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Passion Flower

Scientific Name(s): Passiflora incarnata L.
Common Name(s): Apricot vine, Corona de cristo, Fleischfarbige, Fleur de la passion, Flor de passion, Granadilla (species with edible fruit), Herba passiflorae, Jamaican honeysuckle (Passiflora laurifolia), Madre selva, Maracuja (Brazil), Maracuva (Peru), Maypop, Passion flower, Passion fruit, Passion vine, Passionflower, Passionsblumenkraut, Purple passion flower, Water lemon (P. laurifolia), Wild passion flower

Clinical Overview

Use

Passion flower has been examined for use in treating anxiety, insomnia, diabetes, menopausal symptoms, and cough. However, there are limited quality clinical trials to recommend passion flower for any indication.

Dosing

There are limited quality clinical data to support therapeutic dosing guidance.

Contraindications

Contraindicated during pregnancy. Use should generally be avoided in patients with cardiac arrhythmias and abnormalities.

Pregnancy/Lactation

Passion flower is a known uterine stimulant; avoid use in pregnancy. Information is lacking regarding use during lactation.

Interactions

Caution is warranted with concomitant consumption of CNS-active medicines and coadministration of drugs that prolong the QT interval.

Adverse Reactions

Nausea, vomiting, dizziness, and drowsiness have been reported with passion flower consumption, as well as prolongation of the QT interval and episodes of ventricular tachycardia. Hypersensitivity, occupational asthma, and rhinitis have also occurred.

Toxicology

Information is limited and cannot be extrapolated from one species to another. Passion flower has "generally recognized as safe" (GRAS) status according to the US Food and Drug Administration (FDA). Certain Passiflora species are reported to exhibit genotoxicity and to contain cyanogenic constituents, and are also associated with hepatobiliary and pancreatic toxicity.

Botany

The term "passion flower" refers to many of the approximately 400 species of the genus Passiflora, which primarily grow as vines. Some species are noted for their ornate flowers, others for their edible fruit. Common species include P. incarnata, P. edulis, P. alata, P. laurifolia, and P. quadrangularis. Those with edible fruit include P. incarnata, P. edulis, and P. quadrangularis, the latter being one of the major species grown commercially for its fruit. Passiflora species are native to tropical and subtropical areas of the Americas. In the United States, P. incarnata is found from Virginia to Florida and as far west as Missouri and Texas. It is a woody, evergreen climber and grows rapidly, reaching up to 6 m in height.Mirrodi 2013, Modabbernia 2013 The flowers of Passiflora have 5 petals, sepals, and stamens; 3 stigmas; and a crown of filaments. The ovoid fruit is 4 to 5 cm long, has a pulpy consistency, and includes many small seeds.Khan 2009, USDA 2018, WHO 2007

History

The "passion flower" was discovered in 1569 by Spanish explorers in Peru who saw the flowers as symbolic of the passion of Christ and as a sign of Christ's approval of their efforts, which became the origin of the scientific and common names. The folklore surrounding this plant possibly dates to even earlier than the 16th century. The floral parts are thought to represent the elements of the crucifixion (3 styles represent 3 nails; 5 stamens for the 5 wounds; the ovary resembles a hammer; the corona as the crown of thorns; the petals represent the 10 true apostles; the white and bluish-purple colors those of purity and heaven). In Europe, passion flower has been used in homeopathic medicine to treat pain, insomnia related to neurasthenia or hysteria, and nervous exhaustion. It has also been used for bronchial disorders (particularly asthma), inflammation, inflamed hemorrhoids, climacteric complaints, pediatric attention disorders, pediatric nervousness and excitability, and as a compress for burns.Khan 2009, USDA 2018, WHO 2007

Chemistry

The official passion flower is considered to be P. incarnata, which is used for the herbal supplement form. Variations in constituents among species exist.

