N,N-dimethyltryptamine (DMT) is an indole alkaloid which has psychoactive properties and is present in various beverages all around the world. Legal synthesis of DMT and its use is banned in most countries, which makes it difficult to purchase it. The review article focuses on various methods for the chemical synthesis of DMT.
These include synthesis of DMT from melatonin, synthesis of DMT fumarate and fast method to obtain N,N-dimethyltryptamine (DMT) from inner barks of Mimosa tenuiflora, Fourier transform infrared spectroscopy (FTIR), single and tandem stage mass spectrometry (MS), nuclear magnetic resonance spectroscopy and melting point measurements in order to determine the structural characterization of N,N-dimethyltryptamine. Various results were obtained which were justified by previous literature reports. The percentage purity of the compound (> 95%) was determined by the use of ultraviolet (UV) absorption spectrometry and tryptamine as an analytical standard. Need more info? Read – https://bbgate.com/
Introduction:
Tryptamine derivatives are indole alkaloids which are largely found in biota. DMT was first synthesized in 1931, and was separated from Mimosa tenuiflora by Oswaldo Gonçalves de Lima in 1942. It was confirmed to be hallucinogenic in 1956. It is present in a wide range of plants and also found in the human body (Figure.1).
Figure 1. Shows the molecular structure of N,N-Dimethyltryptamine (DMT). [Retrieved from
Although DMT is also present in human body, it has been classified internationally as a Schedule 1 controlled drug, after the 1971 United Nations Convention on Psychotropic Substances. Substances which come under the Misuse of Drugs Act 1971 in the United Kingdom, are prohibited to be possessed, supplied, produced, imported or exported. Drugs are placed in Class A, B or C, with the Class A drugs considered to pose the greatest harm. DMT is placed in the Class A drugs and its possession can lead to up to 7-years custodial sentence and anything beyond can lead to a lifelong sentence.
However, it is important to give consideration needs to the therapeutic properties of this psychedelic drug. The compound is most commonly synthesized from tryptamine. During this process, the most common difficulty encountered is the presence of impurities in the form of other tryptamine and beta-carboline derivatives. In addition to this, the costs are high as compared to those in case of DMT extracted from plant matrices. Based on current literature, there is no fast method of extraction of DMT from the inner barks of M. tenuiflora and its structural characterization.
5-MeO-DMT (Figure.2) is a natural product of tryptamine and is usually called as the primary psychoactive component in the parotid gland secretions of Incilius alvarius, the Sonoran Desert toad. It is also present in low concentrations in a number of plants, seeds, and shrubs. The consumption of this material by human civilization for its psychoactive properties has been mentioned in scientific literature for decades. As a result of the recent discovery of high concentrations of 5-MeO-DMT in Sonoran toad’s secretions, reports indicate an increase in its recreational and spiritual use. The concentration of 5-MeO-DMT in Incilius alvarius is much higher as compared to sources derived from plants.
Figure 2. Shows molecular structure of 5-MeO-DMT.
Melatonin is similar to 5-MeO-DMT in structure except that it has one methyl group and 1 acetyl group instead of two methyl groups. Therefore, in order to convert melatonin to 5-MeO-DMT, the acetyl group should be switched with a methyl group.
Results and Discussion:
Extraction and isolation of N,N-dimethyltryptamine from M. tenuiflora
The liquid–liquid procedure for isolation of indole alkaloids from plant matrices was used in this procedure. Indole alkaloids lead to the formation of salts in an acidic aqueous medium, and show enhanced solubility and stability at low pH. Moreover, the protons in an acidic aqueous media help in the breakdown of sample matrix, so that the analyte is released more easily. Sodium hydroxide is added to basify the extract, and then combined with hexane, to form crude alkaloids (0.7% yield). Final purification was accomplished by recrystallization from hexane. The appearance of white crystals of N,N-dimethyltryptamine was seen after 24 h at a temperature of 5 °C, and had a yield of 0.3%.
Ultraviolet/visible molecular absorption spectrometry
For the purpose to quantify N,N-Dimethyltryptamine (DMT) isolated from the plant M. tenuiflora, it was assumed that tryptamine has similar molar absorbance at 290 nm as DMT at 275 nm, when these compounds are found in methanol. According to the current data, a DMT content higher than 95% was revealed. This was verified by a N,N-Dimethyltryptamine analytical curve at 275 nm, using the absorbance of eight standard DMT solutions at concentrations between 1.56 × 10− 3 and 0.1 mg mL− 1. Good agreement was obtained between the equations obtained for tryptamine at 290 nm and for N,N-dimethyltryptamine at 275 nm.
