Passionflower

• How It Works

  Passionflower may reduce anxiety, but its long-term safety and effectiveness are not known.

  Passiflora incarnata is a perennial wildflower that is commonly found in the southern United States. Passionflower extract is contained in many dietary supplement products marketed as sleep aids or anxiety relievers. A handful of studies in humans support these claims, although it is still unknown whether passionflower extracts are safe and effective in the long-term. Scientists are not sure how this herb works, but have speculated that compounds in passionflower may interact with receptors in the brain that would mediate a relaxation response. Studies done in mice suggest that passionflower extracts have mild anti-inflammatory and anti-seizure activity.

  Because animal studies show disrupted sexual behavior in male offspring, passionflower should be avoided during pregnancy. It may also interact with certain medications as well as have added effects with St. John’s wort and/or valerian.

• Purported Uses
  • To relieve anxiety
    One small clinical trial suggested that passionflower may be as effective as oxazepam, a common drug used for treating general anxiety. In addition, another clinical trial showed that passionflower reduced anxiety in presurgical patients. However, the safety and effectiveness of its long-term use are not known.
  • As a sleep aid, for insomnia
    Passionflower may reduce anxiety (see above), which may help induce sleep. A small study showed benefits of passionflower in sleep quality in healthy adults.
  • To treat nerve pain
    Passionflower may help reduce anxiety (see above), and could thereby reduce the perception of pain. However, other than this theoretical association, no scientific evidence supports the use of passionflower for nerve pain.
  • To treat attention-deficit hyperactivity disorder (ADHD)
    One small study in children suggests passionflower may reduce ADHD symptoms similar to a prescription drug but with less side effects. However, larger well-designed clinical trials are needed.
• Do Not Take If
  • You are taking pentobarbital: Passionflower may have additive effects.
  • You are taking benzodiazepines such as Ativan® or Valium®: Passionflower may increase the sedative effects of these medications.
  • You are taking drugs that prolong the QT interval (eg, azithromycin, dasatinib, fingolimod): The QT interval shows the electrical activity in the heart’s lower chambers, the ventricles. Because lab analyses suggest passionflower may also prolong QT interval with large doses, it is not known whether passionflower may have added cardiac effects with these medications.
  • You are pregnant: Passionflower should be avoided because it may cause uterine contraction and behavioral dysfunction in offspring. 
• Side Effects
  • Dizziness
  • Sedation
  • Lack of muscle coordination
  • Allergic reaction
  • Impaired cognitive function

  Large doses may result in central nervous system depression and slowed or irregular heart rhythms.

  Case 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.
• Special Point
  • Passionflower may have an additive effect with St. John’s wort and/or valerian.
• Scientific Name

  Passiflora incarnata

• Clinical Summary

  Passiflora incarnata is a perennial wildflower that is commonly found in the southern United States. Passionflower extract is used in supplemental form by patients to treat insomnia, anxiety, epilepsy, neuralgia, and withdrawal syndromes from opiates or benzodiazepines. It may also be found in over-the-counter preparations to reduce symptoms associated with menopause and hyperactivity.

  Animal models suggest antidiabetic ⁽¹⁹⁾, antiasthmatic ⁽²⁰⁾, and seizure suppression effects ⁽²¹⁾. In one study, passionflower reduced seizure severity and immobility periods, and retained brain levels of serotonin and noradrenaline ⁽²¹⁾. Another study found that P. incarnata extracts produced anxiogenic effects in mice, although two of these extracts also showed an anticonvulsant effect against seizures ⁽⁶⁾.

  In humans, a small pilot study of passionflower for generalized anxiety showed comparable efficacy to oxazepam ⁽³⁾, but a systematic review concluded that randomized controlled studies are needed to confirm such effects ⁽⁴⁾. In patients undergoing surgery, preoperative passionflower use reduced anxiety ^(5) (16). In healthy adults, consumption of a low-dose passionflower tea produced short-term benefits in sleep quality ⁽¹⁷⁾. Another small study suggests that the effect of passionflower is comparable to a prescription drug in the treatment of ADHD ⁽²²⁾.

  When used concurrently, passionflower was shown to enhance the pharmacologic effects of St. John’s wort ⁽¹⁸⁾.

  Theoretically, passionflower may potentiate the sedative effect of central nervous system depressants including benzodiazepines, barbiturates, and alcohol ⁽²⁾. Due to potential adverse effects, passionflower should be avoided during pregnancy ⁽²³⁾.

