Evaluation of the anti-inflammatory effects of selected cannabinoids and terpenes from Cannabis Sativa employing human primary leukocytes

Blevins, Lance K.; Bach, Anthony; Crawford, R. J.; Zhou, Jiajun; Henriquez, Joseph E.; Rizzo, Michael D.; Sermet, Sera; Khan, D.M. Isha Olive; Turner, Helen; Small‐Howard, Andrea L.; Kaminski, Norbert E.

doi:10.1016/j.fct.2022.113458

Cited by 12 publications

(11 citation statements)

References 45 publications

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“…As can be seen from Supplementary Figure 1 , CBD is well tolerated by keratinocytes but at concentrations higher than 15 μM, it inhibits DNA synthesis compared to cells treated with vehicle alone (DMSO 0,1%), showing an IC 50 = 20 μM. Therefore, we used a concentration of 10 μM CBD also used by other investigators to study the immunomodulatory effect of CBD ( 10 ). The results of the proteome profile array highlighted that CBD at 10 μM leads to the reduction of TARC, MIP, IL-19, IL-1RA, IFNγ, GM-CSF, ENA-78, TNFα in psoriatic individuals’ PBMCs, compared to PBMCs treated with vehicle alone (DMSO 0,1%) ( Figure 1A ).…”

Section: Resultsmentioning

confidence: 99%

Cannabidiol exerts multitarget immunomodulatory effects on PBMCs from individuals with psoriasis vulgaris

Pagano,

Ciaglia,

Coppola

et al. 2024

Front. Immunol.

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IntroductionThe involvement of endocannabinoid system (ECS) in the inflammatory cascade, and the ability of phytocannabinoids, endocannabinoids and their synthetic analogues to modulate it has become an interesting research area for new therapeutic approaches in inflammatory skin diseases. Cannabidiol (CBD) appears to be the most promising among phytocannabinoids, due to the lack of psychotropic effects and low toxicity profile. Its anti-inflammatory action has been highlighted in different preclinical models, ranging from experimental colitis to arthritis and neuroinflammation. Our aim was to evaluate CBD immune-modulatory effects in peripheral blood mononuclear cells (PBMC) of psoriasis individuals with particular attention to both innate and adaptative immune arms.MethodsWe performed in vitro immune functional experiments to analyze CBD action on various immune cells active in psoriatic lesions.ResultsThe results showed that CBD produced a shift from Th1 to Th2 response, while boosting cytotoxic activity of Natural Killer (NK) cells. Furthermore, it also exerted a potent action on monocyte differentiation as, after CBD treatment, monocytes from psoriatic individuals were unable to migrate in response to inflammatory stimuli and to fully differentiate into mature dendritic cells. Finally, a M2 skewing of monocyte-derived macrophages by CBD also contributed to the fine tuning of the magnitude of immune responses.ConclusionsThese data uncover new potential immunomodulatory properties of this cannabinoid suggesting a possible therapeutic action in the treatment of multiple inflammatory skin diseases.

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Section: Resultsmentioning

confidence: 99%

Cannabidiol exerts multitarget immunomodulatory effects on PBMCs from individuals with psoriasis vulgaris

Pagano,

Ciaglia,

Coppola

et al. 2024

Front. Immunol.

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“…In the last two decades there has been a rapid shift in the legal status of cannabis, and as a consequence, pCBs are increasingly used in commercially available extracts made from the plant, especially in topical formulations ( 50 , 63 , 64 ). The use of pCB-containing treatments has been bolstered by recent research in murine and canine models that highlights the anti-inflammatory potential of both pure compounds and mixed extracts.…”

Section: Discussionmentioning

confidence: 99%

“…Research into non-psychotropic pCBs has increased markedly in the past two decades, driven in part by their use as anti-cancer treatments. These pCBs can indeed be cytotoxic at high doses (>15 μM), especially to cancerous cells ( 67 ), however CBD and CBN did not influence the viability of human PBMCs up to 10 μM ( 50 ). Other results show that pCBs can be cytotoxic, as 4-8 μM of CBD could induce apoptosis in mouse thymocytes ( 68 ), and primary monocytic cells were affected by 1-16 μM ( 69 , 70 ).…”

Section: Discussionmentioning

confidence: 99%

“…In this way, they could assess the proliferation, activation marker expression, cytokine expression, cytokine production and phagocytosis of the cells (where relevant). All cannabinoids (including THC) suppressed the secretion of proinflammatory cytokines (e.g., IL-1β, IL-6, TNFα) to some degree, as well as the phagocytotic activity of monocyte-derived CD14 + cells ( 50 ). Similar effects for DCs have not yet been described.…”

Section: Introductionmentioning

confidence: 99%

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The dual role of cannabidiol on monocyte-derived dendritic cell differentiation and maturation

Pénzes,

Alimohammadi,

Horváth

et al. 2023

Front. Immunol.

