pharmacology

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.

An Introduction to Piracetam

pira Last night I messaged a special acquaintance. During our conversation I couldn’t help but mention my latest pharmacological fascination. My curiosity has been fueled partially by members of the Transhumanist community on Facebook. Many of them, not surprisingly, are enthusiastic about the prospect of passive intelligence amplification. While I am fond of her usually pleasant demeanor, unusually long legs and ample backside, I was not happy to hear her casting aspersions upon my latest research interest. While the safety of the piracetam is not disputed, whether it, its relatives or any alleged nootropic available to the public substantially improves cognition in healthy people is still a matter of contention. Like countless fitness supplements much of the online information about piracetam is filtered through the interpretations of nonprofessionals. However, the average person researching piracetam is likely more intelligent than the fellow discussing the perfect steroid cycle with his gym bros.

Piracetam has several recorded effects on the brain. First, it increases the usage of acetylcholine by the hippocampus. Practically speaking, this means it should be taken with a choline supplement like Alpha GPC, otherwise it can deplete the body’s reserves of this precious neurotransmitter, leading to headaches and other unpleasant side effects in those with already low levels. In a double blind study Kessler showed piracetam assisted with the recovery of verbal fluency in aphasic stroke patients. The results of his experiment? “The placebo group showed an increase of activation effect only in the left vocalization area. In the test battery, the piracetam group improved in 6 language functions, the placebo group only in 3 subtests.”  Racetam drugs appear to stimulate neurogenesis, which could account for the cumulative improvements in cognition observed inside and outside of the lab, however, more research needs to be done before definitive conclusions can be drawn. The evidence for its use in treating dementia and other mental impairments is mixed and it has yet to been seen whether it can delay the onset of mental decline due to aging. Some users, particularly those who take large quantities combined with choline, report immediate effects, but it is not uncommon for the benefits, if any, to go unnoticed for the first few days. Mental clarity is primarily what Aunt Pira provides; this is best noticed when performing a measurable task, like puzzles on a chess tactics trainer or games on Lumosity.

“On the first dose, you won’t notice anything. In all likelihood, you wont notice anything until about a week of taking it consistently. It’s nothing like a stimulant whatsoever. Taking piracetam I notice I have better recall, faster reaction time, words flow more easily in my sentence composition, I’m able to visualize things more clearly, music sounds more intricate and colors seem a little more vivid.”

Significant improvement in functional disability was also found with daily doses of 9.6 g and 16.8 g [very large doses]. The dose-effect relation was linear and significant. More [epileptic] patients showed clinically relevant improvement with the highest dosage and, in individual patients, increasing the dose improved response. Piracetam was well tolerated and adverse effects were few, mild, and transient.”

This user’s account is similar to many others. In a few sentences he encapsulates a great number of reports on Erowid and elsewhere. Racetams drugs do not intoxicate. Although one may feel more energetic under their influence, they are not stimulants like caffeine or methamphetamine. Although they may be calming, they are not depressants. Users also report an enhanced appreciation for music, food, and other items.  Pattern recognition is improved possibly as a  result of improved interhemispheric communication. While it is nontoxic and innocuous for most people, including those with a sundry of preexisting health conditions (nevertheless, please check with your doctor before putting anything into your body), pregnant and nursing women should not take piracetam. As a supplement its purity is not guaranteed by the FDA, meaning one must be very careful about purchasing it from an American company. Since it is a prescription drug in European countries pharmacy grade tablets can be obtained without a tremendous amount of effort. Some American suppliers have their batches analyzed by independent laboratories, like New Star, but if their records are not convincing enough, you can test it yourself, or send it to a lab. I fear if someone ingests a contaminated sample nootropic research as a whole will unfairly suffer because of the inevitable panic it will cause. Association is as bad as guilt in the information age.

In the end, however, adequate sleep, nutrition, exercise, fluid intake, mental stimulation and socialization are still our safest and most effective means of improving our minds, but there is no doubt these molecules show promise and should be investigated further.

 

NEN