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Identification of minimum essential therapeutic mixtures from cannabis plant extracts by screening in cell and animal models of Parkinson’s disease

Medicinal cannabis has shown promise for the symptomatic treatment of Parkinson’s disease (PD), but patient exposure to whole plant mixtures may be undesirable due to concerns around safety, consistency, regulatory issues, and psychoactivity. Identification of a subset of components responsible for...

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Autores principales: Morash, Michael G., Nixon, Jessica, Shimoda, Lori M. N., Turner, Helen, Stokes, Alexander J., Small-Howard, Andrea L., Ellis, Lee D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9586206/
https://www.ncbi.nlm.nih.gov/pubmed/36278152
http://dx.doi.org/10.3389/fphar.2022.907579
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author Morash, Michael G.
Nixon, Jessica
Shimoda, Lori M. N.
Turner, Helen
Stokes, Alexander J.
Small-Howard, Andrea L.
Ellis, Lee D.
author_facet Morash, Michael G.
Nixon, Jessica
Shimoda, Lori M. N.
Turner, Helen
Stokes, Alexander J.
Small-Howard, Andrea L.
Ellis, Lee D.
author_sort Morash, Michael G.
collection PubMed
description Medicinal cannabis has shown promise for the symptomatic treatment of Parkinson’s disease (PD), but patient exposure to whole plant mixtures may be undesirable due to concerns around safety, consistency, regulatory issues, and psychoactivity. Identification of a subset of components responsible for the potential therapeutic effects within cannabis represents a direct path forward for the generation of anti-PD drugs. Using an in silico database, literature reviews, and cell based assays, GB Sciences previously identified and patented a subset of five cannabinoids and five terpenes that could potentially recapitulate the anti-PD attributes of cannabis. While this work represents a critical step towards harnessing the anti-PD capabilities of cannabis, polypharmaceutical drugs of this complexity may not be feasible as therapeutics. In this paper, we utilize a reductionist approach to identify minimal essential mixtures (MEMs) of these components that are amenable to pharmacological formulation. In the first phase, cell-based models revealed that the cannabinoids had the most significant positive effects on neuroprotection and dopamine secretion. We then evaluated the ability of combinations of these cannabinoids to ameliorate a 6-hydroxydopmamine (OHDA)-induced change in locomotion in larval zebrafish, which has become a well-established PD disease model. Equimolar mixtures that each contained three cannabinoids were able to significantly reverse the OHDA mediated changes in locomotion and other advanced metrics of behavior. Additional screening of sixty-three variations of the original cannabinoid mixtures identified five highly efficacious mixtures that outperformed the original equimolar cannabinoid MEMs and represent the most attractive candidates for therapeutic development. This work highlights the strength of the reductionist approach for the development of ratio-controlled, cannabis mixture-based therapeutics for the treatment of Parkinson’s disease.
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spelling pubmed-95862062022-10-22 Identification of minimum essential therapeutic mixtures from cannabis plant extracts by screening in cell and animal models of Parkinson’s disease Morash, Michael G. Nixon, Jessica Shimoda, Lori M. N. Turner, Helen Stokes, Alexander J. Small-Howard, Andrea L. Ellis, Lee D. Front Pharmacol Pharmacology Medicinal cannabis has shown promise for the symptomatic treatment of Parkinson’s disease (PD), but patient exposure to whole plant mixtures may be undesirable due to concerns around safety, consistency, regulatory issues, and psychoactivity. Identification of a subset of components responsible for the potential therapeutic effects within cannabis represents a direct path forward for the generation of anti-PD drugs. Using an in silico database, literature reviews, and cell based assays, GB Sciences previously identified and patented a subset of five cannabinoids and five terpenes that could potentially recapitulate the anti-PD attributes of cannabis. While this work represents a critical step towards harnessing the anti-PD capabilities of cannabis, polypharmaceutical drugs of this complexity may not be feasible as therapeutics. In this paper, we utilize a reductionist approach to identify minimal essential mixtures (MEMs) of these components that are amenable to pharmacological formulation. In the first phase, cell-based models revealed that the cannabinoids had the most significant positive effects on neuroprotection and dopamine secretion. We then evaluated the ability of combinations of these cannabinoids to ameliorate a 6-hydroxydopmamine (OHDA)-induced change in locomotion in larval zebrafish, which has become a well-established PD disease model. Equimolar mixtures that each contained three cannabinoids were able to significantly reverse the OHDA mediated changes in locomotion and other advanced metrics of behavior. Additional screening of sixty-three variations of the original cannabinoid mixtures identified five highly efficacious mixtures that outperformed the original equimolar cannabinoid MEMs and represent the most attractive candidates for therapeutic development. This work highlights the strength of the reductionist approach for the development of ratio-controlled, cannabis mixture-based therapeutics for the treatment of Parkinson’s disease. Frontiers Media S.A. 2022-10-05 /pmc/articles/PMC9586206/ /pubmed/36278152 http://dx.doi.org/10.3389/fphar.2022.907579 Text en Copyright © 2022 Morash, Nixon, Shimoda, Turner, Stokes, Small-Howard and Ellis. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Morash, Michael G.
Nixon, Jessica
Shimoda, Lori M. N.
Turner, Helen
Stokes, Alexander J.
Small-Howard, Andrea L.
Ellis, Lee D.
Identification of minimum essential therapeutic mixtures from cannabis plant extracts by screening in cell and animal models of Parkinson’s disease
title Identification of minimum essential therapeutic mixtures from cannabis plant extracts by screening in cell and animal models of Parkinson’s disease
title_full Identification of minimum essential therapeutic mixtures from cannabis plant extracts by screening in cell and animal models of Parkinson’s disease
title_fullStr Identification of minimum essential therapeutic mixtures from cannabis plant extracts by screening in cell and animal models of Parkinson’s disease
title_full_unstemmed Identification of minimum essential therapeutic mixtures from cannabis plant extracts by screening in cell and animal models of Parkinson’s disease
title_short Identification of minimum essential therapeutic mixtures from cannabis plant extracts by screening in cell and animal models of Parkinson’s disease
title_sort identification of minimum essential therapeutic mixtures from cannabis plant extracts by screening in cell and animal models of parkinson’s disease
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9586206/
https://www.ncbi.nlm.nih.gov/pubmed/36278152
http://dx.doi.org/10.3389/fphar.2022.907579
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