The Power of the Entourage Effect
Mood and anxiety disorders are unfortunately common, affecting hundreds of millions of people worldwide. These disorders, including depression, anxiety, and bipolar disorder, are not fully understood, and there are no definitive cures. Current pharmaceutical treatments have only shown to partially alleviate symptoms in 60%-70% of people and carry with them a host of severe side effects. [1]
A mounting body of research now suggests that the body’s endocannabinoid system (ECS) plays a role in regulating mood. As a result, using phytocannabinoids from Cannabis sativa to treat mood disorders appears to be an effective alternative. There is also research to suggest that terpenes, like the ones found in cannabis, may also aid in treating mood disorders, and the combination of cannabinoids and terpenes may be even more effective still.
Cannabinoids in Treating Mood Disorders
Laboratory tests have shown that delta-9-tetrahydrocannabinol (THC) will bind to CB1 and CB2 receptors in the body’s ECS. While THC readily binds to these receptors, cannabidiol (CBD) does so as well, albeit at lower rates. [1]
Despite this, CBD is most proven to relive symptoms of mood disorders in laboratory pre-clinical studies. [2] THC has also shown to be effective, however, especially when paired with CBD. [3]
For depression, CBD has shown promising results in pre-clinical studies, demonstrating anti-depressant-like effects and reduction of symptoms. [1] Similar results have also been demonstrated in chronic administration of CBD. [4] While the results are promising, little biological evidence of the underlying mechanisms has been found.
There is no shortage of studies demonstrating the positive effects of both THC and CBD on the treatment of anxiety. [5] Evidence suggests that there are multiple structures and mechanisms within the brain involved in the anti-anxiety properties of cannabinoids. [1]
In the treatment of bipolar disorder, it has been suggested that oxidative stress may play a key role. One study concluded that CBD protects against oxidative protein damage, a purported underlying mechanism behind bipolar disorder, and may even boost the brain’s capability to reverse these effects. [6] Other studies have shown, however, that CBD may not be effective during manic episodes. [7]
Terpenes in Treating Mood Disorders
It’s not only cannabinoids that have anti-anxiety properties. Terpenes, of which the cannabis plant produces roughly 400, have also been shown in pre-clinical studies to reduce anxiety-like symptoms. [1]
The terpenes found in lavender have been studied by several research groups and shown to exhibit anti-anxiety properties. One trial of 539 adults with Generalized Anxiety Disorder put a lavender essential oil, Silexan, against an anti-depressant and a placebo. [8] The study found that the lavender essential oil produced more anti-anxiety effects than the pharmaceutical anti-depressant.
The Entourage Effect
The entourage effect is a proposed concept that the combination of cannabinoids and terpenes is more effective than the independent components. Essentially, the cannabinoids and terpenes amplify the effects of one another, creating a more effective treatment. Synergistic effects have been found both between cannabinoids and between cannabinoids and terpenes.
It has also been proposed that different combinations of cannabinoids and terpenes in varying concentrations create different effects. While there is anecdotal evidence to support the idea, it’s difficult to test in a controlled manner. [1]
The entourage effect only serves to enhance the value of cannabis as a treatment for mood disorders and may provide the opportunity for targeted and diverse naturally-derived treatment options.
References
[1] Goldstein Ferber S, Namdar D, Hen-Shoval D, Eger G, Koltai H, Shoval G, Shbiro L, Weller A. The “entourage effect”: terpenes coupled with cannabinoids for the treatment of mood disorders and anxiety disorders. Current Neuropharmacology. 2020;18:87-96. [journal impact factor = 7.363; times cited = 29][2] Abrams DI. The therapeutic effects of Cannabis and cannabinoids: An update from the National Academies of Sciences, Engineering and Medicine report. Eur J Intern Med. 2018;49:7-11. [journal impact factor = 4.487; times cited = 131]
[3] Cuttler C, Spradlin A, McLaughlin RJ. A naturalistic examination of the perceived effects of cannabis on negative affect. J Affect Disord. 2018;235:198-205. [journal impact factor = 4.839; times cited = 51]
[4] Réus GZ, Stringari RB, Ribeiro KF, et al. Administration of cannabidiol and imipramine induces antidepressant-like effects in the forced swimming test and increases brain-derived neurotrophic factor levels in the rat amygdala. Acta Neuropsychiatr. 2011;23(5):241-248. [journal impact factor = 3.403; times cited = 42]
[5] Lisboa SF, Gomes FV, Terzian AL, et al. The endocannabinoid system and anxiety. Vitam Horm. 2017;103:193-279. [journal impact factor = 3.421; times cited = 24]
[6] Valvassori SS, Elias G, de Souza B, et al. Effects of cannabidiol on amphetamine-induced oxidative stress generation in an animal model of mania. J Psychopharmacol. 2011;25(2):274-280. [journal impact factor = 4.153; times cited = 62]
[7] Crippa JA, Guimarães FS, Campos AC, Zuardi AW. Translational investigation of the therapeutic potential of cannabidiol (CBD): Toward a new age. Front Immunol. 2018;9:2009. [journal impact factor = 6.429; times cited = 113]
[8] Kasper S, Gastpar M, Müller WE, et al. Lavender oil preparation Silexan is effective in generalized anxiety disorder–a randomized, double-blind comparison to placebo and paroxetine. Int J Neuropsychopharmacol. 2014;17(6):859-869. [journal impact factor = 4.807; times cited = 129]
