Yangonin

Yangonin at a Glance

Yangonin is one of the six major kavalactones (styryl-2-pyrones) of kava (Piper methysticum), the Pacific root traditionally prepared as a relaxing, anxiety-easing beverage. By quantity it is a minor constituent — a small and chemotype-dependent share of the kavalactone fraction ^{6Reference 6Wang J et al. · 2015Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solventsView study →} — but chemically it is the most fully conjugated of the group, and that extended di-enone chromophore is what gives kava resin its characteristic yellow colour.

Its interest is out of proportion to its abundance. Yangonin is the one kava constituent shown to bind the CB1 cannabinoid receptor ^{1Reference 1Ligresti A et al. · 2012Kavalactones and the endocannabinoid system: the plant-derived yangonin is a novel CB1 receptor ligandView study →}, and it also carries monoaminergic activity — it is among the kava pyrones that inhibit monoamine oxidase B (MAO-B) ^{3Reference 3Uebelhack R et al. · 1998Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)View study →}. That combination places yangonin on a different axis from the anxiolytic workhorse of kava, kavain, whose sedative action runs mainly through GABA-A. Yangonin is a proposed contributor to kava’s mood and relaxation effects beyond GABA, by way of the endocannabinoid and monoamine systems.

Two honesty notes frame everything below. First, almost all yangonin-specific data are in-vitro or animal work on the isolated molecule — the human evidence is for whole kava, not this pyrone. Second, kava’s safety story is a story about plant part and chemotype: the traditional root-derived kavalactones (yangonin among them) have a very different toxicological profile from the aerial-part alkaloids that dominate the hepatotoxicity controversy ^{10,11Reference 10Nerurkar PV et al. · 2004In vitroIn vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactonesView study →Reference 11Teschke R · 2011Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →}.

The Endocannabinoid Angle: Yangonin As A CB1 Ligand

This is the compound-defining fact and the reason yangonin has its own literature apart from “a kavalactone.”

In a structure–activity screen of natural kavalactones and analogues against the endocannabinoid system, only yangonin bound the human recombinant CB1 receptor, with an affinity of Ki ≈ 0.72 μM and clear selectivity over CB2 (Ki > 10 μM); none of the compounds strongly inhibited the endocannabinoid-degrading enzymes FAAH or MAGL ^{1Reference 1Ligresti A et al. · 2012Kavalactones and the endocannabinoid system: the plant-derived yangonin is a novel CB1 receptor ligandView study →}. The authors framed this as a route by which the endocannabinoid system might contribute to kava’s complex psychopharmacology — a mechanism entirely separate from the GABA-A modulation that explains kavain’s sedation.

The binding is not just a test-tube curiosity. In a 2024 rat study, intrathecal yangonin produced antinociception and blunted carrageenan-induced hyperalgesia, and the effect was completely reversed by the CB1 antagonist PF 514273 — while kavain, tested alongside, did nothing in the same paradigm ^{2Reference 2Chow LH et al. · 2024Yangonin, one of the kavalactones isolated from Piper methysticum GView study →}. That is a functional, in-vivo demonstration that yangonin acts through spinal CB1 receptors, not merely near them.

So among kavalactones, yangonin is the endocannabinoid one. It is a modest-affinity CB1 ligand (micromolar, not the nanomolar range of designed cannabinoid drugs), but it is the molecule that gives kava a plausible cannabinoid-system footprint — a distinctive, compound-unique feature that the more abundant kavalactones lack.

What It's Used For

Yangonin’s evidence base is small, mechanistic, and almost entirely about the isolated molecule or kava extracts — not about yangonin dosed in people. The load-bearing signals are the CB1 interaction and a monoaminergic (MAO-B) action; the anxiolytic reputation belongs to whole kava and mostly to other kavalactones.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Yangonin’s isolate data are preclinical, so scores stay modest; the anxiolytic row is a whole-kava effect this molecule only partly shares.

