Fladrafinil (CRL-40941) Review: Benefits, Risks, Uses & Where to Buy

Updated October 9, 2024 by | Reviewed by William Gallagher, MNeuroSci
(Estimated reading time: 11 minutes)

Fladrafinil (bis(4-fluorophenyl)-Adrafinil​, fluorafinil or CRL-40,941) is a novel eugeroic compound that has garnered significant interest in the nootropic community for its potential cognitive-enhancing properties. As a researcher specializing in nootropics and brain health, I have conducted a thorough review of the available scientific literature to provide a concise overview of fladrafinil's origin, chemical composition, and mechanisms of action. So, let's dive in, shall we?

What Is Fladrafinil and Its Chemical Composition?

fladrafinil

Fladrafinil, also known as CRL-40,941 and fluorafinil, is a eugeroic compound closely related to adrafinil and modafinil. It is a bis(p-fluoro) ring-substituted derivative of adrafinil, with the chemical formula C15H13F2NO3S and a molecular weight of 325.33 g/mol. Fladrafinil's chemical structure features two fluorine atoms at the para positions of the diphenylmethyl moiety, which contributes to its unique pharmacological profile.

FormulaC15H13F2NO3S
Molar mass325.33 g·mol−
CAS Number90212-80-9
Routes of administrationOral
Legal statusUS: Not approved

What Is the Origin of Fladrafinil?

Fladrafinil was first developed by the French pharmaceutical company Lafon Laboratories in the 1970s as part of their research into wakefulness-promoting agents. It is structurally related to adrafinil and modafinil, two well-known eugeroic compounds. However, fladrafinil has been found to possess unique properties, such as anti-aggressive effects in animal models, which sets it apart from its parent compounds.

What Is the Chemical Structure of Fladrafinil?

Fladrafinil, also known as CRL-40,941 and fluorafinil, has the chemical formula C15H13F2NO3S and a molecular weight of 325.33 g/mol. It is the bis(p-fluoro) ring-substituted derivative of adrafinil, with the addition of two fluorine atoms at the para positions of the diphenylmethyl moiety. This structural modification contributes to its unique pharmacological profile and enhanced potency compared to adrafinil.

How Does Fladrafinil Enhance Cognitive Function?

Fladrafinil is believed to enhance cognitive function through its effects on key neurotransmitter systems in the brain. It has been shown to increase levels of dopamine, norepinephrine, and histamine, which play crucial roles in regulating wakefulness, attention, and memory. Additionally, fladrafinil has been reported to modulate GABA levels, potentially contributing to its anti-aggressive and mood-enhancing properties.

What Are the Biochemical Processes Influenced by Fladrafinil?

Fladrafinil has been shown to influence several key biochemical processes in the brain. It modulates the levels of neurotransmitters such as dopamine, norepinephrine, and histamine, which are involved in regulating wakefulness, attention, and cognitive function. Additionally, fladrafinil has been reported to affect GABA levels, potentially contributing to its mood-enhancing and anti-aggressive properties. These biochemical processes work together to enhance overall cognitive performance and promote wakefulness.

What Are the Primary Uses and Benefits of Fladrafinil?

Fladrafinil is primarily used as a cognitive enhancer and wakefulness-promoting agent. It has been studied for its potential benefits in treating cognitive disorders, such as attention deficit hyperactivity disorder (ADHD) and narcolepsy, as well as improving cognitive performance in healthy individuals. Fladrafinil's ability to modulate key neurotransmitters in the brain contributes to its cognitive-enhancing effects, including improved attention, memory, and overall mental performance.

How Does Fladrafinil Benefit Cognitive Disorders?

Fladrafinil has shown promise in the treatment of various cognitive disorders, such as attention deficit hyperactivity disorder (ADHD) and narcolepsy. Its ability to promote wakefulness and improve attention may help alleviate symptoms associated with these conditions. Additionally, fladrafinil's potential mood-enhancing and anti-aggressive properties could be beneficial for individuals with cognitive disorders who experience emotional dysregulation or aggressive behavior.

