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Everything posted by Alchemica
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Citizen Plant Science - Exploring the Aizoaceae
Alchemica posted a topic in Pharmacology, Chemistry & Medicine
I feel the succulent dimension holds an interesting element in potentially having more therapeutically useful "in the real world" dimensions than more commonly touted plant medicines for their often more gentle but occasionally empathogenic edge. Also, the combination of often pro-cognitive (PDE4 inhibition seen with mesembrine-type alkaloids) with potent antidepressant effects meets an unmet demand. Part 1: Background and 'citizen analysis' using readily available materials Some Aizoaceae have been analysed [1]: I wanted to see if it was feasible to get some rough idea of the phytochemistry of a plant using only readily available materials eg. making it suitable for citizen science. I've been curious about simple TLC and paper chromatography as tools, particularly how feasible 'citizen TLC analysis' of plants is using a suitable paper, readily available solvent systems and simple visualisation techniques, compared to more conventional TLC. Can simple maceration of a medicinal plant in a readily available benignish solvent, concentration, spotting on common craft materials, developing the plate and OTC visualisation give some rough idea of the phytochemistry of a medicinal plant? Sceletium has in the past been analysed via conventional TLC [2, 3] and more advanced techniques [4] It took about 30 trials to find a readily available solvent system and semi-suitable paper - after many failed attempts, I found an 'etch art paper' that seemed the best I could find. I'm still to follow up with confirmation on silica TLC plates but it seems to give *a very rough idea* Sceletium tortuosum (unfermented, root powder) was used as a reference. This gives a main compound Rf = 0.5-0.54 on the craft paper. I particularly wanted to research D. bosseranum and Trichodiadema stellatum Method: Sample preparation: Samples were dehydrated at 70 deg. C and powdered. The samples were macerated in isopropanol. If no phenolic constituents were expected, NaOH q.s. was used to basify, otherwise basified with ammonia solution. The isopropanol solutions were concentrated to a small sample. Samples were spotted onto a plate, either a suitable craft paper, or silica gel plates. Acetone was used to elute the plate and I2 vapour (from OTC tincture) used as a visualisation technique. Crude technique - Craft Paper Note: this technique is limited in effectiveness and I suggest if you're that keen to play around with something like this, I'd suggest you just stick with silica gel plates to save A LOT of hassle. Delosperma bosseranum Sceletium tortuosum (unfermented, root) was compared to D. bosseranum. A compound with the same Rf as Sceletium was noted along with other constituents. Trichodiadema stellatum (syn. barbatum) Sceletium tortuosum (unfermented, root) was compared to D. bosseranum. A compound with the same Rf as Sceletium was noted along with other constituents. Mesembryanthemum cordifolium (syn. Aptenia cordifolia) This has been studied and seems to contain 4,5-dihydro-4’-O-methylsceletenone and 4’-O-methylsceletenone along with flavanoids, tannins, phenols, saponins, and cinnamic acid derivatives (and esters) The characteristic Sceletium constituent was absent in these but other different compounds were present. Will follow up with more conventional silica TLC which will hopefully have more easily reproducible results -
Anyone have clues on this one just from these pics? Edit: seems it's Mammillaria bocasana
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Have two spare baggies of fresh D bosseranum I can put in an envelope no cost for interested people (No WA/Tas) First two to get in contact - will send ASAP The phytochemistry of this plant is from my understanding unknown but some find it superior to the Sceletiums While some find Sceletium to be "short acting, created anxiety and far too much stimulation", one preliminary report using D. bosseranum "two days of relief from my depression was over. It was a totally transparent experience that was all me. No depressive crash after this was over. It was like being lifted out of depression on angel wings, and just as gently dropped off back in my normal state of being two days later." D. bosseranum is currently used in a similar way to Sceletium species (Kanna/Kougoed), the unfermented dried tuber is used, as well as the fermented whole plant (aerial and underground parts together). [herbalistics]
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3 more free baggies for interested people, last lot were snapped up quick.