01Endocannabinoid / CB1-mediated (analgesia, mood)Shaky40%Isolate: CB1 binding (Ki 0.72 μM) + CB1-dependent anti-hyperalgesia in rats ^{1,2Reference 1Ligresti A et al. · 2012Kavalactones and the endocannabinoid system: the plant-derived yangonin is a novel CB1 receptor ligandView study →Reference 2Chow LH et al. · 2024Yangonin, one of the kavalactones isolated from Piper methysticum GView study →}

02Monoaminergic / MAO-B inhibitionShaky30%Yangonin among kava pyrones inhibiting platelet MAO-B ^{3Reference 3Uebelhack R et al. · 1998Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)View study →}; extract-level CNS receptor engagement ^{4Reference 4Dinh LD et al. · 2001In vitroInteraction of various Piper methysticum cultivars with CNS receptors in vitroView study →}

03Anxiolytic / sedative (as a kavalactone)Shaky24%Whole-kava anxiety trials ^{7,8Reference 7Pittler MH · 2003Systematic reviewKava extract for treating anxietyView study →Reference 8Sarris J et al. · 2013RCTKava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled studyView study →}; the GABA-A/anxiolytic load sits mainly on other kavalactones ^{3,5Reference 3Uebelhack R et al. · 1998Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)View study →Reference 5Seitz U et al. · 1997Seitz U, et al. (1997). [3H]-monoamine uptake inhibition properties of kava pyrones. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/9434608/View study →}

Mechanisms

The load-bearing row is CB1: yangonin is the only kavalactone that engages it, and the in-vivo effect is antagonist-reversible — the cleanest compound-unique mechanism here.

Pharmacokinetics

Dedicated human pharmacokinetics for isolated yangonin do not exist; what is known is inferred from kavalactone pharmacology generally. Kavalactones are lipophilic styryl-pyrones that are absorbed from the gut and cross the blood–brain barrier (consistent with kava’s central effects), and kava constituents are recognised inhibitors of several cytochrome-P450 enzymes, the basis of kava’s herb–drug interaction potential ^{11Reference 11Teschke R · 2011Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →}. Yangonin’s fully conjugated structure makes it the pigment fraction, but its absorption, oral bioavailability, metabolism, active metabolites and half-life as an isolate are uncharacterised — a real hole, since a micromolar CB1 ligand present at low abundance needs PK numbers before any in-vivo relevance at human intakes can be judged.

Clinical Trials

There are no clinical trials of isolated yangonin. The human trial record is for whole kava root extract standardised to total kavalactones — Cochrane-reviewed anxiety trials ^{7Reference 7Pittler MH · 2003Systematic reviewKava extract for treating anxietyView study →} and a generalized-anxiety-disorder RCT ^{8Reference 8Sarris J et al. · 2013RCTKava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled studyView study →} — within which yangonin is only a minor component.

Last checked: July 2026.

Isolate vs. Plant Studies

The split is stark and worth stating plainly. Yangonin’s distinctive pharmacology is all isolate work: the CB1 binding is recombinant-receptor data ^{1Reference 1Ligresti A et al. · 2012Kavalactones and the endocannabinoid system: the plant-derived yangonin is a novel CB1 receptor ligandView study →}, the anti-hyperalgesia is rodent intrathecal dosing of the pure compound ^{2Reference 2Chow LH et al. · 2024Yangonin, one of the kavalactones isolated from Piper methysticum GView study →}, and the MAO-B result is an isolated-pyrone assay ^{3Reference 3Uebelhack R et al. · 1998Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)View study →}. Yangonin’s human evidence is all plant: every clinical outcome belongs to standardised kava root extract ^{7,8Reference 7Pittler MH · 2003Systematic reviewKava extract for treating anxietyView study →Reference 8Sarris J et al. · 2013RCTKava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled studyView study →}, in which yangonin is a minor, chemotype-variable fraction. The two do not substitute for each other — a clean CB1 mechanism for the molecule does not establish that drinking kava delivers a meaningful cannabinoid effect, because the isolate’s abundance and human PK are exactly what is missing. Where extract-level receptor pharmacology exists (the D2/opioid/histamine/serotonin panel), it was measured on cultivar extracts, not on yangonin ^{4Reference 4Dinh LD et al. · 2001In vitroInteraction of various Piper methysticum cultivars with CNS receptors in vitroView study →}.

