Epeña

Among the Yanomami and other Amazonian peoples, the resin is prepared into a fine snuff called epená or nyakwana ^{3,5Reference 3McKenna DJ et al. · 1984Monoamine oxidase inhibitors in South American hallucinogenic plants Part 2: Constituents of orally-active Myristicaceous hallucinogens — analytical/ethnopharmacology studyView study →Reference 5Ott J · 2001Pharmepéna-Psychonautics: Human intranasal, sublingual and oral pharmacology of 5-methoxy-N,N-dimethyl-tryptamine — human self-experiment studyView study →}. It is blown forcefully into the nostrils through a tube, often by another person.

The snuff acts rapidly and violently. Its effects include excitement, numbness of the limbs, twitching of the facial muscles, nausea and hallucinations, followed by a deep sleep ^{38Reference 38Fern · 2024Virola elongata (synView study →}. In some groups only shamans take it, for healing, divination and contact with the spirit world. In others, many adult men use it ^{38Reference 38Fern · 2024Virola elongata (synView study →}.

Some groups instead swallow the boiled resin as a paste or pellets ^{3,38Reference 3McKenna DJ et al. · 1984Monoamine oxidase inhibitors in South American hallucinogenic plants Part 2: Constituents of orally-active Myristicaceous hallucinogens — analytical/ethnopharmacology studyView study →Reference 38Fern · 2024Virola elongata (synView study →}.

Virola resin is applied to the skin as an antifungal, for deep fungal infections. This use is recorded among about 14 Indigenous groups in four countries ^{6Reference 6Plotkin MJ · 1990ReviewVirola: a promising genus for ethnopharmacological investigation — review of antifungal ethnobotanyView study →}. The bark exudate is also used for mouth sores and thrush ^{38Reference 38Fern · 2024Virola elongata (synView study →}.

In the Brazilian states of Amazonas and Tocantins, the resin of Virola surinamensis is a folk remedy for ulcers, gastritis, inflammation and cancer ^{7Reference 7Hiruma-Lima CA et al. · 2009AnimalAntiulcerogenic action of ethanolic extract of the resin from Virola surinamensis Warb. (Myristicaceae) — in vivo rodent studyView study →}. In Brazil the resin of Virola oleifera is used to speed wound healing and for pain and inflammation ^{8Reference 8Pereira AC et al. · 2017AnimalGastroprotective activity of the resin from Virola oleifera — in vivo mouse studyView study →}, and macerated stem bark of Virola elongata for gastric ulcers, infections and inflammation ^{33Reference 33Carvalho MS et al. · 2024In vitroEvaluation of the toxicity of the hydroethanolic extract of the stem bark of Virola elongata (Benth.) Warb. in in vitro and in vivo models — in vivo rodent toxicology studyView study →}.

The Waiãpi inhale the vapour of V. surinamensis leaves for malaria ^{32Reference 32Lopes NP et al. · 1999In vitroAntimalarial use of volatile oil from leaves of Virola surinamensis (Rol.) Warb. by Waiãpi Amazon Indians — in vitro studyView study →}.

Isolated 5-MeO-DMT, the principal Virola tryptamine, is in development for treatment-resistant depression.

In a phase 1 placebo-controlled trial, 44 healthy volunteers who had never taken a psychedelic received single intranasal doses of BPL-003, a 5-MeO-DMT benzoate salt, at 1–12 mg. It was well tolerated, with mostly mild side effects such as nasal discomfort, nausea, headache and vomiting. Blood levels peaked at about 8–10 minutes and fell with a half-life under 27 minutes. At 10–12 mg, 60% of participants had a “complete mystical experience”. Blood levels of its metabolite bufotenine were negligible ^{21Reference 21Rucker JJ et al. · 2024RCTPhase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate) in healthy participants — randomised controlled trialView study →}.

An inhaled formulation, GH001, has been given to 84 healthy volunteers and people with treatment-resistant depression across three studies, and a short rating scale has been developed to guide its dosing ^{22Reference 22Reckweg JT et al. · 2025Clinical trialEvaluation of the peak experience scale as a rapid assessment tool for the strength of a psychoactive experience with 5-MeO-DMT — clinical studyView study →}.

Reviews group 5-MeO-DMT with DMT as promising for depression and substance-use disorders, while noting a high risk of bias and no established efficacy yet ^{23,24Reference 23Wallace LM et al. · 2026Meta-analysisEfficacy of N, N-dimethyltryptamine (DMT) psychedelic therapy for substance misuse: A systematic review and meta-analysis — systematic review and meta-analysisView study →Reference 24Marazziti D et al. · 2026ReviewPsychedelic-assisted pharmacotherapy: clinical applications and regulatory considerations — reviewView study →}.

