Hindawi Publishing Corporation

BioMed Research International

Volume 2014, Article ID 841798, 13 pages
http://dx.doi.org/10.1155/2014/841798

Review Article
Sexual Enhancement Products for Sale Online:
Raising Awareness of the Psychoactive Effects of Yohimbine,
Maca, Horny Goat Weed, and Ginkgo biloba

Ornella Corazza,1 Giovanni Martinotti,2 Rita Santacroce,1,2 Eleonora Chillemi,2

Massimo Di Giannantonio,2 Fabrizio Schifano,1 and Selim Cellek3
1
School of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield AL10 9AB, UK
2
Department of Neuroscience and Imaging, University “G. d’Annunzio”, 66100 Chieti, Italy
3
Cranfield University, Bedfordshire MK43 0AL, UK

Correspondence should be addressed to Ornella Corazza; [email protected]

Received 24 February 2014; Revised 23 May 2014; Accepted 26 May 2014; Published 15 June 2014

Academic Editor: Zsolt Demetrovics

Copyright © 2014 Ornella Corazza et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction. The use of unlicensed food and herbal supplements to enhance sexual functions is drastically increasing. This
phenomenon, combined with the availability of these products over the Internet, represents a challenge from a clinical and a
public health perspective. Methods. A comprehensive multilingual assessment of websites, drug fora, and other online resources
was carried out between February and July 2013 with exploratory qualitative searches including 203 websites. Additional searches
were conducted using the Global Public Health Intelligence Network (GPHIN). Once the active constitutes of the products
were identified, a comprehensive literature search was carried out using PsycInfo and PubMed. Results. The most common
sexual enhancement products available on the Internet were identified. Their active ingredients included yohimbine, maca, horny
goat weed and Ginkgo biloba. These four substances were reported with the occurrence of adverse events and the induction
of psychological symptoms, such as mood changes, anxiety, and hallucinations as well as addictive behaviours. Conclusions.
Uncontrolled availability of sexual enhancement products that contain potentially harmful substances is a major public health
concern. The possible impact on population health, particularly among subjects with psychiatric disorders, usually at risk for sexual
dysfunction, may be significant. This new trend needs to be extensively studied and monitored.

1. Introduction Since herbal supplements are plant products, they are

generally perceived and hence marketed as natural and,
The use of food and herbal supplements to enhance erectile therefore, “safe” [8]. However, several case reports of side
function as well as sexual arousal and desire has become effects to herbs and herbal products have been reported
increasingly popular in the recent years [1, 2]. These products [8, 9], such as on- and off-target effects from biologically
are advertised on the Internet as “natural” and “safer” alter- active ingredients, side effects caused by contaminants, and
natives to pharmaceutical products, such as gold standard for herb-drug interactions. It is difficult to determine the true
treatment of erectile dysfunction and the phosphodiesterase frequency of side effects from herbs and herbal products,
type 5 (PDE5) inhibitors (e.g., sildenafil, tadalafil, and varde- since surveillance systems are much less extensive than those
nafil). However, they often contain potent active constituents in place for pharmaceutical drugs. It is estimated that less
[3–5], which remain undeclared on the packaging [6, 7]. than 1% of side effects or adverse events for herbal products
The effects of the aforementioned products, thus, remain are recorded with the current surveillance systems [10].
unknown until reports on harms expose the problem and Some of the side effects and adverse events due to
accurate clinical evaluation takes place. ingestion of herbs and herbal products are related to their
2 BioMed Research International

