Passionflower
Passiflora incarnata
Evidence Rating
Confidence Level
Traditions
Last Updated
Summary
Passionflower is recognized by all major European monograph bodies (Commission E, ESCOP, WHO) for nervous restlessness and sleep disturbance, making it one of the most broadly endorsed herbs in this collection from a regulatory standpoint. However, the clinical trial evidence supporting these endorsements is limited in quantity and quality. The mechanism involves GABA modulation (both GABA-A and GABA-B receptors), with flavonoids (chrysin, apigenin, isovitexin) and direct GABA content as likely active constituents. One noteworthy trial found passionflower comparable to oxazepam for GAD. It has an excellent safety profile with virtually no reported adverse effects.
Drug Interactions
This herb has significant drug interactions. Do not use if you are taking medications without consulting a healthcare provider first. See detailed interaction information below.
Regulatory Status
| Regulatory Body | Status |
|---|---|
| Commission E (Germany) | ✓ Approved |
| ESCOP (European) | ✓ Approved |
| EMA/HMPC (EU) | ✓ Approved |
Metadata
| Field | Detail |
|---|---|
| Common Names | Passionflower, Passion vine, Passionsblume (German), passiflore (French) |
| Botanical Name | Passiflora incarnata L. |
| Plant Family | Passifloraceae |
| Part Used | Aerial parts (herba) — stems, leaves, flowers (dried) |
| Key Constituents | Flavonoids (chrysin, apigenin, vitexin, isovitexin, orientin, isoorientin), gamma-aminobutyric acid (GABA — as a direct constituent), maltol, indole alkaloids (harman, harmine, harmaline — trace amounts) |
| Major Standardized Extract | No single dominant standardized extract equivalent to WS 1490 or Silexan |
| Evidence Quality Rating | C+ (Moderate-Low) — Strong regulatory consensus but limited clinical trial data |
Approved Indications
Commission E (Germany)
- Approved: Nervous restlessness
ESCOP
- Approved: Tenseness, restlessness, irritability with difficulty in falling asleep
WHO (World Health Organization)
- Monograph issued: Mild to moderate nervous unrest with accompanying sleep disorders
EMA/HMPC
- Traditional use: Relief of mild symptoms of mental stress and to aid sleep
- Preparations covered: powdered herbal substance, herbal tea, ethanol extracts
Agreement/Disagreement
Remarkably consistent across all monograph bodies. Commission E, ESCOP, WHO, and EMA all agree on the dual indication of nervous restlessness and sleep difficulties. However, all classify this under traditional/historical use rather than well-established use, reflecting the limited clinical trial evidence. This represents a case where broad traditional consensus exceeds the available modern clinical data.
Conditions Treated
Primary (Moderate Evidence)
- Nervous restlessness and anxiety — Especially mild to moderate, non-psychotic anxiety
- Sleep disturbances — Particularly difficulty falling asleep related to nervous tension
Secondary (Limited Evidence)
- Preoperative anxiety — One trial showed comparable anxiolysis to midazolam before dental surgery
- GAD (Generalized Anxiety Disorder) — One trial comparable to oxazepam
- Anxiety in children and adolescents with eating/feeding disorders [NEEDS-RESEARCH]
Common Combination Use
- Often combined with valerian, lemon balm, and/or hops in multi-ingredient sleep and calming formulas
Mechanism of Action
Primary Mechanism: GABA System Modulation
Passionflower modulates the GABAergic system through multiple pathways:
- GABA-A receptor binding: In vitro studies demonstrate affinity for GABA-A receptors. Maltol and gamma-pyrone derivatives activate GABA-A receptors.
- GABA-B receptor binding: Also shows affinity for GABA-B receptors, which is less common among sedative herbs.
- Direct GABA content: Passiflora extract contains significant amounts of GABA as a direct constituent. When amino acids (including GABA) were removed from the extract, GABA currents in hippocampal neurons were eliminated, suggesting that the GABA content itself contributes to activity.
- GABA uptake effects: Modulation of GABA uptake has been demonstrated in vitro.
Secondary Mechanisms
- Benzodiazepine receptor binding: Flavonoids chrysin (found in P. caerulea) and apigenin (found in P. incarnata) show affinity for central benzodiazepine receptors, producing non-sedating anxiolysis.
