A Review of the Mechanisms and Risks of Panax ginseng in the Treatment of Alcohol Use Disorder
Abstract
1. Red Ginseng—Introduction
2. Red Ginseng—Active Constituents and Mechanism of Action
2.1. Interference in Alcohol Absorption and Metabolism
2.2. Anti-Inflammatory Effects
2.3. Modulation of Neurotransmitter Systems
2.4. Additional Potential Mechanisms in Long-Term Alcohol Use
3. Red Ginseng—Therapeutic Effects
3.1. Symptom Relief in Ethanol-Induced Hangovers—A Human Study
3.2. Effects on Alcohol Withdrawal in Animal Models
3.3. Modulation of Addiction-Related Neurocircuitry
3.4. Protective Effects Against Alcoholic Fatty Liver Disease
4. Red Ginseng—Side Effects
4.1. Hepatic Concerns
4.2. Cardiovascular Effects
4.3. Neuropsychiatric Effects
4.4. Endocrine and Gynecologic Effects
4.5. Collective Side Effect Profile
5. Red Ginseng—Drug Interactions
5.1. Serotonin Syndrome
5.2. Warfarin and Antiplatelets
5.3. Neuropsychiatric Agents: Selegiline, Phenelzine, and Midazolam
5.4. Imatinib
6. Discussion and Summary of Results from Human Experiments and Case Reports
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
- Christensen, L.P. Chapter 1 Ginsenosides. In Advances in Food and Nutrition Research; Elsevier: Amsterdam, The Netherlands, 2008; Volume 55, pp. 1–99. [Google Scholar] [CrossRef]
- Kompała, M.; Kuc, J.; Skotnicki, Z.; Jasińska-Balwierz, A.; Hudz, N.; Balwierz, R.J.; Lipok, J. Panax ginseng C.A. Mey. As a potential raw material in the treatment of negative effects of alcohol consumption. Acta Pol. Pharm.–Drug Res. 2023, 80, 511–520. [Google Scholar] [CrossRef] [PubMed]
- Baeg, I.-H. The global ginseng market and korean ginseng. J. Ginseng Cult. 2022, 4, 1–12. [Google Scholar] [CrossRef]
- Woo, S.M.; Davis, W.D.; Aggarwal, S.; Clinton, J.W.; Kiparizoska, S.; Lewis, J.H. Herbal and dietary supplement induced liver injury: Highlights from the recent literature. World J. Hepatol. 2021, 13, 1019–1041. [Google Scholar] [CrossRef] [PubMed]
- SAMHSA, Center for Behavior Health Statistics and Quality. 2022 National Survey on Drug Use and Health. Table 5.9A—Alcohol Use Disorder in Past Year: Among People Aged 12 or Older; by Age Group and Demographic Characteristics, Numbers in Thousands, 2022 and 2023; SAMHSA, Center for Behavior Health Statistics and Quality: Rockville, MD, USA, 2024. Available online: https://www.samhsa.gov/data/report/2023-nsduh-detailed-tables (accessed on 21 May 2025).
- Wang, F.; Li, Y.; Zhang, Y.-J.; Zhou, Y.; Li, S.; Li, H.-B. Natural products for the prevention and treatment of hangover and alcohol use disorder. Molecules 2016, 21, 64. [Google Scholar] [CrossRef]
- Raslan, M.A. Natural products for the treatment of drug addiction: Narrative review. Chem. Biodivers. 2022, 19, e202200702. [Google Scholar] [CrossRef] [PubMed]
- Kim, H.J.; Kim, P.; Shin, C.Y. A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system. J. Ginseng Res. 2013, 37, 8–29. [Google Scholar] [CrossRef]
- Rogawski, M.A. Update on the neurobiology of alcohol withdrawal seizures. Epilepsy Curr. 2005, 5, 225–230. [Google Scholar] [CrossRef]
- Kim, H.J.; Oh, T.K.; Kim, Y.H.; Lee, J.; Moon, J.M.; Park, Y.S.; Sung, C.M. Pharmacokinetics of ginsenoside rb1, rg3, rk1, rg5, f2, and compound k from red ginseng extract in healthy korean volunteers. Evid.-Based Complement. Altern. Med. 2022, 2022, 8427519. [Google Scholar] [CrossRef]
- Jiang, R.; Dong, J.; Li, X.; Du, F.; Jia, W.; Xu, F.; Wang, F.; Yang, J.; Niu, W.; Li, C. Molecular mechanisms governing different pharmacokinetics of ginsenosides and potential for ginsenoside-perpetrated herb–drug interactions on OATP 1 B 3. Br. J. Pharmacol. 2015, 172, 1059–1073. [Google Scholar] [CrossRef]
- Swift, R.; Davidson, D. Alcohol hangover. Alcohol Health Res. World 1998, 22, 54–60. [Google Scholar]
- Lee, B. Wild ginseng attenuates anxiety- and depression-like behaviors during morphine withdrawal. J. Microbiol. Biotechnol. 2011, 21, 1088–1096. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Li, G.; Chen, T.; Wu, W.; Yan, Z.; Li, X. Anticancer effect and molecular mechanism of ginsenoside Rg3 in various cancer types. Intell. Pharm. 2023, 1, 52–63. [Google Scholar] [CrossRef]
