No longer friends with 1S-LSD, now 1Fe-LSD is my new best friend

[GulpingBatteryLiquid]

It looks like 1S-LSD has been banned in Germany so there's a new analogue on the block, 1Fe-LSD . My usual source that ships to the UK doesn't have it in yet but it looks like a few other places do.

Does anybody with more chemistry knowledge than me have an opinion on how similar / potent it will be compared to the real deal?

Has anybody tried it yet?

One guy on Reddit seems to be a bit sceptical about it

But with this proposed ferrocenoyl derivative, the "1Fe-LSD," I feel we are stepping into an entirely different and potentially darker territory. The chemistry is undeniably elegant. Attaching a ferrocene moiety, which is an atom of iron sandwiched between two cyclopentadienyl rings, creates a highly lipophilic molecule. It would undoubtedly pass into the central nervous system with great efficiency. But one must ask the pharmacological question. What is the cost of admission?

The direct activity of the molecule itself is highly unlikely. The steric bulk of that iron sandwich is massive. It acts as a rigid cylinder that would almost certainly preclude any direct fit into the tight quarters of the 5-HT2A receptor. So the metabolic cleavage must occur for the compound to show any psychoactive effects at all. The LSD is liberated and finds its target. But the carrier group remains.

Here is where my hesitation turns into genuine concern. We are effectively smuggling a redox-active transition metal directly into the delicate environment of the synapse. We are bypassing the rigorous gating mechanisms the brain has evolved to regulate iron transport. I cannot help but think of the Fenton reaction. Free iron, or iron liberated from a metabolic breakdown of the ferrocene unit, has the potential to catalyse the conversion of hydrogen peroxide into hydroxyl radicals. These are molecular buzzsaws. They are capable of indiscriminate oxidative damage to proteins and lipids.

To invite such oxidative stress into the immediate vicinity of serotonergic or dopaminergic neurons seems to be an unnecessary biological hubris.

 

[SunshineSolutions]

Hi,
I can share various Informations regarding 1FE-LSD (1-Ferrocenecarbonyl-LSD).

At the moment there are 2 opposing camps confront one another:

• Lizard Labs: Argues via classical systemic toxicology. The focus lies on metabolism into stable compounds, rapid excretion, absence of mutagenicity, and a low total dosage ("the dose makes the poison").
• Opposing Chemists/Debaters on reddit: Argues via neuropharmacology and mechanistic toxicology. The focus lies on kinetics ("Trojan Horse"), local oxidative stress (Fenton chemistry) within neurons, and cumulative long-term damage.

1. The Arguments PRO SAFETY (Based on Lizard Labs)​

The defenders of 1Fe-LSD construct a logically cohesive framework based on standard safety assessments for pharmaceutical substances:

1. a) Metabolic Stability ("FCA Scenario"):

• The Thesis: The substance hydrolyses (cleaves) cleanly into LSD and ferrocenecarboxylic acid (FCA).
• FCA is described as toxicologically harmless: non-mutagenic (Ames test negative), non-carcinogenic, with negligible acute toxicity.
• Validity: Chemically, this is the most probable decomposition scenario. FCA is significantly more stable than ferrocene itself.

1. b) Pharmacokinetic Excretion:

• As FCA is a carboxylic acid, it exists as a deprotonated anion (ferrocenecarboxylate) at physiological pH (7.4).
• Argument: Charged molecules are water-soluble and pass through cell membranes poorly via passive diffusion. Consequently, FCA does not exit cells "backwards" into the brain and is efficiently excreted via the kidneys (analogous to benzoic acid vs. benzene).
• LL emphasises that FCA remains extracellular and is not actively transported into the brain.

1. c) Quantitative Argument ("A Drop in the Ocean"):

• A 200 µg dose releases a maximum of ~85 µg of FCA or ~20 µg of iron.
• Compared to the physiological iron pool (~4 g) or brain iron (~60 mg), this represents < 0.01%.
• LL argues that the body's endogenous buffering systems (ferritin, transferrin) absorb this minute quantity effortlessly.

2. The Arguments CONTRA SAFETY​

The critics do not attack systemic safety (liver/kidney) but rather identify a neurotoxic risk scenario overlooked by standard tests:

2. a) The "Trojan Horse" Principle (Lipophilic Penetration):

• In contrast to the hydrophilic metabolite FCA, the intact 1Fe-LSD is extremely lipophilic (high logP).
• LL claims FCA does not enter the brain. The critique counters: The intact prodrug enters the brain massively due to its lipophilicity before it is hydrolysed. The cleavage occurs in situ (within the brain). Thus, the iron is smuggled past the blood-brain barrier (BBB).

2. b) Catalysis instead of Stoichiometry (Fenton Reaction):

• LL downplays the small quantity (~20 µg iron).
• The critique clarifies: Iron is a catalyst. It is not consumed. In redox cycling (Fe²⁺ ↔ Fe³⁺), a single atom can generate thousands of reactive oxygen species (ROS).
• Locus of Action: The iron is released in synaptic clefts—locations with high mitochondrial activity and thus naturally high H₂O₂ levels. This constitutes the perfect powder keg for radical-induced stress.

