Immune Responses Regulated by Cannabidiol

Abstract

Introduction: Cannabidiol (CBD) as Epidiolex Ò (GW Pharmaceuticals) was recently approved by the U.S. Food and Drug Administration (FDA) to treat rare forms of epilepsy in patients 2 years of age and older. Together with the increased societal acceptance of recreational cannabis and CBD oil for putative medical use in many states, the exposure to CBD is increasing, even though all of its biological effects are not understood. Once such example is the ability of CBD to be anti-inflammatory and immune suppressive, so the purpose of this review is to summarize effects and mechanisms of CBD in the immune system. It includes a consideration of reports identifying receptors through which CBD acts, since the ' 'CBD receptor,' ' if a single one exists, has not been definitively identified for the myriad immune system effects. The review then provides a summary of in vivo and in vitro effects in the immune system, in autoimmune models, with a focus on experimental autoimmune encephalomyelitis, and ends with identification of knowledge gaps. Conclusion: Overall, the data overwhelmingly support the notion that CBD is immune suppressive and that the mechanisms involve direct suppression of activation of various immune cell types, induction of apoptosis, and promotion of regulatory cells, which, in turn, control other immune cell targets.

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“…Notably, it was also reported CBD's capacity to modulate immune-system response. CBD is able, as shown for ∆9-THC, to strongly inhibit IL-6 release in different preclinical models of inflammatory diseases, such as diabetes, asthma, pancreatitis, and hepatitis [20]. However, since the molecular targets of these compounds are numerous and the overall effect on the immune system is still partially understood, there are still doubts about their use for human inflammatory diseases [21,22] and further investigations are needed in order to better clarify the pCBs effects on immune system function.…”

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“…CBD has suppressive effects on the immune system, including inflammatory response reduction, cellular and humoral immunity suppression, and induction of apoptosis in some lymphocytes; these effects are beneficial for treating inflammatory diseases [ 113 , 114 ]. Type 1 diabetes is an example of an inflammatory-based disease that can benefit from CBD preemptive treatment; non-obese diabetic mice receiving CBD had delayed development of diabetes, and had significantly lower activation of leukocytes than mice receiving control vehicle [ 115 ].…”

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“…However, research supporting such "protective effects" of CBD is extremely limited. In fact, the authors identified only two (in vitro) studies reporting antimicrobial effects [5,179] and two (in vitro) studies reporting anti-viral effects [119,122] (see Tagne et al [167] and Nichols et al [136] for reviews). In the former, CBD demonstrated anti-microbial activity against various strains of Staphylococcus aureus [5,179], as well as Staphylococcus pyogenes, Staphylococcus milleri, and Staphylococcus faecalis [179] at minimum concentrations of~3.2-15.9 μM; however, one study also found that these effects were virtually abolished when the original media (a nutrient broth agar) was replaced with one containing 5% blood (increasing the minimum concentration to~160 μM CBD) [179].…”

“…In the latter, CBD indicated anti-viral activity against the hepatitis C virus (EC 50 = 3.2 μM) and the Kaposi's sarcoma-associated herpesvirus (EC 50 = 2.1 μM), but not the hepatitis B virus [119,122]. While these findings hint at some promise, others caution that CBD could potentially weaken host defence against invading pathogens because of its tendency to modify the function of various immune cells (see also section "Exercise-Induced Muscle Damage-Muscle Function, Soreness, and Injury") [136,147]. Importantly, a systematic review of studies investigating the safety of CBD in individuals with intractable epilepsy found that upper respiratory tract infections were similarly infrequent in participants who received the active treatment (5-20 mg•kg −1 •day −1 ) and placebo (approx.…”