. DOI: https://doi.org/10.1111/j.1365-2753.2006.00600.x

[132] Hill, C., Guarner, F., Reid, G., et al., 2014. Expert Consensus Document. The International Scientific Association for Probiotics and Prebiotics Consensus Statement on the Scope and Appropriate Use of the Term Probiotic. Nature Reviews Gastroenterology and Hepatology. 11(8), 506–514. DOI: https://doi.org/10.1038/nrgastro.2014.66

[133] Borrego-Ruiz, A., Borrego, J.J., 2024. Psychobiotics: A New Perspective on the Treatment of Stress, Anxiety, and Depression. Ansiedad y Estrés. 30(2), 79–93. DOI: https://doi.org/10.5093/anyes2024a11 (in Spanish)

[134] de Sequeira, C.L.M., Hengstberger, C., Enck, P., et al., 2022. Effect of Probiotics on Psychiatric Symptoms and Central Nervous System Functions in Human Health and Disease: A Systematic Review and Meta-Analysis. Nutrients. 14(3), 621. DOI: https://doi.org/10.3390/nu14030621

[135] de Melo Pereira, G.V., de Oliveira Coelho, B., Magalhães Júnior, A.I., et al., 2018. How to Select a Probiotic? A Review and Update of Methods and Criteria. Biotechnology Advances. 36(8), 2060–2076. DOI: https://doi.org/10.1016/j.biotechadv.2018.09.003

[136] Damián, M.R., Cortes-Perez, N.G., Quintana, E.T., et al., 2022. Functional Foods, Nutraceuticals and Probiotics: A Focus on Human Health. Microorganisms. 10(5), 1065. DOI: https://doi.org/10.3390/microorganisms10051065

[137] Mazziotta, C., Tognon, M., Martini, F., et al., 2023. Probiotics Mechanism of Action on Immune Cells and Beneficial Effects on Human Health. Cells. 12(1), 184. DOI: https://doi.org/10.3390/cells12010184

[138] Tegegne, B.A., Kebede, B., 2022. Probiotics, Their Prophylactic and Therapeutic Applications in Human Health Development: A Review of the Literature. Heliyon. 8(6), e09725. DOI: https://doi.org/10.1016/j.heliyon.2022.e09725

[139] Bodke, H., Jogdand, S., 2022. Role of Probiotics in Human Health. Cureus. 14(11), e31313. DOI: https://doi.org/10.7759/cureus.31313

[140] Chandrasekaran, P., Weiskirchen, S., Weiskirchen, R., 2024. Effects of Probiotics on Gut Microbiota: An Overview. International Journal of Molecular Sciences. 25(11), 6022. DOI: https://doi.org/10.3390/ijms25116022

[141] Plaza-Diaz, J., Ruiz-Ojeda, F.J., Gil-Campos, M., et al., 2019. Mechanisms of Action of Probiotics. Advances in Nutrition. 10(S1), S49–S66. DOI: https://doi.org/10.1093/advances/nmy063

[142] Johnson, D., Letchumanan, V., Thum, C.C., et al., 2023. A Microbial-Based Approach to Mental Health: The Potential of Probiotics in the Treatment of Depression. Nutrients. 15(6), 1382. DOI: https://doi.org/10.3390/nu15061382

[143] Ferrari, S., Mulè, S., Parini, F., et al., 2024. The Influence of the Gut-Brain Axis on Anxiety and Depression: A Review of the Literature on the Use of Probiotics. Journal of Traditional and Complementary Medicine. 14(3), 237–255. DOI: https://doi.org/10.1016/j.jtcme.2024.03.011

[144] Huang, R., Wang, K., Hu, J., 2016. Effect of Probiotics on Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 8(8), 483. DOI: https://doi.org/10.3390/nu8080483

[145] Messaoudi, M., Violle, N., Bisson, J.F., et al., 2011. Beneficial Psychological Effects of a Probiotic Formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in Healthy Human Volunteers. Gut Microbes. 2(4), 256–261. DOI: https://doi.org/10.4161/gmic.2.4.16108