Gap: the human data describe a purified synthetic molecule given under supervision. The snuff has a highly variable mix of alkaloids ^{3Reference 3McKenna DJ et al. · 1984Monoamine oxidase inhibitors in South American hallucinogenic plants Part 2: Constituents of orally-active Myristicaceous hallucinogens — analytical/ethnopharmacology studyView study →}, and none of this research tests traditional epeña as a treatment.

An ethanolic extract of Virola surinamensis resin (500 mg/kg by mouth) reduced ethanol-induced stomach lesions in rodents by about 95%. It also reduced ulcers caused by indomethacin (39%), stress (45%) and pylorus ligation (31%). Its main constituent was epicatechin ^{7Reference 7Hiruma-Lima CA et al. · 2009AnimalAntiulcerogenic action of ethanolic extract of the resin from Virola surinamensis Warb. (Myristicaceae) — in vivo rodent studyView study →}.

Resin of Virola oleifera at 10 and 100 mg/kg reduced ethanol-induced lesions in mice by about 95–97% and indomethacin-induced lesions by about 59–66%, comparable to lansoprazole. The resin is rich in polyphenols (about 82%), including epicatechin and eriodictyol ^{8Reference 8Pereira AC et al. · 2017AnimalGastroprotective activity of the resin from Virola oleifera — in vivo mouse studyView study →}.

A hydroethanolic stem-bark extract of Virola elongata, standardised to gallic acid, catechin and rutin, reproduced the antiulcer effect in a third species ^{9Reference 9Almeida GVB et al. · 2019AnimalChemical characterization and evaluation of gastric antiulcer properties of the hydroethanolic extract of the stem bark of Virola elongata (Benth.) Warb — in vivo rodent studyView study →}.

The activity is attributed to antioxidant, protective phenolics in the stomach lining. All of it is single-dose prevention work in rodents, with no studies of healing established ulcers and no human trials. The authors of one study advised care because local people report toxic symptoms from the crude resin ^{7Reference 7Hiruma-Lima CA et al. · 2009AnimalAntiulcerogenic action of ethanolic extract of the resin from Virola surinamensis Warb. (Myristicaceae) — in vivo rodent studyView study →}.

Aryltetralone lignans from Virola sebifera inhibited lipid peroxidation more effectively than α-tocopherol in vitro ^{10Reference 10Rezende KR et al. · 2005In vitroAntioxidant activity of aryltetralone lignans and derivatives from Virola sebifera (Aubl.) — in vitro studyView study →}. The neolignan otobaphenol blocked iron- and ascorbate-driven lipid peroxidation in mitochondria and delayed the permeability transition ^{11Reference 11Lemeshko VV et al. · 2003In vitroThe natural antioxidant otobaphenol delays the permeability transition of mitochondria and induces their aggregation — in vitro studyView study →}.

The polyphenol-rich resin of V. oleifera showed strong radical-scavenging activity ^{12Reference 12Dos Santos Corrêa A et al. · 2018In vitroVirola oleifera-capped gold nanoparticles showing radical-scavenging activity and low cytotoxicity — in vitro studyView study →}.

In atherosclerosis-prone mice, four weeks of the resin reduced fat deposits in blood vessels by about 50%, independent of cholesterol ^{13Reference 13Coutinho PN et al. · 2017AnimalChronic administration of antioxidant resin from Virola oleifera attenuates atherogenesis in LDLr — in vivo mouse studyView study →}. In a mouse model of contrast-dye kidney damage, it protected kidney function in a dose-dependent way, with better kidney histology than N-acetylcysteine ^{14Reference 14Bôa IS et al. · 2015AnimalResin from Virola oleifera Protects Against Radiocontrast-Induced Nephropathy in Mice — in vivo mouse studyView study →}.

A topical resin formulation also sped wound contraction in rats while lowering tissue lipid and protein oxidation ^{15Reference 15Carvalho GR et al. · 2022AnimalDevelopment and Evaluation of Virola oleifera Formulation for Cutaneous Wound Healing — in vivo rat studyView study →}.

All of it is in vitro or in animals. No human oxidative-stress endpoint has been tested.

The neolignan grandisin from Virola surinamensis reduced writhing in mice in a dose-dependent way, without sedation. It cut inflammatory-phase pain by about 60% and oil-induced ear swelling by about 36% ^{16Reference 16Carvalho AA et al. · 2010AnimalAntinociceptive and antiinflammatory activities of grandisin extracted from Virola surinamensis — in vivo mouse studyView study →}.