How Can Fladrafinil Improve Cognitive Performance in Healthy Individuals?

In healthy individuals, fladrafinil may enhance cognitive performance by improving focus, attention, and memory. Its wakefulness-promoting properties can help combat fatigue and maintain alertness, particularly during periods of sleep deprivation or prolonged mental exertion. Furthermore, fladrafinil's potential mood-enhancing effects may contribute to improved motivation and overall mental well-being, which can indirectly support cognitive performance.

User Experiences and Reviews of Fladrafinil

Fladrafinil, a eugeroic and nootropic compound, has garnered attention from biohackers seeking cognitive enhancement. User reports on forums like Reddit and Longecity detail experiences with increased focus, motivation, and wakefulness. Many describe Fladrafinil as a smoother, less jittery alternative to traditional stimulants like Adderall or Modafinil.

What Do Personal Experiences and Reddit Discussions Reveal About Fladrafinil?

Reddit's nootropics community features numerous Fladrafinil experience reports, with users noting improved concentration, mental clarity, and task engagement. Some describe enhanced verbal fluency and creativity, while others report mild appetite suppression. Discussions also highlight the importance of responsible dosing and cycling to minimize tolerance and maintain efficacy.

My Personal Fladrafinil Experience and Results

I personally experimented with Fladrafinil, starting with a conservative 50mg dose and gradually titrating up to 150mg. At the effective dose, I noticed a pronounced increase in focus, motivation, and mental stamina, allowing for extended periods of productive work. Verbal fluency and recall also seemed to improve, facilitating engaging conversations and brainstorming sessions.

How Does Fladrafinil Feel and What Results Were Observed?

The Fladrafinil experience is characterized by a smooth, clean energy devoid of the physical stimulation and jitteriness associated with caffeine. I found it easier to enter a flow state and maintain concentration on demanding cognitive tasks. Over a 6-week trial, I observed consistent benefits in productivity, idea generation, and mental endurance, without significant side effects or disrupted sleep when taken early in the day.

Practical Aspects of Acquiring Fladrafinil

Fladrafinil is an unscheduled research chemical, available through online nootropic vendors and research chemical suppliers. Purity and quality can vary, making it crucial to source from reputable providers with third-party lab testing. Prices typically range from $30-50 per 5 grams, with discounts for larger quantities.

Where and How to Purchase Fladrafinil Safely and Legally?

Fladrafinil is an unregulated research chemical, available through online nootropic vendors and research chemical suppliers. Purity and quality can vary significantly, making it crucial to source from reputable providers that conduct third-party lab testing to ensure the identity and purity of their products.

How Much Does Fladrafinil Cost?

Prices for Fladrafinil typically range from $30-50, with discounts sometimes available for larger quantities. For example, Science.bio offers 3000mg solutions (100mg/mL) at $39.99 for a single bottle, with bulk pricing as low as $16 per bottle for orders of 500 or more.

Understanding Fladrafinil's Side Effects and Safety Profile

As an unregulated research chemical, the long-term safety and side effect profile of Fladrafinil in humans is not well established. Much of the information on its effects and risks is extrapolated from research on modafinil, its primary metabolite, or based on anecdotal user reports.

What Are the Known Short-Term and Long-Term Side Effects?

Potential short-term side effects of Fladrafinil, based on user reports, may include headaches, nausea, insomnia, anxiety, and increased heart rate, especially at higher doses. Long-term risks are unknown, but chronic use could theoretically lead to tolerance, dependence, or withdrawal symptoms upon discontinuation. Rare but serious adverse reactions seen with modafinil, like severe rash, psychiatric symptoms, or cardiovascular events, may also be possible with Fladrafinil.

What Are the Major Drug Interactions with Fladrafinil?

