Taming THC: potential cannabis synergy and phytocannabinoid‐terpenoid entourage effects

Summary & key facts

This paper is a review of research on cannabis chemicals beyond THC. The authors describe how other plant compounds called phytocannabinoids and terpenoids might work together to change cannabis effects. They point out evidence that cannabidiol and other minor cannabinoids can change how cannabis works, and that common fragrant compounds in the plant may also affect the body at very low levels. The review says these interactions could matter for pain, inflammation, mood, addiction and infections, and it suggests ways future studies could test these "entourage" effects. The authors also note that some non-cannabinoid components might reduce THC's intoxicating side effects, but they stop short of saying this is proven.

Key facts:

• THC was isolated in 1964 and has been the main focus of cannabis research since then.
• Scientists have shown that cannabidiol, a different cannabis chemical, can change how cannabis affects pain and other responses.
• Other plant cannabinoids such as tetrahydrocannabivarin, cannabigerol and cannabichromene are reported to have additional effects that could be useful for therapy.
• The paper highlights a group of fragrant plant chemicals called terpenoids, including limonene, myrcene and linalool, which are common in foods and are generally considered safe by regulators like the US Food and Drug Administration.
• Some terpenoids are active at very low blood levels and can change animal or human behaviour when inhaled, so they might add to or change the effects of cannabinoids.
• The authors present evidence and ideas suggesting that combinations of phytocannabinoids and terpenoids could work together to affect pain, inflammation, depression, anxiety, addiction, epilepsy, cancer and some infections.
• The review reports that plant breeders have created cannabis types high in particular cannabinoids or terpenoids so those combinations can be studied.
• The authors suggest methods for future experiments and say that if these "entourage" interactions are proven, many new medicinal products from cannabis could become possible.

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. http://dx.doi.org/10.1111/bph.2011.163.issue-7.

Topics

Biochemical Analysis and Sensing Techniques Cannabis and Cannabinoid Research GABA and Rice Research

Categories

Health Sciences Medicine Pharmacology

Tags

Biochemistry Cannabidiol Cannabinoid Cannabis Chemistry Dronabinol Effects of cannabis Hallucinogen Medicine Pharmacology Psychiatry Receptor Terpenoid

Substances

Cannabis

Conditions & symptoms

Addiction Anxiety Chronic Pain Depression Addiction or harmful habbits Anxiety or worry Chronic pain Sadness or low mood