5 replies to this topic

[sam7777]

Ultimately, Piracetam is said to be the holy grail of nootropics. It also is said to work far differently than amphetamines, and consequently is therefore safer. Well, that is if it even works.

Some people say piracetam works really well but loses effect and never returns, some say it takes 2 or 3 weeks of continuous headaches before it magically kicks in (could you bare that two or three weeks???). Well, I saw a guy post on here one time about piracetam and fish pills. His name was isochroma. He claimed that taking dozens of grams- up to 50 grams of fish pills, allowed him to use massive attack doses of piracetam at levels far beyond anything anyone else had acheived. Well, most would find this pretty hard to take seriously, but I have some prior experience with taking astronomical doses of fish pills. I can vouch that there is some seriously profound medical anomalies occurring with the giant does of fish pills.

My experience with fish pills is that in order to control my severe IBS/fibromyalgia like symptoms I must take roughly on average 10 grams daily. When I was not taking this, my life was a living hell. I began doing this last fall because of the ever increasing body wide pain I was experiencing. No doctor told me to do this. I found out by accident that these large doses prevented inflammation.

It was later that I also realized that the more I took, the more I could abuse caffeine. Well, I found myself in a bind with an important engineering research project, which 5 people's grade depended on my work. As usual, I could not ever think. My experience is to be in a state of anxiety and disorientation with a compulsive urge to procrastinate till the very last minute. To do this paper, which was nearly 12,000 words. I ended up taking 50 GRAMS of fish pills and about 1000 mg caffeine. I wrote for about 18 hours straight. I have done this sense several times with other papers. I can relate the mental feeling as those described by the people who have very very good responses with piracetam, though piracetam does not work for me.

You see, this caffeine, essentially destroys your body. It is utter hell. The fish pills protect it- in the most simple terms.

I have heard people say that non responders to piracetam are "missing some kind of an important nutrient in the body" or "some sort of underlying physical state needed". I believe, that like any other heavy nootropic stimulant, the neuroendocrine system and CNS must be in a healthy state to optimally benefit from Piracetam. People who describe their selves as having "bad nerves" most likely could have issues with piracetam. I believe that if the body is at it's optimum, than piracetam is going to work for most.

I have been doing intense research for about 8 weeks. It has led me to believe there is little or no such thing as "ADD", not literally. ADD is real, it exists, it is unbearable, but it is not a disease in of itself. It is a side effect of more serious illnesses, of which CAN but not necessarily involve genetic polymorphisms, family histories of substance abuse/alcoholism/bi-polar/depression, emotional trauma, brain damage caused by the ridiculously toxic American diet loaded with artificial sweeteners/MSG/solvents/pesticides/arsenic in the chicken meat/etc..., food allergies such as dairy and gluten are notorious for causing ADD, chronic syndromes such as irritable bowel syndrome, chronic fatigue disorder, Fibromayalgia, psychological stress and constant panic/fear/fight&flight - burnout




Is your brain like Jello? Maybe it is because:

Your body has hyperalgesia - Your Endogeneous Analgesic System, the CNS mediated system containing your opioid receptors for your endorphins is greatly underfunctioning- Symptoms: Excessive pain, fatigue, dysphoria, lack of motivation- pretty much the opposite of the effects of PEA or exercise (runner's high) Sound familiar?

Your Adrenal Medulla, the part of the adrenals responsible for catacholamines has severely atrophied, which affects cognitive and affective function considerably.

Other stereotypical and often mentioned concerns- Hypothyroidism, Depression, Insomnia

I could go on, but the point is pretty clear to me. Not all ADD and cognitive related dysfunction is related to neurological disorders and endocrinological disorders, but a massive amount are. Your diet could be causing you chronic low grade inflammation, and I suspect this down regulates the bodies ability to use endorphins. I have seen in my family, members who suffered injuries (fell off three story scaffold), and as the pain progressed over a decade, their personality completely changed because of the never ending physical pain.

