Posted 18 October 2017 - 09:46 AM



Recently I've been researching some Nootropics that you may not have heard of before; Bromantane, Cerebroslyn, Cortexin, Ladastan, Mildronate...

As Biohackers we have a bit of weak spot for novelty, especially pharmacological novelty, smart drugs that might work a little different than the things we've tried before.

However, pharmacological novelty is not always good and it is not for everyone, amongst Biohackers there's a spectrum of risk tolerance. Similarly, amongst Nootropics and performance enhancers there's a spectrum of risk profiles. Not all Nootropics are equally safe and benign.

My Risk Philosophy

Some Biohackers are VERY risk averse, like Justin who I interviewed, he's the Mind behind the very popular anti-aging forum Longecity.

However, I'm more of a risk seeking or Antifragile Biohacker. Which is not just because I'm reckless and want to treat my neurobiology like an amusement park. I have some quiet rational reasons for seeking risk.

When it comes to Nootropics the upside is so great and the downside is relatively minimal. The sky is the limit with the potential upside of Nootropics. Whereas the downside risk, is very minimal.



For example; one of my favorite smart drugs is Nicotine, but I can't really say that Nicotine is a risk free drug. Some studies have indicated a very weak carcinogenic effect, this is debated though, some researchers say that Nicotine, alone is none-carcinogenic and as safe as say caffeine. However, I'll continue to use Nicotine because the upside of Nicotine is tremendous, I get paid to do creative work and Nicotine is the best stimulator of this that I've found out of the +80 smart drugs I've used.

As an entrepreneur, Nicotine is like a employee that appreciably increases the productivity of my company who I don't have to train or manage who only demands a salary of less than $10 a month. To me, at least, that minimal cancer risk it may have is offset by it's upside. Since I make more money, I can afford other good supplements, good food and good lifestyle habits that significantly mitigate overall cancer risk. Since I make quiet a bit more money, if I get sick, I'll be all the more able to afford it.

Conversely, much of our other lifestyle and consumption habits have very limited upside with either limited downsides or significant downsides.

For example, my avocado salad is not exactly a performance enhancer, it's a relatively healthy meal that's just going to power me through my day. Or perhaps someone eats a more average diet of carbs, sugary snack foods and fried meat along with GMO fruits & veggies. There's barely any upside to this diet, it just barely assuages hunger and the downside is that it causes spikes in blood sugar that drive you to eat every few hours. The long term downsides are heart diseases, diabetes, Alzheimer's and ultimately death.

Everyday we are swimming in a sea of biological risk. Last night my girlfriend surprised me by buying me dinner at a restaurant I've never visited before and we tried a delicacy from her culture whose name I could not properly pronounce. I went hiking in the mountains last weekend and then spent about 45 minutes in a packed bus riding through a pretty impoverished part of the country. Who the hell knows what kind of pathogens I'm exposing myself too? We consume things all day, every day that maybe toxic so I consume Nootropics every day that feed my Mitochondria to fight those toxins. Maybe a very small proportion of those Nootropics have minimal toxicity or negative side effects but the upside benefit drastically outweighs this.

I'll also suggest that amongst Biohackers there's something of a barbell of Biohacking risk tolerance; like a barbell the majority of the Biohackers with higher risk tolerance will be on the far right and far left side of the barbell.

On the far left is Biohackers like me, who are younger, eat a healthy diet, we have quiet resilient biology thanks to our good habits and generally healthy lifestyle. We have more disposable income to spend on our on health, if we do something that hurts our health we have the time and resources to correct it.

On the far right is (mostly elderly) people who have chronic diseases that desperately need Nootropics or anti-aging drugs. Without them their minds to will deteriorate and their quality of life will decline badly. When the alternative is quiet literally losing your mind, just being a burden to those around you or death no side effect of Nootropic drugs could be worse.

In the middle of the bar bell is the all the lay-Biohackers, People who have just a little of time and money to spend on their health. They can't do a lot of experimenting, they need to devote their limited time and resources to Biohacks that work very consistently. They should be exercising, meditating, eating a disciplined diet, sleep hacking and supplementing fish oil, vitamins and Adaptogens.

Since I started using Nootropics 5 years ago, I really have made progress towards being the best version of myself. I've done lot's of Nootropics and experienced very few incidence of negative side effects. I, for one, have experienced tremendous upside and virtually no downside.

I've also spent a lot of time doing sentiment analysis of thousands of different Biohacker reports and anecdotes about smart drugs. I know that anecdotes are less important than scientific data but if trends show up frequently in Biohacker reports about a given drug, I note that and include it in my risk analysis. A few months ago I researched a number of drugs and products by Bayer Pharmaceuticals and came accross numerous anecdotes of really ghastly side effects, in stark contrast to relatively very tame side effects of Nootropics that are reported commonly.

So those are my reasons for being a risk seeking or Antifragile Biohacker, perhaps they'll change how you manage risk as a Biohacker. Next I'll rank the risk of various exotic European Nootropics...

