PRL-8-53: The Social Nootropic


PRL-8-53 (methyl 3-[2-[benzyl(methyl)amino]ethyl]benzoate) is a nootropic drug discovered by Dr. Nikolaus Hansl of Creighton University. Since he patented it in the 1970’s only one clinical trial with humans has been conducted. Based on the study one can conclude it improves recall and verbal memory. Personal accounts on websites like Reddit and Longecity are consistent with one another and corroborate the original findings. Derived from benzoic acid and benzylamine, it chemically and pharmacologically unrelated to the racetams. Although its precise mechanism of action has not been fully elucidated, it is known to act upon several neurotransmitters at once, mostly notably the cholinergic. As Hansl wrote, “retrieval of information that has been accumulated over a period of time, seems mediated by acetylcholine and the cholinergic system.”

PRL-8-53 stories have two fascinating and recurring themes: enhanced recall of events experienced under its influence and a subdued but measurable prosocial effect. In a clinical study on its effects on memory “initial word acquisition performance on PRL-8-53 was only 107.46% of baseline, subjects recalled words at 132.5-142.7% of the baseline rate 24 hours after testing, and at 145.2-146.2% after a week. Stronger effects were noted in the bottom 60% of subjects (who recalled 6 or fewer words on placebo at 24h), with 24 hour retention improved to 187.5-191% of baseline, and one week retention to 200-205%.” It is no doubt a potent potentiator for the creation and retention of memories. Doses range between 2 and 10 milligrams. 5 mg is the most common starting dose. PRL-8-53 is fairly nontoxic; it’s oral LD-50 is 860mg/kg in rats. A man weighing 90kgs (200lbs) would have to consume somewhere in the vicinity of 7740 mg to overdose (assuming the data from rodents does not perfectly translate to humans, and it is doubtful it does, the lesson to be taken is an unreasonable amount of the compound must be ingested before it is even slightly toxic). This is not an exhortation to take more than the recommended amount.

PRL is a cholinergic, a dopamine potentiator and serotonin inhibitor. Unlike MDMA, PRL is not an empathogen. It is not a stimulant either. Nor does it seem to be, like aniracetam, a general anxiolytic since some users list feelings of uneasiness after dosing (even though, somewhat paradoxically, in these same case studies participants have also noticed improved ease in communicating with others). Similar to some racetams, a slight dulling of emotional intensity has been reported. Subjects who have administered the drug to themselves notice “social barriers” evaporating. They do not feel talkative or compulsively gregarious or irrepressibly manic; they feel more at ease in interacting with other people. Severe social anxiety afflicts nearly 7% of American adults. How many more suffer from less crippling forms of the disorder is not known. At this time very little research has been done on pharmaceuticals that specifically target social anxiety (not tranquilizers or general anxiety medications). For this reason PRL and its as of yet undiscovered cousins should be of great interest to researchers looking for the next typhoon in the always engaging field of neuropsychopharmacology.

The richest and most exciting source of information about PRL is Reddit. One fellow “wrote a program based on an NP-Complete math problem that works, and successfully presented another piece of software to a couple of Venture Capitalists without the slightest bit of nervousness or hesitation.” Another “programmed a java assignment the entire day. 8 hours and then 5 hours into the morning.” He was less prone to indulging in distractions. Like many other psychotropics PRL is, anecdotally, a potentiator of vivid dreams. Whether or not it can foster lucid dreaming is not known.” It promotes concentration without stimulation. It is consistently described as a “clean” feeling, an energetic state free from euphoria or rage. One Redditor observed that the hyperfocus it promotes can be cumbersome to someone who wishes to let their mind wander. For someone who needs to complete a particular task within a particular amount of time this should not be an issue. He, one of the least effusive of the reviewers, writes, “this drug does NOT make you happier. It does NOT make you upset. It doesn’t really affect your everyday perception. All it seems to do is make memorization a bit easier, give you a little bit extra energy, and allow reading to be a lot easier because you retain the information that much faster.” It shines brightest in crowded room: “social benefits appear to be an increased recall of events, situations, and details. I’m still fishing around for the right words like I usually do, however. This in turn seems to subjectively boost sociability. I still had mild anxiety issues in certain situations. However, I was able to address a crowd of people on a moment’s notice and it felt completely natural.”

Before concluding it is worth mentioning PRL-8-53’s legendary cousin,  PRL-8-147, which is purported to grant godlike powers to whoever finds the golden chalice in which the only known sample resides dissolved in the finest mead of Middle Earth. Joking aside, Dr. Hansl left his research papers to his family. Right now little is verifiable about 147 and at this time there are no reputable suppliers. Do not despair, PRL-8-53 is quite promising.

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Life Extension and Antioxidants: An Overview


Mitochondria: so powerful and so fragile.

 The question of whether dietary antioxidants can substantially delay death or senescence is important to both researchers and health enthusiasts. While supplementation is known to increase the average lifespans of test animals and to decrease certain mortality risks  in humans, they do not increase the maximum age of test organisms. They do not make Methuselahs out of mice or men. Denham Harman, the father of the original Antioxidant Theory of Aging, despairingly came to this conclusion when his experiments with several potent free radical scavengers, including butylated hydroxytoluene, failed to produce his desired outcome.

