Passiflora incarnata (Passionflower) is a herb that helps to calm the mind and relax the nervous system. Its aerial parts, harvested during flowering and the fruiting period have been traditionally used for stress, anxiety and insomnia.^1,2 Passionflower has been approved by the German Commission E for the treatment of nervous restlessness.³ Phytochemicals found in Passionflower contributing to its anxiolytic, sedative and hypnotic activities include flavonoids, benzoflavone, gamma-aminobutyric acid (GABA), and alkaloids in trace amounts.^4-6

Passionflower’s anxiolytic effects have been proven time and time again within the context of treating neuropsychiatric disorders, particularly anxiety.^7-9 Drawing a comparison to the pharmaceuticals used for conditions associated with anxiety seems like the natural next step; however, it is equally, if not more important, to consider the potential advantages of co-prescription.

Benzodiazepines

Benzodiazepines are a type of medication administered for anxiety and insomnia management; however, they are associated with a range of side effects including, but not limited to, drowsiness, confusion¹⁰ and impaired alertness.¹¹ About 25 to 30% of all patients fail to respond adequately to this treatment, and tolerance and dependence may occur. Stopping benzodiazepine treatment suddenly can induce a withdrawal syndrome, characterised by psychological (e.g. apprehension and irritability) and physiological (e.g. tremors and palpitations) symptoms of anxiety.¹¹ Lastly, it is important to recognise that benzodiazepines are commonly involved in single substance drug-induced deaths in Australia.¹²

On the other hand, excessive sleepiness can greatly increase the likelihood of a workplace accident, which can result in injury and even death in many industries and professions, especially pilots, truck drivers and shift workers. Sleep deprivation also impacts upon job performance (productivity, task management and meeting goals).¹³ And so, finding an appropriate alternative to benzodiazepines with less adverse effects would appear sensible.

Numerous pharmacological effects of Passionflower have been described, with the most compelling evidence supporting its ability to modulate the GABA system, including an affinity to GABA type A (GABAA) and type B (GABAB) receptors, with subsequent inhibitory effects on GABA uptake.¹⁴

Passionflower extract (45 drops/day) has been shown to be as effective as the benzodiazepine oxazepam in the treatment of generalised anxiety disorder (GAD) in a double-blind, randomised trial (n=36). While oxazepam did show a more rapid onset of action, it was also associated with a more problems related to impairment of job performance than Passionflower. Thus, Passionflower extract may be the preferrable treatment option in cases where drug-induced impairment of job performance needs to be avoided.¹¹

In terms of benzodiazepine co-prescription, a real-world study in 186 patients with anxiety and depression found that a dry extract of Passionflower (200 to 600 mg/day) is an effective add-on treatment during benzodiazepine tapering, with significant effects evident after both one and three months (see Table 1). Such findings justify the use of Passionflower in the management of anxiety disorders and dependence.¹⁵

Table 1. Percentage of patients achieving 50% reduction or complete benzodiazepine discontinuation after one and three months¹⁵

Drug Withdrawal

Preclinical research has revealed that the benzoflavone moiety is responsible for the various central nervous system (CNS) effects of Passionflower. Impressively, benzoflavone has been shown to counteract the development of drug tolerance, dependence and/or withdrawal effects of substances like benzodiazepines,⁶ alcohol (benzoflavone¹⁶ and Passionflower extract),¹⁷ morphine,¹⁸ cannabinoids,¹⁹ and nicotine.²⁰

Moreover, a 14-day double-blind, randomised, controlled clinical trial in 65 opiate addicts (opioid dependence) showed that Passionflower extract (60 drops/day) plus clonidine showed significant superiority over clonidine and placebo in the management of mental symptoms of withdrawal syndrome. Both protocols were equally effective in treating the physical symptoms of withdrawal syndromes.²¹

Surgery

Most patients undergoing surgery have a fear of anaesthesia and surgical procedures, resulting in anxiety. The global incidence of preoperative anxiety is estimated at 60 to 92%.²² Passionflower has shown significant effects in allaying the increase in preoperative anxiety experienced by patients ahead of general anaesthesia²³ and spinal anaesthesia²⁴ in double-blind, randomised, placebo-controlled studies. It is reported to do so without affecting preoperative sedation scores, recovery of psychomotor function or delaying discharge time. A single-blind, randomised trial (n=63) found that Passionflower also significantly reduced anxiety in patients undergoing dental procedures (dental anxiety).²⁵

NB: all complementary therapies should be disclosed to the patient’s surgical team prior to surgery.

The Bottom Line

Taken together, the efficacy and safety profile of Passionflower, comparable to or in combination with other medications, is compelling. Practitioners should feel confident in exploring Passionflower as an alternative to anxiety medication, particularly benzodiazepines, as well using Passionflower to support patients who are coming off addictive substances and to ease anxiety prior to surgery. Nevertheless, practitioners should continue to monitor their patients when co-prescribing with pharmaceuticals that have sedative effects.

