ETH-LAD

ETH-LAD
Type	Psychedelic lysergamide (analytical/research)
Indications	No approved medical use; used as analytical/forensic reference standard
Related	LSD; AL-LAD; 1P-LSD
Legal status	Varies by jurisdiction; controlled in some (e.g., UK Class A); analogue/unscheduled in others
Class	Lysergamide
Mechanism	Partial agonist at 5-HT2A; activity at 5-HT1A/2C
Notable risks	Very potent; anxiety/panic; vasoconstriction
Wikidata	Q5324462

ETH-LAD (6-ethyl-6-nor-lysergic acid diethylamide) is a synthetic analogue of LSD (lysergic acid diethylamide) in the lysergamide family of psychoactive compounds. Structurally, it is nearly identical to LSD except for an ethyl group attached at the indole nitrogen (the “6-position”) of the lysergic acid skeleton. Like LSD, ETH-LAD is a powerful psychedelic drug that produces altered perceptions, vivid imagery, and changes in cognition and mood. It is known to be unusually potent – animal studies and human reports agree that ETH-LAD can be roughly two to three times stronger than LSD by dose. This compound is encountered mainly as a research chemical and has been studied in analytical and pharmacological research, but it has no approved medical or therapeutic use.

Definition and Scope

ETH-LAD belongs to the lysergamide class, a group of compounds derived from lysergic acid (itself from ergot fungus). All lysergamides share a common indole–quinoline backbone; LSD is the prototypical example. In ETH-LAD, one hydrogen of LSD’s six-membered ring nitrogen has been replaced by an ethyl group (hence “6-ethyl, 6-nor”). Laboratory studies confirm that this small change makes ETH-LAD slightly more potent than LSD. Like other lysergamides, ETH-LAD acts as a psychedelic or hallucinogen, meaning it profoundly alters sensory perception, mood, and cognition – often producing visual hallucinations, changes in thought patterns, and a distorted sense of time and self.

Class and naming: The name “ETH-LAD” indicates an ethyl substitution (“ETH-”) on the lysergic acid diethylamide (“LAD”) skeleton. Other examples include AL-LAD (allyl), PRO-LAD (propyl), and LSD itself (no extra substituent). These analogs are often informally called “LSD variants.”
Typical potency and dose: ETH-LAD is unusually potent by microgram dose. Typical human dose ranges (oral) are reported as approximately 15–25 µg (threshold), 50–150 µg (common psychedelic range), and 150 µg or above for a very strong experience. By comparison, LSD’s active range is usually 50–150 µg, so ETH-LAD often produces similar intensity at a lower dose (around one-half to one-third of the amount). In laboratory tests it reliably substitutes for LSD in animal experiments at about one-third the dose, reflecting roughly 2–3× the potency of LSD.
Routes of administration: Like LSD, ETH-LAD is typically taken orally, often as a small liquid solution or compound applied to a blotter paper. The effects usually begin within 20–60 minutes of ingestion. Sublingual (under-tongue) or buccal administration are also possible due to its potency, but oral dosing is standard. It has a long duration of action — on the order of 8–12 hours of noticeable effects, followed by a gradual "afterglow" phase.
Legal status: ETH-LAD is generally unscheduled by name in many countries, but it may be covered by “analogue” drug laws or other broad bans on synthetic hallucinogens. Some countries explicitly flag all LSD derivatives or have clauses for psychoactive analogs, making ETH-LAD effectively illegal in practice. It is usually marketed on the internet as a “research chemical” (with disclaimers against human use), but casual consumption is discouraged for legal and safety reasons.

Historical Context and Evolution

The exploration of LSD analogues dates back decades. Albert Hofmann’s invention of LSD in 1938 opened a field of structural chemistry around lysergic acid derivatives. In 1976, Japanese chemists Niwaguchi, Nakahara et al. first reported the synthesis of 6-nor-lysergic acid diethylamide derivatives, including ETH-LAD This early work (published in Yakugaku Zasshi) was mostly chemical and analytical in nature. The following year, Hods. Hashimoto and colleagues tested LSD and related compounds in animals, showing that ETH-LAD produced LSD-like physiological effects (for example, raising body temperature in rabbits and rats, similar to LSD) These studies laid the groundwork by establishing that adding an ethyl group at N(6) did not destroy the compound’s hallucinogenic properties.