Key constituents in P. incarnata include flavonoids, maltol, cyanogenic glycosides, and harman indole alkaloids. The indole alkaloids isolated from P. incarnata (ie, harmol, harmine, harmalol, harmaline) consist of a benzene ring that is fused to a 5-membered heterocycle with 1 nitrogen atom, which closely resembles benzodiazepines.Hamid 2017 Flavonoid content (2.5%) includes flavone di-C-glycosides, schaftoside, isoschaftoside, isovitexin, iso-orientin, swertisin, vicenin, lucenin, saponarin, and passiflorine. Free flavonoids include apigenin, luteolin, quercetin, and kamferol. Additionally, coumarins have been identified in the root of the plant, and lycopene is present in large amounts in the aerial parts. Flavonoid determination by high-performance liquid chromatography, mass spectral analysis, and other methods has been extensively reported.Devi Ramaiya 2013, Dhawan 2004, Khan 2009, WHO 2007, Wohlmuth 2010

Uses and Pharmacology

Anti-inflammatory activity

Animal data

Anti-inflammatory actions of passion flower, including decreases in inflammation, leukocyte migration, and granuloma mass, have been demonstrated in animal models.Sasikala 2011, WHO 2007 A study in rats indicated a potential benefit in treatment of neuropathic pain through opioidergic effects of P. incarnata.Aman 2016

Clinical data

In a clinical study of purple passion fruit peel extract, a reduction in pain and stiffness was shown in adults with osteoarthritis of the knee.Farid 2010

Antimicrobial activity

In vitro data

Antimicrobial activity has also been demonstrated in vitro against Trichomonas vaginalis and Helicobacter pylori, as well as other fungal and bacterial organisms.Lam 2009, Masadeh 2014, Rocha 2012, WHO 2007

Antioxidant activity

Animal and in vitro data

Antioxidant effects have been reported for certain Passiflora species.Lourith 2013, Masteikova 2008, Sathish 2011

Antitussive effects

Animal and in vitro data

In mice with sulfur dioxide–induced cough, a methanolic extract of P. incarnata leaves was associated with 39.4% and 65% cough inhibition at oral doses of 100 and 200 mg/kg, respectively. Effects were comparable to those with oral codeine phosphate 10 and 20 mg/kg, respectively.Dhawan 2002

Clinical data

P. edulis has been clinically evaluated for its effects on coughing. In a randomized, double-blind, placebo-controlled study, purple passion fruit peel extract (P. edulis) 150 mg/day orally for 4 weeks significantly reduced coughing, wheezing, and shortness of breath in patients with asthma (P<0.05).Watson 2008

Cardiovascular effects

Animal and in vitro data

Increased contractility in isolated guinea pig hearts has been demonstrated,WHO 2007 while the presence of a vasorelaxing agent in passion fruit seeds (P. edulis) has been identified.Sano 2011 Antihypertensive activity in rats has been described for passion fruit peel extract and the fruit pulp.Konta 2014, Lewis 2013 Compounds identified from P. edulis extracts have exhibited anticoagulant activity in vitro.Sato 2012

CNS/Anxiolytic effects

The CNS effects of P. incarnata are believed to occur through modulation of the gamma-aminobutyric acid (GABA) system.Appel 2011, Baek 2014 Passionflower extract exerts partial agonistic activity at the benzodiazepine receptor.Baek 2014

Animal and in vitro data

Multiple animal studies exist demonstrating the effects of Passiflora on the CNS, including stimulant and depressant activity.Deng 2010, Sarris 2013 Studies evaluating activity against nicotine sensitizationBreivogel 2012 and use in the setting of alcohol dependency and withdrawal in rats have suggested benefit.Schnuck 2017, Tomczyk 2012 In a study of mice, passionflower extract given for 7 weeks resulted in a reduction in anxiety and improvement in memory.Jawna-Zboinska 2016 The methanolic extract of the aerial part of P. incarnata was associated with anxiolytic effects; however, the roots were devoid of this activity.Dhawan 2001 When compared to P. edulis, the methanolic extract of P. incarnata 125 mg/kg was associated with anxiolytic activity while the P. edulis extract exerted minimal anxiolytic activity.Dhawan 2001 Another study found the chloroform and butanol fractions of a hydroethanol extract from P. incarnata was associated with anxiolytic effects; however, the petroleum ether fraction did not exert any effects.Sampath 2011

In one study, P. incarnata extract exerted antiparkinsonian effects and enhanced cognitive activity in mice.Ingale 2017 In another study, 5 different extracts of P. incarnata were studied, and 2 were found to exert antiepileptic activity in an animal model of PTX-induced seizures. All 5 extracts increased, rather than decreased, anxiety levels.Elsas 2010 Anticonvulsant activity in mice has been reported in other studies.Nassiri-Asl 2007, Singh 2012

