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Polypharmacology Shakes Hands with Complex Aetiopathology
James S Brodie1, Vincenzo Di Marzo2, Geoffrey W Guy1
1GW Pharmaceuticals plc, Sovereign House, Vision Park, Histon, Cambridge, CB24 9BZ, UK.
Trends in Pharmacological Sciences
|October 6, 2015
Summary
Plant cannabinoids offer multitarget, systemic benefits for chronic diseases, unlike single-target treatments. A new
Area of Science:
- Pharmacology and Systems Biology
- Natural Product Medicine
- Drug Discovery and Development
Background:
- Chronic diseases involve physiological system deviations and malfunctioning biological networks.
- Compensatory mechanisms in chronic diseases can impair dynamic responses and reduce treatment efficacy.
- Conventional single-target treatments often fall short for complex, multifactorial chronic conditions.
Purpose of the Study:
- To explore the potential of multitarget, systemic, and prohomeostatic actions of plant cannabinoids as a model for future medicines.
- To re-examine the concept of polypharmacology using emerging cannabinoid medicines as examples.
- To introduce and describe a new empirical model, the 'therapeutic handshake', for predicting the efficacy and safety of compound combinations.
Main Methods:
- Review of existing literature on chronic diseases, compensatory mechanisms, and conventional treatments.
- Analysis of the pharmacological actions of plant cannabinoids, including combined extracts and pure compounds like cannabidiol.
- Development and conceptualization of the 'therapeutic handshake' model for predicting combination therapy outcomes.
Main Results:
- Plant cannabinoids demonstrate multitarget, systemic, and prohomeostatic effects, suggesting a paradigm shift from single-target approaches.
- Examples like Sativex(®) (combined cannabis extracts) and cannabidiol for epilepsy highlight the clinical potential of cannabinoid-based medicines.
- The 'therapeutic handshake' model provides a framework for evaluating the synergistic or antagonistic interactions within compound combinations.
Conclusions:
- The multitarget approach exemplified by plant cannabinoids offers a promising direction for treating complex chronic diseases.
- Polypharmacology, guided by models like the 'therapeutic handshake', is crucial for optimizing the efficacy and safety of natural or synthetic compound combinations.
- Further research into the 'therapeutic handshake' model could advance the development of more effective and safer combination therapies for various pathologies.
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