- Opioidergic modulation: Modulates opioidergic and nicotinic cholinergic systems, potentially relevant to analgesia.
- Monoaminergic effects: Affects dopamine, norepinephrine, and serotonin pathways.
- Glutamatergic modulation: Isovitexin protects against glutamate-induced excitotoxicity. Vitexin inhibits NMDA receptors (NR2B subunits), reducing calcium influx.
- MAO inhibition: Trace amounts of beta-carboline alkaloids (harman, harmine, harmaline) are reversible MAO inhibitors, but concentrations in standard preparations are too low to be clinically significant.
Key Active Constituents
- Chrysin: Benzodiazepine receptor ligand; anxiolytic without sedation
- Apigenin: Benzodiazepine receptor ligand
- Isovitexin and vitexin: Neuroprotective, anti-excitotoxic
- Maltol: GABA-A receptor activator
- GABA (direct): Direct neurotransmitter content in extract
Clinical Evidence Summary
Overview
The clinical evidence is notably sparse relative to the strong regulatory consensus:
Akhondzadeh et al. (2001) — Passionflower vs. Oxazepam for GAD
- Design: Randomized, double-blind, 4 weeks
- n = 36 outpatients with GAD (DSM-IV criteria)
- Passionflower extract 45 drops/day vs. Oxazepam 30 mg/day
- Result: Both treatments were equally effective in reducing HAMA scores. No significant difference in efficacy.
- Key advantage: Oxazepam group showed significantly more impairment of job performance. Passionflower had a slower onset but no cognitive impairment.
- Limitation: Very small sample size
Dantas et al. (2017) — Preoperative Anxiety
- Design: Randomized, double-blind
- n = 40 adult patients undergoing tooth extraction
- Passionflower 260 mg vs. Midazolam 15 mg administered 30 minutes before surgery
- Result: Comparable anxiolytic effects. Passionflower was a safe and effective alternative.
- Limitation: Single-dose acute use; small sample
Ngan & Conduit (2011) — Sleep Quality
- Design: DBRPCT, crossover
- n = 41 healthy adults
- Passiflora incarnata herbal tea (2 g, 1 week)
- Result: Subjective sleep quality (sleep diary) was significantly better than placebo. Polysomnographic measures did not show significant differences.
- Limitation: Short duration; healthy volunteers rather than insomnia patients
Lee & Kim (2020) — Stress and Sleep (Double-Blind RCT)
- Design: DBRPCT
- Participants with stress and sleep problems
- Result: Reduced anxiety and improved sleep quality measures
- [Source: PMC11026993]
Summary of Evidence Quality
- Majority of studies report reduced anxiety following Passiflora incarnata administration
- Effects less evident in people with only mild anxiety symptoms
- Total body of RCT evidence is small (fewer than 200 participants across major trials)
- No large multicenter trials comparable to Silexan or SJW evidence
- The flavonoid content is often proposed for standardization, with daily doses of 20-30 mg total flavonoids (expressed as vitexin) per EMA guidance
European vs. US/Anglophone Consensus
| Aspect | European Consensus | US/Anglophone Consensus |
|---|---|---|
| Regulatory status | Traditional herbal medicine (EMA); Commission E approved | Dietary supplement (GRAS); no formal approval |
| Clinical acceptance | Widely used in combination products (often with valerian and/or hops) | Used in supplement form; some awareness among naturopathic practitioners |
| Evidence assessment | Accepted as traditional remedy; clinical evidence acknowledged as limited | NCCIH: insufficient evidence to draw conclusions |
| Place in therapy | Mild anxiety and sleep difficulty, especially in combinations | Self-care for mild stress and sleep; not recommended by mainstream medicine |
Safety Profile
Contraindications
- Known hypersensitivity
- EMA: Not recommended for children under 12 years (lack of data)
Drug Interactions
- Theoretical additive sedation with CNS depressants (benzodiazepines, barbiturates, alcohol)
- MAO inhibitors: Theoretical interaction due to trace beta-carboline alkaloids, but concentrations are too low for clinical significance at recommended doses
- Overall: No significant drug interactions documented in clinical use
Side Effects
- Remarkably safe. Clinical trials report no adverse effects, including no memory loss or impairment of psychometric functions.
