Hydergine ® Developer Albert Hofmann Turns A Hundred
by David Jay Brown
When Dr. Hofmann addressed the large crowds that gathered in his honor, he spoke eloquently. He was unusually articulate and clear-headed for a man that was over a century old. Many people remarked how sharp his mind was and later, when I had an opportunity to interview Dr. Hofmann for a book that I’m working on, I too couldn’t help but marvel at his remarkable cognitive abilities. I wondered if part of the secret to his extraordinary mental clarity was a result of his development and periodic use of the ergot-derived pharmaceutical Hydergine ® (Ergoloid mesylate).
The development of Hydergine
When Dr. Hofmann began working for Sandoz Pharmaceuticals (now Novartis) in Switzerland during the 1930s his research goal was to work towards the isolation of active principles in known medicinal plants. Dr. Hofmann developed Hydergine in the 1940s, while researching the chemistry of ergot, a fungus that grows on rye and was traditionally used by midwives in Europe to lower blood pressure with birthing mothers. While purifying the ergot-derived substance ergotoxine, Dr. Hofmann had the intuition that this alkaloidal preparation was not homogenous. Dr. Hofmann’s intuition proved correct. Upon further analysis ergotoxine turned out to mixture of three different components. (1)
During testing by Professor Rothlin at Sandoz, medicinally useful properties were discovered, and from these three substances, two pharmaceutical preparations were developed: the blood-pressure-stabilizing compound Dihydergot and the cognitive enhancer Hydergine. Although Sandoz was initially interested in new blood-pressure medications, they began devoting a great deal of resources into researching Hydergine, after studies started to uncover its cognition-enhancing effects. Hydergine was developed because of its ability to improve peripheral circulation and cerebral function in the control of geriatric disorders, and it has proven to be an effective treatment for these indications. Hydergine was the first drug to show efficacy as a treatment for Alzheimer’s disease and dementias. (2)
Today Hydergine is widely used around the world as a treatment for senility, age-related cognitive decline, and as a treatment for a number of other problems. Extensive research has revealed a plethora of brain-boosting and anti-aging benefits that Hydergine has to offer. Hydergine is one of the most tested pharmaceuticals ever developed and it still remains one of Novartis’ most important pharmaceutical products. It has proven to be beneficial and nontoxic in numerous studies. Dr. Hofmann has periodically used Hydergine himself over the years, and I suspect that his use of this cognitive enhancer may play a significant role in his extraordinary mental clarity at the age of a hundred. (3)
The many benefits of Hydergine
Studies indicate that Hydergine has the ability to enhance memory and learning. It improves a range of cognitive abilities, such as concentration and recall (4,5,6) and helps to prevent damage to brain cells from insufficient oxygen. (7) A number of studies even suggest that Hydergine may be able to help reverse existing damage to brain cells. (8)
Some of Hydergine’s cognitive enhancement may be due to the fact that it increases oxygen and blood flow to the brain because it’s a mild vasodilator. (9) It also enhances brain cell metabolism and mitochondrial metabolism. Hydergine’s ability to improve cell metabolism inspired a team of Italian researchers to study how it affects the intracellular features of rat mitochondria, structures within cells that produce energy in the form of ATP (adenosine triphosphate) by respiratory metabolism. In these studies Hydergine not only increased the volume of the mitochondria, it also reduced their size, which is similar to the more efficient mitochondria in younger animals. (10)
Hydergine is an extremely powerful antioxidant. When I spoke with life extension researcher Durk Pearson he said, “We suspected that Hydergine might be a powerful antioxidant due to its structure, so we suggested an experiment that was done at NYU. Every time vitamin C is oxidized and then reduced by the iron in redox cycles, you produce a hydroxyl radical. And the hydroxyl radical is tremendously chemically reactive. It’s about as reactive as fluorine is at eight hundred degrees Fahrenheit–so it can rip up anything. What they found is that Hydergine was the most powerful antioxidant that they tested.”
