Akuammidine

Akuammidine at a Glance

Akuammidine is a monoterpenoid indole alkaloid of the sarpagine (sarpagan) type — C₂₁H₂₄N₂O₃, CAS 639-36-1, also catalogued under the older name rhazine ^{24Reference 24PubChem · 2026Akuammidine, CID 15558574 — C₂₁H₂₄N₂O₃, MW 352.4, CAS 639-36-1View study →}. Structurally it is the 16S epimer of polyneuridine: the two differ at a single stereocentre, and which one a plant makes is decided by tailoring enzymes downstream of the sarpagan bridge ^{5Reference 5Mann SGA et al. · 2025Stereochemical insights into sarpagan and akuammiline alkaloid biosynthesisView study →}.

Its home is the akuamma tree, Picralima nitida — a West African Apocynaceae whose seeds are a traditional remedy for pain and fever, and whose alkaloids (akuammine, akuammicine, akuammigine, pseudo-akuammigine, akuammiline, akuammidine) all take their names from akuamma itself ^{1,2,6Reference 1Menzies JR et al. · 1998Opioid activity of alkaloids extracted from Picralima nitida (famView study →Reference 2Creed SM et al. · 2021Isolation and pharmacological characterization of six opioidergic Picralima nitida alkaloidsView study →Reference 6Laryea MK et al. · 2026Antiplasmodial and anti-trypanosomial monoterpene indole alkaloids from Picralima nitidaView study →}. Akuammidine also occurs across the wider Apocynaceae and its allies: Alstonia scholaris, Aspidosperma quebracho-blanco, Amsonia tabernaemontana, Voacanga africana, Kopsia teoi, and the Loganiaceae genera Gardneria and Gelsemium ^{7,8,9,11,12,15,16Reference 7Adepiti AO et al. · 2025Secondary metabolites from the stem bark of Alstonia boonei and the seeds of Picralima nitida with antibacterial activitiesView study →Reference 8Muhammad MT et al. · 2024Chemodiverse monoterpene indole alkaloids from Kopsia teoi, inhibitory potential against α-amylase, and their molecular docking studiesView study →Reference 9Coon AM · 2023Investigation of small-molecule constituents in Voacanga africana seeds and mapping of their spatial distributions using laser ablation direct analysis in real-time imaging-mass spectrometry (LADI-MS)View study →Reference 11Teng S et al. · 2023A molecular networking-based isolation of gardneria alkaloids from Gardneria distincta and their anti-inflammatory activityView study →Reference 12Mahar R et al. · 2022Assessment of tissue specific distribution and seasonal variation of alkaloids in Alstonia scholarisView study →Reference 15Zhang Q et al. · 2011Zhang Q, Zhang B, Chou G, Wang Z (2011). [Chemical constituents of aerial parts of Gelsemium elegans]. Zhongguo Zhong Yao Za Zhi 36(10):1305–1310. https://pubmed.ncbi.nlm.nih.gov/21837971/View study →Reference 16Lyon RL et al. · 1973Biological and phytochemical evaluation of plantsView study →}.

It is not, on current evidence, a lesser periwinkle (Vinca minor) constituent — see the next section. Pharmacologically it is the most interesting of the akuamma alkaloids and also one of the least studied: a single 1998 paper established it as a µ-opioid-preferring agonist at micromolar concentrations, and essentially nothing has followed up on the molecule itself in the twenty-seven years since ^{1Reference 1Menzies JR et al. · 1998Opioid activity of alkaloids extracted from Picralima nitida (famView study →}.

The Vinca Attribution

This database first met akuammidine through Vinca minor, and that route needs correcting rather than repeating.

The link comes from one 2025 enzymology paper. Mai and colleagues characterised two promiscuous V. minor cytochrome P450 hydroxylases, VmV10H and VmPs10H, and showed that VmV10H hydroxylates structurally diverse indole alkaloids — vincaminoreine, pericyclivine, apparicine and akuammidine — as part of a route toward the µ-opioid alkaloid akuammine ^{4Reference 4Mai Z et al. · 2025Promiscuous and regiospecific Vinca minor hydroxylases for opioid akuammine biosynthesis and monoterpenoid indole alkaloid diversificationView study →}. That is an in-vitro substrate list, not a phytochemical inventory. Akuammidine was fed to the enzyme; it was not reported as isolated from the plant.

