Jump to content
The Corroboree

Alchemica

Moderators
  • Content count

    1,564
  • Joined

  • Last visited

  • Days Won

    71

Posts posted by Alchemica


  1. There's been a bit of research into fermentation of different plants with either lactic acid bacteria or yeasts. I've tried to summarise a bit of it here

    The Science of Fermented Fruits, Veggies and Plant Medicines - Pharmacology, Chemistry & Medicine - The Corroboree (shaman-australis.com)

     

    The bacteria and yeasts are in a way potentially mildly psychoactive, hence their often-termed action as "psychobiotics". I've only tried milk kefir, which is interesting in it's own way, as the kefir peptides are too mildly psychoactive but you're right, fermenting a plant into the mix is an interesting concept and worth exploring more.

    There's the classic example of Sceletium which I've tried to explore here with yeasts 
    yeasts to encourage bioconversion.pdf
     

    Quote

    Alongside the nutritional and psychobiotic effect, a diversity of peptides from casein are released by kefir including at least 5 opioid peptides. Opioid effects have been also reported following oral administration of casein hydrolysates. The peptides may exhibit anxiolytic-like and cognition enhancing activities. Kefir peptides may also act as anti-oxidants, immunomodulators and anti-obesity agents

     

    Let us know if you do any experimenting


  2. Stuck with this for awhile and there's been the slow but gradual return of some seemingly simple cognitive functions when used catalytically with effort and attempting to retrain my mind.


    For example, I was unable to sit and watch something as simple as a short youtube clip and follow the video. I've lately got back into watching inspirational short videos that I'm enjoying and can now watch something like a 30min clip which was previously totally unfeasible. I've started to embrace the need to do a lot more simple cognitive remediation in my day, for example getting back into colouring in an adult colouring books etc as an activity

     

    It hasn't all been linear for recovering some levels of very basic functionality, the cognitive fatigue associated with essentially retraining and forging some new connections of some basic cognitive functions has been extreme and literally left me floored and sometimes come at the expense of maintaining functionality in other domains.


  3. There seems to be several factors that limit berberine's bioavailability to the <1% mark:

    • poor absorption
    • extensive metabolism
    • efflux back to the intestinal lumen by the action of permeability glycoprotein (P-glycoprotein, P-gp)

    As piperine from black pepper works on the cytochrome metabolism and P-gp level, it may very well be worth considering but haven't seen it done

     

    Things that have been studied are detailed here


    The Quest to Enhance the Efficacy of Berberine for Type-2 Diabetes and Associated Diseases: Physicochemical Modification Approaches

     

    the phospholipid-berberine complexes including things like encapsulating it in lecithin seem to have some significant effects on bioavailability in studies but wasn't able to personally tell how effective it was, lets just say I had lots of experiments happening.

     


  4. 12 hours ago, Ishmael Fleishman said:

    Has anyone used Berberine and to what effect?

     

     

    Thanks for the writeup.

     

    I explored a long time ago, also made up a mix of berberine hydrochloride with lecithin trying to improve it's bioavailability and was interested in it's CNS effects and beneficial metabolic effects, the CNS effects particularly related to it's sigma-1 agonism, prolyl oligopeptidase activity and monoaminergic effects

    Berberine may offer benefit in the control of psychotic and depressive symptoms, along with metabolic side effects. It has a broad range of CNS relevant pharmacological actions, including sigma-1 agonism, acetylcholinesterase inhibition and a range of neuroprotective effects including neurotrophin-mediated neuroprotection (NGF). There are some limitations to its use, including bioavailability and difficulties in reaching active levels in the CNS. “The potential use in schizophrenia was suggested when berberine was found to act as a D2-receptor antagonist, although it was also noted that dopamine level was increased in the brain as partly responsible for its antidepressant mechanism. It is unclear if these influences on dopamine level and action may counter each other, diminishing the proposed antipsychotic effect. Future studies may also elucidate whether berberine will exacerbate extrapyramidal motor symptoms due to the blockade of D2 receptors. On the other hand, it was proposed that the anxiolytic effect of berberine resulted from its antagonism at 5-HT2 receptor. This finding may indicate less severe motor side effects, if there are any, when berberine is used as an antipsychotic since atypical antipsychotics also act via 5-HT2 receptor blockade. A possible advantage of berberine over other antipsychotics is its ability to inhibit prolyl oligopeptidases, the activity of which is elevated in psychosis and not targeted by antipsychotics at present.”