action on central nervous system and can present as mood identified in these products, we have found psychological
alterations, anxiety, mania, depression, hallucinations, and safety concerns for only four: yohimbine, maca, horny goat
addictive behaviour; one example of such herbal product is weed, and Ginkgo biloba. Biological, pharmacological, and
ephedra, which was banned in the USA in 2004 [11]. safety profiles of these four substances are presented below.
However, psychological safety profiles of sexual enhance-
ment products have not been characterised. This review,
3.1. Yohimbine
therefore, aimed at identifying the sexual enhancement prod-
ucts advertised and sold on the Internet while collecting 3.1.1. Source and Preparations. Yohimbine is a natural
information about their characteristics (i.e., brand names, tryptamine alkaloid, which can be extracted from the bark
costs, ingredients, availability, declared advantages, and dis- of a variety of plants mostly of African and Asian origin
advantages). We then focused on four substances, which are such as Pausinystalia yohimbe (also known as yohimbe tree)
common in these products: yohimbine, maca, horny goat and the root of Rauvolfia serpentina. Yohimbe bark extract
weed, and Ginkgo biloba, as these were reported to induce is traditionally used in Africa as an aphrodisiac: it has to be
psychological side effects. We also described, less in detail, underlined, though, that tree bark does contain a large num-
other components of sexual enhancer products that may have ber of alkaloids, and yohimbine level in this natural source
both somatic and psychological side effects. may be low. Yohimbine concentration has been suggested to
increase in older branches [13]. A 1995 study by Betz et al. on
2. Methods dietary supplements containing Yohimbe extracts has shown
that the yohimbine content may range from < 0.1 to 489 ppm
A multilingual qualitative assessment of a range of websites, compared with 7089 ppm in the authentic material, which has
drug fora, and other online resources (i.e., e-commerce, e- been attributed to the intense dilution of final product [14].
newsgroups, chat rooms, videos, e-newsletters, and bulletin Currently, yohimbine-containing products are advertised on
boards) was carried out between February 2012 and May 2013. the Internet not only for treating erectile dysfunction and
Exploratory qualitative searches of 203 websites in English enhancing sexual performance, but also as a fast weight-loss
and Italian took place using brand names through Google and body-building supplement [15–17]. Brand names include
search engine. Of these, 106 were considered to be relevant “The Millennium Male Horse Power Capsule” [18], Syntrax
for the study and as such were monitored on a regular basis, [15], and Xytomax (see Table 1).
that is daily (𝑛 = 21), weekly (𝑛 = 32), or monthly (𝑛 =
53), depending on their relevance. The remaining 97 websites
3.1.2. Mechanism of Action. Yohimbine has high affinity to
were considered not to bear any interest for the present
human alpha-2 adrenoceptors, moderate affinity to alpha-
study and thus were no longer monitored. Further specific
1 adrenoceptors, and low affinity to some of the serotonin
searches in the database provided by The Global Public
and dopamine receptors in the central and peripheral ner-
Health Intelligence Network (GPHIN) also took place. This
vous systems [19]. Alpha-2 adrenoceptors mediate erection-
is a secure Internet-based early warning system that gathers
inhibiting impulses in the central nervous system. Yohimbine
preliminary reports of public health significance by mon-
is generally believed to enhance central sexual impulse by
itoring global media sources near “real-time,” 24 hours a
blocking the alpha-2 adrenoceptors in the locus coeruleus
day, 7 days a week basis. GPHIN is operated by the Public
in the brain [20]. In the periphery, yohimbine has been
Health Agency of Canada and monitors news sources and
suggested to inhibit alpha-1 and alpha-2 adrenoceptors as well
websites across the globe in 9 languages (e.g., English, French,
as enhancing the release of nitric oxide (NO) from cavernosal
Farsi, Portuguese, Arabic, Russian, Spanish, and Chinese
endothelial cells [21, 22]. In conclusion, the mechanism of
simplified/traditional) [12]. While a series of algorithms were
action of yohimbine in enhancing sexual function is currently
used and adjusted to capture relevant information, analysis
unclear.
of relevant data since 2003 was also carried out manually by
a multidisciplinary and multilingual team of analysts. Finally,
once the active constituents of these products were identified, 3.1.3. Pharmacokinetics. Yohimbine hydrochloride is rapidly
a comprehensive literature search was carried out using absorbed and the maximum plasma concentration is gener-
PsycInfo and Pubmed databases. Permission for the study ally achieved in less than one hour after oral administration
was granted by the School of Pharmacy Ethics Committee, [23, 24]. The mean bioavailability is low and is subject to
Hatfield, UK (15 December, 2010; PHAEC/10-42). very high variation from one individual to another [25].
The plasma concentration of yohimbine does not appear to
correlate with the dose of the compound administered [26].
3. Results
During the website assessment stage where 136 websites 3.1.4. Efficacy. A meta-analysis in 1998 of seven clinical trials
were monitored for 6 months, we have identified 15 sexual with yohimbine has shown a superiority of the compound
enhancement products advertised and sold on the Internet. over placebo in treatment of erectile dysfunction [27]. Yohim-
The characteristics of these products are summarized in bine has also been reported to be effective in treatment of
Table 1. Yohimbe, ginseng, Ginkgo biloba, maca, horny goat orgasmic disorders such as delayed ejaculation [28]. There
weed, and L-arginine were claimed to be the most common have been no clinical studies testing Yohimbe bark. The Clini-
ingredients in those products. Among all the substances cal Guidelines Panel on Erectile Dysfunction of the American
 Table 1: Characteristics of sexual enhancer products sold online.
Side
Effects/declared advantages effects/disadvantages
Brand name Ingredients Cost Availability
from anecdotal online reports from anecdotal online
reports
BioMed Research International

