Substances purported to beextracts from the yohimbe tree have been marketed asdietary supplements for various purposes, especially forerectile dysfunction, but they contain highly variable amounts of yohimbine, if any; no publishedclinical evidence supports their efficacy for treating sexual dysfunction or any disease.[3][4][5]
In the United States, it is illegal to market anover-the-counter (OTC) supplement product containing yohimbine as a treatment for any supposed health effect without having approval from theFood and Drug Administration (FDA).[3][6][7] In the United Kingdom, yohimbine is an unlicensed drug, rarely and specificallycompounded as a"prescription-only medicine", while yohimbine herbal supplements are banned from manufacturing as dangerous substances.[8]
In 2022, theTennessee Poison Center warned that use of yohimbine supplements may have fatal effects due to the possibility for high, unregulated amounts of yohimbine inover-the-counter (OTC) supplement products.[9] Due to inaccurate product labeling and the potential for seriousadverse effects, yohimbine supplements have been banned in many countries.[3] Use of such products has been associated with cardiovascular problems andseizures.[3][9]
TheEuropean Food Safety Authority Panel on Food Additives determined that it was not possible to conclude about the safety or to establish a health-based guidance value for yohimbine in supplement products.[5]: 38 They wrote:
Overall the missing information include[s] quantitative data on the composition and specifications of yohimbe bark and its preparations used in food and food supplements covering other alkaloids besides yohimbine, data on the bioavailability of active ingredients from the yohimbe bark extract and data on the toxicity of well specified individual preparations of yohimbe bark and the major yohimbe bark alkaloids, especially regarding subchronic toxicity, genotoxicity and reproductive toxicity.
One study found that samples of brands sold in American brick-and-mortar stores contained highly variable amounts of yohimbine, with some brands of "yohimbe" not containing yohimbine from theP. johimbe tree, and other products containing no yohimbine at all.[10]: 368 Labeling claims were often misleading.[10]: 368
In analyses by other laboratories for products sold in the US, in other countries, and on the internet, highly variable content levels of yohimbine were revealed.[11][12][13][14][15]
Yohimbe sold in markets inWest Africa where the tree grows may beadulterated with other species of the genusPausinystalia, which contain little yohimbine.[16] The amounts of alkaloid found even in genuineP. johimbe bark vary considerably, depending on the source of the bark (roots, stem, branches, height).[17]
During the 21st century, the FDA issued multiplewarning letters to American manufacturers of yohimbe supplements for making false health claims and interstate marketing of such products as misbranded, unapproved drugs.[7][10]
There is no evidence that yohimbe herbal supplements are effective as anaphrodisiac or as an OTC replacement forsildenafil (Viagra) for erectile dysfunction.[3][4] Prescriptions for it are rare, and most United States pharmaceutical manufacturers have discontinued production of prescription capsules and tablets.[10]: 357–8 In Canada during 2019, yohimbe products were removed from the market out of concern their use for sexual enhancement, weight loss, or as an exercise aid would pose serious health risks.[18]
It has been studied as a potential treatment for erectile dysfunction, but there is insufficient evidence to rate its effectiveness.[3][19][20] Nevertheless, the quantity of yohimbine in dietary supplements, often advertised as promoting sexual function, has been found to overlap with prescription doses of yohimbine.[6]
In the United Kingdom, supplement preparations of yohimbe are banned as introducing a considerable risk for adverse effects.[8] The drug form of yohimbine, calledYohimbine hydrochloride (yohimbine HCl)[21] – which is not licensed as a medicine for any condition – may rarely and specifically be compounded by apharmacist ("chemist" in the UK) as aprescription-only medicine for treatingdelayed ejaculation[22] – a formulation that cannot be sold, supplied or advertised as a retail product.[23]
Yohimbine has been used to treatfemale sexual dysfunction, but there are few reported clinical trials and these do not show it to be better than placebo.[24][25][26]
In the United States, "yohimbe" preparations are sold as dietary supplements for enhancinglibido, for weight loss and as aids for bodybuilding, but "there is virtually no published research on yohimbe which supports these or any other claims".[3][25]: 861
Yohimbine selectively blocks the pre-synapticα2-adrenergic receptors. Blockade of post-synaptic α2-adrenergic receptors causes only minorcorpus cavernosumsmooth muscle relaxation, due to the fact that the majority ofadrenoceptors in the corpus cavernosum are of the α1 type. Blockade of pre-synaptic α2-adrenergic receptors facilitates the release of several neurotransmitters in the central and peripheralnervous system—thus in the corpus cavernosum—such asnitric oxide andnorepinephrine. Whereas nitric oxide released in the corpus cavernosum is the major vasodilator contributing to the erectile process, norepinephrine is the major vasoconstrictor through stimulation ofα1-adrenergic receptors on the corpus cavernosum smooth muscle. Under physiologic conditions, however, nitric oxide attenuates norepinephrine vasoconstriction.[40]
Yohimbine binds to the a2 adrenergic receptor at a ratio of 40:1 and is the only a2 adrenergic receptor antagonist with noimidazoline receptor activity.[41]
Yohimbine should not be confused withyohimbe[42] but often is.[43] Yohimbe is the common English name for the tree speciesP. johimbe (also calledCorynanthe johimbe) and, by extension, the name of a medicinal preparation made from the bark of that tree, sold as anaphrodisiac.[44] In contrast, yohimbine is a pure alkaloid that can be isolated from yohimbe bark.