From Virola michelli leaves, the natural flavone titonine and two semi-synthetic derivatives reduced carrageenan paw swelling in rats by 22%, 41% and 68%, and the natural flavone was analgesic in a dose-dependent way ^{17Reference 17Carvalho JC et al. · 1999AnimalAnti-inflammatory activity of flavone and some of its derivates from Virola michelli Heckel — in vivo rat studyView study →}.

A hydroethanolic extract of Virola elongata bark lowered TNF-α, IL-1β and nitric oxide and raised IL-10 in mouse models of peritonitis and dermatitis ^{18Reference 18Di Serio BF et al. · 2024In vitroPhytochemistry and Evaluation of the Anti-Inflammatory Activity of the Hydroethanolic Extract of Virola elongata (Benth.) WarbView study →}.

⚠ One V. oleifera study found no effect on LPS-induced nitric oxide in chondrocytes ^{31Reference 31Francisco V et al. · 2021In vitroEvaluation of Virola oleifera activity in musculoskeletal pathologies: Inhibition of human multiple myeloma cells proliferation and combination therapy with dexamethasone or bortezomib — in vitro studyView study →}.

Antifungal use of Virola exudate is recorded among about 14 Amazonian groups in four countries, applied to deep fungal skin infections ^{6Reference 6Plotkin MJ · 1990ReviewVirola: a promising genus for ethnopharmacological investigation — review of antifungal ethnobotanyView study →}.

Racemic 8.O.4′-neolignans typical of Virola inhibited hyphal growth of the mould Neurospora crassa, apparently by interfering with cell-wall synthesis, though inhibition of β-glucan synthase did not fully explain the effect ^{19Reference 19Zacchino S et al. · 1998In vitroIn vitro studies on mode of action of antifungal 8.O.4’-neolignans occurring in certain species of Virola and related genera of Myristicaceae — in vitro studyView study →}.

Broader antimicrobial screening of Virola surinamensis extracts showed activity against microbial panels ^{20Reference 20Costa ES et al. · 2008In vitroAntimicrobial activity of some medicinal plants of the Cerrado, Brazil — in vitro studyView study →}.

Gap: no controlled clinical antifungal trial. The in vitro work uses a model fungus and isolated neolignans, and the active principle of the whole resin has not been pinned down.

Neolignans from Virola species and synthetic analogues were active against Leishmania donovani promastigotes in vitro, but inactive against the intracellular amastigotes. The best synthetic analogue, a sulphur-bridged compound, reduced amastigotes in the liver of mice by 42%, which was not statistically significant ^{25Reference 25Barata LE et al. · 2000In vitroAnti-leishmanial activity of neolignans from Virola species and synthetic analogues — in vitro and in vivo studyView study →}.

A hexane extract of Virola surinamensis leaves killed Leishmania promastigotes, but none of the extracts had any effect on the intracellular amastigotes ^{26Reference 26Veiga A et al. · 2017In vitroLeishmania amazonensis and Leishmania chagasi: In vitro leishmanicide activity of Virola surinamensis (rol.) warb — in vitro studyView study →}.

Lignans from V. surinamensis twigs were the most active fraction against Trypanosoma cruzi in vitro ^{27Reference 27Lopes NP et al. · 1998In vitroFlavonoids and lignans from Virola surinamensis twigs and their in vitro activity against Trypanosoma cruzi — in vitro studyView study →}, and a newly described lignan, (−)-5-demethoxygrandisin B, adds to the antileishmanial series ^{28Reference 28Paes SS et al. · 2023In vitroPaes SS, et al. (2023). (-)-5-Demethoxygrandisin B a New Lignan from Virola surinamensis (Rol.) Warb. Leaves: Evaluation of the Leishmanicidal Activity by In Vitro and In Silico Approaches — in vitro study. Pharmaceutics. 15(9). https://pubmed.ncbi.nlm.nih.gov/37765261/View study →}.

Gap: activity is largely confined to the free-living parasite forms and to isolated or synthetic compounds. No natural Virola preparation has cured an infection in animals.

Polyketides from Virola sebifera leaves were selectively cytotoxic to ovarian (OVCAR03) and multidrug-resistant (NCI-ADR) cancer cell lines at 2–4 µg/mL ^{29Reference 29Denny C et al. · 2008In vitroAntiproliferative properties of polyketides isolated from Virola sebifera leaves — in vitro studyView study →}.

Essential oils from Virola surinamensis bark and leaves inhibited human colon-cancer HCT116 cells in vitro and slowed HCT116 tumour growth in mice ^{30Reference 30Anunciação TAD et al. · 2020In vitroIn vitro and in vivo inhibition of HCT116 cells by essential oils from bark and leaves of Virola surinamensis (Rol. ex Rottb.) Warb. (Myristicaceae) — in vitro and in vivo mouse studyView study →}.