2. c) Steric Hindrance & Reaction Kinetics:

• LL compares 1Fe-LSD with 1P-LSD (propionyl).
• But the ferrocene group is a sterically demanding "sandwich" complex. It blocks access for esterases. Hydrolysis presumably proceeds more slowly.
• Consequence: Longer circulation of the lipophilic prodrug, deeper penetration into adipose tissue (membranes), and "depot formation".

2. d) Worst-Case Scenario: Cyclopentadiene Release

• Should the ferrocene scaffold be metabolically broken down (e.g., by aggressive oxidative processes in inflammatory foci), cyclopentadiene is released.
• This is a highly reactive electrophile ("superglue" for proteins) that irreversibly binds glutathione and alkylates proteins. LL ignores this risk entirely.

3. Conclusion​

LL commits a fundamental toxicological category error. It evaluates a potential local neurotoxin according to the standards of a systemic environmental toxin.

3. a) The molecule is a biochemical anachronism
In modern medicinal chemistry, one attempts to avoid potentially toxic pharmacophores (such as heavy metals or redox-active groups) unless the specific aim is to kill cells (chemotherapy). Introducing a ferrocene group into a recreational psychedelic is pharmacologically unnecessary (1P-LSD achieves the same effect more safely) and toxicologically unwise.

3. b) The "Quantity" argument of the PDF is misleading
The statement that ~20 µg of iron is negligible is incorrect if this iron is released intracellularly or in the synaptic cleft, where no ferritin (storage protein) is available. Free iron induces ferroptosis (iron-dependent cell death). Drug-induced parkinsonism is often based on metal accumulation. We are speaking here of a cumulative burden at critical neural junctions.

3. c) Risk Class: Chronic vs. Acute

• Acute Toxicity: Low. No one will die acutely or suffer liver failure from 200 µg of 1Fe-LSD.
• Chronic Neurotoxicity: High. The repeated introduction of a lipophilic redox catalyst into the brain is a recipe for accelerated ageing (senescence) of neurons.

3. d) The alternatives render the risk unacceptable
If 1Fe-LSD were the only available psychedelic, one could debate the risk/benefit ratio. However, prodrugs exist (1P-LSD, 1V-LSD) that cleave off endogenous fatty acids (propionic acid, valeric acid).

4. Final Verdict​

1Fe-LSD is elegant as a chemical experiment, but toxicologically unjustifiable as a consumer product. The defence (LL) merely proves that it is not a potent acute poison. However, it invalidates none of the mechanistic arguments regarding "Trojan Horse" neurotoxicity and oxidative stress. Whoever consumes this substance is effectively conducting micro-chemotherapy on their serotonergic neurons—with the risk of damaging synaptic plasticity long-term through oxidative stress, rather than promoting it.

Classification:

• Pharmacology: Functional LSD prodrug (presumably delayed).
• Toxicology: Potential neurotoxic ROS generant (Reactive Oxygen Species).

Recommendation: Avoid. Resort to established analogues with inert leaving groups (1P/1V/1S).


Here is the position of LL:

Statement from Alexander Stratford, Founder of Lizard Labs
December 2025

This statement is prepared by me, Alexander Stratford - chemist and founder of the now-defunct Lizard Labs.

1Fe-LSD (1-ferrocenecarbonyl-lysergic acid diethylamide) is the last lysergamide I developed before formally closing the company at the end of 2024.

As with previous derivatives, 1Fe-LSD is a prodrug of LSD, designed using the same approach I’ve always used: subtle molecular modification to maintain legality while preserving LSD-like pharmacology. The active dose is approximately 200 µg, with effects broadly comparable to earlier lysergamides in the family (e.g. 1S-LSD, 1V-LSD). I won’t promote the compound - it will speak for itself, just as the others did.

On Safety​

There are no credible toxicological concerns associated with 1Fe-LSD at or around the standard active dose of 200 µg. Upon metabolic cleavage, 1Fe-LSD yields ferrocenecarboxylic acid (FCA) as a byproduct - estimated at a maximum of 80–85 µg per dose, assuming full conversion.

This quantity is toxicologically negligible and far below any reported threshold for ferrocene-based compounds. FCA is a stable, well-characterised organometallic molecule that shows no measurable toxicity at microgram-scale exposure.

To provide further context:​

• FCA is a simple monocarboxylic acid derivative of ferrocene, a scaffold widely used in medicinal chemistry due to its chemical stability, low systemic toxicity, and redox properties. Babin et al. (2014) report that Ferrocerone, a clinically approved ferrocene compound structurally related to FCA, has an LD₅₀ of 60 mg/kg in vivo, and describe ferrocene derivatives as having “low toxicity” and favourable pharmacological profiles. DOI: 10.1007/s11172-014-0756-7
• Rodionov et al. (2019) administered ferrocene-modified amino acids to rats at doses of 2.0 mg/kg, observing no adverse effects, only neurophysiological modulation. The authors specifically note that the ferrocene moiety “significantly decreases [compound] toxicity.” DOI: 10.1002/aoc.5276
• FCA contains approximately 20 µg of elemental iron per 85 µg dose, which is orders of magnitude below the recommended daily intake for iron in humans (8–18 mg/day), further reinforcing its safety at trace levels.
• Related ferrocene-containing pharmaceuticals, such as Ferroquine (an antimalarial) and Ferrocifen (an anticancer agent), have entered clinical and preclinical development, often involving doses thousands of times higher than FCA exposure from 1Fe-LSD. DOI: 10.1016/j.ccr.2018.04.008

Given the well-documented low toxicity of FCA, the extremely low exposure levels involved (<100 µg), and supporting in-vivo data from higher-dose ferrocene analogues, there is no evidence-based basis for concern over FCA exposure resulting from 1Fe-LSD administration.

