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Research: Cannabis Entourage Effect 2.0

Liquid Life Research: Cannabis Entourage Effect

Introductions and image by @SuperFunker.

1) Gallily et al (2015) compared the dose-response of a CBD isolate to a Clone-202/Avidekel extract (CBD-dominant Cannabis with ~18% CBD and ~1% THC). In assessing the capacity of each to control inflammation and reduce pain, CBD isolate produced a bell-shaped dose-response characterized by a rapid reduction in efficacy with higher doses. In contrast, the full-spectrum Clone-202/Avidekel extract exhibited continued effectiveness as the dosage increased. Thus, the CBD isolate has a very narrow therapeutic window, whereas Clone-202/Avidekel has a much broader response range. It’s the synergistic effect – Entourage Effect – of the naturally occurring pytochemicals within the Clone-202/Avidekel that’s thought to produce this broader application range and resulting versatility.

Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol.

Abstract
Cannabidiol (CBD), a major constituent of Cannabis, has been shown to be a powerful anti-inflammatory and anti-anxiety drug, without exerting a psychotropic effect. However, when given either intraperitoneally or orally as a purified product, a bell-shaped dose-response was observed, which limits its clinical use. In the present study, we have studied in mice the anti-inflammatory and anti-nociceptive activities of standardized plant extracts derived from the Cannabis sativa L., clone 202, which is highly enriched in CBD and hardly contains any psychoactive ingredients. In stark contrast to purified CBD, the clone 202 extract, when given either intraperitoneally or orally, provided a clear correlation between the anti-inflammatory and anti-nociceptive responses and the dose, with increasing responses upon increasing doses, which makes this plant medicine ideal for clinical uses. The clone 202 extract reduced zymosan-induced paw swelling and pain in mice, and prevented TNFα production in vivo. It is likely that other components in the extract synergize with CBD to achieve the desired anti-inflammatory action that may contribute to overcoming the bell-shaped dose-response of purified CBD. We therefore propose that Cannabis clone 202 (Avidekel) extract is superior over CBD for the treatment of inflammatory conditions.

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2) Gallily et al (2018) explored the effectiveness of a CBD isolate and a Clone-202/Avidekel extract (CBD-dominant Cannabis with ~18% CBD and ~1% THC) to Copaxone (glatiramer acetate pharmaceutical injection) in treating multiple sclerosis. Both the CBD isolate and Clone-202/Avidekel extract are as efficient as Copaxone. But when comparing the two Cannabis therapies, Clone-202/Avidekel appeared to exhibit a superior result. The CBD isolate demonstrated a bell-shaped dose-response (see above) which has a narrow/limited application. In contrast, Clone-202/Avidekel had a correlative dose-response (continued effectiveness as the dosage increased) and a superior pain-reducing capacity. Again, Clone-202/Avidekel appears to be more efficacious and versatile than CBD isolates which is attributed to the synergistic effect – Entourage Effect – of the naturally occurring pytochemicals within the Clone-202/Avidekel extract.

Avidekel Cannabis extracts and cannabidiol are as efficient as Copaxone in suppressing EAE in SJL/J mice.

Abstract
Multiple sclerosis (MS) is an autoimmune disease leading to the destruction of myelin with consequent axonal degeneration and severe physical debilitation. The disease can be treated with immunosuppressive drugs that alleviate the symptoms and retard disease aggravation. One such drug in clinical use is glatiramer acetate (Copaxone). The non-psychotropic immunosuppressive cannabinoid compound cannabidiol (CBD) has recently been shown to have benefcial efects on experimental autoimmune encephalomyelitis (EAE). The aim of our study was to compare the efficacy of CBD and standardized extracts from a CBD-rich, ∆9 -THClow Cannabis indica subspecies (Avidekel) with that of Copaxone. Our data show that CBD and purified Avidekel extracts are as efficient as Copaxone to alleviate the symptoms of proteolipid protein (PLP)-induced EAE in SJL/J mice. No synergistic effect was observed by combining CBD or Avidekel extracts with Copaxone. Our data support the use of Avidekel extracts in the treatment of MS symptoms.

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3) Holley et al (2019, under review) reviewed research in an effort to compare full-spectrum Cannabis treatment to mono therapies of a CBD or THC isolate. Although the standard practice is to isolate a single active component such as CBD, research continues to validate greater effectiveness and fewer side-effects with whole-plant strategies. It’s the Entourage Effect of full-spectrum mixtures that produces these superior medicinal results.

Key pharmacological differences between side effects of refined, pharmaceutical CBD formulations and whole plant extracts.

Abstract (under review)
Recent studies on the effectiveness of cannabidiol in the rare seizure disorders Dravet Syndrome and Lennox-Gastaut syndrome have prompted a biopharmaceutical company to perform clinical trials of its own to bring a cannabidiol based drug to the American market through the process of FDA approval. Side effects were very prevalent in 79% of all patients taking a refined CBD product, some of which were severe like thrombocytopenia and transaminase elevations in the liver. However, there are indications from studies done with cannabidiol-rich cannabis extracts in Israel that indicate that less side effects (46%) are achieved with a natural cannabis plant extract containing a 20:1 ratio of CBD to THC. This paper seeks to answer why refined cannabinoids have more side effects than the natural cannabis product, as well as the possible etiology of said adverse reactions. Also discussed are other attempts at affecting the cannabinoid system from a singular standpoint. Ultimately, the cannabinoid system works by way of multiple molecules affecting multiple receptors at once – the entourage effect, and thus such singular approaches to treatment by way of the cannabinoid system are not effective. Traditional plant extracts contain many compounds in addition to THC and CBD that contribute to the medical benefits of cannabis.

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