Plant extracts for ADHD
The presentation of plant extracts for ADHD is for completeness only. The remedies presented have not been sufficiently scientifically investigated for ADHD. Massive side effects are possible. We must therefore urgently warn against their use.
In principle, plant extracts have the disadvantage that they contain a collection of active ingredients and thus often unfold a broad and not easily 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 illustration of this. While tricyclic antidepressants, which brought about considerable improvements in the treatment of depression when they were introduced a few decades ago, were often serotonin, dopamine and noradrenaline reuptake inhibitors at the same time, more modern antidepressants are much more selective (e.g. SSRIs: selective serotonin reuptake inhibitors) and can therefore meet the needs of the person with ADHD much more precisely precisely precisely due to this selectivity.
Another disadvantage of plants as medicinal products is the natural variation of the ingredients. It therefore makes a big difference whether you obtain plants and brew a tea or buy the extract of the plant as a medicine in the pharmacy. Only by controlling the type and quantity of ingredients is it possible to ensure reliable efficacy and dosage.
A search for expressly “alternative treatment methods” - which is sometimes rather emotionally driven - is, on the other hand, 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 forum.adxs.org). Consequences, conversely, are that alternative treatment options that have been known for a long time are barely successful - otherwise they would no longer be alternative.
- 1. Ginseng
- 2. Ginkgo biloba
- 3. Yizhidan (YZD)
- 4. Tiaoshen Liquor (TL)
- 5. Rehmanniae Radix Preparata, Catalpol
- 6. Kratom
- 7. Lycium chinense
- 8. Saffron
- 9. Long Mu Qing Xin Mixture (LMQXM)
1. Ginseng
1.1. Dopaminergic mechanisms of action of ginseng
Ginseng contains
- Ginsenosides. These are known to be powerful antioxidants with neuroprotective properties1
- Saponins
- Phenols
- Polyacetylenes
- 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 to drive and motivation in ADHD)
- after 7 weeks
- reduced in many areas of the brain (which would be detrimental to ADHD overall)
- PFC, striatum, hippocampus, hypothalamus, limbic lobe, midbrain, cerebellum and medulla oblongata
- reduced in many areas of the brain (which would be detrimental to ADHD overall)
- after 2 weeks
- Noradrenaline
- after 2 weeks
- in the PFC increased
- after 7 weeks
- reduced in many areas of the brain (which would be detrimental to ADHD overall)
- PFC, striatum, hippocampus, hypothalamus, limbic lobe, midbrain, cerebellum and medulla oblongata
- reduced in many areas of the brain (which would be detrimental to ADHD overall)
- after 2 weeks
- Serotonin
- after 2 weeks
- increased in the striatum
- increased in the cerebellum
- in the hypothalamus is reduced
- after 7 weeks
- increased in the cerebellum
- reduced in the other areas of the brain
- PFC, striatum, hippocampus, hypothalamus, limbic lobe, midbrain and medulla oblongata
- after 2 weeks
Red Korean ginseng protected the blood-brain barrier and protected - probably by reducing oxidative processes - against dopaminergic neuronal damage in the striatum in a Parkinson’s model.4 One hypothesis is that this could 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 In addition, gintonin appears to reduce synuclein in the substantia nigra and striatum and thus have a neuroprotective effect on dopamine neurons, which would be helpful in Parkinson’s .6
However, these mechanisms cannot simply be transferred to ADHD.
Apart from the increase in tyrosine hydroxylase in the striatum, no mechanisms are recognizable that would be helpful for ADHD.
1.2. Ginseng for ADHD
There are very few studies on the use of ginseng for ADHD.7 On this basis, use should be cautioned against.