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I've been interested in this Lobelia as a potentially superior (?) alternative plant to L. inflata. 'The Penobscot people smoked the dried leaves as a substitute for tobacco. It may also have been chewed'. Lobinaline caused a significant, dose-dependent increase in dopamine release and preclinical and clinical data exist that support nAChR-based ligands as promising therapeutic agents for the treatment of depression, alcohol and drug dependence. The alkaloid has been proposed as a treatment for Parkinson's and psychostimulant abuse [1]. Lobinaline appears to be distinct from nicotine and lobeline in terms of its selectivity and functional effects at nAchRs and is a DAT inhibitor. Compared to other plant metabolites, such as nicotine and lobeline, lobinaline is relatively non-selective with respect to α4β2- and α7-nAchRs Lobinaline displays appropriate pharmacokinetics and low mammalian toxicity in mice relative to lobeline, the most widely studied Lobelia alkaloid. Haven't bioassayed myself but if anyone wants to grow it (say first 3 replies in this thread and PMs) let me know. Seed was collected from the plant pictured. No TAS/WA sorry. [1] https://pubmed.ncbi.nlm.nih.gov/27105955/
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Both gone, should be more seed pods soon so I'll update soon
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Bumping this topic up, I have two small plants available free if someone super keen missed out, let them root up a bit more before sending, they'll die back over cool frosty periods but warmer states or someone with a greenhouse might do well with them this size. Once again, sorry, no WA/Tas. While there is history of traditional use [1] and herbalists suggest it may be a nervine, contemporary use of the plant remains very limited. Lobinaline is devoid of the characteristic actions of lobeline and in mice, lobinaline is less toxic than lobeline (but did lower animals blood pressure) [2]. Toxicology suggests a large quantity ingested is toxic with symptoms reported as being "nausea, vomiting, diarrhea, salivation, exhaustion and weakness, dilation of pupils, convulsions, and coma" but some have used it in smaller quantities as a tea [3]. Lobinaline is an inhibitor of the dopamine transporter (DAT) in vitro and in vivo. It is more potent for inhibiting DAT (IC50 = 11.95 μM) vs lobeline (IC50 = 30-80 μM) [4]. In addition, lobinaline is a weak non-subtype selective partial agonist at nicotinic acetylcholine receptors (nAChRs) and a good free radical scavenger. it is likely that the DAT inhibitory actions are "atypical" in not having abuse liability. Early herbalists noted that a tincture induced the "disposition to sing" and preliminary bioassays by others have noted "...cardinalis is more like nicotine. Seems to give stimulant effects similar to mild nicotine. Seems to have mild aphrodisiac properties. Slight mood lift present it also seems to have anti-depressant properties" [5] The N-oxide has potentially superior dopaminergic activity [6], that said at 25mg/kg it lacked abuse potential in the conditioned place paradigm model and "at the dose we administered does not seem to have a significant effect in the mesolimbic dopaminergic pathways and may not facilitate a role in treating drug abuse" [7] [1] https://www.cargocultcafe.com/cardinal-flower/ [2] https://doi.org/10.1139/cjr38b-055 [3] https://eatwild.weebly.com/blog/cardinal-flower [4] https://doi.org/10.1016%2Fj.fitote.2016.04.013 [5] https://drugs-forum.com/threads/lobelia-cardinalis.213716/ [6] https://pubmed.ncbi.nlm.nih.gov/34648893/ [7] https://uknowledge.uky.edu/cgi/viewcontent.cgi?article=1013&context=medsci_etds
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PM me an addy I can send to and you can have EGA journals 1 and 2 no cost, if I find #3 you're welcome to it
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Have some rooted cuttings (3 x tubestocks) for people interested (No WA/TAS) Free including post. Just starting to root so I'll give them a bit longer before posting but express any interest here.
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OK I'll reserve the above people for cuttings and get in touch soon. Thanks for the interest
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Indole-3-butyric acid to get Tricho to pup?
