research and studies

Landscape analysis Two structural facts define the field. First, the highest-value IP is not raw-plant IP; it sits on new chemical entities, isotopologues, salts/polymorphs, and delivery systems. That is why the strongest granted U.S. positions cluster around mitragynine-class opioid receptor modulators and C11-modified analogs, while 3-deuteromitragynine and its salt forms are protected in later continuation-style filings. The claims are usually framed around pain, mood/anxiety disorders, opioid-use / withdrawal indications, or, more selectively, alcohol use disorder. Second, a broad composition family filed by Caamtech functions almost like a catch-all purified-alkaloid platform. It expressly lists many kratom constituents, including mitragynine, 7-hydroxymitragynine, paynantheine, speciociliatine, speciogynine, mitraphylline, and others, but the family is broad and combinatorial rather than a marker that each listed alkaloid has its own dedicated drug-development program. The original U.S. case was abandoned, while a later continuation remained pending in the retrieved record. Within the papers, the most actionable non-mitragynine signals are narrower. Speciociliatine is being revisited as a meaningful μ-opioid partial agonist and circulating metabolite; paynantheine and speciogynine stand out for serotonergic activity and as scaffolds for δ-opioid-leaning alcohol-use-disorder derivatives; mitraphylline is present in kratom chemistry and ADME studies but does not, in the retrieved English primary sources, anchor a comparably mature therapeutic IP track. Alkaloid and derivative table Rows are ordered from the strongest compound-specific IP programs to broader or earlier-stage research coverage. Where the retrieved source did not expose a date or definitive national-phase status, it is marked unspecified. Dedicated programs and derivative classes Alkaloid / derivative Claimant(s) Patent or application numbers, jurisdiction, status, dates Intended use / indication Development stage Key claims or mechanism from patent / paper Primary sources Mitragynine; also MG, (-)-mitragynine; C23H30N2O4; structure in PubChem CID 3034396 Kures; Syncotrance; University of Florida group / UFRF; NIDA clinical program WO2022234524A1 (PCT, ceased; priority 2021-05-06, filed 2022-05-06, pub 2022-11-10) plus named national phases incl. US20240239798A1, GB2623043A, EP4351573A1; US20230364172A1 (US, abandoned; priority 2022-05-14, filed 2023-05-15, pub 2023-11-16) with continuation US20240366702A1 (pending, filed 2024-03-18, publication date unspecified in retrieved source); WO2024092269A1 (WIPO, published; priority 2022-10-28, pub 2024-05-02); NCT07204171 (ClinicalTrials.gov, Phase 1 oral MG001; sponsor NIDA). Formulation / CMC, improved oral bioavailability, palatability, solubility, and controlled oral delivery; clinical safety/PK for purified mitragynine formulation. Clinical Phase 1 for MG001; otherwise formulation / preclinical. Patents emphasize salts/crystalline forms of mitragynine and phospholipid or oral-bioavailability formulations. Papers characterize mitragynine as a low-efficacy / partial MOR agonist and atypical opioid scaffold rather than a conventional opioid full agonist. PubChem structure; salts/polymorphs family; Syncotrance formulation; UF formulation; ClinicalTrials.gov study. 7-Hydroxymitragynine; also 7-HMG, 7-OH, 7-OH-MIT; C23H30N2O5; structure in PubChem Individual inventors; early Chinese academic synthesis filing; also listed in broad composition family CN106967067A (China, pending; priority/filed 2017-05-25, pub 2017-07-21); US12492201B1 (US, active/granted; priority 2024-05-15, filed 2025-02-13, pub/grant 2025-12-09; priority claimed from US12466830B1 path). Primarily manufacturing / purification IP; research papers tie the compound to analgesia / pain signaling as mitragynine’s active metabolite. Preclinical / unknown as a therapeutic development program in retrieved primary sources. Patent claims cover conversion of mitragynine to high-purity 7-OH via routes including PIFA oxidation, Fenton chemistry, CYP450-mediated