Description

Medicinal Parts

The medicinal part is the bark.

Flower and Fruit

The inflorescence consists of racemes of yellow blooms.

Leaves, Stem, and Root

The evergreen tree grows up to 30 m in height. The bark is gray-brown, fissured and split, and is often spotted. The inner fracture is reddish brown and grooved. The leaves are oblong or elliptical.

Characteristics

The taste is bitter, and the plant is odorless.

Habitat

The plant grows in the jungles of West Africa, Cameroon, Congo, and Gabon.

Production

Yohimbe bark consists of the dried bark of the trunk and/or branches of Pausinystalia yohimbe.

Actions & Pharmacology

Compounds

Indole alkaloids (2.7-5.9%): including among others Yohimbine (quebrachine) and its stereoisomers alpha-yohimbine (rauwolscine), beta-yohimbine, and allo-yohimbine. Including also, ajamalicine, dihydroyohimbine, corynantheine, dihydrocorynantheine, corynanthine (rauhimbin)

Tannins

Effects

A potent alpha-2-adrenoncepter blocker and a weak alpha-1-adrenergic antagonist with some antidopaminergic properties (Langer, 1980), yohimbine interacts with adrenoreceptors that are selectively stimulated by clonidine, alpha-methylnorepinephrine, tramazoline, guanabenz, guanfacine, B-HT 920, B-HT 933, M7, and also with compounds that are nonselectively stimulated by norepinephrine and epinephrine. These receptors are selectively blocked by rauwolscine, nonselectively blocked by phentolamine and tolazoline, and are resistant to blockade by prazosin and corynanthine. Based on radioligand and pharmacological studies, yohimbine can interact with alpha-1 adrenoreceptors. At high concentrations yohimbine may interact with serotonin and dopamine receptors and at very high concentrations it may have a nonspecific local anesthetic action (Goldberg & Robertson, 1983).

Yohimbine is a relatively safe medication that has a modest beneficial effect in the management of erectile dysfunction. No effect on sexual drive in humans has been adequately demonstrated. The therapeutic gain achieved with yohimbine in clinical trials is more effective in patients with psychogenic erectile disorder than with organic disorder. Most trials have shown some degree of benefit of yohimbine relative to placebo, particularly in psychogenic erectile disorder but results have not always been statistically significant. All the trials reported on yohimbine in erectile dysfunction can be criticized on methodological grounds. It is not known if yohimbine has a role in the prevention of myocardial infarction, stroke, or orthostatic hypotension due to autonomic failure.

Alpha-2 adrenergic Antagonist/Norepinephrine Release Effects

Rauwolscine is a selective alpha-2 adrenergic receptor antagonist. Yohimbine increases plasma norepinephrine (NE) levels by stimulating the rate of norepinephrine release from sympathetic nerves (alpha-2 adrenergic antagonist) (Murburg, 1991). Plasma concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), the major central nervous system metabolite of NE, also increase with yohimbine (Piletz, 1998). Central noradrenergic stimulation of yohimbine results in the enhancement of recall and recognition of emotional material (O'Carroll, 1999).

Analgesic Effects

Yohimbine significantly enhanced the overall analgesic effect of morphine with postoperative dental pain (Gear, 1995).

Cardiovascular/Hemodynamic Effects

In a dose-ranging study in normal men yohimbine hydrochloride caused dose-related rises in mean, systolic, and diastolic pressures. Associated with the rise in blood pressure were enhanced pressor and heart rate responses to the cold pressor, isometric handgrip, and Valsalva maneuvers (Goldberg et al, 1983). Yohimbine given in moderate doses increases systolic blood pressure in patients with orthostatic hypotension due to primary autonomic failure (Jordan, 1998). Yohimbine-induced enhancement of sympathetic tone in patients with neurally mediated syncope improves orthostatic tolerance (Mosqueda-Garcia, 1998).

Effects on Sexual Function

Because of the alpha-2 adrenergic blockade, the drug may be an effective treatment for sexual side effects, such as decrease libido and decreased sexual response, caused by selective serotonin reuptake inhibitors (Jacobsen, 1992; Hollander, 1992). There was no therapeutic response to yohimbine in women with hypoactive sexual desire (Piletz, 1998).