Well, what does omega 3 do?! It is a massive bomb of cholesterol and EPA/DHA with astronomically powerful anti-inflammatory properties. It is to your neuroendocrinological system as what the 1 up power bonus mushroom that players leap their Mario onto when playing the SNES (sorry to get old school lol). It is no wonder that this guy was able to essentially abuse a combination of fish pills and piracetam.

I would go farther to extend that you could use fish pills to greatly abuse any stimulant. I could deffinately see adderall crash's being greatly attenuated by the use of a neuroprotectant such as magnolia bark or ashwagandha (which might possibly even prevent adderall from working) and large doses of fish pills.


BUT BUT- I wont to make it clear, fish pills are not a solution to chronic health problems, nootropics are not either, and combining the two - well?! You see where this is going.

A healthy CNS would probably prevent the need for things like adderall and deprenyl in the first place. I have to wonder what has devastated my own CNS and others. Fish pills block PGE2 prostaglandin receptors during inflammatory reactions. There are many other inflammatory cytokines and pathways in the body, as well as path ways. I would like to see nootropics that could regenerate the CNS, not bandaid it. More importantly, it would be nice to see more discussion on ways to help increase the body's endorphin function in a safe way with nootropics-because I believe this process is part of the "creative/inspired" aspect of nootropics (Consider reading in depth how substances such as Phenylethylamine and opiates work: - they actually stimulate dopamine AND serotonin function WHILE increasing endorphins). Think about it- How is dysphoria a helpful state to be in when trying to do intellectually challenging work? Personally, I believe that adderall doesn't even work for the advertised reason. I believe it works more because of the associated changes in endorphin, seroton, and epinephrine function, not dopamine function.

If you think you may be relying on or seeking the use of nootropics because of what you suspect to be inflammation after reading this post, like me, you should probably ask yourself this? How do I completely get rid of this inflammation and CNS stress or damage first?

Doing otherwise seems like trying to sweep dirt under the rug.

[sam7777]

I should be able to bold the important parts later - will wait to see how people respond to this topic.

some internet notes from alternative treatment forums

Stress precipitates depression and alters its natural history. Major depression and the stress response share similar phenomena, mediators and circuitries. Thus, many of the features of major depression potentially reflect dysregulations of the stress response. The stress response itself consists of alterations in levels of anxiety, a loss of cognitive and affective flexibility, activation of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system, and inhibition of vegetative processes that are likely to impede survival during a life-threatening situation (eg sleep, sexual activity, and endocrine programs for growth and reproduction). Because depression is a heterogeneous illness, we studied two diagnostic subtypes, melancholic and atypical depression. In melancholia, the stress response seems hyperactive, and patients are anxious, dread the future, lose responsiveness to the environment, have insomnia, lose their appetite, and a diurnal variation with depression at its worst in the morning. They also have an activated CRH system and may have diminished activities of the growth hormone and reproductive axes. Patients with atypical depression present with a syndrome that seems the antithesis of melancholia. They are lethargic, fatigued, hyperphagic, hypersomnic, reactive to the environment, and show diurnal variation of depression that is at its best in the morning. In contrast to melancholia, we have advanced several lines of evidence of a down-regulated hypothalamic-pituitary adrenal axis and CRH deficiency in atypical depression, and our data show us that these are of central origin. Given the diversity of effects exerted by CRH and cortisol, the differences in melancholic and atypical depression suggest that studies of depression should examine each subtype separately.
The Duality of the Endocrine System;
The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus-norepinephrine (LC/NE)-autonomic systems and their peripheral effectors, the pituitary-adrenal axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. The CRH and LC/NE systems stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the hypothalamic beta-endorphin system, which suppresses pain sensation and, hence, increases analgesia. CRH inhibits appetite and activates thermogenesis via the catecholaminergic system. Also, reciprocal interactions exist between the amygdala and the hippocampus and the stress system, which stimulates these elements and is regulated by them. CRH plays an important role in inhibiting GnRH secretion during stress, while, via somatostatin, it also inhibits GH, TRH and TSH secretion, suppressing, thus, the reproductive, growth and thyroid functions. Interestingly, all three of these functions receive and depend on positive catecholaminergic input. The end-hormones of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoids, on the other hand, have multiple roles. They simultaneously inhibit the CRH, LC/NE and beta-endorphin systems and stimulate the mesocorticolimbic dopaminergic system and the CRH peptidergic central nucleus of the amygdala. In addition, they directly inhibit pituitary gonadotropin, GH and TSH secretion, render the target tissues of sex steroids and growth factors resistant to these substances and suppress the 5' deiodinase, which converts the relatively inactive tetraiodothyronine (T(4)) to triiodothyronine (T(3)), contributing further to the suppression of reproductive, growth and thyroid functions. They also have direct as well as insulin-mediated effects on adipose tissue, ultimately promoting visceral adiposity, insulin resistance, dyslipidemia and hypertension (metabolic syndrome X) and direct effects on the bone, causing "low turnover" osteoporosis. Central CRH, via glucocorticoids and catecholamines, inhibits the inflammatory reaction, while directly secreted by peripheral nerves CRH stimulates local inflammation (immune CRH). CRH antagonists may be useful in human pathologic states, such as melancholic depression and chronic anxiety, associated with chronic hyperactivity of the stress system, along with predictable behavioral, neuroendocrine, metabolic and immune changes, based on the interrelations outlined above. Conversely, potentiators of CRH secretion/action may be useful to treat atypical depression, postpartum depression and the fibromyalgia/chronic fatigue syndromes, all characterized by low HPA axis and LC/NE activity, fatigue, depressive symptomatology, hyperalgesia and increased immune/inflammatory responses to stimuli.

