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Does CBD Interact With Avanafil (Stendra)?

CBD may interfere with the body’s ability to metabolize avanafil (Stendra).

Caution is advised.

Article By
Daily CBD , last updated on February 10, 2022

Avanafil (Stendra) is a medication used to treat erectile dysfunction. Stendra is generally recognized as safe but can interact with other medications and supplements. 

Will Stendra interact with CBD? Is this combination dangerous? 

Illustration of avanafil tablets

Does CBD Interact With Avanafil (Stendra)? 

CBD can interact with avanafil (Stendra), but the interaction is expected to be mild.

The main interaction comes from the combined hypotensive action of both CBD and Stendra — this can lead to side effects such as dizziness, fainting, and fatigue. 

CBD may also inhibit the metabolism of Stendra, leading to a longer duration of effects and a higher chance of side effects like priapism, headaches, or dizziness. 

There are two main ways CBD and avanafil may interact: 

1. Slowed Elimination (Metabolic Inhibition)

When two drugs require the same enzymes to get metabolized, it’s called metabolic inhibition or metabolic competition. It is the primary mode of interaction between CBD and avanafil, but this interaction is considered to be mild.

Avanafil (Stendra) is metabolized by the CYP enzymes, mainly CYP3A4. The same enzyme also metabolizes CBD.

Consuming CBD and avanafil together may result in metabolic competition for these enzymes and cause an increased concentration of either compound due to an overall decrease in metabolism.

This metabolism inhibiting action may enhance the levels of avanafil and increase its duration of action, leading to increased arterial blood flow. This can cause sustained erection of the penis for a long time. 

CBD may also decrease the clearance of avanafil, causing it to last longer in the body and increase the risk of adverse effects like priapism and hypotension. 

2. Increased Effect (Agonistic Interaction)

An agonistic interaction can occur between different compounds when they produce similar effects on the body via different mechanisms.

Studies have revealed that chronic activation of endocannabinoid receptors by CBD leads to an increased level of vascular nitric oxide level and increased plasma level of cyclic guanosine monophosphate (cGMP) [1]. 

These findings support that CBD enhances the vasodilatory effect caused by cGMP. When avanafil and CBD are taken together, the level of cGMP may reach the level where its risk outweighs the benefits.

The longer duration of avanafil in the serum and increased cGMP levels increase the potency of avanafil, making it more effective. However, it also increases the risk of side effects such as hypotension and priapism. 

Similar Medications: CBD & Erectile Dysfunction (ED) Medications

Avanafil (Stendra) is classified as a phosphodiesterase (PDE) inhibitor, erectile dysfunction medications. It selectively inhibits the PDE-5 enzyme and has minor action on the PDE-6 enzyme. 

Virtually all erectile dysfunction medications use this same mechanism of action. Therefore, all CBD and erectile dysfunction medications share a similar risk of interaction and side effects.

Here’s a list of similar medications that share a similar level of risk when combined with CBD:

Is It Safe to Take CBD & Avanafil (Stendra) Together?

CBD and avanafil carry a mild risk of interaction.

Serious side effects aren’t likely to occur when using avanafil or CBD within the recommended dosages. The most common side effect of this interaction is dizziness or lightheadedness. 

In order to reduce the risk of interaction, it’s wise to talk to your doctor before taking CBD along with your avanafil. 

If you’re using CBD for pain and want to take avanafil, you can separate the doses by about 2 hours or more to further minimize risk.   

Is CBD a Viable Alternative to Avanafil (Stendra)?

CBD is not an alternative to avanafil (Stendra)

CBD has been shown to exert vasodilating activity, but this effect is significantly different from the effects induced by avanafil or other PDE5 inhibitors. 

Some evidence has been established that CBD increases vascular nitric oxide synthase level, ultimately increasing the plasma level of cGMP in the blood responsible for arterial dilation [1]. This warrants further research to evaluate the potential of CBD for the treatment of erectile dysfunction.

What is Avanafil (Stendra)?

