Mescaline Properties, Reactions and Applications

Introduction

Mescaline, or 3,4,5-trimethoxyphenethylamine CAS 54-04-6 is a naturally occurring psychoactive compound found primarily in certain cactus species, including the peyote cactus (Lophophora williamsii), the San Pedro cactus (Echinopsis pachanoi), and the Peruvian torch cactus (Echinopsis peruviana). Known for its hallucinogenic effects, mescaline has a long history of cultural and spiritual significance, particularly in the indigenous communities of North and South America.

In addition to its traditional uses, mescaline has garnered scientific interest due to its pharmacological effects, which are primarily mediated through the activation of the 5-HT2A serotonin receptor in the brain. This interaction results in changes in perception, mood, and thought processes, similar to those produced by other classical psychedelics like LSD and psilocybin. Mescaline’s structure, which consists of a phenethylamine core with three methoxy groups attached to a benzene ring, shares similarities with neurotransmitters. Given its psychoactive properties, handling mescaline requires safety precautions.

The legal status of mescaline varies across countries, reflecting its dual role as both a psychoactive compound with historical and cultural importance and a substance with potential for misuse. In many jurisdictions, mescaline is classified as a controlled substance, prohibited for recreational use due to its hallucinogenic effects.

Physical and Chemical Properties of Mescaline

Mescaline, 3,4,5-trimethoxyphenethylamine, CAS 54-04-6 is an alkaloid and a member of the phenethylamine class and is structurally similar to dopamine and other synthetic psychedelics like 2C-B. Mescaline appears as a crystalline powder that is typically white to light beige in color. The compound is highly soluble in ethanol and methanol but slightly soluble in water. Its molecular formula is C₁₁H₁₇NO₃, and it has a molecular weight of 211.26 g/mol. Density of mescaline is 1.067 g/cm³. The melting point of mescaline is 36°C, boiling point is 180°C at 12 mmHg and it undergoes sublimation under reduced pressure.

Chemically, mescaline is relatively stable under normal conditions, but it is sensitive to strong acidic and alkaline environments. Its three methoxy groups (-OCH₃) attached to the benzene ring at positions 3, 4, and 5 make it contribute to its psychotropic properties by affecting its binding affinity for serotonin receptors in the brain. Mescaline acts as an agonist at the 5-HT2A receptor, similar to other hallucinogens, inducing altered perception and cognition. The methoxy substituents increase electron density on the benzene ring, which reduces the reactivity of the ring toward electrophilic substitution but makes it more susceptible to nucleophilic attacks.

How Does Peyote Work? | The Science of Mescaline

Synthesis of Mescaline

The preparation of mescaline, CAS 54-04-6, can be accomplished by several different methods, extraction, and chemical synthesis. Methods for synthesizing mescaline often use 3,4,5-trimethoxybenzaldehyde as the starting material. In the condensation method, 3,4,5-trimethoxybenzaldehyde is condensed with nitromethane in the presence of a catalyst such as acetic acid to produce 3,4,5-trimethoxy-β-nitrostyrene. This intermediate can then be reduced to mescaline by catalytic hydrogenation, typically using palladium on carbon (Pd/C) or sodium borohydride as a catalyst. This reduction converts the nitrostyrene group to an ethylamine side chain, resulting in mescaline as the final product.

3,4,5-Trimethoxybenzaldehyde, acetic acid, and nitromethane are added to a flask with stirring, and cyclohexylamine is added. The mixture is heated to 80 °C and stirred for 3 hours.

​A mixture of isopropanol and water is added to the flask, then sodium borohydride is added. Beta-nitro-3,4,5-trimethoxystyrene is added in small portions so that the temperature of the mixture remains below 60 °C. Copper chloride in distilled water is added dropwise. The reaction mixture is then maintained at 80 °C for 30 min using external heating.

Another method of obtaining mescaline is from 3,4,5-trimethoxybenzaldehyde cyanohydrin acetate (can be obtained from 3,4,5-trimethoxybenzaldehyde cyanohydrin). 3,4,5-trimethoxybenzaldehyde cyanohydrin acetate is dissolved in ethanol and concentrated sulfuric acid and palladium are added. The reduction is carried out at room temperature and atmospheric pressure.

In addition to chemical synthesis, mescaline can be extracted from natural sources such as peyote (Lophophora williamsii), San Pedro (Echinopsis pachanoi), and Peruvian torch (Echinopsis peruviana). The process typically involves several steps: harvesting, drying, maceration, and chemical extraction using acid-base methods.

The first step in the extraction process involves harvesting and drying the cactus material to reduce its water content and concentrate the alkaloids. The dried cactus is then ground into a fine powder to increase the surface area for extraction. The powdered material is soaked in an acidic solution such as dilute hydrochloric acid or sulfuric acid, which protonates the mescaline, converting it to a water-soluble salt form. Following acid extraction, the solution is made alkaline using a strong base such as sodium hydroxide to convert the mescaline to its free base form. Mescaline free base is less soluble in water and can be extracted into an organic solvent such as diethyl ether, chloroform, or toluene. The organic solvent layer is then collected and evaporated.