Fladrafinil likely has drug interactions similar to modafinil, as it is primarily metabolized to modafinil in the body. Modafinil can decrease levels of many medications metabolized by CYP3A4, like birth control pills, benzodiazepines, and certain antidepressants. Drugs that inhibit or induce CYP3A4 may increase or decrease modafinil levels. Combining Fladrafinil with other stimulants may increase cardiovascular strain and side effects.

Administration and Dosage Guidelines for Fladrafinil

There are no official dosage guidelines for Fladrafinil, as it is an unapproved research chemical. Based on anecdotal reports, typical doses range from 30-200mg per day, often starting low and increasing gradually. It is usually recommended to take Fladrafinil early in the day to avoid sleep disruption. As a potent wakefulness-promoting agent, it should be used cautiously, ideally under medical supervision, and never mixed with alcohol, other drugs, or taken before driving or operating machinery.

What Are the Different Forms and Methods of Taking Fladrafinil?

Fladrafinil is available in various forms, including powder, capsules, tablets, and liquid solutions. The most common method of administration is oral, either by swallowing capsules or consuming the powder or liquid mixed into a beverage. Sublingual and intranasal routes have been reported anecdotally but are less common and not well-studied.

How Much Fladrafinil Is Recommended for Desired Effects?

Typical Fladrafinil doses range from 30-200mg per day, usually starting at the lower end and gradually increasing as needed. Most users find 50-150mg to be an effective range for cognitive enhancement, taken early in the day to avoid sleep disruption. Due to individual variability and lack of clinical studies, it's crucial to start low, assess tolerance, and not exceed 200mg/day to minimize risks.

Pharmacokinetics of Fladrafinil

The pharmacokinetics of Fladrafinil, or how the drug is processed by the body, have not been thoroughly studied in humans. However, as a prodrug of modafinil, it is thought to share some similarities in absorption, metabolism, and elimination.

How Is Fladrafinil Absorbed, Metabolized, and Excreted in the Body?

Fladrafinil is rapidly absorbed after oral administration and then extensively metabolized, primarily in the liver, to modafinil as its major active metabolite. This conversion is mediated by amide hydrolysis and is necessary for Fladrafinil's wakefulness-promoting effects. Modafinil is further metabolized by CYP3A4 enzymes to modafinil acid and modafinil sulfone. Elimination occurs mainly through the kidneys, with a half-life of around 12-15 hours for modafinil. However, the specific pharmacokinetic parameters of Fladrafinil in humans, such as bioavailability, peak levels, and excretion rate, remain to be characterized.

Tolerance and Dependency Issues with Fladrafinil

The potential for tolerance and dependency with long-term Fladrafinil use is a concern but not well-established. Modafinil, Fladrafinil's main metabolite, is considered to have a lower abuse potential than traditional stimulants. However, case reports suggest that psychological dependence can develop with prolonged use of high doses. Tolerance, or needing higher doses to achieve the same effect, may also occur over time. To minimize these risks, it's important to use Fladrafinil judiciously, at the lowest effective dose, with regular breaks, and under medical supervision whenever possible. More research is needed to fully characterize the long-term safety and dependence liability of Fladrafinil in real-world settings.

Can Users Develop Tolerance to Fladrafinil?

Tolerance to Fladrafinil may develop with prolonged or frequent use, as the body adapts to its presence. This means that higher doses may be required to achieve the same cognitive-enhancing effects over time. To minimize the risk of tolerance, it's important to use Fladrafinil judiciously, at the lowest effective dose, with regular breaks.

Interactions and Synergies: Fladrafinil Combinations

Fladrafinil, as a potent eugeroic, may interact with various substances, potentially altering their effects or side effect profiles. Understanding these interactions is crucial for safe and effective use, especially when considering Fladrafinil as part of a nootropic stack.

What Substances Interact with Fladrafinil?

Fladrafinil may interact with medications metabolized by CYP enzymes, as it is thought to induce or inhibit these liver enzymes. It may also interact with other stimulants, increasing the risk of adverse effects. Combining Fladrafinil with MAOIs or blood pressure medications is not recommended due to the potential for serious interactions.

