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
  • 1.1. Dopaminergic mechanisms of action of ginseng
  • 1.2. Ginseng for ADHD
• 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)
• 10. Maritime pine bark extract

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
• 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
• 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

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 thereby 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 parent assessment than in the teacher 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

As 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.

RRP brought about improvements at SHR in terms of:

• Impulsiveness²⁴²⁵
• Hyperactivity²⁴²⁵
• spatial learning and memory skills²⁴

RRP significantly reduced neuronal loss and increased the number of hippocampal stem cells and promoted synaptic plasticity. FGF/FGFR signaling was increased.²⁴

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,²⁶ particularly as a self-medication.²⁷
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 potential²⁸ and of the potential to trigger seizures,²⁹ 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.³⁰ 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.³¹
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 worked better on inattention.³² 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.³³³⁴

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:³⁵

• 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.³⁶³⁵

The main active ingredients that bind well to DRD1 and DRD2 are:³⁵

• 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. A significant regulatory effect of LMQXM on DRD2 was not found.³⁵

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.

10. Maritime pine bark extract¶

The French maritime pine bark extract Pycnogenol® is a proprietary product from Pinus pinaster Aiton. Pycnogenol® is a standardized bioflavonoid extract.³⁷ and contains 65-75%³⁸ to 85%³⁹ procyanidins, a variety of biopolymers consisting of monomeric units of catechin and epicatechin.³⁸⁴⁰ It also contains gallic acid, caffeic acid and ferulic acid (phenolic acids) as secondary constituents, each of which has its own biological and clinical effects.³⁹

In a small prospective study, Pycnogenol showed positive effects on ADHD symptoms in children.⁴¹ In another small RCT, it improved the attention of children with ADHD⁴²
An RCT on n = 88 children with ADHD aged 6 to 12 years found an improvement in hyperactivity and impulsivity in the teacher rating⁴³

• through pycogenol of 34
• by MPH of 36 %

Inattention was only significantly improved by MPH in the teacher rating⁴³
In the parent rating, both medications were also effective, but MPH was significantly more effective for hyperactivity and inattention.
At the same time, the side effects of MPH were significantly higher (39 %), while the side effects of Pcnogenol (8 %) were at placebo level (9 %). Pycnogenol did not cause any appetite problems.
higher.
While MPH significantly reduced the “hunger neuropeptide” NPY, which regulates food intake and the reduction of anxiety and stress, by 21%, Pycnogenol did not significantly increase it by 11%.⁴³

Pycnogenol significantly improved spatial working memory and the quality of working memory by 10.9 % and 8.5 % respectively compared to placebo in an RCT involving n = 101 subjects aged between 60 and 85 years with moderately impaired cognitive function. The lipid peroxidation products (F2-isoprostane in plasma) were reduced by 22.9 % compared to 3.7 % with placebo.⁴⁴

One RCT examined the urinary catecholamine concentrations in children with ADHD.³⁷
The concentrations of catecholamines in the urine of ADHD patients were five times higher than in healthy children.
The concentration of noradrenaline correlated positively with the degree of hyperactivity of the ADHD children.
The concentrations of adrenaline and noradrenaline correlated positively with the plasma levels of oxidized glutathione of the ADHD children.
The administration of Pycnogenol showed in the urine

• Dopamine reduced
• Noradrenaline and adrenaline tend to be reduced
• GSH/GSSG ratio increased

Urinary catecholamine levels normalized by Pycnogenol correlated with reduced hyperactivity and reduced oxidative stress in children with ADHD.

For information on the limited significance of peripheral catecholamines in urine for catecholamines in the brain, see Measurement of dopamine.

According to an RCT on children with ADHD, maritime pine bark extract had the following effects

• a reduction in reduced and oxidized glutathione⁴⁵
• an improvement in the antioxidant status⁴⁵⁴²
• this reduced the content of oxidized purines, measured at 8-oxo-7,8-dihydroguanine (8-oxoG)⁴²
• reduced the significantly increased oxidative damage to DNA by 30% in children with ADHD compared to those not affected⁴² but not in adults⁴⁶

Pycnogenol can, under certain circumstances, enhance oxidative stress-mediated DNA damage in vitro and in vivo.⁴⁰

Positive effects on other aspects of health were also reported.⁴³

It is a little surprising that so many studies are investigating a patented preparation.