Passionflower

pasiflora
For many years, passionflower was completely unknown in Croatia. In the “shade” of valerian, passionflower is a plant with very specific purposes and luckily much more is written about it today. Extremely safe, in German phytotherapy it is used even in paediatrics. Insomnia and anxiety have today become the companions of modern society and the application of passionflower has simply become unavoidable. A little caution: when I mention passionflower, especially in coastal areas, everyone immediately says, “Yeah, well, it grows in my garden.” However, beware, there are many species of the genus Passiflora, and only the species P. incarnata is medicinal. Others can be toxic. Passionflower is a fairly well clinically researched plant and today we can recommend it with great certainty. The heavenly flower of passionflower may not create a paradise in your life, but it can bring you a little peace in the hell that surrounds you.
Botanical name:

Passiflora incarnata L., Passifloraceae

Species name:

passionflower

Engl. passionflower, maypop; Fr. passiflore, fleur de la passion; Germ. Passionsblumenkraut, fleischfarbige Passionsblume

Family:

Passifloraceae

Genus:

Passiflora

Medicinal part of the plant:
Green part of plant in bloom (herba cum flore).
Traditional application:
Nervousness, insomnia, bad mood. Stomach upset.
Modern application:
Tension, restlessness, irritability, insomnia.
When to be careful:
Passionflower is a safe plant.
Nutritional value:
The fruit is edible and tasty.
Possibility of confusion:
Other types of passionflower, some of which can be toxic. Only identify with a professional.
Interesting facts:
It experienced its explosion in France as a cure for “PTSD” after the First World War.
Botanical description

Passionflower is a herbaceous creeper, bare, thin, poorly furrowed stems up to 9 meters long, with alternately arranged leaves. The leaves are deeply palmately divided, the leaves are ovate-lanceolate, finely sawn at the top. There are two nectar glands on the long leaf stalks. The flowers are solitary, 3-8 cm in diameter, the petals are pale purple, and from their base grows a series of filamentous pink to purple members of the crown, so that the petals seem to be of two kinds. Passionflower is wild in the eastern and southern parts of North America, and as an ornamental plant is planted all over the world. The entire aboveground part of the plant is used. Passionflower should not be confused with passionfruit, Passiflora edulis Sims. whose leaves are sometimes used to counterfeit drugs.

Official parts of the plant

Green part of the plant (passiflorae herba).

Quality

According to Ph. Eur. Passiflorae herba 01/2008:1459 corr. 6.0

  • at least 1.5% of total flavonoids on vitexin
  • macroscopic and microscopic identification
  • identification by thin layer chromatography with comparators hyperoside and rutin. The chromatogram shows the absence of intense fluorescent zones between the two reference substances, which correspond to diglycosyl-flavones and iso-orientin from species P. edulis and P. coerulea.
  • total ash maximum 13.0%
  • drying loss: maximum 10% (1,000 g of nebulized drug, drying for 2 hours at 105 °C)

There is a separate standard for dry passionflower extract 01/2008:1882 which must not contain less than 2% flavonoids calculated on vitexin.

Forgery is common with other species of the genus Passiflora. Examine microscopically- characteristic hairs of leaves and stems, mostly curved and pointed terminus. The mesophilic leaf contains oxalate crystals 15μm in size, isolated or grouped along the leaf veining.

Chemical composition

Flavonoids (2.5% in the dry weight of the plant): C-glycosides of apigenin and luteolin: iso-vitexin-2 ”-glucoside, shaftozide, iso-shatoside, iso-orientin-2” -β- D-glucoside, vicenin-2.
Sugars: sucrose, fructose, glucose.
Polysaccharides: arabinoglucan.
Essential oils (in traces): limonene, α-pinene, zizaen, zizanen, cumin.
Cyanogenetic heterosides (traces): gynocardin.
Alkaloids (traces): harmin, harmol, hamalol.

Indications/uses

Commission E: states of nervousness.

ESCOP: Tension, restlessness, irritability, insomnia.

Other uses: anxiety, preoperative anxiety, depression (mild to moderate), ADHD, addiction therapy (marijuana/cannabinoids, cocaine, nicotine, alcohol), erectile dysfunction, tinnitus.