Neurology and opioid receptor function in regard to the mid-brain, cerebral cortex and subcortical areas, the spinal cord, and peripheral areas;
The nociceptive stimulation originating from peripheral areas throughout the body ultimately travels via C and A delta fibers along the spinal cord to the hypothalamus. The hypothalamus delivers the pain messages to the periaquaductal gray where enkephalin is released into the nucleus magnus raphe, and ultimately the raphe nuclei. The raphe nuclei secrete serotonin, which induces excitation of the inhibitory interneurons of the dorsal horns within the substantia gelatinosa of the spinal cord. Here the neurons will release either dynorphin or enkephalin to intercept nociceptive pain from the primary spinal C and A delta fibers, preventing secondary messaging. The endogenous analgesic opioid neurotransmitters will activate mu opioid receptors that block substance p from being released throughout the body, thus preventing inflammation.

Summarization of etiology of IBS

RCevuierwrent insights in to the pathophysiology of
Irritable Bowel Syndrome
Theodoros Karantanos†1, Theofano Markoutsaki†2, Maria Gazouli*1, Nicholas P Anagnou1 and
Dimitrios G Karamanolis2

Karantanos et al. Gut Pathogens 2010, 2:3
http://www.gutpathog...m/content/2/1/3

Neurology and opioid receptor function in regard to the mid-brain, cerebral cortex and subcortical areas, the spinal cord, and peripheral areas;
The nociceptive stimulation originating from peripheral areas throughout the body ultimately travels via C and A delta fibers along the spinal cord to the hypothalamus. The hypothalamus delivers the pain messages to the periaquaductal gray where enkephalin is released into the nucleus magnus raphe, and ultimately the raphe nuclei. The raphe nuclei secrete serotonin, which induces excitation of the inhibitory interneurons of the dorsal horns within the substantia gelatinosa of the spinal cord. Here the neurons will release either dynorphin or enkephalin to intercept nociceptive pain from the primary spinal C and A delta fibers, preventing secondary messaging. The endogenous analgesic opioid neurotransmitters will activate mu opioid receptors that block substance p from being released throughout the body, thus preventing inflammation.


