Health Care Professional Information

Scientific Name
Pausinystalia yohimbe, Corynanthe johimbe
Common Name

Yohimbe bark, yohimbine hydrochloride, johimbe, aphrodine, corynine, quebrachine

Clinical Summary

Yohimbe is derived from the bark of the yohimbe tree, an evergreen native to West Africa. It has been used as an aphrodisiac for several centuries. Marketed as a steroid substitute and for weight loss, yohimbe is also used with other supplements in formulas to enhance athletic performance.

The active component, an alkaloid called yohimbine, has been tested in clinical studies to treat sexual dysfunction in men and women (1) (2) (3) (4). It was prescribed as an oral treatment for erectile dysfunction (ED) prior to the approval of phosphodiesterase type 5 (PDE5) inhibitors. However, more recent analyses determined there is a lack of direct evidence regarding the efficacy and safety of oral yohimbine in nonorganic (psychogenic) ED, with no support for its use in organic ED (5) (6). In veterans with posttraumatic stress disorder, yohimbine increased acoustic startle reflex (7). A preliminary randomized trial suggests that it may be effective for improving presyncopal symptoms in patients with severe orthostatic hypotension (8). Other studies have noted its ability to attenuate pressor responses in patients with Parkinson’s disease and neurogenic orthostatic hypotension (9) (10). Preliminary studies of yohimbine on athletic performance (11) and xerostomia provide only limited additional information (12). Yohimbe products are among dietary supplements with the largest number of documented contraindications (13). They are also responsible for the most frequent toxic effects reported (14) and severe events requiring hospitalization (15).

Purported Uses
  • Athletic performance
  • Orthostatic hypotension
  • Salivation
  • Sexual dysfunction
  • Stimulant
  • Weight loss
Constituents
  • Indole alkaloids including yohimbine, ajmalicine, aspidofractine, corynanthine (16)
Mechanism of Action

Yohimbe’s effects on erectile dysfunction may result from the inhibition of presynaptic-α1-adrenoceptor activity in cavernous smooth muscle cells as well as its impact on nitric oxide (NO) and cGMP formation involving endothelium and endothelial NO synthase (eNOS) activity, which is testosterone-dependent (6) (17). It also has dilatory effect on genital blood vessels, enhanced genital tissue sensation, and increased reflex excitability in the sacral region (4). Yohimbine possesses endothelin-like actions and affects NO production in renal circulation (18), and exerts anxiogenic effects through the noradrenergic pathway, which activates the HPA stress axis (19). As an α2-adrenoreceptor antagonist, yohimbine enhances norepinephrine release, increases parasympathomimetic activity, and reduces sympathetic activity (15) (20) (21). Blocking of α2-adrenoreceptors also results in increased blood supply to cavernous body tissue and increased plasma levels of noradrenaline by increasing its release from the sympathetic nervous system (4) (21). In patients with orthostatic hypotension yohimbine produces a pressor effect by engaging residual sympathetic tone (8).

Pharmacokinetics

Yohimbine has a rapid onset due to its highly lipophilic property which assists its absorption and crossing of the blood-brain barrier in a short period of time. Peak plasma levels were observed within 10–45 min of oral administration. The average oral bioavailability is 33% (ranging from 7% to 87%). It is rapidly eliminated with a half-life of 0.58 h following oral intake (22). Other reports indicate plasma half-life between 0.25 and 2.5 h and prolonged effects that may last for >13 hours, which can be traced back to increased plasma norepinephrine (6). An average oral dose of 5–15 mg produces a therapeutic whole blood level range of 40–400 ng/mL. Overdoses leading to neurotoxic effects have been seen with blood concentrations up to 5,000 ng/mL (23). About 1% of administered yohimbine is excreted unchanged in urine, indicating predominantly hepatic clearance (6) (22).

Warnings

Yohimbine can potentially interact with numerous drugs causing severe adverse effects. Do not use if you have high blood pressure, heart disease, arrhythmias, Parkinson's disease, seizure disorders, kidney, thyroid, or liver disease, sexual organ inflammatory disorders, ulcers, or psychiatric disorders. Do not take with antidepressant medications or with foods containing high amounts of tyramine (such as cheese, red wine, liver), or with decongestants, diet aids, or phenylpropanolamine-containing products.  

Contraindications

Cardiovascular disease, hypertension, liver disease, kidney disease, posttraumatic stress disorder, anxiety, bipolar disorder, depression, mania, schizophrenia, benign prostate hypertrophy, pregnancy (6) (7) (13).

Adverse Reactions

Hypertension, anxiety, nervousness, nausea, dizziness, tachycardia, palpitations, insomnia, urinary frequency, diarrhea, manic symptoms (1) (6) (15).

