The “Entourage Effect”: Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders

Abstract

Mood disorders are the most prevalent mental conditions encountered in psychiatric practice. Numerous patients suffering from mood disorders present with treatment-resistant forms of depression, co-morbid anxiety, other psychiatric disorders and bipolar disorders. Standardized essential oils (such as that of Lavender officinalis) have been shown to exert clinical efficacy in treating anxiety disorders. As endocannabinoids are suggested to play an important role in major depression, generalized anxiety and bipolar disorders, Cannabis sativa was suggested for their treatment. The endocannabinoid system is widely distributed throughout the body including the brain, modulating many functions. It is involved in mood and related disorders, and its activity may be modified by exogenous cannabinoids. CB1 and CB2 receptors primarily serve as the binding sites for endocannabinoids as well as for phytocannabinoids, produced by cannabis inflorescences. However, ‘cannabis’ is not a single compound product but is known for its complicated molecular profile, producing a plethora of phytocannabinoids alongside a vast array of terpenes. Thus, the “entourage effect” is the suggested positive contribution derived from the addition of terpenes to cannabinoids. Here, we review the literature on the effects of cannabinoids and discuss the possibility of enhancing cannabinoid activity on psychiatric symptoms by the addition of terpenes and terpenoids. Possible underlying mechanisms for the anti-depressant and anxiolytic effects are reviewed. These natural products may be an important potential source for new medications for the treatment of mood and anxiety disorders.

Terpenes/Terpenoids in <b><i>Cannabis</i></b>: Are They Important?

“…Current evidence of medicinal properties of terpenes was given by Baron [103] and Nuutinen [104] in their reviews. Entourage effect of terpenes/terpenoids and cannabinoids and their pharmacological activity were also studied by Namdar et al [105] and Ferber et al [106]. Blasco-Benito et al [46] extracted fresh cannabis flowers in ethanol, after evaporation, followed by magnetic stirring on hot plate, which achieved cannabinoid decarboxylation.…”

Investigation of early and lifetime clinical features and comorbidities for the risk of developing treatment-resistant depression in a 13-year nationwide cohort study&nbsp;

“…Several ongoing clinical trials of ketamine for the treatment of TRD are ongoing in Taiwan; they have revealed satisfactory effects [65,66]. Other widely discussed antidepressant agent are cannabinoid compounds because the endocannabinoid system is widely distributed throughout the body and serves to modulate mood symptoms [67].…”

Cannabis, One Health, and Veterinary Medicine: Cannabinoids’ Role in Public Health, Food Safety, and Translational Medicine

“…Terpenes exert diverse medicinal effects. 55, [63][64][65][66][67][68][69][70][71][72][73][74][75] Terpenoids are also flavor and fragrance components common to human and pet diets and are considered by the US FDA to be generally recognized as safe (GRAS). The use of terpenoids in food-producing animal feed is being researched due to biotechnological effects on food quality and safety as well as for performance enhancement such as weight gain; feed conversion rate; nutrient absorption; gutlining morphology; relief of intestinal immune defense in gut-associated lymphoid tissue due to antibacterial, antiviral, antifungal properties; intestinal microbiota health; meat lipid oxidation; milk composition; malodors and off-flavor in aquaculture; and palatability of feed.…”