     

    Berberin.svg

     


  5. 1 hour ago, fyzygy said:

    Sounds promising. I hope the positive effects increase over time.Which Acorus species (and plant parts) have you been concentrating your efforts on? 


    I'm just using a likely high asarone Acorus calamus essential oil. I don't want to make it a long-term addition but something to get out of a rut. Early days but small subjectively useful shifts, combined with little lifestyle shifts when I can seem to help slightly. I get very rigid in my routines and behaviours, so if this is a way to potentially plasticise my mind and behavioural repertoire a bit that could be good

     

    Quote

    Would sub-lingual also work while avoiding toxic effects?

    That could be useful and possibly minimise toxicity? I know some people simply chew the calamus rhizome, that seems to be the suggested way to use the Japanese Sweet Flag SAB sells for stimulant effects. This intranasal spray is a bit more full on with quite significant levels of asarone which I think would be hard to reach via plain herb
     

    Quote

    Variegated sweet flag, I think you mentioned that it had been traditionally used among Japanese to treat stuttering? 

     

    Yeah that one's Acorus gramineus, it's got a diverse range of constituents that have interesting pharmacology aside from asarones. Still, whilst it seems to have quite prominent TCM use etc, I'd probably stick with chewing it etc as you mention


    My notes on A. gramineus
     

    Quote


    Acorus gramineus is a traditional medicine used to treat various disorders including cognitive disorders where of all the traditional Chinese medicines used in treating cognitive disorders, the rhizome appears with the highest frequency. In TCM it has an action of "calming heart and inducing tranquilisation"
     
    It contains β-asarone, α-asarone and other phenylpropenes as well as lignans, along with aporphine-type alkaloids with the essential oil having NMDA receptor antagonist-like action and possibly increases NE, DA and 5-HT, also decreasing the activity of acetylcholinesterase. A water extract demonstrated specific binding to striatal dopamine D1 and D2 receptors and competed with [3H]muscimol for specific binding to the GABA binding site of cortex GABAA receptor

     

     




     

    • Thanks 1

  6. A few days in and perhaps the most robust change has been with potential anti-addictive activity, for me being able to say no to smoking which resurged recently and I wasn't able to get on top of (EDIT less sustained anti-addictive potential than I'd hoped). The regulation of neurotrophins, particularly GDNF [1], seems to have quite profound effects on addictive processes, the GDNF pathway implicated in the anti-addictive action of things like ibogaine. Some stability in mood developed over the extreme negative mood states and even some uplift, whilst still having profound motivational deficits and ability to initiate and maintain goal-directed activity. Been trying to have glimmers of sustained attention to focus on tasks like watching short bursts of movies or TV shows which is still incredibly challenging

     

    As the administration via intranasal pathways directly into the olfactory bulb is likely to target the neurotrophic activity directly into the OFC and frontal lobes, it interests me how it could impact severe hypofrontality [2] particularly with regard to OFC functioning where damage can cause neurobehavioural issues

     

    image.thumb.png.fe5153ca8b28ba95e4a639132cfc6a9f.png

     

     

    For a long time I've been walking around like a headless chook with aberrant motor functions, this seems to reduce the 'headless chook' wandering a bit


    Know your brain: Olfactory bulb — Neuroscientifically Challenged

     


  7. Thanks for your input and kind words DL. Hope you get some improvement of your residual symptoms.

    Initially there's not much robust acute improvement but symptoms were severe at baseline so not expecting quick results. If anything perhaps some destabilisation of mood etc but I sometimes feel that can be a part of the 'solve et coagula' of life. I particularly wonder if, as a significant portion of my symptoms was through an inhalation suicide attempt, this might be a very direct way to target the damaged pathways, particularly into the OFC, quite directly.

     

    They did some research using aromatherapy for inhalant abuse, this is like the next level up, intranasal aromatherapy.

    A novel approach of substitution therapy with inhalation of essential oil for the reduction of inhalant craving: A double-blinded randomized controlled trial

     

     


  8. Nose-to-brain delivery of asarones for CNS conditions?

     


    Ayurvedic medicine and traditional Chinese medicine (TCM) use Acorus preferably to treat central nervous system (CNS) related diseases such as epilepsy, insanity, mental weakness, or insomnia, Calamus has been widely used internally in both Chinese and Ayurvedic medicine for degenerative central nervous system disorders associated with communication, focus, memory and learning but there are concerns regarding the safety of such orally. 

     

    The ability of asarones to induce such a broad range of neurotrophic factors (NGF, BDNF,  GDNF, CNTF in a dose-dependent manner), alongside other neuroprotective and neurorestorative pharmacological actions, intrigues me.

