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Daffodils and Withdrawal?

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Stimulated by the recent Transient Receptor Potential (TRP) discussion, the following began as a comment from one of RxISK’s background activists but grew into a post.

RxISK is not about to desert orthodox medicine and turn to herbalism but herbalism may well have a lot to offer.  It looks like many traditional remedies actually do act on systems we knew nothing about until recently.  If any readers have contacts with serious herbalists it would be good to get their input on some of the issues allopathic drug treatments cause and how herbal preparations might help but also anything that is known about risky interactions between allopathic medicines and herbal preparations.

Daffodils

Daffodils are not strictly a herb but as Kevin Stephens found out they echo recent posts on RxISK.  KS became interested because he knew someone with Alzheimer’s, so he took a course in genetics to understand how growing daffodils for medicine could help.

A former shepherd turned software developer and engineering enthusiast, Kevin’s introduction to the world of daffodil farming also came through a chance encounter with biotech expert Professor Trevor Walker.

Daffodil leaves and flower stalks contain crystals of calcium oxalate. This is not unexpected, since some members of almost all plant families, including many crops, synthesise oxalic acid (C2H2O4) as a normal physiological process. Oxalic acid is a strong dicarboxylic acid and the most oxidised organic compound synthesised by plants. The crystals were first seen in plant tissues by Antonie van Leeuwenhoek in the late 1600s as a consequence of his improvements to magnifying lenses. For many years they were thought to form spontaneously, but it is now apparent that the complexity of crystal formation, even extending to morphology, requires a substantial level of genetic and biochemical control.

See Drugs from Daffodils

In daffodils, bundles of needle-shaped calcium oxalate crystals termed raphides are formed. As well as being involved in controlling calcium levels in the tissues, the raphides provide some protection from grazing animals and insects. This extends to people, since an eczematous rash and sores – ‘daffodil picker’s rash – on the hands and arms are a well-documented hazard of the flower bulb industry where ‘cut’ flowers are actually plucked from the base. The rash is partly due to the raphides released into the sap that exudes from broken stems and leaves. Soluble oxalate itself is also toxic to animals through interference with calcium metabolism.

Daffodils also synthesise a wide range of isoquinoline alkaloids. The total level in the bulbs is generally 1-2%, but over 100 individual compounds have been identified among different Narcissus varieties, starting with lycorine identified from N. pseudonarcissus in 1877 by A. W. Gerrard. They are collectively termed the Amaryllidaceae alkaloids, after the taxonomic family to which Narcissus belongs, since the specific chemical structures are unique to that family.

The characteristic features fall into nine principal skeletal subgroups, all containing ring systems derived from the amino acids phenylalanine and tyrosine, and a single nitrogen atom, which can be secondary, tertiary or even quaternary (Figure 1). In addition, all are moderately weak bases (pKa 6 – 9). Biosynthetic pathways were proposed from the 1960s following radiolabelling experiments and isolation of proposed chemical intermediates (Figure 2). However, researchers have yet to isolate and study the relevant Narcissus enzymes.

The alkaloids are undoubtedly why eating all parts of daffodils can cause illness, with symptoms including vomiting, abdominal pain and diarrhoea in animals and people., but fortunately the result is usually a short period of illness without long-term consequences.

Daffodils have been used regularly in folk and traditional medicine, for in addition to the well-documented sickness-inducing properties, extracts can produce numbness, hallucinations, convulsions and cardiac effects, as well as being used for centuries in cancer treatments. Applying juice or aqueous extracts to burns or open wounds can result in numbness and these effects explain why there has been interest in identifying their chemical and pharmacological bases.

Pharmaceuticals

Plants are important for new pharmaceuticals because of the complexity of their secondary metabolic compounds. Indeed, one third of the approximately 1000 new pharmaceuticals registered in the past 25 years originated from or were inspired by natural products. The global market in plant-derived drugs in 2008 was estimated to be worth about £12bn from both prescribed and over-the-counter sales.