[146] Sikorska, M., Antosik-Wójcińska, A.Z., Dominiak, M., 2023. Probiotics as a Tool for Regulating Molecular Mechanisms in Depression: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. International Journal of Molecular Sciences. 24(4), 3081. DOI: https://doi.org/10.3390/ijms24043081

[147] Zhang, N., Zhang, Y., Li, M., et al., 2020. Efficacy of Probiotics on Stress in Healthy Volunteers: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials. Brain and Behavior. 10(9), e01699. DOI: https://doi.org/10.1002/brb3.1699

[148] El Dib, R., Periyasamy, A.G., de Barros, J.L., et al., 2021. Probiotics for the Treatment of Depression and Anxiety: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Clinical Nutrition ESPEN. 45, 75–90. DOI: https://doi.org/10.1016/j.clnesp.2021.07.027

[149] Merkouris, E., Mavroudi, T., Miliotas, D., et al., 2024. Probiotics’ Effects in the Treatment of Anxiety and Depression: A Comprehensive Review of 2014–2023 Clinical Trials. Microorganisms. 12(2), 411. DOI: https://doi.org/10.3390/microorganisms12020411

[150] Johnson, K.V., Steenbergen, L., 2025. Probiotics Reduce Negative Mood Over Time: The Value of Daily Self-Reports in Detecting Effects. NPJ Mental Health Research. 4(1), 10. DOI: https://doi.org/10.1038/s44184-025-00123-z

[151] Li, Y., Hao, Y., Fan, F., et al., 2018. The Role of Microbiome in Insomnia, Circadian Disturbance, and Depression. Frontiers in Psychiatry. 9, 669. DOI: https://doi.org/10.3389/fpsyt.2018.00669

[152] Matenchuk, B.A., Mandhane, P.J., Kozyrskyj, A.L., 2020. Sleep, Circadian Rhythm, and Gut Microbiota. Sleep Medicine Reviews. 53, 101340. DOI: https://doi.org/10.1016/j.smrv.2020.101340

[153] Takada, M., Nishida, K., Gondo, Y., et al., 2017. Beneficial Effects of Lactobacillus casei Strain Shirota on Academic Stress-Induced Sleep Disturbance in Healthy Adults: A Double-Blind, Randomized, Placebo-Controlled Trial. Beneficial Microbes. 8(2), 153–162. DOI: https://doi.org/10.3920/BM2016.0150

[154] Moloney, G.M., Long-Smith, C.M., Murphy, A., et al., 2021. Improvements in Sleep Indices During Exam Stress Due to Consumption of Bifidobacterium longum. Brain, Behavior, and Immunity-Health. 10, 100174. DOI: https://doi.org/10.1016/j.bbih.2020.100174

[155] Ito, H., Tomura, Y., Kitagawa, Y., et al., 2024. Effects of Probiotics on Sleep Parameters: A Systematic Review and Meta-Analysis. Clinical Nutrition ESPEN. 63, 623–630. DOI: https://doi.org/10.1016/j.clnesp.2024.07.006

[156] Singh, R., Zogg, H., Wei, L., et al., 2021. Gut Microbial Dysbiosis in the Pathogenesis of Gastrointestinal Dysmotility and Metabolic Disorders. Journal of Neurogastroenterology and Motility. 27(1), 19–34. DOI: https://doi.org/10.5056/jnm20149

[157] Dimidi, E., Christodoulides, S., Scott, S.M., et al., 2017. Mechanisms of Action of Probiotics and the Gastrointestinal Microbiota on Gut Motility and Constipation. Advances in Nutrition. 8(3), 484–494. DOI: https://doi.org/10.3945/an.116.014407

[158] Black, C.J., Drossman, D.A., Talley, N.J., et al., 2020. Functional Gastrointestinal Disorders: Advances in Understanding and Management. Lancet. 396(10263), 1664–1674. DOI: https://doi.org/10.1016/S0140-6736(20)32115-2

[159] Hojsak, I., 2024. Probiotics in Functional Gastrointestinal Disorders. Advances in Experimental Medicine and Biology. 1449, 157–174. DOI: https://doi.org/10.1007/978-3-031-58572-2_10