Synthesis of DMT from melatonin
Melatonin can be converted to 5-MeO-DMT by switching the acetyl group with a methyl group. Acetic acid is a methyl group combined with a carboxyl group. Carboxyl groups can be easily separated with heat. This process is called decarboxylation. Acetyl groups can be replaced by more reactive components due to the carbon atom which is double bonded to oxygen. Vinegar is added to melatonin and then the solution is microwaved. The carboxyl group in vinegar would be converted to carbon dioxide and dissipated. As a result, methyl and H+ would transform into methane and the water in vinegar would form polar bonds with hydrogen ions. The methyl groups may replace the double bonded oxygen to make the carbonyl group (a methyl group) resulting in the formation of 5-MEO-DMT, CO2, H20, and O2.
Synthesis of DMT fumarate
Freebase DMT is used for this purpose. It is oxidized over time and turns yellowish to red as oxidation is completed. Impurities present on the freebase make this process faster. On the other hand, very pure form of N,N-Dimethyltryptamine is more stable chemically especially if there are larger crystals. The freebase amines are alkaline in nature, therefore they can be neutralized by using an acid to form salts. Depending on the acid used, the most stable form of DMT salt is obtained by the reaction between DMT freebase and fumaric acid. Fumaric acid is used commonly in the food and beverage industry. The advantage of using fumaric acid is that the fumarate is a solid salt as compared to other salts which are very hygroscopic and absorb water from air.
Methods:
Sampling and preparation of plant material
Inner barks of stems and roots of M. tenuiflora were collected and dried at 40 °C to constant mass and powdered using a cutting mill.
Isolation of N,N-dimethyltryptamine from M. tenuiflora
60 grams of powdered plant material was dissolved in 300 mL of 0.1 mol L− 1 HCL acid in a beaker, followed by sonication in an ultrasonic bath for 24 h at a constant temperature of 25 °C. The extract was isolated by filtration and the residual material was washed twice with 300 mL of the acidic solution. The filtrates were combined and in order to remove any plant oils, the solution was washed with hexane. The aqueous solution was basified to pH 10–11 with NaOH, and then extracted with hexane. All the extracts combined were concentrated till they were dried under reduced pressure to form the crude alkaloid. The solid obtained from filtration was air-dried, and recrystallized from hexane.
Preparation of DMT fumarate
Freebase DMT, 350mg of fumaric acid per gram of DMT, anhydrous magnesium sulphate (Epsom salts) and acetone are used in the production of DMT fumarate. Anhydrous magnesium salts are used to remove water from the solvent. Other desiccants can also be used such as alumina, sodium sulphate or molecular sieves. However, Epsom salts are easier to use. The process involves baking the salt in a microwave oven until it becomes a hard and solid, as it has lost almost half of its weight. Once the salt is hard and cools off, it is placed in the solvent and left in it overnight or for a few hours. The dried solvent is then filtered for use without any Epsom salt in it. Freebase DMT is then dissolved in the dried solvent in minimal amounts. 390mg of fumaric acid per gram of DMT is added to the dried solvent. The two solutions are mixed slowly, after which the fumarate salt of DMT will start to precipitate.
It is important to remember that DMT fumarate dosage is not similar to freebase dosage. The reason is that the fumarate salt is heavier than freebase because of the presence of acid ligand.
Conclusion:
As far as the legal synthesis of DMT is concerned, it is a Schedule 1 controlled substance under the 1971 Convention on Psychotic Substances. Under the Misuse of Drugs Act 1971 in the United Kingdom, possession of DMT can lead to a custodial sentence of up to 7 years and its production can lead to life sentence.
Different methods of DMT synthesis have been employed in various researches. Acetyl group in melatonin is switched with methyl group to form 5-MeO-DMT. Fumaric acid and freebase DMT are used to form DMT fumarate. Synthesis of DMT from stems and roots of plants has also been in use. A simple and easy rapid acid–base extraction method was used for the separation of N,N-dimethyltryptamine from the plant stems and roots of M. tenuiflora, which resulted in the formation of white crystals having a purity level of greater than 95%. These crystals were structurally characterized using various absorption techniques such as ultraviolet absorption. Highly pure form of N,N-dimethyltryptamine obtained by this method makes it an analytical standard.
