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Plant extracts for ADHD


Plant extracts for ADHD

The presentation about plant extracts in ADHD is only for completeness. The presented remedies are not sufficiently scientifically studied in ADHD. Massive side effects are possible. Therefore, an urgent warning must be given against their use.

Basically, plant extracts have the disadvantage that they contain a collection of active ingredients and thus often unfold a broad and not well controllable spectrum of mechanisms of action - some of which may be desired and some undesired. Individual active ingredients, on the other hand, can be used much more precisely and selectively to achieve only the desired effects and avoid the undesired ones.
The example of antidepressants is a good way to track this. Whereas tricyclic antidepressants, which brought about considerable improvements in the treatment of depression when they were introduced several decades ago, were often serotonin, dopamine and norepinephrine reuptake inhibitors at the same time, more modern antidepressants are much more selective (e.g. SSRIs: selective serotonin reuptake inhibitors) and can thus serve the needs of the affected person much more precisely precisely precisely because of this selectivity.
Another disadvantage of plants as medicinal products is the natural variations of the ingredients. Therefore, it makes a big difference whether you get plants and brew a tea, or buy the extract of the plant as a medicine in the pharmacy. Only the control of the type and quantity of the ingredients enables reliable efficacy and dosage at all.

A - sometimes rather emotionally driven - search for explicitly “alternative treatment methods”, on the other hand, is a logical short-circuit within a medium period of time. If an “alternative treatment method” were as effective as mainstream treatments, they would very quickly become very successful - and thus mainstream - through simple word-of-mouth (such as in the ADHD Conversely, it follows that alternative treatment options that have been known for some time are hardly successful - otherwise they would no longer be alternative.

1. Ginseng

1.1. Dopaminergic mechanisms of action of ginseng

Ginseng contains

  • Ginsenosides. These are known as powerful antioxidants with neuroprotective properties1
  • Saponins
  • Phenols
  • Polyacetylene
  • Alkaloids
  • Polysaccharides.
  • Gintonin, a non-saponin polymer and lysophosphatidic acid receptor agonist2

Ginseng root is said to influence neurotransmitters in the brain:3

  • Dopamine
    • after 2 weeks
      • increased in the PFC (which could be beneficial in ADHD in terms of organizational problems)
      • in the striatum is reduced (which would be detrimental in ADHD in terms of drive and motivation)
    • after 7 weeks
      • reduced in many areas of the brain (which would be detrimental in ADHD overall)
        • PFC, striatum, hippocampus, hypothalamus, limbic lobe, midbrain, cerebellum, and medulla oblongata
  • Norepinephrine
    • after 2 weeks
      • in PFC increased
    • after 7 weeks
      • reduced in many areas of the brain (which would be detrimental in ADHD overall)
        • PFC, striatum, hippocampus, hypothalamus, limbic lobe, midbrain, cerebellum, and medulla oblongata
  • Serotonin
    • after 2 weeks
      • increased in the striatum
      • increased in the cerebellum
      • in the hypothalamus is reduced
    • after 7 weeks
      • increased in the cerebellum
      • in the remaining brain areas is reduced
        • PFC, striatum, hippocampus, hypothalamus, limbic lobe, midbrain, and medulla oblongata

Korean red ginseng protected the blood-brain barrier and, probably by reducing oxidative processes, protected against dopaminergic neuronal damage in the striatum in a Parkinson’s disease model.4 One hypothesis is that this may be caused by ginsenosides2

Gintonin appears to regulate dopamine transmission in PC12 cells and alleviate MPTP-induced motor impairments by increasing TH levels in the striatum.5 Besides, gintonin seems to decrease synuclein in substantia nigra and striatum and thereby be neuroprotective for dopamine neurons, which would be helpful in Parkinson’s disease .6

However, these mechanisms cannot be easily transferred to ADHD.
Except for the increase in tyrosine hydroxylase in the striatum, no mechanisms are apparent that would be helpful for ADHD.