Interest in LSD analogues surged again in the 1980s. A landmark study by Hoffman and Nichols (1985) systematically synthesized a series of LSD analogues with different N(6) substitutions They found that small alkyl groups at N(6) (ethyl, allyl) could yield compounds more potent than LSD, whereas larger groups eventually reduced activity. In that series, ETH-LAD (the N(6)-ethyl variant) was approximately 2–3 times as potent as LSD in rats trained to recognize LSD’s effects. That finding was consistent with qualitative accounts: Alexander and Ann Shulgin’s TIHKAL (The Continuation) from 1997 included ETH-LAD (#12 in their list) and summarized human testing. Shulgin reported that 20 µg of ETH-LAD taken orally already produces clear psychedelic effects (whereas LSD shows no effect at that dose), and 50–60 µg yields a full “LSD-like” experience These firsthand notes helped document the compound’s subjective profile and active dose range.

After these early studies, attention to ETH-LAD faded as the legal psychedelic era waned. However, with the rise of internet “research chemical” markets in the 2000s, ETH-LAD re-emerged among collectors and enthusiasts. In around 2015–2017, forensic and analytical chemists started encountering ETH-LAD in seized blotter papers or research kits. A series of publications by Brandt, Halberstadt and colleagues (the “Return of the lysergamides” series) provided detailed chemical analyses of ETH-LAD (and related compounds like 1P–ETH-LAD, a prodrug) These modern studies used advanced spectroscopic and chromatographic methods to confirm the identity and purity of ETH-LAD samples, and to compare them with LSD and other analogues. Today, ETH-LAD is recognized as one of the stronger N(6)-alkyl LSD analogues known, and its history spans from niche scientific literature in the 1970s to wider (though still specialized) use in the 2010s.

Core Mechanisms of Action

ETH-LAD produces its effects through the same basic neurochemical pathways as LSD. The hallmark mechanism is agonism (activation) of the serotonin 5-HT_2A receptor in the brain. Like LSD, ETH-LAD is believed to bind tightly to this receptor subtype on cortical neurons, altering neural signaling in circuits involved in perception, mood, and cognition. Activation of 5-HT_2A is widely considered the key step that leads to the profound sensory and psychological effects of classical psychedelics. In addition, ETH-LAD likely interacts with other serotonin receptors (such as 5-HT_1A and 5-HT_2C), as LSD does, and it may have some affinity for dopamine receptors (LSD is a partial D₁ dopamine agonist in some tests). However, the psychedelic experience of ETH-LAD appears largely to come from serotonin-2A–mediated changes in cerebral cortex activity.

Because ETH-LAD has almost the same shape as LSD, it fits into the receptor binding sites in a similar orientation. Animal studies confirm that ETH-LAD binds with high affinity in serotonin-rich areas; it fully substitutes for LSD in drug-discrimination tests, meaning that a rat cannot tell ETH-LAD from LSD if trained on LSD’s cue In practical terms, this means the internal experience is very similar to LSD. The main pharmacological difference is that ETH-LAD achieves this effect at a lower dose (higher potency). Some researchers have also noted that ETH-LAD may act as a partial agonist at certain dopamine receptors (D1 subtype) like LSD, although the behavioral significance of that is unclear.

Because ETH-LAD is so potent, even small dosing errors can produce unintended effects. Its long duration (often 8–12 hours) is also shared with LSD. In general, psychedelics like ETH-LAD do not induce dependence or addiction, and physiological toxicity appears low; the primary risks are psychological (such as anxiety or confusion during a trip) and behavioral (impaired judgment leading to accidents). Nonetheless, ETH-LAD is a powerful active substance, and practical guidelines emphasize starting with a very low dose and ensuring a safe environment.