On the Market​

When Lizard Labs ceased operations, it left behind a vacuum in the lysergamide space. Several emerging labs have since tried to capitalise on what they assume is a lucrative business model. Whether they’ve actually succeeded in synthesising viable new compounds remains unclear.

What is apparent is a wave of questionable tactics and infighting across the sector - perhaps best described as a scramble for attention in the absence of substance.

I have no doubt that eventually someone may step forward with meaningful innovation. But for now, all I see is noise and attempts to trade on my legacy rather than surpass it.

This message can be PGP-verified via our original key. Public key below. I won't respond to any emails.

It’s me. I’m real.
Goodbye.

— Alexander Stratford

Second statement:

Pharmacological-Toxicological Review of 1-FE-LSD and Ferrocene Carboxylic Acid​

ABSTRACT This review summarizes the pharmacological and toxicological properties of 1-FE-LSD (1-Ferrocenylcarbonyl-LSD). The focus is on the evaluation of ferrocene carboxylic acid as a primary metabolite, as well as the classification of the released amount of iron into physiological and toxicological contexts. The data shows that the hydrolysis of 1-FE-LSD occurs rapidly, the substance itself possesses no intrinsic 5-HT2A activity, and the pharmacological effect is mediated entirely by the resulting LSD (Halberstadt et al. 2020, PMID: 31923003). According to toxicological studies, ferrocene carboxylic acid exhibits no mutagenicity, no carcinogenicity, and only low systemic toxicity (Gasiorowski et al. 1999, PMID: 10076192). The amount of iron released (~20 µg) is several orders of magnitude below physiological iron pools.

1. INTRODUCTION​

1-FE-LSD is an N¹-acyl-substituted lysergamide and a structural representative of the so-called LSD prodrugs. In these molecules, the indolic nitrogen (N¹) is chemically blocked, typically by acylation. The pharmacological consequence is a loss of 5-HT2A affinity and thus psychedelic efficacy until the acyl group is enzymatically cleaved. For compounds such as 1P-LSD, ALD-52, or 1B-LSD, it has been experimentally shown that they function entirely as prodrugs, whose efficacy is based exclusively on the resulting LSD (Wagmann et al. 2021, DOI:10.1002/dta.3038; Halberstadt et al. 2019, DOI:10.1016/j.neuropharm.2019.107806).
1-FE-LSD also follows this mechanism: The ferrocenylcarbonyl group prevents any relevant receptor binding, whereby the molecule remains pharmacologically inactive until deacylation occurs. The observed rapid onset of action fits with a rapid enzymatic hydrolysis, as is also documented for other N¹-acyl-substituted lysergamides.

2. BASICS OF THE PRODRUG MECHANISM​

N¹-Acylated lysergamides possess:

• Strongly reduced binding to 5-HT2A receptors (Halberstadt et al. 2019, DOI above)
• Drastically reduced intrinsic activity
• No independent psychedelic effect in vivo

The enzymatic cleavage occurs via:

• Serum esterases
• Amidases
• Hepatic Phase I enzymes

The half-life of the acyl precursor is extremely short. For 1P-LSD, an initial half-life of ~12 minutes was described (Brandt et al. 2017, DOI:10.1002/dta.2211). This shows that such prodrugs are already hydrolyzed in the blood and liver before they distribute systemically.
Application to 1-FE-LSD: Since ferrocenyl substitution is far more voluminous than propionyl or acetyl, the receptor blockade is complete. Although the hydrolysis rate is influenced by steric factors, the presence of a rapid onset of action in anecdotal reports argues for an equally rapid enzymatic cleavage as with other N¹-acyl-substituted lysergamides.
Thus, 1-FE-LSD is functionally clearly classified as a prodrug: It is pharmacologically inactive until the release of LSD.

3. KINETICS OF HYDROLYSIS AND SYSTEMIC PHARMACOKINETICS​

3.1 Enzymatic Hydrolysis of N¹-Acyl-LSD Derivatives The hydrolysis of N¹-acyl-substituted lysergamides is well documented. Central works (Wagmann et al. 2021, DOI:10.1002/dta.3038) show:

• Rapid cleavage by serum esterases (carboxylesterases, butyrylcholinesterase)
• Additional hydrolysis in the liver by amidases and non-specific Phase I enzymes
• Complete deacylation within minutes in vitro

Halberstadt et al. (2019, DOI:10.1016/j.neuropharm.2019.107806) were also able to demonstrate that the prodrugs themselves possess hardly any intrinsic activity and that the pharmacological effects correlate completely with the appearance of LSD.
Since 1-FE-LSD carries the same functional substitution at N¹, the hydrolysis is kinetically comparable.
3.2 Half-lives and Release Rates For 1P-LSD, an initial half-life of about 12 minutes was measured in humans (Brandt et al. 2017, DOI:10.1002/dta.2211). This proves that:

• Deacylation already begins in the blood
• The liver completes the hydrolysis within a short time
• The prodrug is converted almost completely to LSD before relevant systemic distribution can take place

Application to 1-FE-LSD: The ferrocenyl group is larger and sterically more demanding than acetyl/propionyl; however, no unusual stability has been described for ferrocenyl amides and esters (Ullrich et al. 1984, DOI:10.1002/anie.198405651). The observed clinical onset times correspond to 1P-LSD and ALD-52 → rapid hydrolysis is therefore the most probable kinetic reality.
3.3 Systemic Pharmacokinetics of the Resulting LSD After hydrolysis, the distribution of the biologically active LSD follows. The parameters have been investigated in several studies:

• Maximum plasma concentration within 1-2 hours (Holze et al. 2019, DOI:10.1177/0269881119841564)
• Terminal half-life ~8-12 h
• Distribution primarily into well-perfused tissues

Since LSD kinetics are independent of the prodrug, 1-FE-LSD also behaves identically after hydrolysis.
3.4 Systemic Pharmacokinetics of Ferrocene Carboxylic Acid The ferrocene carboxylic acid formed during hydrolysis distributes:

• Predominantly in blood plasma (high polarity)
• Hardly intracellularly, except through non-specific diffusion in liver and kidney cells
• Not actively transported
• Not preferentially into the brain (no relevant BBB transport mechanisms)

Studies on ferrocene preparations such as Ferroceron show that ferrocene derivatives are oxidized in the liver, whereupon free Fe³⁺ is transferred into transferrin/ferritin (Frolov et al. 1975, PMID:1234567; Harrison & Arosio, 1996, PMID:8648576).
3.5 Clearance Ferrocene carboxylic acid is:

• Primarily excreted renally (as free acid or conjugates)
• Partially eliminated via bile
• Not metabolized in the brain

The released iron (~20 µg) is integrated into physiological iron pools to a negligible extent (Arosio & Levi, 2010, DOI:10.1038/nrm2892).
3.6 Toxicokinetic Relevance of the Released Iron Amount Comparison:

• Brain: ~250-350 µg Fe/g tissue (Rouault 2013, PMID:23553167)
• Iron from 200 µg 1-FE-LSD: ~20 µg total amount

Thus, the additional systemic iron amount is <0.01% of the physiological normal range and is toxicologically insignificant.

4. DISTRIBUTION IN THE BODY AND COMPARTMENTALIZATION​

4.1 Passive vs. Active Uptake Processes Ferrocene carboxylic acid is distributed in the body exclusively by passive mechanisms. It possesses:

• No structural features for carrier-mediated uptake,
• No affinity for known metal transporters,
• No ligand structure that could activate DMT-1, ZIP14, or Ferroportin.

While iron ions themselves possess highly regulated transport mechanisms (Gunshin et al. 1997, PMID:9062189), this does NOT apply to organometallic complexes like ferrocene carboxylic acid. Therefore, distribution occurs:

• Along the concentration gradient,
• Via filtration in the kidney,
• Via non-specific hepatocyte uptake.

4.2 Extracellular vs. Intracellular Distribution Ferrocene carboxylic acid is too polar for rapid membrane diffusion. As a result, it remains predominantly:

• In the extracellular space,
• In blood plasma.

Intracellular uptake occurs only:

• In hepatic cells (non-specific endocytosis),
• In renal epithelial cells (secondary via filtration/reabsorption).

Released iron after ferrocene metabolism, on the other hand, is strictly controlled:

• Transferrin-bound in plasma (Harrison & Arosio, 1996, PMID:8648576),
• Intracellularly taken up only via DMT-1 and ZIP14.

4.3 Blood-Brain Barrier and Brain Distribution The brain regulates iron via:

• Transferrin-TfR1-mediated endocytosis,
• Limited export via Ferroportin,
• Strong barrier function of the BBB.

Ferrocene carboxylic acid:

• Possesses no access to TfR1,
• Is not actively transported,
• Shows no lipophilicity that would allow passive diffusion.

Thus, penetration into the CNS is negligible. Data on iron homeostasis also show that the brain has a high intrinsic inventory (~250-350 µg Fe/g; Rouault 2013, PMID:23553167), which is not measurably influenced by <20 µg of additional iron.
4.4 Tissue Distribution: Liver, Kidney, Systemic Circulation After hydrolysis of 1-FE-LSD:

• Ferrocene carboxylic acid and iron first reach the liver,
• Oxidized ferrocene metabolites are formed there (Ullrich et al. 1984, DOI:10.1002/anie.198405651),
• Free iron is stored in ferritin (Arosio & Levi, 2010, DOI:10.1038/nrm2892).

The kidney eliminates ferrocene carboxylic acid efficiently, as it is neither strongly protein-binding nor lipophilic.
4.5 Distribution of LSD (Component Comparison) While ferrocene carboxylic acid remains extracellular, LSD distributes:

• Lipophilically,
• With good membrane permeability,
• Evenly in perfused tissues,
• Including the brain.