The same laboratory’s follow-up settles the question more directly. In a 2025 New Phytologist study of sarpagan and akuammiline stereochemistry spanning six alkaloid-producing species including V. minor, the akuammidine reference standard was purified from Amsonia tabernaemontana, and the compound the authors actually found and purified from V. minor leaves was strictamine, not akuammidine ^{5Reference 5Mann SGA et al. · 2025Stereochemical insights into sarpagan and akuammiline alkaloid biosynthesisView study →}. The genus-level generalisation in that paper’s introduction — that Rauvolfia and Vinca species make 16S derivatives such as akuammidine and sarpagine alongside 16R derivatives such as vincamajine and ajmaline — is a statement about biosynthetic capability across a genus, not a detection in V. minor leaf.

The honest position: V. minor possesses the enzymatic machinery that acts on akuammidine, and the lesser periwinkle monograph is right to name it in that context. But no primary source reports akuammidine isolated or quantified from Vinca minor, and the account is therefore framed by Picralima nitida — the plant where the molecule was named, isolated, and pharmacologically tested.

Akuammidine vs. the Other Akuamma Alkaloids

The akuamma alkaloids share a prefix, a plant and a reputation, and almost nothing else. Readers arriving here expecting “the opioid one” need to know which molecule did what, because the literature is easy to misread by substring.

Alkaloid	Structural type	What was actually shown
Akuammidine	sarpagine	µ-preferring binding (Ki 0.6 µM); agonist in mouse vas deferens, reversed by naloxone and the µ-selective antagonist CTOP 1Reference 1Menzies JR et al. · 1998Opioid activity of alkaloids extracted from Picralima nitida (famView study →
Akuammine	akuammiline (picraline-related)	Similar µ affinity (Ki 0.5 µM) but an antagonist, pK_B 5.7 against DAMGO 1Reference 1Menzies JR et al. · 1998Opioid activity of alkaloids extracted from Picralima nitida (famView study →; a weak agonist in later cell-based work, with minimal antinociception in animals 2Reference 2Creed SM et al. · 2021Isolation and pharmacological characterization of six opioidergic Picralima nitida alkaloidsView study →
Akuammicine	strychnan	Highest κ-opioid affinity of the set (Ki 0.2 µM); full κ agonist in guinea-pig ileum 1Reference 1Menzies JR et al. · 1998Opioid activity of alkaloids extracted from Picralima nitida (famView study →
Akuammigine	heteroyohimbine	Little or no efficacy in the opioid bioassays 1Reference 1Menzies JR et al. · 1998Opioid activity of alkaloids extracted from Picralima nitida (famView study →
Pseudo-akuammigine	akuammiline	Little opioid efficacy in vitro 1Reference 1Menzies JR et al. · 1998Opioid activity of alkaloids extracted from Picralima nitida (famView study →, yet the one akuamma alkaloid with in-vivo anti-inflammatory and partly naloxone-reversible analgesic data in rats 23Reference 23Duwiejua M et al. · 2002AnimalPseudo-akuammigine, an alkaloid from Picralima nitida seeds, has anti-inflammatory and analgesic actions in ratsView study →
Akuammiline / picraline	akuammiline / picraline	Opioid receptors identified as the primary targets in a >40-receptor panel; micromolar at best 2Reference 2Creed SM et al. · 2021Isolation and pharmacological characterization of six opioidergic Picralima nitida alkaloidsView study →

Three consequences follow.

First, “akuamma is opioid” is true at the plant level and misleading at the molecule level. The alkaloids split into µ-agonist, µ-antagonist and κ-agonist roles that would partly cancel one another in a whole-seed preparation.

Second, akuammidine is the family’s clearest µ-agonist — and was left out of the modern re-evaluation. The 2021 study that isolated six akuamma alkaloids by pH-zone-refining countercurrent chromatography and screened them against a large CNS receptor panel reported on akuammine, pseudo-akuammigine, picraline, akuammicine and akuammiline; akuammidine is not among the compounds it characterised pharmacologically ^{2Reference 2Creed SM et al. · 2021Isolation and pharmacological characterization of six opioidergic Picralima nitida alkaloidsView study →}. So the best-resourced modern akuamma pharmacology programme does not contain a data point for this molecule.

Third, do not import Catharanthus pharmacology. Akuammidine is a monomeric sarpagine alkaloid. Vincristine and vinblastine are bisindole alkaloids of Madagascar periwinkle (Catharanthus roseus), a different genus and a different chemical class; none of their cytotoxic-chemotherapy profile has any bearing on this compound.