conversion, or enzyme/light-assisted conversion. The 2019 ACS Central Science paper identifies 7-OH as an active metabolite of mitragynine and a key mediator of its analgesic effect via μ-opioid receptor signaling. PubChem; CN106967067A; US12492201B1; ACS Cent. Sci. 2019. Mitragynine pseudoindoxyl; also MP; C23H30N2O5; structure in PubChem Memorial Sloan Kettering family; later Columbia / MSK / RFMH C11 family Core early family WO2016176657A1 (PCT, ceased; priority 2015-04-30, filed 2016-04-29, pub 2016-11-03); granted national phases listed as US11046692B2, EP3291676B1, CA2983314C; later continuation US20220024923A1 (filed 2021-06-24, pending in retrieved family listing). Analgesia / pain; scaffold optimization for atypical opioid activity. Preclinical. The associated paper reports that conversion from the indole to spiro-pseudoindoxyl form markedly increases opioid-receptor affinity; the pseudoindoxyls showed promise as potent analgesics with MOR agonism / DOR antagonism. Later analog IP also claims C11-substituted pseudoindoxyls. PubChem; WO2016176657A1 family; J. Med. Chem. 2016. 3-Deuteromitragynine; also 3-DM; deuterated mitragynine analog; structure in patent figures Columbia / RFMH / Memorial Sloan Kettering; Kures WO2020160280A1 (PCT, ceased; priority 2019-02-01, filed 2020-01-30, pub 2020-08-06); country-status lines in the retrieved family page show US17/427,502 pending, CA3128726A pending, CN202080024396.7A pending, JP2021544618A pending, EP withdrawn, AU abandoned, KR ceased; follow-on WO2022234524A1 (PCT, ceased; priority 2021-05-06, filed 2022-05-06, pub 2022-11-10) claims salts and polymorphs of mitragynine and 3-DM. Patents state pain, depressive / anxiety / mood disorders, substance-use disorders, opioid use disorder / withdrawal, alcohol use disorder, and physicochemical / purification improvements. Preclinical. The deuterated family claims that deuteration attenuates formation of toxic 3-dehydromitragynine (DHM) while preserving formation of the active 7-OH metabolite; the later Kures family adds salt / crystalline-form claims for manufacturability and properties. WO2020160280A1 family; WO2022234524A1 family. C11-substituted mitragynine-family analogs; includes C11-modified analogs of mitragynine, 7-hydroxymitragynine, mitragynine-ethylene glycol adduct, and mitragynine pseudoindoxyl Columbia / RFMH / Memorial Sloan Kettering WO2020037136A1 (PCT, ceased; priority 2018-08-16, filed 2019-08-15); US11760758B2 (US, active/granted; filed 2021-02-16, grant/pub 2023-09-19); EP3836924A1 (EP, withdrawn in retrieved family record). Pain, mood disorders, substance use disorders, including claims mentioning opioid addiction / withdrawal symptoms. Preclinical. The family claims that C11 substitution unexpectedly tunes opioid-receptor efficacy across MG, 7-OH, MG-EG, and pseudoindoxyl scaffolds, giving medicinal chemists a way to fine-tune receptor signaling rather than simply increase potency. US11760758B2 / WO2020037136A1; site-selective C–H functionalization paper. Mitragynine-class opioid receptor modulators; broader Columbia family covering mitragynine-alkaloid-derived modulators, including deuterium-enriched embodiments Columbia WO2017165738A1 (PCT, ceased; priority 2016-03-25, filed 2017-03-24, pub 2017-09-28); search-result family lines show US10961244B2 (granted 2021-03-30) and US11912707B2 (granted 2024-02-27). Pain, depressive disorder, mood disorder, anxiety disorder; combination claims with NMDAR antagonists, NK antagonists, and DOR agonists. Preclinical. The patent family positions the mitragynine scaffold as a source of opioid receptor modulators with psychiatric and analgesic claims, and it explicitly mentions deuterium-enriched embodiments. Analytically, this family looks like a foundational bridge between the earlier analog work and the later C11/deuterated branches. WO2017165738A1; grant listings; 2016 receptor-signaling / scaffold paper. Natural minor alkaloids and focused derivative leads Alkaloid / derivative Claimant(s) Patent or application numbers, jurisdiction, status, dates Intended use / indication Development stage

