Stress, rest, concentration and mental energy have become central areas of wellbeing. In Spain, the relaxation and sleep products market reached €130.9 million between January and September 2025, with 8.13% year-on-year growth, while the cognitive stimulants category reached €22 million between January and October 2025, 11.73% more than the previous year, according to IQVIA.
These figures describe consumer categories, not an official ranking of individual ingredients. For that reason, this article does not present a list of the “best-selling botanicals”, but rather a selection of ingredients found in high-demand wellbeing areas in Spain and with sufficient scientific literature to explain the mechanisms currently being investigated.
There is also a key idea: botanical ingredients do not work like switches that “turn a neurotransmitter on or off”. Neurobiology is more complex. A compound may interact with receptors, enzymes, neurotransmitter synthesis, release or reuptake, with the stress-response axis, or with neuronal plasticity processes. And a mechanism observed in cells or animals does not by itself demonstrate a clinical benefit in humans.
Why we talk about modulation rather than “activating” neurotransmitters
The brain works through networks. Glutamate is the main excitatory neurotransmitter in the central nervous system; GABA is its main inhibitory neurotransmitter; dopamine participates in motivation, learning and reward; serotonin is involved in multiple circuits related to emotional state, appetite and sleep; noradrenaline participates in alertness and the stress response; and acetylcholine plays an important role in attention, learning and memory.
Alongside them operate hormones such as cortisol, neuroendocrine circuits such as the hypothalamic-pituitary-adrenal (HPA) axis, neuronal growth factors and mechanisms of synaptic plasticity. This is why reducing an ingredient to phrases such as “raises serotonin” or “activates GABA” is usually scientifically imprecise.
In the following sections we distinguish between a preclinical mechanism — what is observed in cellular or animal models — and clinical evidence — what is studied in people. That distinction is fundamental to interpreting the science correctly.
Ingredients and compounds studied by science
1. Ashwagandha KSM-66®: withanolides and the stress response
Ashwagandha (Withania somnifera) is a plant used in Ayurvedic tradition. Its characteristic constituents include withanolides, a group of plant steroidal lactones. Scientific interest is not limited to a single neurotransmitter: a relevant part of the research examines its relationship with the HPA axis, one of the main physiological systems involved in the stress response.
Preclinical models have described interactions with GABAergic and glutamatergic signalling, as well as with neuronal plasticity processes. This does not allow us to state that a capsule “increases GABA” in the human brain. The accurate interpretation is that plausible mechanisms are being investigated and need to be contrasted with clinical trials.
In humans, a 2024 systematic review and meta-analysis included nine randomized trials with 558 participants and found differences versus placebo in stress and anxiety scales and in cortisol. The authors also emphasized heterogeneity in doses and formulations and the need for more long-term safety data.
Practical point: when comparing ashwagandha products, the identity of the extract, its standardization and the dose used all matter; not all products are equivalent.
2. Saffron Affron®: crocins, crocetin and safranal
Saffron comes from the stigmas of Crocus sativus. Its most studied compounds include crocins, crocetin and safranal. Preclinical research has explored their relationship with serotonergic, dopaminergic, GABAergic and glutamatergic systems, as well as antioxidant pathways.
The clinical literature has also grown. A 2026 meta-analysis included 34 randomized trials and 1,769 participants. Some self-reported scales showed favourable changes, while other clinical measures found no significant differences. This discrepancy is a reminder that a positive result on one scale is not the same as demonstrating a universal effect or justifying a therapeutic promise.
Trials on sleep also exist. A 2022 meta-analysis found promising results for certain measures of sleep quality, although the studies were relatively small and used diverse formulations.
3. L-theanine: balance between excitation and relaxation
L-theanine is not a whole botanical extract, but an amino acid naturally present in tea leaves (Camellia sinensis). Its structure is similar to glutamate, which is why its interaction with glutamatergic receptors and with systems related to GABA, dopamine and serotonin has been investigated.
Much of the neurochemical explanation comes from preclinical studies. In humans, a 2026 systematic review and meta-analysis examined 31 randomized trials and 1,168 participants. An acute 200 mg dose showed effects in some reaction-time and attention tests, while findings for stress and anxiety were more variable. The authors noted that more robust trials are needed to define the clinical relevance.
