Ergot-derived Smart Drugs

Discussion in 'Miscellaneous Health Discussions' started by Rachel, Dec 19, 2012.

  1. Rachel

    Rachel Member

    Joined:
    Nov 3, 2012
    Messages:
    166
    Gender:
    Female
    Location:
    San Antonio, Texas USA - for now
    Ergot-derived smart drugs
    (Hydergine, Bromocriptine, Nicergoline)

    by Robert Mason Ph.D.

    Ergoloid mesylates, co-dergocrine, dihydroergotoxine, are all ergot derivatives that share a common ancestry; they all derive from a type of fungus that grows on rye.

    This article evaluates three of the most commercially used ergots: bromocriptine (pronounced brome-o-cript-teen), Hydergine, and nicergoline.

    Hydergine- the most popular ergot

    Now we move onto one of the most popular and widely used smart-drugs that has been in use for over 40-years- Hydergine (pronounced hi-der-gene).

    Hydergine has received only “mild” reviews whilst being used to treat senile dementias, (although it is widely regarded to have been used in dosages that were far too small for those purposes). However, Hydergine presents itself as a remarkable anti-aging medicine and a adjunct for the treatment of age-related mental decline.

    Hydergine is known to have all the following effects:

    Increase blood supply to the brain.
    Increase oxygen delivered to the brain.
    Enhance metabolism of brain cells.
    Protect the brain from insufficient oxygen supply.
    Slow the deposit of the age pigment lipofuscin in the brain.
    Prevent free radical damage to brain cells.
    Increase intelligence, memory, learning and recall.

    Oxygen is unique in that it is both a free radical generator and a free radical scavenger. At optimum concentrations, oxygen neutralizes more free radicals than it produces. Either too much or too little can upset the balance and generate the production of free radicals, which in turn can lead to aging. One of the major ways in which oxygen generates free radicals is its reaction with unsaturated fats, a process called peroxidation.

    Unfortunately, our brain cells contain more unsaturated fats than any other part of the body, therefore it is our brains that are most susceptible to peroxidation. Here are some conditions that can cause major peroxidation and the formation of massive amounts of potent free radicals:

    Heart attack.
    Stroke.
    Pollution (Carbon monoxide greatly reduces the oxygen carrying ability of the blood).
    Smoking cigarettes (Nicotine constricts blood vessels and decreases oxygen supply to the brain. It is estimated that those who smoke more than 20 cigarettes a day lose at least 7% of the normal blood flow to the brain).

    Some European countries use Hydergine for emergencies and accidents that involve shock, hemorrhage, strokes, heart attacks, drowning, electrocution and drug over-dose. Hospitals give Hydergine to patients before an operation in order to gain time in case of any ensuing crises. This is because Hydergine helps to stabilize brain oxygen levels, if they are too high Hydergine lowers them, if they are too low then Hydergine improves them. This was graphically illustrated in a cat experiment.

    Two groups of cats were anaesthetized and their brains electronically monitored. The scientists reduced the brain’s blood supply (and therefore oxygen supply). The cats in the control group (i.e. no Hydergine ) had brain damage within 5-minutes and died within 15-minutes. However, the cats in the pre-Hydergine treated group had strong brain wave patterns up to 45-minutes later. This experiment proved two things, firstly that a decrease in the normal oxygen balance results in tremendous free radical damage and secondly that Hydergine protects against this free radical damage when the oxygen level is upset.

    Hydergine has also been shown to increase the level of neurotransmitters in the brain, whilst this may not be significant enough for the treatment of senile dementia, such action has implications and benefits for the treatment and prevention of age-related mental decline.

    There is also evidence that Hydergine stimulates the growth of dendrite nerve fibers. Dendrites can normally be expected to decline with aging and some scientists have associated the number and density of dendrites with intelligence.

    This decrease in brain cell connection has been hypothesized to be due to an impairment in the energy supply at synaptic regions. Because of Hydergine’s known ability to improve nerve cell metabolism, a group of Italian scientists studied the ultra-cellular features of synaptic mitochondria to see if long-term Hydergine treatment could delay or prevent the loss of synaptic connections.

