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Pharmacology - Warning: 2-FA, 3-FA, 4-FA users risk neurotoxicity

Discussion in 'Phenethylamines' started by sh4mw0w, Jan 12, 2012.

  1. sh4mw0w

    sh4mw0w Silver Member

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    [NOPARSE]Disclaimer[/NOPARSE]: Please be sure to read this thread in its entirity rather than just the first post. While this first post was well received it contains a number of assumptions, errors, and statements that contradict the findings of empirical research. These issues are highlighted throughout the discussion, so the whole thread will give a much more balanced overview of this topic than this post alone. The poster's claim to be an experienced pharmacologist and bioinformatician is also bogus.. he works in IT.
    _____________
    (end mod edit)



    Hello everyone,

    Look I'm posting here as an pharmacologist and bioinformatics researcher to WARN you guys that you are putting yourselves at risk by consuming halogenated amphetamines, which are increasingly sold as Research Chemicals (RCs). The main substances in question I refer to are known as 2-FA, 3-FA, and 4-FA -- in particular, I am warning about 4-FA.

    Some of you know there is a risk of neurotoxicity with compounds such as 4-FA, and choose do consume these substances anyway with informed consent. That's fine. As long as you know there is a risk of brain damage (with the risk level unknown), and you accept that risk , then go ahead.

    I am writing to those young people, without the wisdom of age or a background in pharmacology or chemistry, are are just starting in research chemicals (RCs) who do not understand or are unaware that the risk profile of halogenated amphetamines (2-FA, 3-FA, 4-FA, etc) is MUCH DIFFERENT than older research chemicals with a relatively safe track record (2C-I , etc).

    MDMA and 2C-I etc are relatively safe when used in moderation, and CANNOT be compared to compounds such as 4-FA. Yes, MDMA has a risk of neurotoxicity, but when used in moderation (a few times a year) that risk is relatively low. 4-FA has a MUCH MUCH higher risk.

    Here is why you are at risk if you consume halogenated amphetamines.
    1) Amphetamine is ALREADY neurotoxic due to the formation of reactive oxygen species (ROS) in the brain [1]. The neurotoxicity is dose-dependent and duration dependent. If you are on a low-dose Adderall prescription for a couple of years, this is certainly safer than someone who is consuming 1g of methamphetamine a day for a couple of years, but in both cases there is a risk.

    [1] Prostaglandin H synthase-catalyzed bioactivation of amphetamines to free radical intermediates that cause CNS regional DNA oxidation and nerve terminal degeneration
    http://www.fasebj.org/content/20/6/638.short

    [​IMG]
    Racemic Amphetamine (low-to-moderate neurotoxicity)

    [​IMG]
    Racemic Methamphetamine (moderate-to-high neurotoxicity)

    So listen: Read the link above [1]. Just by consuming amphetamines (especially methamphetamine), you are putting your brain at risk due to the formation of ROS via Prostaglandin H. The impact of amphetamine neurotoxicity be reduced by pre-treating yourself with approximately 500mg of aspirin for every 5mg-10mg of amphetamine, up to a maximum of approx. 4g of aspirin per day. Read the study I linked for more info.

    The risk with regular amphetamine is there, it exists in rats, but there are additional significant risks with compounds like 2-FA, 3-FA , and 4-FA...

    On to the really toxic stuff, the HALOGENATED AMPHETAMINES. ...

    2) Halogenated amphetamines (the Research Chemicals) such as 2-FA, 3-FA, and 4-FA inherit risk profile of dextroamphetamine and methamphetamine above(with low to high neurotoxicity risk) well as inherit toxicity profile of a really dangerous and neurotoxic related compound known as para-chloroamphetamine.

    Para-chloroamphetamine is used to selectively KILL (yes, kill) serotonin neurons in the brain in labs around the world. It is MUCH more toxic than MDMA or Amphetamine. Let's take a look at what this awful amphetamine analog looks like (4-CA).

    [​IMG]
    Para-chloroamphetamine (4-CA): Highly toxic to serotonin neurons.

    Hmmm... that 4-CA alot like a substance sold by unscrupulous research chemical vendors, out to make a buck on your suffering -- even if they cause you brain damage. Compare the above structure of Para-chloroamphetamine (4-CA) to your beloved 4-FA.

    [​IMG]
    4-FA: Almost the exact same thing as the highly serotonin-toxic para-chloroamphetamine pictured above. Oh shi0.

    Oh, you don't believe me that para-chloroamphetamine is toxic?

    Let me quote:

    The ONLY different between the research chemical 4-FA and the highly- neurotoxic Para-chloroamphetamine (4-CA) is the substitution of a single atom -- a fluorine atom for a chlorine atom.

    The Research Chemical 4-FA has a fluorine in a para position on the phenyl group which is VERY CLOSELY RELATED to the highly neurotoxic 4-CA (para-chloroamphetamine), which has a chlorine in a para position on the phenyl group.

    These compounds are SO SUBSTANTIALLY SIMILAR that they are considered 'obvious' functional analogs according to U.S. patent law. If you were to patent para-chloroamphetamine for its neurotoxic properties, it is highly likely the U.S. patent office would consider your beloved 4-FA to also have neurotoxic properties (it is 'obvious' to an expert in the field), and would be considered non-patentable.

    Given that the ONLY difference between 4-FA and 4-CA (para-chloroamphetamine) is the type of halogen atom, it is highly likely that 4-FA retains some of the neurotoxic properties of 4-CA. The nature and scope of the neurotoxicity is up for debate, but the risk is certainly there. And in my opinion the risk is very high. The physical properties of the halogens are just TOO similar (electronegativity, radius, orbital configuration, etc).

    In the same way that anyone who has taken 2C-B will say it is VERY SIMILAR to 2C-I (2c-B / 2c-I causes the same body feelings, the same psychedelic effects, etc and the only difference is ONE HALOGEN ATOM and they only really differ in the biological half-life), anyone taking 4-FA is running the risk of the same neurotoxicity present in 4-CA (difference also = ONE HALOGEN ATOM).

    Let's take a look at the properties of the HALOGEN SUBSTITUENTS ... they are VERY SIMILAR. If you are taking 4-FA, you might as well be taking para-chloroamphetamine (4-CA).

    [​IMG]

    Electronegativity of fluorine and chlorine are VERY SIMILAR.

    [​IMG]

    Fluorine and Chlorine have the SAME VALENCE ELECTRON CONFIGURATION (as they are in the same column in the periodic table.)

    [​IMG]

    Fluorine and Chlorine have VERY SIMILAR ATOMIC RADII
    (look at F- at 136 and Cl- at 181).

    Look at the above properties. 4-FA and 4-CA (para-chloroamphetamine) are so closely related that they might as well be the same chemical. This is like the difference between the OTC antihistamine Chlorpheniramine vs the OTC antihistimine Brompheniramine. They only differ in biological half-life.

    There is a small chance (less than 10%) that 4-FA is safe. But the weight of the evidence points to erring on the side of caution -- we need to assume that halogenated amphetamines are neurotoxic (90% probability) -- and that they are much more neurotoxic than regular amphetamines. The evidence is overwhelming.

    Given that 4-FA is ALMOST IDENTICAL to the highly neurotoxic 4-CA (para-chloroamphetamine), differing by ONLY ONE ATOM,

    Do you really want to take that risk with your brain?


    ---

    P.S.

    To users of 4-FA who are concerned:

    Okay, so you just read my post, and you believe me. You know that you have taken a risk with your brain, and you want to stop. You don't know how much damage is done (if at all), but you want to get a handle on things and minimize the risk.