Prevalence In Nature

Yangonin is essentially a kava-specific kavalactone, occurring in the root and rhizome of Piper methysticum as one of the six major styryl-pyrones alongside kavain, dihydrokavain, methysticin, dihydromethysticin and its close relative desmethoxyyangonin ^{6Reference 6Wang J et al. · 2015Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solventsView study →}. Its share of the kavalactone profile is minor and strongly chemotype-dependent — the ratio of the six lactones (and thus how much yangonin is present) shifts markedly between “noble” cultivars and two-day (tudei)/wichmannii types, and between root and rhizome, so yangonin content is a moving target rather than a fixed number ^{6Reference 6Wang J et al. · 2015Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solventsView study →}.

Structurally, yangonin is the most conjugated of the kavalactones: an extended, fully unsaturated di-enone system linking the 4-methoxyphenyl (styryl) ring to the 2-pyrone. That conjugation is why yangonin absorbs into the visible range and reads as the yellow pigment of kava resin. Its near-relative desmethoxyyangonin is simply yangonin lacking the para-methoxy group on the styryl ring — the two are the “yangonin pair” of the kavalactone family and both feature in kava’s monoaminergic (MAO-B) activity ^{3Reference 3Uebelhack R et al. · 1998Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)View study →}.

Discovery & Synthesis

Yangonin is one of the classically characterised kava constituents, isolated from Piper methysticum during the long arc of nineteenth- and early-twentieth-century kavalactone chemistry that also gave the styryl-pyrone structures their names; the exact first-isolation date is not well documented in accessible modern sources, so it is left uncredited here rather than asserted. The compound’s defining modern discovery is pharmacological, not chemical: the identification of yangonin as a CB1 cannabinoid-receptor ligand by Ligresti and colleagues in 2012 ^{1Reference 1Ligresti A et al. · 2012Kavalactones and the endocannabinoid system: the plant-derived yangonin is a novel CB1 receptor ligandView study →}, followed by the in-vivo CB1-mediated anti-hyperalgesia work in 2024 ^{2Reference 2Chow LH et al. · 2024Yangonin, one of the kavalactones isolated from Piper methysticum GView study →}, is what turned a minor yellow pyrone into a molecule of specific interest.

There is no commodity manufacture of yangonin. It is obtained by extraction from kava root as part of the kavalactone fraction and, for research, isolated chromatographically or purchased as a reference standard; it is not produced at scale as an isolated ingredient.

Patents: not yet researched.

Toxicity & Safety

Yangonin carries a moderate flag — not because the isolated pyrone is a demonstrated toxin, but because it is a CNS-active kavalactone that exists only inside kava, and kava is the subject of a genuine, regulator-level hepatotoxicity controversy. The molecule cannot be waved through as benign, yet the honest reading is that yangonin is not the leading suspect in kava liver injury.

The critical distinction is plant part and chemotype. The traditional aqueous root beverage — the source of the kavalactones, yangonin included — has a long safety record, whereas the hepatotoxicity signal points toward constituents concentrated in aerial parts (leaves, stem peelings) and in some solvent extracts: the piperidine alkaloid pipermethystine is cytotoxic to human HepG2 hepatocytes in vitro, unlike the kavalactones tested alongside it ^{10Reference 10Nerurkar PV et al. · 2004In vitroIn vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactonesView study →}, and reviews of kava hepatotoxicity converge on pipermethystine, the chalcone flavokavain B, and mould-derived hepatotoxins as the primary assumed culprits — not the kavalactone fraction that yangonin belongs to ^{11Reference 11Teschke R · 2011Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →}. In controlled trials of standardised kava root extract, liver-function monitoring did not surface the feared signal ^{9Reference 9Sarris J et al. · 2013RCTKava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction, and sexual effectsView study →}.

Two further cautions attach to yangonin as a kavalactone rather than to yangonin specifically. Kava constituents inhibit multiple cytochrome-P450 enzymes, giving kava real herb–drug interaction potential (and a plausible route by which co-ingested drugs or poor-quality extract could worsen liver risk) ^{11Reference 11Teschke R · 2011Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →}. And as a centrally active preparation, kava can add to alcohol and other CNS depressants; heavy traditional use is also associated with a reversible scaly skin condition (kava dermopathy) — both are whole-kava effects, not yangonin-isolate findings.

