Commonly known as passionflower, purple passion flower, or maypop, Passiflora incarnata is one of approximately 520 species in the family Passifloraceae. Species in this family are found primarily in Central and South America, and, less commonly, in North America, Australia, and Southeast Asia.1 Growing up to 25 feet in length, passionflower is an herbaceous vine that climbs using axillary tendrils, and it spreads aggressively by root suckers. It has deciduous (or evergreen, depending on the climate), three-lobed, dark green leaves that are whitish on the underside. Conspicuous, largely lavender corona flowers with showy pistils and stamens appear in spring through fall and are followed by yellow edible fruit (berries).2
Passiflora incarnata is native to the southeastern United States3 and is currently distributed from Florida west to Texas, north to southeastern Kansas, and east to Virginia,4 where it is cultivated in gardens and found in disturbed sites, along fences, by roadsides, in thickets, and on waste grounds.1 The northern limits of passionflower’s current range are an extension of its original habitat due to increasing anthropogenic effects (i.e., the influence of human activities on nature). Archeological evidence indicates, for example, that P. incarnata did not occur in Arkansas or Kentucky prior to the 1550s.4 In the 17th century, European colonizers brought P. incarnata to Europe, where it was introduced, domesticated, and is still cultivated today, particularly in Mediterranean France and Italy, where there are several certified organic farms growing passionflower for the herbal market.
While some of the material of commerce is obtained from cultivation in the United States and parts of southern Europe, much of the commercial supply of passionflower is still wild-collected in the southeastern United States. The entire vine, including stems, leaves, flowers, and fruits, is harvested by hand starting in the late spring (when it begins to flower) from disturbed areas, fields, and early successional habitats.5*
Although the second edition of the American Herbal Products Association’s Herbs of Commerce also lists other passionflower species — namely, P. caerulea (blue passionflower), P. coriacea (bat-leaf passionflower), P. edulis (purple granadilla or purple passionflower), P. foetida (stinking passionflower), and P. laurifolia (yellow granadilla or bay-leaf passionflower)6 — this article focuses on P. incarnata.
HISTORY AND CULTURAL SIGNIFICANCE
Historically, various P. incarnata plant parts have been used as food or medicine by Native American tribes in the southeastern United States, including the Apalachee and Creek (both of Florida),7 Cherokee (Georgia, North and South Carolina, Tennessee, Virginia), Houma (Louisiana),8 and Powhatan (Virginia).9 Seeds of P. incarnata are often found among archaeobotanical artifacts at excavation sites (e.g., at the Early Historic North American archaeological period [17th century] Creek town of Fusihatchee in Alabama, and at several Apalachee sites in North Florida).7 According to archeological evidence, human use of P. incarnata began in the Late Archaic period (3,500-800 BCE) in North America. Seeds have been identified at Late Archaic period sites in Alabama and Tennessee; Early Woodland period (800 BCE-200 CE) sites in Georgia; Middle Woodland period (100 BCE-550 CE) sites in Alabama and Tennessee; Late Woodland period (550-1000 CE) sites in Alabama, Louisiana, and Tennessee; Mississippian/Protohistoric period (1000-1550 CE) sites in Alabama, Georgia, North and South Carolina, Tennessee, Mississippi, and Virginia; and Historic period (1550-1800 CE) sites in Georgia, North Carolina, and Tennessee.4
In his manuscript The Historie of Travaile Into Virginia Britannia, William Strachey, an English writer who served as the first Secretary of the Colony of Virginia in 1610, documented Algonkian food uses of wild passionflower fruits, which the indigenous referred to as “maracock,” in coastal Virginia.10 It has been suggested that the origin of one of passionflower’s common names “maypop” is an alteration of “maycock,” a name derived from the Powhatan (Virginia) name “mahcawq.” But the name may also refer to the sound made when the buds begin popping in the month of May, or to the popping sound that is made when the fruits are crushed or stepped on.7
The genus name Passiflora and the corresponding vernacular name “passionflower” originate from the Italian fiore della passione, a name given to the flower in a context of Christian symbology (objects associated with the crucifixion of Christ).4 This story can be traced back to 1605 CE at the start of the papacy of Pope Paul V (1552–1621), when a live P. incarnata plant was given to the pope and planted as a gift in his honor. First described in a treatise on New World flora written by the Italian Dominican monk Simone Parlasca and published in 1609,11 as well as in a 1619 publication by Neapolitan Dominican monk and druggist Fra Donato d’Eremita,12 the flower’s corona was represented as resembling the crown of thorns, the three styles being the nails of the cross, the three-lobed leaves the spear, and the five anthers representing the marks of the five wounds, among other correlations.13 Passionflower was first introduced into England in 1629 as a greenhouse plant later described in a folio (pamphlet) titled Six Numbers of Coloured Figures of Passion Flowers by Mary Lawrance.14