- Occasional reports: Dizziness, drowsiness, confusion (rare, at high doses)
- Allergic reactions: Very rare
Pregnancy and Lactation
- Pregnancy: Contraindicated. The beta-carboline alkaloids (harmine, harmaline), though present in trace amounts, have uterotonic activity. Additionally, insufficient human safety data.
- Lactation: Not recommended due to lack of data.
Clinical Dosage
EMA/HMPC Recommended Doses
- Herbal tea: 1-2 g of dried herb per 150 mL water, 1-4 times daily
- Powdered herbal substance: 0.5-2 g, 1-4 times daily
- Liquid extract (1:1, 25% ethanol): 0.5-2 mL, 1-3 times daily
- Tincture (1:8, 45% ethanol): 1-4 mL, 1-3 times daily
- Dry extract (5-7:1, 60% ethanol): 90-180 mg, 1-4 times daily
Total Flavonoid Content
- EMA: Daily dose should correspond to approximately 20-30 mg of total flavonoids expressed as vitexin
Duration
- If symptoms persist after 2 weeks, consult a physician
- No maximum duration specified for traditional use
Sources
- EMA/HMPC Final Assessment Report on Passiflora incarnata L., herba
- Commission E Monograph: Passionflower herb
- ESCOP Monograph: Passiflorae herba
- WHO Monograph: Herba Passiflorae
- Akhondzadeh S et al. Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther. 2001;26(5):363-367
- Ngan A, Conduit R. A double-blind, placebo-controlled investigation of the effects of Passiflora incarnata herbal tea on subjective sleep quality. Phytother Res. 2011;25(8):1153-1159
- Appel K et al. Modulation of the gamma-aminobutyric acid (GABA) system by Passiflora incarnata L. Phytother Res. 2011;25(6):838-843. PubMed 21089181
- Janda K et al. Passiflora incarnata in Neuropsychiatric Disorders — A Systematic Review. Nutrients. 2020;12(12):3894. PMC7766837
- Dantas LP et al. (preoperative anxiety study). PMC11026993
- Altmeyers Encyclopedia: Passiflorae herba
Connections
Related Herbs
Hops
Humulus lupulus
Hops is one of the oldest European sedative herbs, with the female flower cones (strobiles) used medicinally. It is almost never studied or used alone for sleep -- instead, it is nearly always combined with valerian, and this combination has its own EMA/HMPC monograph. The sedative mechanism involves GABA modulation via bitter acid degradation products (particularly 2-methyl-3-buten-2-ol), and possibly melatonin receptor activity. Standalone clinical evidence is very weak, consisting primarily of studies using very low doses in non-alcoholic beer. The valerian-hops combination has somewhat better evidence, though still modest. Hops is very safe with virtually no adverse effects at recommended doses.
Kava
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Kava is one of the best-studied herbal anxiolytics, with a positive Cochrane review (12 RCTs, n=700) and robust evidence from the standardized extract WS 1490. Its anxiolytic effects are mediated through GABA-A potentiation, monoamine reuptake inhibition, and sodium channel modulation, providing anxiolysis without the sedation or cognitive impairment of benzodiazepines. However, the herb's regulatory history is dominated by a hepatotoxicity scare beginning in 1999 that led to market withdrawal in Germany (2002) and across much of the EU. Subsequent analysis strongly suggests the liver injury cases were largely attributable to poor-quality plant material (tudei kava instead of noble kava), inappropriate extraction methods (acetone instead of ethanol or water), use of non-root plant parts, and possibly idiosyncratic/immunoallergic reactions. A German court overturned the ban, but it was reimposed in 2019, despite ongoing scientific criticism of the regulatory reasoning.
Lavender
Lavandula angustifolia
Silexan (Lasea) is a proprietary standardized oral lavender oil preparation (80 mg/day) that has emerged as one of the best-evidenced herbal anxiolytics. Five major RCTs (n=1,213 for the placebo comparisons) demonstrate efficacy comparable to lorazepam 0.5 mg/day and paroxetine 20 mg/day for generalized anxiety disorder, with a superior safety profile (non-sedating, no abuse potential, no dependence). Its mechanism is novel: inhibition of voltage-gated calcium channels (primarily T-type and N-type), similar in concept to pregabalin but with a different binding site and without sedation. Recent data (2024) also suggest efficacy in mild-to-moderate depression. The EMA/HMPC has registered Silexan as a traditional herbal medicine for temporary anxiety in patients aged 12+.