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Yohimbe

Scientific Name(s): Pausinystalia yohimbe (K. Schum.) Pierre ex Beille.
Common Name(s): Aphrodien, Aphrodyne, Johimbi, Yocon, Yohimbe, Yohimbehe, Yohimbine

Clinical Overview

Use

Yohimbine has been used primarily in the treatment of sexual dysfunction, weight (body fat) loss, and xerostomia (dry mouth). It has also been used in studies investigating disorders including autonomic failure and orthostatic hypotension. Effects on the CNS including reductions in fear and increased impulsivity have been reported.

Dosing

Yohimbine 6 mg given 3 times a day has been used in xerostomia trials. A mean dose of 0.4 mg/kg body weight or 30 mg daily, and a maximum of 50 mg, has been used in erectile dysfunction studies. In studies investigating effects on body mass, yohimbine 20 mg daily has been used.

Contraindications

This drug should not be used in the presence of renal or hepatic dysfunction. Contraindicated in pregnancy.

Pregnancy/Lactation

Do not use during pregnancy or lactation.

Interactions

None well documented.

Adverse Reactions

Clinical trials report few serious adverse reactions. There are case reports of rash, lupus-like syndrome, bronchospasm, severe hypotension, dysrhythmia, heart failure, and death. Increased anxiety, irritability, and excitability have also been reported. Animal studies suggest yohimbine may increase motor activity and seizures at higher dosages. Yohimbe may precipitate psychoses in predisposed individuals.

Toxicology

Information is limited.

Botany

Yohimbe (P. yohimbe) is a tall evergreen tree that grows throughout the African nations of Cameroon, Gabon, and the Democratic Republic of the Congo.1 A synonym for yohimbine is Corynanthe johimbe.

History

The bark of the West African yohimbe tree is rich in the alkaloid yohimbine, and the crude bark has been used traditionally as an aphrodisiac. The bark has also been smoked as a hallucinogen and used in traditional medicine to treat angina and hypertension. The drug has been investigated for the treatment of organic and psychogenic erectile dysfunction.2

Chemistry

Authentic yohimbe bark may contain up to 6% total alkaloids, of which 10% to 15% is yohimbine. Other minor indole alkaloids include corynantheidine, beta-yohimbine, pseudoyohimbine, rauwolscine, coryanthine, and allo-yohimbine.3 A comparison of chromatograms of authentic P. yohimbe bark extracts with those of commercial products containing yohimbine found that many products contained measurable quantities of the alkaloid yohimbine, but had very little of the other alkaloids previously reported in the species. Concentrations of yohimbine in commercial products ranged from less than 0.1 to 489 parts per million (ppm) compared with 7,089 ppm in the authentic material.4 The alkaloid yohimbine also is obtained from Aspidosperma quebracho-blanco and Rauwolfia serpentina.

The salt yohimbine hydrochloride has been used in clinical studies, while the free base is usually found in yohimbe extract or bark. Qualitative and quantitative analyses of commercial products and yohimbe bark have been undertaken using high performance liquid chromatography, nonaqueous capillary electrophoresis, and gas chromatography-mass spectrometry.3, 5

Uses and Pharmacology

Body mass/muscle mass

Animal data

The availability of clinical trial data renders findings from recent animal studies largely irrelevant.

Clinical data

A systematic review of 3 high-quality clinical trials using yohimbine to reduce body weight found conflicting results and could not conclude that yohimbine use is effective.1 Studies evaluating the effect on body and muscle mass have also been inconclusive.6, 7 In a study among athletes, yohimbine 20 mg daily for 21 days had no effect on body mass or muscle mass, but did decrease body fat. No effect on exercise performance was found.7

CNS

Animal data

Studies in rodents have shown effects on the CNS, including reduced fear, with yohimbine administration.8

Clinical data

In a study conducted in 40 patients with social anxiety disorder, the use of yohimbine improved self-reported measures, but not clinician-rated outcomes.8 Similarly, in a small trial (n=24) improvements in claustrophobic symptoms were reported with yohimbine administration.9

Among healthy volunteers in another study, however, yohimbine increased panic symptoms10 A study evaluating the effect of yohimbine on impulsivity found increased risk for impulsive behaviour in healthy volunteers,11 while a further trial reported increased craving following cocaine-cue presentation,12 and drug-seeking behaviour13 among dependent individuals.