Etiologic Factors of IBS
The etiology of IBS is most likely multifactorial. Several environmental factors, psychosocial stressors, gut flora alterations contribute to the pathophysiology of IBS,along with abnormal gastrointestinal motility and secretion and altered visceral perception. On the other hand, for the integration of visceral reflexes, the afferent stimuli throughout the hypothalamus stimulate efferent neural fibers which through PNS stimulate or inhibit the contraction of smooth muscle fibers and the secretion of enterocytes in the gastrointestinal tract modifying the gut motility and secretion. The parasympathetic autonomic nervous system is relaying the inflammatory induced release of chemical mediators to the thalamus and than back again to neural fibers in the enteric lining, which results in the IBS attack.
Failure of intestinal clearance may come as a result of impaired intestinal persistalsis, in case of myopathic, neuropathic, autoimmune, infectious, metabolic, endocrine or neoplastic diseases. PI IBS has been reported after Campylobacter, Salmonella and Shigella infections [50]. Those patients, who later on develop IBS, show increased numbers of enterochromaffin (EC) cells and lymphocyte cell counts at 3 months compared to those who do not develop IBS. Recent studies suggest an increase in peripheral blood mononuclear cell cytokine production in unselected patients, an abnormality that may be ameliorated by probiotic treatment. Preexisting damage can lead to over expressed immunological responses. It seems that older subjects have fewer immunocytes in their rectal mucosa and may be less reactive to infection. Depression and the presence of adverse life events double the relative risk of persistent symptoms [51]. Immune responses and perceived pain over stimulate mucosa neurons.
Lactose intolerance, as well as intolerance to sorbitol or fructose, has been implicated in IBS. It is likely that the specific enzyme deficiency is not the cause of IBS, but that the hypersensitive guts of patients with IBS show exaggerated responses to the gaseous and fluid distention caused by incomplete absorption of carbohydrate.

Visceral sensitivity at the level of enteric mucosa and submucosa;
A four step process ensues; inflammation and afferent terminal neuron stimulation, efferent neural fibers and chemical mediator release, PANS to thalamus, neuron stimulation and distention plus cramping. The presence of an injury in enteric mucosa leads to the release of chemical mediators like K+, ATP and bradykinin but also inflammatory mediators like prostaglandin E2 (PGE2) [6]. These substances can directly stimulate the afferent neuron terminals but also can induce the release of algogenic substances (histamine, serotonin (5HT), nerve growth factor (NGF) and prostaglandins).The release of substance P from the neuron terminals induces the production and release of histamine and NGF from mast cells. Recent data attribute the enhancement of neural sensitivity for algogenic stimuli to increased expression of sodium channels on primary afferent endings. Recent studies on pseudoaffective (cardiovascular) reflex responses to gut distension have suggested an action through a 5HT3 receptor subtype coupled to a sodium channel present on primary afferent endings. At the level of mucosa and submucosa, a variety of mediators like adenosine, tachykinin, calcitonin generelated peptide (CGRP) and neurokinins participate in a cascade of events. Mast cells and small nerve fibers are proliferated in regeneration after bacteriologic, physical, or environmentally induced damage. Both BK and 5HT3 subtype receptor antagonists attenuate symptoms of an IBS attack.

