Passion Flowers: Exciting Results when Traditional Knowledge is Confirmed by Modern Science By: Charles Spielholz, Ph.D., Medical Writer/Editor – Nutraceutical Medical Research, LLC Published May 2009

1. Volume 2, Issue 2, May 2009 INDUSTRY NEWS
Passion Flowers: Exciting Results
when Traditional Knowledge is
Confirmed by Modern Science
By: Charles Spielholz, Ph.D., Medical Writer/Editor – Nutraceutical Medical Research, LLC
Published May 2009
N
ow society has modern approaches to
understanding the properties of passion
flowers and, thus far, the results are
very exciting. Recent research has
indicated that several species of passion flowers that
have been used traditionally exhibit anxiolytic (anti-
anxiety) activity. The passion flower species most
often used for this type of research is Passiflora
incarnata (also known as maypop or the purple
passion flower). Data have been collected both from
clinical trials in humans and experimental
procedures in rodents. In this article we are going to
briefly review data showing that passion flowers,
concentrating mostly on Passiflora incarnata,
exhibit anxiolytic effects. We will then discuss
directions for future research on this interesting and Passiflora incarnata (Purple Passion Flower), also known as Maypop
promising flower.
First discovered by Europeans in 1569 (by the
Passion flowers, a genus of flowering plants which Spanish while exploring Peru), passion flowers
exist mostly as vines, contain several hundred have been used by various Native American groups
member species. The genus name is Passiflora. to alleviate the symptoms of a variety of conditions.
The genus is native to the Americas, Asia and These conditions include what we now call anxiety,
Australia; however species of passion flowers have insomnia, pain, hysteria and nervous exhaustion.
been brought to other parts of the world both for European explorers adapted the traditional use of
their beauty and their edible fruit. passion flowers for medicinal purposes.
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Several major references discuss research on the Passiflora incarnata showed dose dependent
anxiolytic and sedative effects of passion flowers changes in anxiety (9). It has also been shown that
(1-3). One clinical study in which 60 patients were the extract from the leaves, stems and flowers
randomized into two groups before (outpatient) exhibited anxiolytic activity whereas the roots did
surgery showed that patients who received an oral not (10).
dose of Passiflora incarnata 90 minutes prior to
surgery scored significantly lower on clinical Additionally, it has been shown that not all species
anxiety tests then patients who received placebo (4). of passion flower exhibit anxiolytic effects. Extracts
A multicenter, double blind trial, using a from Passiflora incarnata exhibited anxiolytic
combination of plant extracts including Passiflora properties while extracts from Passiflora edulis
showed a statistical difference in comparison to (also known as passion fruit and maracuya) did not
placebo for treatment of anxiety (5). Additional (11). Note that in addition to showing that the
clinical data, with 36 patients, have shown that anxiolytic effects are specific to only certain species
Passiflora incarnata not only is an effective of Passiflora, experiments of this sort also serve as
approach for treatment of anxiety, but that it is may important controls helping to prove that the
be as effective as the benzodiazepine oxazepam (6). anxiolytic effect is unique to just some species of
Benzodiazepines are prescribed drugs with sedative, passion flowers, and not all species.
hypnotic, anxiolytic, anticonvulsant and muscle Researchers have begun to isolate and analyze the
relaxing properties. It must be noted that not all components of Passiflora and have made some
studies have replicated these observations astounding observations. First, it has been shown
statistically indicating that much larger clinical
trials are required to completely understand the
properties of Passiflora.
Given the interesting clinical data indicating that
Passiflora species, particularly Passiflora
incarnata, exhibit anxiolytic properties, it is useful
to review some of the experimental work done in
rodents on this botanical. Experiments studying the
anxiolytic effects of substances in animal models
allow researchers to pinpoint the actions of these
substances on the central nervous system. Early
studies using Passiflora extracts have shown that Figure 1: Chrysin, a flavonoid present in extracts of Passiflora
incarnata. Evidence indicates that chrysin may be the active
there are a variety of dose-dependent actions as well anxiolytic agent of Passiflora incarnata.