Risk Grade: A

Piracetam

Grade: A

Number of Clinical Trials: 235

Which has an impressive 31 clinical trials in the last 10 years alone.

A 20 year long term population study was conducted in France.

This is quiet possibly the most popular smart drug, it's been used by millions of people and you can find thousands of Biohackers online reporting their experiences with it.

Because of the vast amounts of anecdotal data about Piracetam, we know the most commonly reported side effect is a headache from a lack of Choline supplemented along with the Piracetam.

Numerous studies have evaluated it's use and determined it safe for children.

Because it's such a popular, un-patented drug it's produced by hundreds of laboratories all over the world and there is a spectrum of quality. You can buy unbranded, generic Piracetam powder very cheaply by the kilo but the quality is suspect. I only buy or consume powdered Piracetam if an accredited American lab has verified it to be >97% purity with spectroscopy.

Piracetam only works for 80% of the people who use it , a minority of people with an aldosterone deficiency won't experience the long term or short term benefits of the drug. In a lot of a cases , a minority of people with an aldosterone deficiency won't experience the long term or short term benefits of the drug. In a lot of a cases this can be fixed , but sometimes not. Piracetam is not for everyone.

Phenylpiracetam

Grade: A-

Number of Clinical Trials: 6

Phenylpiracetam is regarded amongst Biohackers as one of the best smart drugs, it's molecularly very similar Piracetam.

It was created in 1983 behind the iron curtain for soviet cosmonauts.

It has a handful of clinical trials; a few of them recent, all of them Russian.

Online you can find many veteran Biohackers highly praising it

I decided to use the original branded phenylpiracetam called Phenotropil. This is the one I have been using for the past three months and I haven't experienced any side effects from it . One Biohacker took Phenylpiracetam for 3 months and reported : When I started phenylpiracetam I had some bad side effects from it. I tried two different online sellers of powdered phenylpiracetam (they are not the most popular sources, but they are still well known sources) , and after a few days of uses I would get a strange chest pain and difficulty sleeping. I almost discontinued my usage of this nootropic until

The only negative side effects reported consistently about it is choline headaches if you dose to much without supplement an ACh precursor.

Unfortunately, it doesn't deserve get a higher grade because of the relative lack of human clinical trials done specifically on Phenylpiracetam at labs and universities around the world.

Risk Grade: B

Noopept

Grade: B

Number of Clinical Trials: 3

The Racetams are noted for their virtually none-existent toxicity. It's molecularly similar to and in the same category of the very well tolerated Racetams.

Thousands of savvy Biohackers have reported their experiences with it and there's a real lack of undesirable side effects.

It doesn't deserve an A because there's only been three clinical trials rigorously evaluating Noopept in humans.

Semax

Grade: B-

Number of Clinical Trials: 3

All three clinical trials were done in Russia but none were placebo controlled.

A BDNF mediated long term memory promoter that you take nasally.

Approximately 15% of users who wrote Biohacker reports online reported pretty tame negative side effects like lack of motivation, tiredness, slowness, lethargy, irritability or moodiness.

From a Russian study of 187 patients: Semax treatment resulted in significant clinical improvement, stabilization of the disease progress and reduced a risk of stroke and transitory ischemic attacks in the disease course.The drug is featured by minor percent of side-effects and is well tolerated by patients, including those of older age groups.

One researcher reported : As the safety profile is extremely good, the LD50 (the dose at which 50% of the test animals die) is undeterminable. This means that in spite of increasing the dose HUNDREDS of times the therapeutic dose NONE of the animals died. Hence you find that the dosage for every indication is quite flexible.

Strangely, there appears to be a correlation between hair loss and Semax usage , so if you really care about your hair you may want to pass on Semax.

Even though this drug has been around a while and you can find a lot of studies on Pubmed, it's lacking breadth and quality of clinical trials.

Fabomotizole

Grade: B-

Number of Clinical Trials: 5

There's 5 clinical trials, all Russian, the most recent of which is what I consider a high quality, human study encompassing 100 patients given Fabomotizole.

It's a relatively younger drug, invented in the early 2000's.

From the high quality 2016 study : There were a total of 15 and 199 adverse events in the afobazole... groups... No manifestations of afobazole withdrawal syndrome were found... Afobazole is an effective and safe drug to treat patients with [generalized anxiety disorder] and [adjustment disorders] and non-inferior than diazepam in the treatment of these disorders, however it is superior in terms of several variables, including the safety profile.

It's not as popular as say the Racetams or other Gabaergic drugs, so there's not a significant amount of good Biohacker reports about it. Although, amongst the ones out there on Longecity and Reddit, I came across no reports of egregious side effects.

It's a safer alternative to Diazepam or Valium , the Benzodiazepine based tranquilizer.

I don't have any major objections to this Anxiolytic, I just don't think it deserves a higher grade because the clinical research is limited to the Russosphere.

Selank

Grade: B-

Number of Clinical Trials: 3

Like it's cofactor Semax, it has a grand total of three clinical trails, all are from Russia and none were placebo controlled.

