Yohimbe

• How It Works

  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 prescription drugs, and is not recommended for individuals with certain medical conditions.

• Purported Uses
  • To improve athletic performance
    Evidence is lacking to support this claim.
  • To help dizzy spells and “head rush”
    A study in patients with nerve disorders found that yohimbine can help improve these symptoms.
  • To treat sexual dysfunction
    Several research bodies concluded that proof supporting yohimbine was based on weak evidence. Yohimbine is not currently recommended to improve sexual dysfunction.
  • As a stimulant
    Although yohimbine stimulates the nervous system, there are no clinical data to support its use as a stimulant.
• 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.
  • An analysis of 49 yohimbine supplement brands sold in the USA showed that only 4.1% (2/49) provided accurate information about the quantity of yohimbine, and information about yohimbine’s known adverse effects.
• 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 affect 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 blood pressure so taking it may compound the problem.
  • You have psychiatric conditions including post-traumatic 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, cardiotoxicity, 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 treatment with yohimbine for impotence.
• Scientific Name

  Pausinystalia yohimbe, Corynanthe johimbe

• 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. Yohimbe is marketed as a steroid substitute, for weight loss, and is 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, there is a lack of direct evidence regarding the efficacy and safety of oral yohimbine in non-organic (psychogenic) ED, with no support for its use in organic ED ^(5) (6). In veterans with post-traumatic stress disorder, yohimbine increased acoustic startle reflex ⁽⁷⁾; and resulted in greater between-session habituation and improvement in depression ⁽³¹⁾. Preliminary data suggest that it may be effective for improving presyncopal symptoms in patients with severe orthostatic hypotension ⁽⁸⁾; and helps attenuate pressor responses in patients with Parkinson’s disease and neurogenic orthostatic hypotension ^(9) (10). Data on the effects of yohimbine on athletic performance ⁽¹¹⁾ and xerostomia are limited ⁽¹²⁾.

  It is important to note that products containing yohimbe are among the 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
• Mechanism of Action

  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). Yohimbe also has dilatory effect on genital blood vessels, enhanced genital tissue sensation, and increased reflex excitability in the sacral region ⁽⁴⁾.

  The active constituents are indole alkaloids, including yohimbine ⁽¹⁶⁾, which 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⁾.

• 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.
  • An analysis of 49 yohimbine supplement brands sold in the USA showed that only 4.1% (2/49) provided accurate information about the quantity of yohimbine, and information about yohimbine’s known adverse effects ⁽³²⁾.
• Contraindications

  Cardiovascular disease, hypertension, liver disease, kidney disease, post-traumatic 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, cardiotoxicity ^{(1) (6) (15) (33) (34)}

  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⁾.
• 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.

  31. Tuerk PW, Wangelin BC, Powers MB, et al. Augmenting treatment efficiency in exposure therapy for PTSD: a randomized double-blind placebo-controlled trial of yohimbine HCl. Cogn Behav Ther. 2018 Sep;47(5):351-371.

  32. Cohen PA, Wang YH, Maller G, DeSouza R, Khan IA. Pharmaceutical quantities of yohimbine found in dietary supplements in the USA. Drug Test Anal. 2016 Mar-Apr;8(3-4):357-69.

  33. Brown AC. Heart Toxicity Related to Herbs and Dietary Supplements: Online Table of Case Reports. Part 4 of 5. J Diet Suppl. 2018 Jul 4;15(4):516-555.

  34. Rao N, Spiller HA, Hodges NL, et al. An Increase in Dietary Supplement Exposures Reported to US Poison Control Centers. J Med Toxicol. 2017 Sep;13(3):227-237.