Visceral sensitivity at the level of spinal cord;
Synaptic transmission between afferent neurons and dorsal horn neurons must be increased, so they release neurotransmitters through a process called central sensitization. While omega 3 acid can act as an antagonist of the PGE2 receptors, and BK and 5HT3 receptors can have antagonists administered, this focuses on direct afferent neuron stimulatory release. These blockades do not focus on mast cell release of histamine and NGF mediated by SP receptor stimulation. Recent studies support the idea that NMDA receptors are implicated both at the level of spinal cord and peripherally- related to the sensitization of primary afferents. SP receptors lead to phosphorlaytion of NMDA receptors and ultimately to increased electronegative voltage, thus reversing the effects of antagonists such as magnesium. Thus, since SP receptor stimulation releases NGF and histamine, while simultaneously up-regulating NMDA receptors and increasing neurotransmitter release, it is closely associated with the central sensitization which triggers the PANS and thalamus. Interestingly, peripherally released CGRP may modify sensory inputs, causing changes in blood flow, smooth muscle contractions, immune reaction and mast cell degranulation, but causes hyperalgesia when released from central endings of primary afferents. The intravenous administration of the CGRP1 antagonist (h)-CGRP-(8-37) suppresses the abdominal cramps caused by intraperitoneal administration of acetic acid in awake rats [14].
Furthermore, dopaminergic system kappa-opioid receptors are indicated. It seems also that κ agonists may act peripherally to prevent visceral pain and are more active in inflammatory conditions. It must be quoted that opioid receptors have been identified on both smooth muscle fibers and primary afferents localized in the gut [15]. Lastly, somatostatin and its receptors (SST1 and SST2) have also been identified on spinal cord and are probably related to the regulation of visceral pain, like GABAA and a2 adrenergic receptors.

Visceral sensitivity at the level of cerebral cortex and subcortical areas & Abnormal Gut Motility and Secretory Disorders;
It is believed that serotoninergic pathways, inhibit neural impulses at the level of dorsal horn neurons. This would inhibit the afferent neuron synaptic transmission to the dorsal horn neurons via GABA, conversely to the acetylcholine stimulation of the NDMA receptors which create central sensitization. It seems also that the interactions between serotoninergic pathways and limbic system are very important for the sensation of visceral pain. Evidence clearly suggests disruption in the serotonergic pathways could create pain induced psychological problems, and that psychological problems could create visceral pain. Within the submucosa lies the interconnection of cholinergic afferent neurons. Ascending interneurons activate excitatory motor neurons by releasing substance P and acetylcholine (Ach) onto myocytes resulting in circular muscle contraction. Descending cholinergic neurons stimulate inhibitory motor neurons releasing nitric oxide (NO), vasoactive intestinal peptide (VIP) and adenosine triphosphate (ATP) leading to circular muscle relaxation. Other studies evaluated the role of 5HT receptors in the peristaltic reflex and demonstrated the intricate involvement of CGRP. Environmental stress factors stimulate cortitropic release factor hormone which in turn stimulates histamine release from mast cells, leading to efferent neuron terminal stimulation, hypothalamus stimulation, and thus act along with CRF to create IBS attacks. The regulation of intestinal secretions is comparable to the regulation of gut motility, and directly stimulates 5HT4 peripherally and indirectly stimulates 5HT3 throughout the ENS, PANS, CNS, and SNS.

Autonomic Nervous System Dysfunction;
IBS is associated with dysfunction of the ANS, but predominately characterized by increased function in SANS and decreased function in PANS. IBS is fundamentally a immunological and inflammatory reaction within the submucosa and mucosa, mediated by the ENS, PANS, CNS, and SANS, but is a de facto neurological disorder. It is believed that vagal dysfunction is associated with constipation as a predominant symptom whereas adrenergic sympathetic dysfunction is associated with diarrhea as a predominant symptom [35]. Other studies reported that IBS diarrhea-predominant patients were shown to have cortisol hyper-responsiveness unlike that of constipation-predominant IBS patients and controls [36]. Furthermore, large differences in male and female responses to administered pharmacological agents are documented, with high sympathovagal balance in males.

Edited by sam7777, 01 August 2011 - 11:04 PM.

[Isochroma]

Piracetam and other racetams don't work at all - at any dose - in lab animals whose adrenals were removed. Caffeine and stimulants destroy the adrenals due to overstimulation and eventual exhaustion. Most of the populace are daily caffeine users - with a significant percent consuming so much that if it were demonized like some others substances are they would be classed as abusers.