    The mitochondria are the “intracellular powerhouses” where the universal energy molecule- ATP (adenosine triphosphate) is produced. The scientists found that the number of mitochondria are greatest at about 12-months of age in rats (equivalent to a 25-year old in human terms) and then progressively decreases. However, the size of the mitochondria increased progressively after 12 months. Thus in young adult rats, the energy required at synaptic regions is provided by a large number of small, highly efficient mitochondria, whereas in old rats, energy is produced by a smaller number of larger, less efficient mitochondria.

    But, astonishingly after treatment with Hydergine , it can be seen that the total mitochondrial volume of old rats was nearly the same as the young rats. Furthermore, the mitochondrial size was altered to a more youthful direction.

    Like its ergot relatives, Hydergine has also shown itself to be a mild vasodilator (it enhances brain blood flow) and improves the uptake of the brain energy molecule- glucose. Hydergine also reduces the accumulation of the age-related toxin, lipofuscin.

    Time and again, clinical trials indicate that Hydergine can improve cognitive functions, mental alertness, clarity and mood.

    Dosages, Side Effects, and Contraindications

    With literally thousands of published clinical research papers and Hydergine ‘s decades of use around the world, it has proven itself to be nontoxic and relatively safe. Its potential side effects include mild nausea, gastric disturbances and bradycardia. It should be avoided by people who suffer from psychosis, or those with low blood pressure or abnormally slow heartbeat. Seek a health professional’s advice if combining Hydergine (at dosages in excess of 9mg per day) with other ergot derivatives or vasodilators.

    Most people do well at dosages of around 2.25mg to 4.5mg per day with occasional breaks. The most common side effect of stomach upset can be avoided with the use of specially coated tablets (known as FAS) or sublingual liquid versions.

    With its beneficial affects, mild side effects and few contraindications, Hydergine is ranked as one of the most important anti-aging medicines available today.

    Bromocriptine- the most potent ergot

    Bromocriptine is a semi-synthetic derivative of the ergo group of ergot alkaloids is a dopamine receptor agonist and a prolactin inhibitor. It is a potent D2 agonist but also displays partial action on D1 receptors) and a prolactin inhibitor.

    Its first major anti-aging use is the enhancement of dopamine, (a key brain neurotransmitter that undergoes an age-related decline). It is estimated past the age of 40, people undergo a dopamine decline of approximately 13% per decade (Ward, Fowkes & Morgenthaler). Accordingly, some neurologists have stated that “if we all live long enough we shall all become senile.” This is due to the fact that abnormally low levels of dopamine (70% to 80% loss) are then diagnosed as Parkinson’s disease, hence protection and enhancement of the dopamine producing neurons is a key strategy for anti-aging medicine. Not surprisingly, bromocriptine is used in conjunction with drugs such as deprenyl and L-dopa in the management of Parkinson’s disease. But bromocriptine can be used for anti-aging purposes also.

    Bromocriptine is also used to inhibit prolactin, one of the few hormones that actually increases with age. Prolactin is produced by the pituitary gland and bromocriptine inhibits its release.

    Prolactin has been described as a “fat synthesis hormone” because one of its primary functions is to trigger lactation (milk production) and weight gain in pregnancy. In women, bromocriptine has been used to help restore ovulation, but it also helps to reduce serum prolactin levels in men (although the precise role of prolactin in men is unclear).

    A further possible need to control age-related prolactin levels is offered by some researchers who believe that prolactin is an immune system suppressant.

    Bromocriptine increases growth hormone secretion in individuals with normal growth hormone concentrations, but paradoxically suppresses GH secretion in some patients with acromegaly (a condition of excessive-production of GH). Studies indicate that bromocriptine does not affect the release of any other anterior pituitary hormones.

    Due to its dopamine enhancement bromocriptine has even been cited as an aphrodisiac, although little effort has been made to study and confirm this action. There have been several reports of “better controlled” orgasms and “almost orgasms” before the real orgasm occurs. If any countries allow for more medical categories such as “weak orgasm syndrome” or perhaps “clinical sex-drive loss” then dopamine agonists such as bromocriptine are going to receive a lot of attention from the pharmaceutical manufacturers, especially in the wake of Viagra sales.