    What do you do to heal, and to minimize the risk of damage?

    1) Stop taking halogenated amphetamines immediately. Do not take them again. You may choose to take regular amphetamines, but halogenated ones are just too risky.

    2) Start taking a good multivitamin. Not that Centrum crap. Take a good food-based multivitamin at least 1x / 2x a day from Whole Foods or other organic food store.

    3) Eat good diet full of fresh raw foods with fruits and vegetables.

    4) Consume melatonin 3-6mg at bedtime each night. This is a powerful mitochondrial antioxidant and promotes brain cell survival during ischemia and other conditions.

    5) Consume Acetyl-L-Carnitine at a dose of 2-3gday along side a good source of Omega3 fatty acids. The Acetyl-l-carnitine is a cofactor in the transport of Omega3s and also promotes brain tissue survival as well as regeneration. Consume at least 2-6g Omega3s per day alongside the ALCAR (a mitochondrial cofactor).

    Good luck everyone. Please stop taking this 4-FA crap unless you really know what you are doing and have read all the Pubmed literature and made a decision for yourself. Otherwise you are literally playing Russian Roulette with your brain tissue.

    ::
    ::
    ::​
     

    Attached Files:

    Last edited by a moderator: Feb 20, 2013
  2. bean.

    bean.

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    Re: Warning: 2-FA, 3-FA, 4-FA users risk neurotoxicity. 4-FA is likely neurotoxic.

    Good little read although I get what your driving at couldn't you just state the evidence rather than goign into the 'I'm an experienced pharmacologist' line of things. Sorry it's just I read a post a few weeks ago relating to this statement of careers and thought it was relevant here.

    I get what your driving at although I don't have time now to read up other papers so I've only got your word for it at the moment. Aren't you slightly jumping to conclusions with this 'you are pretty much taking 4CA when using 4FA' crap. It was my understanding that each of the 2C halogen family were suprisingly different but again I'm tired and can't read up right now. It was also my understanding that even the smallest change in structure of a molecule could drastically change the properties of that molecule.

    I'm not trying to dampen down what you are saying as personally I do not take any drugs currently let alone halogenated amphetamines but the whole post seemed as if it was scaremongering, for want of a better word. Still thanks for collecting that infomation together and trying to warn users of this danger.
     
  3. w01f

    w01f

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    Re: Warning: 2-FA, 3-FA, 4-FA users risk neurotoxicity. 4-FA is likely neurotoxic.

    I always had the feeling the FA series was really bad for you- considering the toxicity of flourine itself...
    I am a firm advocate of pentedrone as a stim.
    Substitutions on the benzene ring seem to affect potency and duration greatly from what i read, it probably has something to do with the bodies ability to metabolize the molecule and the strong bonds of the benzene ring..
     
  4. sh4mw0w

    sh4mw0w Silver Member

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    Re: Warning: 2-FA, 3-FA, 4-FA users risk neurotoxicity. 4-FA is likely neurotoxic.

    People's health is at risk. Since when did a statement of fact become politically incorrect?
    Fact: I am an experienced pharmacologist, and I have been employed for a number of years at the National Institutes of Health (NIH).
    That's unfortunate a statement of fact would make you uncomfortable, but I think it's relevant to my credibility.

    On to the chemistry...


    Short answer: No, I don't think so. There is a high likelyhood that 4-FA has neurotoxic properties.

    TL;DR Answer:

    I explained this if you read my post carefully -- I used the examples of chlorpheniramine vs brompheniramine -- two OTC antihistamines with markedly similar pharmacological profiles. In fact, they are a good analogy for 4-FA vs. 4-CA because:

    WHY USE CHLOR/BROMPHENIRAMINE AS AN ANALOGY FOR 4-FA/4-CA

    1) Chlorpheniramine and Brompheniramine also differ by ONE HALOGEN ATOM.
    2) Chlorpheniramine and Brompheniramine also are biologically active in the CNS.
    3) Chlorpheniramine and Brompheniramine also contain single highly electronegative substituents on a phenyl ring.
    4) Chlorpheniramine and Brompheniramine are extensively studied in the medical literature.

    Now chlorpheniramine vs brompheniramine are not alone among compounds which differ by a single halogen atom. There are numerous examples across all classes of compounds (benzodiazepines, antivirals, antidepressants, antihistamines, etc) . Literally hundreds of compounds, if not thousands. All these compounds show that halogenated resonance-ring substituents invariably have similar pharmacological and phamacokinetic profiles. Often they are similar as long as the substituent retains the same radius and electronegativity ... This 'rule' holds the vast majority of the time.

    WHY: Pharmacological Similarity of halogen substituents is the RULE -- not the exception. When we are talking a single-atom difference, and that atom is an electron-withdrawing halogen in the same position on a ring, often the compounds will retain similar biological activity. Not always. But usually.

    The burden of proof is on the RC vendors to prove that 4-FA is a non-neurotoxic exception from 4-CA -- not on me to prove this PATTERN applies to 4-FA. This is especially true when we are dealing with human health -- we need to err on the side of caution. The only reason that 4-FA might be different is because Fluorine has some unique properties and has the smallest atomic radius (and is most highly electronegative [electron withdrawing] out of common pharmaceutical phenyl ring substituents). That is ALL it has going for it which might make it an exception to the rule.

    Are you willing to bet your health on the fact that 4-FA is an exception to a rule which is consistent across many classes of pharmaceuticals? I wouldn't, and that's why I've posted. I could less about a pharmacological chest-thumping contest, I'm just trying to help keep people from getting hurt inadvertently.

    I'll elaborate on what I mean here... specifically regarding
    Chlorpheniramine vs Brompheniramine, the two OTC antihistamines .

    [​IMG]
    Chlorpheniramine: OTC Antihistimine.
    Dose: 4 mg orally every 4 to 6 hours.
    Maximum dose 32 mg/day.
    Elimination Half-life: 20 hours



    [​IMG]

    Brompheniramine: OTC Antihistimine.
    Dose: 4 mg to 8 mg orally every 6 hours as needed
    Maximum dose: 24 mg/day.
    Elimination Half-life: 25 hours


    *THESE TWO ANTIHISTAMINE COMPOUNDS ABOVE ARE VERY SIMILAR IN ACTIVITY IN THE HUMAN BODY -- PROBABLY INDISTINGUISHABLE FROM ONE ANOTHER IN A 'BLIND' STUDY. (and like 4-FA/4CA they differ by one halogen atom).


    Notice above, chlorpheniramine and brompheniramine differ by a single atom... a halogen substituent... Chlorine vs Bromine ... which as in 4-FA and 4-CA are both halogens in the same column in the periodic table with the same valence electron configuration.


    Let's look once again at 4-CA (neurotoxic) vs 4-FA (the RC in question):

    [​IMG] [​IMG]
    4-CA (Left): Highly Selective-Serot
    onin Neurotoxic ///// 4-FA (Right): Popular RC with likely Neurotoxicity



    4-CA and 4-FA also differ by one halogen atom... Are we to expect these drugs don't follow the 'natural' pattern in pharmacology?

    Why should we expect the 4-FA is not neurotoxic, when 4-CA is neurotoxic?

    The burden of proof is on the Scientific Establishment and on the RC vendors to prove 4-FA is safe.

    We can reason by analogy and structure-activity relationships between Chlorpheniramine/Brompheniramine and 4-FA and 4-CA (neurotoxic). From this, we can infer that there is a strong likelyhood that 4-FA retains the neurotoxic profiles of 4-CA, since compounds that follow this pattern (like chlorpheniramine/brompheniramine) almost always have similar pharmacological activity.