Evidence gleaned from the laboratory forced Harman to reformulate his original hypothesis: oxidative damage suffered by mitochondria, the powerhouses of cells, is responsible for the slowing of maintenance processes crucial to maintaining cellular and bodily integrity. While other organelles and even macromolecules can suffer in the same way, there are a number of reasons to focus on these organelles in particular: mitochondrial DNA does not repair itself as efficiently as the DNA residing in the cell’s nucleus, it is also located near the electron transport chain, which produces a constant stream of free radicals, and, lastly but perhaps most significantly from a practical standpoint, caloric restriction increases mammalian life span. It is conjectured it does this by reducing the mitochondrial workload, which in turn reduces the number of free radicals produced. This, as one can easily imagine, reduces the damage incurred by ATP generation. The question now becomes whether there are compounds that protect mitochondria in particular. Before turning to these still theoretical therapies, it is best to become acquainted with the tried and true molecules.

Ascorbic acid, better known as vitamin C, is famed for its proclivity to neutralize roving free radicals.  The relationship between heart disease and low vitamin C levels is well established. Men with the lowest levels of vitamin C have a 2.4 fold risk of dying from a stroke compared to those with the highest levels.  Likewise, protection from cancer and dementia has been demonstrated. Vtamin E displays similar properties. One of the most interesting properties of both E and C is the reduction of LDL oxidation and risk of atherosclerosis. Normal amounts of these vitamins and beta carotene can delay the onset of Alzheimer’s, but there seems to be no benefit to exceeding recommended allotments. Participants in a Dutch study with the lowest vitamin E intake were 70% more likely to develop the disease compared to the highest. It good to note here that those who consume nutritious foods the most often are likely health conscious in other ways, although researchers try their best to remove unwanted x factors. Large amounts of these vital molecules can have a prooxidant effect. In lab animals absurd amounts of E and C cut life short by 26%. Although, extra C and E appear to prevent mitochondrial damage after intense physical activity. This data may not translate directly to humans, but one must keep Paracelsus’s immortal maxim in mind: the dose makes the poison. Most people receive their fair share of both from their diets. Bagchi found that grape seed proanthocyanidin extract (GPSE) was 60% more effective. Dihydroquercetin, one of the flavonoids present in grape seed, synergizes with vitamin C by donating electrons back to the oxidized molecules. Dihydroquercetin and its relatives are receiving more attention than ever in their natural and extracted forms.

 Flavonoids hold a prominent place in the popular mind. Catechins, a type of flavonoid in tea, decreases oxidized LDL. This compounded with its calming qualities, is the likely explanation for its heart benefits. By volume tea contains considerably more flavonoids than fruits of vegetables. Those with the highest levels of flavonoid intake were the least likely to develop lung cancer, moreover, these compounds can inhibit tumorigenesis in its initiation and promotion stages. Many of these studies are done with large quantities of phytochemicals than a person would likely consume from unextracted plant material, but some meaning can be extrapolated from them. It is unclear as to how well, if at all, various flavonoids cross the blood brain barrier, yet in animal studies they appear reduce inflammation and to prevent cognitive decline. Midlife tofu consumption increases one’s risk for Alzheimer’s. It is likely something in the whole food, not the soy isoflavones themselves, that caused this unexpected result. This is yet another reason to stay away from soy products. The stilbenoid resveratrol has also captured the public’s attention in recent years. Most likely because it is found in red wine and, to a lesser extent, chocolate. Fueled by this, marketing and the then lauded research coming from the lab of Dipak Das, resveratrol, seemed poised to take center stage. Fortunately for science 12 of Dipak Das’s studies were found to be fraudulent. There is no evidence to support taking supplemental resveratrol for any reason. There is considerably more evidence for red wine itself, and although there is the possibility of overindulgence for those with alcoholic tendencies, an occasional glass of Mourvedre will likely do more good than harm.

Melatonin, a hormone critical to regulating circadian rhythms, is a powerful antioxidant which contributes to sleep quality, bone health, heart health and readily crosses the blood brain barrier. Melatonin improves symptoms in Alzheimers patients, possibly by protecting neurons from beta-amyloids. The importance of quality sleep is not disputed and surely some of the benefits melatonin provides come as an indirect consequence of its somnambulant powers. It is not a miracle drug; melatonin inhibits the secretion of testosterone and prolonged use could in theory shut down endogenous production. Further trials are required before the proper amount to take nightly is determined, likely this will be largely dependent on each person’s needs. In this case personalized medicine and cellular monitoring devices will be a boon. Glutathione (GSH) has been given a number of titles to denote its princely status among common antioxidants. Like melatonin it is made by the body and although it is used intravenously by medical professionals to treat infertility and side effects from chemotherapy, its efficacy when taken orally was and still is doubted. This erroneous and unfounded assumption has been debunked in studies with humans and rats.  While GSH deficiencies are linked with a number of diseases and increased mitochondrial damage, it is hard to say when or who requires supplementation without a blood test. It is also not known yet whether above average levels of plasma GSH delay senescence or not. Although the fact that additional GSH is linked with decreased mitochondrial wear and tear. It has even been proposed as a therapy for diabetics for this reason. Will there be a way to effectively eliminate mitochondrial deterioration without compromising the integrity of the whole organism?

