How many times have you asked yourself, "Where did I put the keys?" or grapple for words during a "senior moment?" While aging is associated with the impairment of multiple metabolic pathways that can erode brain function, we don't have to resign ourselves to dwindling memory, foggy thinking, or poor attention span as we grow older. Thankfully, there is something we can do about it.
The drug hydergine acts on numerous fronts to slow down or even reverse age-related alterations in brain physiology and improve cognitive function. It's one of the safest, most effective, and intensively researched smart drugs available today. Over the past few decades, this potent cerebral enhancer has been shown in innumerable animal and clinical studies to boost memory and retrieval, alertness, intellectual capacity and even mood, while fending off the many deleterious processes that can lead to brain aging and mental decline.
Hydergine (also known as ergoloid mesylates or co-dergocrine mesylate) is the brand name for a mixture of three alkaloids derived from ergot, a fungus that grows on rye. The drug was developed in the 1940's by Albert Hofmann (known famously as the inventor of LSD) when working as a chemist for Sandoz (now Novartis and coincidentally, a former employer of the author of this article) and is still one of that pharmaceutical giant's most important drugs. Since the early 1970's, hydergine has been used clinically to treat senile dementia (including Alzheimer's), cerebral vascular disorders and the typical progressive deterioration of mental capacity known as age-related cognitive decline. Its efficacy has been well documented. The drug was approved by the FDA in 1981 for the treatment of dementia, defined as a loss of mental ability severe enough to interfere with daily life and characterized by symptoms such as decreased mental alertness, confusion, poor short-term memory, depression, emotional instability and problems related to motor skills. But perhaps the drug has an equally important role when used “off-label” as a smart drug, or cerebral enhancer, in healthy people who wish to protect against brain aging, sharpen their wit and mental agility, improve their memory and focus, and even gain a competitive edge in their career or pursuits. It's interesting to note that Hoffman, who lived to be 102, regularly consumed hydergine as a brain tonic, which may in part be responsible for his longevity and brain power.
In animal models, patients with cognitive decline, and aging but otherwise healthy people, hydergine has been shown to improve measures of cerebral function such as learning, memory, attention, as well as mood. Animal studies typically use a maze, or similar apparatus, as a "paradigm" for assessing cognitive behavior. One such study showed that hydergine increased the "intelligence" of rats trained in a maze to receive a liquid reward, as evidenced by increased accuracy in their attempts to obtain the treat. (1) In a similar maze experiment, hydergine improved memory and retrieval processing in mice, with the typical "inverted U" dose-response curve characteristic of memory enhancers. (2) (We’ll see more on the inverted U curve later.)
In clinical studies, hydergine was well tolerated in virtually every study, and often demonstrated statistically significant effects on cognitive measures in healthy subjects exhibiting "normal" aging and in patients with more accelerated cognitive decline. Here are some highlights of the studies, (note; the latter four were placebo-controlled and the first three were double-blind; they are listed in order of clinical severity, from the most to the least mental impairment):
We’ve just seen the proven cognitive-boosting effects of hydergine in animals and humans. Now, let’s take a look at the aging brain, and discuss how hydergine counteracts eroding mental performance.
The brain is especially vulnerable to the effects of aging on numerous fronts: decreased blood and oxygen flow, diminished mitochondrial energy production, hindered neurotransmission, loss of structural integrity, oxidative damage and decreased neuronal activity. Each of these factors alone impairs mental function; in combination, as is often (if not always) the case, the effects can be disastrous. The good news is that hydergine has been shown to influence many aspects of brain metabolism and ameliorate all of the effects of aging we just mentioned. Early research showed that hydergine acted primarily by increasing blood supply and oxygen to the brain, but a plethora of brain-boosting mechanisms have since been discovered:
This list of varied mechanisms underlies the efficacy of hydergine in ameliorating and potentially reversing, age-related brain deterioration and improving cognitive function. Plus, this list is not exhaustive. Undoubtedly, on-going research will uncover additional beneficial effects of this powerful cerebral enhancer.
Even with the wealth of compelling findings obtained in dozens of animal and human trials, some researchers questioned hydergine's efficacy in treating advanced cognitive decline, (i.e., dementia, including Alzheimer's). In response to this uncertainty, meta-analyses were performed to statistically evaluate the data obtained in multiple human trials. Two of these overviews, (one evaluating 21 trials and another analyzing 47 trials) concluded that "hydergine shows significant treatment effects" especially when initiated early and at higher doses than the FDA-approved 3 mg dose. (24-25) One reason why some trials reported only modest improvements in hydergine-treated patients is simply that the dose used was too low and therefore, ineffective. In Europe, the drug is prescribed at doses of at least 9 mg per day, but in the US, the recommended starting point is 3 mg. Since the drug exhibits low, if any, toxicity, and higher quantities have been linked with greater efficacy, it seems counterproductive (and unscientific) to use the lower dose.
The four clinical studies we reviewed earlier, in which significant improvements were obtained, used oral doses of 4.5 mg to 6 mg and an IV dose of 3 mg (note that a 3 mg IV dose has far greater potency than a 3 mg oral dose; directly injecting a drug into the bloodstream markedly increases its bioavailability). Also, unfavorable results in some trials may be due to the fact that treatment was initiated too late in the progression of cognitive decline. This indicates that medication with hydergine should be started as early as possible in those experiencing the first signs of mental deterioration, since treatment may prevent the cascade of brain alterations that can lead to more advanced cognitive decline and Alzheimer's.
Maintaining a healthy brain as we grow older, rather than rescuing cognition later, is a key component of an effective longevity strategy.
It’s difficult to recommend a universal starting dose for everyone, since response depends on each person’s unique physiology, sensitivity to medications and cognitive status. If used alone, you may consider starting with half of a 4.5 mg tablet for a few days, note your response, then increase to a full tablet, again rate your response and increase as necessary. Also, keep in mind that hydergine exhibits an inverted-U dose-response curve, which means that the dose should be increased slowly to reach an ideal response, after which any further increase in dose may lead to a fall-off in effect. Hydergine may also be combined with other smart drugs, such as deprenyl or piracetam, where it acts synergistically (i.e., at higher potency, while enhancing the effects of these other agents), so dosages may need to be adjusted down. As with other smart drugs, the best advice is to start low, increase gradually, evaluate the effect, and fine-tune as necessary.
Whether used alone, or in combination, hydergine should be a central element of any comprehensive antiaging program to preserve brain health, boost cognitive function and defend against the potentially devastating effects of age-related mental decline.