Phytocannabinoids and terpenoids are synthesized in cannabis, in secretory cells inside glandular trichomes ( Figure 1) that are most highly concentrated in unfertilized female flowers prior to senescence ( Potter, 2004 Potter, 2009). Nomenclature follows conventions in Alexander et al. The current review will reconsider essential oil (EO) agents, their peculiar pharmacology and possible therapeutic interactions with phytocannabinoids. Only recently has renewed interest been manifest in THC analogues, while other key components of the activity of cannabis and its extracts, the cannabis terpenoids, remain understudied ( McPartland and Russo, 2001b Russo and McPartland, 2003). While a host of phytocannabinoids were discovered in the 1960s: cannabidiol (CBD) ( Mechoulam and Shvo, 1963), cannabigerol (CBG) ( Gaoni and Mechoulam, 1964b), cannabichromene (CBC) ( Gaoni and Mechoulam, 1966), cannabidivarin (CBDV) ( Vollner et al., 1969) and tetrahydrocannabivarin (THCV) ( Gill et al., 1970), the overwhelming preponderance of research focused on psychoactive THC. Phytocannabinoid-terpenoid synergy, if proven, increases the likelihood that an extensive pipeline of new therapeutic products is possible from this venerable plant.Ĭannabis has been a medicinal plant of unparalleled versatility for millennia ( Mechoulam, 1986 Russo, 2007 2008 ), but whose mechanisms of action were an unsolved mystery until the discovery of tetrahydrocannabinol (THC) ( Gaoni and Mechoulam, 1964a), the first cannabinoid receptor, CB 1 ( Devane et al., 1988), and the endocannabinoids, anandamide (arachidonoylethanolamide, AEA) ( Devane et al., 1992) and 2-arachidonoylglycerol (2-AG) ( Mechoulam et al., 1995 Sugiura et al., 1995). Methods for investigating entourage effects in future experiments will be proposed. Scientific evidence is presented for non-cannabinoid plant components as putative antidotes to intoxicating effects of THC that could increase its therapeutic index. 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). They display unique therapeutic effects that may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts. Terpenoids are quite potent, and affect animal and even human behaviour when inhaled from ambient air at serum levels in the single digits ng 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. This review will explore another echelon of phytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, α-pinene, linalool, β-caryophyllene, caryophyllene oxide, nerolidol and phytol.
Innovative conventional plant breeding has yielded cannabis chemotypes expressing high titres of each component for future study.
Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol and cannabichromene, exert additional effects of therapeutic interest. More recently, the synergistic contributions of cannabidiol to cannabis pharmacology and analgesia have been scientifically demonstrated. Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it.