Quotes from SSDP’s official statement: “The U.S. Food and Drug Administration (FDA) is recommending that the Drug Enforcement Administration (DEA) classify 7-hydroxymitragynine, or 7-OH, as a Schedule I controlled substance under the Controlled Substances Act (CSA). The Department of Health & Human Services sent a press release this past Tuesday, July 25, that the FDA is taking steps to restrict 7-OH products.”“SSDP strongly opposes the proposed federal scheduling of 7-Hydroxy-Mitragynine, or 7-OH — a naturally occurring compound found in kratom.““This proposed scheduling reflects outdated thinking that has failed our generation before. It undermines harm reduction, ignores real-world data, and sends a dangerous message: that consumer voices and lived experiences don’t matter.“ Source: SSDP (Students for Sensible Drug Policy)🔗 Read the full article here

Source: Marwood Group https://www.marwoodgroup.com/

Source: https://pmc.ncbi.nlm.nih.gov/articles/PMC7542979 Abstract Background Kratom (Mitragyna speciosa Korth.) has been used in Southeast Asia for hundreds of years to increase energy, for relaxation, and to diminish opioid withdrawal. Kratom use has recently spread to Western countries. Kratom could potentially be used for the treatment of opioid withdrawal and pain, but more insight is needed into its abuse potential. Therefore, we investigated the rewarding properties of the primary kratom alkaloid mitragynine and its active metabolite 7-hydroxymitragynine, and morphine as a reference drug in male and female rats. These compounds have agonist activity at mu-opioid receptors. read the full study herehttps://pmc.ncbi.nlm.nih.gov/articles/PMC7542979

Source: https://pmc.ncbi.nlm.nih.gov/articles/PMC6598159 Mitragyna speciosa, more commonly known as kratom, is a plant native to Southeast Asia, the leaves of which have been used traditionally as a stimulant, analgesic, and treatment for opioid addiction. Recently, growing use of the plant in the United States and concerns that kratom represents an uncontrolled drug with potential abuse liability, have highlighted the need for more careful study of its pharmacological activity. The major active alkaloid found in kratom, mitragynine, has been reported to have opioid agonist and analgesic activity in vitro and in animal models, consistent with the purported effects of kratom leaf in humans. However, preliminary research has provided some evidence that mitragynine and related compounds may act as atypical opioid agonists, inducing therapeutic effects such as analgesia, while limiting the negative side effects typical of classical opioids. Here we report evidence that an active metabolite plays an important role in mediating the analgesic effects of mitragynine. We find that mitragynine is converted in vitro in both mouse and human liver preparations to the much more potent mu-opioid receptor agonist 7-hydroxymitragynine and that this conversion is mediated by cytochrome P450 3A isoforms. Further, we show that 7-hydroxymitragynine is formed from mitragynine in mice and that brain concentrations of this metabolite are sufficient to explain most or all of the opioid-receptor-mediated analgesic activity of mitragynine. At the same time, mitragynine is found in the brains of mice at very high concentrations relative to its opioid receptor binding affinity, suggesting that it does not directly activate opioid receptors. The results presented here provide a metabolism-dependent mechanism for the analgesic effects of mitragynine and clarify the importance of route of administration for determining the activity of this compound. Further, they raise important questions about the interpretation of existing data on mitragynine and highlight critical areas for further research in animals and humans. read full study herehttps://pmc.ncbi.nlm.nih.gov/articles/PMC6598159