     

    bdnf.thumb.jpg.f6a86a07cc322e9136708978ebb32e5c.jpg


    Pharmacologically, α- and β-asarone at lower doses (<50 mg/kg) exhibits a wide range of therapeutic activities such as antidepressant, antianxiety, anti-Alzheimer, and anti-Parkinson effects [1].

     

    Asarones as a therapeutic are limited by poor absolute bioavailability when administered orally, less than 10%, because it is highly lipophilic and has poor solubility in water, coupled with extensive gastrointestinal and/or hepatic first-pass metabolism. 

     

    There are concerns potentially harmful effects, such as genotoxicity particularly through accumulation in the liver where "both α- and β-asarone can cause hepatomas and might possess mutagenic, genotoxic, carcinogenic, and teratogenic effects". Because the amounts of asarone accumulated in liver may reflect its hepatotoxicity, there is special significance to reducing the amount of asarone in liver. 

     

    Quote

    "The development of more efficient systems to deliver α- and β-asarone to their biological targets, particularly the brain, might allow for effective localized biological action while minimizing toxicity."

     

    Efforts have been centred on exploring nose-to-brain delivery of asarones, particularly as nanoemulsions [1,2] In humans, 20mg asarone has been added to memantine for AD [3]

     

    Quote

    "Drugs can travel from the olfactory epithelium in the nasal cavity straight into brain tissue via the olfactory bulb which gives intranasal administration special significance for brain diseases"

     

    "...intranasal administration of asarone showed significant nose-to-brain transport, especially in the olfactory bulb, and such treatment yields equivalent or higher concentrations in other brain tissues compared to intravenous or oral administration"


    I'm personally curious as to whether a simple spray of asarones emulsified in water with a polysorbate emulsifier, delivered via a nasal spray bottle may be simple enough to make a readily available nose-to-brain delivery system "polysorbates [are] a promising excipient to increase drug concentration in both plasma and brain via intranasal route".

     

    The main beneficial actions of asarones, as described by [1], are summarised as:

     

    " (1) antioxidant properties; (2) the regulation of various neuroprotective signaling pathways; (3) the reduction of aggregate formation and promotion of the clearance of pathogenic protein aggregates; (4) anti-inflammatory properties; (5) the inhibition of microglial activation; (6) the activation of NTFs-mediated neuroprotection; and (7) the modulation of neurotransmitter levels associated with behavioural functions and neuronal cell survival."

     

    Antioxidants 11 00281 g001
     
    Actions of asarones on the CNS, taken from [1]

     

    2079075363_neurotrophinscnsrepair.thumb.jpg.548980256d1af34e9a7a2e885084b55f.jpg

    Normal vs diseased brain aspects


    Asarone functions as a neuroprotective effect in both in vivo and in vitro models of neurodegeneration

     

    - Enhance BDNF via TrkB and activate the ERK pathway, triggering antidepressant-like effects
    - Significantly promoted the expression and secretion of neurotrophins, such as nerve growth factor (NGF), BDNF, and GDNF, in a dose-dependent manner. Also effects on CNTF 
    - Maintain equilibrium between glutamate and GABA in the hippocampus, enhancing learning and memory abilities. β-asarone induced the high potentiation of GABAARs
    -Anxiolytic effects of asarone were partially due to maintaining the balance between excitatory/inhibitory transmissions and attenuating neuronal hyper-excitability of excitatory neurons in the basolateral amygdala.
    - modulates microglial morphological dynamics, may functionally relate to its influence on neurogenesis
    - Other monoaminergic effects, particularly antidepressant effects mediated by noradrenergic (α1 and α2 adrenoceptors) and serotonergic (particularly, 5-HT1A receptors) systems.
    - Enhances tyrosine hydroxylase activity with relevance to Parkinson's

     

    My current line of thinking is to make an emulsion of a polysorbate emulsifier with calamus oil 1:1 in water and explore that. Any input appreciated.

     

    227814043_asaronelipidemulsionpolysorbate.thumb.jpg.a7cbb4da2ceca36234d8f91aa1288001.jpg

     

    1:1:2 Calamus EO:polysorbate solubiliser:saline administered by nasal spray has got quite a strong bit of burn to it but not totally intolerable.

     

    Nasal sprays are normally less than 140uL/spray meaing at 25% EO concentration {assume 80% asarones), about 28mg asarone per spray may be possible. Even at that dose, each spray is quite painful but it may be feasible to - via multiple doses scattered through the day - reach a therapeutic dose of asarones intranasally with such.