[160] Ishizuka, A., Tomizuka, K., Aoki, R., et al., 2012. Effects of Administration of Bifidobacterium animalis subsp. lactis GCL2505 on Defecation Frequency and Bifidobacterial Microbiota Composition in Humans. Journal of Bioscience and Bioengineering. 113(5), 587–591. DOI: https://doi.org/10.1016/j.jbiosc.2011.12.016

[161] Matsumoto, K., Takada, T., Shimizu, K., et al., 2010. Effects of a Probiotic Fermented Milk Beverage Containing Lactobacillus casei Strain Shirota on Defecation Frequency, Intestinal Microbiota, and the Intestinal Environment of Healthy Individuals With Soft Stools. Journal of Bioscience and Bioengineering. 110(5), 547–552. DOI: https://doi.org/10.1016/j.jbiosc.2010.05.016

[162] Kim, S.E., Choi, S.C., Park, K.S., et al., 2015. Change of Fecal Flora and Effectiveness of the Short-Term VSL#3 Probiotic Treatment in Patients With Functional Constipation. Journal of Neurogastroenterology and Motility. 21(1), 111–120. DOI: https://doi.org/10.5056/jnm14048

[163] He, Y., Zhu, L., Chen, J., et al., 2022. Efficacy of Probiotic Compounds in Relieving Constipation and Their Colonization in Gut Microbiota. Molecules. 27(3), 666. DOI: https://doi.org/10.3390/molecules27030666

[164] Liu, B., He, Y., Wang, M., et al., 2018. Efficacy of Probiotics on Anxiety: A Meta-Analysis of Randomized Controlled Trials. Depression and Anxiety. 35(10), 935–945. DOI: https://doi.org/10.1002/da.22811

[165] Riezzo, G., Orlando, A., D’Attoma, et al., 2012. Randomized Clinical Trial: Efficacy of Lactobacillus paracasei-Enriched Artichokes in the Treatment of Patients With Functional Constipation – A Double-Blind, Controlled, Crossover Study. Alimentary Pharmacology and Therapeutics. 35(4), 441–450. DOI: https://doi.org/10.1111/j.1365-2036.2011.04970.x

[166] Gong, P., Tang, X., 2025. The Impact of Probiotic Supplementation on Gastric Motility and Nutrient Absorption in Elderly Patients With Gastrointestinal Disorders. BMC Gastroenterology. 25, 192. DOI: https://doi.org/10.1186/s12876-025-03740-2

[167] Caballero-Franco, C., Keller, K., De Simone, C., et al., 2007. The VSL#3 Probiotic Formula Induces Mucin Gene Expression and Secretion in Colonic Epithelial Cells. American Journal of Physiology − Gastrointestinal and Liver Physiology. 292(1), G315–G322. DOI: https://doi.org/10.1152/ajpgi.00265.2006

[168] Ouwehand, A.C., Lagstrom, H., Suomalainen, T., et al., 2002. Effect of Probiotics on Constipation, Fecal Azoreductase Activity, and Fecal Mucin Content in the Elderly. Annals of Nutrition and Metabolism. 46(3–4), 159–162. DOI: https://doi.org/10.1159/000063075

[169] Borrego-Ruiz, A., Borrego, J., 2025. Microbial Therapeutic Tools for Human Brain Disorders: A Current Overview. Brain Disorders. 19, 100262. DOI: https://doi.org/10.1016/j.dscb.2025.100262

[170] Borrego-Ruiz, A., Borrego, J., 2024. A Current Review on Microbial Therapeutic Approaches Aimed at Improving Cognitive Functions in Older Adults. Gerokomos. 35(4), 235–243. Available from: https://scielo.isciii.es/scielo.php?script=sci_arttext&pid=S1134-928X2024000400005 (in Spanish)

[171] Borrego-Ruiz, A., Borrego, J.J., 2025. Plant-Derived Nutraceuticals in Mental Health and Brain Function: Mechanisms of Action and Therapeutic Potential. International Journal of Molecular Sciences. 26(18), 8849.