Thus, the pharmacokinetic profiles of the two hydrolysis products are completely different and independent of each other.
4.6 Toxicological Significance of Extracellular Storage The extracellular dominance means:

• No intracellular iron overload,
• No involvement in the labile iron pool (LIP),
• No increased risk for intracellular ROS generation.

This is toxicologically decisive, as oxidative damage arises almost exclusively intracellularly - extracellular iron forms, in contrast, are well buffered and not Fenton-active.
4.7 Extracellular Compartmentalization of Ferrocene Carboxylic Acid: Pharmacokinetic Basics The extracellular dominance of ferrocene carboxylic acid is an essential pharmacokinetic mechanism relevant for both toxicological evaluation and systemic classification of the substance. Unlike LSD, which is lipophilic and easily passes biological membranes including the blood-brain barrier, ferrocene carboxylic acid remains predominantly outside of cells due to its chemical and physicochemical properties.
4.7.1 Ionization and Membrane Permeability Ferrocene carboxylic acid exists largely as a deprotonated carboxylate anion at physiological pH. Charged molecules can hardly overcome cell membranes by passive diffusion. This represents the main reason for the extracellular distribution.
4.7.2 Lack of Specific Transport Mechanisms In contrast to iron ions, no transporters exist that actively take up ferrocene carboxylic acid. It is not a substrate for:

• DMT-1 (transports only Fe2+; Gunshin et al. 1997, PMID:9062189)
• ZIP14 (metal ion transport)
• Ferroportin (exports Fe2+)
• OAT1/3 or MCT (structure-dependent selectivity)

This lack of interaction with transport proteins prevents intracellular uptake.
4.7.3 Consequences for Systemic Distribution Ferrocene carboxylic acid thus remains:

• In blood plasma,
• In the interstitial space of tissues.

Intracellular uptake occurs only slightly and non-specifically in liver and kidney cells.
4.7.4 Blood-Brain Barrier The substance does not pass the blood-brain barrier because it:

• Is too polar,
• Possesses no active transport mechanism,
• Does not represent a substrate for transferrin or its receptors (TfR1/TfR2).

4.7.5 Pharmacokinetic and Toxicological Significance The extracellular localization means:

• No intracellular iron overload,
• No contribution to the labile iron pool (LIP),
• No intracellular ROS formation,
• Rapid renal elimination.

This is a central point, as oxidative cell damage arises almost exclusively intracellularly, while extracellular iron forms are efficiently buffered.

5. TOXICOLOGY OF FERROCENE AND FERROCENE CARBOXYLIC ACID​

5.1 Overview: Organometallic Particularities Ferrocene (Fe(C5H5)2) is a stable metallocene with a fully coordinated Fe2+ center. The stability prevents direct Fenton reactivity prior to metabolic cleavage (Stepnička, 2008, DOI:10.1007/978-3-540-46115-7).
Ferrocene carboxylic acid is the primary hydrolytic byproduct of 1-FE-LSD. Its toxicological evaluation is based on works from pharmaceutical chemistry, toxicology, and extensive investigations on ferrocene-containing drugs such as Ferroceron.
5.2 Metabolism of Ferrocene-containing Substances Central metabolic steps (Ullrich et al. 1984, DOI:10.1002/anie.198405651):

• Oxidation of the ferrocene core in the liver
• Conversion into stable carboxylic acids
• Release of Fe3+, which passes into ferritin and transferrin pools (Arosio & Levi, 2010, DOI:10.1038/nrm2892)
• No accumulation in the brain or in critical organs

A study on Ferroceron (Frolov et al. 1975, PMID:1234567) confirmed: → Main distribution in the liver, no toxicity at therapeutic doses.
5.3 Mutagenicity The most important study: Gasiorowski et al. (1999, PMID:10076192, DOI:10.1023/A:1009073905619). Results:

• Ames test in TA98, TA100, TA1535, TA1537 → negative
• Sister Chromatid Exchange (SCE) in human lymphocytes → negative
• No genotoxic effects with or without S9 activation

The National Toxicology Program (NTP) also documents for ferrocene (CAS 102-54-5): → Negative in chromosome aberration and micronucleus tests.
Conclusion: Ferrocene carboxylic acid possesses no mutagenic potential.
5.4 Carcinogenicity There are no indications that ferrocene or ferrocene carboxylic acid act as tumorigenic agents.
Henschler (1992, DOI:10.1007/BF02987543):

• No pre-carcinogenic lesions in 90-day studies
• No tumor induction
• Hepatic changes were adaptive, not pre-carcinogenic

Thus, ferrocene does not meet the criteria of a CMR substance of Class 1 or 2.
5.5 Reproductive Toxicity Data from animal experimental studies (Dunn et al. 1986, PMID:3732212) show:

• No teratogenic effects
• No effects on fertility
• Fetal weight reduced only with maternal toxicity (non-specific)

Thus, reproductive toxicity is not substance-specific, but dose-related and non-specific.
5.6 Oxidative Stress and ROS Formation Essential facts:

• Ferrocene is stable → no Fenton substrate
• Only metabolically released Fe2+/Fe3+ would theoretically be redox-active
• The amount from 1-FE-LSD hydrolysis: ~20 µg Fe
• This value is <0.01% of the brain iron pool (Rouault 2013, PMID:23553167)

Ferritin binds >4500 iron ions per molecule (Harrison & Arosio, 1996 PMID:8648576). → 20 µg iron are completely buffered. → No contribution to the labile iron pool (LIP). → No ROS-induced cell damage possible.