• Purported Uses
  • Benzodiazepine withdrawal
  • Drug withdrawal symptoms
  • Epilepsy
  • Insomnia
  • Neuralgia
  • Attention-deficit hyperactivity disorder (ADHD)
• Mechanism of Action

  The alkaloid constituents harman and harmaline are thought to produce monoamine oxidase inhibition ⁽¹⁾, while maltol and gamma-pyrone derivatives cause activation of gamma amino butyric acid (GABA) receptors that may account for anxiolytic and sedative properties ⁽¹¹⁾. Chrysin has also been identified among the bioactive metabolites with central nervous system (CNS) suppression activity ⁽²¹⁾.

  In vitro, modulation of the GABA system by passionflower includes affinity to GABA(A) and GABA(B) receptors, and effects on GABA uptake ⁽²⁴⁾. Antiradical activities observed are attributed to flavonoids such as isovitexin ⁽²⁵⁾. An isolated benzoflavone moiety is suspected as being the strongest aromatase inhibitor in passionflower, although the flavone chrysin also has these properties ⁽²⁶⁾.

  In an animal reproductive and developmental study, passionflower produced sexual behavioral disruption in male adult rats that was not accompanied by alterations in plasma testosterone levels, reproductive-related organs, and glands weights or sperm count, and was potentially attributed to aromatase inhibition ⁽²⁷⁾. In seizure models, protection against post-ictal depression not seen with diazepam controls point to activity from metabolites in passionflower rather than as a result of its seizure suppression effects ⁽²¹⁾.

  Passionflower also exhibits mild anti-inflammatory activity. An ethanolic extract of passionflower reduced carrageenan-induced edema, leukocyte migration, and granuloma formation in mice, although the effect was less than that seen with aspirin ⁽¹³⁾.

• Contraindications

  Pregnancy: In lab studies passionflower produced sexual behavioral disruption ⁽²⁷⁾. Some constituents in passionflower may cause uterine contractions  ⁽²³⁾.

• Adverse Reactions

  Dizziness, sedation, ataxia, allergic reaction, and impaired cognitive function ^(3) (4).

  Large doses may result in central nervous system depression and bradycardia, prolonged QTc and ventricular tachycardia ⁽⁴⁾.

  Case reports

  Nausea, vomiting, bradycardia, and abnormal electrocardiogram: ECG changes included non-sustained ventricular tachycardia, QTc prolongation, and nonspecific ST-T wave changes in a 34-year-old woman requiring hospital admission ⁽⁷⁾.

  Hand tremors, dizziness, throbbing and muscular fatigue: In a patient who self-medicated with valerian and passionflower while on lorazepam treatment. An additive or synergistic effect is suspected to have caused these symptoms ⁽¹⁴⁾.

• Herb-Drug Interactions

  Pentobarbital: Passionflower may potentiate the effects of pentobarbital ⁽²⁾.
  Benzodiazepines: Passionflower may increase the sedative effects of benzodiazepines by increasing the binding activity of benzodiazepines to GABA receptors ⁽¹⁴⁾.
  Drugs that prolong the QT interval (eg, azithromycin, dasatinib, fingolimod): The pharmacologic profile of passionflower also suggests prolonged QT interval with large doses ⁽⁴⁾, and it is not known whether passionflower may have added cardiac effects with these medications.

  Herb-Herb Interaction
  St. John’s wort: In antidepressant models, passionflower was shown to enhance the potency of St. John’s wort ⁽¹⁸⁾.

• References

  1. Dhawan K, Kumar S, Sharma A. Anti-anxiety studies on extracts of Passiflora incarnata Linneaus. J Ethnopharmacol. Dec 2001;78(2-3):165-170.

  2. Speroni E, Billi R, Mercati V, et al. Sedative effects of crude extract of Passiflora incarnata after oral administration. Phytotherapy Res. 1996;10:S92-S94.

  3. Akhondzadeh S, Naghavi HR, Vazirian M, et al. Passionflower in the treatment of generalized anxiety: A pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther. Oct 2001;26(5):363-367.

  4. Miyasaka LS, Atallah AN, Soares BG. Passiflora for anxiety disorder. Cochrane Database Syst Rev. 2007(1):CD004518.

  5. Movafegh A, Alizadeh R, Hajimohamadi F, et al. Preoperative oral Passiflora incarnata reduces anxiety in ambulatory surgery patients: a double-blind, placebo-controlled study. Anesth Analg. Jun 2008;106(6):1728-1732.

  6. Elsas S-M, Rossi DJ, Raber J, et al. Passiflora incarnata L. (Passionflower) extracts elicit GABA currents in hippocampal neurons in vitro and show anxiogenic and anticonvulsant effects in vivo, varying with extraction method. Phytomedicine. 2010 Oct;17(12):940-9.

