Taming THC: potential cannabis synergy and phytocannabinoid‐terpenoid entourage effects
TLDR
Particular focus will be placed on phytocannabinoid‐terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin‐resistant Staphylococcus aureus).Abstract:
Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it. More recently, the synergistic contributions of cannabidiol to cannabis pharmacology and analgesia have been scientifically demonstrated. Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol and cannabichromene, exert additional effects of therapeutic interest. Innovative conventional plant breeding has yielded cannabis chemotypes expressing high titres of each component for future study. This review will explore another echelon of phytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, α-pinene, linalool, β-caryophyllene, caryophyllene oxide, nerolidol and phytol. Terpenoids share a precursor with phytocannabinoids, and are all flavour and fragrance components common to human diets that have been designated Generally Recognized as Safe by the US Food and Drug Administration and other regulatory agencies. Terpenoids are quite potent, and affect animal and even human behaviour when inhaled from ambient air at serum levels in the single digits ng·mL−1. They display unique therapeutic effects that may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts. Particular focus will be placed on phytocannabinoid-terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin-resistant Staphylococcus aureus). Scientific evidence is presented for non-cannabinoid plant components as putative antidotes to intoxicating effects of THC that could increase its therapeutic index. Methods for investigating entourage effects in future experiments will be proposed. Phytocannabinoid-terpenoid synergy, if proven, increases the likelihood that an extensive pipeline of new therapeutic products is possible from this venerable plant.
LINKED ARTICLES
This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-7read more
Citations
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Cannabis sativa: The Plant of the Thousand and One Molecules
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The draft genome and transcriptome of Cannabis sativa
Harm van Bakel,Jake Stout,Jake Stout,Atina G. Cote,Carling M Tallon,Andrew G. Sharpe,Timothy P. Hughes,Jonathan E. Page,Jonathan E. Page +8 more
TL;DR: The availability of the Cannabis sativa genome enables the study of a multifunctional plant that occupies a unique role in human culture and will aid the development of therapeutic marijuana strains with tailored cannabinoid profiles and provide a basis for the breeding of hemp with improved agronomic characteristics.
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Are cannabidiol and Δ9‐tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review
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Safety and side effects of cannabidiol, a Cannabis sativa constituent.
Mateus M. Bergamaschi,Regina Helena Costa Queiroz,Antonio Waldo Zuardi,José Alexandre de Souza Crippa +3 more
TL;DR: In vivo and in vitro reports of CBD administration across a wide range of concentrations suggest controlled CBD may be safe in humans and animals, but further studies are needed to clarify reported in vitro and in vivo side effects.
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Practical considerations in medical cannabis administration and dosing
TL;DR: Suggestions are offered on cannabis-drug interactions, patient monitoring, and standards of care, while special cases for cannabis therapeutics are addressed: epilepsy, cancer palliation and primary treatment, chronic pain, use in the elderly, Parkinson disease, paediatrics, with concomitant opioids, and in relation to driving and hazardous activities.
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