4-FA || Fluoroamphetamine

History

It first began appearing in the early to mid 2000s, and started seeing common usage a few years ago. Colloquial names include “Gentleman’s Speed” and “Flux”. It has shown up in certain circles in North America, but with more widespread adoption in Europe, especially the Netherlands. It is also sometimes sold as MDMA. 4-FA is a new psychoactive substance, and there is still much unknown about its long term effects, and lot of the knowledge of its effects so far is anecdotal. Therefore, one must be aware that they are a guinea pig when taking this substance. Despite the unknowns, there are some things that are known about the effects of this substance and with this knowledge, harm reduction measures can be practiced!

Chemistry

4-FA or 4-Fluoroamphetamine, or if you wanna get even more nerdy about it, 4-Flouroalphamethylphenethylamine, is a stimulant drug that has some entactogenic (huggy/lovey) effects. It belongs to the chemical class of substituted amphetamines, a sub-category of the substituted phenethylamine class. Chemically, it differs from amphetamine only by a flourine atom substitution at the 4 position of the phenethylamine backbone’s benzene ring. This is fancy talk for “4-FA is only one flourine atom different from amphetamine”. 4-FA can be identified with a sky blue reaction on the Mandelin reagent, orange with the Liebermann reagent.

Pharmacology

4-FA acts as a releasing agent and reuptake inhibitor for serotonin, dopamine, and norepinephrine. This means that these neurotransmitters get both pushed out of the presynaptic neuron into the synaptic cleft, where they activate the corresponding receptors on the post-synaptic neuron, and they are also being blocked from being taken back up to the presynaptic neuron by the drug molecule’s affinity to the transporter proteins on the reuptake pump of the presynaptic neuron, causing these neurotransmitters to activate the receptors to a much greater extent than usual. Essentially, they are pushed out and blocked from being re-used. The way in which it compares to MDMA and amphetamine is that MDMA mostly acts as a releasing agent and reuptake inhibitor for serotonin, while amphetamine acts mostly as a releasing agent and reuptake inhibitor for dopamine and norepinephrine, so 4-FA is kind of a mixture of all three. Although MDMA also acts as a serotonin, dopamine, and norepinephrine releaser, it is much more focused on serotonin than the other two, and amphetamine more focused on dopamine and norepinephrine, with 4-FA being a more even balance in its releasing and re-uptake inhibition of either three. [1]

Thus, it is speculated that 4-FA acting as a releasing agent for three neurotransmitters with a more balanced extent among the three may be the reason for its subjective effects that are somewhere in between amphetamine and MDMA- dopamine and norepinephrine releasing agents are generally more “speedy” and serotonin releasing agents are generally more empathogenic. However, the exact nuances of how pharmacological differences correspond to subjective differences remains speculative

4fa pharmacology.png

Subjective Effects

The character of the 4-FA experiences is usually described as less overtly stimulating than speed or coke, and less “lovey” than MDMA (you might not be asking to pet a strangers hair while waiting in the bathroom line for example – but you still might). Eye wiggles, or nystagmus, can occur at higher doses and many of its effects and side effects are similar to speed and MDMA. It generally presents a biphasic pattern of subjective effects where the first three to four hours feature some of the empathogenic effects of MDMA, although not as highly pronounced and to the extent of being a highly spiritual experience as it may be with MDMA, and is generally more of a “party drug” nature compared to the very poignant, emotionally stirring, and soul revealing feelings experienced on MDMA, with the offset of the experience presenting with a milder feeling dextramphetamine like stimulation.

It should be noted that since adulteration of MDMA has become so widespread, many people do not really know what pure MDMA feels like and the more stimulating “party” style of empathogenic effects may be favoured by some partiers, especially if 4-FA is being sold as MDMA and the person doesn’t know they are taking 4-FA. Pure MDMA, which is quite rare these days, tends to be more of a poignant soul searching type experience where you pretty much become a saint for 6 hours (which is why a Catholic priest who tried it back in the day gave it the nickname “ecstasy”) but it also is less stimulating and doesn’t provide as much energy for dancing as might be usually expected for some.

4-FA is still lovey dovey but in a more fun, hedonistic, and hyped up way, similar to how most adulerated M is like these days. The four hours of the more stimulating and partyish empathogenic phase of effects is followed by a dextroamphetamine like stimulation within the following four hours, but of a generally “smoother” or more encouraged nature compared to dextroamphetamine. It is known colloquially as “Gentleman’s Speed” for this reason.

Despite the cute nickname and more agreeable subjective effects, it should be noted that all the usual harm reduction strategies that apply to other amphetamines as well as MDMA, apply to 4-FA.

