Yohimbine and Naloxone: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Naloxone
Yohimbine
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased adverse effects
Interaction Deep Dive
Concomitant treatment with yohimbine and naloxone has been proposed as a treatment for male erectile dysfunction1. However, at the doses studied, the combination of yohimbine and naloxone resulted in greater nervousness, anxiety, tremors, palpitations, nausea, hot and cold flashes, and plasma cortisol levels over that with either agent alone 1. Yohimbine increases norepinephrine release through alpha2-receptor antagonism. Naloxone is an opiate receptor antagonist which blocks opiate receptors in many areas of the brain. Increased activity in the locus coeruleus and amygdala may result from combined activity of alpha2-receptor blockade by yohimbine and antagonism of the inhibitory effects of endogenous opiates by naloxone. Increased plasma cortisol levels may result from increased norepinephrine release due to yohimbine, which may increase corticotropin-releasing factor. Opiate receptor blockade by naloxone may additively increase corticotropin release 1.
Why it happens (mechanism)
Increased norepinephrine release through alpha2-receptor antagonism by yohimbine
Literature reports
1 report — tap to read
a) Yohimbine and naloxone administered concomitantly caused nervousness, anxiety, tremors, palpitations, nausea, hot and cold flashes, and increased plasma cortisol concentrations in 6 healthy men and 4 healthy women in a double-blind, placebo-controlled trial (p between 0.001 and 0.05). Yohimbine 30 milligrams (mg) was administered orally, followed 15 minutes later by naloxone 1 mg/kg infusion given over 5 minutes. Patients were also tested with yohimbine alone and naloxone alone. Plasma free 3-methoxy-4-hydroxy-phenylglycol (MHPG) was increased by yohimbine (p less than 0.01) and naloxone (p less than 0.01) alone, but was not increased further with concomitant administration of yohimbine and naloxone 1.
Common questions
Can I take Yohimbine and Naloxone together?
Increased adverse effects Always confirm with your pharmacist or prescriber before making any change.
How serious is the Yohimbine and Naloxone interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Yohimbine or Naloxone need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there anything you'd monitor while I'm on both?
References (1)
- Charney DS & Heninger GR: Alpha-2-adrenergic and opiate receptor blockade. Synergistic effects on anxiety in healthy subjects. Arch Gen Psychiatry 1986; 43(11):1037-1041.
Keep reading about Naloxone
Keep reading about Yohimbine
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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