Natural antidepressants: what are they?

What are

Natural antidepressants constitute a vast group of substances of natural origin, capable of exercising antidepressant and mood-regulating activities. These activities are carried out centrally through various mechanisms of action.
Within the large group of natural antidepressants there are numerous plants, whose extracts are able to improve the mood through more or less known mechanisms.

Natural antidepressants: what are they?

In some cases, natural antidepressants are part of the composition of real drugs used for the treatment of depressive syndromes; while in many other cases these substances are found in food supplements, therefore their purchase can be made without presenting a medical prescription. However, this does not mean that such products are free from side effects or have no contraindications of any kind. For this reason, before taking natural antidepressants of any kind, it is necessary to ask for the advice of the doctor, in order to exclude the presence of any contraindications or potential risks deriving from the use of the product.


Ademionionine - also known as S-adenosil metionina o SAMe - it is a coenzyme naturally present in our body. This substance has the task of transferring methyl groups in the context of various metabolic reactions of fundamental importance for the organism.
The interest in ademionionine in the treatment of depression and mood disorders is due to its involvement in the synthesis reactions of various neurotransmitters - such as serotonin, dopamine and noradrenaline - involved in the regulation of mood.
It has been shown that levels of S-adenosyl methionine are lower in the cerebrospinal fluid of patients with depression than in healthy patients. This fact may be sufficient to explain the therapeutic efficacy of adethionine, but the activities of this substance do not end there. In fact, it is also able to regulate the synthesis and increase the levels of other compounds (such as melatonin and folate) which are believed to be involved in the etiology of depressive syndromes.
Since the aforementioned activities have been widely demonstrated, ademionionine belongs to the group of natural antidepressants included in the composition of real drugs for the treatment of depression (Samyr®).
There are, however, also food supplements based on this active ingredient, useful in case of lowering of mood. Of course, in such products the concentration of ademetionine is much lower than that contained in medicinal specialties.

Effetti Collaterali

Although it is an endogenous substance - therefore, of natural origin - following the intake of ademetionine, the following can occur:

  • Anxiety;
  • Headache;
  • Nausea;
  • Diarrhea;
  • Increased frequency of urination.

Pharmacological interactions

Concomitant intake of ademetionine and substances such as tricyclic antidepressants, serotonin reuptake inhibitor (SSRI) drugs, tryptophan medicines and / or supplements increases the risk of developing serotonin syndrome.
Therefore, the simultaneous use of ademetionine and any of the above substances should be avoided.


Hydroxytryptophan - or, more precisely, the 5-hydroxytryptophan - is an amino acid derivative synthesized in the body by the enzyme tryptophan hydroxylase.
5-hydroxytryptophan represents an intermediate in the synthesis of serotonin, one of the neurotransmitters most involved in mood regulation. At the same time, this compound has been shown to be capable of increasing the levels of melatonin in the body.
For this reason, 5-droxytryptophan can be found in various food supplements indicated in all those cases where it is necessary to improve mood and / or counteract sleep disorders.

Effetti Collaterali

Undesirable effects such as vomiting, heartburn and stomach pain, flatulence, diarrhea and insomnia may occur after taking 5-hydroxytryptophan.

Pharmacological interactions

5-hydroxytryptophan can establish drug interactions with carbidopa, monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitors (SSRIs).
For this reason, 5-hydroxytryptophan should not be taken concomitantly with the aforementioned drugs, unless otherwise prescribed.


Griffonia (Griffonia simplicifolia) is a plant belonging to the Fabaceae family, whose seeds are rich in 5-hydroxytryptophan. The latter, as we have seen, is a metabolic intermediate in the synthesis of serotonin. The extracts of the plant, therefore, are part of the composition of food supplements indicated to improve the mood.
The mechanism of action by which griffonia seed extracts exert antidepressant activity, side effects and drug interactions are similar to those described above for 5-hydroxytryptophan.


