YOHIMBINE
Yohimbine is an indole alkaloid extracted from Pausinystalia yohimbe bark that acts as a selective alpha-2 adrenergic receptor antagonist. This mechanism increases norepinephrine release, enhancing sympathetic nervous system activity with effects on metabolism, fat oxidation, and cardiovascular function.
Yohimbine is an indole alkaloid extracted from the bark of the Pausinystalia johimbe tree that acts as an alpha-2 adrenergic receptor antagonist, increasing norepinephrine release and sympathetic nervous system activation. It has been historically used for erectile dysfunction and is commonly found in dietary supplements marketed for weight loss and athletic performance enhancement, though it carries significant cardiovascular risks and side effect concerns.
Research
Reported Effects
Libido Enhancement:: Evidence suggests moderate effectiveness for erectile dysfunction when used alone or in combination with other compounds, though results are inconsistent. Weight Loss:: Despite marketing claims, users report minimal to no actual fat loss benefits, with most concluding it's ineffective as a standalone fat burner. Athletic Performance:: Mixed results with some studies showing altered performance metrics but no clear consensus on meaningful performance improvements. High Individual Variability:: Effects vary dramatically between users, with some experiencing no effects while others have severe reactions to the same doses
- Evidence suggests moderate effectiveness for erectile dysfunction when used alone or in combination with other compounds, though results are inconsistent
- Despite marketing claims, users report minimal to no actual fat loss benefits, with most concluding it's ineffective as a standalone fat burner
- Mixed results with some studies showing altered performance metrics but no clear consensus on meaningful performance improvements
- Effects vary dramatically between users, with some experiencing no effects while others have severe reactions to the same doses
Safety Profile
Safety Profile: Yohimbine
Common Side Effects
- Anxiety, nervousness, agitation, and irritability (common due to alpha-2 adrenergic antagonism and sympathetic activation)
- Elevated heart rate (tachycardia) and palpitations
- Elevated blood pressure (hypertension), particularly in doses above 10 mg
- Headache and dizziness
- Nausea, vomiting, and abdominal discomfort
- Tremor and sweating
- Insomnia when taken later in the day
Serious Adverse Effects
- Hypertensive crisis: Severe blood pressure elevations reported, particularly at high doses or in combination with other sympathomimetics; can lead to end-organ damage
- Cardiac arrhythmias: Tachyarrhythmias, atrial fibrillation, and QT prolongation reported in case reports
- Psychiatric adverse effects: Panic attacks, severe anxiety, psychosis, and manic episodes; yohimbine is used in research to pharmacologically induce anxiety and panic attacks
- Seizures: Reported in overdose cases
- Priapism: Prolonged erection requiring emergency treatment reported with yohimbine, particularly in combination with other erectile dysfunction medications
- Renal failure: Case reports of acute kidney injury associated with yohimbine-containing supplements
- Narrow therapeutic window: effective dose (5–20 mg) is close to toxic dose
Contraindications
- Known hypersensitivity to yohimbine or yohimbe bark
- Uncontrolled hypertension or cardiovascular disease (coronary artery disease, arrhythmias, heart failure)
- Anxiety disorders, panic disorder, PTSD, or schizophrenia (yohimbine is a potent anxiogenic)
- Concurrent use of MAO inhibitors (risk of hypertensive crisis)
- Renal impairment or hepatic impairment
- Pregnancy and lactation
- Bipolar disorder (risk of precipitating mania)
Drug Interactions
- MAO inhibitors: Contraindicated; can cause severe hypertensive crisis and serotonin syndrome
- Antihypertensives (clonidine, alpha-2 agonists): Yohimbine directly antagonizes clonidine and other alpha-2 agonists, negating their therapeutic effect
- Tricyclic antidepressants: Additive cardiovascular effects; increased risk of hypertension and arrhythmias
- Stimulants (caffeine, amphetamines, ephedrine): Additive sympathomimetic effects; dangerous blood pressure and heart rate elevation
- PDE5 inhibitors (sildenafil, tadalafil): Additive effects on erectile function; increased risk of priapism and hypotension