    References:
    Balakrishnan, R.; Cho, D.-Y.; Kim, I.-S.; Seol, S.-H.; Choi, D.-K. Molecular Mechanisms and Therapeutic Potential of α- and β-Asarone in the Treatment of Neurological Disorders. Antioxidants 2022, 11, 281. https://doi.org/10.3390/antiox11020281 


    Lu, J., Fu, T., Qian, Y., Zhang, Q., Zhu, H., Pan, L.,  Zhang, M. (2014). Distribution of α-asarone in brain following three different routes of administration in rats. European Journal of Pharmaceutical Sciences, 63, 63–70. . https://doi.org/10.3390/10.1016/j.ejps.2014.06.006

     

    Pan L, Zhou J, Ju F, Zhu H. Intranasal delivery of α-asarone to the brain with lactoferrin-modified mPEG-PLA nanoparticles prepared by premix membrane emulsification. Drug Deliv Transl Res. 2018 Feb;8(1):83-96. doi: https://doi.org/10.1007/s13346-017-0438-8.

     Dong, Haiying; Wu, Shuqin; Hu, Nan; Xing, Guihua (2018) Efficacy of tenuigenin and β-asarone as augmentations for memantine in the treatment of Alzheimer’s disease https://doi.org/10.1097/WNR.0000000000000952

     

    • Like 2

  9. I'll start to add some items slowly here that are available. PM me if interested.

     

    First up, plain 50g ceremonial cacao hearts (single strong serves) as single or double packs {Edit: only one single heart available]]

     

    273763608_peruviancacaoplain.thumb.jpeg.53dd9626335da8922bbb79afaa48dfed.jpeg

     

    Possible  small donation to a charity of your choice. Single or double packs

     

    DSC_0001699.thumb.jpg.259cfcb41e0baa652f5f062829e14138.jpg

     

    Heart-centred Cacao with Rose, Saffron and Kanna (low dose) ~50g. Please do not combine with pharmaceuticals or MAOI plants etc [Limited quantity available, EDIT: only 2 single hearts available]

     

    235465043_heartcacao2.thumb.jpeg.3f4f204b625cbfb6277ba640d7818064.jpeg

     

    DSC_0001705.thumb.jpg.9d34656175c9340c8c27bb05abe24078.jpg

     

    Possible  small donation to a charity of your choice. Single packs.
     

    Tulsi and Rose tea [EDIT: out of stock]

     

    1408895119_tulsitea2.thumb.jpeg.053524eddcae8b85f2420f588c1f17fd.jpeg

     

    Possible small donation to a charity of your choice

     

     

    DSC_0001700.thumb.jpg.254a9d848619919460f4655204b559e8.jpg

    Functional foods [cognitive and polyphenol blends] still on the way.

    • Like 1

  10. You'd want the products that are intermediates to ethanol formation (pyruvate/acetaldehyde) to condense with the phenethylamine and under acidic conditions, undergo a Pictet-Spengler reaction to form THIQs (below). It wouldn't be a high conversion rate as conditions wouldn't be optimal but you'd likely get some conversion, which given the potency of the compounds, may be enough

     

    1-Me-THIQ has actually found some putative therapeutic actions, "1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) is an endogenous antidepressant and parkinsonism-preventing substance that demonstrates neuroprotective activity." 

     

    Fermentation | Biology OER

    image.thumb.png.b1fafb88beaa928520ac9b4ae1b05128.png
     

    I've tried to cover some fermentations of plants here The Science of Fermented Fruits, Veggies and Plant Medicines - Pharmacology, Chemistry & Medicine - The Corroboree (shaman-australis.com)

    Yeasts are known for reducing some alkene (C=C) and carbonyl (C=O) compounds, which is more applicable to things like mesembrine-type alkaloids in Sceletium

    image.thumb.png.8e8132cf17ce2cb70023ca9dca4d8217.png

     


  11. This is an interesting concept. In theory, you could get a tetrahydroisoquinoline form from pyruvate/followed by decarboxylation = equiv. acetaldehyde and mescaline like such.

