Yohimbine

Overview

Yohimbine, also known as quebrachine, is an indole alkaloid derived from the bark of the African tree Pausinystalia johimbe (yohimbe) and from the bark of the unrelated South American tree Aspidosperma quebracho-blanco. It is a veterinary drug used to reverse xylazine.[1][2] WP

Substances purported to be extracts from the yohimbe tree have been marketed as dietary supplements for various purposes, especially for erectile dysfunction, but they contain highly variable amounts of yohimbine, if any; no published clinical evidence supports their efficacy for treating sexual dysfunction or any disease.[1][2][3] WP

In the United States, it is illegal to market an over-the-counter (OTC) supplement product containing yohimbine as a treatment for any supposed health effect without having approval from the Food and Drug Administration (FDA). In the United Kingdom, yohimbine is an unlicensed drug, rarely and specifically compounded as a "prescription-only medicine", while yohimbine herbal supplements are banned from manufacturing as dangerous substances.[1][4][5][6] WP

Uses, dosage and effects

Sexual dysfunction

There is no evidence that yohimbe herbal supplements are effective as an aphrodisiac or as an OTC replacement for sildenafil (Viagra) for erectile dysfunction. Prescriptions for it are rare, and most United States pharmaceutical manufacturers have discontinued production of prescription capsules and tablets. 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.[1][2][4][7] WP

It has been studied as a potential treatment for erectile dysfunction, but there is insufficient evidence to rate its effectiveness. Nevertheless, the quantity of yohimbine in dietary supplements, often advertised as promoting sexual function, has been found to overlap with prescription doses of yohimbine.[1][4][8][9] WP

In the United Kingdom, supplement preparations of yohimbe are banned as introducing a considerable risk for adverse effects. The drug form of yohimbine, called Yohimbine hydrochloride (yohimbine HCl) – which is not licensed as a medicine for any condition – may rarely and specifically be compounded by a pharmacist ("chemist" in the UK) as a prescription-only medicine for treating delayed ejaculation – a formulation that cannot be sold, supplied or advertised as a retail product.[6][10][11][12] WP

Yohimbine has been used to treat female sexual dysfunction, but there are few reported clinical trials and these do not show it to be better than placebo.[13][14][15] WP

In the United States, "yohimbe" preparations are sold as dietary supplements for enhancing libido, for weight loss and as aids for bodybuilding, but "there is virtually no published research on yohimbe which supports these or any other claims".[1][14] WP

Other uses

Yohimbine has been used to increase peripheral blood flow and to dilate the pupil of the eye.[16] WP

Veterinary use

Yohimbine has been used since the 1970s to reverse the effects of xylazine. A 2011 preliminary study found that intravenous yohimbine has slow elimination and a large distribution in horses. Yohimbine is not commonly used in small animal medicine anymore but is still commonly used in large animal medicine to reverse α₂ adrenergic receptor agonists such as xylazine.[17][18] WP

Risks and side effects

Poison warning and variable content

In 2022, the Tennessee Poison Center warned that use of yohimbine supplements may have fatal effects due to the possibility for high, unregulated amounts of yohimbine in over-the-counter (OTC) supplement products. Due to inaccurate product labeling and the potential for serious adverse effects, yohimbine supplements have been banned in many countries. Use of such products has been associated with cardiovascular problems and seizures.[1][19] WP

The European 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. They wrote:[3] WP

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. WP

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 the P. johimbe tree, and other products containing no yohimbine at all. Labeling claims were often misleading.[4] WP

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.[20–24] WP

Yohimbe sold in markets in West Africa where the tree grows may be adulterated with other species of the genus Pausinystalia, which contain little yohimbine. The amounts of alkaloid found even in genuine P. johimbe bark vary considerably, depending on the source of the bark (roots, stem, branches, height).[25][26] WP

Adverse effects

Adverse effects of yohimbine in humans at high doses include hypertension (high blood pressure), tachycardia (rapid heartbeat), agitation, hypervigilance, anxiety, tremors, nausea, and urinary frequency. The drug is described as producing a psychoactive state of considerable anxiety along with tenseness, restlessness, and irritability and as being "extremely unpleasant", at least at the assessed doses. In animals, yohimbine likewise produces effects suggestive of severe anxiety. Yohimbine has been used in animals as a model of anxiety in the evaluation of novel anxiolytics.[1][2][27–30] WP

