Tests for the medical use of Yohimbine
Today yohimbine in medicine is a niche drug: it was once prescribed for erectile dysfunction, in science it is used to study the noradrenergic system, and in some clinical studies it has been investigated for orthostatic hypotension. But in each of these cases the doctor must assess whether yohimbine is safe for a particular person and be able to correctly interpret tests taken while on it. The editorial team explains which examinations matter and why.
Medical indications for yohimbine: past and present
In the USA yohimbine hydrochloride was for a long time available as a prescription drug in 5.4 mg tablets. The labeling described it as a sympatholytic and mydriatic with a possible aphrodisiac action, and in practice it was used mainly for erectile dysfunction. A meta-analysis by Ernst and Pittler (1998) confirmed an advantage over placebo, but the effect was moderate.
With the appearance of phosphodiesterase-5 inhibitors, yohimbine practically disappeared from clinical guidelines. Modern urological guidelines do not offer it as a treatment for erectile dysfunction.
Another direction is orthostatic hypotension in autonomic failure. A study by Onrot and colleagues (1987) showed that yohimbine can raise blood pressure in patients with autonomic failure who retain part of their sympathetic activity. However, this remained a niche research application.
Most broadly, yohimbine is used in science — as a pharmacological probe to assess the noradrenergic system, in studies of anxiety and post-traumatic stress disorder. Regardless of the context, the basic principles of examination are the same: assess the cardiovascular, psychiatric, and renal status.
Examination before prescription
The first and most important step is assessment of the cardiovascular system. Yohimbine raises blood pressure and the level of noradrenaline in the plasma, as demonstrated by Goldberg, Hollister, and Robertson (1983). Therefore, before prescription, blood pressure is measured (preferably several times and in different body positions), pulse is taken, and an ECG is done. Hypertension, coronary heart disease, and arrhythmias are grounds to refuse yohimbine.
The second step is kidney function. The labeling of prescription yohimbine listed kidney diseases among the contraindications. Creatinine with a calculation of the glomerular filtration rate and a urinalysis make it possible to rule out hidden kidney pathology.
The third step is the liver. Yohimbine is metabolized mainly by the enzyme CYP2D6, and any impairment of liver function can increase the concentration of the substance in the blood. Determining ALT, AST, and bilirubin provides baseline information.
The fourth step is the psychiatric history. Yohimbine can provoke panic attacks in people with panic disorder (Charney et al., 1984), so the doctor clarifies the presence of anxiety disorders, depression, and bipolar disorder. The labeling also warned against use in psychiatric patients and together with mood-altering drugs.
| Examination | Purpose | What may become a contraindication |
|---|---|---|
| Blood pressure lying and standing, pulse | Baseline state, orthostatic reactions | Uncontrolled hypertension |
| ECG | Rhythm, signs of ischemia | Arrhythmias, coronary heart disease |
| Creatinine, GFR, urinalysis | Kidney function | Kidney diseases |
| ALT, AST, bilirubin | Liver function, metabolism | Severe liver diseases |
| Psychiatric screening | Anxiety, panic attacks, depression | Panic, bipolar disorders |
| List of medications | Interactions, CYP2D6 inhibitors | MAOIs, antidepressants, clonidine |
Monitoring during use
The main monitoring indicator is arterial blood pressure. In the first days of use it is advisable to measure it regularly, in particular an hour or two after intake, when the concentration of yohimbine is highest. The patient should keep a diary of blood pressure and pulse and report a persistent increase to the doctor.
Because of variable bioavailability (Owen et al., 1987) and genetic differences in CYP2D6 activity (Le Corre et al., 2004), the reaction to the same dose can differ substantially between people. Therefore the doctor assesses not the dose as such but the individual response: blood pressure, pulse, well-being.
It is important to record subjective symptoms: anxiety, insomnia, tremor, nausea, flushing, frequent urination. It is precisely these that are often the first to signal an excessive effect. The appearance of chest pain, severe headache, or palpitations requires immediate cessation of intake and seeking help.
With prolonged use it is advisable to periodically repeat the monitoring of kidney and liver function, especially in older people or those with comorbidities. If the doctor adds new drugs, they check whether they are CYP2D6 inhibitors.