An observational clinical study of 18 children with ADHD reported that 1000 mg of red Korean ginseng over 8 weeks improved inattention.8
A double-blind randomized placebo-controlled study found a statistically significant improvement in inattention and hyperactivity and a reduced theta-beta ratio in the QEEG after 8 weeks with 2 g Korean red ginseng extract/day. Salivary cortisol and DHEA levels were unchanged.9 Another study investigated a combination of ginseng with omega 3.10
A case study of 3 adolescents with ADHD reported improved inattention and hyperactivity/impulsivity in the parent report using Panax ginseng, which is a dopamine and norepinephrine reuptake inhibitor.11 The same author also reported improvements in ADHD with St. John’s wort12 and true chamomile13 in apparently always the same 3 persons with ADHD. No scientific weight should be attached to these studies. Why a meta-analysis nevertheless cites 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 for ADHD. On this basis, use should be cautioned against.
A randomized double-blind study found Ginkgo biloba to be less effective than MPH for ADHD.14 MPH showed more frequent side effects of loss of appetite, headaches and insomnia. It was significant that the effect was rated much higher in the parents’ assessment than in the teachers’ assessment - a pattern that often occurs with emotionally desirable treatment methods.
Up to 240 mg of Ginkgo biloba improved ADHD behavioral symptoms and electrical brain activity in children in a very small study (n = 20).15
A randomized, placebo-controlled study of children and adolescents with ADHD found that Ginkgo biloba as an additional treatment alongside 20 to 30 mg of MPH improved its effect.16
Simultaneous treatment with Ginkgo biloba and ginseng alleviated ADHD symptoms in children in a small study (n = 36), with few side effects.17
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 fewer side effects.1819
Yizhidan appears to be a Chinese medicinal plant.20
Since there is no other study on this apart from the one mentioned, the study was only single-blind (which can potentially cause a bias in favor of the desired result) and the study itself cannot be verified, the result is in no way certain.
The investigation report also shows a peculiar parallel to 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 means 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 of 100 children showed a significant reduction in symptoms.21
Since there is no other study on this apart from the one mentioned and the study itself cannot be verified, the result is in no way certain.
The investigation report also shows a peculiar parallel to that on Yizhidan (YZD), since in both cases the impairments to be eliminated by the drug in the test animals are caused by the same means and described in the same wording, and it appears to be the same journal.
5. Rehmanniae Radix Preparata, Catalpol
In an article (which at least meets scientific formalities), the effectiveness of Rehmanniae Radix Preparata as a remedy for ADHD, which is frequently used in traditional Chinese medicine (TCM), was investigated. However, there is a complete lack of trials with test subjects and it is openly communicated that the financier of the article influenced the publication.22
Another article confirmed a positive effect of Catalpol, a component of Rehmanniae Radix Preparata, on ADHD symptoms in rats 23
Catalpol is then 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 reduced 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.
There have been reports of kratom being used for ADHD,24 particularly as a self-medication.25
Since the effect of kratom can vary greatly depending on the type of tree and dose, and can even be the opposite, and the effect has not yet been proven, we must urgently warn against self-medication.
There are indications of an addictive potential26 and of the potential to trigger seizures,27 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 performance of CNT and FAIR performance score compared to the placebo group in a double-blind randomized trial against placebo.28 ADHD was an exclusion criterion for the subjects. Application to people with ADHD has not been reported to date.
As always, such research results are only reliable after replication by other research teams.
8. Saffron
A randomized double-blind study found the same improvement in ADHD symptoms in children and adolescents with saffron as with MPH, with the same side effect rate.29
A non-randomized study with authors’ conflicts of interest claimed an equivalent Effect size of saffron extract on ADHD symptoms as methylphenidate with a better effect on hyperactivity than MPH, while MPH had a better effect on inattention.30 7 patients from the methylphenidate group (25.9 %) and 10 patients from the saffron group (31.2 %) reported side effects.
