Passionflower

• Stress reduction
• Sleep quality improvement
• Anxiety relief

• Neuroprotection
• Mild pain relief
• Menopausal symptom relief
• Digestive comfort

Passionflower (Passiflora incarnata) exerts its primary effects through multiple mechanisms centered on the GABAergic system, the main inhibitory neurotransmitter network in the central nervous system. The herb contains numerous bioactive compounds, with flavonoids (particularly chrysin, vitexin, isovitexin, and orientin) being the most well-studied active constituents.

These compounds work synergistically to promote relaxation, reduce anxiety, and improve sleep quality through modulation of GABA receptors, inhibition of GABA reuptake, and effects on other neurotransmitter systems. Unlike benzodiazepines, passionflower appears to work through multiple subtle mechanisms rather than potent action at a single target, which may explain its generally milder effects and favorable safety profile.

The optimal dosage of passionflower varies based on the preparation method, standardization, and individual factors. For anxiety and sleep, research typically uses 300-900 mg of dried herb extract taken 1-3 times daily, with higher doses for sleep and lower doses for daytime anxiety management. Standardized extracts are often calibrated to contain 3.5-4% flavonoids, which serve as marker compounds for quality and potency. There is no established Recommended Dietary Allowance (RDA) for passionflower as it is not considered an essential nutrient.

Individual response varies significantly, with some people requiring higher doses for effect while others may be sensitive to lower doses.

Passionflower (Passiflora incarnata) contains numerous bioactive compounds with varying pharmacokinetic profiles, making its overall bioavailability complex to characterize. The key marker compounds, including flavonoids (vitexin, isovitexin, orientin, chrysin) and alkaloids, have generally moderate to low oral bioavailability due to limited water solubility, extensive first-pass metabolism, and potential efflux transport.

The bioavailability of passionflower’s active compounds is influenced by extraction method, formulation, and individual factors such as gastrointestinal function and genetic variations in metabolizing enzymes. Different preparation methods can significantly affect which compounds are extracted and their subsequent bioavailability.

General Characteristics: Absorption of passionflower’s active compounds occurs primarily in the small intestine, with limited absorption in the stomach. The rate and extent of absorption vary significantly by compound class and are influenced by their physicochemical properties.

Compound Specific Absorption:

General Characteristics: After absorption, passionflower’s active compounds are distributed throughout the body via the bloodstream, with varying degrees of tissue penetration based on their physicochemical properties.

Blood-brain Barrier Penetration: Flavonoid aglycones like chrysin can cross the blood-brain barrier to some extent, which is crucial for their central nervous system effects. Flavonoid glycosides have more limited BBB penetration. Harman alkaloids readily cross the BBB due to their lipophilicity and small molecular size.

Protein Binding: Flavonoids demonstrate moderate to high plasma protein binding (approximately 70-95%), primarily to albumin. This protein binding affects their free concentration and tissue distribution but may also protect them from rapid metabolism and elimination.

Tissue Distribution: Flavonoids show distribution to various tissues including liver, kidney, and to a lesser extent, brain tissue. Harman alkaloids, despite their low concentration, may accumulate in brain tissue due to their lipophilicity and BBB penetration.

General Characteristics: Passionflower’s active compounds undergo extensive metabolism, primarily in the liver through Phase I and II reactions, with some compounds also metabolized by the gut microbiota.

Hepatic Metabolism: Cytochrome P450 enzymes (particularly CYP1A2, CYP2C9, and CYP3A4) catalyze oxidation, reduction, and hydroxylation reactions of flavonoids and alkaloids., Conjugation reactions, including glucuronidation (via UDP-glucuronosyltransferases) and sulfation (via sulfotransferases), are common for flavonoids and their phase I metabolites.

Gut Microbial Metabolism: The gut microbiota plays a significant role in metabolizing flavonoid glycosides, hydrolyzing glycosidic bonds to release aglycones which may then be absorbed or further metabolized. Microbial metabolism can also produce bioactive metabolites with different properties than the parent compounds.