    Another interesting clinical study administered a component of tobacco called DMBA to rats at a level where it is known to be very effective in producing breast cancer. However, rats that had been pretreated with bromocriptine completely avoided any cancer development. Bromocriptine therefore appears to be a very potent free radical quencher.

    One of the most recent studies indicates that bromocriptine may be a candidate for the treatment of Type-2 diabetes. This is because bromocriptine has been shown to suppress lipogenesis and improve glucose tolerance and insulin resistance.

    One animal study suggested that a further action of bromocriptine is to alter CNS (central nervous system) regulating metabolism and as such has another important use in helping to prevent weight gain (this would be in addition to its improvement of diabetic conditions).

    Dosages, Side Effects, Contraindications

    Bromocriptine is a very potent substance and it mustn’t be used by pregnant or lactating women unless under the guidance of a physician. Side effects include nausea, dizziness, lowering of blood pressure, hypotension and confusion. The first three are relatively common, especially when undertaking initial use. It is also known to increase fertility, and thus “extra care” and contraception is advised where necessary.

    It does contraindicate with psychoactive and hypotensive drugs and other dopamine enhancing drugs (such as deprenyl and L-dopa etc) should only be administered concurrently under a physician’s guidance. Its effects can also be exaggerated when combined with other ergots including Hydergine and nicergoline.

    Overall, there is little need to exceed a dosage in excess of 1.25mg or 2.5mg daily for most people unless treating a serious medical disorder (and therefore only under a physician’s guidance). Bromocriptine has a wide and diverse range of clinically applications, it should be considered to only be an anti-aging medicine for the serious longevist.

    Nicergoline- the latest ergot derivative

    Nicergoline (pronounced nice-er-go-lean) is perhaps the latest commercially available variation of all the ergot preparations. It has become most popular in Japan and indeed many of its clinical trials have been performed there.

    Nicergoline appears to be a potent vasodilator (improving brain blood flow). On the cerebral level it prompts a lowering of vascular resistance, an increase in arterial flow and stimulates the use of oxygen and glucose. However, clinical trials confirm that nicergoline also improves blood circulation in the lungs and limbs and that blood platelet aggregation is inhibited.

    Studies also indicate that nicergoline does not affect arterial tension and that in cases of patients suffering from hypertension, it may induce a gradual lowering of the tension.

    Its approved uses to date have therefore included all of the following:

    Migraines (of vascular origin).
    Platelet aggregability and arterial hypertension.
    Eye disorders (retinal thromboses, diabetic retinopathy and macular degeneration).
    Problems of a vascular nature (dizziness, auditory problems, hypoacusis).
    Treatment of senile dementias.

    One interesting Japanese clinical study on rats showed that nicergoline increases nerve growth factor in the brains of aged animals, but it shows no statistical affect upon the brains of young animals!

    Further studies indicate that nicergoline can enhance glutamate re-uptake and protect the brain against ischaemia (lack of blood flow). This appears to be the main action of nicergoline and it presents itself as a mild stimulant and enhancer with long-term protection against brain disorders that may be due to blood, glucose or oxygen deprivation.

    Nicergoline- dosages, side effects and contraindications


    Side effects are usually limited to nausea, hot flushes, mild gastric upset, hypotension and dizziness. At high dosages bradycardia, increased appetite, agitation, diarrhea and perspiration have been known to present themselves.

    Persons suffering from acute bleeding, myocardial infarction or bradycardia should avoid nicergoline use. Persons using alpha or beta receptor agonists (such as propranolol/ Inderal) should not take nicergoline concurrently as nicergoline is known to enhance the cardiac depressive effects. Nicergoline is also known to heighten the effects of pharmaceutical products that produce hypotension, such as other ergot preparations in high doses (i.e. Hydergine and bromocriptine).

    Although not stated by the manufacturer, other potent vasodilatation agents such as vinpocetine, xanthinol nicotinate or picamilone should only be used concurrently under the guidance of a physician.

    Dosages for known conditions are usually administered at 5-10mg three times a day, however anti-aging preventative purposes may want to consider 5mg once or twice a day more adequate.

    Conclusion

    These three ergot preparations are all related and yet we can see their differences in the results of their various clinical studies. Each have differing strengths of reaction and indeed different effects.