In 1838, W.B. Lindsay of Bayou Gros Tête, Louisiana, brought the clinical use of inspissated (thickened or congealed) passionflower juice to the attention of his friend David Lewis Phares of Newtonia, Mississippi, after having prescribed it for 30 years (since about 1808) with reportedly successful outcomes in cases of tetanus neonatorum.† In his early years of dispensing passionflower juice, Lindsay had attributed observed differences in dosage strength and efficacy to an incorrect assumption that preparations were being made from different species of Passiflora. He was later convinced that the medicines had all been made from P. incarnata but that the differences were due to dissimilarities in season of gathering, mode of preparation, and locality of growth. (For example, Lindsay believed that passionflower wild-collected on uplands and in Bayou Gros Tête made the strongest medicine, while passionflower collected near dikes or levees around New Orleans was inferior.) Later, in their clinical practices, both Phares and his son, J.H. Phares, reported success using passionflower juice to treat tetanus erectus in horses.14 D.L. Phares reportedly also carried out human trials, published in the New Orleans Medical Journal, using passionflower preparations made by Lindsay.
In the late 19th century, Isham Jabus Marshall Goss, MD (1819-1896), of Georgia introduced the use of passionflower into Eclectic medical practice. According to the 18th edition of King’s American Dispensatory (3rd Revision), published in 1898, specific indications for use of passionflower liquid extracts in the Eclectic system of medicine included “irritation of brain and nervous system with atony; sleeplessness from overwork, worry, or from febrile excitement, and in the young and aged; neuralgic pains with debility; exhaustion from cerebral fullness or from excitement; convulsive movements; infantile nervous irritation; nervous headache; tetanus; hysteria; oppressed breathing; cardiac palpitation from excitement or shock.”15
Traditional European uses of the plant include for anxiety, constipation, indigestion, insomnia, nervousness, and mild infections.1 In Poland, it has been used for hysteria and neurasthenia, while, in Turkey, in addition to insomnia, it has been used for epilepsy, painful menstruation (dysmenorrhea), neuralgia, and neurosis.1
Defined as the dried herbage of “Passiflora incarnata Linné” collected after some of the berries have matured, “Passiflora” entered the fourth edition of the National Formulary (NF IV) in 191616 and remained officinal through the fifth edition (NF V) until 1936. A monograph for “Tinctura Passiflorae” was also included in the NF V.17 The 20th edition of The Dispensatory of the United States of America, published in 1918, added monographs describing both “Passion Flower N.F.” and “Tinctura Passiflorae N.F.”18
In 1975, the US Food and Drug Administration (FDA) considered inclusion of “passion flower extract” as a sedative active ingredient in its proposal to establish a monograph for over-the-counter (OTC) nighttime sleep-aid and daytime sedative drug products. Although “passion flower extract” was a labeled active ingredient in marketed sedative drug products at that time, the FDA’s Advisory Review Panel on OTC Sedative, Tranquilizer and Sleep-Aid Drug Products was unable to find sufficient evidence to demonstrate that it induced sedation. The panel initially classified the use of passion flower extract in nighttime sleep-aid products as “irrational.”19 In 1978, while still included in the ongoing review of nighttime sleep-aid active ingredients, the FDA issued a tentative final order placing passion flower extract into Category II, meaning “nonmonograph” or “Not Generally Recognized as Safe and Effective” (not GRASE).20
Another eleven years passed before the FDA would issue its final rule in 1989, which classified passion flower extract as nonmonograph. OTC nighttime sleep-aid drug products containing passion flower extract could no longer be marketed unless the product was the subject of an approved New Drug Application (NDA). Existing passionflower drug products were then required to be phased out of the market.21 By the time the Dietary Supplement Health and Education Act (DSHEA) of 1994 was passed, passionflower-based products were transitioned from OTC drug to the newly established dietary supplement framework. In 2000, the FDA ruled that some OTC drug monograph claims would be acceptable as structure-function claim statements, including claims listed in its nighttime sleep-aid monograph (in particular, “for the relief of occasional sleeplessness,” because occasional sleeplessness is not a characteristic symptom of a disease).22 In this case, it turned out that certain passionflower-based dietary supplements could now be marketed with the same claim statement as when previously labeled and marketed as OTC sleep-aid drug products, provided that the notifying company had compiled a substantiation file containing sufficient levels of evidence to support the claim for its specific product.