Metabolic Pathways:

General Characteristics: Passionflower’s active compounds and their metabolites are primarily eliminated via biliary excretion followed by fecal elimination, with some renal excretion of water-soluble metabolites.

Half Life: The elimination half-life varies among compounds: flavonoid aglycones typically have half-lives of 2-5 hours; flavonoid glycosides may have longer half-lives of 5-8 hours due to slower metabolism; harman alkaloids have half-lives of approximately 1-3 hours.

Excretion Routes: Conjugated metabolites are excreted in bile and appear in feces after potential deconjugation by gut bacteria. Water-soluble metabolites are excreted in urine.

Enterohepatic Circulation: Some evidence suggests that flavonoids and their metabolites may undergo enterohepatic circulation, where they are excreted in bile, deconjugated by gut bacteria, reabsorbed, and recirculated. This process can extend their presence in the body and contribute to prolonged effects.

Pharmacokinetic Studies: Very limited human pharmacokinetic studies with small sample sizes; most detailed studies conducted in animals or in vitro

Analytical Challenges: Complex mixture of compounds makes comprehensive pharmacokinetic characterization difficult; focus on marker compounds may not capture full activity profile

Standardization Issues: Variable standardization approaches between products and studies complicates comparison of results

Knowledge Gaps: Limited understanding of active metabolites, enterohepatic circulation, and long-term pharmacokinetics with regular use; limited data on brain concentrations of active compounds

Passionflower (Passiflora incarnata) has a favorable safety profile based on both traditional use spanning centuries and modern clinical research. It is well-tolerated by most individuals at recommended doses, with infrequent and typically mild adverse effects. Unlike many conventional anxiolytics, passionflower does not appear to cause significant tolerance, dependence, or withdrawal symptoms with long-term use. However, certain populations should exercise caution, and potential interactions with medications should be considered.

The safety profile is best established for short to medium-term use (up to 2-3 months), with more limited data on very long-term consumption.

Common Mild:

Rare Serious:

Pediatric:

• Limited data on safety in children. Some traditional use and small clinical studies in children over 3 years for anxiety and sleep issues with good tolerability, but long-term safety not established.
• Reduced dosing based on age and weight; typically 1/3 to 1/2 adult dose for children 3-12 years.
• Potential for increased sensitivity to sedative effects; limited safety data in this population.

Geriatric:

• Generally safe in older adults, with potential benefits for age-related anxiety and sleep disturbances. May be more sensitive to effects due to age-related changes in metabolism.
• Start with lower doses (300 mg) and titrate slowly. May be more sensitive to sedative effects.
• Increased risk of drug interactions due to polypharmacy common in older adults; potential for enhanced sedation or dizziness that could increase fall risk; monitor for morning drowsiness.

Pregnant And Lactating:

• Not recommended during pregnancy due to insufficient safety data and traditional cautions about potential uterine stimulant effects.
• Avoid use during pregnancy; use with caution during lactation and only after consulting healthcare provider.
• No adequate studies in pregnant or lactating women; animal studies insufficient to establish safety profile for pregnancy.

Hepatic Impairment:

• Limited data, but no specific hepatotoxicity concerns identified. Caution advised due to metabolism of key compounds in the liver.
• Consider reduced doses (50% of standard) in moderate to severe impairment if used.
• No specific monitoring required beyond standard care for hepatic disease.

Renal Impairment:

• Limited data, but likely safe in mild to moderate renal impairment as most active compounds undergo hepatic metabolism with limited renal elimination.
• No specific adjustments needed for mild to moderate impairment; use caution in severe renal disease.
• No specific monitoring required beyond standard care for renal disease.

Psychiatric Conditions:

• Generally safe for anxiety and stress-related conditions, but caution advised in bipolar disorder due to theoretical risk of triggering mania (though no specific cases reported).
• Theoretical risk of worsening depression due to sedative effects in some individuals; potential for interaction with psychiatric medications.
• Use under healthcare provider supervision in individuals with significant psychiatric conditions.

