Yohimbe

Scientific Name(s): Pausinystalia yohimbe (K. Schum.) Pierre ex Beille. Family: Rubiaceae.

Common Name(s): Aphrodien , Aphrodyne , johimbi , Yocon , yohimbe , yohimbehe , yohimbine .

Uses

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 autonomic failure and orthostatic hypotension.

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 function impairment.

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

No data.

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 is 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

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 performance was found. 7

Erectile dysfunction

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. 8

Clinical data

A number of meta-analyses have been conducted on older clinical trials, all finding yohimbine to be more effective than placebo in treating erectile dysfunction in most, but not all, men. 8 , 9 , 10 , 11 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. 8 , 11

A more recent open-label study found yohimbine to be effective in managing anorgasmia (orgasmic dysfunction). 12 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. 12 The development of tolerance was suggested by one reviewer. 8

Syncope/orthostatic hypotension

Yohimbine dilates blood vessels, thereby lowering blood pressure; however, its use as an antihypertensive agent has been abandoned. 8 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. 13 , 14 , 15 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. 13 , 16 Other studies did not report increases in heart rate or blood pressure. 14 , 15 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. 17

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. 18 , 19

Other uses

Yohimbine has been investigated for treatment of posttraumatic stress disorder 20 and cancer. 21

Dosage

Yohimbine 6 mg 3 times a day has been used in xerostomia trials. 19 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. 10 , 12 The development of tolerance has been suggested by one reviewer. 8 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

Animal experiments suggest increased analgesic effect with morphine and ethanol, while a clinical study found increased anxiety and agitation among patients with Alzheimer disease receiving both yohimbine and physostigmine. 22 Yohimbine potentiated the effect of the anti-adrenergic agent clonidine in human studies. 16 , 18

Yohimbine may interact with tricyclic antidepressants, central alpha-adrenergic drugs, centrally acting sympathomimetics, monoamine oxidase inhibitors, and antimuscarinic drugs. However, clinical documentation of these effects is lacking. 23 , 24

Adverse Reactions

Clinical trials report few serious adverse events. 8 , 9 , 25 Case reports exist of rash, lupus-like syndrome, bronchospasm, arrhythmias, and death associated with yohimbine consumption. 26 , 27 , 28 , 29 Increased anxiety, irritability, and excitability have also been reported. 22

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. 22

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. 30

Bibliography

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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.
4. Betz JM, White KD, der Marderosian AH. Gas chromatographic determination of yohimbine in commercial yohimbe products. J AOAC Int . 1995;78(5):1189-1194.
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10. Vogt HJ, Brandl P, Kockott G, et al. Double-blind, placebo-controlled safety and efficacy trial with yohimbine hydrochloride in the treatment of nonorganic erectile dysfunction. Int J Impot Res . 1997;9(3):155-161.
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14. Wray DW, Raven PB, Sander M. Diminished baroreflex-induced vasoconstriction following alpha-2 adrenergic receptor blockade in humans. Auton Neurosci . 2008;138(1-2):114-117.
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