pasiflora

Passionflower (Passiflora incarnata L.): A Comprehensive Reference

1. Identity, Taxonomy, and Natural Source

The botanical name for passionflower is Passiflora incarnata L. The species epithet incarnata means "made of flesh" or "flesh-colored," a reference to the pinkish-lavender coloration of its elaborate blooms. The plant belongs to the family Passifloraceae.

Passionflower is referred to by various common names depending on the region and language. These include maypop, apricot vine, wild passion vine, and wild apricot. One of its early names among the Powhatan people of Virginia was mahcawq, which is thought to have evolved into "maycock" or "maypop"—the name also given to the plant's small fruits.

Passiflora species are native to tropical and subtropical areas of North and South America, although they have naturalised elsewhere. The species most often referenced in Western herbal practice is Passiflora incarnata, which is native to the Americas and grows naturally in warm, sunny habitats such as open woodland edges, thickets, and hedgerows.

Among the Passiflora species, P. edulis and P. incarnata are the most frequently used ones in pharmacology and medicine. Purple passionflower (Passiflora edulis), a relative to P. incarnata, has evidence for osteoarthritis and diabetes from the fruit peel. The present article focuses on P. incarnata as the primary medicinal species recognized in major pharmacopeias.

Parts Used and Common Preparations

Practically all aboveground plant parts of Passiflora vines can be included in the compositions of dietary supplements, medicines, and cosmetics. The EMA monograph describes the herbal substance as fragmented or cut, dried aerial parts; the recognized herbal preparations include powdered herbal substance for tea preparation; liquid extracts (1:8 in 25% ethanol), liquid extracts (1:8 in 45% ethanol), liquid extracts (1:1 in 25% ethanol), and liquid extracts (1:1 in 70% ethanol).

The species Passiflora incarnata L. is included in many pharmacopeias and is the most used species in the food, cosmetic, and pharmaceutical industries. Common commercial forms include:

• Dried aerial parts (herbal substance) for infusion (tea)
• Liquid tinctures and fluid extracts in varying ethanol concentrations
• Standardized dry extracts in capsule or tablet form
• Combination products with valerian, hops, or lemon balm

The British Pharmacopoeia drug is required to contain not less than 1.5% total flavonoids calculated as vitexin. The British and French Pharmacopoeias recommend at least 1.5% of flavonoids expressed as vitexin; the EMA Assessment Report recommends that herbal extract prepared with hydroalcohol or acetone solution may contain at least 2.0% of flavonoids expressed as vitexin.

2. Traditional and Historical Use

Pre-Columbian and Indigenous American Use

The prehistoric use of Passiflora incarnata can be dated back to the Late Archaic period in North America, which ranges between 8000 and 2000 B.C. Archaeological evidence indicates that Native Americans developed human-plant mutualism during the pre-Columbian period, and Passiflora incarnata was a common weed crop that often occurred in anthropogenic habitats.

In the pre-Columbian era, Native American tribes of the Southeast used passionflower both medicinally and as food. Historical documentation of Captain Smith's visit to Virginia as early as 1612 provides accounts of Native Americans planting passionflower vines for the fruits, which were eaten raw or boiled to make syrup. Smith's descriptions of uses include the preparation of a tasty beverage made by crushing and straining juice from the fruits, as well as the use of roots for an infusion to treat boils and wounds. Root infusions were also used to treat liver problems and used as a blood tonic, while "the flowers were used as a sedative to treat nervous conditions and hysteria."

The Cherokee people traditionally boiled and fried the young shoots, mixing them with other edible greens, while also using the plant topically as a poultice. Passionflower was traditionally used as a sedative, antispasmodic, and nervine by Indigenous peoples across North, Central, and South America.

Introduction to Europe and Subsequent Western Use

Spanish explorers "discovered" the passionflower in Peru in the 16th century, who perceived the flowers as symbolic of the passion of Christ. It was the Spanish missionaries who looked at the structure of the plant's bloom and gave it the name "passionflower," after the passion of Christ.

The Spanish missionaries and other European settlers promoted passionflower as a medicinal herb throughout their migrations, and by the 18th century, the plant had gained such wide recognition that botanists began singing its praises around the world. According to scientific evidence, Passiflora incarnata has been used in phytotherapy since the mid-19th century in Western Europe.