- Yang, K.; Ryu, T.; Chung, B.S. A meta-analysis of preclinical studies to investigate the effect of Panax ginseng on alcohol-associated liver disease. Antioxidants 2023, 12, 841. [Google Scholar] [CrossRef]
- Zhu, W.; Zhang, Y.; Huang, Y.; Lu, L. Chinese herbal medicine for the treatment of drug addiction. In International Review of Neurobiology; Elsevier: Amsterdam, The Netherlands, 2017; Volume 135, pp. 279–295. [Google Scholar] [CrossRef]
- Christensen, L.P.; Jensen, M.; Kidmose, U. Simultaneous determination of ginsenosides and polyacetylenes in american ginseng root (Panax quinquefolium L.) by high-performance liquid chromatography. J. Agric. Food Chem. 2006, 54, 8995–9003. [Google Scholar] [CrossRef]
- Jeon, J.-H.; Lee, J.; Choi, M.-K.; Song, I.-S. Pharmacokinetics of ginsenosides following repeated oral administration of red ginseng extract significantly differ between species of experimental animals. Arch. Pharmacal Res. 2020, 43, 1335–1346. [Google Scholar] [CrossRef] [PubMed]
- Zhao, L.; Sui, M.; Zhang, T.; Zhang, K. The interaction between ginseng and gut microbiota. Front. Nutr. 2023, 10, 1301468. [Google Scholar] [CrossRef]
- Carai, M.A.M.; Agabio, R.; Bombardelli, E.; Bourov, I.; Luigi Gessa, G.; Lobina, C.; Morazzoni, P.; Pani, M.; Reali, R.; Vacca, G.; et al. Potential use of medicinal plants in the treatment of alcoholism. Fitoterapia 2000, 71, S38–S42. [Google Scholar] [CrossRef]
- Lee, Y.J.; Pantuck, C.B.; Pantuck, E.J. Effect of ginseng on plasma levels of ethanol in the rat. Planta Medica 1993, 59, 17–19. [Google Scholar] [CrossRef] [PubMed]
- Kim, H.J.; Lee, M.Y.; Kim, G.R.; Lee, H.J.; Sayson, L.V.; Ortiz, D.M.D.; Cheong, J.H.; Kim, M. Korean Red Ginseng extract attenuates alcohol-induced addictive responses and cognitive impairments by alleviating neuroinflammation. J. Ginseng Res. 2023, 47, 583–592. [Google Scholar] [CrossRef] [PubMed]
- Lee, M.-H.; Kwak, J.H.; Jeon, G.; Lee, J.-W.; Seo, J.-H.; Lee, H.-S.; Lee, J.H. Red ginseng relieves the effects of alcohol consumption and hangover symptoms in healthy men: A randomized crossover study. Food Funct. 2014, 5, 528. [Google Scholar] [CrossRef] [PubMed]
- Abenavoli, L.; Capasso, F.; Addolorato, G. Phytotherapeutic approach to alcohol dependence: New old way? Phytomedicine 2009, 16, 638–644. [Google Scholar] [CrossRef]
- Ik Lee, D.; Tae Kim, S.; Hoon Lee, D.; Min Yu, J.; Kil Jang, S.; Soo Joo, S. Ginsenoside-free molecules from steam-dried ginseng berry promote ethanol metabolism: An alternative choice for an alcohol hangover. J. Food Sci. 2014, 79, C1323–C1330. [Google Scholar] [CrossRef] [PubMed]
- Je, J.; Kim, H.; Park, E.J.; Kim, S.R.; Dusabimana, T.; Jeong, K.; Yun, S.P.; Kim, H.J.; Cho, K.M.; Park, S.W. Fermentation of sprouted ginseng (Panax ginseng) increases flavonoid and phenolic contents to attenuate alcoholic hangover and acute liver injury in mice. Am. J. Chin. Med. 2021, 49, 131–146. [Google Scholar] [CrossRef] [PubMed]
- Bae, E.-A.; Kim, E.-J.; Park, J.-S.; Kim, H.-S.; Ryu, J.H.; Kim, D.-H. Ginsenosides Rg3 and Rh2 inhibit the activation of AP-1 and protein kinase A pathway in lipopolysaccharide/interferon-gamma-stimulated BV-2 microglial cells. Planta Medica 2006, 72, 627–633. [Google Scholar] [CrossRef]
- Cha, H.-Y.; Park, J.-H.; Hong, J.-T.; Yoo, H.-S.; Song, S.; Hwang, B.-Y.; Eun, J.-S.; Oh, K.-W. Anxiolytic-like effects of ginsenosides on the elevated plus-maze model in mice. Biol. Pharm. Bull. 2005, 28, 1621–1625. [Google Scholar] [CrossRef]
- Zhao, Z.; Kim, Y.W.; Wu, Y.; Zhang, J.; Lee, J.-H.; Li, X.; Cho, I.J.; Park, S.M.; Jung, D.H.; Yang, C.H.; et al. Korean Red Ginseng attenuates anxiety-like behavior during ethanol withdrawal in rats. J. Ginseng Res. 2014, 38, 256–263. [Google Scholar] [CrossRef]
- Bhattacharya, S.K.; Mitra, S.K. Anxiolytic activity of Panax ginseng roots: An experimental study. J. Ethnopharmacol. 1991, 34, 87–92. [Google Scholar] [CrossRef] [PubMed]
- Lee, H.; Ok, H.; Kwon, O. Protective effects of Korean red ginseng against alcohol-induced fatty liver in rats. Molecules 2015, 20, 11604–11616. [Google Scholar] [CrossRef]