     

    This would bring it's pharmacology potentially more in line with the Lophs. The pharmacology of these THIQ's isn't well studied but they seem to be relatively potent serotonin agonists (nM) for a diverse range of serotonin receptors aside from more classical 5-HT2ARs eg pellotine
     

     In Vitro and In Vivo Evaluation of Pellotine: A Hypnotic Lophophora Alkaloid | ACS Pharmacology & Translational Science

    1,2,3,4-Tetrahydroisoquinoline, 6,7,8-trimethoxy-1-methyl-.png

     

    https://pubchem.ncbi.nlm.nih.gov/compound/613648


  12. Thanks for the wise input @Ishmael Fleishman.

    I tend to think people seeking ceremonial cacao are of a different mindset than tastes alone so may tolerate some differences but have to see

    I want to keep it away from business models and involving payment for goods for several reasons, being more a project I self-fund but agree, making it sustainable is essentially an impossible challenge if one does that but we'll see. A project to do, that I value, more than a sustainable business venture, is the aim

    Thanks again for the other points

     

     


  13. I've been having a bit of an existential crisis - absolutely bored with existence - as disability robs me of significant ability to do things that I find meaningful and valuable on a wider scale, trying to find things that are worthwhile and fulfilling, yet still achievable. I'm curious as to if there is interest in these sorts of things below? Which ones would be of interest?

     

    Please note: All items are not intended to diagnose or treat any medical condition.

    This is just a concept at the moment but I've been exploring some prototypes of plant-based options that may meet unmet needs that may have use to the community. I'm writing here to see firstly what sort of interest there may be in the following options, if there is any and where I should potentially put my efforts into development of options?

     

    Even if you have other ideas on things that are legit, I'd like to hear.

     

    I'd be looking to base it on a 'Donation to a greater good' based scheme where for example, one could - at their choice - contribute a donation to a relevant charity as exchange for goods - that would be your part to do and I'd simply trust your end of the deal. If you wanted to, covering postage costs after receiving items would be helpful and maybe help me continue to do more in the way of this sort of thing down the track. Not sure how it's going to work longer term and I'm currently finding the research and development pricey but hopefully once that settles, I can minimise costs

     

    1832133417_widergoodapothecary2.thumb.jpeg.b9adce52fff0d2f637bffd83e8c7e47c.jpeg

     

    They'd be fairly small samples, just to get an idea if these options potentially worked for you, and if they did, you could then feel free to source ingredients to make it yourself, and optimise if you like, which I'd encourage.

    Some of the prototypes I've been exploring:

    Mind Mend Cognitive Blend

     

    992838789_Mindmendcognitiveblend.thumb.jpg.98c12378274271eb07c6a9e5cb319ac0.jpg
     
    Ingredients: Ashwagandha, Brahmi, Shankhpushpi, Lion's Mane, Saffron, Mucuna, Ginkgo, White Peony, Rhodiola.


    Each level teaspoon (2.7g) provides
    Ashwagandha (Withania somnifera) root 675mg
    Brahmi (Bacopa monnieri) 675mg
    Shankhpushpi (Convolvulus pluricaulis)  675mg
    'Neuro Shroom Blend' 675mg
    Saffron (Crocus sativus) 20mg
    Suggested serving size: up to 2 level tsp (2.7g ea tsp) three times daily


    Caution: Not intended to treat any medical condition or replace professional medical advice. Food supplement ONLY. There have been case studies of potential interactions (namely Rhodiola with serotonergics) with some ingredients with pharmaceuticals, please consult your pharmacist for advice.


    "...current pharmacotherapeutics for [cognitive impairment] neither cure nor halt cognitive decline; they just delay the worsening cognitive impairment"


    A narrative review found "nutrients and phytonutrients may be promising for treating some aspects of cognitive impairment" with highlighted findings of reviewed clinical trials displaying a wide range of results on cognitive function, with some showing promising effects eg Bacopa monnieri, curcumin, Rhodiola rosea, Saffron, Withania somnifera, and xanthines [1]. 


     While conventional Western medicine hasn't made much progress in treating cognitive issues, schools of medicine like Ayruvedic ones might have some clues for good strategies to intervene with for early interventions, or more prophylactically.


    As a broader shot-gun approach by utilising a polyherbal formula, the diverse etiology of cognitive issues could potentially be addressed better than the more specific molecular approach adopted commonly in Western medicine. This includes reliance on phytochemical synergies to potentially offer a different, broader and diverse response. That said, as a later intervention in serious cognitive decline, many nutraceuticals offer poor evidence of efficacy.