Epimedium grandiflorum (horny goat weed); maca; Powerful and natural; no

Online suppliers
damiana; L-arginine; Tribulus terrestris; unpleasant side effects;
Endowmax 59.95 $ per box; (orders can be placed
gamma-aminobutyric acid; jujube dates extracts; Muira customers testimonials; Up to 8 weeks for initial
http://www.endowmax six-month supply by fax and phone);
puama (potency woods); Catuaba bark; Xanthoparmelia money back guarantee; it is benefits; expensive.
.com/ for 239.95 $ Ebay; Amazon
scabrosa; Cnidium monnieri; Tongkat Ali (Eurycoma clearly stated the product does
(currently out of stock).
longifolia) not contain Yohimbe.
Niacinamide (vitamin B3); zinc oxide; Epimedium
sagittatum (standardized to 10% icariin); maca root;
It is not to be used in
Guarana extract (standardized to 20% caffeine); Korean
Online suppliers Natural; working from the case of thyroid, kidney,
ginseng root; L-arginine; Muira puama; Longjack 69.96 $ per box;
Xytomax (orders can be placed very first dose; customers or heart diseases or high
extract; Avena sativa; Yohimbe bark extract (2% six-month supply
http://www.xytomax.com/ by fax and phone); testimonials; money back blood pressure; more
yohimbine); Ginkgo biloba extract (24% flavonglycodises for 309.95 $
Ebay. guarantee. expensive than other
& 6% terpene lactones); saw palmetto (berry);
products.
Xanthoparmelia Scabrosa; Cnidium monnieri extract;
GABA; damiana (leaf)
Epimedium grandiflorum (horny goat weed); maca; Online suppliers It could cause stomach
100% natural products; money
Yohimbe; L-arginine; Tribulus terrestris; 89.95 $ per box; (orders can be placed upset if not taken with
Xanogen back guarantee; no negative
gamma-aminobutyric acid; Muira puama (potency six-month supply by fax and phone); food; it does not provide
http://www.xanogen.com/ side effects; permanent effects
woods); Catuaba bark; Xanthoparmelia scabrosa; for 419.95 $ Ebay; Amazon immediate erections but
on corpora cavernosa.
Cnidium Monnieri (currently out of stock). stronger ones.
Some users claim no
Online suppliers
results with this product;
Yohimbe; maca; Elk Antler Velvet; Eleuthero; Longjack; 29.89 C per box; (orders can be placed Stated as: “No side effects;
Virility EX just a couple of customer
Muira puama (potency woods); Catuaba bark; oat six-month supply by fax and phone); 100% natural; money back
http://www.virilityex.it/ testimonials were found
straws. for 89.74 C Ebay; Amazon guarantee.”
on official websites with
(currently unavailable).
no FAQ sections.
Reported hives, facial
Premium natural ingredients;
39.95 $ per box; flushing, insomnia, and
Enzyte Korean red ginseng; Gingko biloba; grape seed extract; Online suppliers; Ebay; no gluten, no preservatives, no
six-month supply internal bleeding; some
http://www.enzyte.com/ horny goat weed; Muira puama; niacin; zinc. Amazon. ephedra, no caffeine, no
for 179 $ users claim no results
Yohimbe.
with this product.
3
 4

Table 1: Continued.
Side
Effects/declared advantages effects/disadvantages
Brand name Ingredients Cost Availability
from anecdotal online reports from anecdotal online
reports
Natural, vegetarian and
59 $ per box;
Online suppliers hypoallergenic; money back Contraindicated in case
six-month supply
Extagen Not clearly listed on website, just “herbs and (orders can be placed guarantee; it is clearly stated of high blood pressure or
for 198 $;
http://www.extagen.com/ phytonutrients.” by phone, and mail the product does not contain other medical
twelve-month
too); Ebay; Amazon. Yohimbe; customers conditions.
supply for 288 $
testimonials.
L-Arginine; Eleutherococcus; Yohimbe bark extract;
nettle; ginseng; folate; micronized DHEA; Muira puama; 59.95 $ per box; Stated as: “all natural; assures
Online suppliers Legal controversies;
pregnenolone; zinc; black pepper; Piper longum; ginger. six-month supply penis enlargement in addition
Extenze (orders can be placed reported increased heart
Cnidium monnieri; Astragalus: Xanthoparmelia Scabrosa; for 305.95 $; to increasing sexual stamina;
http://www.extenze.net by fax, phone, and mail rates, agitation, and
boron; GABA; velvet deer antler; horny goat weed; ten-month supply customers testimonials;
too); Ebay. nervousness.
damiana; pumpkin; licorice extract; Ho Shou Wu for 499.95 $ money back guarantee.”
extract.
Stated as: “works in 10–30
39.95 $ per box; minutes and lasts for up to 4 Slight headache
Eurycoma longifolia; Flos catharmi; Rizoma Curcumae six-month supply Online suppliers days; money back guarantee; reported; expensive;
Maxidus
longae; Gingko biloba; Herba Epimedii; Herba for 399.75 $; (orders can be placed 100% natural; it can be taken clinical tests carried out
http://www.maxidus-
Cistanches; Astragalus membranaceus; Momordica twelve-month by fax, phone, and mail by people with heart or are shown for only one
pill.com/
charantia L (Ku Gua). supply for too); Ebay. prostate problems, ingredient (Eurycoma
479.40 $ hypertension, diabetes; it can longifolia).
be used by women too.”
29.16 £ per box;
six-month supply Online suppliers Stated as: “all natural; works Legal issues; interaction
Orexis Tribulus terrestris; Epimedium sagittatum; Muira
for 135.00 £; (orders can be placed within 45 minutes; customers with antidepressants,
http://www.orexis- puama; Panax ginseng; Catuaba bark extract; damiana;
twelve-month by fax, phone, and mail testimonials; money back diuretics, and high blood
pills.co.uk Yohimbe extract.
supply for too); Ebay. guarantee.” pressure medications.
262.50 £
59.95 $ per box; Reported nausea,
Stated as “all natural; no side
six-month supply Online suppliers hypertension; increased
Pro Solution Pills Solidilin; Korean ginseng; Butea superba; Momordica; effects; multiple orgasms per
for 289.95 $; (orders can be placed heart rate, dizziness; it
http://www.prosolu- apigenin; Amla; Arjuna; Cordyceps; zinc oxide: reishi sexual encounter; customers
twelve-month by fax, phone, and needs 5-6 months before
tionpills.com/ mushroom; Curculigo; drilizen; bladderwrack. testimonials; money back
supply for mail); Ebay; Amazon. the user notices the
guarantee.”
399.95 $ desired results.
BioMed Research International
 Table 1: Continued.
Side
Effects/declared advantages effects/disadvantages
BioMed Research International