Representative Examples and Case Studies

Animal studies: In classic pharmacology tests, ETH-LAD reproduces the key actions of LSD. For example, studies in rodents showed that rats trained to distinguish LSD from saline could not tell ETH-LAD apart from LSD – a phenomenon called “full substitution” – and required much lower doses to do so Similarly, ETH-LAD caused hyperthermia (elevated body temperature) in rabbits and rats just as LSD does, confirming a similar bioactivity profile These experiments help classify ETH-LAD as a true LSD-like hallucinogen.
Human reports (Shulgin): In TIHKAL: The Continuation (1997), Alexander Shulgin documented the first systematic human trials with ETH-LAD. He notes that 20 µg (micrograms) taken orally produced a “very real” effect – at that dose, LSD itself would be inactive A 50 µg dose took effect in about 15–30 minutes, reaching full influence by an hour. Shulgin described this 50 µg experience as having “few visual distortions” but pronounced inner imagery, and lasting about ten hours before tapering off A 60 µg dose began with moving visuals (such as shifting garden plants) and became quite LSD-like over a few hours, though “gentle” in intensity. These notes suggest that ETH-LAD’s qualitative effects are virtually indistinguishable from LSD’s – similar patterns of hallucination, mood change, and thought alteration – just achieved at a lower dose.
Analytical case: When ETH-LAD appears in forensic or clinical chemistry, labs identify it using advanced instrumentation. For instance, one 2017 report described ETH-LAD found in a seized blotter sample. Analysts used gas chromatography–mass spectrometry (GC–MS), high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) and other methods to characterize the compound These analyses showed the exact molecular fragments and spectra unique to ETH-LAD, definitively distinguishing it from LSD or other analogs. Such case studies underscore the need for updated forensic reference data whenever a new analogue emerges on the market.

Methods of Study

Scientists have approached ETH-LAD from several angles:

Chemical Synthesis: ETH-LAD is typically synthesized from lysergic acid or LSM-775 derivatives via amide formation and alkylation. The first reported method (1976) used traditional organic chemistry routes to attach the diethylamide group and introduce the N(6) ethyl substituent Modern chemists can also start from LSD and modify the indole nitrogen. Purification is crucial because impurities in such tiny-dose drugs could have disproportionate effects.
Analytical Chemistry: Because ETH-LAD appears as a law enforcement concern or research chemical, many studies focus on how to detect and confirm it. Common techniques include: Gas chromatography–mass spectrometry (GC–MS), which breaks the molecule into ion fragments to be identified by their mass-to-charge ratio; NMR spectroscopy, which provides a fingerprint of the chemical structure; infrared (IR) spectroscopy, which shows characteristic bond vibrations; and liquid chromatography with diode-array UV detection (HPLC-DAD). For example, Brandt et al. (2017) published detailed IR and MS spectra for ETH-LAD, noting peaks that distinguish it from LSD Such reference data allow toxicology labs to recognize ETH-LAD in a sample.
Biological Assays: In addition to whole-animal tests (see above “case studies”), researchers also use cellular and molecular techniques. Receptor binding assays measure how strongly ETH-LAD hooks to serotonin receptors; these have confirmed high affinity for 5-HT_2A. Animal behavioral assays, like the head-twitch response (HTR) in mice, provide rapid screening of hallucinogenic potency. ETH-LAD robustly induces head-twitches at low doses (reflecting high potency) and correlates well with its subjective potency in humans (HALBERSTADT 2019). Drug discrimination (as mentioned) is another classic behavioral test that quantifies a drug’s similarity to LSD.
Human Reports and Surveys: Beyond Shulgin’s narrative, some information comes from contemporary user reports and self-experimentation in controlled settings. These accounts, often collected online or in psychopharmacology labs (anonymously), describe the qualitative effects and compare them to LSD. Rigorous clinical trials have never been done, so this anecdotal data is the main source for human effects. Researchers and harm-reduction groups may compile questionnaires or case histories, but such “studies” are informal and must be interpreted cautiously.

Debates and Open Questions

Several topics remain under discussion among scientists and policy makers:

Safety and Toxicity: There is very little direct research on ETH-LAD’s safety margins. By inference, it appears physically non-toxic at normal doses (like LSD, where lethal toxicity is extremely low), but this is not proven. The main known risks are psychological: anxiety, panic, or risky behavior during a trip. One open question is whether ETH-LAD’s higher potency makes overdoses more likely (e.g. someone mismeasuring a dose). There are no controlled studies of neurotoxicity or long-term effects. Until more is known, medical professionals advise caution: any high-dose psychedelic carries potential dangers (such as precipitating latent psychiatric issues or causing accidents while intoxicated).

