1S-LSD (1-(3-(trimethylsilyl)propionyl)-lysergic acid diethylamide) is a

psychotropic substance A psychoactive drug, psychopharmaceutical, mind-altering drug, consciousness-altering drug, psychoactive substance, or psychotropic substance is a chemical substance that alters psychological functioning by modulating central nervous system acti ...

and

research chemical Research chemicals are chemical substances which scientists use for medical and scientific research purposes. One characteristic of a research chemical is that it is for laboratory research use only; a research chemical is not intended for human ...

belonging to the

lysergamide Lysergamides, also known as ergoamides or as lysergic acid amides, are amides of lysergic acid (LA). They are ergolines, with some lysergamides being found naturally in ergot as well as other fungi. Lysergamides are notable in containing embedd ...

class. It is the

trimethylsilyl A trimethylsilyl group (abbreviated TMS) is a functional group in organic chemistry. This group consists of three methyl groups bonded to a silicon atom minus;Si(CH3)3 which is in turn bonded to the rest of a molecule. This structural group i ...

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

1P-LSD 1P-LSD, also known as 1-propanoyl-lysergic acid diethylamide (1-propionyl-LSD), is a psychedelic drug of the lysergamide class that is a derivative and functional analogue of LSD and a homologue of ALD-52. It originated in 2015 when it appeared ...

and functions as a

prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...

and functional analogue of

LSD Lysergic acid diethylamide, commonly known as LSD (from German ; often referred to as acid or lucy), is a semisynthetic, hallucinogenic compound derived from ergot, known for its powerful psychological effects and serotonergic activity. I ...

. 1S-LSD was developed in response to legal restrictions on similar compounds, such as

1D-LSD 1D-LSD (1-(1,2-dimethylcyclobutane-1-carbonyl)-lysergic acid diethylamide, SYN-L-229) is a psychotropic substance and a research chemical that has potential psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary eff ...

, which were banned in Germany under the NpSG law in June 2024. The compound was introduced as a legal alternative by incorporating a trimethylsilyl group, which is not covered under current NpSG regulations. This chemical modification allows 1S-LSD to be legally sold in Germany as of September 2024. It is typically distributed in its hemi-D-tartrate form, a common format for lysergamides due to its stability and ease of use.

Chemistry

1S-LSD belongs to the lysergamide class of compounds, which are characterized by the

ergoline Ergoline is a core structure in many alkaloids and their synthetic derivatives. Ergoline alkaloids were first characterized in ergot. Some of these are implicated in the condition of ergotism, which can take a convulsive form or a gangrenous for ...

structure derived from lysergic acid. The compound is closely related to LSD and 1P-LSD but differs by the addition of a trimethylsilyl group on the propionyl chain. The nitrogen atom in the polycyclic indole group of the ergoline structure is a common site for chemical modifications, as it is highly reactive and accessible for various reactions. These modifications often include

alkylation Alkylation is a chemical reaction that entails transfer of an alkyl group. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting al ...

acylation In chemistry, acylation is a broad class of chemical reactions in which an acyl group () is added to a substrate. The compound providing the acyl group is called the acylating agent. The substrate to be acylated and the product include the foll ...

Mannich reaction In organic chemistry, the Mannich reaction is a three-component organic reaction that involves the amino alkylation of an acidic proton next to a carbonyl () functional group by formaldehyde () and a primary or secondary amine () or ammonia () ...

s, and

Michael addition In organic chemistry, the Michael reaction or Michael 1,4 addition is a reaction between a Michael donor (an enolate or other nucleophile) and a Michael acceptor (usually an α,β-unsaturated carbonyl) to produce a Michael adduct by creating a c ...

s. Such alterations are frequently explored in the synthesis of new analogues to modify pharmacological properties or evade legal controls. The addition of the trimethylsilyl group in 1S-LSD represents a strategic modification designed to keep the substance outside the coverage of Germany's New Psychoactive Substances Act (NpSG). Despite these changes, 1S-LSD likely retains a pharmacological profile similar to that of LSD, acting primarily as a serotonergic hallucinogen.

Pharmacology

While specific studies on 1S-LSD are limited due to its recent introduction, it is presumed to share pharmacological properties with LSD and its analogues. These substances typically act as partial agonists at serotonin receptors, particularly the

5-HT2a receptor The 5-HT2A receptor is a subtype of the 5-HT2 receptor, 5-HT2 receptor that belongs to the serotonin receptor family and functions as a GPCR, G protein-coupled receptor (GPCR). It is a cell surface receptor that activates multiple intracellular ...

, which is responsible for their hallucinogenic effects. The addition of the trimethylsilyl group in 1S-LSD is thought to slightly alter its binding affinity and metabolic profile, although empirical data is still needed.

Legal Status

Germany

As of August 2024, 1S-LSD remains legal in Germany, primarily due to the fact that its unique silicon-containing structural alteration circumvent the legislative controls imposed by the NpSG law. The legal status of 1S-LSD in Germany is likely subject to change with future amendments to the NpSG, similarly to its previously banned sister compounds

1V-LSD 1V-LSD (1-valeryl-D-lysergic acid diethylamide), sometimes nicknamed Valerie, is a psychotropic substance and a research chemical with psychedelic effects. 1V-LSD is an artificial derivative of natural lysergic acid, which occurs in ergot alkal ...

and

. However, it is anticipated that 1S-LSD will remain legal at least until mid-2025.

Other Countries

The legal status of 1S-LSD outside of Germany is not well-documented. Given its structural similarity to LSD, it may be considered a controlled substance analogue in jurisdictions like the United States, where laws like the Federal Analogue Act could apply. Potential users and researchers should verify the legal status of 1S-LSD in their respective countries before acquisition or use.

References