Brand name Ingredients Cost Availability

from anecdotal online reports from anecdotal online
reports
Stated as “natural vitamins,
Online suppliers Reported nausea,
Horny goat weed; maca root; saw palmetto; Tongkat Ali; 34.97 $ per box; minerals and herbs”;
Provigro (orders can be placed dizziness, and vomiting;
Mucuna pruriens 10% L-dopa; Muira puama; L-arginine; three-month customers testimonials;
http://www.provigro.com by fax, phone, and it may take up to six
Panax ginseng. supply for 57.80 $ money back guarantee; it does
mail). months to work.
not contain Yohimbe.
Stated as a “climax enhancer,”
Online suppliers No permanent results;
Quantum Pills L-arginine; L-lysine HCL; maca root; Muira puama; 44.95 $ per box; assures increase in ejaculation
(orders can be placed no scientific proofs and
http://www.quantumpills Swedish flower pollen extract; horny goat weed; Catuaba six-month supply volume; natural; money back
by fax, phone, and mail no adequate ingredients
.com bark; Gingko biloba; zinc oxide. for 189.95 $ guarantee; customers
too). explanation.
testimonials.
Bioperine; copper chelate; creatine; Cuscuta seed; Presented as “all natural;
Online suppliers
Gingko biloba; green tea extract; Hawthorn berries; 39.95 $ per box; money back guarantee; At least one month for
Sinrex (orders can be placed
Epunedum Sagitum; inosine; L-arginine; maca; omega 3; six-month supply customers testimonials; semen initial results; possible
http://www.sinrex.com by fax, phone, and mail
saw palmetto; Siberian ginseng; soy proteins; Tribulus for 199.95 $ volume and orgasm allergies to ingredients.
too); Ebay.
terrestris; vitamin E. intensifier.”
Vitamin E; vitamin B3; horny goat weed; hawthorn
Two-month Online suppliers Natural; “Lasting increase of
berry; damiana; Muira puama; Gingko biloba; Chinese
Sizepro supply for 99.95 $; (orders can be placed penis thickness and size;
ginseng; Tribulus fruit extract; Catuaba bark; saw
http://www.sizepro.com six-month supply by fax, phone, and mail money back guarantee;
palmetto; inosine; L-arginine; oat straw; cayenne fruit;
for 245.95 $ too); Ebay. customers testimonials.”
soy protein.
Online suppliers Ingredients are not fully
(orders can be placed listed nor explained in
Not completely listed. Vazomyne includes L-arginine, 39.99 $ per box; Presented as: “natural; money
Vazomyne by fax, phone, and mail details; “It should not be
saw palmetto, Gingko biloba, damiana, Polygonum three-month back guarantee; customers
http://www.vazomyne.net too); Ebay.; Amazon taken in case of heart or
multiflorum, nettle leaf, Muira puama. supply for 99.98 $ testimonials.”
(currently not thyroid problems; will
available). not increase penis size.”
5
6 BioMed Research International

Urological Association (AUA) has concluded that the data medicines for high blood pressure, tricyclic antidepressants, or
available on Yohimbine do not allow it to be recommended phenothiazines (a group of medicines used mostly for mental
as standard treatment in erectile dysfunction particularly not health conditions such as schizophrenia). People with kidney
in organic aetiology [29]. International Society for Sexual problems and people with psychiatric conditions should not use
Medicine (ISSM) Standards Committee has recently stated Yohimbe” [34]. In 1985, Linden et al. have reported a case
“if yohimbine has any potential indications for use in ED of a 16-year-old girl who experienced an acute dissociative
management, it would be among nonorganic ED; apart from reaction accompanied by weakness, paraesthesia, incoordi-
ED, yohimbine has shown a limited efficacy in the treatment of nation, anxiety, headache, and chest pain after the ingestion
premature ejaculation” [21]. of an aphrodisiac called “yo-yo,” which has been later iden-
tified as yohimbine [36]. Acute neurotoxic effects related to
3.1.5. Safety. The side effects of yohimbine include high the ingestion of yohimbine-containing products have been
blood pressure, increased heart rate, manic reactions, bron- reported by Giampreti et al., who has reported the case of a 37-
chospasm, palpitations, insomnia, anxiety, irritability, shiver- year-old bodybuilder presented with malaise, vomiting, loss
ing, sweating, nausea, flushing, and headaches which all can of consciousness, and repeated seizures after ingestion of 5 g
be attributed to its central adrenergic activity [26, 30]. of yohimbine during a competition [37].