Case reports
Fatalities following accidental yohimbine overdose:
Medical examiners attributed 2 unrelated fatalities to accidental acute yohimbine intoxication, due to substantial yohimbine blood concentrations (7,400 and 5,400 ng/mL) and in the absence of other significant positive findings for both cases (23).

Acute neurotoxic effects: Malaise, vomiting, loss of consciousness, and repeated seizures in a 39-year-old body builder following ingestion of yohimbine 5g. Glasgow Coma Score indicated the need for orotracheal intubation. Symptoms subsided 12 h posttreatment with furosemide, labetalol, clonidine, and urapidil as well as gastrointestinal decontamination (24).

Erythrodermic skin eruption, progressive renal failure, and lupus-like syndrome: In a 42-year-old black man following treatment with yohimbine. Patient was admitted and received aggressive hydration, Eucerin cream with 1% hydrocortisone cream for the entire body and betamethasone valerate 0.1 % cream for hands. Patient was discharged after 2 weeks with symptom resolution, although he was readmitted 4 months later for additional clinical presentations (25).

Severe priapism: In a 42-year-old man with complex medical history after ingestion of yohimbe extract. Treatment involved insertion of a proximal cavernosal spongiosum shunt (26).

Herb-Drug Interactions
  • Antianxiety agents: Yohimbine may reduce their therapeutic effects (27).
  • Antidepressants: Yohimbine may augment side effects (28).
  • Antihypertensives: Yohimbine may diminish their effects (8).
  • Bupropion: Coingestion with yohimbe resulted in toxic effects (14).
  • CYP2D6 substrate drugs: Yohimbine inhibits CYP2D6 and may therefore affect the intracellular concentration of drugs metabolized by these enzymes (29).
  • Opioids: May induce withdrawal and anxiety symptoms (30).
Literature Summary and Critique

Shibao C, et al. Comparative efficacy of yohimbine against pyridostigmine for the treatment of orthostatic hypotension in autonomic failure. Hypertension. 2010;56:847-851.
In this single-blind, randomized, placebo-controlled, crossover trial, the use of pyridostigmine 60 mg and yohimbine 5.4 mg was evaluated in 31 patients with severe autonomic failure. In addition, a combination of pyridostigmine and yohimbine was also evaluated in a subset of patients. Primary outcome was standing diastolic BP change 60 min post-drug administration from baseline. Compared with placebo, yohimbine significantly improved standing diastolic BP (11±3 mm Hg [95% CI: 6–16 mmHg]; P<.001), while pyridostigmine did not (0.6±3 mm Hg [95% CI: −5 to 5 mmHg]; P=.823). Yohimbine also significantly improved presyncopal symptoms. However, no evidence of synergistic pressor effect was seen in the subset of 16 patients who received combination pyridostigmine and yohimbine. Investigators concluded that yohimbine could be more effective than pyridostigmine in improving orthostatic hypotension. However, two other preliminary studies that focused on characterizing neurogenic orthostatic hypotension syndromes by using yohimbine as a neuropharmacologic probe also found evidence that it can attenuate pressor response (9) (10).

Porst H, et al. SOP conservative (medical and mechanical) treatment of erectile dysfunction. J Sex Med. 2013;10:130-171.
This systematic review provides an update on levels of evidence for various treatment options for ED, including yohimbe. The research authors conducted PubMed and MEDLINE database searches, evaluated the evidence for efficacy, tolerability, safety, merits, and limitations of various interventions, and also provided their own expert opinions. With respect to yohimbe, the authors determined there was Level 3 (indirect) evidence for its efficacy and safety in nonorganic ED, which is defined as erectile dysfunction having emotional or psychological origins. The authors also pointed to the latest clinical guidelines for ED by the American Urological Association (AUA) (5) which indicate that the data does not support the recommendation of yohimbine for standard ED treatment, and especially not for ED of physiological origins.