    This is a blend of traditional Ayruvedic herbs: Ashwagandha [2], Brahmi [3], Shankhpushpi [4] - all showing promise in addressing cognitive issues - blended with other options with mounting potential benefits for cognitive issues such as Lion's Mane [5], Saffron [6] and Ginkgo [7], Rhodiola and some other herbs


    [1] http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8445631/
    [2] https://doi.org/10.1080/19390211.2017.1284970
    [3] https://doi.org/10.1089/acm.2008.0018
    [4] https://doi.org/10.3389/fphar.2020.00171
    [5] https://doi.org/10.1002/ptr.2634
    [6] http://dx.doi.org/10.2174/1570159X19666210113144703
    [7] https://doi.org/10.3233/jad-215423

     

    Mind mend.pdf

     

    Terpene Dance Spray

     

    936814323_dancespray.thumb.jpg.e7964fc638e04d0d92531092c63bf647.jpg

     

    This one is currently hindered by postage issues as it likely falls under flammable goods and can't be posted. That said, if there is demand, I could maybe look into an option not using ethanol, rather an essential oil solubiliser in water to make it post friendly. That said, I don't want to put effort into things that don't meet a need.

     

    It's designed to be a transdermal essential oil spray that I've found quite effective at loosening up to get into a therapeutic dance. I find with significant transdermal administration, I can personally get loose enough to get into the groove. It does however make you reek like a walking diffuser.


    Essential oil-based dance spray


    Loosen up naturally and feel the good vibes with a symphony of plant-based actives

     

    Terpene Dance Spray.pdf

     

    Other items I've been exploring:

    Ceremonial Cacao bars

     

    1301240948_heartcacao2.thumb.jpeg.eff43d1c760e97d68d509feaa4396221.jpeg

     

    Polyphenol Blend

     

    2032517134_HealingPolyphenolBlend.thumb.jpeg.39c978ccb37df344873d376193c867a2.jpeg

    Trying to utilise rich sources of polyphenols (purple corn anthocyanins, citrus flavonoids etc) to create a broad-spectrum polyphenol blend

     

    A 'Golden Paste' option

    944779830_goldenpaste.thumb.jpeg.52285df325b1446aa2f0d77a30ba6ccc.jpeg

     

    Tea Blends

     

    1840699058_tulsitea2.thumb.jpeg.f0727bc799035801721f34aea26a5cf1.jpeg

     

     

    If there's interest in these sorts of things, let me know what sort of things would be useful through the poll above.

    Much gratitude for any input you can offer.

    Have a lovely day.

     

    • Like 1

  14. Anyone by chance explored?

     

    Agapanthus campanulatus 

     

    Quote

    Unspecified parts are used by the Sotho in South Africa to treat people “who have the spirit”, which appears to be a type of mental disturbance (Laydevant, 1932). The Zulu use unidentified species of Agapanthus for inducing visions (imibono) and dreams in South Africa (Nonkazimlo Podile, pers. comm.).

     

     

     agapanthus.thumb.jpg.08e47afd09dba39773a00f049ba5d05e.jpg

     

    Modified from [1] 

     

    - rhizome of A. campanulatus used in the initiation of traditional healers due to the presence of active principles as yuccagenin and agapanthagenin but both of them cause gastrointestinal tract and kidney problems (Ndhlala et al., 2013; Bonokwane et al., 2022). 


      

    image.pngimage.thumb.png.6fa64a3b248d9e09dd8b99e9563d9655.png



     

    Triterpenoid saponins are thought to be the main actives of ubulawu such as Agapanthus companulatus. No alkaloids were detected in Agapanthus campanulatus

     


    1326980353_agapanthusmonoaminetransporters.thumb.jpg.4737156e42cfb2c13e2df5890cd48f78.jpg

    In vitro assays (ethanol extracts from the leaves) showed good binding affinity to serotonin, dopamine and noradrenaline transporters [2]

     

    It is possible that the triterpenoid saponins found in Agapanthus campanulatus and other ubulawu species and their interactions may be responsible for these antidepressant actions, as well as the other reported psychoactive effects [3,4]


    References
    Ahmed Mohamed Younis, Alshymaa AbdelRahman Gomaa, Alyaa Hatem Ibrahim, Mohamed S.A. Abdelkader, Samar Yehia Desoukey, The genus Agapanthus: A review of traditional uses, pharmacological and phytochemical attributes, South African Journal of Botany, Volume 150, 2022, Pages 1168-1183, ISSN 0254-6299, https://doi.org/10.1016/j.sajb.2022.09.029


    Mikael E. Pedersen, Bernadeta Szewczyk, Katarzyna Stachowicz, Joanna Wieronska, Jacob Andersen, Gary I. Stafford, Johannes van Staden, Andrzej Pilc, Anna K. Jäger, Effects of South African traditional medicine in animal models for depression, Journal of Ethnopharmacology, Volume 119, Issue 3, 2008, Pages 542-548, ISSN 0378-8741, https://doi.org/10.1016/j.jep.2008.08.030