The best-studied Narcissus alkaloids are lycorine, narciclasine, galanthamine and pretazettine, which have several pharmacological activities, and extraction and purification are favoured because it is challenging to synthesise in large quantities compounds with high levels of stereoselectivity.

Galanthamine, also called galantamine, marketed as Reminyl by pharma company Shire Pharmaceuticals, is particularly interesting because it is approved by the National Institute for Health and Clinical Excellence in the UK as a treatment of early stage and moderate Alzheimer’s dementia. Alzheimer’s currently affects at least 600,000 people in the UK and as many as 35m people worldwide, and incidences will increase dramatically as average life expectancies increase.

Alkaloids are of interest because people with Alzheimer’s appear to have a shortage of the neurotransmitter acetylcholine in their brains. In the 1950s, the Russian pharmacologists M. D. Mashkovsky and R. P. Kruglikova-Lvova discovered that galanthamine could competitively inhibit the enzyme acetylcholine esterase. Further work established that its action was long-acting, selective and reversible, with a number of clinical uses such as recovery from a type of curare-induced anaesthesia and, later, Alzheimer’s disease.

SME Alzeim in Brecon in mid-Wales is leading scientific work, with support from the Welsh Assembly and central governments, to develop the necessary chemical expertise. One attraction of Wales for producing alkaloids is that chemical levels can be enhanced by the stresses of growing the plants in the Welsh mountains. Studies include extensive horticultural trials to identify the most appropriate regimens for alkaloid production – such as varietal, location and climatic combinations – in collaboration with Cambridge and Bangor universities. Highly specialised fertiliser treatments as well as unique harvesting and processing equipment have been developed. Harper Adams University in Shropshire is now also involved.

Much work has also been necessary to develop a new, wet-based industrial scale extraction process with chemical engineers at Manchester University.

The daffodil is destined to be at the centre of intense research activity in the near future in order to realise urgently needed commercial expansion of production not just for generic versions of galanthamine-based oral medicines but also for the development of other drug delivery systems and, eventually, other alkaloids that promise to be of value to medicine.

See Welsh Daffodils

 

 

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Comments

  1. To add a serious warning – as well as another note of optimism for treatment for depression Daffodils are seriously toxic so self experimentation is not advisable.
    Traditionally daffodils have been used to induce vomiting and as a poultice for burns and wounds. Unsupervised ingestion has proved fatal.The bulbs are the most poisonous part of these so-called friendly flowers, so you might think twice about planting them if you have a dog who likes to dig. Ingesting too much could cause vomiting, diarrhea, convulsions, tremors, and cardiac arrhythmia. (as well as other effects such as hallucinations – see google searches)

    Modern uses include extracting galantamine from the bulbs to treat Alzheimer’s disease,
    research at the University of Copenhagen to use daffodil compounds as a treatment for depression
    and a Chinese study suggests daffodil compounds can kill off certain cancer cells (such as leukaemia)

    Source: Daily Mail 22 January 2013

    Reply

  2. https://www.research.bayer.com/en/phytotherapy-medicinal-plants-new-applications.aspx
    HomeMedicineMedicinal Plants – New Uses
    New Uses for Ancient Active Substances
    Phytotherapy: Medicinal Plants in Health Care
    When used sincerely for the good of us all integrated science can provide integrated safe less harmful health care . I am not an advocate for herbalism alone but crucially do advocate that those who provide health care should be open minded and listen to what people tell them has been helpful as well as keep up with research outside conventional approaches . (Althogh I wouldn’t trust Bayer based on it’s reputation = just using it as an example but most of us would have no way of checking what is stated)Most sites giving medical advice need to protect themselves by advising users of complementary medicine s to discuss them with their GP. Most of us probably find this fairly risible unfortunately ,I