Erectile dysfunction

Animal data

Yohimbine may act by adrenergic blockade of alpha-2-adrenergic receptors in the corpus cavernosum and centrally in the serotonergic system. It has been investigated for use in treatment of sexual dysfunction.14

Clinical data

The American Urological Association (AUA) guidelines on the management of erectile dysfunction (2005) states that yohimbine is not recommended for the treatment of erectile dysfunction based on review of data and panel consensus.15

A number of meta-analyses published before the above-mentioned AUA guidelines were conducted on older clinical trials, all concluding that yohimbine was more effective than placebo in treating erectile dysfunction in most, but not all, men.14, 16, 17, 18 No serious adverse events were reported in the trials included in the meta-analyses. Limitations of the trials have been noted and include a lack of statistical power, reporting bias, and a strong placebo effect.14, 18

A more recent open-label study found yohimbine to be effective in managing anorgasmia (orgasmic dysfunction).19 Dosing was initiated at 20 mg, with 5 mg escalations to a maximum of 50 mg. A mean dose of 0.4 mg/kg body weight was determined.19 The development of tolerance was suggested by one reviewer.14

Syncope/orthostatic hypotension

Animal data

The availability of clinical trial data renders findings from recent animal studies largely irrelevant.

Clinical data

Yohimbine dilates blood vessels, thereby lowering blood pressure; however, its use as an antihypertensive agent has been abandoned.14 As a selective alpha-2-adrenergic antagonist, yohimbine has been used to test baroreflex-mediated bradycardia and the contribution of endogenous alpha-2-adrenergic blockade to baroreflex regulation in human studies.20, 21, 22, 23 The use of yohimbine in the management of syncope or orthostatic hypotension has, however, not been conclusively established.

Yohimbine increased norepinephrine, epinephrine, muscle sympathetic nerve activity, blood pressure, and heart rate in neurally-mediated syncope patients compared with baseline.20, 24 Other studies did not report increases in heart rate or blood pressure.21, 22 Yohimbine has been used in a study to evaluate symptoms of autonomic failure in patients with Parkinson disease, approximately 40% of whom exhibit orthostatic hypotension.25 Yohimbine was more effective than pyridostigmine at improving orthostatic hypotension in a study population that included multiple system atrophy, pure autonomic failure, and Parkinson disease.26

Xerostomia (dry mouth)

In animal studies and limited human trials, yohimbine increased salivary flow and countered the effects of drugs such as tricyclic antidepressants or neuroleptics that cause xerostomia.27, 28

Other uses

Yohimbine has been investigated for treatment of posttraumatic stress disorder,29 panic disorder,30 emotional stress response,31 pteromerhanophobia (fear of flying),32 and cancer.33

Dosing

Yohimbine 6 mg 3 times a day has been used in xerostomia trials.28 A mean dose of 0.4 mg/kg body weight or 30 mg daily, and a maximum of 50 mg, has been used in erectile dysfunction studies.17, 19 The development of tolerance has been suggested by one reviewer.14 In studies investigating effects on body mass, yohimbine 20 mg daily has been used.7

Pregnancy / Lactation

Do not use during pregnancy or lactation.

Interactions

Antianxiety agents: Yohimbine may diminish the therapeutic effect of antianxiety agents. Monitor therapy.34, 35, 36, 37

Antihypertensive agents: Yohimbine may diminish the antihypertensive effect of antihypertensives. Monitor therapy.34

Iobenguane radiopharmaceutical products: Yohimbine may diminish the therapeutic effect of iobenguane radiopharmaceutical products. Avoid combination.38, 39

Tricyclic antidepressants: Tricyclic antidepressants may increase the serum concentration of yohimbine. Monitor therapy.40, 41, 42, 43, 44, 45

Adverse Reactions

Clinical trials report few serious adverse events.14, 16, 46 Case reports exist of rash, lupus-like syndrome, bronchospasm, arrhythmias, and death associated with yohimbine consumption.47, 48, 49, 50 Increased anxiety, irritability, and excitability have also been reported.10, 51

Animal studies suggest yohimbine may increase motor activity and seizures at higher dosages, may cause CNS stimulation and paralysis, and may precipitate psychoses in predisposed individuals. Signs of yohimbine toxicity include severe hypotension, dysrhythmia, heart failure, and death.51

In the 2016 Scientific Statement by the American Heart Association regarding drugs that may cause or exacerbate heart failure, yohimbine has been recognized as a product with possibly harmful cardiovascular effects, such as hypertension due to increased norepinephrine via alpha2-adrenergic receptor antagonism, and may be harmful in patients with heart failure. The guideline statement noted that naturoceuticals are not recommended for the management of heart failure symptoms or for the secondary prevention of cardiovascular events, and that nutritional supplements are not recommended for the treatment of heart failure [Low-quality; Limited].52

Toxicology

The reproductive toxicology of yohimbine was investigated in rats. At high dosages, increases in the weight of seminal vesicles was noted, as well as decreases in sperm count and motility and increases in sperm abnormalities.53

References

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3. Zanolari B, Ndjoko K, Ioset JR, Marston A, Hostettmann K. Qualitative and quantitative determination of yohimbine in authentic yohimbe bark and in commercial aphrodisiacs by HPLC-UV-API/MS methods. Phytochem Anal. 2003;14(4):193-201.12892413
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