What It's Used For

The molecule-level evidence is thin and old. One 1998 isolate study carries almost all of it; two in-vitro reports and two untranslated 1950s–60s French notes carry the rest. Every row below is in vitro or ex vivo — akuammidine has never been administered to a whole animal in a published study, let alone a person.

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. Every score here is capped low on purpose: no application has in-vivo data for this molecule. Each application links down to its write-up.

01Mu-Opioid Receptor ActivityShaky38%One 1998 isolate study — binding Ki 0.6 µM plus naloxone/CTOP-reversible agonism in isolated tissue ^{1Reference 1Menzies JR et al. · 1998Opioid activity of alkaloids extracted from Picralima nitida (famView study →}

02Anti-Inflammatory (Cytokine Suppression)Shaky26%Purified akuammidine at 20 µM in LPS-stimulated RAW 264.7 macrophages ^{11Reference 11Teng S et al. · 2023A molecular networking-based isolation of gardneria alkaloids from Gardneria distincta and their anti-inflammatory activityView study →}; supporting NF-κB microfraction signal ^{14Reference 14Hou Y et al. · 2012Microfractionation bioactivity-based ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry for the identification of nuclear factor-κB inhibitors and β2 adrenergic receptor agonists in an alkaloidal extract of the folk herb Alstonia scholarisView study →}

03Antiparasitic (Plasmodium / Trypanosoma)Shaky16%Isolate screened in a P. nitida panel and reported as moderate only ^{6Reference 6Laryea MK et al. · 2026Antiplasmodial and anti-trypanosomial monoterpene indole alkaloids from Picralima nitidaView study →}

04Local Anaesthetic (Historical)Shaky15%Two single-author French notes from 1954 and 1961, no abstracts, never replicated ^{19,20Reference 19Raymond-Hamet · 1954Comparison of the local anesthetic activity of akuammidine with that of cocaineView study →Reference 20Raymond-Hamet · 1961Raymond-Hamet (1961). [On the intestinal effects of akuammidine]. Comptes Rendus Hebdomadaires des Séances de l’Académie des Sciences 253:1278–1280. https://pubmed.ncbi.nlm.nih.gov/14490722/View study →}

Mechanisms

The load-bearing point is the first row and its ceiling. Micromolar µ affinity with agonist behaviour is a real pharmacological property, but it is roughly a thousand-fold weaker than the opioids people compare it to, and it has never been shown to produce analgesia in an animal.

Pharmacokinetics

None exists. No absorption, oral bioavailability, distribution, metabolism, half-life, protein-binding or active-metabolite data have been published for akuammidine in any species. There is no validated bioanalytical method for it in plasma, and no exposure figure to compare against the ~0.6–20 µM concentrations at which its in-vitro effects appear — which is exactly the comparison that would decide whether any of them matter after oral intake of akuamma seed. This absence is the single largest hole on the page.

Clinical Trials

There have been none. No trial has administered akuammidine to a human being, and no registered study lists it as an intervention. The nearest human data are observational and concern the whole seed: a 2024 web-based survey of 369 US participants found 28 (7.6%) reporting lifetime akuamma seed use, mostly for pain management and opioid substitution, with 60.7% of users reporting pain relief — self-report, uncontrolled, and about a multi-alkaloid botanical product rather than this molecule ^{21Reference 21Timmons P et al. · 2026Akuamma seed (Picralima nitida) use in the U.S.: findings from a web-based surveyView study →}.

Last checked: July 2026.

Isolate vs. Plant Studies

Unusually for this database, almost everything on akuammidine is isolate work — and that is not the strength it usually is, because the isolate work is so sparse.

The opioid characterisation used alkaloids extracted and purified from P. nitida seeds, assayed as individual compounds in binding and tissue-bath preparations ^{1Reference 1Menzies JR et al. · 1998Opioid activity of alkaloids extracted from Picralima nitida (famView study →}. The anti-inflammatory result used purified akuammidine from Gardneria distincta at a defined concentration ^{11Reference 11Teng S et al. · 2023A molecular networking-based isolation of gardneria alkaloids from Gardneria distincta and their anti-inflammatory activityView study →}. The antiparasitic and antibacterial screens tested isolated, NMR-characterised compounds ^{6,7Reference 6Laryea MK et al. · 2026Antiplasmodial and anti-trypanosomial monoterpene indole alkaloids from Picralima nitidaView study →Reference 7Adepiti AO et al. · 2025Secondary metabolites from the stem bark of Alstonia boonei and the seeds of Picralima nitida with antibacterial activitiesView study →}. The reference standard used in the 2025 biosynthesis work was purified from Amsonia tabernaemontana and structurally confirmed by NMR ^{5Reference 5Mann SGA et al. · 2025Stereochemical insights into sarpagan and akuammiline alkaloid biosynthesisView study →}. There is no whole-extract study whose effect has been attributed to akuammidine on evidence.