    Solution:
    Researchers at Bayer are testing and verifying the efficacy of their plant-based medicines in clinical studies. Important requirements for recognition as a medication include precisely defined production processes and strict quality controls. Phytopharmaceuticals are principally subject to the same approval procedure as chemical drug products.
    Today’s phytopharmacologists use scientific methods to determine the mechanisms of action of plant-based medicines containing extracts from flowers, leaves, roots or essential oils. “The aim of phytotherapy is to prevent, alleviate or heal diseases and complaints using medicinal plants,” explains Dr. Heba Abdel-Aziz of Bayer’s Consumer Health Division, Medical & Clinical Affairs Phytomedicine.
    In contrast to chemically defined medications, phytopharmaceuticals are not isolated substances but a mixture of many natural ingredients. Secondary plant substances play a role here.
    In the case of active substances from plants, two and two often do not equal four, but six or eight instead. That is synergy.

    Dr. Heba Abdel-Aziz
    Although many studies have proven the efficacy of plant extracts, researchers often do not know why the multi-component mixtures are so effective. Abdel-Aziz, who examines the mechanisms of action of phytotherapeutic drugs in cooperation with university researchers, explains it like this. “There are a large number of ingredients that contribute to the effect, some of which we haven’t even identified yet.” This multitude of substances amplifies the effect through synergy: two or more substances together have a greater overall impact than a single individual one. “Two and two does not equal four in such cases, but six or eight instead. That is synergy,” says Abdel-Aziz.

    Escaping Depression: How Saint John’s Wort Works in the Brain

    The plant-based drug products in phytotherapy differ from traditional medicinal herbs in one important way. In order to obtain approval as drug products, phytopharmaceuticals are subject to strict scientific control. Their molecular mechanisms of action are examined in pharmacological or preclinical studies. Researchers then confirm their efficacy and safety in clinical studies and resulting meta-analyses.
    )
    However, phytotherapeutics can also take effect in the brain – such as the Bayer medications Laif™900 and Laif™ 900 Balance, which are derived from Saint John’s wort (Hypericum perforatum). Laif™ 900 helps combat mild to moderately severe depressive episodes and must be prescribed by a doctor. The prescription-free product Laif™900 Balance, by contrast, is approved only for milder forms of the disease. “The cause of depression is unclear,” says Dr. Christiane Kolb, a Medical & Clinical Affairs Phytomedicine Manager and an expert on the drug product derived from Saint John’s wort. “We know, however, that the metabolism in the brain is impaired and that chemical messengers are missing. As a result, impulses are no longer adequately transmitted.” Saint John’s wort extract enables more of the neurotransmitters to reach the synaptic cleft. Substances in Saint John’s wort such as hypericin, hyperforin and flavonoids contribute to this effect. “The extract in Laif 900 has proven therapeutically effective in clinical studies,” says Kolb. “We have observed effects known to us from synthetic medications – but with significantly fewer side effects. That is a big advantage.”

    INTERVIEW: DR. MOHAMED T. KHAYYAL
    Khayyal has conducted numerous pharmacological studies aimed at improving phytotherapy.
    „The Results Are Very Promising“
    research spoke with pharmacologist Dr. Mohamed T. Khayyal about his work in the field of phytotherapy. Khayyal is a professor emeritus at the Faculty of Pharmacy at Cairo University in Egypt. He has conducted many pharmacological studies, including on Iberogast™.

    What should people know about phytotherapy?
    . Herbal total extracts are often better tolerated than isolated active components, since they usually contain other constituents that modify and compensate for undesirable effects of the active ones.
    What should people be aware of?
    Not all manufacturers produce their products according to such strict standards as Bayer. Accordingly, the amount of active substances contained in plant-based products can sometimes vary from one batch to another. It is a problem that some manufacturers are satisfied with minimal results and do not provide sufficient proof of therapeutic benefit. This undermines the credibility of phytotherapy.