- Churchill, J.D.; Gerson, J.L.; Hinton, K.A.; Mifek, J.L.; Walter, M.J.; Winslow, C.L.; Deyo, R.A. The nootropic properties of ginseng saponin Rb1 are linked to effects on anxiety. Integr. Physiol. Behav. Sci. 2002, 37, 178–187. [Google Scholar] [CrossRef] [PubMed]
- Xu, C.; Teng, J.; Chen, W.; Ge, Q.; Yang, Z.; Yu, C.; Yang, Z.; Jia, W. 20(S)-protopanaxadiol, an active ginseng metabolite, exhibits strong antidepressant-like effects in animal tests. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 2010, 34, 1402–1411. [Google Scholar] [CrossRef]
- Paik, D.J.; Lee, C.H. Review of cases of patient risk associated with ginseng abuse and misuse. J. Ginseng Res. 2015, 39, 89–93. [Google Scholar] [CrossRef]
- Bilgi, N.; Bell, K.; Ananthakrishnan, A.N.; Atallah, E. Imatinib and Panax ginseng: A potential interaction resulting in liver toxicity. Ann. Pharmacother. 2010, 44, 926–928. [Google Scholar] [CrossRef] [PubMed]
- Zhou, J.; Zhang, J.; Jing, P.; Lan, Y.; Cao, X.; Feng, H.; Liu, X.; Liu, Q. Ginseng in white and red processed forms: Ginsenosides and cardiac side effects. Food Sci. Nutr. 2023, 12, 1857–1868. [Google Scholar] [CrossRef]
- Parlakpinar, H.; Ozhan, O.; Ermis, N.; Vardi, N.; Cigremis, Y.; Tanriverdi, L.H.; Colak, C.; Acet, A. Acute and subacute effects of low versus high doses of standardized Panax ginseng extract on the heart: An experimental study. Cardiovasc. Toxicol. 2019, 19, 306–320. [Google Scholar] [CrossRef] [PubMed]
- Aravinthan, A.; Kim, J.H.; Antonisamy, P.; Kang, C.-W.; Choi, J.; Kim, N.S.; Kim, J.-H. Ginseng total saponin attenuates myocardial injury via anti-oxidative and anti-inflammatory properties. J. Ginseng Res. 2015, 39, 206–212. [Google Scholar] [CrossRef]
- Torbey, E.; Abi Rafeh, N.; Khoueiry, G.; Kowalski, M.; Bekheit, S. Ginseng: A potential cause of long QT. J. Electrocardiol. 2011, 44, 357–358. [Google Scholar] [CrossRef] [PubMed]
- Norelli, L.J.; Xu, C. Manic psychosis associated with ginseng: A report of two cases and discussion of the literature. J. Diet. Suppl. 2015, 12, 119–125. [Google Scholar] [CrossRef]
- Kabalak, A.A.; Soyal, O.B.; Urfalioglu, A.; Saracoglu, F.; Gogus, N. Menometrorrhagia and tachyarrhythmia after using oral and topical ginseng. J. Women’s Health 2004, 13, 830–833. [Google Scholar] [CrossRef]
- Yang, M.; Lee, H.-S.; Hwang, M.-W.; Jin, M. Effects of Korean red ginseng (Panax ginseng meyer) on bisphenol A exposure and gynecologic complaints: Single blind, randomized clinical trial of efficacy and safety. BMC Complement. Altern. Med. 2014, 14, 265. [Google Scholar] [CrossRef]
- Yuan, C.-S.; Wei, G.; Dey, L.; Karrison, T.; Nahlik, L.; Maleckar, S.; Kasza, K.; Ang-Lee, M.; Moss, J. Brief communication: American ginseng reduces warfarin’s effect in healthy patients: A randomized, controlled trial. Ann. Intern. Med. 2004, 141, 23–27. [Google Scholar] [CrossRef]
- Lee, S.-H.; Ahn, Y.-M.; Ahn, S.-Y.; Doo, H.-K.; Lee, B.-C. Interaction between warfarin and Panax ginseng in ischemic stroke patients. J. Altern. Complement. Med. 2008, 14, 715–721. [Google Scholar] [CrossRef]
- Wang, G.-L.; He, Z.-M.; Zhu, H.-Y.; Gao, Y.-G.; Zhao, Y.; Yang, H.; Zhang, L.-X. Involvement of serotonergic, noradrenergic and dopaminergic systems in the antidepressant-like effect of ginsenoside Rb1, a major active ingredient of Panax ginseng C.A. Meyer. J. Ethnopharmacol. 2017, 204, 118–124. [Google Scholar] [CrossRef]
- Jang, D.; Lee, H.; Lee, K.; Kim, K.-R.; Won, R.; Lee, S.E.; Shim, I. White ginseng ameliorates depressive behavior and increases hippocampal 5-ht level in the stressed ovariectomized rats. BioMed Res. Int. 2019, 2019, 5705232. [Google Scholar] [CrossRef]
- Shin, E.-J.; Jeong, J.H.; Nguyen, B.-T.; Sharma, N.; Nah, S.-Y.; Chung, Y.H.; Lee, Y.; Byun, J.K.; Nabeshima, T.; Ko, S.K.; et al. Ginsenoside Re protects against serotonergic behaviors evoked by 2,5-dimethoxy-4-iodo-amphetamine in mice via inhibition of PKCδ-mediated mitochondrial dysfunction. Int. J. Mol. Sci. 2021, 22, 7219. [Google Scholar] [CrossRef]
- Janetzky, K.; Morreale, A.P. Probable interaction between warfarin and ginseng. Am. J. Health-Syst. Pharm. 1997, 54, 692–693. [Google Scholar] [CrossRef]