    Now, the example above is COMMON.

    Chlorpheniarmine vs. Brompheniramine are just one of hundreds (if not thousands) of examples in Clinical Pharmacology where we can show that two compounds , which differ by a single halogen atom, retain remarkably similar biological activity, pharmacokinetics, and toxicity profiles.

    No one is not jumping to conclusions... As with chlorpheniramine vs brompheniramine.... There are tons of examples like this:

    Examples of Drugs which differ by ONE HALOGEN ATOM which retain remarkably similar properties:

    1) 2C-B / 2C-I /2C-C
    2) DOB / DOI / DOCl
    3) Chlorpheniramine / Brompheniramine
    4) Alprazolam / Triazolam
    5) Clonazepam / Nitrazepam


    Why do you think that DOI and DOB are similar in activity (as well as dose and half-life?) Or why Alprazolam and Triazolam (differing by one chlorine atom vs one hydrogen atom) both have similar 'feel' (as well as onset, poteny, and duration)?

    [​IMG][​IMG]
    Alprazolam (Xanax) vs. Triazolam (Halcyon)

    The differ by the presence or absence of one Chlorine halogen atom on the phenyl ring (analogous to Chlorpheniramine vs Brompheniramine, or 4-FA/4-CA, etc).


    Have you taken them both? Anyone who has taken 2C-B and 2C-I would tell you the two compounds are remarkably similar in 'nature' and only differ in more subtle aspects. The dose ranges similar. The onset is similar. The half-life is similar. The effects are VERY similar. In fact, I would venture to say it would be difficult for an unexperienced user to tell them apart. Of course, an experienced user would be able to tell easily, but that's not my point. My point is that these compounds are remarkably similar in action , and also differ by a single halogen atom.

    The same would apply to alprazolam (Xanax) and triazolam (Halcyon). Both are high-potency benzodiazepines. Anyone who's taken both will of course tell you that they prefer one or the other, that one is more euphoric than the other ,etc, but again, there will not be a consensus on these properties.

    What's remarkable is that Xanax and Halcyon are more 'similar' than 'different'. The Dose range is the same. The onset is rapid in both cases. Both drugs will wear off in a similar amount of time (6-10 hours) The effects are very similar (disinhibition, muscle relaxion, sleepiness, anxiety reduction , etc).

    Sure that's true to an extent, but there are situations where two drugs will behave identically, and we can make reasonable predictions based on Structure-Activity Relationships (SAR) (for example, make inferences based on differences of only a single atom). There is a whole field of study and the pharmaceutical companies spend billions$ on this research each year.

    As I've explained, if you have two compounds that are IDENTICAL with the exception of a single halogen atom, then the PATTERN (I call it a RULE) in pharmacology is that they will be near-identical in activity and half-life (within approximately ONE order of magnitude). There are exceptions to this , but they are just that... EXCEPTIONS.

    The human body treats halogens similarly because it is the STRUCTURE OF THE COMPOUND (and the electron configuration) that determines the chemistry, not the specific atom at any specific place. Chemistry is determined by overall interactions of electrons, their structure, their density, their 'electron cloud shape' and associated probability density functions, quantum orbital structure, charge, hydrophilic/hydrophobic interactions, Van Der Waals radius in water, etc. between molecules according to QED, and at higher levels in biology , is determined by the chemistry of proteins and nucleic acids (RNA, DNA)

    On the basic level, when you have two compounds that are IDENTICAL (4-FA and 4-CA) with the exception of a SINGLE ATOM, it is reasonable to expect the pharmacology to be similar. I think it's incredibly stupid for people to be taking 4-FA, but as long as they are aware that 4-CA is a highly neurotoxic compound and still choose to risk it, then that is your decision as an individual according to principles of individual liberty.

    I have posted because I feel it is my responsibility (by nature of knowledge and position) to try to make people aware of these risks to they do not accidentally screw up their brains and regret making decisions with incomplete information.

    I am always happy to engage on a scientific level. The issue here is that of neurotoxicity and possible harm reduction of RCs.

    Politically, haven't enough people died of the Bromo-dragonFLY nonsense? Wasn't that enough of a tragedy to reconsider and take a more conservative approach to RC safety? I would say the answer is Yes.

    sh4mw0w added 87 Minutes and 27 Seconds later...

    The fluoride ion (F-) is incredibly toxic , but (as mentioned on the other 4-FA thread), when Fluorine is bound to a ring, it forms one of the strongest bonds in organic chemistry. That is, it takes a large amount of activation energy to get the fluorine off the ring (to produce the toxic fluoride ion).

    This process usually only occurs on a lab bench with reagents, and rarely occurs in the body.

    On the other hand, how 4-FA is metabolized in the human body is not known. So this is just another reason not to take it, although I highly doubt any fluoride ion is being produced in the body. Drinking water and toothpaste comprises your main exposure to fluoride (F-).

    Just as a side note, normally amphetamine is metabolized in your body by adding -OH groups to various parts of the molecule. This includes the para-position on the benzene ring, which would suggest that part of the reason 4-FA has a longer duration of action than amphetamine is that the para-fluoride halogen makes the molecule resistant to degradation by the body.

    Most likely, 4-FA is metabolized to para-fluoro-norephedrine prior to being excreted (as opposed to para-hydroxy-amphetamine and para-hydroxy-norephedrine which comprise common dextro-amphetamine metabolites in rats). Or it could result in para-fluoro benzoic acid.

    Well with any RC there is a risk, buy my firm opinion is that the risk of pentedrone is MUCH lower than the para-halogenated amphetamines.

    Pentedrone is basically a methcathinone analog. Due to the latter having an acceptable toxicity profile, I suspect the risk of pentedrone is much much more acceptable than 4-FA (or any halogen-substituted amphetamine for that matter). But my goal here really is to help people avoid poisoning themselves with idiotic RCs off the internet.
     
    Last edited: Jan 12, 2012
  5. KoBe

    KoBe Newbie

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    Re: Warning: 2-FA, 3-FA, 4-FA users risk neurotoxicity. 4-FA is likely neurotoxic.

    Hey, gotta thank you for this. I am gonna stop using this shit. Just one thing, how can you explain that one study done in rats, where serotonin levels returned back with 4FA, but didn't with 4CA and others?
     
  6. Addie Daddy

    Addie Daddy Silver Member

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    Re: Warning: 2-FA, 3-FA, 4-FA users risk neurotoxicity. 4-FA is likely neurotoxic.

    I wonder, do you have any information about the toxicity of it's likely metabolite - para-fluoro-norepinephrine?

    I'm really glad you brought this information out. My lab rat and his lab rat friends have been using 4 FA for the past few months every week or two, and last time did a long binge for the first time on it.

    My lab rats seem to be more affected, physically, by it than most things they've done. More body pains, and they're eyes were extremely sensitive to light (extreme pain upon going outside) after a 3 day bender.

    In the megathread on the fluoro-substituted amphetamines, I think there are mentions of it having little to no serotonin action. I'm not going to confirm if this was mentioned/proved or whatever in that thread, but assuming there is little to no known serotonin action, would that disprove or affect your theory about it resembling CA and damaging, mainly, serotonin neurons?

    I'm really curious to find out as much as I can. I will stop administering 4FA to my lab rats, but I am concerned about the damage that may have been done to them already. So far they haven't showed any behavioral changes, but it is definitely a concern.
     
  7. User-126494

    User-126494

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    Re: Warning: 2-FA, 3-FA, 4-FA users risk neurotoxicity. 4-FA is likely neurotoxic.

