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There is such a variety of 'natural' sleep aids over the counter that it is difficult to give a definitive statement regarding which are safe to take with Cymbalta (duloxetine) and which are not.

Additionally, since so many products marketed for sleep contain more than one ingredient, it can be a challenge to discern the overall safety of a particular product.

What we can do, however, is take a look at a few specific herbals and other 'natural' over the counter products and see if they are known to interact with Cymbalta.

Overall, most appear to be relatively safe to use, but it is important to point out that Cymbalta itself can have side sedative side effects. It is also known to cause dizziness and difficulty concentrating.

Therefore, mixing Cymbalta with a product intended to make you tired can have additive effects in this regard, so it is important to keep this in mind.

Below, I take a look at some of the top-selling 'natural' products for sleep and whether or not they are known to interact with Cymbalta. These products include:

  • Valerian
  • L-tryptophan
  • Melatonin
  • Lemon Balm
  • Kava


Valerian is one of the top-selling natural supplements in the United States, consistently ranking in the top 10 in terms of sales.

While it has a variety of purported effects, it is often used for the treatment of anxiety symptoms and insomnia.

How valerian works isn't completely understood, but its relaxation effects are thought to be due to it acting as an agonist on GABA receptors.

GABA is an inhibitory neurotransmitter and when bound to GABA receptors, produces a variety of effects, including sedation and relaxation.

There are a variety of prescription drugs that work on GABA receptors, including:

Valerian is not known to interact with Cymbalta, aside from the fact that both can cause sedation and drowsiness.

Valerian may have some effect on certain serotonin receptors (5-HT1), but this isn't thought to be overly significant.

Even though Cymbalta can increase serotonin concentrations, there likely isn't any significant interaction here. Valerian has not been reported to interact with other drugs that affect serotonin.


L-tryptophan is widely used as a natural sleep aid. It is an essential amino acid (meaning we need to consume via our diet) and is commonly associated as the compound in turkey that makes people tired.

The purported sedative effects of l-tryptophan aren't simply anecdotal. Studies show that L-tryptophan may decrease sleep latency (i.e. time it takes to fall asleep), but more studies are needed to fully elucidate its effects.

In terms of taking L-tryptophan with Cymbalta, there is a potentially dangerous interaction here, and they shouldn't be used together in most cases since L-tryptophan is a serotonin precursor.

Our body absorbs tryptophan from dietary sources (including supplementation), converts it to 5-hydroxytryptophan (5-HTP), and then to serotonin (5-hydroxytryptamine).

Cymbalta, an SNRI (serotonin-norepinephrine reuptake inhibitor), works partly by increasing serotonin concentrations in the brain.

The prescribing information for Cymbalta warns against its use with other serotonergic agents and specifically, tryptophan:

Based on the mechanism of action of SNRIs and SSRIs, including Cymbalta, and the potential for serotonin syndrome, caution is advised when Cymbalta is co-administered with other drugs that may affect the serotonergic neurotransmitter systems, such as triptans, linezolid (an antibiotic which is a reversible non-selective MAOI), lithium, tramadol, or St. John's Wort. The concomitant use of Cymbalta with other SSRIs, SNRIs or tryptophan is not recommended

Serotonin syndrome, as mentioned in the above excerpt is a rare, but serious disorder that requires immediate medical attention if it occurs. Symptoms include:

  • Increased body temperature
  • Muscle rigidity
  • Sweating
  • Altered mental status (e.g. confusion, delusion)
  • Headache
  • Increased heart rate

Due to the risk of serotonin syndrome, L-tryptophan should not be taken with any other drug that increases serotonin levels until first speaking with your doctor.


Melatonin is a commonly used sleep-aid, and it does have strong evidence for helping to treat certain sleep-related disorders, such as 'jet-lag'.

Melatonin is an endogenous hormone that we produce that, among other things, helps to regulate our sleep-wake cycle.

Supplementing with melatonin seems to be far more effective in helping to get our bodies back on a normal schedule in regard to sleep, as opposed to being used simply intermittently to make you drowsy.

In terms of melatonin interacting with Cymbalta, there is a lack of information available regarding their use together.

Certainly, both can cause sedation, so there is a general precaution regarding that.