Conclusion: The toxicologically relevant species is not ferrocene itself, but free iron. The amounts in the µg range are physiologically unproblematic.

6. OVERALL CONCLUSION​

• 1-FE-LSD is a pure prodrug; the effect comes entirely from LSD.
• Ferrocene carboxylic acid is not mutagenic, not carcinogenic, and not toxic to reproduction.
• The released amount of iron (~20 µg) is biologically irrelevant.
• No BBB passage, no intracellular accumulation, no ROS danger.
• Ferrocene carboxylic acid is completely integrated into normal iron pools and excreted.

Thus, there is no toxicologically relevant burden from ferrocene carboxylic acid when taking 1-FE-LSD.

 

[Allylbenzene]

This is a very reasonable comment on 1Fe-LSDs questionable negative effects:

...
We can definitely conclude that 1Fe-LSD cannot be the first choice when it comes to psychedelics or LSD derivatives in general. There's a reason why 1Fe-LSD appeared after 1P-LSD, 1cP-LSD, 1V-LSD, 1D-LSD, 1T-LSD, 1B-LSD, 1S-LSD, 1-P-AL-LAD, LSZ, ALD-52 etc: It is simply the worst compromise (This is why one should protest for the legalization of LSD).

As far as I understand it: With 1Fe-LSD we are using a chemotherapeutic agent as a psychedelic. As Fredricology said: Ferrocen is by definition cytotoxic. Taking 1Fe-LSD would be comparable to taking a microscopic dose of a cytostatic drug (cancer medication), but the LSD component gives it the ability to cross the blood-brain barrier and accumulate specifically in nerve cells. The neurotoxic potential cannot be ignored because of the catalytic nature of ferrocene damage (one molecule generates many radicals).

Regarding genotoxicity: Ferrocenium ions (oxidized form) can interact directly with DNA or cause DNA strand breaks through the generated hydroxyl radicals (OH⋅OH⋅). Since LSD molecules tend to bind to receptor pockets (and some ergoline derivatives can also intercalate into cells), 1Fe-LSD brings the ROS generator into close proximity with the genetic information of the nerve cell. This is no longer just oxidative stress in the cytoplasm, but potential mutagenicity or direct damage to the nucleus of neurons (which cannot regenerate/divide).

I think the issue with the "Targeting" reversal has to be debated more and Fredricology has already said it:

The function of ferrocene is to kill cells (cytotoxicity): Ferrocene hybrids are specifically designed to trigger apoptosis (programmed cell death). The mechanism explicitly involves ROS generation (Fenton chemistry) and the depletion of cellular antioxidants. The cancer cells often absorb more iron or are more sensitive to ROS and Ferrocene is taking advantage of that, pretty cool. But with 1Fe-LSD the principle is reversed. The "targeting module" is LSD. LSD very specifically targets healthy neurons (5-HT2A-expressing pyramidal cells in the cortex).

So, if we consume 1Fe-Lsd we essentially performing a microscopic chemotherapy on our serotonin receptors.

 

[generation lsd25]

Is this an old post? Forget carbon, in other words organic. Forget Adam. And Eve. And Jehovah.


Remember real dirty black lsd.m.t let Mt=marktrade.

 

[SunshineSolutions]

Hello there,
I've checked 1FE-LSD a little bit more out since it is being sold to thousands of people every month in Europe. 1FE-LSD has the SMILES code: CCN(C([C@H]1CN(C)[C@]2([H])Cc3c4c(C2=C1)cccc4n(C(c5ccc[cH-]5)=O)c3)=O)CC.c6[cH-]ccc6.[Fe+2]

I have conducted a toxicological investigation based on this SMILES code using ProTox-3.0, ADMETlab 2.0, DeepToxLab, and toxCSM.

This analysis focuses on organ toxicity, toxicity endpoints, molecular mechanisms, as well as physicochemical and medicinal chemistry (e.g., Lipinski's or Pfizer's rules). The evaluation reveals predictions regarding hepatotoxicity, nephrotoxicity, respiratory toxicity, cardiotoxicity, and neurotoxicity; it assesses carcinogenicity, mutagenicity, immunotoxicity, and cytotoxicity; and it examines stress response pathways (e.g., p53, oxidative stress) alongside nuclear receptors (e.g., oestrogen and androgen receptors).

The predictions present a mixed picture, with clear indications of potential risks in specific areas:

1. Critical Toxicity Signals​

• Neurotoxicity: Classified as active in the ProTox assessment (probability 0.77).
• Immunotoxicity: Very high probability of activity (0.99). DeepToxLab also predicts immune cell cytotoxicity (0.824).
• Respiratory Toxicity: Multiple models classify the substance as active (probability 0.81 to 0.939).
• Mutagenicity/Genotoxicity: ProTox rates mutagenicity as active (0.63); DeepToxLab predicts genotoxicity with a probability of 0.999.
• Mitochondrial Toxicity: DeepToxLab forecasts a high risk in this domain (0.998).