Alchemica replied to Ishmael Fleishman's topic in Cacti & Succulents
I tend to hear of 6-benzylaminopurine being used for pupping which is quite a distinct compound (synthetic cytokinin with stimulatory effects on cell division) with a different mechanism to IBA That said, try it and see what happens. IBA has: - auxin-like effects such as root initiation, stem bending, and leaf epinasty - IBA-derived auxin has strong roles in various aspects of root development, including regulation of root apical meristem size, root hair elongation, lateral root development, and formation of adventitious roots. - IBA-derived auxin plays distinct roles in shoot development, with particular roles in cotyledon expansion and apical hook formation. Some studies indicate: - IBA application promotes elongation of stems in intact pea plants "IBA could act as an important source of auxin to boost stem elongation in intact plants" - In carrots it seems to cause longer plants "IBA significantly increased the overall plant length." -
Anyone have personal experience with these plants? Curious as I can only find limited info on their use. Trichodiadema stellatum (syn. barbatum) This plant has been used as a yeast substitute for brewing beer and is reported to contain the psychoactive alkaloid mesembrine (Watt & Breyer-Brandwijk, 1962). Laidler (1928) also states that this plant known as kareemoer is “one of the beer making roots, a deliriant and intoxicant with an earlier stimulant action”. HARGREAVES 1998 notes that it is believed to contain an intoxicating alkaloid (“probably mesembrine”) Positive general alkaloid tests (ZWICKY) were had for Trichodiadema barbatum Mesembs reported to contain mesembrine alkaloids Trichodiadema barbatum (unconfirmed) Trichodiadema bulbosum (unconfirmed) Trichodiadema intonsum (unconfirmed) - FESTI & SAMORINI 1995 They have a nice fat root system that could be useful (similarly to D. bosseranum)
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Can offer free cuttings of Lampranthus spectabilis (Red) if interested. I can't properly explore as my serotonin transporter is heavily occupied but as it's a rampant grower and a different colour for the garden, it might be a useful addition. Have dried research material if needed too. Let me know in this thread if interested and I'll get back to you once the festive craziness has quietened down While it is claimed "...it would be almost impossible to achieve any pharmacological response from genera other than Sceletium" [1], recently Lampranthus species have been specifically marketed as "Chinese Kanna", alongside being used as an adulterant, one source stating Lampranthus spectabilis generally contains about 1–1.5% total alkaloids [2]. A high concentration of phenolics has been noted in Lampranthus [3], along with other phytoconstituents [4] "Of the five Lampranthus species tested, only L. aureus and L. spectabilis yielded mesembrenol, while all the other Lampranthus species investigated appeared to contain mesembrenone, but all at very low levels." Lampranthus aureus appears to contain other indolic alkaloids Mesembrine: SERT inhibition [other claims of 5-HT releasing activity], PDE-4 inhibition, Anti-inflammatory, Cytoprotective, Upregulates VMAT-2, Mild inhibition of AChE, Mild MAO inhibition, limited reuptake of NE and DA at high concentrations Mesembrenone/mesembrenol: SERT inhibition, PDE-4 inhibition [1] https://doi.org/10.1076/phbi.36.3.173.6350. [2] https://botany.bio/product/chinese-kanna-1-25-powder/ [3] https://doi.org/10.15835/nbha47411617 [4] https://doi.org/10.1016/j.sajb.2018.07.014
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Aptenia cordifolia (A Zulu traditional medicine) Please note: this plant contains oxalates. While it may be safe in the right doses and prepared correctly, please do not use medicinally unless you are skilled in using it. But you can grow it! This is a plant that got me through real dark times. Today I give a plant to a "Grow Free Box". I found after fermentation ca. 15g was active and antidepressant with a different quality, more groundedly hearty than Kanna. It was really nice, so much so I made a full spectrum ethanol extract of the fermented material. "Aptenia cordifolia is a species of succulent plant in the iceplant family known by the common names heartleaf iceplant and baby sun rose. Native to southern Africa, this species has become widely known as an ornamental plant." Growing Aptenia cordifolia Aptenia cordifolia is a well-known groundcover. It is an ideal plant for coastal gardens as it tolerates sea spray and grows in sandy soil. It can be used in rockeries or outcrops, terraced slopes and along roadside embankments. It requires full sun or semi-shade; it can be planted underneath trees. If grown in unfavourable conditions, the plant will die. Aptenia