Additionally, there is some evidence that melatonin can inhibit a metabolizing enzyme in our body known as CYP2D6.

This enzyme is responsible for Cymbalta metabolism and inhibiting this enzyme, could potentially result in increased Cymbalta concentrations.

Nevertheless, it isn't likely that melatonin is a strong inhibitor of CYP2D6 and studies haven't shown any significant interaction with melatonin and this enzyme.

Overall, it doesn't appear that there is a significant interaction between melatonin and Cymbalta and they are likely safe to take together.

It is important to speak with your doctor first however, before combining the two, so you can be monitored appropriately.

Lemon Balm

Lemon balm is a lemon-scented herb that is often used to treat anxiety symptoms and insomnia.

It is not a fruit (like lemon) but is rather part of the mint family.

Studies are actually pretty positive when it comes to lemon balm's effectiveness in treating insomnia.

For example, one study, published in the Mediterranean Journal of Nutrition and Metabolism, found that a lemon balm extract (dosed twice daily for 15 days) reduced the incidence of insomnia by 42% in patients with a sleep disorder.

Fortunately, lemon balm is thought to have very few drug interactions and may be a safe option for you to try.

It may interact with thyroid hormone replacement drugs (like levothyroxine or liothyronine) and certain sedatives, but isn't thought to be a problem with Cymbalta.

Aside from the drowsiness they can both cause, lemon balm and Cymbalta appear to be safe to take together.


Kava, sometimes referred to as 'kava kava', has some of the strongest clinical evidence for herbal products in its efficacy for treating anxiety. Less commonly, it is used for insomnia.

Unfortunately, kava has been strongly linked to causing an increase in liver enzymes and liver dysfunction.

In fact, as far back as 2002, the FDA released a safety warning regarding kava supplements. Per the NIH (National Institutes of Health):

In March 25, 2002, the Food and Drug Administration (FDA) issued an advisory notifying consumers that kava-containing dietary supplements may be associated with severe liver injury. The FDA reported that kava-containing products have been associated with liver-related injuries, including hepatitis, cirrhosis, and liver failure, in over 25 reports of adverse events in other countries. In the U.S., FDA received a report of a previously healthy young female who required liver transplantation, as well as several reports of liver-related injuries.

There isn't a known drug interaction between kava and Cymbalta, but since Cymbalta is metabolized through the liver, it shouldn't be used in those with liver dysfunction.

If you plan on taking kava to treat insomnia symptoms, you should hold off until speaking to your doctor about it first.

Final Words

Most over-the-counter 'natural' remedies don't have a documented interaction with Cymbalta.

However, since they all can make you feel drowsy or tired, there is a chance that combining them with Cymbalta can enhance those effects (since Cymbalta itself can cause sedation).

The only definitive interaction we know about is with L-tryptophan, and therefore, that should not be taken with Cymbalta in most cases.

As with all supplements, you should speak with your doctor first before combining them with prescription medication.

Even if there isn't a documented interaction between them, it is important for your doctor to be aware of everything you are taking so you can be monitored appropriately.


  • Most natural sleep aids aren't known to interact with Cymbalta (duloxetine).
  • However, since Cymbalta can cause sedation and dizziness on its own, combining it with a sleep aid can enhance these effects.
  • One well-documented interaction with Cymbalta is with L-tryptophan, a serotonin precursor. Taking L-tryptophan with Cymbalta increases the risk of a rare, but serious condition known as serotonin syndrome.

  • References
    1. Cymbalta Prescribing Information. AccessFDA
    2. Mediterranean Journal of Nutrition and Metabolism. Springer
    3. Kava Health Information. NIH
    4. Valerian for Sleep: A Systematic Review and Meta-Analysis. PubMed
    5. Sales of Herbal Dietary Supplements in US Increased 7.5% in 2015 Consumers spent $6.92 billion on herbal supplements in 2015, marking the 12th consecutive year of growth. HerbalGram
    6. L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. PubMed
    7. Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis. PubMed
    8. Melatonin for Treatment of Sleep Disorders: Summary. NIH
    9. Melatonin: In Depth. NIH
    10. Kava for the treatment of generalised anxiety disorder (K-GAD): study protocol for a randomised controlled trial. PubMed