Comparison of Subjective Effects Between Amphetamine, 4-FA, and MDMA

Amphetamine

4-FA

MDMA

Most stimulating, with stimulation feeling harsh or forced in mid to high doses, making it difficult to unwind

Prominent stimulant effects, enhances energy for activities like dancing, but feels more controllable and easier to unwind than amphetamine

Has some stimulating effects that promote dancing, but mild enough that one does not feel too antsy for chill activities like cuddle puddles, and with a distinct anxiety reduction effect that promotes unwinding rather than inhibits unwinding  

Sociability enhancement tends to be based on feelings of ego inflation- social effects result from confidence enhancement. Confidence enhancement may turn to paranoia with high dose/repeated use.  

Aspects of both ego softening and ego inflation. The sociability enhancement is warmer than amphetamine and has some empathogenic effects, but not to an entheogenic (aka catalyzing spiritual experiences) extent

Sociability enhancement is based on feelings of ego softening. Immense feelings of unity, love, and trust that may lead to deep bonds and spiritual experiences. The euphoria is often of a profound nature.

Minimal sensory enhancement relative to stimulation

Minimal sensory enhancement relative to stimulation

Pronounced sensory enhancment- music sounds better than ever, touch feels magical, extreme urge to cuddle

Tendency for compulsive redosing

Tendency for compulsive redosing

Lower rate of compulsive redosing compared to amphetamine or 4-FA

Harsh come-down

Moderate harsh come-down

Softest come-down of the three

Does not feature emotional catharisis

Does not feature emotional catharisis

Ability to induce emotionally cathartic experiences in the right setting

Dosage and Duration

Dosage is usually similar to MDMA, about 80-120 mg or a mostly full small (size 4) capsule, depending on the consistency of the powder. If one is eyeballing this substance, it is recommended to take a few sprinkles, wait for the little bit to take effect, and stagger it out based on how the starter dose feels. Volumetric Liquid Dosing is one way to accurately measure milligram amounts.

Doses between 20mg and 80mg produce effects similar to about 10-40mg of dextroamphetamine, but with a generally more encouraged stimulation that doesn’t feel as harsh, speedy, or tweaky as dextroamphetamine.

The oral onset time is about 30-60 minutes, with a 45-90 minute come-up, which is more gradual than dextroamphetamine, and especially MDMA. MDMA is well known for having a fast onset where one goes from feeling nothing to rolling balls between the 40 minute mark to the 60 minute mark, which is not the case with the more gradual come up of 4-FA. It peaks at about 2 hours after dosing, with effects staying close to peak between 3-6 hours, and about a 4-8 hour offset, with after effects of feeling drained and fuzzy that persist for another few hours. The overall duration is slightly longer than with dextroamphetamine. This will vary based on individual sensitivities. Route of administration is also a variable, and onset time, and duration are decreased if snorted or taken in other ways, in which the onset time tends to be within about 5-15 minutes, with about a 3-4 hour peak and 3-6 hour offset. Snorting 4-FA really burns and is not recommended due to its possibly caustic nature.

4fa duration chart.png

Physical Effects

The physical effects are marked by increased alertness, heart rate, blood pressure, appetite suppression, bruxism (jaw clenching), and nystagmus (eye wiggles). Seizures appear to be rare but possible, especially in those prone or physically stressed. The risk for seizures can be reduced by following the harm reduction measures and not combining with drugs that also decrease the seizure threshold, the details of which are discussed later in this literature.

Sleep may be difficult or impossible until a few hours after it wears off and eating may be an unappealing concept, but still recommended. It’s ideal to eat and be well slept before dosing because appetite will be suppressed and one may not feel hungry or sleepy until 12-16 hours after dosing. These effects are magnified in higher dose scenarios. Some people feel urges to redose when the effects start to fade- this is best avoided if possible due to the long duration, and the risk for adverse mental health consequences like mania or psychosis with repeated use similar to stimulant psychosis that may occur with long binges of other amphetamines. If one does choose to re-dose, set boundaries regarding getting enough sleep and food, and not going on too long of a bender. One thing to keep in mind if one experiences the urge of compulsive redosing is that redosing will generally add more to the comedown type effects rather than restoring the high.

Use as an ADHD Treatment

Due to 4-FA being a research chemical with unknown long term effects, it is not recommended to use this substance at sub recreational doses to self medicate for ADHD, and even if it may be indeed helpful for managing ADHD symptoms and smoother and more easygoing feeling than prescribed amphetamines, there is too much that is yet unknown about this compound for it to be used frequently as an ADHD drug.

