FGL

Other names Fibroblast Growth Loop, FGL Peptide, Pentadecapeptide FGL, EVYVVAENQQGKSKA, HA-FGL, Hyaluronate-FGL, FGL(L)

FGL is a research chemical and synthetic peptide that mimics the function of Neural cell adhesion molecule. NCAM is present naturally in the brains of every single living human on this planet and plays a role in neurite outgrowth and synaptogenesis, to neural mechanisms linked to cognitive functioning. Some evidence suggests the use of FGL is effective for improving learning and memory. But how strong is this evidence? And is this drug safe? Read on to find out what the science says about the risks and cognitive benefits of FGL.

This nootropic has no healthy human placebo-controlled studies that meet our inclusion criteria. Negative side effects can occur if used carelessly, so make sure you’re aware of the risks of FGL.

Browser our suppliers for FGL

Benefits

Read about the effects of FGL in relation to the amount of evidence we've found

FGL for improved learning and memory

No published studies have examined the effects of FGL on cognition in humans.

The lack of evidence on the efficacy of FGL entails it is impossible to know what its effects on cognition are.

Because of the lack of research on FGL, we never recommend that people use it.

But we do recommend that people learn about it because it is one of the most special (in mechanisms) but underresearched nootropics out there.

So, for educational purposes, let's dive into the science of the cognitive effects of FGL, as far as they are known.

The only science that exists on the effects of FGL for cognitive enhancement comes from animal studies.

In one study, rats completed two memory and learning tasks, fear conditioning and the water maze learning task. [2] FGL improved spatial memory and fear learning when administered intracerebroventricularly in rats. It was also found that FGL had no effects on emotional behavior and locomotion, so the learning and memory benefits found could not be due to such effects.

It is far from obvious that such beneficial effects would occur in humans. For one thing, the route of administration included injection into the brains of these rats. [3] This is not practical in humans, but if oral administration would have similar benefits, it may be best to use FGL just after learning something, since it was found that it enhanced the process of memory consolidation and recall of the learned information 2-4 weeks after training.

The learning and memory benefits were found 24h after the training event and persisted 14 days (spatial learning task) and 28 days (fear conditioning task).

The authors of the study concluded:

"Although a proactive effect on retrieval cannot be excluded, the pattern of effects favors the view that FGL affected memory consolidation processes occurring in the hippocampus." [4]

However, in one version of the fear conditioning task, FGL only improved memory after 28 days, but not after 24h or 14 days. [5] It is not known why the peptide had such effects. It could be that the effect that was found was a false positive and that it didn't actually improve this specific aspect of memory after 28 days. But considering its known mechanism of action, it is plausible that long term brain changes are to thank for these potential long term memory benefits. It could also be that the animals in the control group remembered the fear-inducing stimuli well after 24h and 14 days and that this was the reason why a potential memory consolidation enhancement was found between the FGL group and the control group only after 28 days.

The study authors also concluded that the peptide appears to have the ability to facilitate behavioral flexibility and subsequent learning processes.

It was also found in another rat study that FGL improved spatial learning. [7]

Risks

The legality and side effects of FGL

You should always consider the risks of a nootropic before you use it.

Negative side effects of FGL

Single intranasal doses of 25, 100, and 200mg FGL(L) were given to 24 healthy male participants in one study.

The following negative side effects were reported:

"A transient (<3 minutes) burning sensation in the nose was reported in two subjects at the 200mg dose level while runny eyes (<2 minutes) were experienced in one subject at 25mg. These events had an onset immediately following intranasal administration, and a relationship to FGL(L) was suspected." [8]

One of the men that experienced a burning sensation in the nose also experienced dizziness, vomiting, and headache with 2 days of 200mg FGL, but the study authors concluded that this was unlikely due to the peptide.

The enhancement of fear learning that FGL was found to induce can be both a good and a bad thing. It is a sign of general learning improvements, but specifically it is evidence of learning relating to fear. Increased fearfulness is generally not something good for a healthy person, so if you're already walking around with more fear than you need in your life, FGL may exacerbate that for you.

It is known that this peptide activates several molecular pathways regulating synaptic plasticity and neurotransmission. This has the potential to result in long term cognitive enhancement from just a single dose [7], but it could also lead to long-lasting negative effects on cognitive functioning (no evidence suggests such negative effects, but it is a possible risk).

Considering that FGL use appears to result in long-lasting brain changes, young people should be extra cautious with FGL.

It is not known whether FGL might result in any negative side effects in humans. Single appropriate doses are likely safe for the average user.

Is FGL toxic?

"Preclinical studies in rats, dogs and monkeys have demonstrated exposure in plasma and cerebrospinal fluid after parenteral or intranasal administration of FGL(L), with no systemic toxicity." [10]

FGL(L) was also found non-toxic in single doses of 25, 100, and 200mg in 24 healthy human participants. [11]

Side effects

Interactions

Supplements and drugs can interact with FGL to increase or decrease the positive or negative effects you experience. If you are already using any supplements or drugs, speak with your trusted medical professional before you experiment with FGL. To learn more about the potential interactions between FGL and other substances, use interaction-checker.

Legality

Is your country not included? Learn how to find out if FGL is legal in your country.

Legality Disclaimer

FAQ

Frequently asked questions about FGL

What is FGL?

FGL is an acronym for Fibroblast Growth Loop. [12]

It is a research chemical and synthetic peptide that mimics the function of Neural cell adhesion molecule.

FGL has been found to enhance learning and memory in animals, but its cognitive effects in humans are unknown.

What's the difference between FGL, FGL(L), and HA-FGL?