A 2025 review of sleep outcomes also found improvements in some subjective measures. This does not make L-theanine a sedative or allow us to claim that it causes sleepiness in everyone; its interest is studied more in the context of relaxation and attention.
4. Bacopa monnieri: bacosides, acetylcholine and plasticity
Bacopa is another plant used in Ayurvedic tradition. Its characteristic constituents include bacosides. Preclinical models have described mechanisms related to the cholinergic system — including enzymes linked to acetylcholine — as well as serotonergic, dopaminergic and GABAergic signalling, antioxidant defence and synaptic plasticity.
In 2026, a systematic review with network meta-analysis evaluated Bacopa and Ginkgo across 29 trials involving 2,107 healthy adults. Some Bacopa preparations and doses ranked favourably for certain memory measures, but the authors highlighted important limitations: heterogeneity, lack of direct comparisons between many interventions, and dependence on formulation and dose.
Therefore, findings from an extract used in a trial should not automatically be transferred to any product containing Bacopa. The actual composition and amount of extract matter.
5. Rhodiola rosea: salidroside, rosavins and response to demand
Rhodiola contains compounds such as salidroside and rosavins. Research has examined its relationship with stress-response systems and with serotonergic, dopaminergic and noradrenergic signalling. Again, an important part of these mechanisms comes from preclinical models.
In humans it has been studied particularly in contexts of fatigue and performance. A 2025 meta-analysis included 26 randomized trials with 668 healthy participants and found changes in some endurance-related variables, although with considerable heterogeneity. It is therefore more prudent to describe it as an ingredient investigated in relation to the response to physical and mental demand rather than as a stimulant with a guaranteed effect.
6. Valerian: valerenic acid and GABA-A receptors
The root of Valeriana officinalis contains a variety of compounds. One of the most interesting from a neuropharmacological perspective is valerenic acid. In experimental receptor studies, valerenic acid has been associated with allosteric modulation of certain GABA-A receptors.
This does not mean that valerian is “natural GABA”. A receptor modulator, a neurotransmitter and a medicine are different concepts. In addition, a plausible molecular mechanism does not guarantee clinical efficacy.
An umbrella review of reviews published in 2024 concluded that valerian generally has a reasonable safety profile, but that objective evidence does not robustly support the claim that it treats insomnia. Some research does report subjective improvements in sleep quality. The distinction between the two is essential.
7. Ginkgo biloba: flavonoids, terpene lactones and cognitive function
Ginkgo mainly contains flavonoids and terpene lactones, including ginkgolides and bilobalide. Research extends far beyond neurotransmitters: cerebral circulation, mitochondrial function, oxidative stress and different neuronal signalling systems have all been studied.
In healthy adults, the evidence on cognition is heterogeneous. The 2026 network review that indirectly compared different Bacopa and Ginkgo preparations does not allow the conclusion that there is a universally superior ingredient for memory, attention or processing speed. Formulation, dose, population and study duration modify the results.
How these ingredients relate to GABA, serotonin, dopamine and acetylcholine
GABA: it is the main inhibitory neurotransmitter in the central nervous system. Valerian stands out for experimental research on valerenic acid and GABA-A receptors. Ashwagandha and L-theanine also appear in preclinical studies related to GABAergic signalling, but this should not be extrapolated into the statement that they “raise GABA” in humans.
Glutamate: it is the main excitatory neurotransmitter. L-theanine is studied because of its structural similarity and interaction with glutamatergic receptors. Ashwagandha has also been investigated in preclinical models of GABA/glutamate balance.
Serotonin and dopamine: they participate in very broad circuits; they are not simply “the happiness molecule” or “the motivation molecule”. Saffron, rhodiola, bacopa and L-theanine appear in preclinical literature related to these systems. The clinical meaning of these interactions needs to be demonstrated independently in people.
Acetylcholine: it is particularly linked to attention, learning and memory. Bacopa has been investigated in experimental models for its effects on enzymes of the cholinergic system and on neuronal plasticity.
Cortisol and the HPA axis: they are not neurotransmitters, but they are fundamental to understanding the stress response. Clinical research on ashwagandha has examined cortisol as one of its markers.