    With all due respect...

    The only facts you state are that,

    1. Cloroamphetamine and Flouroamphetamine are both halogenated amphetamines.

    2. Cloroamphetamine is used to selectively kill off serotonin neurons in mice. Seem to recall reading that the other day, but don't have the paper handy.

    3. Methamphetamine is neurotoxic, indeed in large quantities.

    However, animal studies are many times quite different from human trials. Brain chemistry can be quite different from one animal to another. It is by no means definitive proof.

    Also your statement about MDMA being neurotoxic has been called into question as of late, partially due to the fact that Richarte performed just plain bad research and dosed his research subjects with methamphetamine rather than MDMA, and passed the study off as a study of MDMA neurotoxicity. I believe funded by the NIDA or the NIH, I forget which, and it was at a time when it was the government's agenda to step up the war on drugs, so good research wasn't really called for, only research which met the objective.


    You state this, but we have no real proof of this as being true statement of fact. We must take your word on that.

    I would think that if you were a true professional pharmacologist you would be able to pay attention more to little details like sentence construction, especially with such a dire warning and would want to phrase things in the most correct manner possible in order to add to your credibility.


    All that said, let's have a look at some actual research and use of p-CA in human trials, and other halogenated amphetamines.

    Note that these were used as anti-depressants and as anorexics. The use in vivo showed "physical or psychic dependence developed, no cardiovascular complications, and no sleep or appetite problems. There was no mention made of mental disturbances that might be considered psychotomimetic."

    However, problems were found in animal studies. :However, indications of raphe-nucleus degeneration (Yunger et al., 1974) and relatedneurotoxicity (Harvey and McMaster, 1976) in experimental animals have discouraged further clinical study."

    Interesting to note that the primary reason for modifying the aromatic phenyl ring is "In the case of the simplest unsubstituted compounds such as amphetamine and methamphetamine, there was a desire to interfere with the known oxidative attack at the aromatic para position. It was hoped to create a molecule that might have some of the pharmacological virtues of amphetamine (anoxia, alerting) without the dependence problems." Essentially slowing their metabolism and reducing the desire to redose due to longer half-lives.



    Actually very few have died due to Bromo-dragonFLY. The majority of those were due to it being mislabeled and presented as something else as in the case of 2C-B-FLY and recently 2C-E.

    The interesting part here is that you initially state the the 2C-x compounds are relatively safe, as much as MDMA or perhaps more so. Very few have died from the 2C's and those can be attributed to poly drug use and in a few cases overdose. This is not neurotoxicity.

    However, if this were to make political sense Bromo-DragonFLY would be banned rather than the relatively safe 2C's or the previously banned MDMA. Politically none of it makes sense.

    A more conservative approach would be to regulate and the distribution of these chemicals in a controlled manner to those who want to use them and allow them to be monitored by a healthcare professional. This would ensure standardization of dosages, and quality control.

    Education is also a key to this as well to educate the user of the proper manner in which these substances can be used safely or with reduced harm.

    Banning them only costs more money for the enforcement of ever increasing drug laws and an ever growing bureaucracy which can't even keep up with the current challenges.

    Additionally, if these were legal and allowed to be used under medical supervision for all who would like to use them with informed consent, then we might even discover that a few of these chemicals have some real practical value.

    Your basic position can be summed up here in that you want all RC chemicals banned at all cost because you have a theory, which has not yet been backed with any evidence, studies or references. If you can provide something more than just your "opinion as a pharmacologist", then you might be able to carry a bit more credibility.

    Agreed that there are individuals who are binging on these chemicals and not using them in any form of responsible manner and are more than likely causing themselves harm and should probably cut down on their use. A very good point, but I can see nothing definitive in your "theory" or "conclusions" other than a thought experiment and your opinion.

    That was not made as a personal attack, but just pointing out the lack of any hard evidence or references.

    Be well...


    34. Benington, F., Morin, R. D., Beaton, J., Smythies, J. R., and Bradley, R. J., 1973, Comparative effects of stereoisomers of hallucinogenic amphetamines, Nature 242:185-186.

    69.
    Cohen, S., 1960, Lysergic acid diethylamide: Side effects and complications. J. Nerv. Mental. Dis. 130:30-40.

    79. De Vries, J. X., Moyna, P., Dias, V., Agurell, S., and Bruhn, J. G., 1971, Alcaloides de cactos del Uruguay, Rev. Latinoam. Quim. 2:21-23.

    80. De Zan, P., 1971, Analysis and identification of 2,5-dimethoxyamphetamine, Microgram 4:5-11
     
    Last edited: Jan 13, 2012
  8. sh4mw0w

    sh4mw0w Silver Member

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    Re: Warning: 2-FA, 3-FA, 4-FA users risk neurotoxicity. 4-FA is likely neurotoxic.

    Hey guys,

    I'm glad to see people are taking what I'm saying seriously. My goal here is to bring the evidence out into the open and encourage a discussion. After people study the information and ask questions , they will be in a position to make good decisions about whether to use 4-FA (and related compounds) or whether to abstain from them.

    I posted because I think of people are unaware of the fact that 4-CA is a potent serotonin-selective neurotoxin, and it's structure -- as I mentioned -- is very similar to 4-FA.

    I'm continuing to do more research on this, and I'll post it as I get it over the next few days and weeks.

    Regarding your questions, which are good ones:

    Okay first of all, I am just speculating on metabolites. Please don't take my pronouncements on possible metabolites to be anything more than conjecture and thinking out loud! As it turns out, that metabolite if it exists, likely only exists in rats.

    It's very difficult to correctly analyze metabolites because they vary significantly from rats, to guinea pigs , to humans. All creatures metabolize drugs differently, so you can't necessarily extrapolate results from rats to humans.

    In rats, amphetamine is metabolized to something called para-fluoro-norephedrine. In guinea pigs (and I believe humans) it's metabolized to benzoic acid.

    I was just speculating on a hypothetical metabolite, based on rat metabolism, which is called para-fluoro-norephedrine (not norepinephrine). I don't have any information on it at the moment.

    Here's what we know based on amphetamine metabolism...


    [​IMG]
    Para-hydroxy-norephedrine: A standard amphetamine metabolite in rats


    [​IMG]
    Benzoic Acid: A standard amphetamine metabolite in guinea pigs (and humans).


    Anyway, based on the rat metabolite, I speculated that 4-FA might be metabolized to a similar compound -- para-fluoro-norephedrine. This is a compound that I considered as a plausible 4-FA metabolite, but I have no evidence it exists in the body. It probably only exists in rats if it exists anywhere.

    [​IMG]
    Para-fluoro-norephedrine: Hypothetical 4-FA metabolite. Unknown if exists in body, unkown toxicity. Probably only exists in rats if it exists at all.


    As for what 4-FA is metabolized into in the body, (which is believe is your actual question) , the answer is that I don't know for sure. What is most likely is that 4-FA is metabolized to a para-fluoridated benzoic acid . But this is speculation as well .

    ::
    ::

    Well glad to hear it as well. I've done stupid things in the past that have probably burned out some of my neurons, but you just have to learn from your mistakes and keep on .
    ::
    ::
    That's unfortunate... what sort of doses were you doing? The toxic dose of 4-CA in rats is approximately 15mg/kg via I.P. injection.

    Let's assume that 4-CA is dose equivilant via I.P. and P.O. (oral) ... if this is the case, then the toxic dose for 4-FA for a 65kg human is approximately 975mg

    This math actually works out in everyone's favor, because we know that 4-FA is nowhere near as toxic as 4-CA. Assuming this 'back of the envelope' math, the real danger zone starts at around 1000mg of 4-FA.

