The secrets of the production of mescaline have been revealed - a natural hallucinogenic drug with therapeutic potential * The drug extracted from the extinct peyote cactus has been used in religious ceremonies for thousands of years. Its effect on the serotonin receptors in the brain brought it back to consciousness as a research object in the field of psychiatric disorders
In the first half of the 20th century, mesqueline - an ancient hallucinogenic drug derived from cacti - starred not only among artists and bohemians but also in brain research. But in the fifties of the same century, he was pushed aside by the synthetic LSD molecule, which possessed him by thousands of counters. Recently, interest in mescaline research has been rekindled as part of a general trend to harness psychedelic substances for research and medicine in the field of mental health - a trend that has already given rise to directions for some promising psychiatric drugs. But a cactus and a thorn in it: the renewed interest in the old drug threatens to destroy the main natural source of mescaline - a modest-sized and slow-growing plant called peyote. now, Weizmann Institute of Science scientists reveal, step by step, the secrets of mescaline production in Peyote and pave the way for sustainable production of the substance in the laboratory.
"We revealed in research the natural production process of mescaline. If we fully copy this process in the laboratory using biotechnological tools - and we have already made considerable progress in this task - we can ensure a continuous supply of mescaline for the benefit of research and development of new psychiatric drugs without endangering the dwindling peyote population," says Dr. Shirley (Paula) Berman, who led the The research in the laboratory of Prof. Assaf Aharoni in the Department of Plant and Environmental Sciences. Dr. Berman adds that the peyote population is dwindling in the wild because cactus hunters tend to pick it in a way that harms its regrowth: too close to the root.
"The medical potential of mescaline is embodied in the fact that it acts on the same receptors in the brain as serotonin - the neurotransmitter whose effect is the basis of a whole family of antidepressants, anxiety and other mood disorders", Dr. Berman clarifies the promise inherent in the drug, although it has been outlawed in the states Many, but its use is still allowed in religious ceremonies and, under a special permit, in scientific and medical research. "It is possible that on the basis of mescaline and other natural psychedelic substances it will be possible in the future to develop a new generation of drugs with fewer side effects and with a longer-term effect than the existing drugs," she adds.
Cactus without thorns
Why do some cacti even produce psychedelic substances in the first place? This question intrigues Prof. Aharoni and his group. It is possible that the peyote - a round and thornless ground cactus - needs mescaline to protect itself from predators who are put off, according to this hypothesis, by the bitter taste it imparts to the plant and the physiological consequences of eating it. But, if we are talking about protection, why is the mescaline produced - even if in much smaller quantities - in San Pedro, the distant cousin of the peyote that is covered in thorns throughout?
One way or another, although there was a hypothesis regarding the biochemical route of mescaline production that had been studied for decades, most of the production steps remained in the dark and it was not even known which enzymes work in the process throughout. To dispel the fog, Dr. Berman and her colleagues first decoded the peyote genome in its entirety and found out which genes are expressed in different parts of the plant, and especially in the outer layers of the cactus dome where the highest concentrations of mescaline were measured. With the help of advanced tools of mass spectroscopy, a series of molecules suspected of being involved in the production of mescaline were identified. In addition, genes expressing enzymes with the potential to catalyze relevant biochemical reactions in the production process were located. Using tools of genetic engineering, the scientists examined the activity of these genes outside the cactus - in bacteria, yeast cells or model plants. After gathering pieces of knowledge from different directions, the researchers assembled all the pieces of the puzzle and succeeded in reconstructing the complete route of mescaline production in Peyote.
They discovered that the journey to mescaline begins with one step, or rather with one amino acid - tyrosine - and progresses further in six steps that include four enzyme families and three types of biochemical reactions. The scientists documented the entire process in detail and compared the production of mescaline in Peyote with its production process in San Pedro.
In the last phase of the research, the scientists harnessed the knowledge they had gained and recreated in the laboratory - using a model plant from the tobacco family - five of the six steps of mescaline production, including the production of all the intermediate molecules. The task was challenging because the plant "hijacked" some of the molecules for processes unrelated to mescaline production. "In future studies, we hope to reproduce the entire pathway in the laboratory in order to develop a method for producing natural mescaline in large quantities in yeast cells or in plants larger than peyote, which also grow faster," says Dr. Berman.
When the development is fully completed, the psychedelic substance will be available not only for the benefit of medical research, but will also make it possible to find out once and for all what role it plays in cacti. Dr. Berman explains: "If we see, for example, that insects avoid approaching a plant that has been engineered to produce large amounts of mescaline, or that this plant is particularly resistant to ultraviolet radiation - we will know much more about the natural functions of mescaline."
Also participating in the study were Dr. Louis de Haro, Dr. Anna-Rita Kabko, Dr. Shantan Panda, Dr. Gabriel Lichtenstein, Hila Hart, Dr. Adam Jozbiak, Dr. Jingoh Tsai, Dr. Dr. Shagit Meir and Dr. Ilana Rogachev from the Department of Plant and Environmental Sciences; Dr. Yonghui Dong, Dr. Yoav Peleg and Dr. Eva Heinig from the Department of Life Sciences Research Infrastructures; and Dr. Nikolai Kuzmich from the Israeli National Center for Personalized Medicine named after Nancy and Steven Grand.
Science books
- Mescaline is 1,000 to 3,000 times weaker than LSD and 30 times weaker than psilocybin, which is produced from hallucinogenic mushrooms, but its effect lasts longer - about 11 hours, compared to about 8 hours for LSD and close to 5 hours for psilocybin.
- To produce mescaline in sufficient quantity to affect the mood, no less than 6 peyote domes are needed.
- Peyote produces 3 times more mescaline than San Pedro per gram of plant tissue.
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