Types of extracts and posology
  • infusion of 4-8g of drug per day as an infusion
  • tincture 1-4mL (1: 8 50% ethanol w/v) 3-4x a day, 4mL in the evening for insomnia
  • EPS 5mL/2 capsules 2x daily; 5-10mL 2-4 capsules in the evening for insomnia
  • SIPF 5mL 2x daily, 5-10mL in the evening for insomnia
  • dry standardized extracts equivalent to dry drug
Application time

There are no restrictions. Addictions and habituation have not been reported.

Contraindications

No contraindications.

Drug Interactions

No interactions (Commission E, ESCOP).

Suspect: benzodiazepines (Carrasco et al.). Possible parallel application under supervision.

Pregnancy and breastfeeding

No data. Do not take without first consulting a professional.

Side effects

Rare. Very rarely hypersensitivity to passionflower. One case of bradycardia, nausea, and ventricular arrhythmia (ESCOP) has been reported.

Ability to operate vehicles and machinery

Unknown. In case of drowsiness do not drive or use machines.

Mechanism of action

Anxiolytic effect
Soulimani et al. examined hydroethanol and aqueous extracts of passionflower in mouse models. The hydroethanol extract reduced anxiety in models of unknown environment, while the aqueous extract had a sedative effect in the same models. The aqueous extract also had a hypnotic effect. This study was one of the first to confirm the different mechanism of action of the compounds depending on the polarity, and also confirmed the importance of extracts containing increasingly important groups of passionflower compounds. Zanoli et al. tested purified compounds, apigenin and krizin which is found in the composition of German chamomile and passionflower. They measured the effect on locomotor activity in rats and the anxiolytic effect. Both compounds at a minimum dose of 25 mg/kg showed a decrease in locomotor activity, but only chrysin showed an anxiolytic effect. Crisin activity, in contrast to apigenin, was mediated by benzodiazepine receptors. From this study we learned the diversity of the mechanism of action of flavonoids, but as the whole extract was not examined, we cannot estimate from it the full mechanism of action of passionflower or German chamomile.

Brown et al. proved the anxiolytic effect of crises in rats a which was comparable to midazolam, but the authors did not examine the native extract but only the purified compound. Ethanol extract of passionflower flower also showed anxiolytic activity in a model of anxiety in mice (Grundmann et al.).

Which active compounds are responsible for the effect?

Dhawan et al. tried in a little more detail to work out exactly which one of the compounds are responsible for the anxiolytic effect. They used methanolic passionflower extract and found that benzoflavones are the group of compounds that show the best anxiolytic effect in an anxiety model in mice. This is in line with published data. However, the study itself has already been designed with an extract that is methanolic and it is possible that other compounds that are not optimally extracted into methanol also have biological activity. Consequently, Dhawan et al. critically review standardization to vitexin, since other benzoflavones are responsible for the effect. Benzoflavones from the methanol extract have a beneficial effect on both nicotine and alcohol induced decreased libido and azoospermia in rats Dhawan et al.). The observed effects are probably due to the action on aromatase, a key enzyme for the synthesis of female sex hormones (Dhawan et al.). A similar effect was proved by the same group of authors in rats in which decreased sperm count and decreased cannabinoid-induced libido. Dhawan et al. demonstrated an increase in libido with passionflower extract in mice. A few years later Holbik et al. opposed the opinion of this group scientists from India because in three extracts of passionflower from India, France and Italy they did not detect the presence of benzoflavones. They proved the presence of the phytol isomer as one of the molecules of “benzoflavones”. Sampath et al. found that chloroform showed the best anxiolytic effect extract, partly butanol, and strongly lipophilic extract in petroleum ether does not show anxiolytic effect. Unfortunately, the authors did not perform a detailed analysis of the constituents of individual extracts.

Unfortunately, studies of passionflower are mainly focused on the flavonoid fraction. There is almost no data on the importance of alkaloids from the passionflower itself and whether they also affect the effect except for the study Soulimani et al.. There is a real abundance of work on the effects of the alkaloids harmin, harmol, and hamalol (Khan et al.). These alkaloids are probably not dominant compounds – they are otherwise inhibitors of MAO, monoamine oxidase, and side effects associated with the use of MAO are not found in the use of passionflower.