    Now, this could be way off. 4-FA could be neurotoxic at 100mg or less, or it could be neurotoxic at 5000mg or more. There is no way to know without more studies, particularly ones in guinea pigs or primates.
    Here's the details from the study I found.​
    ::
    ::
    ::
    This really depends on the receptor binding affinities and the mechanism of toxicity. If the mechanism of toxicity is the generation of Reactive Oxygen Species (ROS) which are somehow getting in the cell bodies, this may not be exclusive to 4-FA.

    Regardless, this is skating on thin ice. I would not base my health on this assumption; I think it's much too risky and the research is incomplete.

    You are right , though, in the sense that there is an outside chance that the toxicity of 4-FA is relatively low compared to the active dose. I don't doubt, however, that there exists a neurotoxic dose of 4-FA, even it might be measured in grams. The risk is that the toxic dose might be lower than we think.
    I'm planning on going back and getting a copy of Nichols' study to see what specifically is different regarding 4-FA, but honestly, it can't be -that- different. Receptor affinities might change by an order of magnitude, but they aren't going to go to zero from a halogen substitution. Thus, these properties might make 4-FA 10x less toxic, 100x less toxic, or 1000x less toxic than 4-CA, but the fact remains that it is probably still neurotoxic at some level.

    If someone is abusing 4-FA to the point they are doing more than 0.5g per day, via mechanisms of dependence and tolerance, it could relatively easy to reach the neurotoxic threshold of 4-FA, where ever that may be.

    Unlike cocaine , which has high abuse liability, moderate cardiac toxicity, yet low neurotoxicitiy, 4-FA is unlikely to be as forgiving as cocaine or amphetamine.
    ::
    ::
    ::
    Well, you are lucky in the sense that the rough (conservative) calculation shows that 4-CA equivalent toxicity would start in the 500mg to 1000mg and higher level of dosing, and the neurotoxicity threshold of 4-FA could be significantly higher. Most people are doing less than that.

    But of course, neurotoxins are dose-dependent and exposure-dependent. Obviously 4-FA is not as toxic as MPTP otherwise we'd see 24 year olds with some wierd serotonin-version of Parkinsons. The risk is that this is something more subtle or something which is cumulative. You do not want to be the person who discovers that 4-FA is toxic after developing a daily habit for 10 years.

    You will probably be fine if your use was moderate and short term. The brain has a remarkable ability to recover as long as it's damage control systems are not overwhelmed (as is the case with the more severe neurotoxins like MPTP).
    Just stay off the 4-FA and related halogenated amphetamine crap. You are much safer with more conventional stimulants with proven track record and more reasonable (and known/studied) toxicity profiles.

    So don't worry too much if you feel okay now; just stay away from it unless you are certain it's not toxic. I suspect it's toxic like its cousin 4-CA, that's why I'm warning people to avoid it. Hell even cocaine is safer.
    ::
    ::


    Sure. I've only read excerpts of the study. It is on my reading list.

    However, I'd be delighted to speculate!

    What probably is going on is that 4-FA is probably some multiple, possibly an order of magnitude LESS TOXIC than 4CA.

    Thus, if 4-CA is irreversibly neurotoxic to humans at 100mg orally, 4-FA might be irreversibly neurotoxic to humans at 1g... or 5g .... or 10g....

    ...or at 1g/day administered for 90 days...

    ...or at 100mg/day administered for 2 years....


    See what I'm getting at?

    The reason it didn't show up in the study is for a number of reasons, but primarily that 4-FA might just be LESS TOXIC such that it did damage to the neurons, but not at a level to induce apoptosis. The actual neurotoxic effects of 4-FA might not show up until longer, higher-dose , repeated dosings occurred.

    Other reasons might include: The study was in a lab animal with different metabolism than humans, the study was short-term (not intermediate or long term), the study didn't study 'abuse' dosing patterns, the study didn't study dose-escalation due to tolerance, etc.

    There is an outside possiblity that 4-FA is completely safe, but I think this is unlikely, and I would be unwilling to bet my health on this possibility. I think it's more likely that it is just LESS TOXIC than 4-CA due to its different receptor binding affinities and different pharmacological profile.

    The reason I am posting is that I have my doubts that 4-FA is different enough from 4-CA to avoid the issue of neurotoxicity entirely. The one saving grace is that we can hope that the toxicity threshold for 4-FA is 100x higher than 4-CA, and that is what has spared users so far from any severe effects.

    But that is not a license to keep using it, that's incentive to stop using it and find a better replacement! Even dextro-amphetamine is safer than 4-FA. So is cocaine for that matter. Both are well known in their profiles and toxicity , and these properties can be managed. With the latter compounds, the risk is tolerance/addiction, which I think is much better situation than risking possible neurotoxicity.




    sh4mw0w added 39 Minutes and 46 Seconds later...

    With all due respect,

    I stated plenty of facts with plenty of reasoning by analogy.

    This is a form of inductive reasoning.

    If you cannot understand this, that is certainly unfortunate, but I don't have the time to engage you in an argument about what constitutes valid reasoning and what does not.

    Did you come here for a title match on who's top pharmacologist?

    If so you're on the wrong thread. This is a harm reduction thread.

    I know a lot of people here like to play armchair scientist, but don't actually
    know anything. That seems to be the case here. That's pretty sad. People's minds and health are at stake, and you are acting like a spoiled young college student.

    I came here to warn people about frying their minds (or worse) on RCs.
    MDMA is neurotoxic due to the 5-HT reuptake pump taking up dopamine ROS. This is a well established fact, and I don't understand what that has to do with 4-FA, which is a completely unrelated compound.

    Regarding, Ricaurte and his 'mix-up' with the bottle of methamphetamine and the bottle of MDMA, I know all about that. Some people think it was accidental, some people think it was intentional. My friends and I discussed it over lunch at the NIH complex in Building 50 at Bethesda MD.

    But That has NOTHING to do with this topic. Again , if you are coming here to try to show off, you've come to the wrong place. Not much impresses me besides honesty and integrity -- something which based on reading your responses, you lack.

    By the way, his name is spelled Ricaurte , not Richarte.


    You're wrong. I've provided plenty of evidence which can be critiqued scientifically -- it's just you don't have the capability to do it. I'm sorry you are unable to -- I know you want to criticize -- unfortunately, based on your responses, it's clear to me that your knowledge is not up to par to be able to respond with coherent thoughts of your own and to stay on topic. I know that's hard for someone with such a narcissistic personality complex such as yourself to be wrong. Perhaps talk to your therapist?

    I don't care whether you believe it or not.

    I came here to warn people about 4-FA so they can protect their health. Why did you come here for?

    Haha I've written many pages of original material tonight to protect people's health. This is a site called Drugs Forum.com , not the academic journal Virology . I know you don't have any papers published though ,so I won't expect you to know that either!

    I'd think someone as yourself claiming such holier-than-thou high ground would pay more attention to the morality of this situation, such that you'd be concerned with people's health and well-being, and their right to avoid being hurt or damaged due to lack of information . On the other hand,it seems you came you due to some ulterior psychological need, as you have offered absolutely ZERO information to contribute to the scientific discussion (besides a weak block quote, which we will get to in a minute)

    If you believe so strongly that 4-FA is safe (although you apparently don't have the courage to come out and make this claim) , will you volunteer to conduct the first controlled human trials? Will you take a dose of 1g / day for 365 days, undergoing fMRI and PET scans before and after, so we can see how brain blood flow and glucose utilization change after exposure to 4-FA?