Resin from Virola oleifera reduced the viability of multiple-myeloma cells and combined favourably with dexamethasone, but it antagonised the cancer drug bortezomib ^{31Reference 31Francisco V et al. · 2021In vitroEvaluation of Virola oleifera activity in musculoskeletal pathologies: Inhibition of human multiple myeloma cells proliferation and combination therapy with dexamethasone or bortezomib — in vitro studyView study →}.

Gap: mostly cell-line work, with a single mouse tumour study.

The Waiãpi of Amapá inhale the vapour of Virola surinamensis leaves for malaria. The essential oil of young leaves stopped 100% of Plasmodium falciparum development from young trophozoite to schizont in vitro. The sesquiterpene nerolidol, at 100 µg/mL, was one of the active constituents, and its activity was linked to inhibition of glycoprotein synthesis ^{32Reference 32Lopes NP et al. · 1999In vitroAntimalarial use of volatile oil from leaves of Virola surinamensis (Rol.) Warb. by Waiãpi Amazon Indians — in vitro studyView study →}.

Gap: one in vitro study, using the volatile leaf oil rather than the bark resin.

The snuff. 5-MeO-DMT is one of the most powerful serotonergic psychedelics known. The snuff acts rapidly and violently, causing excitement, numbness of the limbs, twitching of the face, nausea and hallucinations, followed by deep sleep ^{38Reference 38Fern · 2024Virola elongata (synView study →}.

MAOI combinations. Deaths have been reported when 5-MeO-DMT was combined with monoamine oxidase inhibitor (MAOI) drugs, and rhabdomyolysis and agitation have also been recorded ^{35Reference 35Rached G et al. · 2026Clinical trialSafety and Efficacy of Monoamine Oxidase Inhibitors in Patients Who Use Psychoactive Substances: Potential Drug Interactions and Substance Use Disorder Treatment Data — review of drug interactionsView study →}. MAO-inhibiting β-carbolines from Banisteriopsis are sometimes added to the snuff, and they strengthen the tryptamines ^{5Reference 5Ott J · 2001Pharmepéna-Psychonautics: Human intranasal, sublingual and oral pharmacology of 5-methoxy-N,N-dimethyl-tryptamine — human self-experiment studyView study →}.

How 5-MeO-DMT is cleared. 5-MeO-DMT is broken down mainly by monoamine oxidase A; the liver enzyme CYP2D6 turns a smaller share into the active metabolite bufotenine, and blocking MAO-A raised 5-MeO-DMT and bufotenine levels several-fold in mice ^{39Reference 39Shen HW et al. · 2010In vitroEffects of monoamine oxidase inhibitor and cytochrome P450 2D6 status on 5-methoxy-N,N-dimethyltryptamine metabolism and pharmacokinetics — in vitro and mouse studyView study →}.

Unpredictable strength. Alkaloid content differs widely between species, collections and preparations, so the strength of any given snuff cannot be known in advance ^{3Reference 3McKenna DJ et al. · 1984Monoamine oxidase inhibitors in South American hallucinogenic plants Part 2: Constituents of orally-active Myristicaceous hallucinogens — analytical/ethnopharmacology studyView study →}.

Other interactions. In human liver preparations, the lignan grandisin inhibited the drug-metabolising enzymes CYP2C9 and CYP3A4/5, but not CYP1A2 or CYP2D6 to any real degree, and it raised CYP2E1 activity ^{34Reference 34Habenschus MD et al. · 2017In vitroIn Vitro Inhibition of Human CYP450s 1A2, 2C9, 3A4/5, 2D6 and 2E1 by Grandisin — in vitro studyView study →}. Virola oleifera resin antagonised the cancer drug bortezomib in multiple-myeloma cells ^{31Reference 31Francisco V et al. · 2021In vitroEvaluation of Virola oleifera activity in musculoskeletal pathologies: Inhibition of human multiple myeloma cells proliferation and combination therapy with dexamethasone or bortezomib — in vitro studyView study →}.

Non-alkaloid extracts. A hydroethanolic Virola elongata bark extract was not toxic to cells or DNA in vitro, and in rats the no-observed-adverse-effect level was above 1,200 mg/kg ^{33Reference 33Carvalho MS et al. · 2024In vitroEvaluation of the toxicity of the hydroethanolic extract of the stem bark of Virola elongata (Benth.) Warb. in in vitro and in vivo models — in vivo rodent toxicology studyView study →}. That finding does not extend to the alkaloid-rich snuff.

Legal status. DMT and 5-MeO-DMT are controlled substances (Schedule I or equivalent) in most countries.