Passionflower

Passiflora incarnata L. belongs to Passifloraceae, the passionflower family. Miroddi and colleagues (Journal of Ethnopharmacology 2013) note that the genus has around 520 species, most of them vines of Central and South America. NCBI Taxonomy files P. incarnata as taxon 159425. The USDA plant guide describes a native perennial vine, 2–6 m long, that climbs with tendrils arising where the leaves meet the stem. The alternate leaves are 6–15 cm long and wide, palmately three-lobed, with finely toothed edges. The flowers are pale lavender or rarely white, with five petals and five sepals beneath a crown, or corona, of many fringe-like segments banded white and purple. It blooms from June to September and grows in open fields, roadsides, fencerows, and thickets; USDA warns it can become invasive.

The fruit is the maypop: an oval, egg-sized, yellowish fruit 4–10 cm long, with many dark seeds wrapped in an edible pulp (USDA). USDA lists alternative names including maypop, apricot vine, old field apricot, and granadilla, and NCCIH adds maracuja and water lemon. Several of those names are also used for other Passiflora species, including the passion fruit of commerce, Passiflora edulis. That overlap matters. The herbal medicine defined by the European Pharmacopoeia and EMA is the dried aerial parts of P. incarnata only, which may contain flowers and fruits (EMA). Passion fruit is a food, and eating it or drinking its juice is not a way of taking passionflower as a medicine.

EMA’s assessment report lists the main constituents as flavonoids, mostly C-glycosides of apigenin and luteolin such as isovitexin, isoorientin, schaftoside, isoschaftoside, vicenin-2, and swertisin, with considerable variation in composition from source to source. The European Pharmacopoeia requires at least 1.5% total flavonoids in the dried herb and 2.0% in dry extracts, expressed as vitexin (PubChem CID 5280441, C21H20O10). The plant also contains maltol (possibly an artefact of processing), traces of essential oil, and gynocardin, a cyanogenic glycoside. Beta-carboline alkaloids such as harman and harmol may be present in traces but are undetectable in most commercial material. A benzoflavone once claimed to be the main active compound could not be found by later researchers in plants from India and France, and only in traces in Italian material (EMA).

Passionflower was a food and medicine in North America long before it reached European pharmacies. The USDA plant guide records that the Houma, Cherokee, and other Native American peoples used it for food, drink, and medicine, and that Captain Smith reported in 1612 that Native Americans in Virginia planted the vines for their fruit. The fruit was eaten raw or boiled into syrup, the juice was drunk or thickened with flour or cornmeal, and young shoots and leaves were cooked as greens. Root infusions were used for boils, wounds, earache, and liver complaints, and the plant was used as a sedative for nervous conditions (USDA).

NCCIH notes that sixteenth-century Spanish explorers learned of passionflower in the Americas and that the plant was taken to Europe, where it was widely cultivated and entered folk medicine. The name comes from the flower itself: according to USDA, early Spanish explorers saw in its elaborate structure a representation of the sufferings, or Passion, of Christ. Miroddi and colleagues document a wide spread of later folk uses: insomnia and anxiety in Europe, a sedative tea in North America, hysteria and neurasthenia in Poland, epilepsy, neuralgia, and painful periods in Turkey, and a range of complaints from diarrhoea to burns and haemorrhoids in the Americas.

In European herbal medicine, passionflower became a standard calming herb. EMA traces continuous documentation of passion flower tea, powder, and alcoholic extracts for mild mental stress and sleep through handbooks from 1938, 1958, 1977, and 2003, often in combination with other sedative herbs such as valerian, hops, and lemon balm. Germany’s Commission E gave a daily dose of 4–8 g of herb, and one Austrian liquid extract has been sold since 1963 (EMA). The EU herbal committee adopted its first passionflower monograph in September 2007 and revised it after a systematic review on 25 March 2014, again granting traditional use only. Methanol extracts, authorised in Germany only since 1992, were left out because they lacked the required 30 years of use.

EMA concludes that passionflower’s mechanism of action cannot be regarded as clarified, though newer studies point to the GABA system, the brain’s main calming signalling pathway and the target of benzodiazepines. In laboratory work reviewed by EMA, a 50% ethanol extract bound to GABA-A and GABA-B receptors and inhibited GABA uptake (Appel and colleagues, 2011). In mice, an oral extract reduced anxiety-like behaviour at 375 mg/kg, comparable to diazepam, but not at 150 or 600 mg/kg, a U-shaped pattern; the effect was blocked by flumazenil, which acts at the benzodiazepine site (Grundmann and colleagues, 2008). Another group found that extracts contained GABA itself and produced anxiety-like rather than calming effects in mice (Elsas and colleagues, 2010). EMA notes that doses in animal experiments are high compared with what people take.

Which constituents matter is not known. MSKCC lists several candidates: the harmala alkaloids harman and harmaline, which inhibit monoamine oxidase; maltol and related compounds acting on GABA receptors; and the flavone chrysin. But EMA notes that the alkaloids are undetectable in most commercial material, and the benzoflavone once proposed as the key active compound has not been reliably found in the plant. No human pharmacokinetic data are available (EMA), so it is not known how much of any constituent reaches the brain after a cup of tea or a tablet.

Some laboratory findings bear on safety. MSKCC notes that analyses suggest passionflower may prolong the QT interval, an electrical measure of heart rhythm, at large doses; that harman has been linked to uterine contractions in old experiments; and that in a developmental study in rats, exposure produced disrupted sexual behaviour in male offspring, possibly through inhibition of the enzyme aromatase. These are animal and laboratory signals, not proven human effects, but they underpin the advice to avoid passionflower in pregnancy.