In summary: biological mechanism, an effect in a trial and a meaningful benefit for a person are three different levels of evidence.
How to orient your choice according to your wellbeing goal
Choosing a supplement should not begin by searching for the most fashionable ingredient, but by defining what you want to support and then reviewing the evidence, formulation and safety.
Fitobotanic selection: for each goal we highlight the active product in the catalogue whose formula has the most direct correspondence with the evidence described in this article. This selection expresses alignment between formula and scientific literature; it does not mean treatment, clinically demonstrated superiority over all products, or guaranteed efficacy.
Calm and everyday stress management
In this area, ashwagandha, saffron and L-theanine are among the ingredients being investigated.
Product with the closest correspondence: KSM-66® Plus Ashwagandha — 60 VegCaps. It is the Fitobotanic option that corresponds most directly with the clinical research on ashwagandha described above. Each capsule provides 300 mg of KSM-66® root extract standardized to 5% withanolides. Extract identity, standardization and dose are relevant when comparing study findings with a commercial formula.
View KSM-66® Plus Ashwagandha → · To compare alternatives, visit Rest, calm and stress or see the SERENA selection.
Night-time routine and rest
Valerian and L-theanine are among the ingredients studied in relation to rest.
Product with the closest correspondence: KAL Melatonin 1 mg — 120 tablets. For a goal specifically focused on sleep onset, this is the catalogue product with the most precise regulatory correspondence: in the European Union, the claim that melatonin contributes to the reduction of time taken to fall asleep is authorized when the food provides 1 mg per quantified portion and information is given that the beneficial effect is obtained by consuming 1 mg of melatonin close to bedtime.
View KAL Melatonin 1 mg → · To compare alternatives, visit Rest, calm and stress or see NŌCTIA.
Concentration, memory and mental clarity
Bacopa and Ginkgo frequently appear in cognitive research, while L-theanine has been studied in attention tasks.
Product with the closest correspondence: SharpMind Focus — 30 VegCaps. It is the Fitobotanic formula most directly built around ingredients related to attention and cognitive function: it combines 250 mg of Cognizin® citicoline, 125 mg of fermented Lion's Mane and 100 mg of Bacopa extract. Evidence for an individual ingredient does not prove that the complete combination is clinically superior or allow a specific cognitive effect to be guaranteed.
View SharpMind Focus → · You can compare other options in Mental clarity and focus or see the CŌGNIA selection.
Vitality and response to demand
Rhodiola is one of the botanicals studied in contexts of fatigue and performance.
Product with the closest correspondence: Super Rhodiola — 60 VegCaps. It is the catalogue option that links most directly with the evidence on Rhodiola discussed in this guide. Each capsule provides 500 mg of standardized root extract, with 15 mg of rosavins (3%) and 5 mg of salidrosides (1%). The available research does not imply a guaranteed performance response in every person.
View Super Rhodiola → · To compare alternatives, visit Vitality and energy.
Important: these categories are a way of organizing products by wellbeing goals. They do not constitute a diagnosis, a prescription, or a claim that supplements prevent, treat or cure disease.
Frequently asked questions about botanicals and neurotransmitters
What is the best natural supplement for stress?
There is no universally best ingredient. Ashwagandha, saffron and L-theanine have been studied in contexts related to stress or emotional wellbeing, but results depend on formulation, dose, population and the outcome being studied. A supplement also does not replace professional assessment when stress is intense, persistent or interferes with daily life.
What is GABA and how is it related to valerian?
GABA is the main inhibitory neurotransmitter in the central nervous system. Valerenic acid from valerian has shown, in experimental models, the ability to modulate certain GABA-A receptors. This does not mean valerian is GABA or that it produces the same effect as a medicine acting on that system.
Does ashwagandha increase GABA?
That cannot be stated in this way in humans. Preclinical studies suggest interaction with GABAergic and glutamatergic signalling, but clinical trials in people evaluate outcomes such as perceived stress or cortisol, not a direct and demonstrated increase in brain GABA.
What is the difference between Bacopa and Ginkgo for memory?
