Published in full in the British Journal of Pharmacology.
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.
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There’s nothing that can hide the sweet smell of cannabis. But what is responsible for that impressive aroma? Terpenes not only give cannabis its signature scent, but may also have a role to play in its therapeutic effects.
Cannabis terpenes interact synergistically to create what scientists refer to as an “entourage effect” that magnifies the therapeutic benefits of the plant’s individual components—so that the medicinal impact of the whole plant is greater than the sum of its parts.
In this edition of Cannabis Conversations, Project CBD Director, Martin A. Lee, discusses the benefits of CBD, the “entourage effect” and the microbiome with Dr. Ethan Russo.
The entourage effect was a term first used to describe the various endocannabinoids that work together. Recent research emphasizes how two of these chemicals (OEA and PEA) exert subtle anti-inflammatory and antidepressant effects through a receptor called PPAR-alpha. PPAR-alpha regulates gene expression. Many plant cannabinoids - including CBD and THCA - activate the related protein, PPAR-gamma.