3.1.6. Case Reports Concerning Safety of Yohimbine. Adverse 3.2. Maca

events mostly due to self-administration of yohimbine have
3.2.1. Source and Preparations. Maca (Lepidium meyenii) is
been reported since 1980s. In 1993, Sandler and Aronson have
a Peruvian plant, which belongs to the Brassicaceae family.
described the development of progressive renal failure, cuta-
It grows in central Andes at more than 4000 m altitude; it
neous eruption, and a lupus-like syndrome in a 42-year-old
is constituted of a flat overground portion and underground
Afro-American man following yohimbine use [31]. Myers has
hypocotyl and roots. Hypocotyl colour allows the distinction
reported a case of refractory priapism in a 42-year-old HIV
of three different varieties: white, yellow, and black maca.
infected and depressed man who self-administered a product
Naturally dried hypocotyls have been used for centuries by
containing yohimbine to treat his erectile dysfunction and
native Andean populations as aphrodisiac, energizer, and
was subsequently admitted to emergency department with
enhancers of fertility and sexual function [38]. With the
a 20-hour lasting erection which required insertion of a
advent of Internet, maca has become a common ingredient
proximal corpus cavernosum to spongiosum shunt (Quackles
of sexual enhancer products available worldwide.
shunt) [32]. According to California Poison Control System,
238 cases of adverse reactions after yohimbine consump-
tion have been identified within a 7-year period (2000– 3.2.2. Active Ingredients and Mechanism of Action. Maca
2006): most commonly reported adverse events have been extracts have been shown to contain benzyl glucosino-
gastrointestinal distress, tachycardia, anxiety, agitation, and lates and polyphenols, (1R,3S)-1-methyl-1,2,3,4-tetrahydro-𝛽-
hypertension [33]. US National Institute of Health also warns carboline-3-carboxylic acid (MTCA), and p-methoxybenzyl
consumers about taking yohimbine supplements if they suffer isothiocyanate among many other chemicals [39]. The mech-
from schizophrenia, anxiety, depression, or posttraumatic anism of action of maca in altering sexual behaviour is
stress disorder [34]. Additional situation of emergency has unknown.
been reported in Amman where the public corporation of the
food and the medicine warned the citizens about the use of 3.2.3. Pharmacokinetics. No information could be found
some unlicensed sexual stimulants, such as yohimbine, for related to the pharmacokinetics properties of Maca.
its inclusion of poisonous substance strychnine that caused
convulsions, hallucinations, and heart and kidney failure [35]. 3.2.4. Efficacy. Zheng et al. reported increased sexual
More recently, Yohimbine was detected in a product labelled behaviour in male rats and mice and decreased latency to
as OxyELITE Pro and sold online as slimming pills. This erection in testes-removed rats following oral administration
caused the hospitalisation of two female patients aged 34 and of lipid extracts of maca roots [40]. Cicero et al. demonstrated
21 in Hong Kong for acute hepatitis symptoms. As a result, the that sexual behavioural activity as well as locomotor activity
Department of Health opened an investigation and appealed was increased in rats treated with pulverised maca root orally
to members of the public not to buy or consume the product [41]. In a further study, the same group has demonstrated
[30]. that the hexanic extract of maca had more effect on sexual
behaviour of rats than the methanolic and chloroformic
3.1.7. Psychological Safety. As mentioned above, anxiety and extracts [42]. Lentz et al. measured ejaculatory and mounting
agitation are among the most common side effects of yohim- behaviour and postejaculatory intervals in rats treated with
bine or yohimbine-containing products [33]. US National maca orally for 30 days. They found that maca had only a
Institute of Health warns consumers about taking yohimbine small effect on sexual behaviour and locomotor activity but
or Yohimbe supplements with some of the antidepressants no effect on anxiety [43].
and antipsychosis drugs: “People should not combine Yohimbe The studies with maca on human subjects were reviewed
with monoamine oxidase (MAO) inhibitors as effects may be in 2010 [44]. Four randomised clinical trials met the authors’
additive. Yohimbe should be used with caution when taken with inclusion criteria: two trials suggested a significant positive
BioMed Research International 7

Table 2: Subjective reports of forums’ users about sexual enhancers side effects.

