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Polymorph prediction through structural isomorphism and discovery of a new crystalline form of cannabidiol

Lookup NU author(s): Lina Mardiana, Glen Hebberd, Elle Watson, Dr Paul Waddell, Professor Mike ProbertORCiD, Dr Michael HallORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Cannabidiol (CBD) is a naturally occurring phytocannabinoid, approved for use in the US and other countries for the treatment of seizures associated with Dravet syndrome, Lennox-Gastaut syndrome and tuberous sclerosis complex, and is commonly isolated and used in its well-known stable crystalline form (Form 1). We present a study of the crystal structures of an homologous series of CBD analogues, containing variations in the alkyl sidechain at C-5’, which shows that CBD form 1 is an unusual structural outlier. CBD C-5’ homologues display homologous isomorphism, existing as isomorphic variants in the solid state, whereas CBD form 1 shows notably different crystal packing, suggesting the potential existence of a previously uncharacterized isomorphic CBD polymorph. This predicted isomorphic CBD polymorph (Form 2) was subsequently discovered through the use of high throughput crystallisation techniques (ENaCt) in combination with CBD homologue seeding, with single crystal X-ray diffraction analysis demonstrating its fit within the larger isomorphic series. This work represents the first example of directed polymorph discovery using high throughput ENaCt techniques.

Publication metadata

Author(s): Straker H, McMillian L, Mardiana L, Hebberd G, Watson E, Waddell PG, Probert MR, Hall MJ

Publication type: Article

Publication status: Published

Journal: CrystEngComm

Year: 2023

Volume: 25

Issue: 16

Pages: 2479-2484

Print publication date: 28/04/2023

Online publication date: 29/03/2023

Acceptance date: 29/03/2023

Date deposited: 31/03/2023

ISSN (electronic): 1466-8033

Publisher: Royal Society of Chemistry


DOI: 10.1039/D3CE00041A


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Funder referenceFunder name
Indonesian Endowment Fund for Education (LPDP)
Newcastle University