    I highly doubt you would take this offer up if it were available, as it's clear you are not interested in the scientific process, but rather are a critic from the far reaches of the internet that does not have the health of the public in mind.

    Unlike you, I care about people who are taking 4-FA. This is not a game to me.




    Oh wow , you've pasted me a NIDA monograph from 1993. Great.

    It's obvious that you are unable to engage in a scientific argument about the facts, so instead, you dump a big block quote from a literature review.
    That is in your block quote. "Potent and Long-lasting depletion of serotonin" . This is evidence of toxicity. In higher doses , this will invariably induce apoptosis. You can look the word 'apoptosis' up at Wikipedia if you need to.

    Are you kidding ? There have been a handful of really violent, painful, awful, and unnecessary deaths.

    Are you really that callous and insensitive to the families of the dead? You must be a college kid enamored with psychadelics to talk like this. Why don't you go meet the families of the 22 year olds who met horrible , painful , violent deaths due to drug toxicity, then come backhere and tell us all how great and safe Bromo-dragonFLY is. Jesus.

    This has NOTHING to do with the thread. This is a thread about 4-FA pharmacology and possible toxicity, not politics.


    What on earth are you talking about! Are you brain damaged? You are talking absolute incoherent nonsense. I said NOTHING about banning RCs. I am encouraging people not to consume a potentially toxic subclass of research chemicals.

    I suggest you get out your reading glasses and review the many pages I've written so far -- which are absolutely FILLED with references, structures, and diagrams. For your information, I am a supporter of drug decriminalization. My approach here is harm reduction. You are absolutely ridiculous, and as far as I'm concerned you have absolutely zero credibility. Lol hillarious I regret wasting time on you.
    I provided plenty of evidence. But apparently, based on what you've written, you just can't understand it.

    That's unfortunate, but somebody's got to flip the burgers! Lol I'm looking forward to a real scientific response from someone who has not fried themselves on 2c-t-7 . Lol
     
    Last edited: Jan 12, 2012
  9. kailey_elise

    kailey_elise Gold Member

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    Re: Warning: 2-FA, 3-FA, 4-FA users risk neurotoxicity. 4-FA is likely neurotoxic.

    That's great that you are an NIH pharmacologist, but we have no way of knowing that. Even if you gave us your real name & all, we have no way of knowing if the name you gave us to research is really *your* name, know what I mean?

    Generally (not everyone, surely), people who feel the need to state, in every post, 'I'm a XYZ, so what *I* say is important' have some issue that they are trying to fulfill. As I said, not everyone, of course. But if the research is good, the work can speak for itself, kwim? :)

    We've had issues with alleged professionals over the years (alleged, only because there's no real way for us to verify who is really a professional via an internet forum). In fact, we just recently had an issue with someone who stated they were, in fact, a professional (doctor, I believe), who clearly wasn't, because not only did the story keep changing, but s/he could barely form a coherent sentence, and got some fairly basic stuff incorrect.

    Anyway, people tend to go on 'alert' when someone repeatedly mentions they are a professional, because of past issues. If someone says 'I think ABC, and I'm a doctor', there are people out there who will give more weight to their statements because they think they are coming from 'one who knows' - but we have no idea if they really know what they say they know, know what I mean? ;)

    Very interesting information brought up here; I hope to have a chance to read through it again more carefully & to be able to read the sources & such as well, very soon. Thanks for bringing this to the attention of the community.

    All the best,

    ~Kailey
     
  10. User-126494

    User-126494

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    Re: Warning: 2-FA, 3-FA, 4-FA users risk neurotoxicity. 4-FA is likely neurotoxic.

    You have presented some commonly known facts, but no hard evidence by means of research studies and scientific evidence with references.

    "Facts" by reason of analogy are nothing more than speculation unless there is empirical evidence to back them up. Otherwise it's merely a thought experiment, and will not necessarily hold up to scientific method and be observable through experimentation as well as verified by peer review.

    Now, now, let's not go to name calling. I have made no claims to my credentials, haven't name dropped, or anything else to fluff up the appearance of something I am not, nor pretend to be.

    As far as harm reduction, I don't think anyone here is against that. Far be it from me to not promote harm reduction, my reputation and post history will attest to my dedication to harm reduction.

    Harm reduction, again, is a noble endeavor, and most are aware if the inherent risks of experimenting with RC's.

    EDIT: Actually, it's not oxidative stress on the re-uptake pump, this never factors in, it's oxidative stress caused by hydroxides formed following reductive oxidation of dopamine by MAO-A and MAO-B into 3,4-Dihydroxyphenylacetic acid and binding to the 5-HT receptors, effectively burning them out.

    You actually brought the subject up in your OP:

    By the way, could you please explain what your work as a bioinformatics researcher has to do with pharmacological and metabolism studies? Just curious how it fits in, I'm interested in this area, though work with bioinformatics as a means of positive identification of individuals through various observable characteristics. As I say, just curious how the pharmacology fits in with being a bioinformatics researcher, it's an interesting field and perhaps you have some other aspect you are studying which I am not aware of.

    Name dropping again in an attempt to emphasize your credibility, but it really means nothing. I am perfectly able to pull names, dates, and locations into my posts, but it means little.

    Well, actually it does have something to do with the subject. It's bad science whether it was intentional or accidental. The study should never have been published but he went ahead and did so with the knowledge that his research was fraudulent.

    There has been a recent study from 26 October 2010 which calls the neurotoxicity of MDMA into question here:

    Residual neurocognitive features of long-term ecstasy users with minimal exposure to other drugs.

    A rather unique and interesting study given the population in the study were all from Salt Lake City, Utah. Also some real research is being done by people like Dr David Nichols at Purdue and the people at MAPS, to create unbiased studies on psychoactives which should have been done long ago. But due to political and legal issues has been impossible to conduct.

    Real research, not thought experiments and inductive reasoning. Granted that's how one comes out with a theory, but it must hold up to research, experimental proof and peer review.

    Sorry, my bad, typo. The hour was late and the "H" key is in close proximity to the "U" key and I've never learned to touch type. Thank you for correcting my misspelling.

    Well, now who's making personal attacks here?

    Actually, I would have pulled out more research and references, but it was late and I was tired and didn't have the time to pull everything together. However I wanted to write some response. Mostly due to your lack of providing evidence and research.

    I never stated that 4-FA was without risk. Just found in a number of places that it didn't appear nearly as risky as you are sounding the alarm without anything particularly substantial to back it up with, again other than your admitted speculation, thought experiments and inductive reasoning.

    The passage I quoted actually was speaking of human trials and showed that halogenated amphetamines have been shown effective with minimal risk and given in chronic doses of 75-90mg to participants for a period of up to a year.

    It related to actual human studies, with an aside that there had been issues discovered with the neurons in the "raphe-nucleus degeneration (Yunger et al., 1974) and related neurotoxicity (Harvey and McMaster, 1976) in experimental animals have discouraged further clinical study." Further, animal studies are not necessarily relevant, because the metabolism, brain structure, and neurotransmitters do not always correspond to how drugs will interact pharmacologically in humans. That's not to say that animal studies aren't valuable.

    It wasn't an NIDA monograph, it was from Chapter 6 in Handbook of Psychopharmacology, Volume 11: Stimulants, Shulgin, Alexander T.,Plenum Press, New York 1978. I also included the references cited in the passage, so it's not something random I just puled out of the air.

    And you've quoted an abstract from a research paper which was accepted 3 February 1987.

    I've searched the archive here and the complete paper is not available, but I've made a request for it so we can all have a look.

