Passiflora and its anxiolytic and anticonvulsant effects

Author: Francesco Cilla
Date: 08/07/2015


(Passiflora incarnate)

FAMILY : Passifloraceae
HABITAT : Central and South America, southern United States. Currently it is grown in many countries with temperate climates -hot.

PART USED : the aerial parts of the plant.


Passiflora incarnata is an indigenous American vine with white and blue or purple flowers and an edible fruit. Its medicinal use originated with native Americans, and its most popular uses are for insomnia and anxiety ( Carlini 2003).
Passiflora incarnata is listed in the pharmacopoeias of Great Britain, United States, India, France, Germany, Switzerland and others ( Dhawan et al. 2001b).


- Flavonoids(flavonoids glycoside: schaftoside, isoschaftoside, isovitexina-2’’- O-glucopiranoside, isoorientina-2’’- O-glucopiranoside, swertisina)
- Phenolic compounds
- Alkaloids armanici
- Chrysin , a 5,7-diidroxyflavon1

The structure of these compounds has recently been the subject of a thorough analysis, conducted with analytical methods (HPLC and mass spectrometry).2

The aerial parts of Passiflora are the subject of a Pharmacopoeia monograph
European that reports as a quality standard the determination of total flavonoids, expressed as
vitexin. The drug is compliant if it has a content of less than 1.5% of vitexin (European Pharmacopoeia).
Finally, they were also identified 21 amino acids, sugars and a cyanogenic glycoside (ginocardina) of
which it is still uncertain attribution to the species Passiflora_incarnate.3

The composition in flavonoids of Passiflora_incarnata it varied widely in the various stages of cultivation, and, therefore, great attention must be paid to the collection and treatment of the plant complex to be able to get a final product standardized in its active. Flavonoid production and accumulation during the ontogenic cycle of Passiflora_incarnata L. was studied. The highest
concentration of isovitexin occurred between pre-flowering and flowering stages. The greatest accumulation of flavonoids took place in the leaves. Furthermore some pharmacodiagnostic characteristics of the drug of P. incarnata were specified using a Scanning Electron Microscope.4


In the more recent literature, flavonoids are considered the most likely active ingredient ( Speroni and Minghetti, 1988, Dhawan et al., 2001b and Dhawan et al., 2004), because some flavonoids have anxiolytic properties in mice similar to benzodiazepines ( Zanoli et al. 2000), and modulate (Kavvadias et al. 2004) or inhibit ( Goutman et al. 2003) GABAA and GABAC receptor currents.
Recents studies have shown that specific benzodiazepine-induced pharmacological effects are mediated by specific GABAA receptor subtypes (This effect of Passiflora can be inhibited by the benzodiazepine site antagonist Ro 15-1788, suggesting the involvement of GABAA receptors ( Medina et al. 1990)). Agonists acting on the α1 subunit show predominantly sedative effects and partially anticonvulsant effects, while agonists acting on the α2 subunit show predominantly anxiolytic effects ( Rudolph and Möhler, 2006 and Fradley et al., 2007). Since the natural flavonoids tested to date (hispidulin, apigenin, and quercetin) all seem to modulate α1GABA receptors, they may be more effective as anticonvulsants than as anxiolytics.
It is also conceivable that the unexpected anxiogenic activity of Passiflora extracts resulted in one study6 , may result from flavonoids which change from weak agonists to weak antagonists at specific GABAA receptor subtypes ( Rudolph and Möhler 2006).
The reported narrow dose range of anxiolytic effects of Passiflora ( Dhawan et al., 2001b and Grundmann et al., 2008) may also suggest the presence of both anxiolytic and anxiogenic components with different dose/response profiles, possibly with increased anxiogenic effect at higher doses.

Here we can see effects of whole Passiflora extract in CA1 pyramidal cells in hippocampal slices. The extract did evoke a direct current with a dose-dependent amplitude ( Fig. 4A and C). This was mediated by GABAA receptors, as evidenced by its complete but reversible block by the GABAA receptor antagonist GABAzine (10 M, Fig. 4A). The GABAA receptor current was likely elicited by GABA present in the extract, because no current was induced by extracts from which GABA and other amino acids had been largely removed ( Fig. 4B–D).
Recents studies have shown that 5,7-dihydroxyflavone (chrysin) possesses anxiolytic actions without inducing sedation and muscle relaxation. We postulate that this natural monoflavonoid is a partial agonist of the central BDZ receptors5.


Many studies show that Passiflora extracts not only contain a high amount of GABA, but are also able to induce direct GABAA in CA1 hippocampal pyramidal neurons. Since the extract with reduced amino acid levels induced no current, it is likely that the GABA content of the extract is sufficient to explain the observed GABA currents in vitro. As the main endogenous inhibitory neurotransmitter, GABA might be expected to act as a natural anticonvulsant. However, we did not find a correlation between an extract’s GABA content and its anticonvulsant activity in vivo. Since orally administered GABA is subject to active transport across membranes both in the intestinal tract as well as across the blood-brain barrier , the pharmacological significance of GABA-content in Passiflora extract is still unclear6.