How yohimbine affects test results
The most important laboratory effect of yohimbine is an increase in the level of noradrenaline in the blood plasma and its metabolites. This is a direct consequence of the blockade of alpha-2 receptors, which normally inhibit the release of noradrenaline. In scientific studies it is precisely this effect that is used as a marker of yohimbine's action.
The practical conclusion: if a person is prescribed a test for catecholamines or metanephrines (for example, to rule out pheochromocytoma), taking yohimbine can distort the result. The doctor who refers a patient for such an examination must know about all the drugs and supplements the patient is taking, including fat burners.
Yohimbine also affects carbohydrate metabolism. The alpha-2 adrenoreceptors of the pancreatic beta cells inhibit insulin secretion, and their blockade can change insulin and glucose levels. For people with diabetes this is a reason to monitor glycemia more often.
Finally, when blood pressure is measured in the clinic, a person who took yohimbine the day before or the same day may get elevated readings. This leads to a false diagnosis of hypertension or an incorrect adjustment of antihypertensive therapy.
- Noradrenaline and metabolites in plasma and urine — a possible increase.
- Glucose and insulin — possible changes.
- Blood pressure and pulse — elevated readings after intake.
- Results of anxiety tests in studies — intensification of symptoms.
Taking supplements on your own: what to check
Most people encounter yohimbine not through a prescription but through fat burners and "test boosters." Since the composition of such products often does not match the label (Cohen et al., 2016), and in the EU yohimbe bark is banned in food products, the real dose remains unknown.
If a person has already used such products, especially for a long time or with unpleasant symptoms, it is reasonable to undergo a basic examination: measure blood pressure at rest and keep a diary for several days, do an ECG, determine creatinine, liver enzymes, and fasting glucose. In case of muscle pain after training — creatine kinase.
During any medical examination it is worth telling the doctor about taking supplements with yohimbine. This will help to correctly interpret elevated blood pressure, an accelerated pulse, or changes in catecholamine tests.
Normal test results do not mean that using yohimbine is safe. The main risks — a hypertensive reaction, arrhythmia, a panic attack — develop acutely, and no prior test guarantees their absence.
Editorial conclusions
Before the medical use of yohimbine, the key steps are assessment of blood pressure and the heart, kidney and liver function, the psychiatric history, and a list of drugs that may interact via CYP2D6.
During use, the main monitoring is regular measurement of blood pressure and pulse and attention to symptoms of anxiety, since the individual reaction to yohimbine is very variable.
Yohimbine raises the level of noradrenaline in the blood and can affect glucose and insulin, so its use should be reported to the doctor before examinations.
We also recommend reading our articles on the effect of yohimbine on the liver and kidneys, on yohimbine overdose, and on tests for the medical use of ephedrine.
References
- Ernst E, Pittler MH. Yohimbine for erectile dysfunction: a systematic review and meta-analysis of randomized clinical trials. J Urol. 1998;159(2):433–436.
- Goldberg MR, Hollister AS, Robertson D. Influence of yohimbine on blood pressure, autonomic reflexes, and plasma catecholamines in humans. Hypertension. 1983;5(5):772–778.
- Onrot J, Goldberg MR, Biaggioni I, et al. Oral yohimbine in human autonomic failure. Neurology. 1987;37(2):215–220.
- Owen JA, Nakatsu SL, Fenemore J, et al. The pharmacokinetics of yohimbine in man. Eur J Clin Pharmacol. 1987;32(6):577–582.
- Le Corre P, Parmer RJ, Kailasam MT, et al. Human sympathetic activation by alpha2-adrenergic blockade with yohimbine: bimodal, epistatic influence of cytochrome P450-mediated drug metabolism. Clin Pharmacol Ther. 2004;76(2):139–153.
- Charney DS, Heninger GR, Breier A. Noradrenergic function in panic anxiety: effects of yohimbine in healthy subjects and patients with agoraphobia and panic disorder. Arch Gen Psychiatry. 1984;41(8):751–763.
- Tam SW, Worcel M, Wyllie M. Yohimbine: a clinical review. Pharmacol Ther. 2001;91(3):215–243.
- Cohen PA, Wang YH, Maller G, et al. Pharmaceutical quantities of yohimbine found in dietary supplements in the USA. Drug Test Anal. 2016;8(3-4):357–369.
Andriy Melnyk
A strength-sports coach and author of programs for beginner and intermediate levels. Writes about training planning.