Hydergine stimulates new interconnective growth between neurons. It causes the release of brain-derived neurotrophic factor (BDNF), which is involved in the repair of damaged neurons and the growth of neurons and neurites. (11) According to Pearson, “If you deprive the brain of BDNF the neurites die back and eventually the cell bodies connected to them die. The brain normally produces BDNF, but as you get older you produce less and less. You end up with some nuerites dying back and your brain sort of gets disconnected. The neurons get disconnected from each other.”
This is an important mechanism by which Hydergine may enhance learning and memory in the elderly. Hydergine mimics the effect of a substance found in the brain called nerve growth factor, which stimulates protein synthesis that results in the growth of new dendrites (tiny tree-like branches at the receiving ends of brain cells). (12) Many neuroscientists believe that intelligence is correlated with the number of interneural connections in the brain. Studies have demonstrated that Hydergine actually increases cortical thickness in the brain through this process and that it also raises levels of the neurotransmitter dopamine. (13)
Studies have shown that Hydergine helps to stabilize brain oxygen levels. (14) If brain oxygen levels are too low then Hydergine raises them, and if they’re too high then Hydergine lowers them. This is why some European countries use Hydergine preoperatively in surgery and after strokes, hemorrhages, and heart attacks to gain precious time. It is also sometimes used to gain more time after certain types of accidents, such as drowning, electrocution and drug overdoses.
Hydergine reduces deposits of the age-related toxin lipofuscin in the brain (15), and normalizes systolic blood pressure. (16) It has also been shown to reduce symptoms of lethargy and, in some cases, even lower abnormally high levels of cholesterol. (17) Many people report that their brain simply feels more awake and more lucid on Hydergine.
Some studies on Hydergine have demonstrated only mild effects, leading some people to believe that it’s not very effective. (18) However many European physicians believe that these studies were less dramatic than others simply because the dosages used were too low, and studies comparing the effects of a 3 mg daily dose to a 6 mg daily dose support this notion. (19) The U.S. recommended dose is 3 mg. per day, while the European recommended dose is 9 mg. per day in 3 divided doses. Some people need to take Hydergine for several months before they notice any significant effects.
Hydergine is extremely nontoxic and has very few side-effects. Initially, Hydergine may cause some mild nausea, gastric disturbances, and bradycardia. It is contraindicated for people who are allergic to it, who suffer from psychosis, or who have an abnormally slow heartbeat or low blood pressure. (20)
Combining Hydergine with other ergot derivatives or other cognitive enhancers may have a synergistic effect, so you may need to scale down the dosages of all the drugs. One should seek the advice of a physician when combining Hydergine with other cognitive enhancers in excess of 9 mg. per day. Most people do well at dosages of around 3 mg. to 9 mg. per day, in divided doses, with occasional breaks. The most common side effect is stomach upset. This can be avoided by using specially coated (FAS) tablets or by using a sublingual liquid preparation.
Other Ergot-derived cognitive enhancers
Albert Hofmann’s intuition about ergot turned out to be extremely fruitful. This remarkable fungus has proven itself to be a gold mine of medicinal treasures; Hydergine is only one of numerous drugs to be derived from ergot. Some of the other ergot-derived cognitive enhancers include the more potent pharmaceutical bromocriptine and the recently developed pharmaceutical nicergoline.
Bromocriptine is a dopamine receptor agonist, which activates dopaminergic neurons and mimics the effect of the excitatory neurotransmitter dopamine. (21) It is the most potent of the ergot derivatives and although it is primarily used to treat Parkinson’s disease, it also has profound antiaging effects because it enhances dopamine, which tends to decrease significantly with age. It also effects the pituitary gland production of the hormones prolactin and growth hormone (GH) in some very beneficial ways that appear to counteract some of the symptoms of aging. (22)
Bromocriptine inhibits prolactin, which tends to increase with age, and it increases GH secretion, which tends to decrease with age. Although bromocriptine increases GH secretion in healthy individuals with normal GH concentrations, it actually suppresses GH production in people with a condition known as acromegaly, which causes excessive GH production. Studies indicate that bromocriptine does not affect the release of any