In 1985, the German Commission E approved the use of passionflower herb, prepared as an herbal tea infusion or equivalent galenical preparation, as a nonprescription medicine for treating nervous restlessness.23 Since then, national labeling standards monographs of European Union (EU) member states, such as those of the German Commission E, have been superseded by monographs of the European Medicines Agency (EMA). In Germany, the aerial parts (herb) of P. incarnata remains classified as both medicine and food (depending on dose) and appears on List B in Germany’s List of Substances, meaning that restricted use in foods is recommended because pharmacological effects occur above a certain dose.24
A quality standards monograph for “Passiflorae Herba” first entered the European Pharmacopoeia (PhEur) in the 2000 supplement to the 1997 third edition25 and has remained official through the current ninth edition published in July 2016.26 In 2007, a comprehensive monograph (quality and therapeutics) for “Herba Passiflorae” entered volume three of the WHO Monographs on Selected Medicinal Plants.27 In the same year, the EMA published a labeling standards monograph (later superseded by a 2014 revised monograph),28 and the following year, Health Canada published its labeling standards monograph.29 Although a quality standards monograph for “Pasiflora, Parte Aérea” entered the Mexican Pharmacopoeia in 2013,30 remarkably there is not yet an official quality standards monograph available in the United States Pharmacopeia (USP) for this widely used medicinal plant that is native to the United States.
Currently, herbalists employ P. incarnata for its analgesic, antispasmodic, hypnotic, nervine, and hypotensive effects. It has proven useful as a sedative for intractable insomnia, for relieving nerve pain, and for addressing seizures and asthma associated with spasms and tension.31
An online retrospective survey of the use of herbal anxiolytics by college students published in 2012 revealed that passionflower was the most commonly used herbal dietary supplement for reducing anxiety. Of 235 students who responded, 85 (36.2%) used passionflower in the previous 12 months (of those 85 students, 55 used it less than 10 times, 19 used it monthly, nine weekly, and two daily).32 The most common reasons given for using an herbal dietary supplement were recommendation by friends or family (38%), ease of obtaining dietary supplement (36.3%), and lower cost compared to prescription drugs (23.1%).
CURRENT AUTHORIZED USES IN COSMETICS, FOODS, AND MEDICINES
In the United States, passionflower may be used as a natural flavoring substance, so long as the minimum quantity to produce the intended effect is used.33 (The FDA regulation specifically lists “passion flower [Passiflora incarnata L.],” but it may be safe to assume that passionflower fruit and extracts thereof are included in the scope of the regulation.) Passionflower is also permitted as a component of dietary supplement products, requiring FDA notification within 30 days of marketing if a structure-function claim is made and product manufacturing according to dietary supplement current good manufacturing practices (cGMPs).34
In Canada, passionflower is regulated as an active ingredient of licensed natural health products (NHPs) requiring pre-marketing authorization from the Natural and Non-prescription Health Products Directorate (NNHPD). Labels of licensed NHPs prepared from British or European pharmacopeial-quality passionflower may carry the claim statement “Traditionally used in Herbal Medicine as a sleep aid (in cases of restlessness or insomnia due to mental stress).”30 Additionally, passionflower is listed in the draft “Cognitive Function Products” monograph as a sedative active ingredient.35 At the time of this writing (September 2016), 547 licensed NHPs list P. incarnata as an ingredient, of which 543 products list it as a medicinal ingredient, and four NHPs list it as a non-medicinal ingredient.36
For herbal medicinal product companies in the EU, or in non-EU countries where the PhEur is an official compendium (e.g., Australia and Canada), there are quality standards monographs established by the European Directorate for the Quality of Medicines (EDQM) for “Passion Flower Herb” containing a minimum of 1.5% flavonoids (expressed as vitexin), and “Passion Flower Dry Extract” containing a minimum of 2.0% flavonoids (expressed as vitexin), which can be used as the basis for active ingredient specifications.29 Registered Traditional Herbal Medicinal Products (THMPs) composed of PhEur-quality passionflower and prepared as herbal teas, liquid extracts, or as solid dosage forms containing dry extract, may be labeled and marketed “for relief of mild symptoms of mental stress and to aid sleep.”28