Hormonal Effects

In a double-blind, crossover study of normal men, yohimbine raised plasma norepinephrine and altered mood. When prolactin, cortisol, ACTH, beta-endorphin, TSH, and growth hormone were measured after 45 minutes of yohimbine infusion, there were no changes from baseline. The results suggested that alpha-2 adrenoreceptors in the hypothalamus, adenohypophysis, or other brain areas do not tonically modulate release of these hormones into the blood (Goldberg et al, 1986).

Salivary Effects

Yohimbine (18 mg daily) increases salivary flow in patients treated with psychotropic drugs (tricyclic antidepressants or neuroleptics) suffering from xerostomia (Bagheri, 1997).

Clinical Trials

Body composition/exercise performance

Twenty athletes (top-level male soccer players) were allocated to two randomly assigned trials to investigate the effects of yohimbine supplementation on body composition and exercise performance. Subjects ingested tablets that contained either yohimbine at a dose of 20 mg/day in two equal doses or cellulose (placebo) for 21 days. No statistically different changes in body mass, muscle mass, and performance indicators were found within or between trials (P>0.05). In contrast, fat mass was significantly lower in the yohimbine group in comparison to placebo (P<0.05) (Ostojic, 2006).

Depression

A six-week, randomized, double-blind, placebo-controlled clinical trial examined the effects of combining Yohimbine, an alpha2-antagonist, with fluoxetine, a selective serotonin reuptake agent (SSRI). Fifty subjects with a DSM-IV diagnosis of major depressive disorder confirmed by SCID interview were randomly assigned to receive either 20 mg fluoxetine plus placebo or 20 mg fluoxetine plus a titrated dose of Yohimbine. The results showed that addition of Yohimbine to fluoxetine results in a more rapid onset of antidepressant action as compared to SSRI alone (Sanacora et al, 2004).

Erectile Dysfunction

Yohimbine hydrochloride improved organic erectile dysfunction in 50% of subjects (n=9) ages 34 to 69 years. Eighteen subjects received Yohimbine hydrochloride 5.4 mg orally 3 times daily for 4 weeks and 10.8 mg orally 3 times daily for 4 more weeks. Nonsmoking subjects without major psychiatric problems who had normal initial serum testosterone and prolactin levels and an organic cause of erectile dysfunction were enrolled in the study. A sexual questionnaire was administered and nocturnal penile tumescence and rigidity testing was performed before treatment and after 4 weeks and 8 weeks of treatment. Four parameters of base and tip tumescence and rigidity were measured at baseline and after taking 5.4 mg and 10.8 mg Yohimbine hydrochloride. Responders demonstrated an increase in these parameters that either achieved significance or demonstrated a trend toward significance compared to non-responders. Responders were defined as those achieving successful intercourse for at least 75% of endeavors. It was less difficult obtaining an erection for intercourse taking Yohimbine hydrochloride 10.8 mg compared with baseline (p=0.011) (Guay et al, 2002).

Yohimbine was found superior to placebo (odds ratio 3.85, 95% CI 6.67-2.22) in a meta-analysis of 7 randomized, double-blind, placebo-controlled clinical trials involving male erectile dysfunction. Computerized literature searches were performed on all randomized controlled trials of Yohimbine for erectile dysfunction. Articles that scored less than 3 points out of 5 on the Jadad scale assessing methodological quality were excluded. Inclusion criteria included only randomized, placebo-controlled, double-blind trials that used adequate statistical evaluation. All studies examined found a positive response of Yohimbine versus placebo. Few adverse events were reported, with only 8 withdrawals due to adverse effects overall (Ernst & Pittler, 1998).

Hypotension

In 35 patients with severe orthostatic hypotension due to multiple system atrophy or pure autonomic failure, the effect was determined on seated systolic blood pressure (SBP) of placebo, phenylpropanolamine (12.5 mg and 25 mg), Yohimbine (5.4 mg), indomethacin (50 mg), ibuprofen (600 mg), caffeine (250 mg), and methylphenidate (5 mg). The pressor response was significant for phenylpropanolamine, Yohimbine, and indomethacin compared with placebo. In a subgroup of patients, the pressor effect was confirmed of phenylpropanolamine, Yohimbine, and indomethacin corresponding to a significant increase in standing SBP. The pressor responses to ibuprofen, caffeine, and methylphenidate were not significantly different from placebo, and phenylpropanolamine and midodrine exerted similar pressor responses (Jordan, 1998).