Risks and Harm Reduction

Very little is known about the long term risks of taking 4-FA, and it is likely neurotoxic, like most drugs in the amphetamine family.  A fairly closely related drug, 4-Chloroamphetamine, is highly neurotoxic, but it is unknown whether the fluorine substitution at the 4 position of the benzene ring on the phenethylamine backbone differs in terms of neurotoxicity compared to the chlorine substitution.

The extent to which the neurotoxic effects of 4-FA compare to either MDMA or amphetamine are not very well known. The mechanism of the neurotoxic effects is due to the oxidative stress to the serotonergic neurons that occurs when the drug binds to the serotonin transporter at the presynaptic neuron’s reuptake pump. Normally, serotonin is “recycled” through the reuptake pump back into the presynaptic neuron from the synaptic cleft, with only a specific amount of serotonin present in the synaptic cleft being broken down by the monamine oxidase enzyme. When drugs such as MDMA or 4-FA bind to the serotonin transporter and block serotonin from being reuptaken back up from the synaptic cleft back to the presynaptic neuron, a larger than usual amount of serotonin remains in the synaptic cleft that eventually gets broken down by the monoamine oxidase enzyme. Since more serotonin than usual is oxidised, this causes something called oxidative stress, which can be thought of being like “rusting” of the serotonergic neurons. However, there are strategies that can be used to mitigate this possible risk, which are discussed in more detail in A No-Nonsense Guide to MDMA Harm Reduction, where 4-FA is mentioned as a common MDMA adulterant. Note that due to the RC nature of 4-FA, not much is known about it, and this harm reduction info is based on the assumption that 4-FA has similar risks on the serotonergic system as MDMA.

Such harm reduction measures include:

  • Using only once a season. The biggest variable for neurotoxic effects is frequency of use. It takes a while for the body to replenish depleted neurotransmitters, and the effects of oxidative stress tend to be cumulative. Both MDMA and 4-FA have deleterious effects when used every weekend, and should be spaced out every three months, and once per month at the most.
  • Do not take more than you need to feel the effects. Once you have achieved euphoric effects, taking more will not only take away from the euphoria and increase unpleasant side effects, but also add to the neurotoxicity. Doses exceeding 120mg are not recommended.
  • Body temperature is a huge variable. Chemical reactions generally occur at a much faster rate when the body temperature is higher, and this is especially a sensitive factor in terms of the activity of enzymes that like monoamine oxidase. 4-FA can cause overheating due to the increased serotonin signalling signalling the body to increase temperature, and if the body temperature is higher than usual, monoamine oxidase is much more active and much more oxidative stress occurs compared to a cool environment. Consider the set and setting- if you are using this substance at a summer festival, for example, ensure there are shaded areas and lots of water available, and take breaks from dancing. If the weather is above 30*C, it may be best to wait until after the sun sets to dose.
  • Antioxidants like vitamin C help reduce the extent of oxidative stress, although this is by no means a security blanket for other forms of harm reduction.
  • 5-HTP is not a miracle cure and can be dangerous if not used correctly. 5-HTP must be taken AFTER one has fully come down, NEVER during or before, as this could cause serotonin syndrome- a medical emergency. Do not rely on 5-HTP as a magical serotonin replenisher- it takes a while for all the serotonin in your gut to be transported to the central nervous system. 97% of serotonin exists in the gut, and taking 5-HTP will not necessarily immediately replenish serotonin levels quickly or immediately. The only benefit it has is that it skips one enzymatic conversion from tryptophan- a dietary amino acid that is converted into 5-HTP and then serotonin. 5-HTP should also not be used as a substitute for a healthy diet that contain sufficient levels of tryptophan.

Cardiac Risks

Based on anecdotal reports, it appears as if 4-FA presents a higher risk of adverse cardiovascular effects than other amphetamines. There have been reports from the Netherlands, where this substance is most commonly used, where a migraine like syndrome consisting of a severe headache occurred after moderate usage of this substance, which has been associated with strokes. IF YOU HAVE A SEVERE HEADACHE DURING/AFTER 4-FA USE, DISCONTINUE THIS SUBSTANCE AND SEEK MEDICAL ATTENTION. [2]

Combinations with other psychoactives:

High risk, potentially fatal:

25x-nBOME: This class of substances is notorious for causing seizures, hospitalization, and even death on its own, and 4-FA exponentially adds to these dangers by decreasing the seizure threshold even more. Not only that, but the subjective experience of a stimulant with an unpredictable and dose sensitive psychedelic is very likely to be extremely traumatizing.