    Jean-Francois Sobiecki, Psychoactive Ubulawu Spiritual Medicines and Healing Dynamics in the Initiation Process of Southern Bantu Diviners Journal of Psychoactive Drugs, 44 (3), 216–223, 2012 https://doi.org/10.1080/02791072.2012.703101


    Bonokwane Melia Bokaeng, Lekhooa Makhotso, Struwig Madeleen, Aremu Adeyemi Oladapo Antidepressant Effects of South African Plants: An Appraisal of Ethnobotanical Surveys, Ethnopharmacological and Phytochemical Studies  Frontiers in Pharmacology, 13, 2022 https://doi.org/10.3389/fphar.2022.895286   

     

     

     


  15. 5 hours ago, Ishmael Fleishman said:

    Alchemica - the cuttings are doing well green and lush with some going into bloom and all - however the Sceletium emarcidum cuttings are not looking so good - their is obvious browning and drying out have you got any advice? Will it come right or do I need to do something different?

    These I find tend to get quite battered before they look slightly better as cuttings but they seem quite hardy. I think the lot of emarcidum I sent maybe wasn't in the best of health for cutting as it was flowering etc. I can maybe send more if you need it, or try to root some up for you

    • Like 1

  16. Quote

    Can you recommend a supplier of ceremonial grade cacao?

    I've used two, one that was sold as 'ceremonial grade cacao' was nothing particularly noteworthy. The other, more expensive, was a bit richer and nicer and available at the local market in whatever quantity one wants https://houseofhealthcollective.com.au/lines/ceremonial-cacao-chunks but it comes with the price-tag

     

    Quote

    Cacao does not seem to get much traction as a psychoactive drug. Our cultural consumption of hyper processed diluted and sachrine chocolate maybe blinding us to the possible potential of cacao.

    I agree, particularly initially I had some quite profound experiences using high dose cacao powder/paste

     

    5 hours ago, Ishmael Fleishman said:

    @Alchemica what are your thoughts of mixing cacao with harmala?

    Haven't tried it but would guess it could be rather potent

    More on the β-carbolines in Cacao [1]

     
    Quote

     

    We have previously reported that several foods and fermented alcoholic beverages contain appreciable amounts of two of those THβCs found in chocolates, THCA and MTCA, reaching up to several mg/kg (Herraiz et al., 1993, Herraiz, 1996-2000). Interestingly, the concentration of THCA and MTCA in chocolate and cocoa is comparable to that of alcoholic beverages such as wine, beer, and liquor, which contain a relatively high amount of those compounds.
     
    The origin of these tetrahydro-β-carbolines is a reaction involving L-tryptophan and aldehydes that are present or otherwise released during the processing of foods and beverages. Its chemical formation depends on the amount of precursors, storage time, pH, temperature, and processing conditions (Herraiz and Ough, 1993; Herraiz, 1996).

    The same reaction is likely to occur in chocolates that suffer a fermentation from cacao beans and heating processes. Then, it is expected that serotonin, L-tryptophan, and tryptamine afford the corresponding THβCs (6OHMTHβC, MTCA, and MTHβC) through a Pictet-Spengler condensation with acetaldehyde

    The biological significance of tetrahydro-β-carbolines and β-carbolines is related to their potential pharmacological actions on the nervous system, playing a role as neuromodulators via effects on monoamine oxidase (MAO), biogenic amine (serotonin) uptake/release, and benzodiazepine receptor binding. Then, these compounds exogenously supplied, or hypothetically produced in vivo, might become bioactive, exhibiting behavioral and/or toxicological implications. In this regard, it is very likely that part of the β-carbolines found in the human tissues and fluids have a dietary origin.

     

     

  17. On 22/10/2023 at 7:20 AM, Ishmael Fleishman said:

    The ceremonial grade stuff is not easy to get were I am and I have just not been able to justify the cost at this time - however I am keen to try if their is any difference.

     

     

    If I get the chance, I'll grab you some. I think it's easy enough to get decent effects with the cheap powder but it's not as 'in' as having Peruvian ceremonial grade cacao
     

    I did a lot of experimenting with Cacao. It seems quite a useful medicine particularly for cognitive stuff, and in the shorter term as a mood lift. I was playing around with lots of fermenting and other things trying to boost effects but in the long run, simple seems best. Some popular blends were Sceletium, Saffron and Cacao and a few others
     

     

     
    Quote

     

    The broader cognition-enhancing effects seem dose-dependent, sustained, cumulative and in part, due to cacao flavonols and other constituents that act in a more long-lasting way.
     