The plant-level layer belongs to something else. Akuamma seed — the traditional West African analgesic and the botanical now sold in the US — is a mixture in which akuammine and pseudo-akuammigine are the abundant alkaloids, and in which the µ-agonist, µ-antagonist and κ-agonist activities documented in ^{1Reference 1Menzies JR et al. · 1998Opioid activity of alkaloids extracted from Picralima nitida (famView study →} would interact. The one in-vivo analgesia study on any akuamma alkaloid used pseudo-akuammigine, not akuammidine ^{23Reference 23Duwiejua M et al. · 2002AnimalPseudo-akuammigine, an alkaloid from Picralima nitida seeds, has anti-inflammatory and analgesic actions in ratsView study →}. So the traditional use is evidence about a seed; it is not evidence about this molecule, and it is not treated as such.

One further caution about identifications: akuammidine is increasingly reported by LC-MS annotation rather than isolation — in kratom leaf metabolomics ^{10Reference 10Veeramohan R et al. · 2023Comparative metabolomics analysis reveals alkaloid repertoires in young and mature Mitragyna speciosa (Korth.) Havil. leavesView study →}, and, as “(Z)-akuammidine”, among the docking-selected “active components” of a cicada-slough traditional medicine in a network-pharmacology study ^{25Reference 25Liang H et al. · 2025Investigation of c-Fos/c-Jun signaling pathways in Periostracum Cicadae’s inhibition of EMT in gastric tissueView study →}. Annotations of that kind are hypotheses about identity, not isolations, and they are treated accordingly.

Prevalence in Nature

Akuammidine is a widely distributed but never-quantified alkaloid. No source has been assigned a percentage dry-weight figure, so the occurrence story below is qualitative by necessity.

The type source — Picralima nitida (akuamma), Apocynaceae. The seeds are the classical source and the material for every pharmacological study of the compound ^{1,6,7Reference 1Menzies JR et al. · 1998Opioid activity of alkaloids extracted from Picralima nitida (famView study →Reference 6Laryea MK et al. · 2026Antiplasmodial and anti-trypanosomial monoterpene indole alkaloids from Picralima nitidaView study →Reference 7Adepiti AO et al. · 2025Secondary metabolites from the stem bark of Alstonia boonei and the seeds of Picralima nitida with antibacterial activitiesView study →}. Akuammidine sits alongside akuammine, akuammicine, akuammigine, pseudo-akuammigine, akuammiline, rhazimol and alstonine there ^{6Reference 6Laryea MK et al. · 2026Antiplasmodial and anti-trypanosomial monoterpene indole alkaloids from Picralima nitidaView study →}.

Apocynaceae beyond Picralima.

• Alstonia scholaris (devil’s tree) — quantified by NMR across leaves, stems, trunk bark, fruits and flowers; akuammidine was low in every tissue except fruit, which the authors identify as the best part for isolating it ^{12Reference 12Mahar R et al. · 2022Assessment of tissue specific distribution and seasonal variation of alkaloids in Alstonia scholarisView study →}. It also appears in bioactivity-guided fingerprints of the leaf alkaloid fraction ^{14Reference 14Hou Y et al. · 2012Microfractionation bioactivity-based ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry for the identification of nuclear factor-κB inhibitors and β2 adrenergic receptor agonists in an alkaloidal extract of the folk herb Alstonia scholarisView study →}.
• Aspidosperma quebracho-blanco — isolated in 1967 and again in a 1973 phytochemical evaluation, alongside aspidospermine, quebrachidine and rhazinilam ^{16,17Reference 16Lyon RL et al. · 1973Biological and phytochemical evaluation of plantsView study →Reference 17Markey S · 1967Isolation of rhazidine and akuammidine from Aspidosperma quebracho blancoView study →}.
• Amsonia tabernaemontana (blue star) — the species from which the modern NMR-verified akuammidine standard was purified, and the one shown to possess a dedicated akuammidine aldehyde reductase ^{5Reference 5Mann SGA et al. · 2025Stereochemical insights into sarpagan and akuammiline alkaloid biosynthesisView study →}.
• Voacanga africana — mapped by laser-ablation imaging mass spectrometry to the seed endosperm, with strictamine, polyneuridine and vobasine ^{9Reference 9Coon AM · 2023Investigation of small-molecule constituents in Voacanga africana seeds and mapping of their spatial distributions using laser ablation direct analysis in real-time imaging-mass spectrometry (LADI-MS)View study →}.
• Kopsia teoi — isolated from the bark and explicitly labelled sarpagine-type ^{8Reference 8Muhammad MT et al. · 2024Chemodiverse monoterpene indole alkaloids from Kopsia teoi, inhibitory potential against α-amylase, and their molecular docking studiesView study →}.