Syncope

Yohimbine significantly improved hemodynamic and sympathetic tilt response in neurally mediated syncope subjects (NMS) (n=8). All subjects experienced an upright tilt at 15-degree intervals every 3 minutes until reaching a 75 degree tilt. Subjects were placed in a supine position when presyncope or syncope developed. Blood samples of plasma catecholamines were obtained during tilting and after presyncope or syncope. Tilting was repeated after subjects had been supine for 3 hours. Patients developed a significant decrease in blood pressure that slowly worsened, resulting in syncope between 45 degrees and 75 degrees. Yohimbine significantly increased norepinephrine (p less than 0.05), epinephrine (p value not provided), muscle sympathetic nerve activity (p<0.01), systolic blood pressure (p<0.02), diastolic blood pressure (p<0.01), and heart rate (p<0.02) in NMS subjects compared to baseline (Mosqueda-Garcia et al, 1998).

Indications & Usage

Unproven Uses

Yohimbe bark is used as an aphrodisiac, and for debility and exhaustion.

Tyramine-Containing Foods (such as wine and aged cheese)

Due to its monoamine oxidase inhibitory effect, Yohimbine is contraindicated with tyramine-containing foods (Langer, 1980).

Contraindications

The drug should not be used by patients with liver and kidney diseases or chronic inflammation of the sexual organs or prostate gland, or with a history of gastric or duodenal ulcers. Yohimbine is not for use in psychiatric patients. Not recommended for long-term use.

Pregnancy

Not to be used during pregnancy.

Breastfeeding

Not to be used while breastfeeding.

Pediatrics

Not to be used by children under 12.

Precautions & Adverse Reactions

Side effects that can appear include anxiety states, elevated blood pressure, exanthema, nausea, insomnia, tachycardia, tremor, and vomiting.

Anxiety

Yohimbine was reported to exacerbate anxiety/panic and PTSD-specific symptoms after oral ingestion of the drug (Southwick, 1997, 1999). Patients with agoraphobia with panic attacks had greater autonomic anxiety symptoms, increase in SBP and cortisol responses to Yohimbine than healthy patients. Yohimbine also induced panic episodes in these patients (Gurguis, 1997). Patients with Parkinson's disease have demonstrated a vulnerability to Yohimbine-induced somatic symptoms such as panic attacks (Richard, 1999).

Hypertension

Yohimbine increased blood pressure in hypertensive and normotensive patients in several studies (Musso et al, 1995; Grossman et al, 1993; Damase-Michel et al, 1993; Goldstein et al, 1991; Murburg et al, 1991).

Mania

Yohimbine precipitated a manic episode in a depressed patient taking desipramine. The authors concluded that patients with a bipolar diathesis may be predisposed to the psychogenic effect of Yohimbine (Price et al, 1984).

Drug Interactions

Moderate Risk

Alcohol

Concurrent use of Yohimbine and alcohol significantly increased intoxication and also increased symptoms of anxiety and blood pressure in humans (McDougle et al, 1995). Clinical Management: Avoid concomitant use. Patients taking Yohimbine should avoid alcohol ingestion. If patients elect to use alcohol despite this advice, activities which require alertness (i.e. driving, operating heavy machinery) should be avoided.

Antihypertensive Agents (including Alpha-1 adrenergic blockers, Angiotensin Converting Enzyme (ACE) inhibitors, Angiotensin II receptor antagonists, Beta-adrenergic blockers, Calcium channel blockers, Diuretics, Hydralazine, Methyldopa)

Theoretically, Yohimbine may counteract the hypotensive effect of these medications, resulting in inadequate blood pressure control. Clinical Management: Avoid concomitant use of Yohimbine and these agents.

Carbamazepine

Yohimbine may exacerbate bipolar disorder by precipitating manic episodes. This effect has been noted in 3 case reports, generally within 1 to 2 hours of Yohimbine administration (Price et al, 1984). Clinical Management: Avoid Yohimbine use in patients taking carbamazepine for treatment of bipolar disorder.

Clomipramine

Concurrent use of Yohimbine and clomipramine may result in increased risk of hypertension. Clinical Management: Monitor orthostatic and sitting blood pressure in patients taking clomipramine who initiate therapy with Yohimbine, as Yohimbine may increase blood pressure.

Clonidine

Concurrent use of Yohimbine and clonidine may result in a reduced antihypertensive effect of clonidine. Clinical Management: Avoid concomitant use.