Reproductive and developmental toxicity for isolated yangonin is not characterised; pregnancy/lactation decisions belong to the kava herb page, where intake is actually decided, not to this molecule page.

Safety at a Glance

⚠️ Moderate toxicity

• The kavalactone fraction is not the hepatotoxic suspect. In-vitro and review evidence points to aerial-part pipermethystine, flavokavain B and mould toxins — not the root kavalactones — as the primary hepatotoxicity culprits ^{10,11Reference 10Nerurkar PV et al. · 2004In vitroIn vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactonesView study →Reference 11Teschke R · 2011Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →}.
• Kava carries a real hepatotoxicity controversy. Yangonin exists only inside kava, which has been restricted in several countries over liver-injury reports; provenance (noble root vs aerial parts/tudei) and extract quality matter ^{11Reference 11Teschke R · 2011Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →}.
• CYP450 inhibition → interactions. Kava constituents inhibit several cytochrome-P450 enzymes, so kava has genuine herb–drug interaction potential ^{11Reference 11Teschke R · 2011Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →}.
• Additive CNS depression. As a component of a centrally active preparation, yangonin’s context (kava) can compound alcohol and other sedatives; the isolate has no standalone human safety data.

Dosage

There is no established or recommended dose for isolated yangonin, and it is not used as a standalone ingredient. It is encountered only as a minor fraction of whole kava root, where dosing is standardised to total kavalactones — commonly around 120–240 mg kavalactones/day in anxiety research (e.g. the LKGD extract used in the generalized-anxiety RCT, and the extracts pooled in the Cochrane review) ^{7,8Reference 7Pittler MH · 2003Systematic reviewKava extract for treating anxietyView study →Reference 8Sarris J et al. · 2013RCTKava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled studyView study →}. The yangonin delivered by any such dose depends on the cultivar’s kavalactone ratio and is not itself titrated ^{6Reference 6Wang J et al. · 2015Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solventsView study →}.

Preclinical yangonin figures (recombinant-receptor binding, rodent intrathecal dosing) are experimental and not convertible to human use ^{1,2Reference 1Ligresti A et al. · 2012Kavalactones and the endocannabinoid system: the plant-derived yangonin is a novel CB1 receptor ligandView study →Reference 2Chow LH et al. · 2024Yangonin, one of the kavalactones isolated from Piper methysticum GView study →}. These are doses studied in research and are not a personal recommendation.

References

1. Ligresti A, et al. (2012). Kavalactones and the endocannabinoid system: the plant-derived yangonin is a novel CB1 receptor ligand. Pharmacological Research. https://pubmed.ncbi.nlm.nih.gov/22525682/
2. Chow LH, et al. (2024). Yangonin, one of the kavalactones isolated from Piper methysticum G. Forst, acts through cannabinoid 1 (CB1) receptors to induce an intrathecal anti-hyperalgesia. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/38823663/
3. Uebelhack R, et al. (1998). Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava). Pharmacopsychiatry. https://pubmed.ncbi.nlm.nih.gov/9832350/
4. Dinh LD, et al. (2001). Interaction of various Piper methysticum cultivars with CNS receptors in vitro. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/11458444/
5. Seitz U, et al. (1997). [3H]-monoamine uptake inhibition properties of kava pyrones. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/9434608/
6. Wang J, et al. (2015). Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solvents. Journal of Food Science and Technology. https://pubmed.ncbi.nlm.nih.gov/25694734/
7. Pittler MH, Ernst E (2003). Kava extract for treating anxiety. Cochrane Database of Systematic Reviews. https://pubmed.ncbi.nlm.nih.gov/12535473/
8. Sarris J, et al. (2013). Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. Journal of Clinical Psychopharmacology. https://pubmed.ncbi.nlm.nih.gov/23635869/
9. Sarris J, et al. (2013). Kava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction, and sexual effects. Phytotherapy Research. https://pubmed.ncbi.nlm.nih.gov/23348842/
10. Nerurkar PV, et al. (2004). In vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactones. Toxicological Sciences. https://pubmed.ncbi.nlm.nih.gov/14737001/
11. Teschke R (2011). Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culprits. Digestive and Liver Disease. https://pubmed.ncbi.nlm.nih.gov/21377431/

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