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References
  1. Riley AJ. Yohimbine in the treatment of erectile disorder. Br J Clin Pract. May-Jun 1994;48(3):133-136.
  2. Ernst E, Pittler MH. Yohimbine for erectile dysfunction: a systematic review and meta-analysis of randomized clinical trials. J Urol. Feb 1998;159(2):433-436.
  3. Kunelius P, Hakkinen J, Lukkarinen O. Is high-dose yohimbine hydrochloride effective in the treatment of mixed-type impotence? A prospective, randomized, controlled double-blind crossover study. Urology. Mar 1997;49(3):441-444.
  4. Montorsi F, Strambi LF, Guazzoni G, et al. Effect of yohimbine-trazodone on psychogenic impotence: a randomized, double-blind, placebo-controlled study. Urology. Nov 1994;44(5):732-736.
  5. Montague DK, Jarow JP, Broderick GA, et al. Chapter 1: The management of erectile dysfunction: an AUA update. J Urol. Jul 2005;174(1):230-239.
  6. Porst H, Burnett A, Brock G, et al. SOP conservative (medical and mechanical) treatment of erectile dysfunction. J Sex Med. Jan 2013;10(1):130-171.
  7. Morgan CA, 3rd, Grillon C, Southwick SM, et al. Yohimbine facilitated acoustic startle in combat veterans with post-traumatic stress disorder. Psychopharmacology (Berl). Feb 1995;117(4):466-471.
  8. Shibao C, Okamoto LE, Gamboa A, et al. Comparative efficacy of yohimbine against pyridostigmine for the treatment of orthostatic hypotension in autonomic failure. Hypertension. Nov 2010;56(5):847-851.
  9. Sharabi Y, Imrich R, Holmes C, et al. Generalized and neurotransmitter-selective noradrenergic denervation in Parkinson's disease with orthostatic hypotension. Mov Disord. Sep 15 2008;23(12):1725-1732.
  10. Sharabi Y, Eldadah B, Li ST, et al. Neuropharmacologic distinction of neurogenic orthostatic hypotension syndromes. Clin Neuropharmacol. May-Jun 2006;29(3):97-105.
  11. Ostojic SM. Yohimbine: the effects on body composition and exercise performance in soccer players. Res Sports Med. Oct-Dec 2006;14(4):289-299.
  12. Bagheri H, Schmitt L, Berlan M, et al. A comparative study of the effects of yohimbine and anetholtrithione on salivary secretion in depressed patients treated with psychotropic drugs. Eur J Clin Pharmacol. 1997;52(5):339-342.
  13. Tsai HH, Lin HW, Simon Pickard A, et al. Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review. Int J Clin Pract. Nov 2012;66(11):1056-1078.
  14. Haller C, Kearney T, Bent S, et al. Dietary supplement adverse events: report of a one-year poison center surveillance project. J Med Toxicol. Jun 2008;4(2):84-92.
  15. Kearney T, Tu N, Haller C. Adverse drug events associated with yohimbine-containing products: a retrospective review of the California Poison Control System reported cases. Ann Pharmacother. Jun 2010;44(6):1022-1029.
  16. Chen Q, Li P, Zhang Z, et al. Analysis of yohimbine alkaloid from Pausinystalia yohimbe by non-aqueous capillary electrophoresis and gas chromatography-mass spectrometry. J Sep Sci. Jul 2008;31(12):2211-2218.
  17. Filippi S, Luconi M, Granchi S, et al. Endothelium-dependency of yohimbine-induced corpus cavernosum relaxation. Int J Impot Res. Aug 2002;14(4):295-307.
  18. Ajayi AA, Newaz M, Hercule H, et al. Endothelin-like action of Pausinystalia yohimbe aqueous extract on vascular and renal regional hemodynamics in Sprague Dawley rats. Methods Find Exp Clin Pharmacol. Dec 2003;25(10):817-822.
  19. Zheng H, Rinaman L. Yohimbine anxiogenesis in the elevated plus maze requires hindbrain noradrenergic neurons that target the anterior ventrolateral bed nucleus of the stria terminalis. Eur J Neurosci. Apr 2013;37(8):1340-1349.
  20. Murburg MM, Villacres EC, Ko GN, et al. Effects of yohimbine on human sympathetic nervous system function. J Clin Endocrinol Metab. Oct 1991;73(4):861-865.
  21. Kirkeby HJ, Forman A, Sorensen S, et al. Alpha-adrenoceptor function in isolated penile circumflex veins from potent and impotent men. J Urol. Nov 1989;142(5):1369-1371.
  22. Guthrie SK, Hariharan M, Grunhaus LJ. Yohimbine bioavailability in humans. Eur J Clin Pharmacol. 1990;39(4):409-411.
  23. Anderson C, Anderson D, Harre N, et al. Case study: two fatal case reports of acute yohimbine intoxication. J Anal Toxicol. Oct 2013;37(8):611-614.
  24. Giampreti A, Lonati D, Locatelli C, et al. Acute neurotoxicity after yohimbine ingestion by a body builder. Clin Toxicol (Phila). Sep 2009;47(8):827-829.
  25. Sandler B, Aronson P. Yohimbine-induced cutaneous drug eruption, progressive renal failure, and lupus-like syndrome. Urology. Apr 1993;41(4):343-345.
  26. Myers A, Barrueto F, Jr. Refractory priapism associated with ingestion of yohimbe extract. J Med Toxicol. Dec 2009;5(4):223-225.
  27. Mattila M, Seppala T, Mattila MJ. Anxiogenic effect of yohimbine in healthy subjects: comparison with caffeine and antagonism by clonidine and diazepam. Int Clin Psychopharmacol. Jul 1988;3(3):215-229.
  28. Fugh-Berman A. Herb-drug interactions. Lancet. Jan 8 2000;355(9198):134-138.
  29. VandenBrink BM, Foti RS, Rock DA, et al. Prediction of CYP2D6 drug interactions from in vitro data: evidence for substrate-dependent inhibition. Drug Metab Dispos. Jan 2012;40(1):47-53.
  30. Stine SM, Southwick SM, Petrakis IL, et al. Yohimbine-induced withdrawal and anxiety symptoms in opioid-dependent patients. Biol Psychiatry. Apr 15 2002;51(8):642-651.