  7. Fisher AA, Purcell P, Le Couteur DG. Toxicity of Passiflora incarnata L. J Toxicol Clin Toxicol. 2000;38(1):63-66.

  8. Dhawan K, Kumar S, Sharma A. Anxiolytic activity of aerial and underground parts of Passiflora incarnata. Fitoterapia. Dec 2001;72(8):922-926.

  9. Grice ID, Ferreira LA, Griffiths LR. Identification and simultaneous analysis of harmane, harmine, harmol, isovitexin, and vitexin in Passiflora incarnata extracts with a novel hplc method. J Liq Chrom Rel Technol 2001;24(16):2513-2523.

  10. Newall CA, Anderson LA, Phillipson JD. Herbal Medicines: A Guide for Health-Care Professionals. 1st ed. London: Pharmaceutical Press; 1996.

  11. Grundmann O, Wang J, McGregor GP, et al. Anxiolytic Activity of a Phytochemically Characterized Passiflora incarnata Extract is Mediated via the GABAergic System. Planta Med. 2008 Dec;74(15):1769-73.

  12. Soulimani R, Younos C, Jarmouni S, et al. Behavioural effects of Passiflora incarnata L. and its indole alkaloid and flavonoid derivatives and maltol in the mouse. J Ethnopharmacol. Jun 1997;57(1):11-20.

  13. Borrelli F, Pinto L, Izzo AA, et al. Anti-inflammatory activity of Passiflora incarnata L. in rats. Phytotherapy Res. 1996;10:S104-S106.

  14. Carrasco MC, Vallejo JR, Pardo-de-Santayana M, et al. Interactions of Valeriania officilanis L. and Passiflora incarnata L. in a patient treated with lorazepam. Phytother Res. 2009;23:1795-1796.

  15. Brinker F. Herb Contraindications and Drug Interactions. 3rd ed. Sandy (OR): Eclectic Medical Publications; 2001.

  16. Aslanargun P, Cuvas O, Dikmen B, Aslan E, Yuksel MU. Passiflora incarnata Linneaus as an anxiolytic before spinal anesthesia. J Anesth. 2012 Feb;26(1):39-44.

  17. Ngan A, Conduit R. A double-blind, placebo-controlled investigation of the effects of Passiflora incarnata (passionflower) herbal tea on subjective sleep quality. Phytother Res. 2011 Aug;25(8):1153-9.

  18. Fiebich BL, Knörle R, Appel K, et al. Pharmacological studies in an herbal drug combination of St. John’s wort (Hypericum perforatum) and passion flower (Passiflora incarnata): In vitro and in vivo evidence of synergy between Hypericum and Passiflora in antidepressant pharmacological models. Fitoterapia. 2011 Apr;82(3):474-80.

  19. Gupta RK, Kumar D, Chaudhary AK, et al. Antidiabetic activity of Passiflora incarnata Linn. in streptozotocin-induced diabetes in mice. J Ethnopharmacol. Feb 15 2012;139(3):801-806.

  20. Dhawan K, Kumar S, Sharma A. Antiasthmatic activity of the methanol extract of leaves of Passiflora incarnata. Phytother Res. Aug 2003;17(7):821-822.

  21. Singh B, Singh D, Goel RK. Dual protective effect of Passiflora incarnata in epilepsy and associated post-ictal depression. J Ethnopharmacol. Jan 6 2012;139(1):273-279.

  22. Akhondzadeh S, Mohammadi MR, Momeni F. Passiflora incarnata in the treatment of attention-deficit hyperactivity disorder in children and adolescents. Therapy. 2005;2(4):609-614.

  23. Tung YC, Hwang YS, Wu CY. Studies on Beta-Carbolines. 3. Effect of Harman Hydrochloride on Monoamine Oxidase and the Uterine Contractility Induced by N-Monomethyltryptamine Hydrochloride. Tsa Chih Gaoxiong Yi Xue Yuan Tong Xue Hui. Jan 28 1965;64:44-50.

  24. Appel K, Rose T, Fiebich B, et al. Modulation of the gamma-aminobutyric acid (GABA) system by Passiflora incarnata L. Phytother Res. Jun 2011;25(6):838-843.

  25. Masteikova R, Bernatoniene J, Bernatoniene R, et al. Antiradical activities of the extract of Passiflora incarnata. Acta Pol Pharm. Sep-Oct 2008;65(5):577-583.

  26. Dhawan K, Dhawan S, Sharma A. Passiflora: a review update. J Ethnopharmacol. Sep 2004;94(1):1-23.

  27. Bacchi AD, Ponte B, Vieira ML, et al. Developmental exposure to Passiflora incarnata induces behavioural alterations in the male progeny. Reprod Fertil Dev. 2013;25(5):782-789.