Blockade of the nootropic action of piracetam-like nootropics by adrenalectomy: an effect of dosage

Cesare Mondadori, a, Thomas Ducreta and Friedel Petschkea

Pharmaceutical Research Department, CIBA-GEIGY Limited, Basle (Switzerland)

Received 6 June 1988; revised 14 December 1988; accepted 3 January 1989. Available online 17 November 2006.

The present experiments demonstrate that the absence of any memory-improving action of nootropics in adrenalectomized animals cannot be ascribed to an effect of dosage. Doses of 1, 10, 100, 1000 and 3000 mg/kg p.o. of piracetam, oxiracetam, aniracetam or pramiracetam are ineffective in adrenalectomized mice.

Involvement of a steroidal component in the mechanism of action of piracetam-like nootropics

Since adrenalectomy abolishes the memory-enhancing effects of piracetam and its derivatives, oxiracetam, aniracetam and pramiracetam, the question arises whether endogenous steroids play a role in their mechanism of action. We show that inhibition of steroid biosynthesis by aminoglutethimide and blockade of the aldosterone receptors by epoxymexrenone completely suppress the memory-improving effects of the nootropics. These results indicate that steroids, or, more precisely, activities mediated by the aldosterone receptors, might be involved in the mechanism of action of this class of nootropics. Blockade of aldosterone receptors, however, does not block the effects of cholinomimetics on memory, indicating the involvement of another mechanism of action.

Edited by Isochroma, 02 August 2011 - 04:01 AM.

[kassem23]

Piracetam and other racetams don't work at all - at any dose - in lab animals whose adrenals were removed. Caffeine and stimulants destroy the adrenals due to overstimulation and eventual exhaustion. Most of the populace are daily caffeine users - with a significant percent consuming so much that if it were demonized like some others substances are they would be classed as abusers.

Blockade of the nootropic action of piracetam-like nootropics by adrenalectomy: an effect of dosage

Cesare Mondadori, a, Thomas Ducreta and Friedel Petschkea

Pharmaceutical Research Department, CIBA-GEIGY Limited, Basle (Switzerland)

Received 6 June 1988; revised 14 December 1988; accepted 3 January 1989. Available online 17 November 2006.

The present experiments demonstrate that the absence of any memory-improving action of nootropics in adrenalectomized animals cannot be ascribed to an effect of dosage. Doses of 1, 10, 100, 1000 and 3000 mg/kg p.o. of piracetam, oxiracetam, aniracetam or pramiracetam are ineffective in adrenalectomized mice.

Involvement of a steroidal component in the mechanism of action of piracetam-like nootropics

Since adrenalectomy abolishes the memory-enhancing effects of piracetam and its derivatives, oxiracetam, aniracetam and pramiracetam, the question arises whether endogenous steroids play a role in their mechanism of action. We show that inhibition of steroid biosynthesis by aminoglutethimide and blockade of the aldosterone receptors by epoxymexrenone completely suppress the memory-improving effects of the nootropics. These results indicate that steroids, or, more precisely, activities mediated by the aldosterone receptors, might be involved in the mechanism of action of this class of nootropics. Blockade of aldosterone receptors, however, does not block the effects of cholinomimetics on memory, indicating the involvement of another mechanism of action.

Very interesting, but I'm not convinced we can extrapolate from 1988 studies, and no studies in human. That said, I was very intrigued by your post about Piractam Hydrazine. Care to tell me if you've tried it yourself, or in the process of procuring it? What would dosages be, and what would the potential differences in subjective effects be, as well?

Thanks.

[Isochroma]

Too expensive for my current budget. If you can find a supplier at a decent price I'd like to give the stuff a try. It's the hydrazide btw - hydrazine is explosive rocket fuel.

[kassem23]

Too expensive for my current budget. If you can find a supplier at a decent price I'd like to give the stuff a try. It's the hydrazide btw - hydrazine is explosive rocket fuel.

Haha, yeah, oops, sorry about that. Yeah, it's pretty expensive. Would be interesting though