Synthetic Pathway of Nonpsychoactive Cannabidiol from Psychoactive Tetrahydrocannabinol: A DFT Guide.
Sirilak Kongkaew, Waraporn Parasuk, Vudhichai Parasuk
The Journal of Organic Chemistry July 24, 2026 DOI: 10.1021/acs.joc.6c00898 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or computational chemistry study Peer reviewed |
|---|---|
| Topics | Cannabis CBD |
| Key points | Proposes a two-step reaction pathway converting Δ9-THC to CBD via boron trichloride and a selective base, with TS4-5 as the rate-determining transition state (activation free energies of 49.4, 50.3, and 54.1 kcal mol-1 for Δ9-THC, Δ8-THC, and CBN). The authors report the overall reaction is highly exergonic (ΔGrxn = -33.9 to -32.9 kcal mol-1), suggesting spontaneous conversion under mild conditions. |
Abstract
In this study, a reaction pathway for converting the psychoactive compound Δ9-THC into the nonpsychoactive cannabidiol (CBD) was proposed. Related cannabinoids, including Δ8-THC and cannabinol (CBN), were also examined. The transformation proceeds via two key steps: (i) hydrogen elimination and cyclic ether ring cleavage, and (ii) hydrolysis to form hydroxyl groups, facilitated by boron trichloride (BCl3) as a Lewis acid and 2,6-di-tert-butyl-4-methylpyridine as a selective base. Energy calculations indicate that TS4-5 is the rate-determining transition state for Δ9-THC, Δ8-THC, and CBN, with corresponding activation free energies of 49.4, 50.3, and 54.1 kcal mol-1, respectively. The overall reaction is highly exergonic (ΔGrxn = -33.9 to -32.9 kcal mol-1), indicating spontaneous conversion under mild conditions. These results provide a foundation for developing efficient and scalable production of nonpsychoactive cannabinoids, supporting the development of safe and commercially viable therapeutic applications.
Comparable studies
Other theoretical and historical papers on CBD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabis Use and Neuroadaptation: A Call for Δ9-Tetrahydrocannabinol Challenge Studies | 2022 | Theoretical or philosophical paper | |
| Informing the Cannabis Conjecture: From Life's Beginnings to Mitochondria, Membranes and the Electrome-A Review. | 2023 | Theoretical or philosophical paper |
Citations in the library
Cites 4
- Hexahydrocannabinol and closely related semi-synthetic cannabinoids: A comprehensive review. Drug Testing and Analysis June 2, 2023
- THC and CBD: Similarities and differences between siblings. Neuron February 1, 2023
- Differential Enantiomer-Specific Signaling of Cannabidiol at CB1 Receptors. Molecular Pharmacology December 2022
- Cannabis induced psychosis: a systematic review on the role of genetic polymorphisms. Pharmacological Research May 1, 2022