- Tian, Z.; Pang, H.; Du, S.; Lu, Y.; Zhang, L.; Wu, H.; Guo, S.; Wang, M.; Zhang, Q. Effect of Panax notoginseng saponins on the pharmacokinetics of aspirin in rats. J. Chromatogr. B 2017, 1040, 136–143. [Google Scholar] [CrossRef]
- Tian, Z.; Pang, H.; Zhang, Q.; Du, S.; Lu, Y.; Zhang, L.; Bai, J.; Li, P.; Li, D.; Zhao, M.; et al. Effect of aspirin on the pharmacokinetics and absorption of Panax notoginseng saponins. J. Chromatogr. B 2018, 1074–1075, 25–33. [Google Scholar] [CrossRef]
- Yang, L.; Li, C.-L.; Tsai, T.-H. Preclinical herb–drug pharmacokinetic interaction of Panax ginseng extract and selegiline in freely moving rats. ACS Omega 2020, 5, 4682–4688. [Google Scholar] [CrossRef]
- Malati, C.Y.; Robertson, S.M.; Hunt, J.D.; Chairez, C.; Alfaro, R.M.; Kovacs, J.A.; Penzak, S.R. Influence of Panax ginseng on cytochrome p450 (CYP) 3A and P-glycoprotein (P-gp) activity in healthy participants. J. Clin. Pharmacol. 2012, 52, 932–939. [Google Scholar] [CrossRef]
- Kim, D.-S.; Kim, Y.; Jeon, J.-Y.; Kim, M.-G. Effect of Red Ginseng on cytochrome P450 and P-glycoprotein activities in healthy volunteers. J. Ginseng Res. 2015, 40, 375–381. [Google Scholar] [CrossRef]
- Jones, B.D.; Runikis, A.M. Interaction of ginseng with phenelzine. J. Clin. Psychopharmacol. 1987, 7, 201. [Google Scholar] [CrossRef] [PubMed]
- Halegoua-DeMarzio, D.; Navarro, V. Challenges in herbal-induced liver injury identification and prevention. Liver Int. 2025, 45, e16071. [Google Scholar] [CrossRef]
- Teschke, R.; Eickhoff, A.; Schulze, J.; Danan, G. Herb-induced liver injury (HILI) with 12,068 worldwide cases published with causality assessments by Roussel Uclaf Causality Assessment Method (Rucam): An overview. Transl. Gastroenterol. Hepatol. 2021, 6, 51. [Google Scholar] [CrossRef]
- Jing, J.; Teschke, R. Traditional chinese medicine and herb-induced liver injury: Comparison with drug-induced liver injury. J. Clin. Transl. Hepatol. 2018, 6, 57–68. [Google Scholar] [CrossRef] [PubMed]
- Le, T.T.; McGrath, S.R.; Fasinu, P.S. Herb-drug interactions in neuropsychiatric pharmacotherapy–a review of clinically relevant findings. Curr. Neuropharmacol. 2022, 20, 1736–1751. [Google Scholar] [CrossRef]
- Choi, M.-K.; Song, I.-S. Interactions of ginseng with therapeutic drugs. Arch. Pharmacal Res. 2019, 42, 862–878. [Google Scholar] [CrossRef]
- Boyer, E.W.; Shannon, M. The serotonin syndrome. N. Engl. J. Med. 2005, 352, 1112–1120. [Google Scholar] [CrossRef]
- Hou, W.; Wang, Y.; Zheng, P.; Cui, R. Effects of ginseng on neurological disorders. Front. Cell. Neurosci. 2020, 14, 55. [Google Scholar] [CrossRef] [PubMed]
- Jung, S.Y.; Kim, C.; Kim, W.; Lee, S.; Lee, J.; Shim, B.S.; Kim, S.; Ahn, K.S.; Ahn, K.S. Korean red ginseng extract enhances the anticancer effects of imatinib mesylate through abrogation p38 and stat5 activation in kbm-5 cells. Phytother. Res. 2015, 29, 1062–1072. [Google Scholar] [CrossRef]
Reference | Human or Animal Study | Sample Size | Country Study Conducted In | Major Findings |
---|---|---|---|---|
[22]-Kim et al. | Animal-mice | 45–75 mice for each part of experiment | Republic of Korea | KRG alleviated withdrawal symptoms, improved spatial memory, lowered neuroinflammatory markers (TNF-α and NF-κβ), and restored BDNF signaling in a dose-dependent fashion, suggesting neuroprotective effects against alcohol-induced damage. |
[10]-Kim et al. | Human | 13 Korean men | Republic of Korea | Key ginsenosides Rg3, Rk1 + Rg5, F2, and compound K all showed higher oral bioavailability when KRG was given in its bioconverted form with hydrophobic ginsenosides removed (e.g., Rb1) compared to its usual extract form. |
[23]-Lee et al. | Human | 25 men | Republic of Korea | After consuming ethanol, men who consumed ginseng directly after had lower plasma ethanol concentrations in the initial hour and reported less subsequent hangover symptoms than the placebo group. Interestingly, ginseng group also had higher acetaldehyde levels despite this compound being associated with hangover symptoms, suggesting ginseng’s antioxidative effects may have masked the detrimental symptoms of higher acetaldehyde levels. |