Across cultures, it became best known as a calming "nervine" herb, traditionally used to settle restlessness, nervous tension, and an overactive mind. Traditional use strongly linked passionflower with evening wind-down routines, supporting relaxation and smoother transitions into sleep. It was typically prepared from the aerial parts (leaves, stems, flowers) as a tea or tincture, with occasional topical use in compresses or poultices.

3. Key Constituents and Active Compounds

A wide range of chemical compounds has been isolated from P. incarnata, mainly alkaloids, flavonoids, phenols, and carbohydrates. A considerable body of literature has explored the chemical composition of the raw material and of various products derived from passionflower. The results of this literature clearly show that various bioactive constituents can contribute to the reported clinical effects, probably in a synergistic manner.

Flavonoids

The active constituents include the flavonoids apigenin and its C-glycosides (vitexin, isovitexin, schaftoside); chrysin, luteolin (and its C-glycosides orientin and iso-orientin), quercetin, and kaempferol. Constituents of the genus include flavonoids, mainly C-glycosides of apigenin and luteolin such as vitexin, isovitexin, orientin, iso-orientin and their 2′′-β-d-glucosides.

Chrysin (5,7-dihydroxyflavone) is a flavonoid isolated from plants such as Passiflora coerulea, Passiflora incarnata, and Matricaria chamomilla. This natural molecule exerts diverse pharmacological effects, which include antioxidant, anti-inflammatory, anti-cancer, neuroprotective, and anti-apoptotic effects.

Alkaloids

β-carboline alkaloids (which are MAO inhibitors), including harman, harmol, harmine, harmalol, and harmaline, may be present as minor constituents, but are not always detectable. For many years, plant researchers believed that a group of harman alkaloids were the active constituents in passionflower. Recent studies, however, have pointed to the flavonoids as the primary constituents responsible for its relaxing and sedative properties.

Other Constituents

Several pharmacological studies indicate that various bioactive components, such as polyphenols, triterpenes, carotenoids, polysaccharides, amino acids, essential oils, and flavonoids, contribute to the antioxidant, antimicrobial, antidiabetic, hepatoprotective, and anti-inflammatory effects of Passiflora species. Additionally, GABA (gamma-aminobutyric acid) was found to be a prominent ingredient of Passiflora extract itself.

4. Mechanisms of Action

GABAergic Modulation

The first evidence was shown that numerous pharmacological effects of Passiflora incarnata are mediated via modulation of the GABA system including affinity to GABA(A) and GABA(B) receptors, and effects on GABA uptake. Historically, the scientific investigation of Passiflora's well-documented anxiolytic effects has focused primarily on its interaction with the γ-aminobutyric acid (GABA) system, the central nervous system's major inhibitory neurotransmitter network. Flavonoid components, particularly chrysin and apigenin, have been shown to selectively bind to the benzodiazepine (BZ) site on GABA receptors. This interaction typically manifests as partial agonism, enhancing GABAergic inhibition and thereby reducing neuronal hyperexcitability.

Using the same batch of plant material, total flavonoid yields as measured by HPLC-DAD increased substantially with hot versus cold extraction methods. Whole Passiflora extract induced prominent, dose-dependent direct GABA(A) currents in hippocampal slices. GABA was found to be a prominent ingredient of Passiflora extract, and GABA currents were absent when amino acids were removed from the extract. This suggests that the plant's own GABA content, in addition to flavonoid ligands, may contribute to its GABAergic activity.

Beyond GABAergic Pathways

Reviews have identified significant evidence supporting its anxiolytic, sedative, and antidepressant properties, mediated through GABAergic modulation, serotonergic pathways, and other neurochemical mechanisms. In brain structures such as the hippocampus, prefrontal cortex, raphe nucleus, and striatum—involved in the physiopathology of anxiety and depression disorders—several neuropharmacological activities, including the activation of neurotransmitter systems (GABAergic, serotonergic, dopaminergic, and noradrenergic), neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and the nerve growth factor (NGF), and some signaling pathways are affected.

The mechanism of action is still under discussion. Despite gaps in understanding of neurophysiological processes, it is increasingly being recognized that dysfunction of the GABA system is implicated in many neuropsychiatric conditions, including anxiety and depressive disorders.