References

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3. Blumenthal M, Busse WR, Goldberg A, Gruenwald J, Hall T, Riggins W, et al. The complete German Commission E monographs: therapeutic guide to herbal medicines. Austin: American Botanical Council; 1998.

4. Elsas SM, Rossi DJ, Raber J, White G, Seeley CA, Gregory WL, 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):940-949. DOI: 10.1016/j.phymed.2010.03.002

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9. Nojoumi M, Ghaeli P, Salimi S, Sharifi A, Raisi F. Effects of passion flower extract, as an add-on treatment to sertraline, on reaction time in patients ‎with generalized anxiety disorder: a double-blind placebo-controlled study. Iran J Psychiatry. 2016 Jul;11(3):191-197.

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12. Australian Institute of Health and Welfare. Alcohol, tobacco & other drugs in Australia [Internet]. Canberra: Australian Government; 2024 [cited 2024 Aug 2]. Available from: https://www.aihw.gov.au/reports/alcohol/alcohol-tobacco-other-drugs-australia/contents/drug-types/non-medical-use-of-pharmaceutical-drugs

13. Sleep Foundation. Excessive sleepiness and workplace accidents [Internet]; Seattle: OneCare Media; 2023 [cited 2024 Aug 2]. Available from: https://www.sleepfoundation.org/excessive-sleepiness/workplace-accidents

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15. Zanardi R, Carminati M, Fazio V, Maccario M, Verri G, Colombo C. Add-on treatment with Passiflora incarnata L., herba, during benzodiazepine tapering in patients with depression and anxiety: a real-world study. Pharmaceuticals (Basel). 2023 Mar;16(3):426. DOI: 10.3390/ph16030426

16. Dhawan K, Kumar S, Sharma A. Suppression of alcohol-cessation-oriented hyper-anxiety by the benzoflavone moiety of Passiflora incarnata Linneaus in mice. J Ethnopharmacol. 2002 Jul;81(2):239-244. DOI: 10.1016/s0378-8741(02)00086-7

17. Schunck RVA, Macedo IC, Laste G, De Souza A, Valle MTC, Salomón JLO, et al. Standardized Passiflora incarnata L. extract reverts the analgesia induced by alcohol withdrawal in rats. Phytother Res. 2017 Aug;31(8):1199-1208. DOI: 10.1002/ptr.5839

18. Dhawan K, Kumar S, Sharma A. Reversal of morphine tolerance and dependence by Passiflora incarnata – a traditional medicine to combat morphine addiction. Pharm Biol. 2002;40(8):576–580. DOI: 10.1076/ phbi.40.8.576.14660

19. Dhawan K, Kumar S, Sharma A. Reversal of cannabinoids (delta9-THC) by the benzoflavone moiety from methanol extract of Passiflora incarnata Linneaus in mice: a possible therapy for cannabinoid addiction. J Pharm Pharmacol. 2002 Jun;54(6):875-881. DOI: 10.1211/0022357021779069

20. Dhawan K, Kumar S, Sharma A. Nicotine reversal effects of the benzoflavone moiety from Passiflora incarnata Linneaus in mice. Addict Biol. 2002 Oct;7(4):435-441. DOI: 10.1080/1355621021000006044

21. Akhondzadeh S, Kashani L, Mobaseri M, Hosseini SH, Nikzad S, Khani M. Passionflower in the treatment of opiates withdrawal: a double-blind randomized controlled trial. J Clin Pharm Ther. 2001 Oct;26(5):369-373. DOI: 10.1046/j.1365-2710.2001.00366.x

22. Adhikari SP, Pathak BD, Ghimire B, Baniya S, Joshi P, Kafle P, et al. Prevalence of pre-operative anxiety and associated risk factors among patients awaiting elective surgery in a tertiary care hospital. F1000Res. 2023;12:1207. DOI: 10.12688/f1000research.136320.2

23. Movafegh A, Alizadeh R, Hajimohamadi F, Esfehani F, Nejatfar M. Preoperative oral Passiflora incarnata reduces anxiety in ambulatory surgery patients: a double-blind, placebo-controlled study. Anesth Analg. 2008 Jun;106(6):1728-1732. DOI: 10.1213/ane.0b013e318172c3f9

24. 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. DOI: 10.1007/s00540-011-1265-6

25. Kaviani N, Tavakoli M, Tabanmehr M, Havaei R. The efficacy of Passiflora incarnata Linnaeus in reducing dental anxiety in patients undergoing periodontal treatment. J Dent (Shiraz). 2013 Jun;14(2):68-72.