[172] Matias, J.N., Achete, G., Campanari, G.S.D.S., et al., 2021. A Systematic Review of the Antidepressant Effects of Curcumin: Beyond Monoamines Theory. Australian and New Zealand Journal of Psychiatry. 55(5), 451–462.

[173] Ramaholimihaso, T., Bouazzaoui, F., Kaladjian, A., 2020. Curcumin in Depression: Potential Mechanisms of Action and Current Evidence—A Narrative Review. Frontiers in Psychiatry. 11, 572533. DOI: https://doi.org/10.3389/fpsyt.2020.572533

[174] Pan, X., Chen, L., Xu, W., et al., 2021. Activation of Monoaminergic System Contributes to the Antidepressant- and Anxiolytic-Like Effects of J147. Behavioral Brain Research. 411, 113374. DOI: https://doi.org/10.1016/j.bbr.2021.113374

[175] Barati, S., Yadegari, A., Shahmohammadi, M., et al., 2025. Curcumin as a Promising Therapeutic Agent for Diabetic Neuropathy: From Molecular Mechanisms to Functional Recovery. Diabetology and Metabolic Syndrome. 17(1), 314.

[176] Dold, M., Bartova, L., Volz, H.P., et al., 2023. Efficacy of Silexan in Patients With Anxiety Disorders: A Meta-Analysis of Randomized, Placebo-Controlled Trials. European Archives of Psychiatry and Clinical Neuroscience. 273(7), 1615–1628.

[177] Kasper, S., Eckert, A., 2024. Silexan in Anxiety, Depression, and Related Disorders: Pharmacological Background and Clinical Data. European Archives of Psychiatry and Clinical Neuroscience. 275, 1621–1635. DOI: https://doi.org/10.1007/s00406-024-01923-8

[178] Chen, P., Hei, M., Kong, L., et al., 2019. One Water-Soluble Polysaccharide From Ginkgo biloba Leaves with Antidepressant Activities via Modulation of the Gut Microbiome. Food Function. 10(12), 8161–8171.

[179] Singh, S.K., Srivastav, S., Castellani, R.J., et al., 2019. Neuroprotective and Antioxidant Effect of Ginkgo biloba Extract Against AD and Other Neurological Disorders. Neurotherapeutics. 16(3), 666–674.

[180] Jakaria, M., Ezazul Haque M., Kim, J., et al., 2018. Active Ginseng Components in Cognitive Impairment: Therapeutic Potential and Prospects for Delivery and Clinical Study. Oncotarget. 9, 33601–33620.

[181] Lu, C., Wang, Y., Lv, J., et al., 2018. Ginsenoside Rh2 Reverses Sleep Deprivation-Induced Cognitive Deficit in Mice. Behavioural Brain Research. 349, 109–115.

[182] Borrego-Ruiz, A., Borrego, J.J., 2025. A Holistic Review of Cannabis and Its Potential Risks and Benefits in Mental Health. Psychiatry International. 6, 92.

[183] Khoury, J.M., Neves, M.C.L.D., Roque, M.A.V., et al., 2019. Is There a Role for Cannabidiol in Psychiatry? World Journal of Biological Psychiatry. 20(2), 101–116.

[184] White, C.M., 2019. A Review of Human Studies Assessing Cannabidiol’s (CBD) Therapeutic Actions and Potential. Journal of Clinical Pharmacology. 59(7), 923–934.

[185] Borrego-Ruiz, A., Borrego, J.J., 2025. Nutritional Psychiatry: A Novel Approach to the Treatment of Mental Health Disorders. Actas Españolas de Psiquiatría. 53(2), 443–445. DOI: https://doi.org/10.62641/aep.v53i2.1920

[186] Miech, R., 2008. The Formation of a Socioeconomic Health Disparity: The Case of Cocaine Use During the 1980s and 1990s. Journal of Health and Social Behavior. 49(3), 352–366. DOI: https://doi.org/10.1177/002214650804900308

[187] Siegel, R.K., 1984. Cocaine and the Privileged Class: A Review of Historical and Contemporary Images. Advances in Alcohol and Substance Abuse. 4(2), 37–49. DOI: https://doi.org/10.1300/J251v04n02_04