In one study, passionflower extract was shown to positively modulate circadian rhythms in NIH3T3 cells and in mice.Toda 2017

One study using in vitro and in vivo models suggested antidepressive therapeutic effects with a combination extract of Hypericum perforatum and P. incarnata.Fiebich 2011

Clinical data

A published Cochrane review evaluating the efficacy of Passiflora in anxiety included trials through 2005; the authors concluded that too few quality clinical trials of Passiflora exist to provide a definitive recommendation regarding a place in therapy. Two studies were included in the review, with one of the studies suggesting equivalence with benzodiazepines. Dosages used in the 2 trials were 45 drops/day of a P. incarnata extract, or a 90 mg/day tablet.Miyasaka 2007 In a small clinical trial, P. incarnata extract 500 mg was effective as a preoperative anxiolytic, with reductions in numerical rating scale anxiety scores compared to placebo (P<0.001).Movafegh 2008 In a small crossover study in adults undergoing dental surgery (N=40), P. incarnata 260 mg (1 pill) orally 30 minutes prior to surgery demonstrated a preoperative anxiolytic effect similar to midazolam. The study evaluated effects on blood pressure, heart rate, and oxygen saturation (as physical parameters associated with anxiety level), with no differences, except in diastolic blood pressure, observed. However, data reflected a much higher proportion of anxious feelings during the second extraction in patients who received P. incarnata during the first extraction compared to those who received midazolam during the first extraction. P. incarnata administration was not associated with memory interference, while midazolam was associated with amnesia.Dantas 2017 Similarly, patients undergoing periodontal treatment experienced a reduction in anxiety levels with passion flower extract given as 20 drops the night before and 20 drops the morning of the procedure. Kaviani 2013 Despite widespread acceptance as a natural anxiolytic, other reviews similarly report on the lack of clinical evidence for P. incarnata in anxiety-related disorders.Lakhan 2010, Sarris 2013, Sarris 2011 One small, randomized, placebo-controlled, crossover pilot study in adults with mild fluctuations in sleep quality evaluated the effects of P. incarnata administered as a tea (tea bags containing 2 g of dried P. incarnata leaves, stems, seeds, and flowers) at bedtime for 7 days. Patient-rated sleep quality was improved with active treatment compared with placebo tea bags, but no other measures (ie, total sleep time, sleep efficiency, feeling of refreshment) were different. No difference between groups in anxiety scores at the end of the 7-night treatment period was reported. A 1-week washout between treatments was used in the study.Ngan 2011 Another study found the product Passiflora Compose to improve anxiety and sleep disorders.Villet 2016

In a prospective, randomized, double-blind, placebo-controlled study, 60 patients scheduled for spinal anesthesia were randomized to receive an oral aqueous extract of P. incarnata 700 mg per 5 mL or placebo 30 minutes before anesthesia. A statistically significant increase in anxiety scores was noted from baseline to just prior to spinal anesthesia in those receiving placebo compared to P. incarnata. The authors suggest that preoperative administration of P. incarnata suppresses the increase in anxiety associated with spinal anesthesia.Aslanargun 2012 Similar findings were demonstrated in another study, in which P. incarnata 1,000 mg was given an hour before elective surgery; P. incarnata was associated with reductions in anxiety comparable to reductions in patients receiving melatonin. However, P. incarnata was associated with more cognitive impairment than melatonin.Rokhtabnak 2016

In a multicenter, prospective observational study of children 6 to 12 years of age with a history of nervousness and agitation due to affective disorders, treatment with a combination of P. incarnata, Hypericum perforatum, and Valeriana officinalis improved symptoms of nervous agitation such as depression, school/examination anxieties, other anxieties, sleeping problems, and various physical problems.Trompetter 2013

In a study of patients experiencing opiate withdrawal, a combination of P. incarnata and clonidine was superior to clonidine alone in improving mental symptom scores.Akhondzadeh 2001

Twelve weeks of treatment with a dried ethanolic extract improved resilience and quality of life in patients with "nervous restlessness."Gibbert 2017