Acute Toxicity:

• No established LD50 in humans; animal studies show very low toxicity with LD50 > 15 g/kg for extracts in rodents
• No formal maximum tolerated dose established; doses up to 10 g of dried herb have been used in traditional medicine without serious adverse effects
• Theoretical symptoms might include excessive sedation, confusion, dizziness, and nausea, though documented cases are extremely rare
• Supportive care; symptoms expected to resolve within 24-48 hours due to relatively short half-life of active compounds

Chronic Toxicity:

• Clinical studies up to 8 weeks show favorable safety profile; traditional use suggests safety with long-term consumption, though modern controlled studies of very long-term use are limited
• No evidence of carcinogenic potential in available studies
• No mutagenic effects observed in standard assays
• Insufficient data in humans; some traditional sources suggest avoiding during pregnancy due to potential uterine stimulant effects
• No specific organ toxicity identified in clinical studies or post-marketing surveillance at recommended doses

Adulteration:

• Substitution of Passiflora incarnata with other Passiflora species (P. edulis, P. caerulea); adulteration with other plant materials; synthetic additives to enhance sedative effects
• HPLC analysis of flavonoid profile (vitexin, isovitexin, orientin are markers for P. incarnata); microscopic analysis; DNA barcoding
• Purchase from reputable sources; look for products with third-party testing certification; standardized extracts with specified flavonoid content offer more reliable quality

Contamination:

• Heavy metals, pesticide residues, microbial contamination, mycotoxins
• Should meet USP, EP, or equivalent pharmacopeial standards for herbal preparations
• Third-party testing, Good Manufacturing Practices (GMP) certification, organic cultivation when possible

Standardization Issues:

• Variability in active compound content between products; different standardization markers used by different manufacturers
• Total flavonoid content (typically 3.5-4% in high-quality extracts); specific marker compounds include vitexin, isovitexin, and orientin
• Look for products that specify standardization parameters; check for expiration dates and proper storage conditions

Us Fda: Sold as dietary supplement under DSHEA regulations; not approved as a drug; listed as GRAS (Generally Recognized as Safe) for use in foods

European Medicines Agency: Approved as a traditional herbal medicinal product for relief of mild symptoms of mental stress and to aid sleep in several EU countries

Health Canada: Approved as a Natural Health Product (NHP) with monograph for sleep aid and anxiolytic

Australia Tga: Listed complementary medicine with approved indications for relief of nervous tension, stress, and mild anxiety

International Status: Recognized in many pharmacopoeias including European Pharmacopoeia, British Pharmacopoeia, and German Commission E monographs

Reported Adverse Events: Very few serious adverse events reported despite widespread use; most common reports involve mild sedation, dizziness, and gastrointestinal symptoms

Pharmacovigilance Data: Consistent with favorable safety profile established in clinical studies

Case Reports: Isolated case reports of allergic reactions; rare reports of vasculitis but causal relationship not definitively established

Longest Duration Studies: Clinical studies up to 8 weeks show continued favorable safety profile; longer-term safety based primarily on traditional use and post-marketing surveillance

Theoretical Concerns: Potential for rare idiosyncratic reactions with long-term use; theoretical concern for mild dependence with very long-term use (though not observed in available studies)

Monitoring Recommendations: No specific monitoring required for long-term use in healthy individuals; periodic assessment of continued need and effectiveness

Acute Effects:

• Mild impairment of complex cognitive tasks and psychomotor performance in approximately 10-15% of users, typically dose-dependent
• Higher doses (>600 mg); individual sensitivity; concurrent use of other sedatives
• Significantly less impairment than benzodiazepines in comparative studies; Akhondzadeh et al. (2001) found significantly less impairment of job performance compared to oxazepam

Next Day Effects:

• Morning drowsiness reported in less than 5% of users, typically mild and transient
• Higher doses (>900 mg); taking late at night; individual sensitivity; concurrent use of other sedatives
• Less morning impairment than many conventional sleep medications

Driving Safety:

• Avoid driving or operating heavy machinery until individual response is known, particularly after initial doses or dose increases
• Limited specific research on driving performance; Movafegh et al. (2008) found no significant impairment of psychomotor performance at 500 mg dose
• No specific legal restrictions on driving after use in most jurisdictions, unlike some prescription medications