    Also, the abstract you included is another animal study too, not that that really matters, it's still worth a look.

    Again, see above, it's not a block of text from a literature review, unlike copying and pasting a research paper abstract and calling it a reference.

    But, "potent and long-lasting depletion of serotonin", which was taken out of context here refers to 4-CMA, which according to the publication seems to fit the same profile of 4-FA as Amphetamine does to Methamphetamine.

    The phrase "potent and long-lasting depletion of serotonin" in and of itself dose in no way imply neurotoxicity, nor does the passage qualify the length of time for what they refer to as "long lasting". For that matter MDMA produces potent and long-lasting serotonin depletion, many other things do as well, but they are not necessarily more or less neurotoxic than one another. Serotonin depletion is just one small part of the picture when it comes to neurotoxicity.

    I don't disagree that they have the potential to be neurotoxic, but it is a matter of dose and frequency. Both amphetamine and methamphetamine are approved psychiatric medications for the treatment of various disorders, most commonly ADD and ADHD as well as treatment resistant depression.

    How many deaths have been attributed to Bromo-dragonFLY over the past 10 years? I believe the number is less than 10. Compared to aspirin or prescription pharmaceuticals, that's quite small. I'm not sure that all the deaths attributable to prescription pharmaceuticals weren't "violent, painful, awful and unnecessary."

    The Bromo-dragonFLY deaths were, of course a tragedy due to numerous mistakes and there's plenty of blame to go around. It has been discussed in these forums many times, and I've even written about it. I in no way minimize the pain the families feel for their tragic losses, but they were completely avoidable.

    If you actually read what I wrote, I stated that it was ironic that the 2C's are up for legislative action while more harmful substances like Bromo-dragonFLY are not even on the list.

    Personally, I've never taken 2C-T-7, and I'm happy to overlook the personal attacks and sarcasm.

    But all you seem to do here is rant, and offer little if any evidence which can be verified. Also to point out quoting you above, you're the one who brought up politics and I was just responding to your statement.

    So far I can agree with you and I do see lots of pretty pictures, but only one cited reference. I'll agree with you that there is potential for neurotoxicity for the halogenated amphetamines, just like with amphetamine and methamphetamine. In fact, there is probably enough to conjecture that the potential is higher, again along with dosage and frequency of use and given that the reason they are halogenated on the aromatic phenyl ring is to slow down the metabolic breakdown of these chemicals and increase the half-life and thereby reduce the potential for addiction.

    Be well...
     
    Last edited: Jan 13, 2012
  11. snarkymalarky

    snarkymalarky

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    Re: Warning: 2-FA, 3-FA, 4-FA users risk neurotoxicity. 4-FA is likely neurotoxic.

    sh4mw0w,

    thanks for taking the time to carefully explain your concern. you clearly understand the subject matter and have thought out your position. i've taken approximately 500 mg total of 4-fa over the past few months, so i'm interested in this issue greatly. i've enjoyed the compound but it's certainly not worth any serious damage.

    i do have a few questions though:

    i think it's pretty clear that 4-fa has the potential for serious neurotoxicity, but so do dextroamphetamine, methamphetamine, etc. no one is under the impression that these drugs are completely safe. the question, then, is dose --the idea that 1g or 10g of 4-fa could be seriously toxic doesn't say much to me about the toxicity of a typical recreational dose because everything is toxic if taken in large enough quantities and everything is benign if taken in small enough amounts. i wouldn't want to take 10g of dextroamphetamine either, but this doesn't stop me from taking smaller amounts...

    is there any reason to be worried about low doses (say, under 100mg) of 4-fa other than the fact that we don't really know what the toxic doses are because of lack of study? i'm wondering if your concern is merely coming from a "better safe than sorry" point of view, or if you have positive reasons to think that a low dose of 4-fa would be substantially more toxic than a similar dose of dextroamphetamine? would it actually be harmful to take a low dose of 4-ca, one well under the 15mg/kg threshold for toxicity you mentioned, like 50 mg? i'm trying to put these neurotoxicity claims into context. how far below the toxicity threshold should one be to safely ingest a substance?

    suppose 4-fa is just as toxic, or even more so, than 4-ca and that i've caused myself brain damage through abuse -- what would the symptoms be? how would i know? would this cause a noticeable difference in cognitive functioning, or would it be more similar to small amounts of brain damage we all experience every day from radiation, pollution, chemicals in foods, more common recreational drugs, etc? are there any symptoms 4-fa users should be looking out for?

    thanks for sharing your concerns with DF. i have no way of knowing if you're really a pharmacologist since people on the internet can say anything they want, but you do appear to have more background knowledge and better reasoning skills than many. i'm sorry that some people have found your criticism threatening and i hope you continue to contribute.
     
    Last edited: Jan 12, 2012
  12. kailey_elise

    kailey_elise Gold Member

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    Re: Warning: 2-FA, 3-FA, 4-FA users risk neurotoxicity. 4-FA is likely neurotoxic.

    I just want to say that I don't think anyone has found the criticism to be 'threatening' at all. There have been no personal attacks towards the OP, just the typical questions that get asked when people post as facts. That people question is in NO manner a bad thing - it's how we learn, how we suss out information, how we develop better theories & come up with more/better questions to ask, so that we can then go do studies that address these questions to come up with pertinent facts. :)

    The discussion of various points brought up in ANY thread on ANY subject here on d-f is typical & common & I thought encouraged. Information is greatly appreciated, and source material to back up your claims is preferred, so that others might look up where we got the information to form our theories from, to see if we too come up with the same conclusions. If not, we should question each other to get a better handle/idea/whatever on the subject.

    All the best,

    ~Kailey
     
  13. snarkymalarky

    snarkymalarky

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    Re: Warning: 2-FA, 3-FA, 4-FA users risk neurotoxicity. 4-FA is likely neurotoxic.

    I did some reading on this topic and I thought I'd share some points that stood out to me.

    The paper was "Psychostimulant-like effects of*p-fluoroamphetamine in the rat" by Danuta Marona-Lewicka, Gyu-Seek Rhee, Jon E. Sprague, David E. Nichols. European Journal of Pharmacology, Volume 287, Issue 2, 12 December 1995, Pages 105–113.

    http://www.sciencedirect.com/science/article/pii/0014299995004785

    Unfortunately I'm having trouble saving the file as a pdf so I can upload it.

    While I'll admit that I don't have enough expertise to interpret all the technical information here, I do think that these passages make it clear that there are substantial differences in the ways 4-CA and 4-FA affect the body. Whether or not 4-FA is different from 4-CA in a way that makes it substantially safer is still unclear to me though.

    To me, this suggest that 4-FA does not have the long term serotonin depleting effects as 4-CA, insofar as these studies are trustworthy.

    Not clear to me how MAO inhibition directly affects neurotoxicity, but this does say that 4-IA has much weaker serotonergic neurotoxic properties than 4-CA, in spite of the only difference between the two compounds being a single atom. 4-IA is different than 4-FA, but this does serve as a counterexample to the general claim that different halogens are mostly identical in terms of neurotoxicity. Of course 4-FA could still be neurotoxic for other reasons, but I don't think its similarity to 4-CA is a sufficient reason to jump to this conclusion.

    So 4-FA and 4-CA affect adrenocortical activity as well as 5-HT activity through different mechanisms. Perhaps the mechanisms of 4-FA are less harmful?

    Distinct, yes. Toxic in it's own right? Still inconclusive.

    So the para-subsituents [F,C,I, etc.] have very different effects on monoamine uptake. Perhaps the small difference of one atom in the molecule does make a bigger difference in the effects of the molecule.