Hypericum (Hypericum perforatum) - also known as St. John's Wort - is considered the natural antidepressant par excellence.
The antidepressant properties of hypericum are attributed to the set of substances contained in its extracts, including hyperforin, hypericin, pseudohypericin, anamentoflavone and rutin.
Although the mechanism underlying the antidepressant activity of hypericum is not yet fully understood, it is believed that the extract of the plant carries out this action through the interaction with the norepinephrine, serotonin and dopamine receptors. Interaction that leads to an increase in the signal of the aforementioned neurotransmitters, which results in an improvement in mood.
Furthermore, the extracts of St. John's wort are also able to inhibit the reuptake of GABA at the presynaptic level. Although this activity justifies its anxiolytic properties more than anything else, it seems that it may also be implicated in the antidepressant mechanisms of action of the plant extracts.

The antidepressant activity of hypericum has been amply confirmed by numerous studies, which have shown that its extracts are able to exert an action similar to that of various antidepressant drugs (such as, for example, imipramine). For this reason, hypericum dry extract is part of the composition of medicines (Quiens®, Nervaxon®) indicated for the treatment of mild and moderate depressive syndromes.

Natural antidepressants: what are they?

Effetti Collaterali

Although these are natural antidepressants, the side effects that can occur following the intake of hypericum extracts are many. Among these, we remember:

  • Gastrointestinal disorders;
  • Photosensitivity reactions;
  • Headache;
  • Fatigue;
  • Restlessness;
  • Hypertensive crisis;
  • Increased frequency of urination.

Pharmacological interactions

Unfortunately, hypericum extracts can cause numerous drug interactions with:

  • Other antidepressant drugs;
  • Oral anticoagulants;
  • Immunosoppressori;
  • Anticancer drugs;
  • Anticonvulsants;
  • Antiarrhythmics;
  • Antibiotics;
  • Antivirals;
  • Beta-blocking drugs;
  • Hypoglycemic agents;
  • Antihypertensive and antianginal drugs;
  • Contraceptives and other estrogen-based drugs;
  • Theophylline;
  • Caffeine;
  • Foods containing tyramine.

Concomitant intake of the aforementioned substances and hypericum extracts should therefore be avoided.


Rhodiola (Rhodiola rosea) is a perennial herbaceous plant belonging to the Crassulaceae family.

The extracts obtained from this plant are certainly known for their nootropic and stimulating properties. However, some studies have shown that the intake of the aforementioned extracts can also be useful to counteract depressive asthenia, that is the state of severe fatigue that occurs in many patients suffering from depressive syndromes.
This action seems to be exerted through the inhibition of monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT), or through the inhibition of enzymes responsible for the metabolism of neurotransmitters such as serotonin, noradrenaline and dopamine.
By virtue of these properties, rhodiola is used in various food supplements that can be useful in case of mood disorders and in case of particularly stressful periods.

Pharmacological interactions

The concomitant intake of rhodiola extracts and other drugs or substances with a stimulating action can give rise to potentially harmful and dangerous additive effects. Therefore, such associations should be avoided.


In addition to the classic contraindication in case of known hypersensitivity to rhodiola and its extracts, these natural antidepressants should not be used in patients with bipolar disorders who develop manic episodes after taking antidepressant or stimulating drugs.


Often, cocoa - and, more precisely, the chocolate obtained from it - is referred to as a natural antidepressant. In fact, cocoa contains various substances (such as, for example, 2-phenylethylamine) capable of increasing noradrenergic and dopaminergic transmission, which can lead to an improvement in mood.
Despite this, cocoa is not included in the composition of any type of drug or supplement intended for the treatment of mood disorders or depressive syndromes.
However, thanks to the sense of gratification that its intake is able to induce, chocolate is considered by many to be the best natural remedy for sadness and depression (not pathological).

Pregnancy and breastfeeding

Can Natural Antidepressants be used in Pregnancy and Breastfeeding?

As a precaution, the use of natural antidepressants during pregnancy and breastfeeding is generally contraindicated due to the potential risks that may arise.
However, pregnant women and mothers who are breastfeeding should always seek the advice of their doctor or gynecologist before taking substances of any kind for therapeutic purposes (medicines or supplements).
Also, remember that pregnancy depression and postpartum depression are serious ailments that should not be underestimated. Therefore, in case of mood alterations, before resorting to do-it-yourself treatments based on natural antidepressants, it is advisable to contact specialized medical personnel.

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