(i) Head rush

(ii) Anxiety
(iii) Feeling of blood flowing through skin/feeling blood warming
(iv) Tinnitus
http://www.drugs-forum.com/forum/showthread.php?t=77902
Gingko (i) Increased heart rate
biloba (ii) Dizziness
(iii) Chest pain
(iv) Phosphenes
http://forum.lef.org/default.aspx?f=35&m=16405

Anxiety and nausea (Ginkgo tea consumption while assuming clomipramine)

http://www.socialanxietysupport.com/forum/f11/ginkgo-biloba-197737/
(i) Altered menstrual cycle (length modifications, anovulatory cycles)
(ii) Painful intestinal cramps
(iii) Severe gastritis
(iv) Increased blood pressure
(v) Moodiness
http://archive.tcoyf.com/forums/t/119232.aspx
(i) Increased heart rate
Maca (ii) Insomnia
(iii) Depression/anxiety
(iv) Worse premenstrual syndrome symptoms
(v) Acne breakout
http://www.highonhealth.org/what-nobody-tells-you-about-maca-root-powder-dangers-and-side-effects/

Mood swings
http://babyandbump.momtastic.com/pregnancy-tests/419834-gallery-o-tests-1075.html#post9282851
(i) Fever
(ii) Increased heart rate
Horny
(iii) Aggressiveness
goat weed
(iv) Irritability
http://www.muscleandstrength.com/supplements/ingredients/horny-goat-weed.html#5

effect of maca on sexual dysfunction or sexual desire in assumption that MTCA is deactivated during the boiling
healthy postmenopausal women [45] or healthy adult men process of the maca roots [53]. MTCA-like compounds
[46], while the other trial failed to show any effects on have also been suggested to be associated with craving
healthy cyclists [47]. A further trial assessed the effects behaviour, which is common in addictions [51]. Side effects
of maca in patients with erectile dysfunction using the subjectively reported by fora users were altered menstrual
International Index of Erectile Function Questionnaire and cycles, moodiness, cramps, gastritis, and insomnia (see
showed significant effects [48]. Lee et al. have reviewed the Table 2).
literature to determine maca’s possible effects on menopausal
symptoms and confirmed the inadequacy of the present
data to clearly state efficacy and safety [49]. An overview 3.3. Horny Goat Weed
of systematic reviews on various complementary medicine
products for sexual dysfunction in elderly patients has found 3.3.1. Source and Preparations. Epimedium is a genus of plants
that the evidence for maca was insufficient [50]. of the Berberidaceae family, including more than 50 species.
Among the most frequently used in sexual enhancer products
are Epimedium grandiflorum and Epimedium sagittatum.
3.2.5. Safety. Piacente et al. (2002) have shown the Epimedium grandiflorum is commonly known as horny goat
existence of 1R,3S-1-methyl-1,2,3,4-tetrahydro-𝛽-carboline- weed named after the legendary discovery of its aphrodisiac
3-carboxylic acid (MTCA) in the extracts of maca. MTCA properties, attributed to a Chinese goat herder who noticed
has been suggested to be an inhibitor of the monoamine an increased sexual activity in his herd after they ate the
oxidase (MAO) enzyme and is a comutagenic or a precursor plant’s leaves [54], and sold online with various names includ-
to mutagenic compounds [51]. Because of these potential ing ViaXtreme, which also contains undeclared sildenafil [17].
mutagenic properties of MTCA, the French Agency for
Sanitary Security warned consumers of powdered maca root
about possible health risks from its ingestion [52]. These 3.3.2. Active Ingredients and Mechanism of Action. The active
findings have been disputed by others based on the ingredient of horny goat weed has been suggested to be
8 BioMed Research International