FDA warning letters

During the 21st century, the FDA issued multiple warning letters to American manufacturers of yohimbe supplements for making false health claims and interstate marketing of such products as misbranded, unapproved drugs.[4][5] WP

Interactions

Drug interactions

Yohimbine has extensive interactions with prescription drugs, some with severe health consequences, including sudden hypotension, irregular heart rate, heart failure, and death.[1][2][16] WP

Barbiturates and benzodiazepines can reduce the anxiety produced by yohimbine. Conversely, combination with imipramine, which is notably known to act as a norepinephrine reuptake inhibitor, has been reported to augment the restlessness and anxiety of yohimbine and to convert them into panic.[30] WP

Pharmacology

Pharmacology

Yohimbine has high affinity for the α₂-adrenergic receptor, moderate affinity for the α₁ receptor, 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1F, 5-HT2B, and dopamine D₂ receptors, and weak affinity for the 5-HT1E, 5-HT2A, 5-HT5A, 5-HT₇, and dopamine D₃ receptors. It behaves as an antagonist at α₁-adrenergic, α₂-adrenergic, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, and dopamine D₂, and as a partial agonist at 5-HT1A. Yohimbine interacts with serotonin and dopamine receptors in high concentrations.[31–36] WP⚠ A table follows this text in the source and is not copied here. Open the source to see it.

Yohimbine selectively blocks the pre-synaptic α₂-adrenergic receptors. Blockade of post-synaptic α₂-adrenergic receptors causes only minor corpus cavernosum smooth muscle relaxation, due to the fact that the majority of adrenoceptors 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 peripheral nervous system—thus in the corpus cavernosum—such as nitric oxide and norepinephrine. Whereas nitric oxide released in the corpus cavernosum is the major vasodilator contributing to the erectile process, norepinephrine is the major vasoconstrictor through stimulation of α₁-adrenergic receptors on the corpus cavernosum smooth muscle. Under physiologic conditions, however, nitric oxide attenuates norepinephrine vasoconstriction.[37] WP

Yohimbine binds to the a₂ adrenergic receptor at a ratio of 40:1 and is the only a₂ adrenergic receptor antagonist with no imidazoline receptor activity.[17] WP

Research

Post-traumatic stress disorder

Yohimbine has been studied as a way to improve the effects of exposure therapy in people with post-traumatic stress disorder (PTSD).[38][39][40] WP

History

History

Yohimbe (Pausinystalia johimbe) is a tree that grows in western and central Africa; yohimbine was named as originally extracted from the bark of yohimbe in 1896 by Adolph Spiegel (but see § Aspidosperma quebracho-blanco below). Yohimbe is used in folk medicine as an aphrodisiac. In 1900, it attracted scientific interest in Germany, where an initial report claimed that yohimbe exerted a strong aphrodisiacal effect in animals and humans. Attention soon shifted from the plant to its active constituents, particularly yohimbine. In 1943 the correct constitution of yohimbine was proposed by Witkop. Fifteen years later, a team led by Eugene van Tamelen used a 23-step synthesis to become the first persons to achieve the synthesis of yohimbine.[14][41–46] WP

Legal status

Doping in sport

There was a case in the World Anti-Doping Agency practice in 2007, when an athlete, who reportedly consumed Yohimbine prior to a given athletic event, was later tested positive for 19-norandrosterone, which is a prohibited substance. However, WADA did not yet list Yohimbine (which can come into a body via an energy drink, also in a form of pre-workout supplement or fat burner) as a prohibited substance, nor did it confirm that its use can increase the endogenous level of anabolic steroids, in particular of 19-norandrostenedione and testosterone.[47][48][49] WP

Chemistry

Formula

C21H26N2O3 PC

CAS number

146-48-5 PC

Molar mass (g/mol)

354.4 PC

IUPAC name (computed by PubChem)

methyl (1S,15R,18S,19R,20S)-18-hydroxy-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylate PC

SMILES

COC(=O)[C@H]1[C@H](CC[C@@H]2[C@@H]1C[C@H]3C4=C(CCN3C2)C5=CC=CC=C5N4)O PC

InChIKey

BLGXFZZNTVWLAY-SCYLSFHTSA-N PC

PubChem CID

8969

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

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49. Other Doping substances in dietary supplements

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