Avanafil is a drug that belongs to the phosphodiesterase-5 (PDE5) inhibitor family. It’s a prescription medicine approved by the FDA to treat erectile dysfunction.

Avanafil is produced and marketed as Stendra — there are no generic options available for this medication yet. It helps increase blood flow in the penis by causing vasodilation. Its vasodilatory actions can help initiate and maintain an erection during sexual activity. 

Avanafil (Stendra) Specs:

Illustration of avanafil molecule
Drug Name Avanafil
Trade Name  Stendra
Classification Phosphodiesterase Inhibitors, Erectile dysfunction (ED) medication
CYP Metabolism CYP3A4
Interaction With CBD Metabolic Competition, Agonistic Interaction
Risk of Interaction Low

What Does Avanafil (Stendra) Do?

Avanafil is a phosphodiesterase inhibitor that treats erectile dysfunction. It is a potent and selective inhibitor of phosphodiesterase-5 (PDE-5), the enzyme that catalyzes the metabolism of cyclic guanosine monophosphate (cGMP) [2]. It also exerts minor inhibition on phosphodiesterase-6.

The penis contains two muscles, namely the corpus spongiosum and corpus cavernosum. The artery supplying the penis passes through the corpus cavernosum. 

Nitric Oxide (NO), synthesized and released from neurons into the corpus cavernosum, increases the formation of cGMP (cyclic guanosine monophosphate), which is responsible for causing vasodilation of the arteries responsible for penile erection.

cGMP gets metabolized to its inactive form GMP (Guanosine monophosphate) by the enzyme phosphodiesterase-5. When drugs like avanafil inhibit PDE-5, the level of cGMP increases, resulting in increased arterial blood flow. 

Absorption of avanafil occurs quickly following oral administration and has a half-life of 5 hours. It’s best to use a single dose of avanafil 15 to 30 minutes prior to sexual activity. 

In patients with erectile dysfunction, avanafil (Stendra) helps initiate and sustain an erection of the penis, easing sexual intercourse. Avanafil does not treat the root cause of erectile dysfunction but can alleviate its symptoms.

Side Effects of Avanafil (Stendra)

Avanafil is associated with numerous side effects. Most of the side effects are attributable to its PDE-5 inhibitory action on blood vessels. 

Even though avanafil exerts minor inhibition on PDE-6 (phosphodiesterase-6) enzymes, the effect is enough to aggravate serious complications such as AION (Anterior Ischemic Optic Neuropathy) that may result in a sudden loss of vision.

Side effects of avanafil include:

  • Back pain
  • Dizziness
  • Dyspepsia
  • Flushing
  • Headache
  • Hypotension
  • Myocardial Infarction
  • Nasal Congestion
  • Nasopharyngitis
  • Priapism
  • Sinusitis
  • Sudden loss of hearing
  • Tinnitus
  • Unstable Angina

Key Takeaways: Is it Safe to Take Avanafil (Stendra) With CBD?

While the risk of interaction between CBD and avanafil is minimal, it’s important to ask your doctor before you take these compounds in combination. Some people are at a higher risk of experiencing more severe side effects. Your doctor will take into consideration your other medications, underlying health conditions, prescribed dosages, and other factors to assess your level of risk. 

The most common reported side effect from this combination is dizziness — which is caused by the combined effect of CBD and avanafil on blood pressure. 


  1. Matouk, A. I., Taye, A., El-Moselhy, M. A., Heeba, G. H., & Abdel-Rahman, A. A. (2017). The Effect of Chronic Activation of the Novel Endocannabinoid Receptor GPR18 on Myocardial Function and Blood Pressure in Conscious Rats. Journal of cardiovascular pharmacology, 1, 23–33
  2. Dhruva, A., Hamsavardhini, V. K., Kamatham, S., Kataria, A., Kumar, A., Shanthi, M., & Peedicayil, J. (2019). Avanafil Inhibits the Contractility of the Isolated Caprine Detrusor Muscle. International journal of applied & basic medical research, 4, 231–235.

Learn More About CBD-Drug Interactions

Learn More About CBD-Drug Interactions

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