[29]-Zhao et al. | Animals—rats | 4–6 rats for each part of experiment | Republic of Korea and China | Rats induced with ethanol withdrawal that received KRG expressed less anxious behavior than those that did not. A subsequent experiment showed this anxiolytic effect was blocked by a selective D2 receptor antagonist, but not a D1 receptor antagonist. |
[31]-Lee et al. | Animals—rats | 40 rats | Republic of Korea | Rats receiving ethanol and KRG showed dose-dependent lower liver weight, hepatic triglycerides, total cholesterol, and plasma triglycerides compared to ethanol-only group. Additionally, they had less hepatic inflammatory cells, less fat droplets, no necrotic cells, and reversed AMPK suppression, all of which suggest a protective effect for AFLD. |
[18]-Jeon et al. | Animals—various | 4 rats, 5 mice | Republic of Korea | Rats and mice were found to have differences in the ginsenosides they absorbed from oral KRG extract, with mice showing Rg3 and compound K in the plasma (akin to humans), while rats did not. Additionally, the species metabolized certain ginsenosides (i.e., Rb1, Rb2, Rc, and Rd) at different rates. Highlights the importance in species selection when extrapolating findings to human models. |
[13]-Lee | Animals—rats | 36 rats | Republic of Korea | Rats with induced morphine withdrawal that were given ginseng were found to have reduced anxious and depressed behavior using an elevated plus maze and forced swimming test. Changes in these rats’ CRF and neuropeptide Y expressions were identified in the hypothalamus when compared to controls. |
[21]-Lee et al. | Animals—rats | 32 rats | Republic of Korea, USA | Absorption of ethanol in the GI tract was found to be 21.0% less in rats that received KRG compared to controls, with little difference found when administered intraperitoneally. Demonstrates KRG lowers ethanol’s oral bioavailability when given concurrently. |
[25]-Lee et al. | Animals—mice | 20 mice | Republic of Korea | Serum ethanol and acetaldehyde levels of mice were reduced in groups that were administered non-ginsenoside compounds from steam-dried ginseng berries. Most abundant of these compounds included linoleate, palmitic acid, and linoleic acid. |
[26]-Je et al. | Animals—mice | Republic of Korea | ALT and AST activity in mouse plasma, along with ethanol and acetaldehyde levels, were reduced in mice that received injections from ginseng sprouts prior to being given alcohol. This coincided with PCR determining higher expression of alcohol and aldehyde dehydrogenase genes in the mice that received ginseng sprouts. Finally, the study showed the ginseng sprouts had a strong antioxidative effect in vitro. | |
[28]-Cha et al. | Animals—mice | 10–15 mice for each experiment | Republic of Korea | Elevated plus-maze model was used to examine anxiolytic effects of ginsenosides in mice. Found that those receiving ginsenosides Rb1, Rg1, and a Rg5/Rk showed less anxious behavior than those without. Anxiolytic mechanism of the compounds was hypothesized to be due to their interaction with GABAA and GABAB receptors, but this mechanism was not thoroughly explored in this study. |
[30]-Bhattacharya et al. | Animals—various | 58–88 rats or mice for the 5 experiments conducted | India | Red and white ginseng were given orally to mice and rats, with their behaviors in open-field and elevated plus-maze tests. Neither showed effects on first dose, but when given twice over 5 days, anxiolytic effects were comparable to that of mice given diazepam. |
[32]-Churchill et al. | Animals—chicks | 80 + 64 five-day-old male chicks | USA | 64 five-day-old male chicks were injected with between 0.25 and 5.0 mg of ginsenoside Rb1. The chicks were found to have dose-dependent decreases in separation distress compared to the negative control chicks. |
[33]-Xu et al. | Animals—various | 10 mice or rats for each experiment | China | An intestinal metabolite of ginseng, 20(s)-protopanaxadiol (S111), was found to have antidepressant effects in mice and rats comparable in potency to fluoxetine. This was consistent with dissection results that showed increased levels of monoamines in the brains of groups receiving S111 through anti-reuptake effects. |
