Jujube and the risk of serotonin syndrome

Hi all!

I’ve been eager to grow jujube as I’ve heard many great things about it, and it is perfectly adapted to my climate.

However, I have come across several reports suggesting that consuming jujube may negatively interact with certain antidepressant medications, potentially leading to serotonin syndrome. This is a very unpleasant condition and can be life-threatening if severe.

Jujube is often heralded for its beneficial effects on anxiety, insomnia, and relaxation due to its impact on serotonin in the brain. This is what can supposedly lead to the danger of using it concurrently with antidepressants.

Have any of you come across these concerns before? Have you noticed any mild sedative or anxiety-relieving properties after consuming jujube?

I’ve been advised to avoid grapefruit, for example, as it too can interact with drug metabolism.

As with anything though, the dose makes the poison. Pawpaw is often discussed for its possible risks, as frequent and high consumption can be neurotoxic. But occasional consumption is probably completely fine.

Thanks!

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I’m not finding any direct research on it, with only one known instance in 2004 (with an SSNRI, not an SSRI), so seems extremely rare but possible:

Interactions

There has been a case report of a severe, acute serotonin reaction of venlafaxine with coadministration of jujube. Jujube 0.5 g/day was consumed regularly, and the reaction occurred after a single dose of venlafaxine 37.5 mg.Stewart 2004

Potentiation of effect of phenytoin and phenobarbitone in rodents has been reported. No effect on carbamazepine was noted.Pahuja 2012

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It seems pharmacological research is sorely lacking with many of the more obscure and unusual fruits.

They’ve been consumed for hundreds if not thousands of years in their native range so are clearly safe for the most part. It’s just that jujube is widely known for its sedative effects in traditional Chinese medicine so there is likely something going on there that could interact with certain medications.

There are many traditional herbs that have been well-studied for their interaction with not only psychiatric meds but chemotherapy drugs, blood thinners, and statins too, which should probably be avoided by those who are taking certain medications. St. John’s wort, gingko, echinacea, ginseng, etc…

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There’s a bit more research in China: Regulation of GABAA and 5-HT Receptors Involved in Anxiolytic Mechanisms of Jujube Seed: A System Biology Study Assisted by UPLC-Q-TOF/MS and RT-qPCR Method - PMC

Alkaloids in jujube (in this case the study was done on jujube seeds, but these alkaloids seem present in the fruit as well) cause up-regulation of GABA and serotonin receptor production. It’s possible that’s the reason for the effects and for that 2004 acute reaction to venlafaxine.

There are other food components found to do the same, though: omega-3, some polyphenols and flavanoids (present in many fruits and vegetables), and curcumin (in turmeric).

As far as I know, no one recommends avoiding these other foods when on anti-depressants. Not to mention there are plenty of behaviors that can up-regulate serotonin receptor expression, like physical exercise. So there must be some kind of threshold for how big the effect needs to be, before it can precipitate SSRI/SNRI-induced serotonin syndrome. And I’m sure that threshold is different for different people. It’s well known that some people tolerate larger doses of the same medication than others – is this because, in addition to genetics, some people get more exercise or eat more fruits and vegetables (or get more sunlight, or have lower stress levels, or get better sleep, etc.) and thus have greater or lesser sensitivity to serotonin (due to higher/lower behavior-induced receptor density)?

I’m watching a lecture series on human behavior, and several lectures are focused on the complex interplay of genetics and environment, and I’m struck by how unbelievably dense the web of interactions is. You could research jujubes (or any food) for 100 years and find millions of effects it has on mRNA expression and the regulation of various pathways, but amazingly (at least to me) you still wouldn’t know if it’s okay to take with SSRIs until you did a clinical trial and saw that 5 extra people out of 100 had an adverse reaction. And even then you still wouldn’t know if you’d be one of the 5 people or one of the 100 until you spent another few decades researching the genetics and behavioral differences between those two groups and which group you’d likely fall into. Incredible!

Back to your original question though: I suppose it’s better safe than sorry, and people taking serotonin-increasing drugs shouldn’t take any of the obvious culprits that seem to have marked subjective effects. Maybe 1 in 5 times I eat jujube I really note a subjective, psychological effect. I don’t note this when I eat blueberries or take a fish supplement or lift weights (well, maybe 1 in 10 times from lifting weights, though I know others who feel great after ever workout – lucky bastards). So perhaps jujube is slightly stronger in its effects and is worth avoiding. On the other hand, when one eventually weens off their serotonin-increasing drugs, it’s equally worth trying to increase jujube consumption (as well as polyphenol/flavanoid rich fruit and vegetable consumption, physical exercise, early morning light exposure, improve sleep hygiene, etc. – all the myriad behaviors known to modulate serotonin receptor density/sensitivity) to see if that helps with symptoms post-medication.

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I think it may be the dose makes the poison in this case. like grapefruit, smaller amounts are usually ok- unless you’re on a higher dose of a medication

so if you were on a lower dosage medication and ate a jujube or two it wouldn’t be the same as the highest dose of venlafaxine/ssri plus an arm load of fruit.

I’m cautious with grapefruit because I take medications that can interact; I’ll have a sip of juice or a quarter of one, once in a while. but I wouldn’t go eating a bunch or drinking a big glass of it. likely the same here; I just won’t eat a bowl of them, only a few.

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