    International Users
    This website is checked, operated and updated by BAYER at Leverkusen, Germany. It is intended for international use.
    then confirm their efficacy and safety in clinical studies and resulting meta-analyses.

    Laif™ 900 helps combat mild to moderately severe depressive episodes and must be prescribed by a doctor. The prescription-free product Laif™900 Balance, by contrast, is approved only for milder forms of the disease. “The cause of depression is unclear,” Saint John’s wort. “We know, however, that the metabolism in the brain is impaired and that chemical messengers are missing. As a result, impulses are no longer adequately transmitted.” Saint John’s wort extract enables more of the neurotransmitters to reach the synaptic cleft. Substances in Saint John’s wort such as hypericin, hyperforin and flavonoids contribute to this effect. “The extract in Laif 900 has proven therapeutically effective in clinical studies,” says Kolb. “We have observed effects known to us from synthetic medications – but with significantly fewer side effects. That is a big advantage.”

    This website is checked, operated and updated by BAYER at Leverkusen, Germany. It is intended for international use. However BAYER gives no guarantee that the details presented on this website are correct worldwide,
    proven therapeutically effective in clinical studies,” says Kolb. “We have observed effects known to us from synthetic medications – but with significantly fewer side effects. That is a big advantage.”
    What should people know about phytotherapy?
    Many people choose active substances from plants because they are concerned about harmful side effects caused by chemical products. However, herbal-based medicines often offer more important advantages than that. They could sometimes have a broader spectrum of activity when multiple herbal combinations are used and often have milder side effects than conventional therapies. However, there can be no effect without any side effects. Herbal total extracts are often better tolerated than isolated active components, since they usually contain other constituents that modify and compensate for undesirable effects of the active ones.
    , we try to explore new therapeutic strategies. That is what motivates us as scientists.

    Nevertheless, some doctors doubt that plant-based medications are as effective as synthetic ones. Bayer specialist Müller cannot understand this skepticism among his colleagues. “Plant-based and chemical medications are scientific equals in terms of efficacy. Plants are in fact at the very root of medicine.”

    International Users
    This website is checked, operated and updated by BAYER at Bayer Corporation.
    Last updated: January 16, 2020 Copyright © Bayer AG

    BUT maybe some people are more suspicious of pharma companies than herbalism

    There are many Serious warnings about St Johns Wort are described although
    St. John’s wort is one of the most commonly purchased herbal products in the United States.
    St. John’s wort Information | Mount Sinai – New Yorkwww.mountsinai.org › herb › st-johns-wort
    Hypericum perforatum; Klamathweed. Share. St. John’s wort (Hypericum perforatum) has a history of use as a medicine …..

    And Bayer has a vile history (see wikipidia)
    Bayer’s reputational issues continue as ‘watch list’ scandal …www.prweek.com › article › bayers-reputational-issues-…eg
    20 Jun 2019 — Controversy. Sold by Bayer under the brand name Roundup, the weedkiller has been described as carcinogenic in numerous lawsuits. The existence of the lists, which include details of journalists, politicians and agricultural and non-profit leaders, has prompted an investigation by the Paris Public Prosecutor’s Office.

    Bayer – Drug Manufacturer’s History, Problematic Drugs …www.drugwatch.com › manufacturers › bayer
    More than 10,000 women filed Yaz lawsuits against Bayer. The company settled more than 8,000 cases for $1.7 billion. About 60 federal lawsuits remained pending as of May 2018.
    ‎History · ‎Products · ‎Lawsuits and Settlements