The idea of targeting mitochondria is not entirely new. MitoQ, a modified ubquinone, has been through clinical trials. It was given to patients with advanced Parkinsons and to people with hepatitis C. Why this was done and who thought MitoQ would be of any use  to these sample groups is not clear. Predictably, the placebo and control groups in the Parkinsons study showed no difference. It showed some promise as a therapeutic for those with liver disease, but much more work needs to be done before MitoQ is hailed as the savior of humankind. Lipophilic cations and SS-peptides assist in shuttling the compound to the mitochondria. Members of the latter group may be useful in the treatment of heart disease, but it is still to early to say. Anything remotely related to anti-aging research, even if it has real and immediate medical applications, is shunned by the establishment which to this day considers biological aging, something that is neither universal nor inevitable, an irreversible consequence of the laws of thermodynamics. It is agonizing to endure such stupid arguments rooted more in folk wisdom than in hard science. It is even harder to endure more so when the sources for these proclamations do not come from the fringes but from the lofty peaks of the ivory tower itself. Within the next decade, however, these drugs are likely to experience an explosion in research and in use. A nearly universal solution to human disease with no drawbacks is simply too good to pass up. Such a compound will not cure death, but it will buy us all a little more quality time.




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Aniracetam as Nootropic, Anti-Dementia Drug and Anxiolytic



Aniracetam is a fat soluble cousin of piracetam. It is non-toxic and non-addictive. It is a quantitatively and qualitatively more powerful nootropic than piracetam. Lab mice given standard doses of either drug perform better than control groups, but aniracetam-fed mice, including the dimwitted D2 variety, perform better on a wider range of cognitive tests, suggesting aniracetam  has greater therapeutic potential than piracetam. In a study conducted on 100 elderly patients showing signs of  Alzheimers or dementia ” the aniracetam group differed significantly from the placebo group by the end of the study and also showed a statistically significant improvement versus baseline in the psychobehavioural parameters, while in the placebo group a steady deterioration was observed. Tolerability to aniracetam was excellent.”

From the (translated) manufacturer’s label:

“This is an original pharmaceutical product by Roche, which acts on the central nervous system (CNS), stimulating the learning process and the memory. Pharmacological studies have shown that Aniracetam stimulates the functions of certain neuronal receptors by means of glutamic acid, bringing about memorization processes (AMPA receptors) and protection of nerve cells (metabotrophic receptors). Clinical studies have shown specific therapeutic activity in elderly patients affected by alterations of the cognitive functions. Both long and short term memory improvement have seen in addition to learning, attention span, alertness, concentration, reasoning and absent mindedness.”

As or more interesting are aniracetam’s anxiolytic properties and its potential as a pro-social drug. Drug makers have been searching for the holy grail of anxiety suppressants for some time. Benzodiazpenes, which come with a slue of nasty side effects including memory impairment and dependence, seem unattractive compared to this orphaned pharmaceutical. For although research continues to be done, the medical community still seems largely uninterested and unaware. Outside of the arcane realm of psychoneuropharmacology, aniracetam has attracted the attention of a growing group of people fascinating by the possibilities intelligence amplification holds for homo sapiens.

“In a social interaction test in which all classes (serotonergic, cholinergic and dopaminergic) of compounds were effective, aniracetam (10-100 mg/kg) increased total social interaction scores (time and frequency), and the increase in the total social interaction time mainly reflected an increase in trunk sniffing and following…Aniracetam also showed anti-anxiety effects in two other anxiety models (elevated plus-maze and conditioned fear stress tests), whereas diazepam as a positive control was anxiolytic only in the elevated plus-maze and social interaction tests.”

There has yet to be a clinical trial to test its usefulness as an anxiety medication for humans, however there is a substantial body of anecdotal evidence already and it seems likely in this instance its effects on mice can are the same for other mammals. A user on Longecity reports:

“Aniracetam, especially in high doses, produces the strongest effects I’ve experienced from nootropics as of yet. A single two-four gram dose (common for me) of aniracetam starts to affect my mind in about 45-60min after oral ingestion. It then peaks after about 90min, and goes down some 2-4hours after ingestion. My mind gradually seems to accept all my stressful and anxious thoughts of the day, and I feel truly at peace with my environment, internal and external. Often this involves me sitting down, barely moving because of my extreme satisfaction, and watching my mind and body heal.”

This is not an uncommon experience. It is unfortunate pharmaceutical grade aniracetam is not widely available; it more unfortunate that the companies currently supplying it are not regulated by the FDA (although some are kind enough to offer independent laboratory analyses of their products). Its time will come.

New Effective Nootropics

For a Brighter Future


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