    Cacao is an interesting nutraceutical tool to protect human cognition and counteract different types of cognitive decline - research investigating the relations between cacao and cognition shows dose-dependent improvements in general cognition, attention, processing speed, and working memory [1]. The CNS effects of cacao have been divided into several components by various authors [2].
     
    There is a large amount of scientific evidence that the flavonoids, more in particular cacao flavonols, are involved in the cognition-enhancing effects. Epicatechin, the most abundant flavanol in cacao, displays various beneficial effects on the CNS by stimulating perfusion (via a nitric oxide mediated pathway), angiogenesis, and neurogenesis (BDNF-TrkB). It induces changes in neuron morphology, especially in regions involved in memory and learning. These effects should be cumulative. The metabolites of the larger polyphenols also likely stimulate BDNF mediated processes.
     
    At the second level, the methylxanthines caffeine and theobromine have additive and maybe synergistic effects on cognition and alertness, although the role of theobromine remains unclear. That said, it seems the theobromine improves working memory [3] via upregulation of BDNF, also an effect that likely builds over time, rather than being acute.
     
    At the third and gradually more specific level, the tetrahydroisoquinoline alkaloids, more in particular salsolinol, may exert additive or synergistic activities.

     

     



    The β-carbolines are so common in foods as they form in condensation reactions between tryptophan and carbonyl compounds/breakdown products of sugars, which condense in a Pictet-Spengler reaction (often undergoing decarboxylation on roasting). Practically fermenting and roasting many foods will form some (and this seems to be their origin in Cacao), the main ones that seem to be often seen are (nor)harman, which results in measurable MAO-A inhibition from repeated coffee drinking, and tobacco use, which likewise results in significant MAO-A inhibition over long-term use "coffee is the most important exogenous source of these alkaloids in addition to cigarette smoking." [1]. 

     

     

    • Like 1

  18. It's pretty hard to get efficacy matching benzodiazepines IMO, even if the plant-based options retain some efficacy in treating symptoms. Also, if there's GABAergic tolerance through use of pharmaceutical GABAergics or drinking etc in prior history, most of these can seem comparatively mild/insufficient. Also, I wouldn't even consider relying on them for serious medical conditions eg seizure control

     

    I've in the past tried to rank subjective potency (which considering all my brain has been through shouldn't be taken as representative of normal) of some here as anxiolytics (note: not all GABAergic MoA):
     

    Lemon balm < Lower dose Passiflora < Lower dose skullcap < Zizyphus seed < Hops = Valerian < Oral lavender oil 80-160mg = lower dose kava = low dose CBD < Erythrina mulungu < Higher dose 25g+ Passiflora < CBD 600mg + < Higher dose skullcap < High dose kava.


    In general the flavonoid GABAergic plants can seemingly have some decent GABAA mediated  therapeutic effects but often without the abuse potential seen with BZDs eg baicalin

     

    That said, sometimes maintaining efficacy can be challenging with such and I can't say that the flavonoid GABAergics tend to have the "enjoyable" nature of BZDs

     

    There seems to be distinction between seeking actual symptom reduction eg. anxiolysis vs. desiring inebriation that can make people who enjoy GABAergics dismiss some plant options IMO

     

    Then there's things like tetrahydropalmatine which through non-GABAergic mechanisms seems to have potent muscle relaxing activity


  19. 2 hours ago, fyzygy said:

    Is Sceletium emarcidum comparable to tortuosum? Haven't come across that one before. 

    It's said by some including herbalistics to be "valued as highly as S. tortuosum in Southern Africa by different tribes and makes a very good Kougoed product". and I vaguely remember Torsten (but don't quote me) making mention of it not really mattering if you grow emarcidum vs tortuosum. Personally, there's something nicer about tortuosum but my brain isn't a good test subject. Phytochemically, it seems the emarcidum is 4'-O-demethylated mesembrine-type alkaloids (phenolic alkaloids) over the parent mesembrine-type alkaloids. It seems to root up a lot easier from cuttings, grows quickly and grows a lot easier in many climates. That said, some people have fermented up emarcidum and not noted much effect but even tortuosum can be hit and miss with some people. 

     

    Quote

    I had no luck rooting the lampranthus you sent a while back. But D. bosseranum seed has yielded a cluster of tiny seedlings.

     

    Yeah I have varied success with different cuttings at the best of times but good to hear what's worked for you.

×