as binding sites in the central nervous system in
rodents (7, 8). Mice treated with extracts from
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that Passiflora contains a number of chemical receptor) indicating that the extract was functioning
constituents including flavonoids, glycosides, through the GABAA receptor and not the serotonin
maltol and indole alkaloids. The flavonoids show receptor (16).
the most interesting properties in rodents and we
will focus on one flavonoid in particular, chrysin. There is no evidence that extracts of Passiflora
Chrysin is a naturally occurring flavonoid that is incarnata are addicting in humans, unlike the
extracted from Passiflora incarnata and some other various benzodiazepines that the extracts appear to
Passiflora species. mimic. Preliminary evidence in mice indicates that
the extracts are non-addicting, but also may
Evidence that a benzoflavone isolated from attenuate benzodiazepine dependence to a small
Passiflora incarnata has anxiolytic properties in extent (12). In fact, one report suggests using
mice has been reported (12, 13). Since chrysin is passion flower extract as an adjuvant during opiate
isolated from Passiflora incarnata, several withdrawal (17). That report presented data
investigations have examined the anxiolytic indicating patients who used a passion flower
properties of chrysin in rodents. The results of those extract during opiate withdrawal suffered fewer
studies indicate that chrysin does have anxiolytic mental symptoms of withdrawal then patients who
properties in rats while another flavonoid, apigenin, did not use the extract.
isolated from Matricaria chamomilla (camomile)
and provided at equal doses, did not (14). It was
also reported that the anxiolytic activity of chrysin Figures 2-5: show a comparison of different benzodiazepine
derivatives. Note how similar the structures are to chrysin.
was blocked by flumazepil, a competitive inhibitor
of the benzodiazepine binding site on the GABAA
receptor (14). This observation is consistent with
the idea that chrysin’s anxiolytic properties function
through the GABAergic receptor in the central
nervous system. Another report showed that chrysin
was as effective an anxiolytic agent as midazolam
(a short acting benzodiazepine) and that the
anxiolytic effect was inhibited by flumazepil (15).
In another set of experiments performed in mice, an
extract prepared from Passiflora incarnata exerted
an anxiolytic effect equal to diazepam (Valium),
another benzodiazepine (16). In this study, the
anxiolytic effects of the extract were inhibited by
flumazepil but not by WAY-100 635, an antagonist
Figure 2: Molecular structure of Midazolam
of the serotonin receptor (5-hydroxtryptamine
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Figure 3: Molecular structure of Oxazepam Figure 5: Molecular structure of Diazepam
The anxiolytic properties of the passion flower are
exciting. Clinical data collected thus far indicates
that Passiflora incarnata, the purple passion flower,
exhibits anxiolytic activity. Experiments in rats and
mice show extracts from the flowers, leaves and
stems of Passiflora incarnata contain anxiolytic
activity and that these extracts contain the flavonoid
chrysin. Furthermore, it has been shown that
chrysin possesses anxiolytic activity and that this
property appears to function through the GABAA
receptor. However, direct evidence showing that
the chrysin in extracts of Plassiflora incarnata is
the agent responsible for the anxiolytic effects that
have been observed is not yet available. The
evidence collected so far has allowed the German
Commission E to approve the use of passion flower
for nervous restlessness.
Figure 4: Molecular structure of Flumazepil
Now that modern approaches appear to be
confirming traditional knowledge about Passiflora
incarnata, what is the next step? First, a large scale
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5. Volume 2, Issue 2, May 2009 INDUSTRY NEWS
clinical trial is needed. Such a trial will show speak with a health care provider before using
conclusively that the purple passion flower, passion flower.
Passiflora incarnata, does indeed have clear
anxiolytic properties. So far, clinical data collected
indicates that the anxiolytic properties of Passiflora REFERE CES
incarnata are non-addicting and have no effect on
memory. Only one adverse event (18) has been 1) Chevallier A. Encyclopedia of Medicinal Plants.
reported and, to date, there are no known toxic (1996) New York, NY: DK Publishing, 117.
effects associated with use of passion flower. The
2) Bruneton J. Pharmacognosy, Phytochemistry,
adverse event included nausea, vomiting and
Medicinal Plants. (1995) Paris, France: Lavoisier
nonsustained ventricular tachycardia; however, it is
Publishing Inc., 284-285.
not clear exactly what that patient was taking and if
the patient might have been taking other 3) J. CRC Handbook of Medicinal Herbs. (1985)
medications that were not reported to the physician. Boca Raton FL: CRC Press, 347.