cordifolia is easily grown from seed and cuttings. Sow seed in summer. The plant can be divided and runners can be planted directly into the ground. Before planting, prepare the garden bed by digging over the soil; add compost and a slow-release fertilizer. Once established it requires less water. Trim or prune the plant to maintain its shape. The plant can become weedy. Aptenia's Medicine: Aptenia cordifolia is used medicinally as an anti-inflammatory, as a dressing (poultice) and deodorant. The plant is also used as a love and good luck charm. Zulu medicinal uses include making a mild enema for babies; the black powder is used for vaccination and against witchcraft (sorcery). Burnt stems and leaves are applied to aching joints. "Aptenia cordifolia is used by Zulu healers in S. Africa as one of their important medicinal plants. The leaves may be infused to relieve sore throat and perspiration; the herb is also anxiolytic, and acts as an antiinflammatory when applied externally.Interestingly, a black powder prepared from the plant is reputedly endowed with magical properties, and used to protect against sorcery (Van Wyk & Gericke 2000, Van Wyk et al. 1997) Prepared in the same manner as Sceletium spp., this common and attractive ornamental plant has been found to have similar effect to S. tortuosum, but is of lower potency (pers. comms.)... The plant contains mesembrine-type alkaloids which have antidepressant effects through serotonin and other pathways and may be superior to SSRIs currently used to treat depression. Aptenia cordifolia may contain significant levels of mesembrine-type alkaloids, as compared to other Aizoaceae, though still only 13.6% of the levels found in Sceletium tortuosum. Mesembrine [c. 9.7% of the extract], 4'-O-demethylmesembranol [c. 14.4% of extract] and three unidentified compounds were observed; 2 of these, comprising c.4.8% of the extract, appear to be indoles (Smith, M.T. et. al. 1998)" It is worth considering that perhaps some of the alkaloids identified by Smith et al. as being present in Aptenia samples (4’-Odemethylmesembrenol, mesembrine and mesembrenone) may have been mis-identified, more recent analysis presence of the mesembrine-type of mesembrane alkaloids 4,5-dihydro-4’-O-methylsceletenone and 4’-O-methylsceletenone [1] The phytochemical screening of the ethanolic extract of the leaves of A. cordifolia, which was a strong antiinflammatory, revealed the presence of alkaloids, flavanoids, tannins, phenols, saponins and steroids. Aside from mesembrine-type alkaloids and unidentified indole alkaloids, ferulic acid, 3,4-dimethoxy-dihydrocinnamic acid were isolated as well as the corresponding Me and Et esters respectively. Also identified were pinoresinol and syringaresinol, respectively. Oxyneolignans such as apteniol G were discovered. It's listed as a 'safe plant' on databases and suggested as being safe for consumption by multiple sources.
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Aptenia cordifolia (A Zulu traditional medicine)
Alchemica replied to Alchemica's topic in Ethnobotany
Just updating this - there seems to be confusion between A. cordifolia (Mesembryanthemum cordifolium) and A. lancifolia and there are common hybrids between the two. Aptenia cordifolia and A. lancifolia are very popular garden plants around the world, and are particularly useful as attractive ground covers on dry slopes as they rapidly form lush green carpets with decorative reddish purple flowers. A. cordifolia has cordate or heart-shaped leaves, while the leaves of A. lancifolia are lance-shaped, tapering gradually towards their bases. Leaf shape is used as a rather tenuous character in distinguishing A. cordifolia from its nearest relative, A. lancifolia. -
Aptenia cordifolia (A Zulu traditional medicine)
Alchemica replied to Alchemica's topic in Ethnobotany
Mesembryanthemum cordifolium L.f. (syn. Aptenia cordifolia) Think there's some variety in colour -
Aptenia cordifolia (A Zulu traditional medicine)
Alchemica replied to Alchemica's topic in Ethnobotany
I've just mashed it and put it in a jar, sun fermented then oven dried (smells a bit...) before to get a usable powder as per herbalistics DIY Sceletium fermentation page. Bigger batches including roots were problematic with mold. I needed high doses to get effects but I'm a bit of a serotonergic hard head. I personally don't think you'd get enough of a dose via insufflation. -
treating hypertension with herbs
Alchemica replied to withdrawl clinic's topic in Pharmacology, Chemistry & Medicine
One I've heard of and seems to be very otherwise benign is Hibiscus/Rosella Rosella appears to be a safe and well-tolerated treatment option, which may have a place in the treatment of mild-to-moderate essential hypertension. Data suggests that it may provide comparable effectiveness to some pharmaceutical antihypertensive medications. [1] -
