nootropics

PRL-8-53: The Social Nootropic

prgal

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.

Branconnier, Roland J. “The human behavioral pharmacology of the common core heptapeptides.” Pharmacology & therapeutics 14.2 (1981): 161-175.

 

Brewster, Marcus E., et al. “Brain-enhanced delivery of anti-dementia drugs.”Novel Approaches to the Treatment of Alzheimer’s Disease. Springer US, 1989. 173-183.

 

Esler, William K. “Physiological studies of the brain: implications for science teaching.” Journal of Research in Science Teaching 19.9 (1982): 795-803.

 

Hansl, Nikolaus R., and Beverley T. Mead. “PRL-8-53: Enhanced learning and subsequent retention in humans as a result of low oral doses of new psychotropic agent.” Psychopharmacology 56.3 (1978): 249-253.

 

Hull, Ronald W. “Metaperspectives for the Future: Technology.” (1980).

 

1 Kessler RC, Chiu WT, Demler O, Walters EE. Prevalence, severity, and comorbidity of twelve-month DSM-IV disorders in the National Comorbidity Survey Replication (NCS-R). Archives of General Psychiatry, 2005 Jun;62(6):617-27.

 

Valenta, Vladimír, et al. “Potential nootropic agents: Synthesis of a series of (2-oxo-1-pyrrolidinyl) acetic acid piperazides.” Collection of Czechoslovak Chemical Communications 55.6 (1990): 1613-1629.

 

Various. “PRL-8-53 Experiences • /r/Nootropics.” Reddit. N.p., Nov.-Dec. 2013. Web. 16 Sept. 2014.

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Aniracetam as Nootropic, Anti-Dementia Drug and Anxiolytic

 

ani

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

 

Bartolini, L., F. Casamenti, and G. Pepeu. “Aniracetam restores object recognition impaired by age, scopolamine, and nucleus basalis lesions.” Pharmacology Biochemistry and Behavior 53.2 (1996): 277-283.
Greenblatt, David J., and Richard I. Shader. “Dependence, tolerance, and addiction to benzodiazepines: clinical and pharmacokinetic considerations.” Drug metabolism reviews 8.1 (1978): 13-28.
Martin, J. R., and W. E. Haefely. “Pharmacology of Aniracetam.” Drug Investigation 5.1 (1993): 4-49.
Roth, T., et al. “Benzodiazepines and memory.” British journal of clinical pharmacology 18.S1 (1984): 45S-49S.
 Senin, Umberto, et al. “Aniracetam (Ro 13-5057) in the treatment of senile dementia of Alzheimer type (SDAT): results of a placebo controlled multicentre clinical study.” European Neuropsychopharmacology 1.4 (1991): 511-517.
Smith, Amy M., and Jeanne M. Wehner. “Aniracetam improves contextual fear conditioning and increases hippocampal γ‐PKC activation in DBA/2J mice.” Hippocampus 12.1 (2002): 76-85.
Vincent, George, Anthony Verderese, and Elkan Gamzu. “The effects of aniracetam (Ro 13–5057) on the enhancement and protection of memory.” Annals of the New York Academy of Sciences 444.1 (1985): 489-491.