Comment · Wed, October 9, 2013 · Ceretropic
Adrafinil Experience - Effects & Review
Original post in this thread
hoodyhoodyhoo · 4 points
Subject Details - Male, 22, 5'6", 130 lbs. Currently taking Venlafaxine 220mg and Caffeine 150mg in the morning with Melatonin 2mg and Hydroxyzine Pamoate 25mg before bed.
Previous Experiences - Piracetam, Nefiracetam, Noopept, Clonazepam, Lorazepam, Alprazolam, Bupropion, Propylhexedrine, Cocaine.
Backstory - About a year ago I was diagnosed with Dysthymia, a chronic low-grade depression which primarily effects motivation, mood, and energy. Because my psychiatrist is employed by my university and sees me for free, he isn't allowed to prescribe stimulants due to the large number of students who fake ADHD hoping to get Adderall. He's been understanding about my issues, prescribing antidepressants with stimulant effects and encouraging me to see an independent psychiatrist if I want to try an amphetamine; I chose not to, opting to try OTC meds and Nootropics first. I tried various Racetams, none of which provided any noticeable effects except Nefiracetam, which provided very mild improvements in focus, but not strong enough to be considered effective. After researching I decided to try Adrafinil as an introduction to Eugeroics before diving in and buying Modafinil. The…
What they were answering
MisterYouAreSoDumb · 12 points
Adrafinil is NOT toxic to the liver. That is a myth being propagated over the internet without citation. Please don't spread it.
It does raise liver enzymes over time. Many drugs that are metabolized in the liver raise the levels over time. Modafinil is metabolized in the liver, and raises liver enzymes. As with anything, the effects are dosage-dependent. Take too much acetominophen, and you will damage your liver. Take adrafinil consecutively for two months or more, and you could see your liver enzymes rise. Take large amounts of it for a long period of time, and yes you can damage your liver. That does not mean it is toxic to your liver at normal doses.
Would I suggest people take adrafinil every day? No, definitely not. I would not suggest people take modafinil every day either. They are not nootropics, and should be treated with a higher level of care. That does not mean they are toxic.
u/MisterYouAreSoDumb · Ceretropic
Here are sources and reasonings for my assertion that adrafinil is NOT toxic to human livers. As if its approval for use since the 1980 wasn't enough.
http://www.shirecanada.com/en/shire-canada/PDF/Alertec.Product%20Monograph.03-01-2012.pdf
In Phase 1, 2, and 3 studies, mean plasma levels of gamma glutamyltransferase (GGT) and alkaline phosphatase (AP) were found to be higher following administration of ALERTEC, but not placebo. Few subjects, however, had GGT or AP elevations outside of the normal range. Shifts to higher, but not clinically significantly abnormal, GGT and AP values appeared to increase with time in the population treated with ALERTEC in the Phase 3 clinical trials. No differences were apparent in alanine aminotransferase, aspartate aminotransferase, total protein, albumin, or total bilirubin.
So as I said, modafinil raises these enzymes just like adrafinil does, as the metabolism of the modafinil molecule still happens once the adrafinil converts. However, these increases only went outside of normal range for a few people. The shifts were not not clinically significantly abnormal, and returned to baseline after ceasing the drug.
In a single dose 200mg modafinil study, compared to healthy individuals, modafinil plasma concentrations were unchanged in patients with severe chronic renal failure (creatinine clearance 20mL/min). However, the renal clearance of the active metabolite, modafinil acid, was reduced, leading to a 9-fold increase in exposure. No adverse events were reported in this small number of patients. The clinical significance of increased modafinil acid plasma concentrations is unknown.
So obviously people with severe renal failure are going to metabolize drugs more slowly. However, it did not lead to an increase in plasma concentrations of modafinil, nor did it lead to any adverse events. It did lead to an increase in modafinil acid, as the impaired livers had a harder time metabolizing it. The clinical significance of that metabolite is not know, but has not caused any adverse events. Obviously I would suggest that people with sever chronic renal impairment not take drugs that require renal clearance.
So what is the difference between modafinil and adrafinil? Well adrafinil is simply a modafinil molecule with an extra oxygen atom off the nitrogen.
So an enzyme in your body has to cleave off that oxygen to create modafinil. This is what leads to an increase in liver enzymes compared to modafinil. From there the metabolism is the same. I believe the enzyme responsible for that action is alkaline phosphatase, which would be higher in people that take adrafinil compared to people who take modafinil.
http://www.nevapress.com/cnsdr/full/5/3/193.pdf
No toxic signs were seen in sub-acute toxicological studies with doses of 100, 200, and 400 mg/kg in rats treated over 1 month, or with doses of 50, 100, and 200 mg/kg of adrafinil administered over 3 months.
As one indication of the safety level of modafinil in humans, Bastuji and Jouvet (2) described a subject who unsuccessfully attempted to commit suicide by taking 45 tablets of modafinil (a quantity 15 times greater than a normal high dose). Bastuji and Jouvet (2) also found that the long-term use (≥ 3 years) of modafinil did not result in harmful side effects, peripheral side effects or disturb nocturnal sleep. Patients treated with modafinil for at least 3 years did not develop tolerance or dependence.
So no long-term adverse effects are seen in either rats of humans. Those with severe chronic renal failure have taken modafinil without issue. Adrafinil simply raises the enzyme responsible for cleaving off the oxygen to create modafinil, and does not damage the liver. So I can confidently say there is no evidence that adrafinil is toxic to the liver.