Consumer Information

How It Works

Bottom Line: Yohimbe is not recommended for treating erectile dysfunction (ED).

Yohimbe is a tree native to West Africa. Yohimbine, an alkaloid derived from the bark of Yohimbe tree, has been used for many years as an aphrodisiac. Although widely used to treat erectile dysfunction before the approval of newer drugs, current guidelines do not recommend its use. In addition, yohimbine can cause many side effects, interact with many drugs, and is not recommended for individuals with certain of medical conditions.

Purported Uses
  • To improve athletic performance
    No scientific evidence supports this use.
  • To help dizzy spells and “head rush”
    A study in a small group of patients with nerve disorders suffering from these symptoms found that yohimbine improved symptoms.
  • To treat sexual dysfunction
    Yohimbine is not currently recommended to improve sexual dysfunction.
  • As a stimulant
    Although yohimbine stimulates the nervous system, no clinical data support its use as a stimulant. Instead, there are many reports of negative side-effects due to blood pressure effects as well as a number of drugs with which yohimbine can interact.
  • To increase salivation
    A small study showed that yohimbine could increase saliva flow compared with another drug. However, no further studies were ever done to confirm effectiveness and safety.
  • To lose weight
    There are no clinical data to support this use. Instead, there are many reports of negative side-effects due to blood pressure effects as well as a number of drugs with which yohimbine can interact.
Research Evidence
  • Treatment of erectile dysfunction
    Although yohimbine used to be widely prescribed for ED, it had numerous side effects and newer drugs were approved. In addition, several research bodies concluded that proof supporting yohimbine was based on weak evidence. The American Urological Association does not recommend yohimbine to improve sexual dysfunction.
Patient Warnings

Yohimbine can interact with numerous drugs and cause serious adverse effects. Do not use if you have high blood pressure, heart disease, arrhythmias, Parkinson's disease, seizure disorders, kidney, thyroid, or liver disease, sexual organ inflammatory disorders, ulcers, or psychiatric disorders. Do not take with antidepressant medications or with foods containing high amounts of tyramine (such as cheese, red wine, liver), or with decongestants, diet aids, or phenylpropanolamine-containing products. 

Do Not Take If
  • You take antianxiety agents: May reduce their effectiveness.
  • You take antidepressants: May increase side effects.
  • You take blood pressure medications:  May lessen their effects.
  • You take drugs that are substrates of CYP2D6: May effect how these drugs are metabolized.
  • You take bupropion: Coingestion can result in toxic effects.
  • You take opioids: May cause withdrawal and anxiety symptoms.
  • You are pregnant or nursing: May cause serious side effects.
  • You have cardiovascular disease, liver disease, or kidney disease: May cause serious side effects.
  • You have high blood pressure: Yohimbine can raise your blood pressure even more.
  • You have psychiatric conditions including posttraumatic stress disorder, anxiety, bipolar disorder, depression, mania, schizophrenia: Yohimbine may make your condition worse.
  • You have an enlarged prostate or sex organ inflammation: Yohimbine may make your condition worse.
Side Effects
  • High blood pressure, anxiety, nervousness, nausea, dizziness, rapid heartbeat, irregular heartbeat, sleeplessness, urinary problems, diarrhea, psychiatric symptoms

Case reports

  • Two unrelated deaths caused by yohimbine overdose that could not be explained by any other condition.
  • Severe pain and persistent erection in a 42-year-old man with complex medical history after taking yohimbe extract. A surgical procedure was necessary.
  • Acute neurotoxic effects including malaise, vomiting, loss of consciousness, and repeated seizures in a 39-year-old body builder after taking a large amount of yohimbine. Symptoms improved 12 hours after treatment.
  • Skin eruption, kidney failure, and lupus-like syndrome in a 42-year-old man following yohimbine treatment for impotence. Since the patient did not have these symptoms before treatment with yohimbine, doctors believed these symptoms were treatment-related.
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