1.2. Ginseng for ADHD

There are very few studies on the use of ginseng in ADHD. On this basis, it is necessary to warn against its use.
An observational clinical study of 18 children with ADHD reported that 1000 mg of Korean red ginseng over 8 weeks improved inattention.7
A double-blind randomized placebo-controlled study found a statistically significant improvement in inattention and hyperactivity and a decreased theta-beta ratio in QEEG with 2 g Korean red ginseng extract/day after 8 weeks. Salivary cortisol and DHEA levels were unchanged.8 Another study investigated a combination of ginseng with omega 3.9

A case study on 3 adolescents with ADHD reported improved inattention and hyperactivity/impulsivity in the parent report by Panax Ginseng, which was a dopamine and norepinephrine reuptake inhibitor.10 The same author also reported improvements in ADHD by St. John’s Wort11 and Real Chamomile12 on apparently the same 3 sufferers each time. Scientific weight should not be given to these studies. Why a meta-study nevertheless names this study without comment as an argument for the effectiveness of ginseng in ADHD is incomprehensible.1

2. Ginkgo biloba

There are very few studies on the use of Ginkgo biloba in ADHD. On this basis, it is necessary to warn against its use.
A randomized double-blind trial found Ginkgo biloba less effective than MPH for ADHD.13 MPH showed more frequent side effects of loss of appetite, headache, and insomnia. Significantly, the effect was rated much higher in parent ratings than in teacher ratings - a pattern that is common with emotionally desired treatments.
Up to 240 mg of Ginkgo biloba improved ADHD behavioral symptoms and brain electrical activity in children in a very small study (n = 20).14
A randomized, placebo-controlled trial in children and adolescents with ADHD found that ginkgo biloba, as an additional treatment alongside 20 to 30 mg of MPH, improved its effects.15

Concurrent treatment with ginkgo biloba and ginseng alleviated ADHD symptoms in children, with few side effects, in a small study (n = 36).16

The extract from the leaves of Ginkgo biloba is used as a herbal medicine against dementia.1

3. Yizhidan (YZD)

Yizhidan is said to have a comparable level of efficacy to methylphenidate with lower side effects.1718

Yizhidan seems to be a Chinese medicinal plant.19

Since there is no study on this other than the one mentioned, the study was designed to be only single-blind (which can potentially bias in favor of the desired outcome), and the study itself cannot be verified, the result is in no way certain.
The study report also has a peculiar parallel with that on Tiashen Liquor, since in both cases the impairments to be eliminated by the drug in the test animals were caused by the same agents and are described in the same wording, and it appears to be the same journal.

4. Tiaoshen Liquor (TL)

Tiaoshen Liquor is said to be made from Chinese medicinal herbs. A study on 100 children had shown a high reduction of symptoms.20

Since there is no other study on this besides the one mentioned and the study itself cannot be verified, the result is in no way certain.

The study report also has a peculiar parallel with that on Yizhidan (YZD), since in both cases the impairments in the test animals to be eliminated by the drug are caused by the same means and described in the same wording, and it seems to be the same journal.

5. Rehmanniae Radix Preparata, Catalpol

In an article (which at least complies with scientific formalities), the efficacy of Rehmanniae Radix Preparata as a remedy frequently used in Traditional Chinese Medicine (TCM) for ADHD was investigated. However, trials with test persons are completely missing and it is openly communicated that the financier of the article influenced the publication.21

Another article confirmed a positive effect of catalpol, a component of Rehmanniae Radix Preparata, on ADHD symptoms in rats 22
Catalpol is said to increase the levels of

  • BDNF (Brain-Derived Neurotrophic Factor)
  • Cdk5 (Cyclin-Dependent Kinase 5)
  • P35
  • FGF 21 (Fibroblast Growth Factor 21)
  • FGFR 1 (FGF 21 receptor)

which should have a positive effect on learning ability, which is reduced in ADHD due to decreased levels of BDNF and other neurotrophic factors.

6. Kratom

Kratom (Mitragyna speciosa) is a tree found in Asia. The dried leaves are used. Other names are biak, gra-tom, biak-biak, katawn, krton, mabog or mambog.