Prevalence: Rare; estimated at less than 1% of users

Risk Factors: Known allergies to plants in the Passifloraceae family; multiple plant allergies; atopic conditions

Manifestations: Typical allergic reactions including skin rash, itching, hives; rarely more severe reactions including difficulty breathing

Cross Reactivity: Potential cross-reactivity with related plants in the Passifloraceae family; limited data on cross-reactivity with other plant families

Physical Dependence:

• No significant evidence of physical dependence in clinical studies or post-marketing surveillance
• Unlike benzodiazepines, passionflower does not appear to cause dependence even with long-term use

Psychological Dependence:

• Limited evidence of mild psychological dependence in some long-term users
• Primarily concerns about ability to manage anxiety or sleep without supplement rather than craving or drug-seeking behavior

Withdrawal Symptoms:

• No significant withdrawal syndrome documented in clinical studies
• Some anecdotal reports of mild and transient symptoms including rebound anxiety for 1-3 days after discontinuing long-term use
• Gradual tapering not generally necessary but may be prudent after very long-term use

Pharmacokinetic Interactions:

Pharmacodynamic Interactions:

Driving And Machinery Operation:

• Moderate risk of impairment, particularly at higher doses or when initiating use
• Avoid driving or operating heavy machinery until individual response is known; particular caution with higher doses or when combined with other sedatives

Workplace Considerations:

• Low risk of significant impairment at standard doses for most occupations; higher risk for safety-sensitive positions
• Consider lower doses for daytime use; avoid use before or during safety-critical tasks until individual response is known

Alcohol Interaction:

• Moderate risk of enhanced sedation and impairment when combined with alcohol
• Avoid alcohol consumption when using passionflower, particularly when driving or operating machinery

Classification: Dietary supplement ingredient under DSHEA (Dietary Supplement Health and Education Act of 1994)

Approved Uses: No approved drug uses; marketed as dietary supplement only

Supplement Status: Legal for sale as dietary supplement; not approved as a food additive

Labeling Restrictions: Cannot make disease claims; structure/function claims must include disclaimer that FDA has not evaluated the claim

Adverse Event Reporting: Serious adverse events must be reported by manufacturers to FDA within 15 days

Manufacturing Requirements: Must comply with dietary supplement cGMP (current Good Manufacturing Practices) under 21 CFR Part 111

United States Pharmacopeia: Not currently monographed in USP-NF (United States Pharmacopeia-National Formulary)

European Pharmacopoeia: Official monograph for Passiflora incarnata L., herba (passionflower herb)

British Pharmacopoeia: Official monograph for Passionflower Herb

German Commission E: Positive monograph for nervous restlessness and sleep disorders

French Pharmacopoeia: Official monograph for Passiflora incarnata

Brazilian Pharmacopoeia: Official monograph for Passiflora incarnata

Low to moderate, depending on form and quality

$0.10-$0.60 per day for standard passionflower extract (300-900mg daily); $0.20-$0.80 per day for premium standardized extracts; $0.05-$0.25 per day for bulk dried herb or tea

Overview: Passionflower offers good value for its anxiolytic and sleep-promoting effects compared to both conventional pharmaceuticals and many alternative supplements. The cost-benefit ratio is particularly favorable for mild to moderate anxiety and sleep issues, where its efficacy approaches that of some prescription medications but at a fraction of the cost and with fewer side effects. Generic and store-brand products provide adequate quality for most users, though standardized extracts with guaranteed flavonoid content may offer more consistent results and better value despite higher initial cost.