Specificity of species P. incarnata

Type P. edulis (passion fruit) is often used to forge the species P. incarnata (passionflower). In a simple but clear study, Dhawan et al. compared anxiolytic effect of extract of both species in mice. Unlike passionflower, green passion fruit extract did not show an anxiolytic effect. The same group of authors compared green herb extract and root extract of passionflower where it was found that the traditional application of green herb is completely justified: root extract in anxiety models showed no effect.

Passionflower and addiction models

Because a positive effect of passionflower in opiate withdrawal has been observed, Dhawan et al. confirmed in a model of alcohol dependence in mice that passionflower extract reduces addictive behaviour. Dhawan et al. confirmed a similar positive effect against the development of addiction in an addiction model and cannabinoids from marijuana, and reduce the symptoms of nicotine addiction (Dhawan et al.). Passionflower extract in mice is not addictive and is effective in preventing benzodiazepine dependence (Dhawan et al.). Dreivogel et al. also confirmed these results by observing locomotor sensation in rats induced by nicotine.

Passionflower extract showed no hypnotic effect in a rat-disturbed sleep model (Shinomya et al.).

Mechanism of action

Nassiri-Asl et al. proved the anticonvulsant effect of passionflower in mice in which convulsions were induced by pentylene-tetrazole and the effect was comparable to diazepam. Similar results were confirmed by Singh et al.. The anticonvulsant effect is probably mediated by GABA-A receptors in the brain (Nassiri Asl et al., Grundmann et al.) because both groups the authors found that a GABA-A antagonist, flumazenil, reversed the effects of passionflower.

Still, in one of the best-designed preclinical studies of passionflower published so far, Elsas et al. refuted several theses. First, like Holbik et al. proved that postulated benzoflavone is absent in passionflower extract. Second, in their models, passionflower extracts surprisingly showed an anxiogenic rather than an anxiolytic effect that was weak in some and more pronounced in some. The anticonvulsant effect was also variable. It is very confusing that biological activities did not correlate with total flavonoid content. As there were no differences in the proportion of individual flavonoids, obviously the observed differences cannot be explained by the difference in the profile of individual flavonoids. The authors speculate that differences in effects may be related to effects on different GABA receptor subunits, but conclude that the story of the relationship between chemistry and action of passionflower is far more complicated than testing individual compounds, and that the actual molecular mechanism of passionflower action remains to be explored.

ExtractMaterialExtraction agentTemperatureTotal flavonoids (%)Anxiogenic effectAnticonvulsant effect
PAS1Fresh65% EtOH25°C for 14 days3MediumAbsent
PAS4FreshWater100°C 72 min
4°C 21h
30,6LowPresent
PAS5Dried65% EtOH4°C for 14 days2,8HighPresent
PAS7Dried65% EtOH100°C 65 min
4°C 19h
46,4LowAbsent
PAS8DriedWater100°C 60 min
4°C 20h
20,3HighAbsent

Appel et al. have with very accurate in vitro methods confirmed how passionflower extract acts on: 1) entry of GABA (gamma-aminobutyric acid) into rat synaptosomes, 2) binding to GABA-A and 3) binding to GABA-B receptor. Given the previous study, it will still take time to determine which compounds are most responsible for the effect.

Other actions

Dhawan et al. in a model of cough caused by sulfur dioxide in mice show the antitussive effect of passionflower extract. Passiflora extract also reduces acetylcholine-induced bronchospasm in guinea pigs (Dhawan et al.).
As passionflower has traditionally been used in gastritis, Mahady et al. have demonstrated a modest antibacterial effect on Helicobacter pylori, but it is not clear whether this result is relevant for clinical use. Masteikova et al. proved in vitro the action of passionflower extract against free radicals which is not uncommon for an extract rich in flavonoids. The significance of this study on clinical effects is questionable.

Gupta et al. demonstrated an antidiabetic effect in mice in which is diabetes caused by streptozotocin, but so far no other study has been conducted based on this work and its relevance has yet to be confirmed or refuted.

Clinical studies

In a double-blind, multicenter, and placebo-controlled study, 91 patients with adjustment difficulties and anxiety were treated with a fixed preparation containing Passiflora incarnata, Ballota nigra, Crataegus sp. and Valeriana officinalis, and 92 patients with placebo. Using Hamilton’s Anxiety Questionnaire (HAM-A) Bourin et al. found that this preparation was more effective than placebo.