Use of kratom for ADHD has been reported,23 particularly as a self-medication.24
Since the effect of Kratom can be extremely different up to opposite depending on tree species and dose, and the effect is not yet secured, must be urgently warned against self-medication.

There are indications of an addictive potential25 and of the potential to trigger seizures,26 each described on the basis of individual cases.

7. Lycium chinense

A fruit extract of Lycium chinense showed significant improvement in verbal learning test, digit span forward test, digit span backward test, auditory continuous CNT performance, and FAIR performance score in a double-blind randomized study against placebo compared to the placebo group.27 ADHD was an exclusion criterion for the subjects. Application to ADHD sufferers has not been reported to date.
As always, such study results are not robust until replicated by other study teams.

8. Saffron

A randomized double-blind trial found the same improvement in ADHD symptoms in children and adolescents for saffron as for MPH, with the same rate of side effects.28
A nonrandomized study with conflicts of interest of the authors claimed an equivalent effect size of saffron extract on ADS(H)S symptoms as methylphenidate with, in addition, a better effect on hyperactivity than MPH, whereas MPH had a better effect on inattention.29 seven patients in the methylphenidate group (25.9%) and 10 patients in the saffron group (31.2%) reported side effects.
Two randomized double-blind clinical trials found an improved effect of MPH plus saffron compared with MPH alone.3031

  1. Corona (2018): Natural Compounds for the Management of Parkinson’s Disease and Attention-Deficit/Hyperactivity Disorder. Biomed Res Int. 2018 Nov 22;2018:4067597. doi: 10.1155/2018/4067597. PMID: 30596091; PMCID: PMC6282143.

  2. Lee BR, Sung SJ, Hur KH, Kim SE, Ma SX, Kim SK, Ko YH, Kim YJ, Lee Y, Lee SY, Jang CG (2022): Korean Red Ginseng inhibits methamphetamine addictive behaviors by regulating dopaminergic and NMDAergic system in rodents. J Ginseng Res. 2022 Jan;46(1):147-155. doi: 10.1016/j.jgr.2021.05.007. PMID: 35058731; PMCID: PMC8753524.

  3. Itoh, Zang, Murai, Saito (1989): Effects of Panax ginseng root on the vertical and horizontal motor activities and on brain monoamine-related substances in mice. Planta Med. 1989 Oct;55(5):429-33. doi: 10.1055/s-2006-962058. PMID: 2813579.

  4. Choi JH, Jang M, Nah SY, Oh S, Cho IH (2018): Multitarget effects of Korean Red Ginseng in animal model of Parkinson’s disease: antiapoptosis, antioxidant, antiinflammation, and maintenance of blood-brain barrier integrity. J Ginseng Res. 2018 Jul;42(3):379-388. doi: 10.1016/j.jgr.2018.01.002. PMID: 29983619; PMCID: PMC6026382.

  5. Hwang SH, Lee BH, Choi SH, Kim HJ, Jung SW, Kim HS, Shin HC, Park HJ, Park KH, Lee MK, Nah SY (2015): Gintonin, a novel ginseng-derived lysophosphatidic acid receptor ligand, stimulates neurotransmitter release. Neurosci Lett. 2015 Jan 1;584:356-61. doi: 10.1016/j.neulet.2014.11.007. PMID: 25445364.

  6. Jo MG, Ikram M, Jo MH, Yoo L, Chung KC, Nah SY, Hwang H, Rhim H, Kim MO (2019): Gintonin Mitigates MPTP-Induced Loss of Nigrostriatal Dopaminergic Neurons and Accumulation of α-Synuclein via the Nrf2/HO-1 Pathway. Mol Neurobiol. 2019 Jan;56(1):39-55. doi: 10.1007/s12035-018-1020-1. PMID: 29675576.