2. Organ-Specific Risks & Clinical Predictions​

• Cardiovascular: While general cardiotoxicity is often deemed inactive, there are indications of a risk for hypertension (0.656) and arrhythmias (0.555). Furthermore, the risk of clinical cardiac disorders is high (0.82).
• Gastrointestinal: Very high probability of clinical adverse effects in the gastrointestinal tract (0.969).
• Cytotoxicity: CytoSafe provides mixed results: non-toxic to human embryonic kidney cells (HEK-293), but toxic to embryonic mouse cells (BALB/c 3T3).

3. Safety-Relevant Thresholds & Rules​

• Acute Toxicity (Rat): The oral LD50 is estimated at 612.9 mg/kg.
• Medicinal Chemistry Rules: The substance fails almost all standard filters (Lipinski, Pfizer, GSK, Golden Triangle), primarily due to its high lipophilicity ($logP = 5.195$) and structural complexity. According to Pfizer's rule, the combination of a high $logP$ and low polarity (TPSA) strongly indicates toxic potential.

Based on these values, it can be demonstrated that the manufacturer's argumentation resembles a toxicological Potemkin village: it relies on idealised wishful scenarios (rapid peripheral hydrolysis) and systematically ignores pharmacokinetics. However, when these public relations claims are confronted with the hard, in-silico calculated toxicological data (from ProTox-3.0, ADMETlab 2.0, and toxCSM), the defence collapses entirely. When contrasting the computational data with the manufacturer's position, the situation presents itself as follows:

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1. The Lipophilicity Lie: Evidence of the "Trojan Horse"​

Manufacturer's Claim: The resulting ferrocenecarboxylic acid (FCA) is purportedly too polar to cross the blood-brain barrier (BBB), thereby preventing intracellular accumulation.

The Data: It is not FCA that is consumed, but the intact 1FE-LSD. Toxicological analyses demonstrate extreme lipophilicity with a $logP$ value of 5.19 (according to toxCSM) or in the range of >4.5. ADMETlab 2.0 rigorously rejects the molecule based on Pfizer's rule, as a $logP > 3$ in combination with the specific structure is highly problematic from a toxicological standpoint.

The BBB Evidence: ProTox-3.0 confirms precisely the "Trojan Horse" scenario. BBB passage is classified as "Active" with a value of 0.92 (92% probability). The prodrug shoots through the blood-brain barrier before peripheral enzymes can degrade it. The toxin is smuggled directly into the brain.

2. The Denial of Mitochondrial Damage (SR-MMP: 0.879)​

Manufacturer's Claim: Ferrocene is allegedly stable, redox-inert, and possesses "no intracellular site of action" as well as no ROS (Reactive Oxygen Species) danger.

The Data: ADMETlab 2.0 provides the "smoking gun" evidence for cytotoxicity here. The Tox21 pathway parameter SR-MMP (Mitochondrial Membrane Potential) triggers dramatically at 0.879 ("Active"). ProTox-3.0 similarly classifies sr_mmp as "Active".

Critique: A probability of nearly 88% for the destruction of the mitochondrial membrane potential is catastrophic for nerve cells. This ruthlessly proves that the ferrocene is not inactive within the neuron. Driven by the membrane potential, it migrates into the mitochondria, encounters hydrogen peroxide (H2O2) there, and ignites the Fenton reactor (redox cycling Fe2+/Fe3+). The cell's powerhouses are shredded from the inside by reactive oxygen species (ROS).

3. The "Dilution Lie" and Hard Neurotoxicity (Neuro-Tox: 0.77)​

Manufacturer's Claim: The 20 µg of iron released is allegedly "toxicologically insignificant" (<0.01%) compared to the 250–350 µg of total iron in the brain.

The Data: ProTox-3.0 explicitly classifies 1FE-LSD as a neurotoxin ("neuro Active") with a value of 0.77 (77% probability).

Critique: The manufacturer is committing deliberate toxicological disinformation by confusing stoichiometry with catalysis. The 20 µg does not end up in the brain's secure ferritin vault but massively replenishes the labile iron pool (LIP). Because LSD specifically docks to 5-HT2A receptors, this iron is deposited precisely as a microscopic toxic hotspot at the synapse. There, the iron acts as a non-consuming catalyst for cellular destruction. Selling a substance with a 77% neurotoxicity probability as a "safe prodrug" borders on gross negligence.

4. The Concealed Immune Collapse (Immuno-Tox: 0.99)​

Manufacturer's Claim: FCA supposedly remains in the blood plasma, is excreted, and causes no cellular damage.

The Data: ProTox-3.0 delivers an absolutely devastating value for the "Toxicity end points": Immunotoxicity immuno Active 0.99. This represents a 99% certainty of immunotoxic effects.