Beyond Apocynaceae. Gardneria distincta (Loganiaceae) yields akuammidine among its gardneria alkaloids ^{11Reference 11Teng S et al. · 2023A molecular networking-based isolation of gardneria alkaloids from Gardneria distincta and their anti-inflammatory activityView study →}, and the aerial parts of Gelsemium elegans yield the geometric isomer 19-(Z)-akuammidine ^{15Reference 15Zhang Q et al. · 2011Zhang Q, Zhang B, Chou G, Wang Z (2011). [Chemical constituents of aerial parts of Gelsemium elegans]. Zhongguo Zhong Yao Za Zhi 36(10):1305–1310. https://pubmed.ncbi.nlm.nih.gov/21837971/View study →}. A tentative LC-MS annotation places it in kratom (Mitragyna speciosa) leaf, reported as one of several alkaloids newly added to that species’ repertoire — an annotation, not an isolation ^{10Reference 10Veeramohan R et al. · 2023Comparative metabolomics analysis reveals alkaloid repertoires in young and mature Mitragyna speciosa (Korth.) Havil. leavesView study →}.

What it is not. No primary report places akuammidine in lesser periwinkle tissue; the Vinca minor connection is enzymatic (see above) ^{4,5Reference 4Mai Z et al. · 2025Promiscuous and regiospecific Vinca minor hydroxylases for opioid akuammine biosynthesis and monoterpenoid indole alkaloid diversificationView study →Reference 5Mann SGA et al. · 2025Stereochemical insights into sarpagan and akuammiline alkaloid biosynthesisView study →}. And it is absent from the Catharanthus bisindole story entirely.

Its role in plants. Akuammidine is a downstream product of the central monoterpenoid-indole-alkaloid pathway. Geissoschizine is oxidatively cyclised by sarpagan bridge enzymes, which can generate both the 16S akuammidine aldehyde and the 16R polyneuridine aldehyde; downstream reductases, deformylases and decarbomethoxylases then epimerise C16, and it is this tailoring — not the cyclisation itself — that decides a species’ stereochemical output ^{5Reference 5Mann SGA et al. · 2025Stereochemical insights into sarpagan and akuammiline alkaloid biosynthesisView study →}. Whether the plant ends up with akuammidine, polyneuridine, strictamine or ajmaline is therefore a matter of which tailoring enzymes it carries.

Discovery & Synthesis

The compound is named for akuamma, the West African name for Picralima nitida, which it shares with akuammine, akuammicine, akuammigine and akuammiline — all products of the early-twentieth-century surveys of the tree’s seed alkaloids. (The primary 1920s–30s papers were not read directly; the date is given as approximate and the point is flagged in the gaps tracker.)

Structure and stereochemistry came later, and slowly. Akuammidine belongs to a cluster of closely related sarpagine stereoisomers that were difficult to tell apart by the methods of the day; the group was resolved by mass spectrometry in 1963, in a study devoted specifically to the stereoisomers of the sarpagine–akuammidine group ^{18Reference 18Ohashi M et al. · 1963Mass spectrometry in structural and stereochemical problemsView study →}. Modern work still distinguishes akuammidine from its C16 epimer polyneuridine by ¹H-NMR chemical shift (H5 at δ 3.06 vs δ 4.27) ^{5Reference 5Mann SGA et al. · 2025Stereochemical insights into sarpagan and akuammiline alkaloid biosynthesisView study →}.