Two dry extracts of Passiflora, containing respectively 3.0% and 9.1% of total flavonoids, have been studied for their binding affinity for three different receptors. At concentrations between 10 and 1000 micrograms / ml showed no interaction with the binding sites, including subtypes of benzodiazepine, dopamine and histamine. The two main flavonoids, isovitexin-2 '' - glucoside and isoorientina-2 '' - glucoside, did not inhibit the binding site for benzodiazepines at concentrations up to 30 μM.
A total ethanolic Hypericum extract potently inhibited GABAA binding at approximately 3 micrograms/ml. This inhibitionis however not specific to Hypericum, since extracts of plants like Valeriana officinalis and Passiflora_incarnata showed similar inhibitions. Binding to neither histamine nor metabotropic glutamate receptors was affected by Hypericum extracts.
These results support the hypothesis that several active constituents of Hypericum might in a synergistic way contribute to its antidepressant effect in the central nervous system.7
Passiflora bioactivity may also result from synergistic actions of several compounds, such as a combination of GABA with additional compounds which may facilitate its membrane permeation, and possibly along with second order positive modulation of GABAA receptors by flavonoids ( Campbell et al. 2004). The recent literature, e.g. on interactions between multiple sedative ingredients of Valeriana_officinalis ( Marder et al., 2003, Fernández et al., 2004 and Granger et al., 2005), suggests that such synergistic interactions between several active constituents within the same extract may be a common finding in natural products ( Johnston et al. 2006).

Comparing ingredient and biological activity from all extracts, there was no correlation between total flavonoid or GABA content with anxiogenic or anticonvulsant effects. The two extracts with the highest GABA content (PAS 1 and PAS 8) did not show anticonvulsant effects, and the two extracts with anticonvulsant effects differed widely in their total flavonoid content (PAS 4 and PAS 5). Similarly, there was no correlation between GABA content and anxiogenic effects.

Table 4.
Content and biological effects of the five Passiflora extracts.

ExtractExtract yield Flavonoid (% w/w of dry plant material)Extract yield Flavonoid content (% w/w of the extract)GABA content (% w/w of the extract)Dose of passiflora herb equivalent to 1000 mg/kg/day of extract (g/kg/day)Anxiogenic effectsAnticonvulsant effects
PAS 18.53.0%3.8%11.8MediumAbsent
PAS 424.030.6%2.0%4.2LowPresent
PAS 57.72.8%2.1%13.0HighPresent
PAS 79.846.4%2.2%10.2LowAbsent
PAS 88.820.3%2.9%11.4HighAbsent

The effects of the extracts maybe depends  on the basal level of anxiety of patients.
The extracts might function as modulators of one or several neurotransmitter systems, similar to positive and negative allosteric modulators whose action critically depends on the presence or absence of endogenous neurotransmitters whose levels would vary with baseline anxiety states. 
No therapeutic relevance, due to the lack of concentration in which they would be present, has to be attributed to the alkaloids in the plant8.


Especially useful in insomnia type brain, where it causes a sleep similar to the physiological and an awakening without stunning.
In 3 clinical trials Passiflora extracts showed anxiolytic efficacy. One of the trials compared Passiflora to placebo ( Movafegh et al. 2008), and two others showed Passiflora to have anxiolytic efficacy similar to benzodiazepines ( Mori et al., 1993 and Akhondzadeh et al., 2001b). In addition, Passiflora extract showed sedative effects in 2 clinical trials ( Akhondzadeh et al., 2001a and Movafegh et al., 2008).
A clinical study has evaluated the effect of passionflower in patients with anxiety disorders. These were 36 patients with diagnosis of anxiety syndrome, for receiving the mouth dry extract of passionflower or 30 mg per day of oxazepam (note benzodiazepine) for 4 weeks. The evaluation was made using the Anxiety Scale (a test that can measure anxiety) before and after therapy. It is seen that both treatments were effective at the end of the trial, even if oxazepam showed its benefits more quickly. But it caused problems of sleepiness and poor concentration at work in many patients, the problems were much less pronounced in patients treated with Passiflora. In neither group were observed significant adverse reactions9.
A clinical study has evaluated the anticonvulsant effects of passiflora in many patients, but at the end of this study is not clear the correlation between an extract’s GABA content and its anticonvulsant activity in vivo.

Authors: Francesco Cilla and Lorenza Palmero


1 Role of chrysin in the sedative effects of Passiflora incarnata.” E, Billi R, Crespi Perellino N, Minghetti A. Role of chrysin in the sedative effects of Passiflora incarnata L. Phytotherapy Research 1996; 10: S98-S100.

2 Mass spectral characterization of C-glycosidic flavonoids isolated from a medicinal plant(Passiflora_incarnata)

3 Raffaelli A, Moneti G, Mercati V, Toja E. Mass spectrometric characterization of flavonoids in
extracts from Passiflora incarnata. Journal of Chromatography 1997; A. 777: 223-231

4 TLC determination of flavonoid accumulation inclonal populations of Passiflora incarnata L.

5 Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from Passiflora coerulea

6 Passiflora incarnata L. (Passionflower) extracts elicit GABA currents in hippocampal neurons in vitro, and show anxiogenic and anticonvulsant effects in vivo, varying with extraction method

7 Extracts and constituents of Hypericum perforatum inhibit the binding of various ligands to recombinant receptors expressed with the Semliki Forest virus system. J Recept Signal Transduct Res. 1999; 19(1-4):59-74). Simmen U, Burkard W, Berger K, Schaffner W, Lundstrom K.

8 Meier B: Passifloræ Herba: Pharmazeutische Qualitat. Zeitschrift-fur-Phytotherapie. 1995B; 16/2: 90-99

9 Dhawan K. et al. Anti-anxiety studies on extracts of Passiflora incarnata Linneaus. J. Ethnopharmacol. 78, 165-170, 2001

2015-07-08T20:26:36 - Francesco Cilla

Authors: Francesco Cilla and Lorenza Palmero

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