Cost Comparison To Alternatives:

Cost Effectiveness By Form:

Conventional Insurance: Generally not covered by health insurance in the United States and most Western countries

Health Savings Accounts: May be eligible for HSA/FSA reimbursement with a Letter of Medical Necessity in the US

Integrative Medicine Plans: Some specialized integrative medicine insurance plans may provide partial coverage

International Variations: Covered by some national health insurance systems in countries where approved as a traditional herbal medicinal product (parts of Europe); typically requires prescription in these cases

Dried Aerial Parts: 1-2 years when stored properly in airtight containers away from light, heat, and moisture

Powdered Herb: 6-12 months due to increased surface area and exposure to oxidation

Standardized Extracts: 2-3 years when stored in original container at room temperature away from moisture

Tinctures: 3-5 years due to preservative effect of alcohol content

Capsules Tablets: 2-3 years when stored in original container with desiccant if provided

Synthesis Methods

Natural Sources

Quality Considerations

Common Adulterants

Sustainability Considerations

Geographical Considerations

Commercial Forms

Extraction Methods

Supply Chain Considerations

Authentication Methods

Cultivation Details

Wild Harvesting Considerations

Processing Technologies

Native Habitat: Indigenous to southeastern United States from Virginia to Florida and west to Texas and Oklahoma; thrives in disturbed areas, woodland edges, and open fields

Early Cultivation: Initially harvested from wild populations; cultivation began in the late 19th century for medicinal purposes

European Introduction: Introduced to Europe in the 16th century initially as an ornamental curiosity; later cultivated for medicinal use

Commercial Cultivation Development: Commercial cultivation expanded in the 20th century, with significant production in the United States, Europe (particularly Germany and Italy), and South America

Traditional Contraindications: Pregnancy (in some traditions due to theoretical uterine stimulant effects), Very young children (though used in reduced doses for older children), Individuals with ‘excessive lethargy’ or depression (in some traditional systems)

Historical Side Effects: Drowsiness (considered an expected effect rather than adverse reaction when used for sleep), Occasional digestive discomfort with strong preparations, Potential for excessive sedation when combined with alcohol or other sedatives

Historical Toxicity Cases: Very few documented cases of significant toxicity; generally considered one of the safer nervine herbs in traditional systems

Safety Reputation Evolution: Consistently regarded as having a favorable safety profile throughout historical usage; modern research has largely confirmed traditional safety observations

Passionflower (Passiflora incarnata) has been the subject of scientific investigation for its effects on anxiety, insomnia, and related conditions for several decades. The evidence base includes in vitro studies, animal models, and human clinical trials, with the strongest evidence supporting its use for anxiety and stress-related conditions. While the quality of studies varies and results are not uniformly positive, meta-analyses generally support modest benefits for anxiety and sleep with minimal adverse effects. Research on the individual active compounds, particularly flavonoids like chrysin, vitexin, and isovitexin, provides supporting evidence for passionflower’s mechanisms of action.

The overall body of evidence suggests that passionflower is a mild to moderate anxiolytic and sedative with a favorable safety profile, though its effects may be less potent and consistent than conventional pharmaceutical options.

Investigation of specific passionflower compounds for targeted drug development, Exploration of potential applications in substance withdrawal syndromes, Research on effects on specific anxiety disorders beyond GAD, Studies on genetic factors affecting individual response to passionflower, Development of enhanced delivery systems to improve bioavailability, Investigation of potential applications in neurodegenerative conditions, Research on long-term effects on stress resilience and neuroplasticity, Exploration of synergistic effects with other herbs and nutrients

Strength Of Evidence: Moderate overall; stronger for anxiety (particularly situational anxiety) than for sleep or other applications

Consistency Of Findings: Generally consistent positive findings for anxiety across studies; more mixed results for sleep and other applications

Applicability To General Population: Most studies conducted in adults with mild to moderate anxiety or sleep issues; limited evidence in specific clinical populations

Risk Of Bias: Variable quality of studies; many with methodological limitations including small sample sizes and short duration

Overall Assessment: Sufficient evidence to support use for mild to moderate anxiety and anxiety-related sleep issues in generally healthy adults; promising but not definitive evidence for other applications

Traditional Use Validation: Modern research generally supports traditional applications for anxiety, nervous tension, and sleep difficulties

Discrepancies: Traditional use for pain and muscle spasms has limited modern research support; traditional use in higher doses than typically studied in clinical trials

Evolving Understanding: Traditional attribution of effects to various compounds has evolved with scientific identification of specific active constituents like flavonoids and harman alkaloids

Significance: Demonstrates value of traditional knowledge in guiding modern research while refining understanding through scientific methods