Insomnia will be a thing the past you can happily forget about. Scientific advancements in the arena of neurosteriods have proven the potent power of allopregnanolone to flood the gamma amnio butyric acid receptors in the brain, inducing deep slow wave sleep. The gamma amnio butyric acid receptors are the same ones the popular benzodiazepines target and act on to quell anxiety, anesthetize and sedate in even the worst cases of insomnia.
Allopregnanolone has numerous advantages over benzodiazepines and other pharmaceutical tranquilizers.
Pregnenolone (allopregnanolone is a metabolite of pregnenolone and progesterone)
Pros: 1. actually boosts cognitive performance, memory, learning, neurogenesis, neuroprotection and overall mood
2. generates the most restoring delta slow wave sleep, when growth hormone is released
3. increases brain levels of acetylcholine
Benzodiazepines, Ambien and tranquilizers
Cons: 1. decrease REM and delta wave sleep
2. cause cognitive decline, memory loss
3. long term use results in brain damage
The diagram above shows the hormonal cascade and synthesis of allopregnanolone.
Controlled double blind placebo research (cited and linked below) suggests that both progesterone and pregnenolone both increase levels of allopregnanolone through oral or injected routes of administration.
J Pharmacol Exp Ther. 1997 Sep;282(3):1213-8.
Allopregnanolone affects sleep in a benzodiazepine-like fashion.
Source
Max Planck Institute of Psychiatry, Clinical Institute, Munich, Germany. lancel@mpipsykl.mpg.de
The sleep effects of allopregnanolone are very similar to those elicited by larger doses of progesterone, which produce comparable brain levels of allopregnanolone. These data indicate that the steroid allopregnanolone has benzodiazepine-like effects on sleep. Recent research in rats and humans has shown that exogenous progesterone evokes a sleep profile similar to that induced by agonistic modulators of g-aminobutyric acid receptors, such as benzodiazepines. This finding suggests the involvement of the neuroactive metabolite of progesterone, allopregnanolone.
Both doses of allopregnanolone reduced the latency to non-rapid eye movement sleep (nonREMS) and 15 mg/kg allopregnanolone significantly increased the time spent in pre-REMS, an intermediate state between
non-REMS and REMS.
Steroid hormones affect neurotransmission in the brain. Data from animal experiments have shown that progesterone metabolites enhance the action of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the cortex, producing benzodiazepine-like (e.g., diazepam and lorazepam) physiologic and behavioral effects.
Several lines of evidence indicate that the central-depressant action of progesterone is due not so much to the binding of progesterone to intracellular steroid receptors but rather is chiefly mediated by the action of its 5 alpha reduced metabolite 3a-hydroxy-5a-pregnan-20-one (allopregnanolone) at the membrane-bound GABAA receptors. Both endogenous and exogenous increases in the level of progesterone result in rapid elevations of allopregnanolone concentrations in plasma and brain (Barbaccia et al., 1996; Korneyev and Costa, 1996; Lancel et al., 1996b; Paul and Purdy, 1992). Electrophysiological and biochemical experiments showed that allopregnanolone is a potent allosteric agonistic modulator of GABAA receptors. In agreement with these findings in the rat, a dose of 300 mg of micronized progesterone given orally to male subjects has been shown to reduce non-REMS latency, to promote stage 2 sleep, to slightly suppress slow-wave sleep and to decrease EEG activity in the lower frequencies and enhance activity in the frequencies .15 Hz during nonREMS (Friess et al., 1997). Two observations suggest that allopregnanolone is implicated in the influence of progesterone on sleep.
The present data show that systemic administration of allopregnanolone mixed with oil produced rapid, long-lasting (.5 hr), seemingly dose-dependent increases in the levels of allopregnanolone in both plasma and brain. The present study shows for the first time that exogenous allopregnanolone significantly influences sleep. Both doses (7.5MG/KG AND 15MG/KG) tended to reduce non-REMS latency (table 1), which indicates a rapid hypnotic action. The higher dose significantly promoted pre-REMS, which occurred mainly during the first 2 postinjection hr. The influence of allopregnanolone both on the amount of time spent in the different vigilance states and on EEG activity during non-REMS and REMS is reminiscent of the effects induced by benzodiazepines, which suggests that the influence of allopregnanolone on sleep is mediated by GABAA receptors. Nevertheless,the comparison of the sleep changes induced by allopregnanolone with those observed earlier after the administration of various doses of progesterone (Lancel et al., 1996b) shows that the overall effects of 15 mg/kg allopregnanolone are similar to those evoked by 90 mg/kg progesterone. As with the higher dose of allopregnanolone, 90 mg/kg progesterone shortened sleep latency, significantly increased the time spent in pre-REMS and was too low to suppress REMS or affect the number and average duration of the sleep episodes. The hypnotic effects of progesterone are to a large extent mediated by the positive allosteric interaction of its metabolite allopregnanolone with GABAA receptors. From the pharmacological point of view, steroids related to allopregnanolone, known as epalons, are likely to affect sleep in a benzodiazepine-like fashion.
epalons: Class of neuroactive steroids. Name derived from epiallopregnanolone, an endogenous metabolite of progesterone that has activity on the GABA-A receptor complex. Have anxiolytic, anti-convulsant and sedative-hypnotic properties.
Crit Rev Neurobiol. 1995;9(2-3):207-27. A putative receptor for neurosteroids on the GABAA receptor complex: the pharmacological properties and therapeutic potential of epalons. Gee KW, McCauley LD, Lan NC.
Crit Rev Neurobiol. 1995;9(2-3):207-27. A putative receptor for neurosteroids on the GABAA receptor complex: the pharmacological properties and therapeutic potential of epalons. Gee KW, McCauley LD, Lan NC.
Source Department of Pharmacology, College of Medicine, University of California, Irvine 92717, USA.
Abstract: A critical mass of evidence now supports the existence of a novel class of neuroactive steroids. These steroids are devoid of any known steroid hormone activity and have high specificity for the gamma-aminobutyric acidA receptor complex (GRC), which is a ligand-gated chloride channel that mediates the inhibitory action of the neurotransmitter gamma-aminobutyric acid (GABA).
These neuroactive steroids have anxiolytic, anticonvulsant, and sedative-hypnotic properties. Based upon some of the unique characteristics of the epalons relative to barbiturates and the BZs, it is plausible that the epalons can be developed into a novel class of therapeutic agents for the treatment of anxiety, epilepsy, and insomnia.
These neuroactive steroids have anxiolytic, anticonvulsant, and sedative-hypnotic properties. Based upon some of the unique characteristics of the epalons relative to barbiturates and the BZs, it is plausible that the epalons can be developed into a novel class of therapeutic agents for the treatment of anxiety, epilepsy, and insomnia.
Editors note: Pregnenolone and Progesterone should not be taken by anyone in their 20's unless blood and saliva tests show levels are below range, because this will prevent the body's own production of these hormones from cholesterol. All hormones applied by a creme, IV or injection will dodge the infamous first pass through the liver, greatly reducing bio-availability. Make sure you always implement a liver detox (standardized milk thistle, dandelion, phosphatidyl choline) into your daily regimen if you plan on taking oral steriods, and have your liver functioning tested annually.
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