Our evidence-based analysis of PRL-8-53 features
What Is PRL-8-53?
PRL-8-53 is a synthetic research chemical that has intrigued the nootropic community for decades. There has been only one small human study, funded by the patent holder, on the compound in over 40 years, but the results suggested that a single dose of PRL-8-53 could improve short-term memory by more than 200%.
PRL-8-53, a derivative of benzoic acid and phenylmethylamine, was discovered in 1972 by the late neuropharmacologist Dr. Nikolaus Hansl, who patented it three years later.
Hansl died in 2011, and the development of PRL-8-53 has not been continued, but the compound is available for purchase. It has developed a following of users who say it compares favorably to known memory enhancers like noopept.
Preliminary animal studies conducted in the 1970s indicated that PRL-8-53 was both safe and significantly nootropic, boosting avoidance learning in rodents with no adverse effects. But the real interest in PRL-8-53 was sparked by a 1978 study on human volunteers, which showed that a single dose could more than double memory as measured by word retention scores.
The one-day study involved a group of 47 healthy volunteers between 24 and 86 years of age. While participants who had good baseline word retention scores showed little improvement after taking PLR-8-53, participants who had low initial scores or who were over 30 demonstrated significant improvement following a 5 mg dose of PLR-8-53, in many cases more than doubling their rate of recall. No adverse effects were noted in the human study.
Counterculture interest in PRL-8-53 was fueled by comments from author and longevity specialist Durk Pearson, who was quoted in the underground magazine “High Frontiers” (which later became “Reality Hackers” and then “Mondo 2000”) as follows: “PRL-8-53 is a terrific memory enhancer. Normally you can memorize about seven or eight digits just by looking at them for a second. PRL-8-53 gives the average person a memory span of about 21 to 22 digits.”
Anecdotal evidence appears to support claims for PRL-8-53’s safety and nootropic capabilities, but it is still considered an experimental drug due to its limited testing.
PRL-8-53 is currently an unscheduled drug and can be legally purchased in the US.
Benefits and Effects of PRL-8-53
The only human study on PRL-8-53 indicates that it may significantly boost memory, particularly in older people. 
The double-blind study used word memorization as a measure, testing the participants’ ability to recall a list of 12 one-syllable words, first to establish a baseline and then again after ingesting PRL-8-53 or a placebo. The subjects were tested on their ability to recall the words 24 hours after hearing them and then again one week later.
The study results indicate that participants who had higher baseline scores showed the least improvement after ingesting PRL-8-53, while subjects who had demonstrated poorer initial memory or who were over 30 years of age showed significant improvement in recall.
Hansl described the effect on the older participants as follows:
“This group was age 30 or older. As might be expected, rote memory did not come as easily to this group as the younger students. The average retention after 24 hours when on placebo was just under three words out of a possible 12. The average retention after one week was two words. However, the same subjects, when learning subsequent to drug administration, retained an average of 5.85 words after 24 hours and 5.25 words after one week. Again the increases were statistically significant. The improvement expressed in percent of placebo performance was 108% for the 24-hour test and 152% for the one-week recall.”
How It Works
PRL-8-53’s exact mechanisms of action are not well understood, but it is believed to regulate the brain’s production of and response to several crucial neurotransmitters.
In the only available article on the human study, Hansel said PRL-8-53 potentiates dopamine, partially restricts serotonin production, and enhances the brain’s response to acetylcholine. Though Hansl’s research report on the 1978 human study suggests those actions, it does not detail the mechanism of action.
The fact that older subjects saw the most nootropic benefit from taking the drug supports the concept that dopamine modulation plays a significant role in PLR-8-53’s effects. Upregulating the normal age-related slowdown of dopamine production associated with cognitive decline could significantly positive impact both learning and memory.
In the same article, Hansl suggested that PRL-8-53 works in part by converting short-term memory to long-term information storage. “PRL-8-53 has been shown to augment responses to noradrenaline in the animal model, both peripherally and centrally. Therefore, it seems reasonable to assume that a similar function may be present in humans. Translated into behavioral effects, it implies that this drug is also capable of facilitating the conversion of short-term to long-term memory, causing an increased storage of informational code.”
Hansl also noted that PRL-8-53 enhances the response to acetylcholine and further said, “The drug is not a stimulant, and in the experimental animal toxicity appears only after it is given a dose more than one thousand times as large as the projected human dose. In summary, we now have a potentially useful drug that will boost a specific chemical system in the brain, the cholinergic system, and thereby improve our ability to recall, to retrieve information from a pre-existing information pool.”
The only human study on PRL-8-53 was based on the ingestion of a single 5 mg dose. There is no data on the effectiveness or potential toxicity of any other dosage in humans.
PRL-8-53’s mechanisms of action and potential interactions with other nootropics are unknown, so making informed recommendations on how it could be used in nootropic stacks is impossible.
No adverse effects from a single 5 mg dose of PRL-8-53 were observed in the human study.
Animal studies suggest that the compound has a high therapeutic threshold, but the evidence is minimal because no comprehensive toxicity studies have been completed.
Though no side effects have been documented, PRL-8-53 is a highly experimental research chemical, and caution is advised.
Where to Buy
It’s particularly important to purchase experimental drugs like PRL-8-53 from reputable nootropic vendors you can trust to deliver an authentic product.
Based on our research, we recommend the following product that can be ordered directly from Amazon:
PRL-8-53 is a largely unexplored synthetic nootropic that might have real value as a cognitive enhancer. Still, at this time, there are many more questions than answers about its safety and potential benefits.
Though it triggered strong interest when it was introduced more than 40 years ago, research on its possibilities came to a halt less than a decade after its discovery. Little has been learned about it since the study that sparked such strong interest in its potential as a memory enhancer; its optimal dosage, side effects, toxicity, interactions with other drugs, and even mechanisms of action remain unknown.
There doesn’t appear to be any ongoing research on PRL-8-53. Still, curiosity about its potential continues, and it has a small but enthusiastic following who consider it to be one of the best short-term memory boosters available.
Planning to start a new supplementation regimen? See our medical disclaimer.
This page was last updated on July 16, 2021.