Kanna Drug Interactions: What Is Documented, Theoretical or Unknown

We found no documented kanna interaction in people, so this page sorts the cautions by how much evidence stands behind each one.

Kanna drug interactions are poorly mapped. Nobody has run the studies, so no one can hand you a reliable list of "avoid" and "fine." What exists is a set of cautions based on how kanna acts in lab tests, plus a few lists from reference sources. This post sorts those cautions by the strength of evidence behind them, which is more useful than a flat list. It is a companion to kanna and SSRIs and a spoke of is kanna safe?

How are the cautions sorted?

We use three labels, and none of them means "safe."

• Documented: a human study or published case report of kanna combined with the drug. We found none for any drug.
• Theoretical: a reference source flags the drug, or the mechanism makes a problem plausible, but nothing has been shown in people.
• Unknown: we found no source that addresses the combination at all.

To check for "documented," we searched PubMed on October 29, 2026 for Sceletium, kanna, Zembrin and mesembrine papers mentioning serotonin syndrome, case reports, adverse events, toxicity, interactions, safety, overdose, poisoning, pregnancy, CYP enzymes or liver toxicity. It returned 13 records, and none reported a drug interaction or a case of serotonin syndrome. We also found no Sceletium entry in NIH's LiverTox (checked October 29, 2026). No reports is not the same as no risk. It may just mean few people have been studied or reported.

Kanna interaction cautions at a glance

Every row ends in the same place: ask a pharmacist. The table says where the caution comes from.

Antidepressants, triptans and other serotonin-affecting medicines

These are the best-flagged group, and the full reasoning is in kanna and SSRIs.

In short: a standardized Sceletium extract blocked the serotonin transporter (IC50 4.3 ug/ml) and PDE4 (IC50 8.5 ug/ml) in a 2011 lab study [2]. Serotonin syndrome is a reaction that MedlinePlus says most often occurs when two or more medicines or drugs that affect serotonin are combined [5]. Putting those two facts together produces a theoretical concern, which is why labels and reference sites warn. It does not show that kanna has ever caused the reaction. It also does not show that it hasn't.

MedlinePlus adds one practical rule that applies to every medicine in this post: do not stop taking your medicine, and talk to your health care provider about your concerns first [5]. It also says serotonin syndrome is more likely when you first start a medicine or increase the dose [5], which is a reason to be especially careful around changes.

Kanna and St. John's wort, 5-HTP and tramadol

These are common search pairings, and the honest answer for each is "no data on the pairing; ask a pharmacist."

St. John's wort. WebMD lists it among the concerns for sceletium [1]. Separately, NCCIH says combining St. John's wort with certain antidepressants can lead to a potentially life-threatening increase of serotonin, and that it can weaken many prescription medicines [3]. The risk is documented for St. John's wort with those drugs. For St. John's wort with kanna, it is theoretical.

Tramadol. Tramadol is a prescription pain medicine. The label we opened carries a serotonin syndrome warning that names SSRIs, SNRIs, tricyclic antidepressants, triptans, MAO inhibitors and several other drug types, and tells prescribers to discontinue the drug if serotonin syndrome is suspected [4]. MedlinePlus's tramadol page also says St. John's wort and tryptophan may interact with it [8]. No source we found mentions kanna with tramadol. If you take it, ask about every supplement, not just kanna.

5-HTP. This supplement is associated with serotonin production. We looked for an NIH or MedlinePlus page on it that we could open and could not, so we are not making claims about its interactions here. Because both it and kanna are talked about in connection with serotonin, a pharmacist should hear about the combination before it happens.

What about ADHD medication, sedatives, caffeine and alcohol?

For these we found nothing that studies the pairing, and we would rather say so than guess.

• ADHD stimulants. No kanna data. MedlinePlus lists amphetamines among substances that can cause serotonin syndrome when combined with other serotonin-affecting drugs, in its list of street drugs [5]. Whether prescription stimulants plus kanna matter is not addressed by any source we found.
• Sedatives and sleep aids. One kanna trial reported positive changes in sleep [9], but that is not an interaction study. Ask a pharmacist before combining kanna with anything that makes you drowsy.
• Caffeine. Some kanna drinks include it; many do not. See kanna and caffeine.
• Alcohol. WebMD says there is not enough research to know whether sceletium interacts with foods or drinks, including alcohol [1]. We recommend not combining them; details are in can you mix kanna and alcohol.
• Other supplements. A product that combines kanna with other botanicals multiplies the unknowns. For one common pairing, see kanna and lion's mane.