Chemical Reactions of Mescaline

Mescaline, CAS 54-04-6 as a phenethylamine derivative with three methoxy groups on the aromatic ring. Mescaline can undergo reactions typical for both amines and substituted aromatics, including oxidation, demethylation, and acetylation.

One key reaction of mescaline is oxidation, which targets the ethylamine side chain. In the presence of strong oxidizing agents, such as potassium permanganate, mescaline can be oxidized to produce 3,4,5-trimethoxyphenylacetic acid. This reaction serves as a model for studying mescaline’s metabolic pathways in vivo, as similar transformations can occur in biological systems.

Mescaline also reacts readily with acylating agents, such as acetyl chloride or acetic anhydride, to form N-acetylmescaline. This acylation of the primary amine is a straightforward modification that can alter the compound’s pharmacokinetic properties, such as its solubility and permeability across biological membranes.

The methoxy groups on mescaline’s benzene ring make it resistant to electrophilic substitution reactions, such as nitration, as the electron-donating nature of the methoxy groups significantly decreases reactivity toward electrophiles. However, demethylation with boron tribromide produces 3,5-dimetoxy-4-hydroxyphenethylamine, a catecholamine derivative.

Applications of Mescaline

Mescaline, CAS 54-04-6 has a range of applications, primarily in psychopharmacology, neurobiology, and psychiatry, due to its structural similarities to neurotransmitters like dopamine and serotonin. The compound is historically and culturally significant, particularly in indigenous spiritual practices in North and South America, where it has been used for centuries in rituals to induce altered states of consciousness.

In psychopharmacology, mescaline is used as a model compound to study the mechanisms of psychedelic effects in the brain. Its action as a 5-HT2A receptor agonist provides insight into how serotonergic systems influence perception, mood, and cognition. Researchers use mescaline in controlled settings to investigate its effects on neural circuits, comparing it with other hallucinogens like LSD and psilocybin to understand how these compounds alter brain activity. For instance, mescaline-induced changes in perception and emotion have been studied with functional MRI (fMRI) and electroencephalography (EEG) to reveal alterations in neural connectivity, which may offer clues about potential therapeutic effects for conditions like depression and anxiety.

Beyond its therapeutic potential, mescaline serves as an important chemical template for the development of novel psychoactive compounds in medicinal chemistry. By modifying the mescaline structure—such as altering its side chain or methoxy groups—chemists have developed analogs with varying potency, selectivity, and duration of action. These analogs help researchers assess structure-activity relationships (SAR) within the phenethylamine class, contributing to the design of compounds with specific pharmacological profiles.

Health Effects of Mescaline

Mescaline, CAS 54-04-6 is used under strict regulatory guidelines due to its potent psychoactive effects and potential health risks. Exposure, even in small amounts, can lead to these effects, that underlining the need for controlled environments and personal protective equipment.

Acute exposure to mescaline can cause a range of physiological symptoms, including elevated heart rate, blood pressure fluctuations, nausea, and dizziness. Inhalation or accidental ingestion of mescaline, even in microgram quantities, may lead to mild to moderate psychoactive effects within 30 minutes to an hour.

Chronic exposure and high doses of mescaline in research animals have highlighted potential neurotoxic effects, especially with prolonged or repeated administration. Animal studies suggest that mescaline can induce oxidative stress in neural tissues, which may lead to cellular damage. Although these effects are not fully understood in humans, they underscore the importance of careful dosage control in research settings. Long-term exposure in humans has not been systematically studied due to legal constraints, but these findings in animal models raise important considerations for laboratory safety and the potential risks of chronic exposure.

Safety Precautions

Working with mescaline, CAS 54-04-6, in the laboratory requires safety protocols due to its strong psychoactive effects. Basic safety precautions when working with mescaline include wearing PPE such as gloves, lab coats, and safety goggles to prevent direct skin contact, which could lead to absorption and unintended psychoactive effects.

It is recommended to work with mescaline in a well-ventilated area or under a fume hood to avoid inhalation of any powder or vapors, which could lead to respiratory effects. In the laboratory, avoid eating, drinking, or applying cosmetics in areas where mescaline is handled to prevent accidental ingestion.

It should be kept in a cool, dry, and well-ventilated storage area away from heat sources, open flames, or other flammable materials. Additionally, it should be stored away from strong oxidizers, acids, or bases, which could react with the compound.

Conclusion

Mescaline, CAS 54-04-6 a naturally occurring psychoactive compound. As a 5-HT2A receptor agonist, mescaline induces profound alterations in perception, mood, and cognition. Its structure, characterized by a phenethylamine with methoxy substitutions, offers insights into the relationship between molecular configuration and receptor activity. From a chemical perspective, mescaline’s synthesis and extraction methodologies provide pathways to obtaining this compound for different purposes. Mescaline’s significance spans diverse fields, from ethnobotany and chemistry to neuroscience and psychiatry.

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