[188] Tokle, R., Pedersen, W., 2025. “Cubs of Wall Street”: Cocaine Use in Top-Boy Culture. British Journal of Sociology. 76(4), 757–766. DOI: https://doi.org/10.1111/1468-4446.13212

[189] Bertucci, C., Tedesco, D., Fabini, et al., 2014. Determination of Levamisole and Tetramisole in Seized Cocaine Samples by Enantioselective High-Performance Liquid Chromatography and Circular Dichroism Detection. Journal of Chromatography. 1363, 150–154. DOI: https://doi.org/10.1016/j.chroma.2014.07.069

[190] Choe, A.J., Ellison, R., Ramaswamy, S.R., et al., 2023. Profound Hyperthermia Associated With Fentanyl and Cocaine Use With Suspected Synephrine Adulteration. Journal of Emergency Medicine. 64(2), 259–262. DOI: https://doi.org/10.1016/j.jemermed.2022.11.003

[191] Evrard, I., Legleye, S., Cadet-Taïrou, A., 2010. Composition, Purity and Perceived Quality of Street Cocaine in France. International Journal of Drug Policy. 21(5), 399–406. DOI: https://doi.org/10.1016/j.drugpo.2010.03.004

[192] Kudlacek, O., Hofmaier, T., Luf, A., et al., 2017. Cocaine Adulteration. Journal of Chemical Neuroanatomy. 83–84, 75–81. DOI: https://doi.org/10.1016/j.jchemneu.2017.06.001

[193] Magalhães, E.J., Nascentes, C.C., Pereira, L.S., et al., 2013. Evaluation of the Composition of Street Cocaine Seized in Two Regions of Brazil. Science and Justice. 53(4), 425–432. DOI: https://doi.org/10.1016/j.scijus.2013.05.003

[194] Urzola-Ortega, J., Mendoza-Goez, L., Acevedo, D., 2021. Personal Doses of Cocaine and Coca Paste Are Adulterated in Cartagena de Indias (Colombia). Scientific World Journal. 2021, 5562315. DOI: https://doi.org/10.1155/2021/5562315

[195] Wagner, K.D., Fiuty, P., Page, K., et al., 2023. Prevalence of Fentanyl in Methamphetamine and Cocaine Samples Collected by Community-Based Drug Checking Services. Drug and Alcohol Dependence. 252, 110985. DOI: https://doi.org/10.1016/j.drugalcdep.2023.110985

[196] Ciccarone, D., 2021. The Rise of Illicit Fentanyls, Stimulants and the Fourth Wave of the Opioid Overdose Crisis. Current Opinion in Psychiatry. 34(4), 344–350. DOI: https://doi.org/10.1097/YCO.0000000000000717

[197] Sugaya, L.S., Salum, G.A., de Sousa Gurgel, W., et al., 2022. Efficacy and Safety of Methylphenidate and Behavioural Parent Training for Children Aged 3–5 Years With Attention-Deficit Hyperactivity Disorder: A Randomised, Double-Blind, Placebo-Controlled, and Sham Behavioural Parent Training-Controlled Trial. The Lancet Child & Adolescent Health. 6(12), 845–856. DOI: https://doi.org/10.1016/S2352-4642(22)00279-6

[198] Anand, S., Bharadvaja, N., 2022. Potential Benefits of Nutraceuticals for Oxidative Stress Management. Revista Brasileira de Farmacognosia. 32(2), 211–220. DOI: https://doi.org/10.1007/s43450-022-00246-w

[199] Gul, S., Durante-Mangoni, E., 2024. Unraveling the Puzzle: Health Benefits of Probiotics-A Comprehensive Review. Journal of Clinical Medicine. 13(5), 1436. DOI: https://doi.org/10.3390/jcm13051436

[200] Gullo, G., Carlomagno, G., Unfer, V., et al., 2015. Myo-Inositol: From Induction of Ovulation to Menopausal Disorder Management. Minerva Ginecologica. 67(5), 485–486.

Downloads

Issue

Vol. 3 No. 1 (January 2026): In Progress

Section

Review

License

Copyright (c) 2026 Food and Drug Safety

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.