Total synthesis arrived only in 2022. A structure-units-oriented strategy built the indole-fused azabicyclo[3.3.1]nonane core by a new Mannich-type cyclisation, fused the aza-bridged E-ring by SmI₂-mediated coupling, and installed the 19-E or 19-Z alkene stereoselectively; it delivered fourteen sarpagine–ajmaline–koumine alkaloids, of which akuammidine and 19-Z-akuammidine were synthesised for the first time ^{13Reference 13Chen W et al. · 2022Structure units oriented approach towards collective synthesis of sarpagine-ajmaline-koumine type alkaloidsView study →}.

Supply today is by isolation, not synthesis: purification from P. nitida seed by pH-zone-refining countercurrent chromatography and related preparative methods is the practical route to gram-scale akuamma alkaloids ^{2Reference 2Creed SM et al. · 2021Isolation and pharmacological characterization of six opioidergic Picralima nitida alkaloidsView study →}, and research standards have been purified from A. tabernaemontana ^{5Reference 5Mann SGA et al. · 2025Stereochemical insights into sarpagan and akuammiline alkaloid biosynthesisView study →}. There is no commercial-scale production — the molecule is a research chemical.

Patents: not yet researched.

Toxicity & Safety

Akuammidine’s toxicity is genuinely unknown, and the badge reflects that literally. There is no acute or repeat-dose toxicology, no genotoxicity or reproductive-toxicity package, no organ-toxicity study, no human exposure report, and no adverse-event record for the isolated compound. It has never been administered to a whole animal in a published study. Absence of reported harm here means absence of testing, not evidence of safety.

Two indirect signals are worth stating, because both concern the plant and are the reason a reader might land here.

The µ-opioid signal implies opioid-class questions that have never been asked. A compound with µ-agonist behaviour raises the standard opioid concerns — respiratory depression, tolerance, dependence, additive CNS depression with alcohol, benzodiazepines or other opioids, and interaction with opioid antagonists. None of these has been studied for akuammidine, and its micromolar potency and unknown bioavailability mean it is unclear whether they are reachable at all. They are listed as unassessed, not as established risks.

Akuamma products have already caused an opioid-type harm. A 2026 case report describes a man in sustained remission from opioid use disorder who developed severe opioid-like withdrawal — refractory to benzodiazepines, resolving on buprenorphine/naloxone — after heavy use of a gas-station beverage marketed as “kava”; product labelling indicated akuamma (Picralima nitida), and independent testing of the same product found kratom derivatives and kavalactones ^{22Reference 22Malhotra A et al. · 2026Case reportWhen “kava” isn’t kava: opioid-like withdrawal responsive to buprenorphine — a case reportView study →}. That is a harm of a mislabelled polyherbal product, and the case cannot be attributed to any single alkaloid, let alone this one. It nonetheless establishes that akuamma-containing products circulate in the unregulated supplement market with µ-opioid-active content and real clinical consequences ^{21,22Reference 21Timmons P et al. · 2026Akuamma seed (Picralima nitida) use in the U.S.: findings from a web-based surveyView study →Reference 22Malhotra A et al. · 2026Case reportWhen “kava” isn’t kava: opioid-like withdrawal responsive to buprenorphine — a case reportView study →}.

Safety at a Glance

❔ Toxicity unknown

• Toxicity genuinely unknown. No toxicology, genotoxicity, reproductive or human data exist for isolated akuammidine. Nothing here should be read as a safety clearance.
• Opioid-class questions unassessed. µ-agonist behaviour in vitro means respiratory-depression, dependence and CNS-depressant-interaction questions apply in principle — none has been tested for this molecule.
• Akuamma seed products are not this molecule and carry documented risk. Opioid-like dependence and withdrawal have been reported from an unregulated akuamma-labelled product that also contained kratom derivatives.
• No interaction data at all. No CYP or transporter work, no protein binding, no co-administration study. Interactions cannot be ruled out because they have never been looked for.

Dosage

There is no dose for akuammidine and no basis for one. The molecule has never been given to a person or a whole animal in a published study. The only numbers attached to it are assay concentrations, and they are not doses:

Akuamma seed dosing does not transfer. Products sold as akuamma are whole-seed preparations containing several alkaloids with opposing opioid actions ^{1Reference 1Menzies JR et al. · 1998Opioid activity of alkaloids extracted from Picralima nitida (famView study →}, and the human use that exists is self-reported and uncontrolled ^{21Reference 21Timmons P et al. · 2026Akuamma seed (Picralima nitida) use in the U.S.: findings from a web-based surveyView study →}. Whatever dose someone takes of a seed product, the fraction that is akuammidine is unmeasured and its absorption unknown.