  7. Lee SH, Park WS, Lim MH (2011): Clinical effects of korean red ginseng on attention deficit hyperactivity disorder in children: an observational study. J Ginseng Res. 2011 Jun;35(2):226-34. doi: 10.5142/jgr.2011.35.2.226. PMID: 23717065; PMCID: PMC3659525. n = 18

  8. Ko, Kim, Kim, Moon, Whang, Lee, Jung (2014): Effects of Korean red ginseng extract on behavior in children with symptoms of inattention and hyperactivity/impulsivity: a double-blind randomized placebo-controlled trial. J Child Adolesc Psychopharmacol. 2014 Nov;24(9):501-8. doi: 10.1089/cap.2014.0013. n = 70

  9. Lee, Lee, Kim, Shin, Kim, Cho, Lee (2020): Effect of Omega-3 and Korean Red Ginseng on Children with Attention Deficit Hyperactivity Disorder: An Open-Label Pilot Study. Clin Psychopharmacol Neurosci. 2020 Feb 29;18(1):75-80. doi: 10.9758/cpn.2020.18.1.75. PMID: 31958908.

  10. Niederhofer (2009): Panax ginseng may improve some symptoms of attention-deficit hyperactivity disorder. J Diet Suppl. 2009;6(1):22-7. doi: 10.1080/19390210802687221. PMID: 22435351. n = 3

  11. Niederhofer (2010): St. John’s wort may improve some symptoms of attention-deficit hyperactivity disorder. Nat Prod Res. 2010 Feb;24(3):203-5. doi: 10.1080/14786410802076259. PMID: 20140799. n = 3

  12. Niederhofer (2009): Observational study: Matricaria chamomilla may improve some symptoms of attention-deficit hyperactivity disorder. Phytomedicine. 2009 Apr;16(4):284-6. doi: 10.1016/j.phymed.2008.10.006. PMID: 19097772. n = 3

  13. Salehi, Imani, Mohammadi, Fallah, Mohammadi, Ghanizadeh, Tasviechi, Vossoughi, Rezazadeh, Akhondzadeh (2010): Ginkgo biloba for attention-deficit/hyperactivity disorder in children and adolescents: a double blind, randomized controlled trial. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Feb 1;34(1):76-80. doi: 10.1016/j.pnpbp.2009.09.026. PMID: 19815048. n = 50

  14. Uebel-von Sandersleben, Rothenberger, Albrecht, Rothenberger, Klement, Bock (2014): Ginkgo biloba extract EGb 761® in children with ADHD. Z Kinder Jugendpsychiatr Psychother. 2014 Sep;42(5):337-47. doi: 10.1024/1422-4917/a000309. PMID: 25163996. n = 20

  15. Shakibaei, Radmanesh, Salari, Mahaki (2015): Ginkgo biloba in the treatment of attention-deficit/hyperactivity disorder in children and adolescents. A randomized, placebo-controlled, trial. Complement Ther Clin Pract. 2015 May;21(2):61-7. doi: 10.1016/j.ctcp.2015.04.001. PMID: 25925875.

  16. Lyon, Cline, Totosy de Zepetnek, Shan, Pang, Benishin (2001): Effect of the herbal extract combination Panax quinquefolium and Ginkgo biloba on attention-deficit hyperactivity disorder: a pilot study. J Psychiatry Neurosci. 2001 May;26(3):221-8. PMID: 11394191; PMCID: PMC1408291. n = 36

  17. Chen, Huang, Zhao (2001): [Clinical and experimental study on treatment of childhood hyperkinetic syndrome with yizhidan]. [Article in Chinese]; Zhongguo Zhong Xi Yi Jie He Za Zhi. 2001 Jan;21(1):19-21.


  19. Rakel, Integrative Medicine, Elsevier, Seite 110

  20. Wang, Li, Li (1995): [Clinical and experimental studies on tiaoshen liquor for infantile hyperkinetic syndrome].[Article in Chinese]; Zhongguo Zhong Xi Yi Jie He Za Zhi. 1995 Jun;15(6):337-40.