From a 2016 Russian paper that you can find the whole text of online: Clinical studies have shown that the effect of Selank is similar to that of tranquilizers at low doses, but is not accompanied by the unwanted side effects of benzodiazepine tranquilizers.

I came across one very negative report from an anonymous Biohacker of bad side effects when combined with Semax and NSI

Mildronate

Grade: B

Number of Clinical Trials: 25

It does have some recent placebo controlled trials

All the clinical trials are either Russian or China, the drug apparently is not on the radar of researchers in the Western world.

The recent Chinese study reported No serious adverse events were observed. A 2015 trial of 67 Russians agreed No side effects were registered during the course of mildronate treatment.

Bromantane

Grade: B

Number of Clinical Trials: 8

10 articles of human research in the past 10 years

A significant trial was published in 2010 ; it was carried out in 28 different clinical centers and included data from over 700 Russians.

It was developed in the 1970's in Russia so it's been around for +40 years and it's a highly praised smart drug by some very veteran Biohackers but I would expect it to be more studied internationally by now.

From the study of 700 Russian patients Adverse effects were observed only in 3% of patients, the therapy was discontinued in 0.8%. No serious adverse effects were found.

Cerebroslyn

Grade: B

Number of Clinical Trials: 64

Around the internet you can find numerous reports from younger, otherwise healthy Biohackers who used Cerebrolysin as a performance enhancing smart drug. This contrasts with the vast majority of the studies which were done with elderly patients suffering from cognitive decline.

Anti-aging drugs typically have a performance enhancing effect when taken by healthy people and in the case of Cerebrolysin you can find veteran Biohackers praising it as a quiet effective smart drug.

It is derived from the proteins of pig brains, which seems a little weird. Could they not just synthesize the proteins?

There's also some fairly well reasoned objections to otherwise healthy people using it . So I would NOT categorize Cerebrolysin as a low risk Biohack that everybody or anybody should use.

It's specific purpose is to treat diseases of cognitive decline. I would not recommend it to new Biohackers or those who are just looking for a study drug.

It's an injectable drug and really clumsy people should not be using needles.

It was first approved in 1954, so it's not a newer drug that we don't know if it may or may not cause cancer in it's users after 10 years of dosing.

Ultimately I feel the risk is small with Cerebroslyn because it's produced and patented by a major Austrian pharmaceutical company. If they produced a drug that passed a pig pathogen to their customers they would face titanic lawsuits and a deluge of brand-sinking negative press. They would be out of business fast! I did a bit more research on this and Google searched:

"Ever Pharma" "Cerebrolysin" "Lawsuit"

Which produced no lawsuits involving either Ever Pharma or Cerebrolysin. Then I thought, well this is an Austrian company so I searched:

"Ever Pharma" "Cerebrolysin" "Klage" (German for lawsuit)

Nothing interesting. I even Google Translated a few articles.

Finally I searched:

"Cerebrolysin" "Lawsuit"

Which similarly yielded no lawsuits involving the drug. So, it's a +60 year old drug with no lawsuits serious enough to have make it onto the Internet . Not bad! Compare this to Piracetam which is unpatented and produced by hundreds of anonymous laboratories all over the world. The financial incentives are really stacked for EVER Pharma to produce a safe product.

Risk Grade: C

Cortexin

Grade: C+

Number of Clinical Trials: 19

It's synthesized in a very sterile laboratory environment.

According to a study that evaluated it in 45 patients: The drug was well-tolerated, no side-effects were observed.

It's been studied extensively in Russian but lacks international studies that have been peer reviewed and published in English for the public in open journals.

It's an injectable drug and really clumsy people should not be using needles.

However, a few Biohackers on noted an undesirable side effect persistent muscle fasciculations

Risk Grade: D

Phenibut

Grade: D+

Number of Clinical Trials: 4

There's only 4 trials, none-recent, all in Russia with limited or poor translations into English.

Phenibut is a popular drug amongst Biohackers and lifehackers.

It gets a poor risk grade because it really is habit forming for a significant proportion of people that try it. It works on your Gaba receptors in a way similar to alcohol. So if you have any personal or family history with alcohol addiction, Phenibut is a bad idea for you.

If you're a disciplined person with healthy psychology, you'll be fine using Phenibut in moderation . It's really is a great anti-anxiety agent; a quintessential On the other hand I've used it myself for several years on and off. I'll use it 2-3 times a week maximum and I've never had problems or experienced negative side effects. But I don't have an addictive personality.. It's really is a great anti-anxiety agent; a quintessential social smart drug

Similar to alcohol if you consume too much you may act a little stupid, trip up a flight of stairs and be hungover the next day.

If you make a daily habit out of Phenibut you'll get hooked and experience some real unpleasant withdrawals if you run out of it.

In the comments below...

Let me know what kinds of Biohacking risks you've taken. What was really worth it? What wasan't?

Edited by jroseland, 18 October 2017 - 09:50 AM.