These are research assay concentrations, reported for transparency, and are not a personal recommendation.

References

1. Menzies JR, Paterson SJ, Duwiejua M, Corbett AD (1998). Opioid activity of alkaloids extracted from Picralima nitida (fam. Apocynaceae). European Journal of Pharmacology 350(1):101–108. https://pubmed.ncbi.nlm.nih.gov/9683021/
2. Creed SM, Gutridge AM, Argade MD, Hennessy MR, Friesen JB, Pauli GF, van Rijn RM, Riley AP (2021). Isolation and pharmacological characterization of six opioidergic Picralima nitida alkaloids. Journal of Natural Products 84(1):71–80. https://pubmed.ncbi.nlm.nih.gov/33326237/
3. Hennessy MR, Gutridge AM, French AR, Rhoda ES, Meqbil YJ, Gill M, Kashyap Y, Appourchaux K, Paul B, Wang ZJ, van Rijn RM, Riley AP (2023). Modified akuamma alkaloids with increased potency at the mu-opioid receptor. Journal of Medicinal Chemistry 66(5):3312–3326. https://pubmed.ncbi.nlm.nih.gov/36827198/
4. Mai Z, Richardson MB, Mann SGA, Greene J, Paul AA, Perley JO, Deslongchamps G, Qu Y (2025). Promiscuous and regiospecific Vinca minor hydroxylases for opioid akuammine biosynthesis and monoterpenoid indole alkaloid diversification. Plant Physiology and Biochemistry. https://pubmed.ncbi.nlm.nih.gov/40168857/
5. Mann SGA, Paz-Galeano M, Shahsavarani M, Perley JO, Guo J, Garza-Garcia JJO, Qu Y (2025). Stereochemical insights into sarpagan and akuammiline alkaloid biosynthesis. New Phytologist 247(3):1335–1351. https://pubmed.ncbi.nlm.nih.gov/40458973/
6. Laryea MK, Abotsi KMW, Woode E, Dickson RA, Webster L, Ekuadzi E (2026). Antiplasmodial and anti-trypanosomial monoterpene indole alkaloids from Picralima nitida. Natural Product Research 40(6):1548–1557. https://pubmed.ncbi.nlm.nih.gov/39605297/
7. Adepiti AO, Nyamboki DK, Bedane KG, Elujoba AA, Spiteller M, Matasyoh JC (2025). Secondary metabolites from the stem bark of Alstonia boonei and the seeds of Picralima nitida with antibacterial activities. Natural Product Research 39(16):4751–4756. https://pubmed.ncbi.nlm.nih.gov/38684042/
8. Muhammad MT, Beniddir MA, Phongphane L, Abu Bakar MH, Hussin MH, Awang K, Litaudon M, Supratman U, Azmi MN (2024). Chemodiverse monoterpene indole alkaloids from Kopsia teoi, inhibitory potential against α-amylase, and their molecular docking studies. Fitoterapia 174:105873. https://pubmed.ncbi.nlm.nih.gov/38417682/
9. Coon AM, Musah RA (2023). Investigation of small-molecule constituents in Voacanga africana seeds and mapping of their spatial distributions using laser ablation direct analysis in real-time imaging-mass spectrometry (LADI-MS). ACS Omega 8(30):27190–27205. https://pubmed.ncbi.nlm.nih.gov/37546641/
10. Veeramohan R, Zamani AI, Azizan KA, Goh HH, Aizat WM, Razak MFA, Yusof NSM, Mansor SM, Baharum SN, Ng CL (2023). Comparative metabolomics analysis reveals alkaloid repertoires in young and mature Mitragyna speciosa (Korth.) Havil. leaves. PLoS One 18(3):e0283147. https://pubmed.ncbi.nlm.nih.gov/36943850/
11. Teng S, He J, Wang X, Li Y, Khan A, Zhao T, Wang Y, Cheng G, Liu Y (2023). A molecular networking-based isolation of gardneria alkaloids from Gardneria distincta and their anti-inflammatory activity. Phytochemistry 209:113639. https://pubmed.ncbi.nlm.nih.gov/36889562/
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