- SSRIs/SNRIs: Increased risk of serotonin-related side effects
Population-Specific Considerations
- Men with erectile dysfunction: Historically prescribed at 5.4 mg TID; largely replaced by PDE5 inhibitors due to better safety profile
- Fat loss users: Popular in bodybuilding at 2.5–20 mg/day; narrow therapeutic index; medical supervision recommended
- Elderly: Higher cardiovascular risk; avoid or use at lowest effective dose with monitoring
- Psychiatric patients: Strongly contraindicated in anxiety, panic, and psychotic disorders
- Athletes: Not currently WADA-prohibited but included in some sport organization banned lists; check specific regulations
Pharmacokinetic Profile
Quick Start
- Typical Dose
- Most supplements and studies use 2.5-5mg doses, though even these lower amounts cause significant side effects in many users
Molecular Structure
- Formula
- C21H26N2O3
- Weight
- 354.4 Da
- PubChem CID
- 8969
- Exact Mass
- 354.1943 Da
- LogP
- 2.9
- TPSA
- 65.6 Ų
- H-Bond Donors
- 2
- H-Bond Acceptors
- 4
- Rotatable Bonds
- 2
- Complexity
- 555
Identifiers (SMILES, InChI)
InChI=1S/C21H26N2O3/c1-26-21(25)19-15-10-17-20-14(13-4-2-3-5-16(13)22-20)8-9-23(17)11-12(15)6-7-18(19)24/h2-5,12,15,17-19,22,24H,6-11H2,1H3/t12-,15-,17-,18-,19+/m0/s1
BLGXFZZNTVWLAY-SCYLSFHTSA-NSafety Profile
Common Side Effects
- Severe Cardiovascular Effects:: Dangerous blood pressure spikes (cases of 198/93 documented), tachycardia, heart palpitations, and documented cases of intracranial hemorrhage and cardiac arrest
- Anxiety and Panic:: Intense anxiety, nervousness, and panic-like symptoms are the most commonly reported side effects, often severe enough to warrant discontinuation
- Gastrointestinal Distress:: Users report nausea, vomiting, and stomach upset, particularly when taken on an empty stomach as recommended
- Drug Interactions:: Dangerous interactions with medications like clonidine and potential MAOI-like effects requiring dietary restrictions and medication awareness
References (8)
- [5]Intracranial hemorrhage after a single dose of Yohimbine in a chronic user of clonidine
→ Case report documented a 39-year-old female who developed acute basal ganglia hemorrhage with severe hypertension (198/93) and neurological sequelae after taking a single dose of yohimbine while on clonidine.
- [1]Ergogenic and Sympathomimetic Effects of Yohimbine: A Review
→ Comprehensive review showing yohimbine acts as an α2-adrenergic receptor antagonist that increases norepinephrine release, with implications for improving cardiovascular function, blood flow, lactate metabolism, and muscle function during exercise.
- [2]Yohimbine as a treatment for erectile dysfunction: A systematic review and meta-analysis
→ Meta-analysis found yohimbine alone showed significantly greater probability of erectile function improvement compared to placebo (OR 2.08), with combination therapy showing even stronger effects (OR 6.35).
- [6]Severe acute intoxication with yohimbine: Four simultaneous poisoning cases
→ Report of four middle-aged men experiencing severe yohimbine poisoning simultaneously, with one death, highlighting the serious toxicity risks associated with yohimbine overdose.
- [7]Cardiovascular toxicity associated with supplement use
→ Review identifying yohimbine as a stimulant supplement that can cause adverse cardiovascular effects including tachycardia, hypertension, hyperthermia, myocardial infarction, and cardiac arrest through adrenergic mechanisms.
- [8]Yohimbine: the effects on body composition and exercise performance in soccer players
→ Study examining yohimbine's effects on body composition and athletic performance in soccer players, though full results were not accessible.
- [3]Effects of Acute Yohimbine Hydrochloride Supplementation on Repeated Supramaximal Sprint Performance
→ Study in physically active females found 2.5mg yohimbine increased heart rate and altered performance metrics during repeated Wingate tests, though effects on power output were mixed.
- [4]Pharmaceutical quantities of yohimbine found in dietary supplements in the USA
→ Analysis of 49 commercial supplements found yohimbine content ranged from none detected to 12.1mg per serving, with 39% containing pharmaceutical quantities, highlighting significant quality control and labeling accuracy issues.
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