    Reply

  4. Let ‘thy body ‘do the healing.
    I am a strong believer in treating the body, with the dignity and respect it deserves.
    We have all been given a magnificent piece of machinery and most of the mind blowing health maladies can be supported and assisted with proper diet, drinking plenty of water, exercise, learning about herbs, supplements, vitamins, meditation, tai chi and whatever will induce happiness and inner contentment.
    Please take care of your mental well-being by looking/researching other alternatives.
    Fixing a health issue (s), induced by meds or compounding the issue(s) with new and promising pharmaceutical products or other alternatives, may make ones conditions worse.
    Unless, they can manufacture something without side effects or adverse reactions, I would err on the side of caution- coming from the hard knocks of life!
    I have been on the receiving end an understand all too well that:
    many procedures + tests + unnecessary medicines can sadly = more harm than good.
    On the other hand, in emergency situations, many procedures/tests and meds = save lives.
    Don’t get me wrong, western medicine can benefit however, only if it is absolutely necessary.
    Some medicines are needed for certain health issues however, some are totally and utterly unnecessary.
    Once a damage has been done, we go on journey to finding a cure, that leaves one despondent and demoralized, if no remedy can be found.
    It’s similar to finding a pin in the haystack.
    If you find something that works- stick with it!
    If you find someone who loves to help, without the added hoo-ha – stick with them~!
    If the daffodil promises a cure without the unnecessary side effects or adverse reactions, then they are certainly onto something good.

    Reply

  5. There are some establishments where integrated research is already established but nowhere is it seems are any prepared to challenge the domination of beliefs held by psychiatry – or at least can’t find funding to start any of the sort of collaboration carried out in Bath
    University of Bath
    COURSES RESEARCH COLLABORATE DEPARTMENTS
    Dept of Pharmacy & PharmacologyMenu
    Using daffodils to create cancer treatments
    We’re exploring how compounds derived from natural products found in daffodils could be used in potential cancer treatments.
    Pancratistatin and narciclasine exhibit potent anti-cancer activities, but their extremely limited availability makes it impossible to obtain them in quantities large enough to be considered as viable drug candidates.
    Until recently, making these products synthetically required too many steps to be suitable for detailed biological evaluation and clinical development.
    Synthesising compounds with anti-cancer potency
    But researchers in the Department of Pharmacy & Pharmacology have developed and published a new synthetic methodology addressing this issue.
    They are now applying this methodology to make new compounds which are closely related to the pancratistatin and narciclasine found in daffodils.
    This technique allows the research team to improve the efficiency of the process, while retaining the anti-cancer potency of the compounds.
    These synthetic routes are extremely efficient – requiring only two or three steps from cheap, commercially available starting materials – and can be synthesised on large scale.
    The advantage of a totally synthetic compound is that it gives the research group complete control over the design and framework – so they can alter the structure to improve potency, selectivity and the ability to used it commercially as a pharmaceutical drug
    They are currently working on optimising the synthesis, and conducting biological evaluations to fine-tune the design – hopefully culminating in the identification and preliminary investigation of a lead compound for clinical development.

    Cancer Research at Bath (CR@B)
    A dedicated cancer research network facilitates interaction between departments and institutes to allow multi-disciplinary activities in the field of cancer research.
    The network provides a forum to enable discussion and collaboration between academics, clinicians, students, and interest groups. It promotes opportunities for interdisciplinary research and aims to promote awareness of cancer research both within academia and the wider community.
    The network currently includes around 40 researchers and a wealth of high-impact projects.

    Whereas the likelihood pf psychiatrists opeining their minds is shown on this video (one parent did get in a question re ritalin and herbs which wasn’t answered)
    S Wessely has published more than 650 peer reviewed academic papers in these fields and has received over £20million in research funding. On the video he gets angry at the accusation he has received pharma cash.
    Psychiatrists and the pharma industry are to blame for the current ‘epidemic’ of mental disorders
    11 May 2015
    Intelligence Squared
    352K subscribers
    Want to join the debate? Check out the Intelligence Squared website to hear about future live events and podcasts:

    If pharma and medico- politicos gets too involved and it looks as though they might be sniffing at the cash opportunities ,there must be concerns that research will be corrupted Hopefully those taking novel approaches won’t sell out but encourage others to join a new movement in science

    Reply

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