What Are the Most Effective Fladrafinil Stacks?

Popular Fladrafinil stacks often include cholinergics like Alpha-GPC or citicoline to synergistically enhance cognitive function. Combining Fladrafinil with L-theanine may smooth out its stimulatory effects while preserving the cognitive benefits. Stacking with a low dose of caffeine is another common practice to potentiate Fladrafinil's effects.

Exploring Alternatives to Fladrafinil

While Fladrafinil is a promising nootropic, it's not the only option for cognitive enhancement. Exploring alternatives can help individuals find the most suitable compound for their unique needs and neurochemistry.

What Are Viable Alternatives to Fladrafinil?

Modafinil, Fladrafinil's primary metabolite, is a well-studied and widely used alternative.[1] Other eugeroics like Adrafinil and Flmodafinil may provide similar benefits. Non-eugeroic nootropics such as Noopept, Phenylpiracetam, and Oxiracetam are also potential alternatives for cognitive enhancement.

Insights from Scientific Research on Fladrafinil

Although Fladrafinil has shown promise in preliminary studies and anecdotal reports, more rigorous research is needed to fully characterize its effects, safety profile, and mechanisms of action. Insights from studies on Fladrafinil's pharmacokinetics, neuroprotective properties, and potential therapeutic applications will be invaluable in guiding its responsible use as a nootropic.

What Have Animal and Human Studies Revealed About Fladrafinil?

I couldn't find any published studies directly examining the effects, safety, or pharmacokinetics of fladrafinil in animals or humans. However, several studies have investigated the properties of modafinil, which is the active metabolite of fladrafinil. Animal studies have shown that modafinil, the active metabolite of fladrafinil, can increase wakefulness, reduce food intake, and exhibit anti-aggressive properties in rats and monkeys.[2][3]Human studies suggest that modafinil enhances cognitive function, particularly in sleep-deprived individuals, and may have potential as a cognitive enhancer.[4][5] However, these findings cannot be directly extrapolated to fladrafinil due to the lack of specific research on this compound.

Evaluating the Value of Fladrafinil for Cognitive Enhancement

Given the absence of direct research on fladrafinil, its value as a cognitive enhancer remains speculative and is largely based on anecdotal reports from users. While modafinil has shown promise in enhancing cognition, particularly in sleep-deprived states, more research is needed to determine if fladrafinil confers similar benefits and to assess its safety and tolerability.

Is Investing in Fladrafinil a Good Decision for Cognitive Enhancement?

Without conclusive scientific evidence supporting the efficacy and safety of fladrafinil, investing in this compound for cognitive enhancement is not advisable. The lack of regulation and quality control in the production of fladrafinil also raises concerns about purity and potential adverse effects. Until more rigorous research is conducted, it is prudent to explore well-studied alternatives for cognitive enhancement, such as maintaining a healthy lifestyle, engaging in cognitively stimulating activities, and considering medications with established safety and efficacy profiles under medical supervision.

Frequently Asked Questions (FAQ) About Fladrafinil

Your questions about Fladrafinil are answered below.

How Long Does It Take for Fladrafinil to Kick In?

User reports suggest fladrafinil's effects may be felt within 45-60 minutes of oral ingestion, but this onset time has not been scientifically verified.

How Long Does the Effect of Fladrafinil Last?

Anecdotal accounts indicate fladrafinil's effects could last 12-15 hours, similar to modafinil, but controlled studies are needed to establish the true duration of action.

What Does Fladrafinil Taste Like?

Information on fladrafinil's taste is limited, as it is typically sold in capsules or powder and not consumed for flavor. User reports do not commonly describe the taste profile. From my personal experience, fladrafinil is flavorless.

Is Fladrafinil Legal?

Fladrafinil's legal status is ambiguous and varies by jurisdiction. In the US, it is an unregulated research chemical, unapproved for human consumption. Laws may differ internationally, so it is crucial to check local regulations.

Is Fladrafinil FDA-Approved?