For use in cosmetic products, the European Commission Health and Consumers Directorate lists “Passiflora Incarnata Extract” (extract of whole plant) for astringent function. “Passiflora Incarnata Flower Extract” is listed for skin-conditioning and skin-protecting functions, and “Passiflora Incarnata Water” (aqueous solution of the steam distillates obtained from passionflower) is listed for masking and skin-conditioning functions.37
Passiflora incarnata herb contains 1-2.5% flavonoids (pharmacopeial quality contains minimum 1.5% flavonoids, expressed as vitexin), consisting almost exclusively of C-glycosyl flavones. The proportion of each individual flavonoid is, however, highly variable. For example, isovitexin-2”-O-glucoside is present at 0.1 to 0.8%, isoshaftoside at 0.05 to 0.5%, shaftoside at 0.02 to 0.61%, and isoorientin-2”-O-glucoside at 0.1 to 0.46%, and in some types swertisin is present (at about 0.3%). There are only small amounts of vicenin-2 and lucenin-2, and very low levels of orientin and vitexin. Passionflower also contains polysaccharides (especially arabinoglucan), free amino acids including gamma-aminobutyric acid (GABA), and trace amounts of harmala alkaloids.38 Wohlmuth et al. (2010) attribute the high variability of flavonoid levels in different samples to the existence of two distinct chemotypes. The type that contains swertisin is almost absent of shaftoside and isoshaftoside.39
In vivo and in vitro studies of P. incarnata show limited support of its anti-anxiety, antiasthmatic, anticonvulsant, antidiabetic, antiseizure, antitussive, and sedative properties.1,40-44
Passionflower is primarily used in combination with other herbs, and clinical evidence of its efficacy as a monopreparation is limited. There are, however, at least six clinical studies on P. incarnata
In a randomized, single-blind study from 2013, 63 patients needing periodontal treatment were randomly assigned into one of three groups of 21 to test the efficacy of passionflower in reducing dental anxiety. One group was given 20 drops of passionflower extract (Pasipay, 30% hydroalcoholic extract with total flavonoid content of 4% w/w, including vitexin and rutin; Iran Darouk Pharmaceutical Co.; Tehran, Iran) the night before treatment and 20 drops following treatment. In the placebo group, the placebo drops were administered in the same way. The third group received no intervention. Patients filled out the Corah’s Dental Anxiety Scale, Revised (DAS-R) at the initial interview and following the intake of medication before periodontal treatment. The passionflower group experienced a significant reduction in anxiety following administration of the drops, from 12.09 ± 2.42 down to 8.47 ± 2.08 (P < 0.0001). There was no significant reduction in anxiety in the other two groups.45
A randomized, double-blind, placebo-controlled (RDBPC) prospective study published in 2011 investigated the effect of passionflower on preoperative anxiety. Forty-five minutes prior to receiving spinal anesthesia, 60 patients completed both parts of the State-Trait Anxiety Inventory (STAI) questionnaire to measure basic anxiety and induced anxiety. Sedation level and psychomotor function were also measured. Thirty minutes prior to receiving anesthesia, hemodynamics were measured via heart rate and systolic, diastolic, and mean arterial pressures, and the patients were randomly assigned to two groups. Patients received either passionflower syrup (700 mg/5 mL aqueous extract; Sandoz, Kocaeli, Turkey; no additional information provided) or placebo. All of the tests were performed again just prior to administration of anesthesia, and there was a statistically significant increase in STAI scores in the placebo group but no other statistically significant differences. The authors state that oral administration of P. incarnata suppresses the increase in anxiety before spinal anesthesia without affecting psychomotor function, sedation level, or hemodynamics.46
Another RDBPC study published in 2008 evaluated the efficacy of passionflower in reducing preoperative anxiety. Sixty patients scheduled for inguinal herniorrhaphy (surgical repair of a hernia in which a loop of the intestine has protruded through a weak area of the adominal wall) were randomly assigned into one of two groups. One group received 500 mg of Pasipay 90 minutes before surgery; the other received placebo. Each patient’s anxiety and sedation were assessed using a numerical rating scale (NRS) before taking medication and at 10, 30, 60, and 90 minutes after. Psychomotor function also was assessed upon arrival in the operating room and 30 and 90 minutes after tracheal extubation. The Pasipay group experienced significantly lower mean NRS scores over time (P < 0.001) with no other significant differences between groups. This suggests that oral administration of passionflower prior to surgery can reduce anxiety without inducing sedation.47