MAOIs such as syrian rue, banisteriopsis caapi, 2C-T-2, 2C-T-7, αMT, and some antidepressants These combinations can cause a potentially fatal medical emergency called serotonin syndrome. Other drugs that can cause serotonin syndrome in combination with 4-FA include DXM and tramadol. This is not an exhaustive list.

Buproprion (aka Wellbutrin, Zyban, etc.): This prescription antidepressant is notorious for decreasing the seizure threshold, and seizures are more likely with this combination than with either substance alone.

Cocaine: The stimulant effects of cocaine can cause the physical effects of both drugs to stack up to a dangerous extent.

MDMA and its stimulant adulterants: The neurotoxiticity is increased with this combination, and the stimulant effects can stack to a dangerous extent.

Other amphetamines (meth, speed, Dexedrine, Adderall, Vyvanse, etc.): Since these drugs have very similar effects to 4-FA, a dangerous extent of stacking of effects can occur, and the neurotoxiticy from either drug alone is increased in combination.

5-HTP: If 5-HTP is taken before 4-FA, or while the effects of 4-FA are still occuring, serotonin syndrome can occur. It is imperative that 5-HTP is taken the next day, not only with 4-FA but any serotonin releasing drug such as MDMA.

Take caution:

Alcohol: Both of these substances enhance each other’s neurotoxic effects. Alcohol increases dehydration and the risk of overheating and increased oxidative stress on serotonergic neurons. The long lasting stimulating effects of 4-FA may also mask the subjective feeling of alcohol intoxication, and increases the risk of an alcohol overdose, which should be kept in mind when determining the alcohol dosage. The combination of a stimulant with alcohol also increases the risk for erratic behaviour while intoxicated compared to alcohol on its own due to the dual effect of disinhibition from alcohol with the increased energy and confidence from a stimulant. Although this may sound awesome, in its extreme form, this can result in events like gaining a reputation for getting too fucked up and wrecking peoples’ houses. Being disinhibited and confident may be part of the partying mindset, but only to a specific extent that results in behaviours more along the lines of opening up, letting your confidence shine, and making new friends, rather than biting peoples’ couches and pissing in the ashtray.

For more information on how to more safely embark on this combo, consult Drug Combination and Poly Drug Use under Amphetamines+ Alcohol.

GHB: This is another example where being careful will not only prevent you from going to the hospital, but will only make you high as balls only within a very specific and moderate dosage range that also corresponds to the dosage range where harms are reduced. This combination can produce the subjective experience of a very powerful (and often pleasurable) body high where the body feels both light as a feather but also comfortably weighed down. If you feel extremely amazing, that means do not take any more G and/or 4-FA or you will end up in the hospital. If you are feeling high as balls, remember that more will not make you feel even higher than balls if you are tempted to redose, and just sit back and enjoy your high as it currently is and do not redose.

For more information about G dosing and the combination with amphetamines, consult Drug Combination and Poly Drug Use under GHB+ Amphetamine.

Ketamine and its dissociative adulterants: With unadulterated ketamine, the risk of this combination mainly stems from the stimulant subjectively masking the dissociative effects of the ketamine, making it easier to inadvertently slip into a K hole. The combination of stimulation and dissociation is also often very panic inducing for people due to having so much energy within the void of a dissociative hole. This combination is generally only regarded to have agreeable subjective effects with light doses of either substance, with anything higher generally being very panicky. Combinations with RC dissociatives that may be sold as ketamine can become very dangerous, particularly with the PCP analogues- there is an extremely high risk for mania, psychosis, and adverse cardiovascular effects when PCP and its analogues are combined with simulants. Test before you ingest!

Opioids: Beware of the tendency for stimulants to subjectively mask the sedation from opioids despite the opioid still exerting its full physical effect. This makes it easier to slip into an OD. With Tramadol, there is a high risk of serotonin syndrome.

Presumably Physiologically benign (tentatively so due to 4-FA’s RC nature!), with a risk for an adverse subjective experience:

Psychedelics: As of so far, there are no known reports of physically dangerous interaction with 4-FA in combination with classical psychedelics like LSD and mushrooms, but due to the stimulating effects of 4-FA, there is a high risk of psychedelic crisis. 4-FA does not work as an alternative for MDMA for candy flipping. With psychedelics of the substituted phenethylamine class that have a higher body load (such as the 2C-x drugs), physical safety with this combination is less assured. Beware of bunk acid that is actually 25i-NBOMe, which can be a lethal combination- test before you ingest!

Cannabis: As of so far, there have been no reports of physically dangerous interactions between 4-FA and cannabis, although the tendency for cannabis to enhance the effects of other drugs should be taken into consideration in regards to the subjective outcome of this combination.