Looking for various Tabernaemontana - divaricata, pandacaqui etc. Any that may be phytochemically interesting Message me if you have surplus Many thanks in advance
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Kanna - Sceletium Tortuosum Seed Confiscated & Destroyed
Alchemica replied to Ishmael Fleishman's topic in Chill Space
There may possibly be if someone has cancers etc, BDNF participates in the process of metastasis and in the migration of cancer cells . That said, exercise induces similar sorts of elevations of BDNF and it's generally considered wholesomely healthy -
Kanna - Sceletium Tortuosum Seed Confiscated & Destroyed
Alchemica replied to Ishmael Fleishman's topic in Chill Space
There'd likely be BDNF elevations [seen in animal studies here] and enhanced neurogenesis on chronic dosing (in line with the therapeutic activity seen in depression where case-studies note delayed improvements, eg 1-2 weeks, 10 days etc) from both the serotonergic effects and PDE4 inhibition -
Kanna - Sceletium Tortuosum Seed Confiscated & Destroyed
Alchemica replied to Ishmael Fleishman's topic in Chill Space
Trying to root up cuttings at the moment, if I have success I'll be in touch It's really annoying as it's a potent therapeutic and it would be good to have it remain therapeutically appreciated, rather than abused. It's made the list of the United Nations “plants of concern.” and features in some drug testing/analysis papers so probably be an issue soon [1]. -
Kanna - Sceletium Tortuosum Seed Confiscated & Destroyed
Alchemica replied to Ishmael Fleishman's topic in Chill Space
"Based on the venation type, the species is mainly classified as either emarcidum or tortuosum types. In the emarcidum type, the leaf is more flat and the dried leaf venation pattern shows a central main vein with the curved secondary vein which branches off the main vein, reaching the leaf margins. In plants of the tortuosum type, the dry leaves are more concave and usually show about three to five or sometimes up to seven major parallel veins. The secondary veins run straight up to the apex on both sides of the middle vein." https://www.intechopen.com/chapters/53426 While the emarcidum is much easier to grow it seems to be devoid of mesembrine and instead comprised of 4'-O-demethylated mesembrine-type alkaloids [1, 2] which are poorly characterised pharmacologically. S. strictum seems to again have a different alkaloid profile centred on mesembrine and mesembrenone and is proposed to be useful based on that [1] https://doi.org/10.3389%2Ffnut.2022.819753 [2] https://www.intechopen.com/chapters/53426 Pretty sure the first one I have is emarcidum-type and the second tortuosum if that helps you ID. -
Essential oils I've Known and Loved - add yours
Alchemica posted a topic in Pharmacology, Chemistry & Medicine
Here's an interesting paper and some research I compiled: Essential Oils and Their Constituents: An Alternative Source for Novel Antidepressants Calamus oil: β-asarone produces an antidepressant effect, increases TH and could promote expression of GDNF, BDNF, and CNTF genes. β-Asarone functions as a neuroprotective effect in both in vivo and in vitro models of PD. α-asarone or β-asarone potentiated the NGF-induced neuronal differentiation. The antidepressant-like effect of α-asarone could be mediated through both noradrenergic (α1 and α2 adrenoceptors) and serotonergic (particularly, 5-HT1A receptors) systems. α-asarone effectively modulates microglial morphological dynamics, this effect of α-asarone may functionally relate to its influence on neurogenesis. α-asarone improved m1 mAChR expression and ACh levels, and attenuated the increased AChE activity in a mouse model of FXS. β-asarone antagonised Aβ neurotoxicity in vivo and improved the learning and memory ability. β-asarone might be effective for the treatment of AD Chamomile - anxiolytic: Bisabolol (α-(-)-bisabolol) is a sesquiterpene which is a part of the essential oil of a variety of plants, but its common source is German chamomile. It is a potent GABAAR modulator at the BZD site - the anxiolytic-like activity of bisabolol occurs via the GABAergic but not serotonergic transmission Copaiba oil: Anti-inflammatory, analgesic, anti-addictive, antidepressant etc. ~50% β-caryophyllene. CB2 agonist, PPARγ modulator. Regulates μ opioid receptors increasing analgesic effects, alters expression of 5-HT2ARs, activates TrkA receptors mimicking NGF exerting antidepressant effects. Frankincense: Contains significant quantities of α-pinine which is anxiolytic via GABAA BZD site modulation, antiinflammatory (PGE2) and memory enhancing via AChE. Also in rosemary EO. Also contains the psychoactive incensole acetate which is a potent TRPV3 agonist that causes anxiolytic-like and