    Fungi’s from rye were used by our ancestors for many different reasons, some of them as rites of passage into adulthood, most were considered to be “mind-expanding.” Now we know many of the pharmacological actions and roles they play in mental and memory enhancement and in the slowing of age-related brain disorders.

    Today, we understand that brain protection and enhancement is a most important factor- if not the most important factor for anti-aging medicine and successful longevity.

    References


    Bromocriptine:

    “DMBA induced tumors in rats treated with Bromocryptine” Trends in Pharmacological Sciences March 1981.

    Carter C, “Hormones and Sexual Behavior” Dowden Hutchinson & Ross 1974.
    Debono, “Bromocryptine and Dopamine Receptor Stimulation” British Clinical Pharmacol 3: 977- 982 1976.
    DeMartino M, “Sex and the intelligent women” Springer Publishing Co 1974.
    Parlodel drug insert, November 2000, Novartis.
    Luo S, Hodge J, Castro S, Cincotta A, “The Anti-Diabetic Effects of Bromocriptine Effectively Mediated via Intracerebroventricular Administration” Ergo Science, Boston, MA, USA.
    Yanagisawa N, Kanazawa I, Goto I, et al, “Seven year follow-up study of bromocriptine therapy for Parkinson’s disease” European Neurology 1994: 34 (suppl. 3): 29-35.
    Medscape Drug Info, “Bromocriptine mesylate oral pharmacology and chemistry” Dec. 2000.

    Hydergine :


    Emmenhegger H, Meier Ruge W, ” The actions of Hydergine on the brain” Pharmacology (1968) 1:65-78.
    Boismare F, “Biochemical and behavioral effects of hypoxic hypoxia in rats, study of the protection afforded by Hydergine” Gerontology (1978) 24, No 1 6- 13.
    Boula G, “Effects of Dihydroerogotoxine mesylate on aging neurons in vitro” Gerontology (1978) 24: 66- 70.
    Cahn J, Borzeix M, “Aging and Hypertension as risk membranes.” Aging (1983) 23: 413- 425.
    Ditch M, “An ergot preparation in the treatment of Cerebrovascular disorders in the geriatric patient” Journal of the American Geriatrics society (1971) 19 No 3 208- 217.
    Sandoz Inc., “Hydergine” Manufacturers product information sheet (1999)
    Hughes J, “An ergot alkaloid preparation in the treatment of dementia” Journal of the American Geriatric society (1976) 24 490- 497.
    Yoshilawa M, “A dose response study with dihydroergotoxine mesylate in cerebrovascular disturbances” Journal of the American Geriatric Society (1983) 31 1 1-7.
    Cranton M: Franckelton J: “Treatment of Free Radical Pathology in chronic degenerative diseases with EDT chelation therapy” Journal of Holistic Medicine (1984) 6-1.
    Pearson D: Shaw S: “Life Extension” Warner books, New York (1982).
    Copeland R: “Behavioural and Neuro chemical effects of Hydergine in rats” Archives of International Pharmacodynamics (1981) 252: 113- 123.
    Rao B: Norris J: “A double blind investigation of Hydergine in the treatment of cerebrovascular insufficiency in the elderly.” John Hopkins Medical Journal (1971) 130 317- 323.
    Weil C, “Pharmacology and clinical pharmacology of Hydergine” Handbook of experimental Pharmacology (1978) Springer Verlag New York.
    Fanchamps A, “Dihydroergotoxine in senile cerebral insufficiency” Aging (1983) 23 311- 322.
    Hindmarch I, “The effects of an ergot alkaloid derivative on aspects of psychomotor performance” The journal of clinical pharmacology (1979) 726- 731.
    Speigel R, “A controlled long term study with Hydergine, in healthy elderly volunteers” Journal of the American Geriatrics society (1983) 31, No 9 549- 555.
    Yesavarage J, “Dihydroergotoxine 6mg v 3mg dosage in the treatment of senile dementia” Journal of the American Geriatric Society (1979) No 2 80-82.
    Dean W, “Hydergine, potential anti-aging drug still highly recommended” Anti-Aging Bulletin, Volume 3 Issue 4, January 1998, International Anti-Aging Systems.
    Bertoni-Freddari C, Fattoretti P, Casoli T, Spanga C, Meier-Ruge W, “Morphological alterations od synaptic mitochondria during aging- the effect of hydergine treatment in the pharmacology of the aging process- methods of assessment and potential interventions.” New York Academy of Sciences, Volume 717 by Imre Zs-Nagy and Kenichi Kitani eds.) NYAS, NY 1994.
    Cucinotta D, DeLeo D, Frattola L, Trabucchi M, Parnetti L, “Dihydroergokryptine vs. placebo in dementia of Alzheimer type: Interim study after a 1 year follow up.” Archives of Gerontology and Geriatrics, 22, 169-180 (1996).