Diabetes

Animal and in vitro data

In studies evaluating effects of P. edulis in rodents, increased high-density lipoprotein and decreased low-density lipoprotein and free fatty acids have been achieved, possibly due to pectin content of the supplementation.de Souza Mda 2012, Silva 2011 Reductions in fasting blood glucose levels have been achieved in mice with induced diabetes.Barbalho 2011, Gupta 2012 Reductions noted may be due to changes in absorption secondary to inhibition of alpha-glycoside activity.Sudasinghe 2018

Clinical data

In a small clinical trial of patients with type 2 diabetes, passion fruit peel flour (from P. edulis), which is rich in soluble fiber and pectin, was used as a supplement and led to improvements in fasting blood glucose and glycosylated hemoglobin levels.de Queiroz Mdo 2012

Diverticular disease

In vitro data

Results of a study show yellow passion fruit rind is a potential dietary fiber source, and may help protect against diverticular diseases.Yapo 2008

Menopausal symptoms

Clinical data

In a study of menopausal women, passion flower significantly reduced menopausal symptoms (ie, vasomotor symptoms, insomnia, depression, anger, headache, muscular/joint pain, numbness) in the third and sixth weeks of the study (P<0.05).Fahami 2010

Dosing

Published clinical data are lacking to support therapeutic dosing guidance.

Traditional doses for use as a mild sedative have included 0.5 to 2 g of P. incarnata aerial plant parts taken 3 to 4 times daily; 2.5 g of aerial parts as an infusion 3 to 4 times daily; or 1 to 4 mL of a tincture (1:8) 3 to 4 times daily.WHO 2007

Various doseforms and dosages have been used in small clinical trials evaluating P. incarnata as a preoperative anxiolytic. In a Cochrane review, dosages used in clinical trials evaluating Passiflora for anxiety disorder included 45 drops/day of an extract, or a 90 mg/day tablet.Miyasaka 2007

A small pilot study in adults used a tea solution (prepared by steeping bags containing 2 g of dried P. incarnata for 10 minutes in boiling water) administered over 7 days to evaluate effects on sleep quality.Ngan 2011

Pregnancy / Lactation

Use of passion flower is contraindicated during pregnancy because of uterine stimulant action of its alkaloids harman and harmaline, as demonstrated in animal models and in vitro studies, and the content of the cyanogenic glycoside gynocardin.Ernst 2002, WHO 2007 Information regarding use of passionflower during lactation is lacking.

Interactions

Caution is warranted with coadministration of CNS-active medicinesDhawan 2004, Modabbernia 2013; an additive effect with St. John's wort has been suggested.Fiebich 2011 A case report describes a patient with hand tremors, dizziness, throbbing, and muscular fatigue, which were attributed to coadministration of P. incarnata, valerian, and lorazepam. Upon discontinuation of the herbal products, the patient's symptoms dissipated.Carrasco 2009

Case reports are lacking regarding interactions with warfarin and other anticoagulants; however, compounds identified from P. edulis extracts have exhibited anticoagulant activity in vitro.Sato 2012 Therefore, there is theoretically an increased risk for prolonged bleeding with coadministration of P. incarnata and anticoagulants.

Caution is warranted with coadministration of drugs that prolong the QT interval.Dhawan 2004, Miyasaka 2007, WHO 2007

Adverse Reactions

Nausea, vomiting, dizziness, confusion, ataxia, and drowsiness have been reported with passionflower consumption, as well as prolongation of the QT interval and episodes of ventricular tachycardia. Hypersensitivity, occupational asthma, and rhinitis have also been reported.Baek 2014, Dhawan 2004, Fisher 2000, Miyasaka 2007, Rodriguez-Fragoso 2008, WHO 2007, Wohlmuth 2010

Toxicology

Information is limited and cannot be extrapolated from one species to another. P. incarnata has GRAS status according to the FDA.FDA 2018 Some Passiflora species reportedly exhibit genotoxicity.Boeira 2010, Mills 2006, Tabach 2009, WHO 2007 The constituents harman and harmine are considered mutagenic and genotoxic.Mills 2006 Several species of Passiflora have cyanogenic constituents, while others are associated with toxicological reports of immunoglobulin E–mediated allergy, vasculitis, altered consciousness, hepatobiliary, and pancreatic toxicity.Braga 2013, Devaki 2012, Dhawan 2004 A report of disruption of sexual behavior in adult male rat progeny has been published, and is possibly due to aromatase inhibition by P. incarnata.Bacchi 2013

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