New frontiers in the biosynthesis of psychoactive specialized metabolites
Ginny Li, Peter J. Facchini
Current Opinion in Plant Biology September 16, 2024 DOI: 10.1016/j.pbi.2024.102626 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | LSD Mescaline Psilocybin |
| Keywords | Hallucinogen Tryptamine Pharmacology Biochemistry |
| Citations | 6 |
| Key findings | Biosynthetic pathways for hallucinogenic metabolites from plants, fungi, and animals can be reconstituted in microorganisms, enabling synthetic biology to produce novel derivatives with potentially superior pharmacological properties. |
Abstract
The recent relaxation of psychedelic drug regulations has prompted extensive clinical investigation into their potential use to treat diverse mental health conditions including anxiety, depression, post-traumatic stress, and substance-abuse disorders. Most clinical trials have relied on a small number of known molecules found in nature, such as psilocybin, or long-known synthetic analogs of natural metabolites, including lysergic acid diethylamide (LSD). Elucidation of biosynthetic pathways leading to several psychedelic compounds has established an opportunity to use synthetic biology as a complement to synthetic chemistry for the preparation of novel derivatives with potentially superior pharmacological properties compared with known drugs. Herein we review the metabolic biochemistry of pathways from plants, fungi and animals that yield the medicinally important hallucinogenic specialized metabolites ibogaine, mescaline, psilocybin, lysergic acid, and N,N-dimethyltryptamine (DMT). We also summarize the reconstitution of these pathways in microorganisms and comment on the integration of native and non-native enzymes to prepare novel derivatives.
Comparable studies
Other narrative reviews on mescaline, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Study of a New Schizophrenomimetic Drug—Sernyl | 1959 | Review | |
| Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways | 2017 | Review | |
| Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine | 2020 | Review | |
| Legal highs: staying on top of the flood of novel psychoactive substances | 2015 | Review | |
| Psychedelic Drugs in Biomedicine | 2017 | Review |
Citations in the library
Cited by 3
- Pathway engineering for the biosynthesis of psychedelics Current Opinion in Biotechnology May 15, 2025
- Psychedelic Drugs Rediscovered-In Silico Study of Potential Fetal Exposure to Analogues of Psychedelic Drugs During Pregnancy. Molecules January 8, 2026
- Genome-based optimization of psilocybin and N,N-dimethyltryptamine biosynthetic pathways in E. coli using CRISPR-associated transposases Metabolic Engineering June 14, 2026
Cites 34
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- Lysergic Acid Diethylamide-Assisted Therapy in Patients With Anxiety With and Without a Life-Threatening Illness: A Randomized, Double-Blind, Placebo-Controlled Phase II Study. Biological Psychiatry February 1, 2023
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- Enzymatic Synthesis of Psilocybin Angewandte Chemie International Edition August 1, 2017
and 29 more in the library