Hydergine

Description
Hydergine is an ergot derivative of the famous chemist Albert Hofmann for the pharmaceutical company Sandoz (now part of Novartis)^[1]. It is an extremely popular nootropic among nootropic enthuiasts for its synergy with Piracetam^[1]. In my opinion due to the risks associated with this compound^[4] as well as the legality of the substance, it is not a preferable nootropic.

Mechanism of Action

Despite the fact that hydergine has been used in the treatment of dementia for many years, its mechanism of action is still not clear. It stimulates dopaminergic and serotonergic receptors and blocks alpha-adrenoreceptors. It is a nootropic. Current studies imply that the major effect of hydergine may be the modulation of synaptic neurotransmission rather than solely increasing blood flow as was once thought. A prominent feature that accompanies aging is an increase in monoamine oxidase (MAO) levels which results in decreased availability of catecholamines in the synaptic cleft. In one study, an interaction between age and hydergine treatment was observed in the hypothalamus, hippocampus and cerebellum. The hydergine effect was more pronounced in the aged group in the hypothalamus and cerebellum, and more pronounced in the adult in the hippocampus. These findings imply that increased brain MAO activity in aging can be modified by hydergine treatment in some brain regions.^[1]

"Co-dergocrine (Hydergine), an ergot preparation composed of four dihydrogenated peptide ergot alkaloids (dihydroergocornine, dihydroergocristine, dihydro-alpha-ergokryptine, dihydro-beta-ergokryptine, 3:3:2:1), has been reported to exert in vivo effects suggesting an interaction with dopaminergic systems. The present investigation provides evidence that, in the striatum of the rat, co-dergocrine and its components interact directly with D1- and D2-subtypes of dopamine receptors. In homogenates of rat striatum, co-dergocrine and three of its components (dihydroergocornine, dihydro-alpha-ergokryptine, dihydro-beta-ergokryptine) stimulate cyclic AMP formation (D1-receptor response) having similar EC50 values but different efficacies. The same compounds inhibit electrically evoked tritium overflow from rat striatal slices preincubated with [3H]choline (D2-receptor response) at about 50 times lower concentrations. Here again the compounds exhibit differential maximal effects. One component, dihydroergocristine, antagonises both receptor types. The effect of co-dergocrine in functional responses mediated by both D1- and D2-receptors seems to reflect the summation of the contribution of its components."^[3]

"This semi-synthetic derivative of the ergo group of ergot alkaloids is a dopamine receptor agonist (for those who like precise detail it is a potent D2 agonist but also displays partial action on D1 receptors) and a prolactin inhibitor."^[2]

Reputed Benefits

1. Increase blood supply to the brain.
2. Increase oxygen delivered to the brain.
3. Enhance metabolism of brain cells.
4. Protect the brain from insufficient oxygen supply.
5. Slow the deposit of the age pigment lipofuscin in the brain.
6. Prevent free radical damage to brain cells.
7. Increase intelligence, memory, learning and recall.^[2]

Dangers

"Pleural and peritoneal fibrosis have been reported with prolonged daily use. Cardiac valvular fibrosis has also been associated with ergot alkaloids."^[4]

Possible Psychological Side Effects
From my own observation of those people who have taken this product (one finds many on nootropic forums across the internet), I have seen the following:
- Increased abnormal beliefs
- Arrogance increases
- Lack of ability to filter
- A certainty of one's intelligence

Research

"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."^[2]

"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."^[2]

References
^[1] Wikipedia: Ergoloid

^[2] Ergot-derived smart drugs (Hydergine, Bromocriptine)

^[3] Dopamine receptor profile of co-dergocrine (Hydergine) and its components.

^[4] Ergoloid Mesylates