Anxiety: Akhondzadeh and colleagues (Journal of Clinical Pharmacy and Therapeutics 2001) randomized 36 outpatients with generalized anxiety disorder to passionflower extract, 45 drops a day, or oxazepam 30 mg a day for four weeks. Both groups improved, with no significant difference at the end; oxazepam worked faster, and more people on oxazepam reported impaired job performance. EMA pointed out that the trial had no placebo group, only 18 patients per arm, an unclear preparation, and was not designed to show equivalence, while six visits to a psychiatrist could have helped on their own. A Japanese trial of a passionflower product against mexazolam in 134 patients found improvement in four of eight neurotic symptoms with passionflower and all eight with the drug (EMA). Miyasaka and colleagues (Cochrane 2007) found just these two trials, with 198 participants, and concluded that randomized trials were too few to permit any conclusions.

Anxiety before surgery and dental work is the most consistent signal. Movafegh and colleagues (Anesthesia and Analgesia 2008) gave 60 adults having day surgery 500 mg of passionflower or placebo 90 minutes beforehand; anxiety scores were significantly lower with passionflower, with no difference in sedation, psychomotor recovery, or time to discharge. EMA notes that the type of extract was not reported. In a similar 60-patient trial before spinal anaesthesia, Aslanargun and colleagues (Journal of Anesthesia 2012) found a small but statistically significant reduction in the rise in anxiety, with no change in sedation or blood pressure; EMA notes the placebo did not match the extract’s taste and colour. Dantas and colleagues (Medicina Oral 2017) gave 40 people having both lower wisdom teeth removed either 260 mg of passionflower or 15 mg of midazolam before each operation in a crossover design. Over 70% felt calm or a little anxious with either, and 20% had amnesia with midazolam. A 2021 BMJ Open systematic review of oral sedation for dental procedures read the same trial as showing greater anxiety reduction with midazolam, and judged the evidence base too weak to be confident about any oral sedative.

Sleep: Ngan and Conduit (Phytotherapy Research 2011) had 41 healthy adults aged 18–35 drink a cup of passionflower tea or a parsley placebo tea before bed for a week each. Of six sleep-diary measures, only subjective sleep quality improved, by about 5% relative to placebo according to EMA, and overnight sleep recordings in 10 participants showed no changes. EMA notes that people with sleep disorders were excluded. Lee and colleagues (International Clinical Psychopharmacology 2020) randomized 110 adults with insomnia disorder to a passionflower extract or placebo for two weeks. Total sleep time measured by polysomnography increased more with passionflower (P = 0.049); sleep efficiency and waking after sleep onset improved within the passionflower group but did not differ from placebo. NCCIH concludes that passionflower might improve total sleep time, with mixed effects on falling and staying asleep.

Other uses lack meaningful evidence. EMA reviewed a trial of passionflower added to clonidine in 65 people withdrawing from opiates and a trial in 34 children with ADHD that compared it with methylphenidate but had no placebo and used a dose several orders of magnitude below traditional European doses; it regarded both as pilot studies. NCCIH says there is not enough evidence for ADHD, heart failure, menopausal symptoms, fibromyalgia, or stress. Janda and colleagues (Nutrients 2020), cited by NCCIH, found that most of nine trials reported reduced anxiety, with less evident effect in people with mild symptoms, while Miroddi and colleagues judged that published trials share crucial weaknesses, including poorly described extracts, small samples, and unreported blinding and randomization.

EU traditional use (EMA/HMPC/669740/2013, adopted 25 March 2014), for mild symptoms of mental stress and to aid sleep in adolescents over 12, adults, and the elderly: herbal tea, 1–2 g of the dried, cut herb in 150 ml of boiling water as an infusion, one to four times daily; powdered herb, 0.5–2 g one to four times daily; or one of several liquid extracts, for example a 1:8 extract in 25% ethanol at 2–4 ml up to four times daily, or a 1:3.6 extract in 60% ethanol at 1 ml three to five times daily. Dry extracts corresponding to these teas and liquid extracts are also covered. Use in children under 12 is not recommended. If symptoms last longer than two weeks, or worsen, see a doctor or qualified health care practitioner.

Trial products varied widely and were often poorly described: 45 drops a day of an extract for anxiety (Akhondzadeh), a single 500 mg tablet 90 minutes before surgery (Movafegh), 260 mg 30 minutes before dental surgery (Dantas), and tea made from about 2 g of dried herb (Ngan and Conduit, as described by EMA). Commission E specified 4–8 g of herb a day (EMA). Many products, in Europe and elsewhere, combine passionflower with valerian, hops, lemon balm, or other herbs; EMA’s monograph covers only single-herb preparations. In the United States most passionflower products are sold as dietary supplements, which the FDA does not approve before sale (NCCIH), so strength and identity depend on the manufacturer.

Practical safety: passionflower may impair the ability to drive and use machines, and anyone affected should not drive (EMA). Do not combine it with sedative medicines without medical advice, and tell your surgeon, anaesthetist, or dentist if you have taken it within two weeks of a procedure (NCCIH). NCCIH notes that passionflower tea may be safe when taken for up to seven nights and daily extract for up to eight weeks; longer use has not been studied. Liquid extracts contain alcohol, which EMA requires to be labelled.