    Again, I don't think any of this constitutes solid proof that 4-FA is safe enough to be used recreationally, but I think this does establish that the molecular similarity between 4-FA and 4-CA doesn't necessarily mean much either. I think it also suggests that 4-FA is safer than 4-CA, although how much safer is still unclear.
     
    Last edited: Jan 12, 2012
  14. snarkymalarky

    snarkymalarky

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    Re: Warning: 2-FA, 3-FA, 4-FA users risk neurotoxicity. 4-FA is likely neurotoxic.

    Here's some more homework.

    Neuropharmacology. 1975, 14. 739-746. Pergamon Press. Printed in Gt. Brrtain.

    COMPARISON OF 4-CHLORO-, 4-BROMO- AND 4-FLUOROAMPHETAMINE IN RATS: DRUG LEVELS IN BRAIN AND EFFECTS ON BRAIN SEROTONIN METABOLISM

    R. W. FULLER, J. C. BAKER, K. W. PERRY and B. B. M~LLOY
    The Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46206

    Paper attached this time

    EDIT: Added to archive. http://www.drugs-forum.com/forum/local_links.php?action=ratelink&catid=35&linkid=11303

    So 4-FA doesn't deplete serotonin long term.

    Again, these are substantial differences between 4-FA and the other halogenated amphetamines. It's still not clear just how safe 4-FA is, and it could indeed be unsafe, but the similarities to 4-CA aren't necessarily cause for alarm on their own.
     
    Last edited: Jan 13, 2012
  15. User-126494

    User-126494

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    Re: Warning: 2-FA, 3-FA, 4-FA users risk neurotoxicity. 4-FA is likely neurotoxic.

    Thanks snarky, other than the hamster's second post, he hasn't had enough time today to continue to do in-depth research on the subject matter. Looks like some good material to pour over there.

    Do you think you could put in a request into the "Help from Medline Thread" to get the article you couldn't download? One of the fine critters who monitors that thread will be happy to help, no doubt.

    Also, could you upload the document attachment in the above post to the archive? If you have a problem, just holler.

    Be well...
     
  16. NeuroChi

    NeuroChi is not his mind Staff Member

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    Re: Warning: 2-FA, 3-FA, 4-FA users risk neurotoxicity. 4-FA is likely neurotoxic.



    Psychostimulant-like effects of p-fluoroamphetamine in the rat
     
  17. smogzahoy

    smogzahoy

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    I am also having a hard time believing whole heatedly what is said in this thread. It seems like the OP is stating an opinion and providing loosely correlated information as a backing for his points. Not only was I a bit befuddled while following the OP's points I also reflected back on SWIM's prior use (about 4-5 grams in the past 6-7 months) and concluded that SWIM has experienced no side effects, cognitive or otherwise. I hope this reply doesn't come of as condescending I just have a hard time truly believing the points that the OP brought up.
     
  18. C0nstanc3NF0rtitud3

    C0nstanc3NF0rtitud3

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    Re: Warning: 2-FA, 3-FA, 4-FA users risk neurotoxicity. 4-FA is likely neurotoxic.

    I think the OP has brought some genuine concerns to light, it's just unfortunate that he felt the need to use uncalled for, burger flipping, ad-hominim attacks, which may ultimately weaken his argument and be counter-productive to his intentions.
    In general, the people he is trying to reach with these warnings do not have the necessary skills and understanding to read the science and many, not understanding rigorous debate, will see this as an argument with a "winner" and a "loser" and as said, ad-hominem attacks really do not help and when taken in the context of this discussion, may lead some people to believe that the OP lost the argument and was "wrong", which from what I can understand is not the case, as it seems there are valid points raised by the OP.

    Just a small point, wanderer, (in the spirit of balance :p )
    Sorry, while I'm not making any claim either way and don't have the figures to hand, you just can't link these death rates in this manner.
    As I'm sure you know, you need to look at the case fatality rate, the ratio of deaths per specific user group of each substance, i.e like for like.
    And actually the numbers of worldwide accidental deaths for both aspirin and paracetamol are quite low, (although this is a very tricky area to get accurate figures for, due to the stigma attached to deliberate overdose).
     
  19. User-126494

    User-126494

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    Re: Warning: 2-FA, 3-FA, 4-FA users risk neurotoxicity. 4-FA is likely neurotoxic.

    Valid points, however, one does not start out claiming to be something they are not or are possibly that they are not. The first thing stated:

    This immediately raised alarm bells. Took a look at his profile, as many others following this thread have done, and it states that his profession is "IT".

    I don't claim to be a doctor, though I do have an active interest in medicine and try to stay up-to-date with research. If that makes me an "armchair pharmacologist" then call me guilty.

    But I do stay on top of things, and research thoroughly. I also ask questions when 'm not sure of something, and get helpful answers. I'm also quite willing to go back and correct a post where I've accidentally put incorrect information and have happily admitted being wrong. After all, the OP did ask why I was here, and I guess the answer to that is to learn, share knowledge, and keep from spreading rumor, false claims, and myths. The bottom line is to work with the facts and the facts are what matters most other than conjecture, opinion and at the end of the day, most who are here and have stuck around contributing have managed to establish a reputation with the others who come here. Every one of the long-time high ranking members all have the interest of maintaining everything as factual as possible with the highest standards of integrity.

    Absolutely agree with you here. I've also never taken the position counter to the possibility of these being neurotoxic, on the contrary I've stated in the posts that indeed there may be some concerns. I found research that indeed showed these halogenated amphetamines and methamphetamines have been used in human research and at therapeutic doses over a period of time don't appear to show any adverse effects or ones which are not minimal and subject to complete reversal.

    That's not to say that recreational doses, which are typically higher than a therapeutic dose, and frequency of use are not factor for concern and users should be warned, however, there's been no evidence so far presented which can state these compounds are any more harmful than their non-halogenated counterparts are.

    I think snarkymalarky's first post in this thread outlined all the salient points quite well.

    He then went on to do some very thorough research to determine whether or not there were answers to the questions he proposed, and did an excellent job of finding some excellent information.

    I think this is true of the community in general here and the members here try to raise the bar for knowledge and accuracy compared to other sites. The members here also come from a diverse set of backgrounds and all walks of life and experiences. Well above and beyond your typical site who's typical post is something along the lines of:

    Not that there aren't posts like this from time to time, but they are generally the exception rather than the rule, and those who post like this are typically weeded out by the mods and staff, or other members.

    Fair enough. ;)

    I can stand to get called on the carpet for making claims off the top of my head, but I actually do have the data around here because I have researched it and posted it here before and promise to make a follow-up post with that as soon as I can collect it, I promise later today.

    But back on topic and back to your opening statement, "may lead some people to believe that the OP lost the argument and was "wrong", which from what I can understand is not the case, as it seems there are valid points raised by the OP."

    I don't think anyone has disagreed with the point that there may be the potential for neurotoxicity in these halogenated amphetamine analogs, but there are many questions, and just shouting fire in a crowded theater in unacceptable when there is no evidence to shout fire.

    Any rodent, hamster, labrat, or other critter who decides to do research on these or any "research chemicals" should do their homework and understand the risks and potential harms involved. After all, if everything were known about them, they wouldn't be called "research chemicals" would they?

    Be well...
     
    Last edited: Feb 7, 2012
  20. GermanTank

    GermanTank Newbie

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    I appreciate the information that is presented here. Can you extrapolate this information for 2FMA......which is relatively new to the scene...or 4FMA which has more wide use...
    Are there any animal studies with 2FMA?