Two randomized double-blind clinical trials found an improved effect of MPH plus saffron compared to MPH alone.3132
9. Long Mu Qing Xin Mixture (LMQXM)
Long Mu Qing Xin Mixture (LMQXM) is an empirical Chinese medicine formula for ADHD in children, consisting of:33
- Radix astragail (Mongolian tragacanth)
- Radix angelicae sinensis (Chinese angelica)
- Ramulus uncariae cum uncis (Uncaria twigs and thorns / cat’s claw)
- Fructus jujubae (red date)
- Radix paeoniae alba (white peony root)
- Fructus schisandrae (Schisandra chinensis fruits)
- Radix scutellariae (Scutellariae baicalensis radix / Baikal skullcap root)
- Cortex phellodendri (yellow tree bark)
- Calcined dragon bones (fossils used as medicines and miracle cures)
- Calcined oyster shells
- Mussel margartifera usta (river pearl mussel)
- Magnetitum (magnetic iron stone / magnetite / iron oxide / mangetite / magnetic stone. Chinese name: Ci Shi)
- Mixed roasted licorice
- Light wheat and
- caulis polygoni multiflori (multiflorous knotweed stalk).
Long Mu Qing Xin Mixture (LMQXM) is said to have relieved hyperactivity, learning and memory problems in SHR as well as MPH.3433
The main active ingredients that bind well to DRD1 and DRD2 are:33
- Beta-sitosterol
- Stigmasterol
- Rhynchophylline
- Baicalein and
- Formononetin.
LMQXM appears to act via the DA and cAMP signaling pathways.
While MPH and medium-dose LMQXM-MD increased DA and cAMP levels, mean optical density (MOD) of cAMP, and MOD and mRNA expression of DRD1 and PKA in the prefrontal cortex (PFC) and striatum of SHR, low- and high-dose LMQXM increased DA and cAMP levels in the striatum, MOD of cAMP in the PFC, and mRNA expression of PKA in the PFC. There was no significant regulatory effect of LMQXM on DRD2.33
As there are no further studies on LMQXM in ADHD apart from the 2 studies cited here, which are also from the same group of authors, its use is strongly discouraged.
The broader the range of products, the higher the risk of side effects.
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. ↥ ↥ ↥
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. ↥ ↥
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. ↥
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. ↥
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. ↥
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. ↥
Sharma G, Sharma N, Nguyen BT, Jeong JH, Nah SY, Yoneda Y, Shin EJ, Kim HC (2021): Protective Potential of Ginkgo biloba Against an ADHD-like Condition. Curr Mol Pharmacol. 2021;14(2):200-209. doi: 10.2174/1874467213666200424152454. PMID: 32329705. REVIEW ↥
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 ↥
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 ↥
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. ↥
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 ↥
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 ↥
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 ↥
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 ↥
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 ↥
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. ↥
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 ↥
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. ↥
http://www.biomedsearch.com/nih/Clinical-experimental-study-treatment-childhood/12577370.html ↥
Rakel, Integrative Medicine, Elsevier, Seite 110 ↥
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. ↥
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 ↥
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. ↥
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. ↥
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. ↥
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. ↥
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. ↥
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 ↥
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 ↥
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 ↥
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 ↥
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, https://doi.org/10.1016/j.aimed.2022.01.002. n = 44 ↥
Li X, Xiao Z, Pu W, Jiang Z, Wang S, Zhang Y (2023): Network pharmacology, molecular docking, and experimental validation to explore the potential mechanism of Long Mu Qing Xin mixture for the treatment of attention deficit hyperactivity disorder. Front Pharmacol. 2023 Mar 17;14:1144907. doi: 10.3389/fphar.2023.1144907. PMID: 37007045; PMCID: PMC10063801. ↥ ↥ ↥ ↥
Li X, Xiao Z, Jiang Z, Pu W, Chen X, Wang S, Liu A, Zhang H, Xu Z (2024): Long Mu Qing Xin mixture improves behavioral performance in spontaneously hypertensive rats (SHR/NCrl) by upregulating catecholamine neurotransmitters in prefrontal cortex and striatum via DRD1/cAMP/PKA-CREB signaling pathway. Front Pharmacol. 2024 Jul 4;15:1387359. doi: 10.3389/fphar.2024.1387359. PMID: 39027341; PMCID: PMC11254830. ↥