[34]-Paik et al. | Human | 4 case reports Double-blinded study with 30 young adults-13 men, 17 women | Republic of Korea | Documents two cases of mania: a 56-year-old woman with previously diagnosed major depressive disorder with psychotic symptoms on haloperidol and clomipramine, and the other a 26-year-old male with no psychiatric history, both of whom experienced a manic episode after starting to take ginseng capsules for 2 weeks and 2 months, respectively. Neither had any further instances of similar episodes with cessation of ginseng. Documents a pair of case reports describing potential ginseng-induced gynecomastia: one in a man who had ingested ginseng for a long period of time, and the other a 12 y/o boy who had experienced gynecomastia after consuming ginseng for a month. Gynecomastia resolved for the 12 y/o boy after discontinuation of ginseng. Documents a 2001 study [34] with 30 healthy young adults that found KRG administration slightly prolonged QTc interval (15 ms) compared to placebo group (3 ms), while also mildly reducing diastolic blood pressure. |
[35]-Bilgi et al. | Human | 1 case report | USA | 26 y/o man taking imatinib for 7 years for chronic myelogenous leukemia presented with elevated ALT, AST, ALP, and total bilirubin along with acute lobular hepatitis on liver biopsy 3 months after starting to drink energy drinks containing Panax ginseng. Ginseng was discontinued with no subsequent liver enzyme elevations. Suspected to be a result of ginseng’s interaction with CYP3A4, which is essential for imatinib metabolism. |
[36]-Zhou et al. | Animal | 30 male rats | China | Extracts of white and red ginseng were injected into mice, with no significant EKG or obvious histological abnormalities being observed compared to controls. However, mice receiving ginseng did have comparatively high creatine kinases and decreased calcium ATPase activity, suggesting potential subclinical myocardial damage or calcium mishandling. |
[37]-Parlakpinar et al. | Animal | 40 male rats | Turkey | Rats given KRG extract were found to have decreased blood pressure, elevated troponin I and myoglobin levels, and signs of diastolic dysfunction in comparison to negative controls. Histopathologic changes suggestive of potential myocardial injury and altered Cu-Zn superoxide dismutase gene expression were identified in these rats as well. |
[38]-Aravinthan et al. | Animal | 45 guinea pigs | Republic of Korea | Following an hour of normothermic ischemia followed by 2 h of reperfusion, guinea pigs previously fed for two weeks with KRG were found in comparison to negative controls to have improved aortic flow, coronary flow, cardiac output, and left ventricular systolic pressure. Animals also were found to have less dramatic EKG changes, suppressed lactate dehydrogenase and cardiac troponin I levels, and lower oxidative stress markers. |
[39]-Torbey et al. | Human | 1 case report | USA | 43 y/o woman consuming multiple caffeinated beverages along with 4 L of KRG beverages daily for at least six months presented with multiple instances of syncope, tonic clonic seizure, and prolonged QTc (up to 720 ms). No subsequent episodes occurred when the patient stopped consuming KRG. Suggests that prolonged use of KRG may pose cardiac risks when taken with other stimulants. |
[40]-Norelli et al. | Human | 2 case reports | USA | Documents two instances of patients experiencing manic episodes with no prior psychiatric history: one was a 23 y/o man who had been administered cannabis and unspecified “large quantities” of red ginseng every day for a month prior to his breakthrough manic episode; the other was a 79 y/o male who experienced a manic episode after he started consuming more than his baseline ginseng intake at around 3 to 4 “condensed drinks” per day. Symptoms of mania disappeared a few days after stopping ginseng intake. |
[41]-Kabalak et al. | Human | 1 case report | Turkey | 39 y/o woman with history of smoking, coffee consumption, and frequent use of ginseng orally and topically developed menometrorrhagia and sinus tachycardia with atrial premature beats. Symptoms were resolved within two weeks of stopping consumption of all these things. Authors speculate that ginseng could have contributed to abnormal uterine bleeding and tachycardia. |