Critique: This is the final nail in the coffin for chronic users (e.g., microdosers). The cell death caused by Fenton chemistry in the brain (lipid peroxidation/ferroptosis) alarms the brain's immune system (microglia). Microglia react to the oxidative debris with neuroinflammation ("smouldering inflammation"). Chronic brain inflammation is the absolute primary driver for "brain fog", depression, and the accelerated onset of neurodegenerative diseases such as Alzheimer's or Parkinson's. 1FE-LSD disrupts the delicate immunological balance of the neurons with almost 100% certainty.

5. Further Cellular and Systemic Alarm Signals​

Alongside neurotoxicity and immunotoxicity, toxCSM warns of general "High Toxicity" across almost all relevant categories.

ADMETlab 2.0 indicates a value of 0.808 for DILI (Drug-Induced Liver Injury), denoting a "high risk of DILI". This demonstrates that even the liver, which possesses massive ferritin buffers, is potentially damaged by the extreme reactivity of the ferrocene metabolite to be cleaved off.

6. Conclusion​

The hard in-silico data fully corroborate the worst fears of bioorganometallic chemistry: 1FE-LSD is not a harmless prodrug like 1P-LSD or 1S-LSD. It is a defectively designed Trojan horse that smuggles an immunotoxic (0.99) and neurotoxic (0.77) warhead—one which specifically destroys mitochondria (0.879)—directly into serotonergic brain cells. A mechanism that oncologists utilise (via ferrocifens) to eradicate malignant tumours is being marketed here to unwitting consumers as a "safe psychedelic" for healthy brain cells.

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Attached Reports:

1. ProTox-3.0

Spoiler

2. ADMETlab

Spoiler

3. DeepToxLab

Spoiler

4. toxCSM

Spoiler

Regarding the Credibility of the Data:

The reports (ProTox, ADMETlab, etc.) are based on machine learning. The artificial intelligence has "learnt" from thousands of known toxins and medications. When 1FE-LSD is inputted, the software compares the structural components (e.g., the ferrocene sandwich) against this database and calculates a probability. The advantage is that the AI recognises patterns that human researchers might overlook (e.g., the risk to the mitochondrial membrane potential). However, it must be noted that these are not genuine laboratory experiments conducted on cells or animals; rather, they are high-quality estimations. There are two primary factors why these data should nonetheless be taken extremely seriously:

• Convergence (Agreement): If a single programme indicates immunotoxicity, it could be an anomaly. But when ProTox-3.0 (0.99), toxCSM, and DeepToxLab independently raise alarms regarding genotoxicity, immunotoxicity, and respiratory toxicity, the statistical probability is exceptionally high that a tangible biological risk exists.
• Structural Logic: The software recognises that 1FE-LSD contains a transition metal (iron) in a highly lipophilic form. This aligns perfectly with the established chemistry of the Fenton reaction, which critics of 1FE-LSD have consistently warned against. The AI is effectively corroborating theoretical chemistry.

Furthermore:

• Credibility of physicochemical data (logP, MW, BBB): Very high (~95%). These physical values can be mathematically derived from the structure with remarkable precision.
• Credibility of toxicity endpoints (Immune/Genotox): High (~80%). Probabilities of 0.99 or 0.92 are statistically so significant that they would be treated as a "major red flag" in pharmaceutical research. Any drug candidate presenting such values would be halted immediately.
• Credibility of clinical prognoses: Moderate (~60%). Too many individual variables (such as diet and the user's genetics) play a role in this context.

Naturally, there are inherent weaknesses: AIs are only as reliable as their training data. Given that organometallics (like ferrocene-LSD) are exceedingly rare in standard pharmacology, the AI might overestimate or underestimate certain effects. The software informs us that a molecule is toxic at a specific location; however, it struggles to predict definitively whether the molecule will arrive there in sufficient quantities (although the BBB prediction of 0.92 serves as a formidable indicator).

 

[Skorpio]

Even though I take in silico predictions with more than a grain of salt, I think it is worthwhile to take a “guilty until proven innocent” approach with ingesting organometallic compounds, especially as the ferrocene is just a part of a sacrificial moiety– there are other prodrugs for LSD, why take any possible risk?

 

[SunshineSolutions]

Even though I take in silico predictions with more than a grain of salt, I think it is worthwhile to take a “guilty until proven innocent” approach with ingesting organometallic compounds, especially as the ferrocene is just a part of a sacrificial moiety– there are other prodrugs for LSD, why take any possible risk?

1FE-LSD is currently consumed by thousands of people per month in Germany alone.

I am pretty much shocked by the data. I knew that ferrocene wasn't something you wanted in your body. But I didn't expect it to have such a bad prognosis.
The earlier derivatives were significantly safer, but there is a massive disinformation campaign regarding 1FE-LSD, which I find extremely alarming, as the manufacturer has long enjoyed a good reputation in the industry. Even Hamilton Morris made an interview with the chemist behind the lab.

But I think the manufacturer is simply not honest in its information and this is a huge scandal if this is all true.

 

[kcrocker802]

"Acute Toxicity (Rat): The oral LD50 is estimated at 612.9 mg/kg." Idk that sounds pretty tame

 

[cnnka]

So has anyone tried it ? This post is a good reason to freak out during a trip lol

 

[Ismene2]

Why not just take LSD? Are the analogues better in some way or are they just more legal?