A large clinical trial will sort out and confirm these
important observations. In addition, adverse effects 4) Movafegh A., Alizadeh R., Hajimohamadi F,
would be understood and appropriate warnings Esfehani F, Nejatfar M. (2008) Preoperative oral
could then be provided. Further studies using Passiflora incarnata reduces anxiety in ambulatory
rodents as a model system will allow investigators patients: a double-blind, placebo controlled study.
to determine exactly which molecules in Passiflora Anesth Analg. 106: 1728-1732.
incarnata extracts are involved in the anxiolytic
5) Bourin M, Bougerol T, Guitton B, Broutin E.
effects. This would then allow for quality exact
(1997) A combination of plant extracts in the
quality control to be used in preparing extracts for
treatment of outpatients with adjustment disorder
use commercially and also allow for optimal
with anxious mood: controlled study vs placebo.
dosages to be determined.
Fundam Clin Pharmacol. 11:127-132.
Currently, passion flower is commercially available
6) Akhondzadeh S, Naghavi HR, Varirian M,
as capsules and as a liquid extract. Since passion
Shaveganpour A, Rashidi H, Khani M. (2001)
flower can cause sleepiness, one should not drink
Passion flower in the treatment of generalized
alcohol with passion flower. Manufacturers
anxiety: a pilot double-blind randomized controlled
currently advise users not to drive or operate
trial with oxazepam. J Clin Pharm Ther. 26:363-
machinery or heavy equipment while using passion
367.
flower. Passion flower is not meant for people with
low blood pressure. If a person is taking an MAO 7) Speroni E, Minghetti A. (1988)
inhibitor or is pregnant or nursing, they should Neuropharmacological activity of extracts from
Passiflora incarnata . Planta Med: 54:488-491.
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8). Burkard W, Kopp B, Krenn L, Berger D, apigenin and chrysin. Fitoterapia. 71: Suppl 1:S117-
Schaffner W. (1997) Receptor binding studies in the S123.
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Pharmacol Lett. 7:25-26. 15) Brown E, Hurd NS, McCall S, Ceremuga TE
(2007) Evaluation of the anxiolytic effects of
9) Grundmann O, Wahling C, Staiger C, chrysin, a Passiflora incarnata extract, in the
Butterweck, V. (2009) Anxiolytic effects of a laboratory rat. AANA J. 75:333-337.
passion flower (Passiflora incarnata L.) extract in
the elevated plus maze in mice. Pharmazie. 64:63- 16) Grundmann O, Wang J, McGregor GP,
64. Butterweck V (2008) Aniolytic activity of a
phytochemically characterized Passiflora extract is
10) Dhawan K, Kumar S, Sharma A. (2001) mediated via the GABAergic system. Planta Med.
Anxiolytic activity of aerial and underground parts 74:1769-1773.
of Passiflora incarnata. Fitoterapia. 72: 922-926.
17) Akhondzadeh S, Kashani L, Mobaseri M,
11) Dhawan K, Kumar S, Sharma A, (2001) Hosseini SH, Nikzad S, Khani M. (2001) Passion
Comparative biological activity study on Passiflora flower in the treatment of opiates withdrawal: a
incarnata and P. Edulis. Fitoterapia. 72: 698-702. double-blind randomized controlled trial. J Clin
Pharm Ther. 26: 369-373
12) Dhawan K, Kumar S, Sharma A, (2001). Anti-
anxiety studies on extracts of Passiflora incarnata 18) Fisher AA, Purcell P, LeCouteur DG. (2000)
Linneaus. J Ethnopharmacol. 78:165-170. Toxicity of Passiflora incarnata L. J Toxicol Clin
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13) Dhawan K, Dhawan S, Chhabra S (2003)
Attenuation of benzodiazepine in mice by tri-
substituted benzoflavone moiety of Passiflora
incarnata Linneaus: a non-habit forming anxiolytic.
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14) Zanoli P, Avallone R, Baraldi M (2000)
Behavorial characterisation of the flavonoids
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