icariin, a flavonol glycoside [55]. Icariin and its derivatives contains flavonoid glycosides, mainly composed of kaemp-
have been suggested to increase NO synthesis in the penis ferol, quercetin glucorhamnoside esters, and terpenes of
[56], inhibit PDE5 in cavernosal smooth muscle [57–59], have ginkgolides and bilobalides. These ingredients have been
positive neurotrophic effect on nitrergic nerves [56], enhance suggested to have the ability to inhibit MAO enzyme and
smooth muscle proliferation [60], and decrease advanced uptake of certain neurotransmitters such as noradrenaline
glycation endproduct formation [60] and mimic endogenous and serotonin in the central nervous system [72]. A recent
androgens [61]. Icariin has also been suggested to have anti- meta-analysis of 28 clinical studies with Ginkgo has found no
inflammatory, antiosteoporotic, and neuroprotective proper- significant effect on cognitive function [73]. Ginkgo extracts
ties [62–64]. have been suggested to improve sexual function by improving
the blood flow to the brain as well as to the genital organs.
3.3.3. Pharmacokinetics. Icariin has been shown to have low These extracts have also been suggested to increase NO
oral bioavailability, poor absorption, and short plasma half- bioavailability, which may have positive impact on sexual
life [65]. Because of these unfavourable pharmacokinetics function [74].
profiles, liposome encapsulated formulations of icariin are
being developed [66].
3.4.3. Pharmacokinetics. Extracts of Ginkgo are a mixture
of substances with a wide variety of physical and chemical
3.3.4. Efficacy. Although icariin has been shown to be effi- properties and activities. A recent review on the pharma-
cacious in treatment of erectile dysfunction in aged [67], cokinetic properties of these substances concluded that the
diabetic [68], and castrated [69] animal models, it has not available pharmacokinetic data are rare and more studies
been tested in any randomised clinical trial. need to be conducted [75]. It is generally accepted that
Ginkgo extract is well absorbed in humans, rats, and rabbits
3.3.5. Safety. No long-term toxicity study has been conducted after oral administration [75].
using horny goat weed (or icariin) in any animal species.
Partin and Pushkin have presented a case of a 66-year-old
man with a history of cardiovascular disease who, after two 3.4.4. Efficacy. Ginkgo extracts have been tested as a treat-
weeks of consumption of herbal sexual enhancer containing ment for antidepressant-induced sexual dysfunction, which
horny goat weed, was admitted to hospital with a new- is a common side effect in depressive disorder therapy,
onset tachyarrhythmia and hypomanic symptoms (sexual especially when using selective serotonin reuptake inhibitors
and verbal inappropriate behaviour, irritable mood, and (SSRIs). Despite the initial positive effect on sexual function
hyperverbal speech). The patient needed to undergo an based on various case reports [76], two randomised placebo
electric cardioversion and to be treated with a therapy based controlled trials have found no significant benefit on sexual
on olanzapine and lorazepam [70]. Metz et al. reported a case function with Ginkgo extracts [77, 78]. Although Ginkgo
of a painful vasculitic rash in a 77-year-old man, who had extracts have been suggested for the treatment of female sex-
started a treatment with Ginkgo biloba and horny goat weed ual arousal disorders [79], no placebo controlled randomised
tablets four days before. The man improved after three days trial has been reported.
as an inpatient, with the suspension of the herbal supplement
[71].
3.4.5. Safety. A recent long-term study by National Tox-
icology Program has demonstrated that oral administra-
3.3.6. Psychological Safety. As mentioned above, one case tion of Ginkgo extract caused cancer of thyroid gland and
has been reported with hypomanic symptoms combined liver, atrophy of the olfactory epithelium, nephropathy, and
with tachyarrhythmia [70]. During the online monitoring mononuclear cell leukaemia in rats and mice [80]. One of
of discussion fora, several cases of aggressive behaviour and the major ingredients, quercetin, is a known mutagen [81].
irritability were noted (see Table 2). In reviews of the efficacy and safety of Ginkgo extracts in
human subjects, no serious side effects were reported in
3.4. Ginkgo biloba clinical trials and side effects were similar to those seen in
the placebo groups [82]. Ginkgo extract has been suggested
3.4.1. Source and Preparations. Ginkgo biloba is a living fossil to affect platelet aggregation, which may not only be useful in
tree, belonging to Ginkgoaceae family. Typically grown in prevention of pathological events as thrombosis, but may also
China, Ginkgo plants are tall, normally reaching 20–35 m of cause spontaneous bleeding in healthy individuals or patients
height, with fan-shaped leaves. The extracts obtained from treated with anticoagulants such as warfarin and aspirin [83].
Ginkgo leaves contain flavonoid glycosides (e.g., myricetin There have been case reports of subdural hematoma or cere-
and quercetin) and terpenoids (e.g., ginkgolides and bilob- bral haemorrhage with headache, confusion, blurred vision,
alides) and have been used for centuries in traditional nausea, and vomiting after Ginkgo administration [84]. Some
Chinese medicine, particularly for memory enhancement Ginkgo extracts may contain 4󸀠 -O-methylpyridoxine, which
and blood flow improvement. is a neurotoxin also known as “ginkgotoxin.” Ginkgotoxin
poisoning is characterised by epileptic convulsions, vomiting,
3.4.2. Active Ingredients and Mechanism of Action. The most unconsciousness, and irritability, which may be fatal if not
commonly used Ginkgo biloba extract is EGb761, which promptly treated [85].
BioMed Research International 9