In 2001, a randomized, double-blind, controlled study compared the efficacy of passionflower to the conventional pharmaceutical sedative drug oxazepam in treating generalized anxiety disorder (GAD). Outpatients diagnosed with GAD (N = 36) at least six months prior to the study were randomly assigned to receive either 45 drops/day of Pasipay plus a placebo tablet or 30 mg/day oxazepam plus placebo drops for four weeks. Both Pasipay and oxazepam were effective in treating GAD, and while there were no significant differences between the two groups regarding total side effects, patients on oxazepam experienced significantly more problems related to impairment of job performance.48
One double-blind, placebo-controlled, repeated-measures study published in 2011 investigated the effects of passionflower tea on sleep. Healthy volunteers (N = 41) were recruited and provided information regarding their health and sleeping patterns. All had mild sleep difficulties and were not taking any medications or remedies other than contraception. Passionflower tea bags (2 g of dried P. incarnata leaves, stems, seeds, and flowers; Hilde Hemmes’ Herbal Supplies Pty. Ltd.; Ridgehaven, South Australia) or parsley tea bags (2 g of Petroselinum crispum[Apiaceae]; same producer) were provided with brewing instructions. Each participant drank one tea or the other each night for a week while keeping a sleep diary (which included a subjective report of their sleep, as well as the number and duration of naps, types and amounts of caffeine and alcohol consumption, and bedtime). Participants also completed the STAI questionnaire on the seventh morning. After a one-week washout period, participants switched to the other tea and repeated the process for another week. Additionally, 10 volunteers participated in overnight polysomnography (PSG) on the last night of each treatment period, the results of which were used to validate sleep diaries. Of the PSG and subjective sleep parameters analyzed, subjective sleep quality alone was significantly better in the passionflower group than in the placebo group. The authors opined that the small sample size limited the power of the statistical analysis. Furthermore, they stated that the passionflower tea dose was three times less than the recommended dosage and questioned if tea might not be the most effective way of administering passionflower. They also suggested that using volunteers with mild sleep issues rather than clinically diagnosed insomnia left little room for improvement and that their study may have been too short to observe significant improvement.49
Based on the German Commission E’s approval of passionflower for nervous restlessness and the British Herbal Compendium’s indication of passionflower for ADHD, researchers in 2003 conducted an eight-week, randomized, parallel group study on 34 children diagnosed with ADHD. One group was administered Pasipay (0.04 mg/kg/day, twice daily) and the other methylphenidate (1 mg/kg/day, twice daily). Patients were assessed by a child psychiatrist at baseline, 14, 28, 42, and 56 days. There were no significant differences between the two groups at baseline or during the course of the study, and both groups showed significant improvement over eight weeks of treatment. The methylphenidate group did experience more probable side effects than the Pasipay group, including decreased appetite (seven subjects vs. two subjects, respectively) and anxiety/nervousness (six subjects vs. no subjects, respectively). The authors suggest that passionflower may be an appropriate treatment for ADHD, especially in children who do not tolerate pharmaceutical stimulants, but that larger studies are needed to confirm their findings.50
One RDBPC study from 2001 investigated the efficacy of passionflower as an adjuvant to help with anxiety and insomnia during detoxification from opioids using clonidine. Male opioid addicts (N = 65) were randomly assigned to receive either 0.8 mg/day of clonidine plus 60 drops of “passiflora extract” (no further information provided) or 0.8 mg/day of clonidine plus 60 drops of placebo, three times per day in divided doses. Severity of opioid withdrawal syndrome was measured on days 0, 1, 2, 3, 4, 7, and 14 using the Short Opiate Withdrawal Scale (SOWS). Both groups experienced significant alleviation of physical withdrawal symptoms, but the passiflora-clonidine group experienced a significant reduction in mental symptoms starting on day 2, which was not the case in the clonidine-only group. The authors suggest that passiflora may indeed be an effective adjuvant in the management of opioid withdrawal but that further, larger studies are needed to confirm these results.51
As mentioned previously, passionflower is most often used in combination with other herbs, and there have been studies that have investigated the efficacy of these combinations. In a randomized, controlled trial published in 2013, NSF-3 (410 mg of polyherbal extract containing 80 mg of passionflower, 300 mg of valerian [Valeriana officinalis, Caprifoliaceae], and 30 mg of hops [Humulus lupulus, Cannabaceae]; M/s Tablets India; Chennai, India) performed as well as the conventional pharmaceutical sedative zolpidem in improving total sleep time, sleep latency, and insomnia index scores, and decreasing number of nightly awakenings.52