5. Scientific Evidence by Area of Use

5.1 Anxiety

Two double-blind RCTs (n = 198, total) of passionflower for anxiety are available. One study compared passionflower with oxazolam 30 mg (a long-acting benzodiazepine). The second trial compared it with mexazolam. Passionflower could not be differentiated from the benzodiazepines in these studies. However, the degree to which this equivalence was attributable to small sample sizes versus similar action cannot be determined. No published trials are available that compare passionflower with placebo or with conventional antidepressants.

Movafegh et al. investigated the effects of passionflower (500 mg) on anxiety in surgery patients. The authors concluded that P. incarnata at 500 mg/day provides a safe and effective anxiolytic effect, without impairing psychomotor function. At the same time, they strongly stressed that their sample was too small (n = 60) and urged that research should be continued with a larger group.

A randomized, triple-blinded clinical trial allocated 54 patients into three groups (Valeriana officinalis L., Passiflora incarnata L., and placebo). Anxiety levels were assessed using the State-Trait Anxiety Inventory (STAI) index. There was evidence that both Valeriana officinalis L. and Passiflora incarnata L. reduced STAI-S scores between baseline (T0) and after surgery (T2) (p < .05), unlike placebo (p = .129).

Strength of evidence for anxiety: Although numerous Passiflora incarnata L. derivative products have been commercialised as alternative anxiolytic and sedative remedies based on their long tradition of use, their supposed efficacy does not appear to be adequately corroborated by the literature, with clinical studies often featuring inadequate methodologies and descriptions of the products under investigation. The overall evidence is preliminary and limited by small sample sizes and the absence of rigorous placebo-controlled design in several key trials.

5.2 Sleep and Insomnia

The aim of one double-blind, placebo-controlled study was to investigate the efficacy of Passiflora incarnata herbal tea on human sleep, as measured using sleep diaries validated by polysomnography (PSG). This study featured a double-blind, placebo-controlled, repeated-measures design with a counterbalanced order of treatments (passionflower vs. placebo tea), separated by a 1-week washout period. Forty-one participants (18–35 years) were exposed to each treatment for a week, consuming a cup of the tea and filling out a sleep diary for 7 days. Ten participants also underwent overnight PSG on the last night of each treatment period. Of six sleep-diary measures analyzed, sleep quality showed a significantly better rating for passionflower compared with placebo.

The participants drank 250 mL of the herbal tea once a day, in the evening (to avoid the sedative effect during the day), and the measurements were performed in the morning, upon rising.

The initial findings of this study suggest that the consumption of a low dose of Passiflora incarnata, in the form of tea, yields short-term subjective sleep benefits for healthy adults with mild fluctuations in sleep quality.

A separate double-blind randomized placebo-controlled study published in 2020, by Lee et al., examined the effects of Passiflora incarnata Linnaeus on polysomnographic sleep parameters in subjects with insomnia disorder (International Clinical Psychopharmacology, 35(1), 29–35). The positive effects of passionflower on objective sleep parameters including total sleep time (TST) on polysomnography in adults with insomnia disorder were demonstrated.

A randomized, double-blind, placebo-controlled clinical study found that Passiflora incarnata extract showed a statistically significant reduction in the mean score of stress on the Perceived Stress Scale and significantly increased the mean score of total sleep time compared to placebo. General psychological health was found to be significantly improved in the Passiflora incarnata extract group compared to the placebo group on day 15 and day 30.

Strength of evidence for sleep: Evidence is promising but preliminary, based on small, short-duration trials. Several controlled experiments have demonstrated enhanced sleep in laboratory animals, but clinical trials in humans are still limited.

5.3 Opiate Withdrawal

A 14-day double-blind trial enrolled 65 men addicted to opiate drugs and compared the effectiveness of passionflower and the drug clonidine together against clonidine alone. Clonidine does not help emotional symptoms such as drug craving, anxiety, irritability, agitation, and depression. These symptoms can be quite severe and often cause enrollees in drug treatment programs to end participation. In this 14-day study, the use of passionflower along with clonidine significantly eased the emotional aspects of withdrawal compared with clonidine alone.