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IntroductionExtracts and compounds isolated from hemp (Cannabis sativa) are increasingly gaining popularity in the treatment of a number of diseases, with topical formulations for dermatological conditions leading the way. Phytocannabinoids such as ( )-cannabidiol, ( )-cannabinol and ( )-Δ9-tetrahydrocannabivarin (CBD, CBN, and THCV, respectively), are present in variable amounts in the plant, and have been shown to have mostly anti-inflammatory effects both in vitro and in vivo, albeit dominantly in murine models. The role of phytocannabinoids in regulating responses of dendritic cells (DCs) remains unclear.MethodsOur research aimed to investigate the effects of CBD, CBN, and THCV on human DCs differentiated from monocytes (moDCs). moDCs were treated with up to 10 μM of each phytocannabinoid, and their effects on viability, differentiation, and maturation were assessed both alone, and in conjunction with TLR agonists. The effects of CBD on cytokine production, T cell activation and polarization as well as the transcriptome of moDCs was also determined.ResultsPhytocannabinoids did not influence the viability of moDCs up to 10 μM, and only CBD had effects on maturational markers of moDCs, and neither compound influenced LPS-induced activation at 10 μM. Since only CBD had measurable effects on moDCs, in our subsequent experiments we tested the effect only of that pCB. On moDCs differentiated in the presence of CBD subsequent activation by LPS induced a markedly different, much more tolerogenic response. CBD-treated moDCs also produced significantly more interleukin (IL)-6, TNFα and, importantly, IL-10 in response to LPS, which shows a shift toward anti-inflammatory signaling, as well as a more robust secretory response in general. To rule out the possibility that these effects of CBD are specific to TLR4 signaling, we determined the effect of CBD on TLR7/8-induced maturation as well, and saw similar, although less marked responses. CBD-treated moDCs were also less efficient at activating naïve T cells after LPS stimulation, further supporting the tolerogenic effect of this phytocannabinoid on moDCs. Reactome pathway analysis showed an inflammatory response to LPS in moDCs, and to a lesser extent to CBD as well. In contrast CBD-treated moDCs responded to LPS with a shift towards a more tolerogenic phenotype, as IL-10 signaling was the most prominently induced pathway in this group.DiscussionOur results show that CBD achieves an anti-inflammatory effect on adaptive immune responses only in the presence of an activating stimuli on moDCs by reprogramming cells during long-term treatment, and not through acute, short-term effects.

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“…Cannabidiol (CBD), a major non-psychotropic constituent of Cannabis sativa, promotes the osteogenic differentiation of DPSC (26). CBD has certain biological activities required for bone tissue engineering such as anti-in ammatory (27), antioxidant (28), chemotactic (29), angiogenic, and osteogenic (30) properties. However, whether CBD could promote the osteogenic potential of DPSCderived micro-spheroids is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Dental pulp stem cells-derived cannabidiol-pretreated micro-spheroids showed robust osteogenic potential via upregulation of WNT6

Liu

et al. 2023

Preprint

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Dental pulp stem cells (DPSC)-derived 3D-aggregates/spheroids have shown robust soft/hard tissue regeneration potential. However, difficulties to control the cell number, size, and shape of DPSC-aggregates/spheroids cause cell necrosis and difficulties in homogenous seeding of aggregates/spheroids in the 3D-printed microporous bone grafts. Moreover, inducing the osteogenic potential of these aggregates/spheroids is still a challenge. This study developed cannabidiol (CBD)-pretreated, self-assembled, and injectable DPSC-derived osteogenic micro-spheroids (70 μm) that robustly promoted in situ bone regeneration. We developed micro-spheroids by seeding 250 cells/microwell in agarose gel microwells of 200 µm diameter developed using prefabricated mold and cultured with CBD for 14 days to induce osteogenic potential. In vitro study results showed that CBD did not affect the viability of DPSC but promoted osteogenic differentiation during 2D culture. In micro-spheroids, 3D cytoskeleton visualization showed better integrity and robustly higher expression of osteogenic markers and promoted in situ bone regeneration compared with DPSC. CBD-pretreated micro-spheroids showed robustly higher bone-regenerative capacity via upregulation of WNT6. Taken together, our approach of developing organoid-like injectable osteogenic micro-spheroids can be used as the effective carrier of the effect of in vitro drug treatment during in situ bone tissue engineering which eliminates the direct in vivo drug application-related adverse effects.

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Evaluation of the anti-inflammatory effects of selected cannabinoids and terpenes from Cannabis Sativa employing human primary leukocytes

Cited by 12 publications

References 45 publications

Cannabidiol exerts multitarget immunomodulatory effects on PBMCs from individuals with psoriasis vulgaris

Cannabidiol exerts multitarget immunomodulatory effects on PBMCs from individuals with psoriasis vulgaris

The dual role of cannabidiol on monocyte-derived dendritic cell differentiation and maturation

Dental pulp stem cells-derived cannabidiol-pretreated micro-spheroids showed robust osteogenic potential via upregulation of WNT6

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