Yohimbine is just one of at least 55 indole alkaloids that have been isolated from the bark;[45] and, while it has been described as the most active of these,[10] it constitutes only 15% of the total alkaloid content.[25] Others includerauwolscine,corynanthine andajmalicine;[25] the bark also contains non-alkaloids about which virtually nothing is known.[25]
Yohimbe, thus a complex mixture, has been studied far less thoroughly than yohimbine, the pure compound.[25] Pharmaceutical grade yohimbine is usually presented as thehydrochloride,[5][25] which is more soluble.
The traditional source of yohimbine is the bark of the African treeP. johimbe. It has other uses, but the tree is sought out primarily for its bark; in practice, harvesting the bark kills the tree. Tree density is relatively low (average ≈ 4 harvestable trees/hectare). The high demand for medicines based on the bark has led to the tree's over-exploitation. The bark is traded in local markets and, because it is scarce, it is often adulterated with that of other species which contain little yohimbine.[16] The species is becoming endangered.[46]
Around the year 2000,Cameroon was shippingP. johimbe to Europe at the rate of about 100 tonnes annually. Most bark is collected illegally by local people who are paid 150CFA francs per kilo (about US$0.10 per pound) for delivery of pre-dried bark at the roadside. In practice they confuse and mix it withP. macroceras ("false yohimbe"), a species that contains little yohimbine.[47]
Aspidosperma quebracho-blanco is an unrelated tree whose common name isquebracho blanco.[48] It is found in large areas of central South America, particularly theGran Chaco, where it is often the dominant species in thecanopy.[49] It is one of the most widely distributed Argentine arboreal species.[50][51] Traditionally it was logged for fuel, timber and railway sleepers.[51] While in recent times cattle ranching and soya cultivation have led to considerable habitat loss,[52] and while there is stillillegal logging, no shortage of the bark is reported. The tree has not been described as endangered: a few members of the genusAspidosperma are on theIUCN Red List. but thequebracho blanco species is not one of them.[53]
In its bark an alkaloid is found which was given the name quebrachine. In 1914, two scientific papers claimed quebrachine was chemically identical to yohimbine.[54] This was disputed,[55] and the matter long remained in doubt.[56] However, in 1972, Effler and Effler using modern analytical techniques, includingmass spectrometry,UV absorption,IR absorption, andNMR, established that quebrachine and yohimbine are one and the same thing. They wrote:
While it was almost unthinkable in 1914 ... that the same alkaloid was formed in [completely] different plants, recent studies have shown that this is certainly the case for indole alkaloids.[57]
The term 'quebrachine' may be used as a synonym for yohimbine.[58][59][60][61][62]
Strictly speaking, wroteGeorge Barger, yohimbine should have been given the scientific namequebrachine, seeing that it was first isolated from the quebracho tree and first named in the scientific literature. However, the later work onP. yohimbe was better known.[54]
Yohimbe (Pausinystalia johimbe) is a tree that grows in western and centralAfrica;[64] yohimbine was named as originally extracted from the bark of yohimbe in 1896 by Adolph Spiegel[65] (but see§ Aspidosperma quebracho-blanco below). Yohimbe is used in folk medicine as anaphrodisiac. In 1900, it attracted scientific interest in Germany, where an initial report claimed that yohimbe exerted a strong aphrodisiacal effect in animals and humans.[25] Attention soon shifted from the plant to its active constituents, particularly yohimbine.[25] In 1943 the correct constitution of yohimbine was proposed by Witkop.[66] Fifteen years later, a team led byEugene van Tamelen used a 23-step synthesis to become the first persons to achieve the synthesis of yohimbine.[67][68][69]
There was a case in theWorld Anti-Doping Agency practice in 2007, when an athlete, who reportedly consumed Yohimbine prior to a given athletic event, was later tested positive for19-norandrosterone, which is a prohibited substance.[70] However, WADA did not yet list Yohimbine (which can come into a body via anenergy drink,[71] also in a form ofpre-workout supplement orfat burner[72]) as aprohibited substance, nor did it confirm that its use can increase the endogenous level of anabolic steroids, in particular of 19-norandrostenedione and testosterone.
Yohimbine has been used since the 1970s to reverse the effects of xylazine.[41] A 2011 preliminary study found thatintravenous yohimbine has slow elimination and a large distribution in horses.[41][76] Yohimbine is not commonly used in small animal medicine anymore but is still commonly used in large animal medicine to reverseα2 adrenergic receptor agonists such asxylazine.[41]
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^Raman V, Avula B, Galal AM, Wang YH, Khan IA (January 2013). "Microscopic and UPLC-UV-MS analyses of authentic and commercial yohimbe (Pausinystalia johimbe) bark samples".Journal of Natural Medicines.67 (1):42–50.doi:10.1007/s11418-012-0642-2.PMID22402817.S2CID11977944.Of 12 commercial samples tested, yohimbine was not detected in one; its presence in other samples was found to be in the range 0.1–0.91%.
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