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. http://dx.doi.org/10.1111/bph.2011.163.issue-7.
© 2011 The Author. British Journal of Pharmacology © 2011 The British Pharmacological
Society.