HA-FGL is FGL conjugated with hyaluronate (HA), which improves its enzymatic stability. [13]

HA-FGL may be more effective than FGL, or FGL(L) because it allegedly is absorbed better in the brain. [14]

Much more research is needed on the different forms of FGL before it can be known which is the safest and most effective form for cognitive enhancement purposes.

How does FGL work?

The neuropsychopharmacological effects of FGL have not yet been fully discovered by researchers.

Here are some of the mechanisms which researchers have explored and found involved in the effects of the peptide on cognition:

Enhances NMDA receptor-dependent long-term potentiation (LTP) (in hippocampal CA1 neurons) [15]
- Synapses remained "sensitized" to LTP long after FGL was cleared from the system (in rats)
Facilitates synaptic delivery of AMPA receptors (in hippocampal CA1 neurons) [16][17]
Induces long-lasting improvements in synaptic transmission (in hippocampal CA1 neurons) [18]
- “The effect on synaptic transmission is impressive, and represents the only peptide that I know of that is capable of enhancing transmission and plasticity” scientist Roberto Malinow wrote to Alzforum
Increases neurite outgrowth through activation of FGFR and the MAPK and PI3K intracellular signalling pathways (in neurons, in a cell study)[20]
Enhances presynaptic function through activation of FGFR1 and promotes synapse formation (in hippocampal neurons, based on evidence from two cell studies) [2][3]
Exerts neurotrophic and anti-inflammatory effects (in cell and animal studies) [23]
- Reduces IL-1β, IL-6, and TNF-α (in mice given lipopolysaccharide, but only when not deficient in CD200) [24]
Increases PKC activity and the CaMKII pathway for 24–48h after administration through a transient activation of FGFR-NCAM signaling (in rats) [7]
Increases IGF-1 release (in primary neurons, in cell study) [26]
Induces neuronal Akt phosphorylation and CD200 ligand expression (in cell study) [27]
Reverses age-associated "IFNgamma-induced increases in markers of glial cell activation, including major histocompatibility complex class II (MHCII) and CD40" (in cell study) [28]
Alters hippocampal neurogenesis associated with LTP and increases LTP (in the dentate gyrus in rats) [29]
Inactivates GSK3β (in CA1 pyramidal neurons) [30]
Induces neural stem cell mobilization (in a cell and animal study) [31]
Supports oligodendroglial differentiation and healthy myelination (in a cell and animal study) [32]
Acts as an agonist at the FGFR receptor [33]

Is FGL neuroprotective?

It is likely that the neuroprotective effects of FGL depend on what the factor that is damaging neurons in the brain is. For example, lack of oxygen or dangerously high glutamate levels in the brain can lead to increased neuronal death. FGL is likely to protect neurons from different forms of neurochemical toxicity. While FGL may be protective in many instances, it is likely not going to protect you from everything you might expose your brain to.

It has been found neuroprotective in several cell and animal studies. [34][35] For example, after the chemical induction of cell death, FGL promoted neuronal survival (in dopaminergic, hippocampal, and cerebellar granule neurons). [36]

It protected working memory functioning but not learning performance against chemically induced impairments in one rat study. [37]

However, some researchers believe it may be neuroprotective only in disease conditions, and that it may impair neuronal functioning in non-pathological conditions. [38]

How much and how often should you dose FGL?

Because of the lack of research on FGL, we never recommend that people use it.

If you have already decided to use it, here are some guidelines to maximize the benefits and minimize the risks.

Since no studies have examined the cognitive effects of FGL in humans, it is not known what dose is best for cognitive enhancement. Single intranasal doses of 25, 100, and 200mg FGL(L) were given to 24 healthy male participants in one study and all of these doses were found safe. The 25mg dose was undetectable in plasma but the other two doses were detectable, suggesting 25mg may not be enough to exert any biological effects. This is all very speculative and should be taken with a large grain of salt. More research is needed on the safety and efficacy of FGL before it can be known which doses may be safe and effective for cognitive enhancement purposes.

It is possible that 100-200mg intranasal FGL(L) would be effective for improving learning and memory, but it is not known to science whether it is.

How does it feel when you take FGL?

The following qualitative user experience reports and reviews are included to give you an understanding of what the experience of taking FGL is like.

Anecdotal FGL experience reports and reviews from Reddit

Two people who appear to have used FGL reported (undefined) side effects, and a lack of "cool effects". [39]

Anecdotal FGL experience reports and reviews from Longecity

One person said the following about FGL:

"It's insanely potent and better than dihexa because it increases AMPA receptor density." [40]

And another user reported the following:

"So far (~10 days) I am seeing some pretty amazing results. I'm taking 250mcg x 2 daily. It may sound outlandish, but I do feel like my brain is becoming more 'plastic': learning seems easier, and I am experiencing a definite lift of mood." [41]

What is the pharmacokinetic profile of FGL?

FGL(L) moves in the body in the following ways:

"Quantifiable plasma concentrations of FGL(L) were observed up to 1 hour after intranasal administration of the 100mg dose and up to 4 hours after the 200mg dose (plasma FGL(L) concentrations were undetectable at all timepoints for the 25mg dose). Increasing doses of FGL(L) were associated with higher systemic exposures: mean C(max) 0.52 ng/mL and 1.38 ng/mL (100mg and 200mg, respectively); mean AUC(24) 1.27 ng x h/mL and 4.05 ng x h/mL (100mg and 200mg, respectively)." [8]

Studies

Studies conducted on the effects of FGL in healthy humans

Last updated Saturday, June 10, 2023