No, fladrafinil is not approved by the FDA for any medical use. It remains an unapproved research chemical, lacking the rigorous safety and efficacy testing required for legitimate medications.

Fladrafinil vs Adrafinil: What's the Difference?

Fladrafinil and adrafinil are both precursor drugs that are metabolized into modafinil in the body. However, fladrafinil is believed to be more potent and faster-acting than adrafinil due to its higher bioavailability and more efficient conversion to modafinil. Adrafinil has been more extensively studied than fladrafinil, with a longer history of human use, while fladrafinil remains a relatively novel and under-researched compound.

Fladrafinil vs Adderall: What's the Difference?

Fladrafinil and Adderall are both used for their stimulant and cognitive-enhancing effects, but they work through different mechanisms. Fladrafinil is metabolized into modafinil, which primarily acts as a wakefulness-promoting agent, while Adderall is an amphetamine that directly stimulates the release of dopamine and norepinephrine. Adderall is FDA-approved for treating ADHD and narcolepsy, while fladrafinil is an unapproved research chemical with limited safety and efficacy data.

Hydrafinil vs Fladrafinil: What's the Difference?

Hydrafinil (9-fluorenol) and fladrafinil are both analogs of modafinil, sharing similar chemical structures and mechanisms of action. However, there is even less research available on hydrafinil compared to fladrafinil, making it difficult to draw definitive comparisons between the two. Both compounds are considered research chemicals and lack sufficient evidence to support their safety or efficacy for human use.

Fladrafinil vs Flmodafinil: What's the Difference?

Fladrafinil and flmodafinil (also known as CRL-40,940) are both fluorinated analogs of modafinil, differing in the position and number of fluorine atoms on the diphenylmethyl sulfinyl acetamide structure. While both compounds are believed to exhibit wakefulness-promoting and cognitive-enhancing effects similar to modafinil, there is a lack of comparative research to determine which one is more potent, longer-lasting, or better tolerated. Both fladrafinil and flmodafinil are unregulated research chemicals with limited safety and efficacy data.

Fladrafinil vs Modafinil: What's the Difference?

Fladrafinil is a precursor drug that is metabolized into modafinil in the body, while modafinil is the active drug itself. Fladrafinil is considered to be more potent than modafinil on a weight basis due to its higher bioavailability and more efficient conversion. However, modafinil has been extensively studied and is FDA-approved for treating narcolepsy, obstructive sleep apnea, and shift work disorder, while fladrafinil remains an unapproved research chemical with limited safety and efficacy data.

Is Fladrafinil Considered a Nootropic?

Yes, fladrafinil is considered a nootropic or a cognitive enhancer. It is often marketed as a "smart drug" or "study drug" purported to improve memory, focus, and overall cognitive function. Fladrafinil is chemically similar to modafinil, a well-known nootropic, and is believed to exert its effects by increasing levels of dopamine and histamine in the brain.

References
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  2. Perez, Gydmer A et al. “Modafinil decreases food intake in humans subjected to simulated shift work.” Pharmacology, biochemistry, and behavior vol. 90,4 (2008): 717-22. doi:10.1016/j.pbb.2008.05.018 â†‘
  3. van Vliet, Sanneke A M et al. “Behavioral effects of modafinil in marmoset monkeys.” Psychopharmacology vol. 185,4 (2006): 433-40. doi:10.1007/s00213-006-0340-4 â†‘
  4. Kredlow, M Alexandra et al. “The Efficacy of Modafinil as a Cognitive Enhancer: A Systematic Review and Meta-Analysis.” Journal of clinical psychopharmacology vol. 39,5 (2019): 455-461. doi:10.1097/JCP.0000000000001085 â†‘
  5. Nardone, Raffaele et al. “Modafinil reverses hypoexcitability of the motor cortex in narcoleptic patients: a TMS study.” Sleep medicine vol. 11,9 (2010): 870-5. doi:10.1016/j.sleep.2010.05.007 â†‘