Researchers at Tehran University of Medical Sciences compared the use of clonidine alone to clonidine plus passionflower extract as a treatment to ease opiate withdrawal symptoms. Subjects in the first group received a daily dose of up to 0.8 mg clonidine plus 60 drops of passionflower extract. Subjects in the second group received the same daily dose of clonidine plus 60 drops of an inert placebo substance.

Strength of evidence for opiate withdrawal: A single positive RCT supports this application for the emotional symptoms of withdrawal when used adjunctively with clonidine. The physical symptoms of withdrawal showed no advantage of the combination over clonidine alone. Replication and larger trials are needed.

5.4 Attention-Deficit/Hyperactivity Disorder (ADHD)

A small study in children suggests that passionflower may reduce ADHD symptoms similar to a prescription drug but with fewer side effects. One small clinical study of children with ADHD found that taking passionflower for 8 weeks was comparably as effective as taking the drug methylphenidate, but without the same negative side effects.

Strength of evidence for ADHD: Based on a single small trial; evidence is very preliminary and cannot support firm conclusions.

5.5 Perioperative (Preoperative) Anxiety

In a placebo-controlled trial involving sixty surgical patients, passionflower significantly reduced anxiety up to ninety minutes prior to surgery. This application has been replicated in more than one small RCT, making it one of the better-evidenced clinical contexts for passionflower, though sample sizes remain small.

5.6 Benzodiazepine Tapering

A study was conducted to investigate the safety and efficacy of P. incarnata L., herba in reducing benzodiazepine (BDZ) misuse in a real-world population of depressed and anxious patients in long-term treatment with BDZs. Findings suggested a role of P. incarnata as an effective add-on treatment during benzodiazepine tapering, with complete benzodiazepine discontinuation at 1 month and 3 months significantly favoring the passionflower group. These findings highlight the need for further studies to better investigate these promising properties.

5.7 Anticonvulsant Activity

Studies in animal models show efficacy of Passiflora extracts and flavonoid fractions against pentylenetetrazol (PTZ)-induced seizures. Passion flower is used in traditional medicine of Europe and South America to treat anxiety, insomnia, and seizure, and recently has shown antianxiety and sedative effects in humans. However, no human clinical trials specifically addressing epilepsy or seizures have been identified in the literature; this area remains in the preclinical phase.

5.8 Other Investigated Areas

Studies show passionflower to have anti-inflammatory, anti-asthmatic, antitussive, glucose-lowering, anticonvulsant, sedative, and anti-anxiety effects. Research attention has been paid to various medical applications including anti-inflammatory, nephroprotective, anti-depressant, antidiabetic, hepatoprotective, antibacterial and antifungal, and antipyretic effects. Most of these additional applications are supported only by in vitro or animal studies and lack human clinical trial data.

6. Body Systems and Health Areas

Based on both traditional use and the available preclinical and clinical literature, passionflower is primarily associated with the following body systems:

• Central Nervous System: Passiflora demonstrates positive effects in episodes of anxiety, restlessness, sleeplessness, and depressive states.
• Cardiovascular System: Bradycardia and hypotensive effects have been reported in pharmacological profiles, and passionflower is listed in herbal medicine for treating palpitations and cardiac rhythm abnormalities.
• Neuroendocrine/Stress Response: A rat study demonstrated that long-term use of passionflower was correlated with reduced stress levels and, consequently, increased motivation to act and improved motor activity.
• Respiratory System: P. incarnata has been described as used for treatment of cough and has shown anti-asthmatic and antitussive effects in studies.
• Addiction/Withdrawal: Passionflower has been studied for treating alcohol and opiate withdrawal.

7. Dosage Forms and Reported Clinical Dosages

The EMA monograph lists recognized herbal preparations including: powdered herbal substance for tea preparation; liquid extract (1:8 in 25% ethanol); liquid extract (1:8 in 45% ethanol); liquid extract (1:1 in 25% ethanol); and liquid extract (1:1 in 70% ethanol).

The range of daily dosage varies from 30 mg to 120 mg of total flavonoids expressed as vitexin in a herbal medicine made from Passiflora. According to the EMA Assessment Report on P. incarnata, the herbal extract prepared with hydroalcohol solution or acetone solution may contain at least 2.0% of flavonoids expressed as vitexin, and the daily dose recommended corresponds in most cases to about 20–30 mg of total flavonoids.