An Italian study published in 2011 showed that children taking 0.5 mL/kg body weight of Vagostabil Junior (containing California poppy [Eschscholzia californica, Papaveraceae] aerial parts dry extract titrated to 0.8% total alkaloids expressed as protopine, and passionflower aerial parts dry extract titrated at 4% minimum total flavonoids expressed as vitexin; Cristalfarma; Milan, Italy) had significantly improved sleep quality without adverse effects over the course of 14 days.53
There are no known comprehensive reports available on the conservation status of wild P. incarnata in its native southeastern United States habitat. However, the passionflower vine thrives in human-disturbed areas, and its geographical distribution has expanded over time. In some places where it has been introduced outside of its native habitat, the species is considered invasive.8 Even within its geographical origin, the vines spread from its natural areas along edges of forested areas into agricultural fields, pastures, and citrus groves.5 According to Lockard and Swanson (1998), “Many farmers find this plant to be a nuisance and might very well accept your offers to harvest it.”54 For sustainable wild-collection, Lockard and Swanson recommend that harvesters should not disturb the roots, leave at least 10% of a passionflower vine patch unharvested in order to facilitate regeneration, and rotate patches rather than returning to the same patch year after year. Harvesting should be carried out “on sunny days, late in the morning after the dew has dried.”54
In recent decades, some herbal product companies have switched from wild-collected passionflower herb to material produced under controlled cultivation. One reason for this switch is that passionflower vines are climbers that attach to, and get tangled up with, other plants, particularly with other climbing vines. This can make it difficult for harvesters to completely separate out passionflower aerial parts and avoid unintentional adulteration with plant parts of non-target species.54 Furthermore, highly invasive Asian climbing vines, including kudzu (Pueraria montana var. lobata, Fabaceae) and precatory (Abrus precatorius, Fabaceae), now share habitat with P. incarnata vines in the southeastern US. Both kudzu and precatory are listed as noxious weeds in Category I of the Florida Exotic Pest Plant Council (FLEPPC) list of invasive plant species. Category I species are defined as “invasive exotics that are altering native plant communities by displacing native species, changing community structures or ecological functions, or hybridizing with natives.”55 Toxic precatory vine plant parts have been implicated in the past as potential adulterants to various wild-harvested materials.56 And for passionflower cultivated outside its native habitat, potential contamination with pyrrolizidine alkaloid (PA)-containing weeds (particularly in Europe) was identified in a May 2016 public statement by the EMA. The EMA listed “Passiflorae herba” among the top 10 herbal ingredients most likely affected by PA contamination and therefore made recommendations for risk management and quality control, including that farms should implement “significantly enhanced” good agricultural and collection practices (GACPs) to mitigate the risk.57
Although in recent years there have been occasional market shortages of certified organic passionflower of pharmacopeial quality, there is evidence that passionflower production is occurring increasingly through sustainable agricultural practices, along with very recently enhanced GACPs to avoid contamination with non-target weed species. Presently, the main source countries for certified organic cultivated passionflower are France and Italy, but organic cultivation is also increasing in the United States, especially at farms in Kentucky, Missouri, North Carolina, and California. Given that P. incarnata is not an endangered or threatened species in its native habitat (although potentially competing with highly invasive climbing vines), and that controlled cultivation is also increasing, it appears that increased global demand can be satisfied through sustainable production methods.
The use of passionflower herb (or extracts thereof) as an active ingredient of traditional herbal medicines, modern phytomedicines, and herbal dietary supplements is likely to continue to increase globally, as are sustainable production systems, whether through controlled cultivation or wild-harvesting. Some experts, however, have cautioned that care must be taken by companies to identify and select specific chemotypes in order to ensure reproducible quality and efficacy.39
–Gayle Engels and Josef Brinckmann
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