Comprehensive Guide to LSD Synthesis: Pathways, Mechanisms & Historical Overview

A Simplified Guide to LSD Synthesis and Its Historical Context

Lysergic acid diethylamide (LSD) is a compound that has been the subject of much interest, research, and controversy over the years. Its synthesis has evolved, and many methodologies have emerged. This article provides a comprehensive overview of the LSD synthesis pathway, exploring its history, mechanisms, and practical approaches.

Historical Background:

The LSD synthesis year was in 1938 when Dr. Albert Hofmann first synthesized LSD from lysergic acid derivatives extracted from ergot fungus. The historical context sets the foundation, with figures like Tim Scully playing pivotal roles in the underground LSD synthesis during the countercultural movement. Websites like Erowid have since documented user experiences and some aspects of the synthesis process.

Basic Mechanism:


At its core, the LSD synthesis mechanism involves the conversion of lysergic acid to its diethylamide derivative. The reaction's intricacy requires attention to detail, and understanding the LSD synthesis diagram can significantly assist. There are various LSD synthesis offshoots that have been developed over the years, giving chemists options based on available reagents and desired yields.

Step-by-Step Synthesis for Beginners:


  • Lysergic acid (cas 82-58-6)2.80 g;
  • Methylene chloride (DCM; CH2Cl2) 190 ml;
  • N,N-Diethylmethylamine (cas cas 616-39-7) 1.81 g;
  • PyBOP (cas 128625-52-5) 5.70 g;
  • Diethylamine (cas 109-89-7) 0.84 g;
  • Ammonium hydroxide (NH4OH) 100 ml 7.5 M;
  • Sodium bicarbonate (cold saturated aq solution) NaHCO3 40 ml;
  • Ethyl acetate (EtOAc) 60 ml;
  • Sodium sulphate (MgSO4) ~50 g;
  • Deionized H2O ~200 ml;


  • Round bottom flask 250 mL;
  • Retort stand and clamp for securing apparatus;
  • Magnetic stirrer;
  • Separatory funnel 500 mL (optional);
  • Glass rod and spatula;
  • Laboratory scale (0.1-100 g is suitable);
  • Measuring cylinder 100 mL;
  • Funnel;
  • Filter paper;
  • Rotovap machine (optional);
  • Vacuum source;
  • Buchner flask and funnel;
  • Beakers 100 ml x2 and 250 ml x2;


  • Begin by adding 2.80g of lysergic acid into 100 ml of methylene chloride (DCM; CH2Cl2) with stirring.
  • Incorporate 1.81 g of N,N-Diethylmethylamine into the reaction mix and stir for 5 minutes.
  • Introduce 5.70 g of PyBOP and stir for another 5 minutes.
  • Add 0.84 g of diethylamine and maintain stirring at room temperature for 60 minutes.

To halt the reaction, quench it with 100 ml of 7.5 M concentrated ammonium hydroxide (NH4OH). Subsequently, separate the layers, extracting the aqueous phase with DCM thrice, each time using 30 ml. Pool the organic layers and concentrate the mixture using a rotovap machine at 35°C under a high vacuum setting.

Dissolve the residual matter in 40 ml of cold saturated sodium bicarbonate (NaHCO3) solution. Extract this with ethyl acetate (EtOAc) three times, using 20 ml for each extraction. Merge the organic layers, wash them with deionized water, brine, and then dry over MgSO4. After filtering, evaporate the solution in a rotovap machine at 40°C under vacuum until a constant weight is reached. This procedure typically yields approximately 3.13 g of product with a purity of 93% before optional chromatography purification.

Exploring the Process of Synthesis:

This process, originating from ergotamine to LSD synthesis and leading to LSD from lysergic acid synthesis, showcases the transformation of natural compounds into more complex derivatives. Additionally, it's worth noting that LSD interacts with serotonin receptors in the brain, suggesting that LSD increases serotonin synthesis.

LSD organic synthesis is a fascinating journey that reflects humanity's urge to understand, manipulate, and benefit from the world of molecules. Books like PIHKAL and TIHKAL by Alexander Shulgin further explore these aspects and delve into the synthesis and effects of numerous psychoactive compounds, shedding light on the vast world of organic synthesis and its myriad possibilities.

Disclaimer: While this article provides an overview of the synthesis process, it's essential to understand that producing LSD without the requisite legal permissions is illegal in many jurisdictions. Always prioritize safety and legality.

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