    Nicergoline :

    Bernd Saletu, et al, “Nicergoline in senile dementia of Alzheimer type and multi-infarct dementia: A double blind, placebo controlled, clinical and EEG/ ERP mapping study.” Pharmacia & Upjohn
    Nicergoline drug insert, Pharmacia & Upjohn, October 2000.
    Asai S, Zhao H, Yamashita A, Jike T, Kunimatsu T, Nagata T, Kohno T, Ishikawa K, “Nicergoline enhances glutamate re-uptake and protects against brain damage in rat global brain ischaemia.” European Journal Pharmacology 1999 Nov 3: 3;383(3):267-74.
    Takeshi N, Nobuhiko S, Shoei F, Ichiro A, Yukitsuka K, “Repeated injections of nicergoline increase the nerve growth factor level in the aged rat brain.” Japanese Journal Pharmacology, 76 (3), 321-323 (1998).
    Iliff L, DuBoulay GH, Marshall J, et al, “Effect of nicergoline on cerebral blood flow.” Journal Neurol. Neurosurg. Psychiatry, 1977, 40:746-7.

    http://smart-drugs.net/hydergine-article.htm#more-%27
     
  2. charlie

    charlie The Law & Order Admin

    Joined:
    Jan 4, 2012
    Messages:
    11,445
    Gender:
    Male
    Location:
    USA
    I have my eye on that bromocriptine. If my serotonin and prolactin are high I am going to push to get it from my doctor.
     
  3. WilltoBelieve

    WilltoBelieve Member

    Joined:
    Nov 25, 2012
    Messages:
    34
    Hydergine is a great contribution of Albert Hofmann if I'm not mistaken.
    I'm sure he had a good understanding of these things.
    What an inspiration it is to see Mr. Hofmann in various videos and pictures, and to read and hear his insights.

    I always thought he must have used hydergine and his great health up to 102 years suggests he was not slacking off when it came to health.

    Of course, if I had to choose between the hydergine or living in the Swiss Alps, I think the alps would win. But both would be even better.
     
  4. Ray-Z

    Ray-Z Member

    Joined:
    Oct 16, 2012
    Messages:
    321
    Good topic, Rachel.

    Kick some serotonin! :woo
     
  5. DaveFoster

    DaveFoster Member

    Joined:
    Jul 23, 2015
    Messages:
    4,910
    Gender:
    Male
    Occupation:
    Writer
    Location:
    Spokane, Washington
    I'm going to bump this, as this is a very interesting topic that deserves some more input.

    So far it seems that there is a lack of clarity as to the ideal ergot derivative.

    LSD is expensive, and is hallucinogenic in higher doses due to its very interesting action on the 5HTA receptor. It's also illegal, and no doubt the most controversial alkaloid.

    LSA is also illegal, but easily obtainable through Hawaiian Baby Woodrose seeds, or rather Morning Glory seeds, but it accompanies itself with some intense vasoconstriction and could hardly be considered on the same tier as LSD as far as mental effects. It is neither expensive nor particularly helpful.

    Cabergoline seems to have a reputation of inducing cardiac fibrosis over long-term use, but this is debatable. It's also the second most expensive alkaloid next to Lisuride.

    Bromocriptine is promising, but also comes with a relatively high cost. Also, the neurotropic effects of bromocriptine may be dwarfed in the presence of LSD of hydergine, but this is purely speculative, as I have never heard of it used for such. Long-term use comes with undesirable cardiac complications due to its serotonergic effects.

    Lisuride comes with a fairly high cost, and it seems to be one of the safest derivatives. It's definitely one of the prime options next to LSD, bromocriptine, and hydergine.