[42]-Yang et al. | Human | 22 women 21–30 y/o | Republic of Korea | KRG was found to reduce urinary levels of bisphenol A and malondialdehyde, an oxidative stress biomarker, in young women. Also improved constipation and menstrual pain/irregularity. |
[43]-Yuan et al. | Human | 20–9 men, 11 women | USA | Healthy adults part of a 4-week study received warfarin consecutively over 3 days at the start of week 1 and 4. Starting in week 2, half took American ginseng twice daily, and the others took a placebo. The group receiving ginseng exhibited significantly lower peak INR and plasma warfarin concentrations two weeks after starting ginseng, indicating that American ginseng reduced warfarin’s anticoagulant effect. While the authors suggested the ginsenosides may have increased warfarin’s metabolism or clearance through interactions with hepatic enzymes, no specific mechanism was explored or proposed. |
[44]-Lee et al. | Human | 25–13 men, 12 women | Republic of Korea | 2-week study of 25 ischemic stroke patients receiving warfarin either with or without Panax ginseng showed no significant differences in INR, peak prothrombin time, or area under the curve between the two groups, even though all patients showed increased anticoagulation relative to baseline. This suggests that Panax ginseng may not consistently antagonize warfarin, or that its impact could depend on unclear patient-specific factors, ginseng species, preparation method, or dosing regimens. |
[45]-Wang et al. | Animals—various | 10 mice/6 rats per experiment | China | Ginsenoside Rb1 was found to improve mobility and reverse depressive behavior in rodents subjected to chronic stress, with neurochemical assays finding associated increases in brain levels of serotonin, norepinephrine, and dopamine. Suggests Rb1 may exert antidepressant effects through modulation of monoamine systems in the CNS. |
[46]-Jang et al. | Animals—rats | 24 rats per experiment | Republic of Korea | In tail suspension and forced swim tests, white ginseng alleviated immobility and depressive behaviors in rats, with associated decreases in serum corticosterone levels and increased hippocampal serotonin concentrations noted. Serotonin concentrations were even higher than the rats receiving fluoxetine as a positive control. Suggests white ginseng may have antidepressant effects through modulation of stress responses and serotonin activity. |
[47]-Shin et al. | Animals—mice | 4–6 mice per group, 5–9 groups per experiment | Republic of Korea | Mice induced with serotonin syndrome with 5-HT2A agonist showed improvement to symptoms with administration of ginsenoside Re. Researchers observed protein kinase C δ (PKCδ) inhibition in the groups receiving ginsenosides, suggesting PKCδ may be a therapeutic target for ginsenoside Re against serotonergic symptoms. |
[48]-Janetzsky et al. | Human | 1 case report | USA | 47 y/o man on a stable warfarin regimen had his INR dropped from 3.0–4.0 to 1.5 within two weeks of starting Panax ginseng, without any other changes to his medications, lifestyle, or diet. After discontinuing ginseng, the patient’s INR returned to baseline, suggesting a reduction in warfarin efficacy potentially linked to ginseng intake, although the relevant mechanism was stated to be unclear at the time. |
[49]-Tian et al. | Animals—rats | 12 rats | China | Co-administration of Panax notoginseng and aspirin significantly increased plasma salicylate concentrations in rats, roughly doubling them compared to rats that received aspirin alone. In tandem with an in vitro MDCK-MDR1 cells showing increased apparent permeability, the findings suggest that P. notoginseng might facilitate GI absorption of aspirin. |
[50]-Tian et al. | Animals—rats | 12 rats | China | Co-administration of Panax notoginseng with aspirin showed increased absorption of ginsenosides Rg1, Rb1, Re, Rd, and notoginsenoside R1 in rats. Results of MDCK-MDR1 cell assays indicated that aspirin and salicylic acid disrupted tight junction proteins, which likely contributed to the improved absorption. This, in tandem with [49], suggests a mutual enhancement of absorption when ginsenosides and aspirin are used together. |