antidepressive-like effects. Jasmine: Contains methyl jasmonate. Antidepressant effects, established in animals, may be related to suppression of oxidative stress and release of TNFα. Recently, it has been discovered to have anti-psychotic activity, suppressing pro-psychotic activity of dopaminergics and NMDA antagonists: MJ demonstrated antipsychotic-like property via mechanism related to its antioxidant property and interference with dopaminergic neurotransmission It has strong anti-neuroinflammatory activity and suppresses memory dysfunction in mice. MJ also suppressed the expression of COX2, iNOS and NFκB. It has anti-amyloidogenesis-like effects. Lavender - contains linalool and linalyl acetate etc: Anti-convulsant, analgesic, potent anxiolytic. VDCC blocker, GABAA modulator, DAergic, glutamate/ NMDAR modulator, 5-HT modulator (particularly altering 5-HT1AR binding). 80mg orally as efficacious as lorazepam and paroxetine for GAD. (-)-linalool to stimulates opioidergic, cholinergic M2 and dopaminergic D2 systems, as well as interacts with potassium ion (K+)-channels. The effects of (-)-linalool on pain responses are mediated, at least in part, by the activity of adenosine A1 and A2A receptors and by the reduction of nitric oxide (NO) production/release, probably through mechanisms involving opioidergic, cholinergic and/or glutamatergic systems. Reverses the effects of stress at the transcriptional level on inhalation, increasing things like oxytocin. Lemon - limonene reversed increased immobility time in the FST induced by neuropathic pain in rats. The putative mechanism by which lemon oil produces antidepressant-like effects seems to be mediated by 5-HT and dopamine neurotransmission. The pretreatment with buspirone (5-HT1A partial agonist), DOI (5-HT2A receptor agonist), miaserin (5-HT2A/C receptor agonist), apomorphin (nonselective dopamine receptor agonist) and haloperidol (nonselective dopamine receptor antagonist), blocked the antidepressant effects of lemon oil. Moreover, the acute inhalation of this oil significantly increased dopamine contents in the hippocampus and 5-HT in the prefrontal cortex and hippocampus. As commented before, dopamine and 5-HT are intrinsically involved in the modulation of mood states, and hippocampus and prefrontal cortex are the main stages of this action. Thus, the antidepressant-like effects of Citrus limon oil might be mediated by limonene. Indeed, modulation of 5-HT and dopamine neurotransmission in brain areas highly involved with mood states could be on the basis of the antidepressant effects of lemon oil. Limonene also seems to have effects on adenosine receptors. Oregano - contains carvacrol - antidepressant and antiinflammatory/ PPARα/γ dual agonist, TRPV3 agonist, modulates DA and 5-HT, decreases COX expression Patchouli: Antidepressant. This aroma oil exposure may modulate the blood platelet serotonergic regulation through MAOA depending on the dose, duration, and conditions of exposure. Patchouli alcohol exerts antidepressant effects orally. Piper: Piper species are considered to play a role in alleviating neuronal ailments that are associated with inhibition of acetylcholinesterase (AChE). Sesquiterpenes and phenylpropanoids were found to be rich in these EOs, of which asaricin, caryophyllene, caryophyllene oxide, isospathulenol, (+)-spathulenol, and β-bisabolene are the major constituents. The EOs from the leaves and stems of Piper austrosinense, P. puberulum, P. flaviflorum, P. betle, and P. hispidimervium showed strong AChE inhibitory activity with IC50 values in the range of 1.51 to 13.9 mg/mL. A thin-layer chromatography (TLC) bioautography assay was employed to identify active compound(s) in the most active EO from P. hispidimervium. The active compound was isolated and identified as asaricin, which gave an IC50 value of 0.44 ± 0.02 mg/mL against AChE, comparable to galantamine with an IC50 0.15 ± 0.01 mg/mL. Spearmint (Mentha spicata) and caraway (Carum carvi) essential oils - sodium channel antimanics: Contain ®-(-)-carvone and (S)-(+)-carvone which prevent mania in animal models. (S)-(+)-carvone decreased spontaneous locomotor activity in sleep deprivation experiment, indicating a sedative effect while ®-(-)-carvone is not sedating Some Australian Natives I love: -
I used to think more was better particularly as there seems to be dose-dependent increases in DA levels but then noticed low doses cumulatively ie a pinch seems better... and likely safer as increased doses seem to come with notable toxicity. Not sure where the cut off for CNS toxicity is but considering the clinically used doses are low and they seem effective, maybe wise to keep to lower doses? " saffron constituents such as crocin, crocetin and safranal can exert antioxidant or toxic effects depending on their endogenous concentration. " [1]