  21. Haixia Yuan, Meng Yang, Xinmin Han, Xinqiang Ni (2018):The Therapeutic Effect of the Chinese Herbal Medicine, Rehmanniae Radix Preparata, in Attention Deficit Hyperactivity Disorder via Reversal of Structural Abnormalities in the Cortex; Evid Based Complement Alternat Med. 2018; 2018: 3052058. doi: [10.1155/2018/3052058]; PMCID: PMC6204205; PMID: 30405737

  22. Yuan, Ni, Zheng, Han, Song, Yu (2019): Effect of catalpol on behavior and neurodevelopment in an ADHD rat model. Biomed Pharmacother. 2019 Oct;118:109033. doi: 10.1016/j.biopha.2019.109033.

  23. Bath, Bucholz, Buros, Singh, Smith, Veltri, Grundmann (2019): Self-reported Health Diagnoses and Demographic Correlates With Kratom Use: Results from an Online Survey. J Addict Med. 2019 Sep 17. doi: 10.1097/ADM.0000000000000570.

  24. Grundmann O, Veltri CA, Morcos S, Smith KE, Singh D, Corazza O, Cinosi E, Martinotti G, Walsh Z, Swogger MT (2023): Correlations of kratom (Mitragyna speciosa Korth.) use behavior and psychiatric conditions from a cross-sectional survey. Exp Clin Psychopharmacol. 2023 Jan 12. doi: 10.1037/pha0000632. PMID: 36634016.

  25. Schmuhl, Gardner, Cottrill, Bonny (2019): Home induction and outpatient treatment of kratom use disorder with buprenorphine-naloxone: A case report in a young adult. Subst Abus. 2019 Oct 23:1-4. doi: 10.1080/08897077.2019.1671945.

  26. Afzal, Esang, Rahman (2020): A Case of Kratom-induced Seizures. Cureus. 2020 Jan 7;12(1):e6588. doi: 10.7759/cureus.6588. PMID: 32051800; PMCID: PMC7001130.

  27. Chung, Kang, Hong, Bae, Cho (2019): Standardized Lycium chinense Fruit extract enhances attention and cognitive function in healthy young people by a double-blind, randomized, placebo-controlled, crossover trial. J Res Med Sci. 2019 Dec 23;24:102. doi: 10.4103/jrms.JRMS_851_18. PMID: 31949453; PMCID: PMC6950474. n = 86

  28. Baziar S, Aqamolaei A, Khadem E, Mortazavi SH, Naderi S, Sahebolzamani E, Mortezaei A, Jalilevand S, Mohammadi MR, Shahmirzadi M, Akhondzadeh S (2019): Crocus sativus L. Versus Methylphenidate in Treatment of Children with Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind Pilot Study. J Child Adolesc Psychopharmacol. 2019 Apr;29(3):205-212. doi: 10.1089/cap.2018.0146.. PMID: 30741567. n = 54

  29. Blasco-Fontecilla H, Moyano-Ramírez E, Méndez-González O, Rodrigo-Yanguas M, Martin-Moratinos M, Bella-Fernández M. Effectivity of Saffron Extract (Saffr’Activ) on Treatment for Children and Adolescents with Attention Deficit/Hyperactivity Disorder (ADHD): A Clinical Effectivity Study. Nutrients. 2022 Sep 28;14(19):4046. doi: 10.3390/nu14194046. PMID: 36235697; PMCID: PMC9573091. n = 63

  30. Khaksarian M, Ahangari N, Masjedi-Arani A, Mirr I, Jafari H, et al. (2021): A Comparison of Methylphenidate (MPH) and Combined Methylphenidate with Crocus sativus (Saffron) in the Treatment of Children and Adolescents with ADHD: A Randomized, Double-Blind, Parallel-Group, Clinical Trial. Iran J Psychiatry Behav Sci.15(3):e108390. doi: 10.5812/ijpbs.108390. n = 70

  31. Pazoki, Zandi, Assaf, Sanjari Moghaddam, Zeinoddini, Reza Mohammadi, Akhondzadeh (2022): Efficacy and safety of saffron as adjunctive therapy in adults with attention-deficit/hyperactivity disorder: A randomized, double-blind, placebo-controlled clinical trial. Advances in Integrative Medicine, Volume 9, Issue 1, 2022, Pages 37-43, ISSN 2212-9588, n = 44