[51]-Yang et al. | Animals—rats | 6 rats | Taiwan | Selegiline’s bioavailability in rats was dropped from approximately 18% to 7.2% with low-dose ginseng but increased markedly to 29% with high-dose ginseng administration. The authors suspect these effects to be mediated by cytochrome P450 enzymes, particularly CYP3A4, CYP2B6, and CYP1A2, which metabolize selegiline into desmethyl-selegiline and L-methamphetamine. |
[52]-Malati et al. | Human | 12–8 men, 4 women | USA | Participants were given single doses of midazolam and fexofenadine before and after 28 days of receiving oral KRG. KRG treatment was found to reduce midazolam exposure, indicating CYP3A enzyme induction, while fexofenadine pharmacokinetics were scarcely altered, indicating a lack of P-glycoprotein interaction. Recommended to check if patients are on any CYP3A substrates before permitting ginseng use. |
[53]-Kim et al. | Human | 14 healthy men | Republic of Korea | 14 men had plasma samples collected after being given a variety of medications, including caffeine, losartan, dextromethorphan, omeprazole, fexofenadine, and midazolam both before and after being supplemented with KRG for two weeks. Weak inhibition of CYP3C9 and CYP3A4, and weak induction of CYP2D6 were identified through pharmacokinetic changes, but none were clinically significant. |
[54]-Jones et al. | Human | 1 case report | Canada | 42 y/o woman who regularly consumed ginseng experienced symptoms of overstimulation (i.e., insomnia, tension headaches, visual hallucinations) after being started on phenelzine for depression. When phenelzine was reintroduced without ginseng, depression did not improve, but overstimulation was not experienced. Authors propose ginseng may have enhanced phenelzine’s psychoactive effects through inhibition of cAMP phosphodiesterase, though evidence of this mechanism is limited. |
System | Reported Side Effect (Excluding Drug Interactions) | Evidence Type | Number of Cases (Patient Count) or Incidence Rate |
---|---|---|---|
Hepatic | Herbal-induced liver injury (HILI)-nonspecific to ginseng | Literature review [4,55,56] | China: Incidence of 6.38 per 100,000; Iceland: 3 per 100,000 [4,55] 12,068 cases worldwide across 80 publications [56] |
Cardiovascular | Cardiac pathologies/myocardial damage (QT prolongation, tachycardia, ST depression, T wave inversion, AV block, troponin elevation, LDL elevation, diastolic dysfunction, HFpEF) | Animal study (rats) [37] | Dose dependent: 100 mg/kg Panax ginseng extract: Not specified 500 mg/kg Panax ginseng extract: Not specified |
QT prolongation | Review [34] | 30 | |
Arrhythmia | Case study [39,41] Review [34] | 3 [34,41] | |
Elevated creatine kinase, increased cardiac contractility | Animal study [36] | Not specified | |
TIA secondary to hypertensive crisis | Review [34] | 1 | |
Hypotension | Review [34] | ~13 | |
GI | Morning diarrhea | Review [34] | ~45 |
CNS/ Psychiatric | Manic psychosis | Case study [40] | 2 |
Manic episode | Review [34] | 2 | |
Nervousness | Review [34] | ~33 | |
Sleeplessness | Review [34] | ~26 | |
Depression | Review [34] | ~13 | |
Reproductive/endocrine | Menometrorrhagia | Case study [41] | 1 |
Gynecomastia | Review [34] | 2 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Frazer, E.; Zhao, C.; Lee, J.; Shaw, J.; Lai, C.; Bota, P.; Allee, T. A Review of the Mechanisms and Risks of Panax ginseng in the Treatment of Alcohol Use Disorder. Diseases 2025, 13, 285. https://doi.org/10.3390/diseases13090285
Frazer E, Zhao C, Lee J, Shaw J, Lai C, Bota P, Allee T. A Review of the Mechanisms and Risks of Panax ginseng in the Treatment of Alcohol Use Disorder. Diseases. 2025; 13(9):285. https://doi.org/10.3390/diseases13090285
Chicago/Turabian StyleFrazer, Eli, Candi Zhao, Jacky Lee, Jonathan Shaw, Charles Lai, Peter Bota, and Tina Allee. 2025. "A Review of the Mechanisms and Risks of Panax ginseng in the Treatment of Alcohol Use Disorder" Diseases 13, no. 9: 285. https://doi.org/10.3390/diseases13090285
APA StyleFrazer, E., Zhao, C., Lee, J., Shaw, J., Lai, C., Bota, P., & Allee, T. (2025). A Review of the Mechanisms and Risks of Panax ginseng in the Treatment of Alcohol Use Disorder. Diseases, 13(9), 285. https://doi.org/10.3390/diseases13090285