They are different ingredients, with different compositions and studied mechanisms. Bacopa is particularly associated with bacosides and cholinergic/plasticity mechanisms; Ginkgo contains flavonoids and terpene lactones and is also studied from vascular and mitochondrial perspectives. The clinical evidence is heterogeneous and does not support declaring a universal winner.
Does L-theanine make you sleepy?
It should not be described as a sedative. It has been studied both for attention and for subjective measures of sleep and relaxation. Individual responses can vary, and the evidence does not justify claiming that it causes drowsiness in everyone.
Can ashwagandha, saffron, valerian and L-theanine be combined?
The fact that several ingredients are plant-derived does not mean that combining them is automatically appropriate. Additive effects, contraindications or interactions with medicines may occur. The decision should take age, pregnancy or breastfeeding, diagnosed conditions and concomitant medication into account.
What does it mean for an ingredient to “modulate” a neurotransmitter?
It means that an experimental model has observed an interaction with some part of its system: receptor, enzyme, release, degradation or another related pathway. It does not necessarily mean that it increases or decreases the amount of the neurotransmitter in the human brain or produces a specific clinical benefit.
Scientific references and sources
- Lopresti AL, et al. Effects of Ashwagandha (Withania Somnifera) on stress and anxiety: A systematic review and meta-analysis. Explore (NY). 2024;20(6):103062. PubMed 39348746.
- Speers AB, et al. Potential clinical applications of Ashwagandha (Withania somnifera) in medicine and neuropsychiatry. Expert Rev Clin Pharmacol. 2022. PubMed 36062480.
- Effect of saffron on depression, anxiety and mood disorder: a GRADE assessed systematic review and meta-analysis of 34 randomized controlled trials. Nutr Neurosci. 2026;29(7):816-837. PubMed 41693488.
- Bukhari SI, et al. Saffron: a natural product with potential pharmaceutical applications. J Pharm Pharmacol. 2015;67(12):1634-1649. PubMed 26272123.
- Effects of saffron supplementation on improving sleep quality: a meta-analysis of randomized controlled trials. Sleep Med. 2022;92:24-33. PubMed 35325766.
- Cognitive and affective effects of L-Theanine: a systematic review and meta-analysis of 31 randomized trials. Mol Psychiatry. 2026. PubMed 42410082.
- Nathan PJ, et al. The neuropharmacology of L-theanine (N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother. 2006;6(2):21-30. PubMed 17182482.
- The effects of L-theanine consumption on sleep outcomes: A systematic review and meta-analysis. Sleep Med Rev. 2025. PubMed 40056718.
- Aguiar S, Borowski T. Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation Res. 2013. Related mechanistic literature is summarized in PubMed 26413131.
- Comparative effects of Bacopa monnieri and Ginkgo biloba on cognitive functions: A systematic review and network meta-analysis. Phytomedicine. 2026;153:157915. PubMed 41678913.
- Rhodiola rosea L. as a putative botanical antidepressant. Phytomedicine. 2016. PubMed 27013349.
- The effect of Rhodiola rosea supplementation on endurance performance and related biomarkers: a systematic review and meta-analysis. Front Nutr. 2025. PubMed 41080184.
- Khom S, et al. Modulation of GABAA receptors by valerian extracts is related to the content of valerenic acid. Planta Med. 2008;74(1):19-24. PubMed 18095218.
- Does valerian work for insomnia? An umbrella review of the evidence. Eur Neuropsychopharmacol. 2024;82:6-28. PubMed 38359657.
- European Commission. Commission Regulation (EU) No 432/2012: authorized claim for melatonin and reduction of time taken to fall asleep. EUR-Lex.
Market sources
- IQVIA Spain. Evolution of the Spanish pharmacy market, September 2025 data.
- IQVIA Spain. Evolution of the Spanish pharmacy market, October 2025 data.
Responsible use of botanical supplements
This content is educational and does not replace diagnosis or treatment. Food supplements should not be used as a substitute for a varied and balanced diet and a healthy lifestyle. If you are pregnant, breastfeeding, taking medication or have a diagnosed medical condition, consult a healthcare professional before using botanical supplements.
In commercial communication, explaining a scientific mechanism is not the same as making an authorized health claim. Information about botanicals should distinguish between preclinical research, clinical evidence and claims permitted in the European Union.