Desipramine

Concurrent use may result in an increased risk of manic episodes. Clinical Management: Avoid concomitant use.

Guanabenz, Guanadrel, Guanethidine, and Guanfacine

Theoretically, Yohimbine may counteract the antihypertensive effect of these substances. Clinical Management: Avoid concomitant use.

Lithium

Yohimbine may exacerbate bipolar disorder by precipitating manic episodes. This effect has been noted in 3 case reports, generally within 1 to 2 hours of Yohimbine administration (Price et al, 1984). Clinical Management: Avoid concomitant use of Yohimbine and lithium.

Minoxidil

Theoretically, Yohimbine may counteract the antihypertensive effect of minoxidil. Opposing mechanisms of action resulted in opposite effects on blood pressure by Yohimbine and clonidine (Charney et al, 1983). Clinical Management: Avoid concomitant use.

Morphine

Yohimbine may enhance and/or prolong the analgesic effect of morphine. Pretreatment with Yohimbine prior to dental surgery enhanced the analgesic effect of morphine in patients (Gear et al, 1995). Clinical Management: Patients taking Yohimbine and morphine concomitantly should be monitored closely for analgesic effect and adverse effects. Patients taking morphine chronically should be advised not to self-initiate Yohimbine without close medical monitoring.

Naloxone

Yohimbine may increase symptoms of nervousness, anxiety, tremors, palpitations, nausea, hot and cold flashes, and increased plasma cortisol levels when taken concomitantly with naloxone. Clinical Management: Use caution if initiating treatment with naloxone in patients taking Yohimbine. Concomitant treatment with Yohimbine and naloxone has been proposed as a treatment for male erectile dysfunction. However, at the doses studied, the combination of Yohimbine and naloxone resulted in greater nervousness, anxiety, tremors, palpitations, nausea, hot and cold flashes, and increased plasma cortisol levels over that with either agent alone.

Naltrexone

Yohimbine and naltrexone administered concomitantly may symptoms of anxiety or nervousness, which may decrease compliance with treatment. Clinical Management: Use with caution.

Reserpine

Concurrent use of Yohimbine and reserpine may result in reduced reserpine effectiveness. Clinical Management: Avoid concomitant use.

Sibutramine

Concomitant use may result in adverse cardiovascular effects (Jordan & Sharma, 2003). Clinical Management: Avoid concomitant use.

Valproic Acid

Yohimbine may exacerbate bipolar disorder by precipitating manic episodes. Clinical Management: Avoid Yohimbine use in patients taking valproic acid for treatment of bipolar disorder.

Potential Interactions

OTC Stimulants

These may have alpha-1 adrenergic receptor activity to potentiate hypertension when Yohimbine is given concomitantly. Clinical Management: Avoid concomitant use.

Overdosage

Overdosage leads to salivation, mydriasis, evacuation, hypotension and disorders of the cardiac impulse-conducting system with negative-inotropic effect. Death occurs through cardiac failure.

Treatment of overdosage includes gastrointestinal emptying (inducement of vomiting, gastric lavage with burgundy-colored potassium permanganate solution, sodium sulfate) and administration of activated charcoal. For cardiac rhythm disorders, treat with lidocaine; possibly using physostigmine for its anticholinergic effect and electrolyte substitution. For cases of acidosis, treat with sodium bicarbonate infusions. In case of shock, plasma volume expanders should be infused.

Dosage

How Supplied

• Capsule - 500 mg
• Liquid - 1000 mg/mL
• Tablet - 5.4 mg, 800 mg

Daily Usage

• Erectile Dysfunction - Yohimbine hydrochloride was effective for nonorganic erectile dysfunction administered as 30 mg daily (10 mg 3 times daily). Given up to 30 mg daily and 36 mg daily, Yohimbine, showed no effect for mixed-type impotence and erectile problems (Kunelius, 1997; Rowland, 1997). For erectile impotence, Yohimbine 5.4 mg (1 tablet) three times daily is recommended, and if side effects of nausea, dizziness or nervousness are reported, reduce to one-half tablet three times daily. Gradually increase to 1 tablet three times daily and therapy should not exceed 10 weeks (Prod Info Yocon®, 1985).
• Xerostomia Treatment (for increasing salivary flow in patients treated with psychotropic drugs): 6 mg 3 times daily (Bagheri, 1997).

Literature