Therapeutic Potential: LSD and a few other psychedelics are undergoing research for mental health uses (depression, anxiety, PTSD, etc.). In theory, ETH-LAD could have similar benefits, but no clinical trials have been conducted. Because ETH-LAD is not patented or developed as a drug, there is little incentive for formal research. Some advocates speculate that an analog might someday offer advantages (for instance, different duration or subjective profile), but currently this is speculative. A key open question: Does the small molecular change produce any qualitative difference in the experience that would be therapeutically useful? Anecdotes suggest ETH-LAD is a slightly “cleaner” or less anxious experience than LSD for some users, but this is unproven and subjective.

Legal and Ethical Issues: The emergence of ETH-LAD in the research chemical market raises questions about regulation. Many jurisdictions have analogue laws that ban any unscheduled drug “substantially similar” to a controlled substance like LSD. Enforcement is inconsistent. Some argue that prohibiting novel psychedelics prevents research and potential therapeutic discoveries; others point out that without oversight, users face unknown risks. There is also debate in the psychedelic community about whether searching out analogs like ETH-LAD is responsible, given that LSD itself is generally source of most clinical research.

Pharmacological Questions: From a chemistry standpoint, ETH-LAD presents an interesting structure-activity problem. Small changes to the lysergamide scaffold can have unpredictable effects on potency or subjective quality. Researchers continue to study how N(6)-substitutions (ethyl, allyl, propyl, etc.) alter binding at serotonin receptors. Insights from these analogues could inform the design of new compounds that are potentially non-hallucinogenic (as a recent line of research has attempted with bromine-substituted LSD analogs for anxiety treatment) or highly selective in action. ETH-LAD’s relative potency confirms that N(6)-ethyl is a favorable modification for receptor activation, which may interest medicinal chemists studying neuropharmacology.

Significance and Applications

In practical terms, ETH-LAD’s significance lies mostly in scientific and forensic domains rather than widespread use. Key points include:

Neuroscience and Medicinal Chemistry: ETH-LAD (like LSD) serves as a tool for exploring serotonin receptor function and brain circuitry of perception. By comparing ETH-LAD to LSD and other analogues, researchers can refine their understanding of how molecular shape and flexibility translate to hallucinogenic effect. This knowledge can eventually contribute to drug development, whether of novel psychotherapeutics or novel imaging agents.

Forensic and Toxicological Relevance: As a substance encountered in the context of recreational drug markets, knowing about ETH-LAD is important for law enforcement and laboratories. Analytical data on ETH-LAD help toxicologists correctly identify it in biological samples or confiscated materials Such data also assist emergency doctors in case of accidental ingestion, as they can distinguish ETH-LAD symptoms from those of other drugs and provide appropriate care. The “Return of the lysergamides” studies have already populated many forensic databases with ETH-LAD’s fingerprint.

Cultural Impact: Within psychedelic subcultures, ETH-LAD is sometimes marketed as a legal or novel alternative to LSD. It has been sold in small quantities online under the suggestion that it causes fewer negative side-effects. However, mainstream recognition is low. It has not sparked significant cultural trends beyond niche forums. Its existence does highlight a recurring theme: whenever one psychedelic is controlled, chemists often create analogues in an attempt to circumvent the law. ETH-LAD is one example of this cycle.

Potential Therapeutic Insight (Very Tentative): While ETH-LAD itself is not used clinically, the broader class of LSD analogs is of interest in psychedelic therapy research. For example, LSD therapy is being revisited for anxiety and cluster headaches. In the future, different analogues might be explored to fine-tune duration or intensity. ETH-LAD’s slightly higher potency could theoretically allow lower dosing, which might reduce some side effects (though this is untested). At present, however, ETH-LAD does not have an established clinical role.

In summary, ETH-LAD is best understood as a research chemical that sharpens our picture of LSD-like psychedelics. It exemplifies how minor chemical modifications can sustain or even enhance the psychedelic experience. To a chemist or pharmacologist, ETH-LAD is a case study in structure–activity relationships. To a harm-reduction educator, it is a reminder that “different drip” variants of known substances continue to emerge. For the general public, ETH-LAD remains an obscure compound, but its study contributes to scientific knowledge about the effects of psychedelics on the brain.