Could kanna change how other drugs are processed?

We do not know. A 2015 toxicology study (Meyer and colleagues) looked at how the body breaks down the two main kanna alkaloids, mesembrine and mesembrenone, in rat urine and pooled human liver preparations. It found that they are demethylated, hydroxylated and partly excreted as conjugates [10]. That describes what happens to kanna. It does not tell us whether kanna affects the enzymes that process other drugs, and we found no study that tested that. So metabolic interactions, where one substance changes the blood level of another, can neither be ruled in nor ruled out.

Do you need to tell your surgeon?

Yes. Tell every clinician about every supplement, including kanna drinks.

The American Society of Anesthesiologists says to mention all herbal and dietary supplements before surgery, because some can prolong the effects of anesthesia, increase bleeding risk, raise blood pressure, interfere with other medications or cause heart problems. It says in some cases an anesthesiologist may recommend stopping supplements at least two weeks before a procedure, and suggests bringing your bottles to the pre-surgery visit [6]. The ASA brochure does not mention kanna specifically. We include it because the principle applies to any supplement with unstudied effects.

What should you do?

1. Make a list of everything you take, including over-the-counter products and supplements.
2. Bring the kanna product or a photo of the label, with the milligrams per serving and the other ingredients.
3. Ask a pharmacist or prescriber whether it is a good idea to combine them. Pharmacists can check interaction databases in minutes.
4. Do not stop or change a prescribed medicine on your own to make room for a supplement.
5. Be extra careful when anything on your list changes, since new or increased doses are when serotonin syndrome is more likely [5].

WebMD's overall advice is to check with a provider before combining sceletium with any medicine, and that research on interactions is incomplete [1]. We agree, and we would add that this page will be updated if studies appear. For the broader picture see is kanna safe?, and for the plant itself, what is kanna?

This page is general information, not medical advice. These statements have not been evaluated by the FDA, and kanna products are not intended for any disease or health condition.

References

1. WebMD. Sceletium: Uses, side effects, interactions. webmd.com
2. Harvey AL, et al. Pharmacological actions of the South African medicinal and functional food plant Sceletium tortuosum and its principal alkaloids. J Ethnopharmacol 2011;137(3):1124-9. PubMed
3. National Center for Complementary and Integrative Health. St. John's wort and depression: in depth. nccih.nih.gov
4. DailyMed (National Library of Medicine). Tramadol hydrochloride tablets, prescribing information, section 5.9 serotonin syndrome. dailymed.nlm.nih.gov
5. MedlinePlus. Serotonin syndrome. National Library of Medicine. medlineplus.gov
6. American Society of Anesthesiologists. Herbal and dietary supplements and anesthesia (patient brochure, 2020). asahq.org (PDF)
7. Coetzee DD, et al. High-mesembrine Sceletium extract (Trimesemine) is a monoamine releasing agent, rather than only a selective serotonin reuptake inhibitor. J Ethnopharmacol 2016;177:111-6. PubMed
8. MedlinePlus. Tramadol. National Library of Medicine. medlineplus.gov
9. Chiu S, et al. Proof-of-concept randomized controlled study of cognition effects of the proprietary extract Sceletium tortuosum (Zembrin) targeting phosphodiesterase-4 in cognitively healthy subjects. Evid Based Complement Alternat Med 2014;2014:682014. PubMed Central
10. Meyer GM, Wink CS, Zapp J, Maurer HH. GC-MS, LC-MS(n), LC-high resolution-MS(n), and NMR studies on the metabolism and toxicological detection of mesembrine and mesembrenone, the main alkaloids of the legal high "Kanna" isolated from Sceletium tortuosum. Anal Bioanal Chem 2015;407(3):761-78. PubMed

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