In an exploratory, cross over study Schulz et al., 12 study participants received extracts of different plant species (Valeriana officinalis, Lavandula officinalis, Passiflora incarnata, kava-kava, Melissa officinalis, Eschscholzia californica, Hypericum perforatum and Ginkgo biloba) and diazepam. Diazepam decreased the theta frequency and increased the beta frequency, while passionflower (and some other species) increased theta and decreased the beta frequency recorded in the EEG. The study showed a different net effect of passionflower compared to diazepam, and probably a different mechanism of sedation. This is a valuable fact when considering the use of passionflower in people who do not respond well to benzodiazepines.

Akhondzadeh et al. designed a double-blind, randomized study. In addition to placebo, the comparator oxazepam 30mg daily was used. Passionflower was given in a dose of 45 drops a day (tincture). The number of participants was small, 36, and the inclusion criterion was anxiety. Passionflower extract was significantly more effective than placebo. Oxazepam showed a faster action but also a more significant side effect profile accompanied by reduced efficiency in the workplace. Although a small pilot study, its value is in the observed different side effect profile of passionflower and benzodiazepines.

Akhondzadeh et al. designed a second randomized study where have used passionflower extract as adjuvant therapy with clonidine in patients who are in the process of opiate withdrawal. A total of 65 patients received clonidine plus placebo and clonidine plus passionflower. In the group of patients treated with clonidine and passionflower extract, according to the Short Opiate Withdrawal Scale (SOWS), they showed a significantly better score than the group receiving clonidine plus placebo. The conclusion of the study is that the use of passionflower as an adjuvant therapy makes sense in the process of opiate withdrawal.

In a randomized, placebo-controlled study (60 patients) Movafegh et al. found that 500mg of dry passionflower extract reduces peroperative anxiety without inducing sedation. Aslanargun et al. obtained comparable results in an anxiety reduction study before sipanal anesthesia in 60 patients without affecting psychomotor functions, sedation, and hemodynamic parameters. Kaviani et al. designed unilaterally blinded studies with a total of 63 a patient with anxiety due to periodontal surgery. They were divided into three equal groups in which one received liquid passionflower extract one placebo and one received no therapy. The dose was 20 drops the evening before the procedure and 20 drops in the morning before

procedure. Measuring the score of the Corah DAS-R questionnaire before and after therapy, they found that passionflower extract significantly reduced anxiety compared to the placebo group and the group that did not receive therapy.

In a double-blind, placebo-controlled study in 41 patients with a minor sleep quality disorder, Ngan et al. concluded that passionflower tea was better than placebo. Sleep quality was assessed by sleep diary and polysomnography.

In a randomized, controlled, double-blind study Maroo et al. have shown that an herbal preparation containing hops, valerian and passionflower is as effective as zolpidem in the treatment of primary insomnia. The study was not placebo-controlled and as it is a multi-plant preparation based on it, we cannot assess the effect of passionflower.

Personal experiential practice

I was sceptical for a while about the full potential of this plant. Over time, I disproved myself, which is always a nice feeling. My French teachers told me that passionflower became popular after the First World War, as one of the remedies for PTSD in soldiers. It has become much more than that over time.

The main reason I recommend it is insomnia. For insomnia, I usually suggest a dose of 5-10mL EPS or SIPF preparation, taken at night before bed. It should be borne in mind that insomnia is a very individual problem and that all circumstances and other ailments should be investigated. In people who have problems with a “restless heart” before bed (stress that manifests itself on the sympathetic system), my favourite combination of EPS hawthorn and passionflower in equal proportions. However, sometimes a combination of valerian and California poppy will be more effective in some patients. For anxiety and nervousness, 5mL is used twice a day.

One of the main advantages of passionflower is its great safety and really rare side effects.

Commission E strictly states the paediatric use of passionflower, so passionflower is sometimes useful as an adjuvant therapy for ADHD. However, it should be borne in mind that the basis for the use of passionflower is empiric rather than clinical research. The approach to ADHD is complex and individual and includes not only pharmacological substances, but statistically it is most often combined with pycnogenol and DHA (omega-3).

Passionflower is sometimes used in both mild and moderate depression in terms of anxiety correction, and passionflower has a key advantage over the planet-known preparations of St. John’s wort. It is not a PXR agonist, i.e. it does not act on cytochromes, and thus does not show unpleasant drug interactions.

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