    Hydergine seems to be the most promising in the context of cognitive enhancement (along with LSD of course.) I am unfamiliar with the pharmakinetics of the substance, however. For example, does it affect MAO inhibition in the brain, thereby raising serotonin. I've also heard it facilitates cholinergic transmission in the same manner as racetamic compounds, so does this mean it enhances acetylcholine production in the brain? Both of these are questions that need answers, as these are undesirable and "non-Peaty" effects.

    As a side note, Hoffman provides a n=1 experiment of an individual who regularly consumed hydergine and retained a great degree of cognitive ability well into his later years, but this may simply be correlative.

    The comparison is as follows:

    Lisuride vs LSD vs Bromocriptine vs Hydergine

    Any input into this discussion would be much appreciated. Additionally, hydergine seems to enhance verbal usage and short-term memory, which seems to be very advantageous for learning a new language.


    PEAT'S QUOTE ON BROMOCRIPTINE "Bromocriptine shouldn't be used for more than a few weeks, prolonged use can cause heart valve fibrosis (a sign that it has serotoninergic effects, as well as anti-)." - Ray Peat

    It looks like Bromo is out for long-term use.

    It looks like hydergine is the only viable option for long-term use from the standpoint of cardiac safety.

    We must now investigate any undesirable cholinergic effects if such effects are present.

    Looks like we're good on both the fronts of acetylcholine and likewise histamine.
     
  6. mujuro

    mujuro Member

    Joined:
    Nov 14, 2014
    Messages:
    695
    For me the bromocriptine and LSD are easiest to acquire. I cannot even think of where to get the hydergine or the lisuride.

    I think for me bromocriptine as a DA will interfere with my quetiapine, which is working successfully in treating my bipolar disorder. LSD is something I'd very much like to tinker with.
     
  7. DaveFoster

    DaveFoster Member

    Joined:
    Jul 23, 2015
    Messages:
    4,910
    Gender:
    Male
    Occupation:
    Writer
    Location:
    Spokane, Washington
  8. Makrosky

    Makrosky Member

    Joined:
    Oct 5, 2014
    Messages:
    2,390
    Gender:
    Male
    Awesome post!!!! Thanks guys for the info.

    Btw, don't forget about 1P-LSD. It's the closest LSD analogue. Some users in drug forums and reddit says it's undistinguishable from LSD. And it's legal (still). I think I'm gonna try it one of these days...
     
  9. Greg says

    Greg says Member

    Joined:
    Nov 6, 2014
    Messages:
    335
    Gender:
    Male
    http://researchchemist.co.uk/research-c ... 1p-lsd-new ;)
     
  10. Blossom

    Blossom Moderator

    Joined:
    Nov 23, 2013
    Messages:
    8,438
    Gender:
    Female
    Thank you, thank you, thank you!!!! I've been having trouble finding Lisuride lately.
     
  11. Makrosky

    Makrosky Member

    Joined:
    Oct 5, 2014
    Messages:
    2,390
    Gender:
    Male
    LOL! Thanks mate. Uhhh hmmmm should I? Hmmm... No I shouldn't ... Hmmm just for stocking it up in case it becomes illegal.... :roll:
     
  12. Parsifal

    Parsifal Member

    Joined:
    Aug 6, 2015
    Messages:
    1,073
    What makes me cautious here is that it seems to reduce heart rate and blood pressure a lot whereas we try to increase our heart rate?
     
  13. Hitchens

    Hitchens Member

    Joined:
    Jan 27, 2019
    Messages:
    25
    Gender:
    Male
    Anyone have a source for Hydergine?
     
  14. No_Energy

    No_Energy Member

    Joined:
    Dec 16, 2017
    Messages:
    66
    Gender:
    Male
  15. milkboi

    milkboi Member

    Joined:
    Sep 25, 2018
    Messages:
    1,363
    Gender:
    Male
    Location:
    Germany
    1P-LSD is now illegal in germany. 1cP-LSD is its successor. Anyone has any experiences with it?
     
  16. SOMO

    SOMO Member

    Joined:
    Mar 27, 2018
    Messages:
    853
    Gender:
    Male
    I would love to try Hydergine but it's quite expensive.
     
Loading...