The following dosages have been reported in specific published studies:

• A preoperative anxiolytic trial used 500 mg/day of passionflower extract, with researchers concluding it provided a safe and effective anxiolytic effect without impairing psychomotor function.
• The sleep quality study (Ngan and Conduit) involved participants drinking 250 mL of passionflower herbal tea once a day, in the evening.
• The opiate withdrawal trial used up to 0.8 mg clonidine plus 60 drops of passionflower extract per day.
• A separate study used 200 mg of dry extract (obtained using ethanol 60% V/V as the extraction solvent), 1–2 tablets per day, as recommended by EMA guidelines.
• For ADHD, a dose of 0.04 mg/kg/day (twice daily) was referenced in the literature.

The use of passionflower in children under 12 years of age is not recommended according to the EMA monograph.

8. Safety Considerations and Interactions

General Tolerability

Passionflower is generally well tolerated. Side effects can include dizziness, ataxia, and confusion. Passiflora incarnata extract did not show any adverse effects in at least one placebo-controlled clinical study.

No acute toxicity was observed after intraperitoneal administration of Passiflora extracts to mice in doses up to 900 mg/kg body weight. No signs of toxicity were observed on repeat-dose administration to rats for 21 days.

Documented Adverse Event Reports

A 34-year-old woman required hospital admission with symptoms of nausea, vomiting, decreased heart rate, and heart rhythm abnormalities after using a passionflower supplement.

A patient who self-medicated with valerian and passionflower while on anti-anxiety therapy experienced hand tremors, dizziness, throbbing, and muscular fatigue suspected to be caused by using these products together.

Pharmacological Risk Profile

Based on the pharmacological profile of the plant, theoretical adverse effects could include CNS depression and bradycardia. Large doses may result in central nervous system depression and slowed or irregular heart rhythms.

Drug Interactions

CNS Depressants and Sedatives: Caution is advised when combining passionflower with sedative medications due to potential interactions. The GABAergic mechanism of passionflower creates a plausible pharmacodynamic basis for additive CNS depression when combined with benzodiazepines, barbiturates, alcohol, or other sedative agents.

MAO Inhibitors: β-carboline alkaloids (which are MAO inhibitors) may be present as minor constituents. Passionflower contains small amounts of harmala alkaloids, which are known to act as monoamine oxidase inhibitors (MAOIs). This raises a theoretical concern for additive MAOI activity when passionflower is combined with pharmaceutical MAO inhibitors, potentially leading to serotonergic or hypertensive effects, although this has not been confirmed in clinical reports specific to passionflower alone.

Interaction Case Report — Lorazepam: A case report described a patient self-medicated with Valeriana officinalis L. and Passiflora incarnata L. while on lorazepam treatment, resulting in a clinically significant interaction.

Contraindications and Special Populations

The EMA monograph lists hypersensitivity to Passiflora species as a contraindication, and notes that passionflower preparations may impair ability to drive and use machines.

No case of overdose has been reported in the literature reviewed by the EMA monograph.

According to the EMA, neither dependence nor withdrawal symptoms have been associated with passionflower use.

Pregnancy and Lactation

Safety data in pregnancy and lactation are insufficient to establish safety. The EMA monograph does not support use during pregnancy or lactation due to lack of adequate data.

9. Regulatory and Pharmacopeial Status

The species Passiflora incarnata L. is included in many pharmacopeias and is the most used species in the food, cosmetic, and pharmaceutical industries. Published clinical data are insufficient to support a well-established use designation according to the EMA HMPC, meaning passionflower is classified as a traditional herbal medicine rather than a pharmacologically well-established medicine.

The pharmacological effects or efficacy are based on long experience (at least 30 years, including at least 15 years within the European Community), but the safety of the product must be ensured and the quality must be verified according to the European Pharmacopoeia monographs or those in the Pharmacopoeia of a Member State.

The results of major reviews have shown that Passiflora species have health benefits but clinical trials are still scarce. Future well-designed, larger-scale RCTs are necessary to better characterize the dose-response relationship, identify optimal extract standardization, and confirm findings across the range of purported indications.

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