3.4.6. Psychological Safety. Ginkgo may interact with other Ptychopetalum olacoides (Muira puama), also called
medications particularly those acting on the central ner- “potency wood,” grows primarily in Brazil. Popular belief
vous system. It may decrease (alprazolam, citalopram, and claims that it can improve sexual function especially in old
diazepam) or increase (clozapine, methadone, olanzapine, men [7]. This herb may be found in plant markets or in
and fluvoxamine) effects and side effects of such drugs; it may herbal formulations, usually sold to increase physical, mental,
also induce hypomanic symptoms when taken together with and/or sexual performance. Few clinical studies have so far
St. John’s wort, fluoxetine, and melatonin [86]. Anxiety was examined the prosexual effects of Muira puama. Waynberg
the most common psychological effect reported by Ginkgo reported in 1994 that 60% of men with low libido have
users at Internet discussion fora (see Table 2). reported increased sexual desire and 50% of men with poor
erection have reported improved erectile function following
3.5. Other Substances. Velvet antler has been used in tradi- Muira puama administration [99]. Another study has shown
tional Chinese medicine for centuries, mainly as an ener- that Muira puama improved sexual desire, sexual fantasies,
gizer and to treat joint pain, cardiovascular diseases, and and the ability to achieve orgasm in 65% of women with prior
impotence. The name refers to the velvety skin covering sexual dysfunction [100].
growing antlers of male elk, deer, and moose, which can be
removed with no harm for the animal. In western countries,
3.5.1. Synthetic Substances. Among synthetic substances used
elks and deer are anesthetized with xylazine or lidocaine
as sexual enhancers, well-known examples include MDPV
before having velvet removed; this practice had determined
(methylenedioxypyrovalerone), known as “Ivory Wave,” 2C-
an ethical controversy among veterinarians, to find balance
B, and mephedrone (4-methylmethcathinone), also called
between animal welfare and food safety (not being known
with the nickname of “Miaow Miaow.” The aforementioned
drugs’ withdrawal time for velvet) [87]. The most relevant
substances have stimulating and aphrodisiac properties sim-
issue currently identified for elk or deer velvet antler con-
ilar to amphetamines and MDMA (“Ecstasy”). Because of
sumption is related to an infectious neurodegenerative prion
their partially synthetic and partially natural composition,
disease known as chronic wasting disease (CWS). The core
some sexual enhancer substances are defined ”mixed.” Lust
symptoms of this encephalopathy are notable weight loss and
is a stimulant made up of Sida cordifolia extract. This
behavioural abnormalities (e.g., progressive hyperexcitabil-
plant contains L-ephedrine, which is a natural amphetamine
ity) [88]. Though currently interspecies transmission has not
acting on both central and peripheral nervous systems. The
been yet demonstrated, the presence of CWS prions in animal
effects of L-ephedrine are mainly linked to an expansion of
muscle, fat, glands, and antler velvet may expose humans to
sexual perception [101]. Another component of Lust is saw
infection by handling or consumption of diseased cervids
palmetto (Serenoa repens, Serenoa serrulata), another natural
products [89, 90]. No psychoactive properties have been yet
aphrodisiac; the plant’s berries are used to increase muscular
demonstrated for velvet antler.
power and libido. The last Lust component is L-arginine, an
Turnera diffusa, also known as “damiana,” is a small shrub
amino acid believed to have positive effects on impotence and
common in Mexico, Central and South America, and the
infertility [102].
Caribbean. Turnera diffusa leaf is traditionally thought to be
stimulant, aphrodisiac, tonic, diuretic, laxative, and useful to
treat menstrual and pregnancy disorders [91]. Aphrodisiac 4. Discussion and Conclusions
and psychoactive properties have been ascribed for centuries
to damiana. Its leaves are usually boiled to make an infusion The exponential increase in the use of unlicensed sexual
with the aim of intensifying sexual sensations; moreover, enhancing products, often characterized by the undeclared
when smoked, damiana leaves may produce similar effects presence of psychoactive agents, represents a serious chal-
to marijuana [92]. It has recently been found in products lenge both from clinical and public health point of view,
advertised on the Internet to increase sensuality, especially despite their large and uncontrolled distribution on the
among women [16], as legal and safer alternative to Cannabis Internet, including e-commerce websites (Ebay, Amazon).
and sold as “mystical incenses” [93, 94]. These also often It has been estimated that approximately six million men
contain synthetic cannabinoids such as JWH-18, JWH-73, in the EU purchase these products from the Internet [103].
and HU210 that may cause severe intoxication and death Possible reasons behind such a risky behaviour include (a)
[95, 96]. the embarrassment to speak with a doctor, (b) the thought
Nymphaea caerulea is a lotus flower belonging to that buying them online would be the fastest and cheapest
Nymphaeaceae family. It is also known as “Blue Water Lily” way to solve the problem, (c) curiosity, (d) peer-pressure,
or “Egyptian Lotus” and it is sold as a powder named “Blue and (e) the increase of sexual confidence and performance
Lotus.” The flower has been used by ancient Egyptians not [5].
only to enhance sex drive and to improve sexual performance, In a performance-based society, the e-commerce of food
but also to stimulate blood flow and as an antiageing treat- and herbal supplements sold for sexual enhancing purposes
ment. It has also recreational potential when added to wine is becoming a highly profitable market as a result of low-
or smoked, due to its psychoactive properties [97]. The flower cost manufacturing capacity in countries such as China and
may indeed induce both narcotic and euphoric effects and, India as well as the globalization of free trade and the Internet
if taken in large amounts, may cause slightly hallucinogenic as a platform for rapid distribution [94, 103, 104]. In this
symptoms [98]. context, unscrupulous manufacturers/retailers are exploiting
10 BioMed Research International

the common belief that “natural” products are healthier Conflict of Interests
alternatives to pharmaceutical treatments and infiltrate unde-
clared harmful psychoactive substances in their products The authors declare that there is no conflict of interests
[5]. This represents a growing public health threat, which is regarding the publication of this paper.
putting the population at risk. The frequent occurrence of side
effects and the potential induction of symptoms of psychiatric Acknowledgments
interest, such as mood elevation, anxiety, hallucinations, and
other psychotic symptoms, are issues that need to be clarified Authors would like to acknowledge the contribution of the
and constantly monitored at the international level [105, 106]. Public Health Agency of Canada and the World Health
The possible impact on subjects with psychiatric disorders, Organization (WHO) for granting access to the GPHIN
usually at risk for sexual disjunctions and therefore possible database as well as the Canadian Centre on Substance Abuse
consumers, may be devastating. (CCSA).
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