Immunosuppressive activity of non-psychoactive Cannabis sativa L. extract on the function of human T lymphocytes

Devi, S. Soundarya; Zimmermann-Klemd, Amy Marisa; Fiebich, Bernd L.; Heinrich, Michael; Gründemann, Carsten; Schmitz, Peter; Kowarschik, Stefanie; Huber, Roman

doi:10.1016/j.intimp.2021.108448

Cited by 13 publications

(6 citation statements)

References 39 publications

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“…We also evaluated for changes in lymphoid cells in the lungs of exposed mice, and in particular differences in CD4 + and CD8 + T cells, since cannabinoids can module T cell numbers via alterations in proliferation and survival in vitro (Devi et al 2022 ; Wu et al 2008 ). However, the impact of cannabis smoke on the number of T cell subsets in the lungs in vivo is not known.…”

Section: Resultsmentioning

confidence: 99%

Differential inflammatory profile in the lungs of mice exposed to cannabis smoke with varying THC:CBD ratio

et al. 2023

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Cannabis contains cannabinoids including Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD). THC causes the psychoactive effects of cannabis, and both THC and CBD are thought to be anti-inflammatory. Cannabis is typically consumed by inhaling smoke that contains thousands of combustion products that may damage the lungs. However, the relationship between cannabis smoke exposure and alterations in respiratory health is poorly defined. To address this gap in knowledge, we first developed a mouse model of cannabis smoke exposure using a nose-only rodent inhalation exposure system. We then tested the acute effects of two dried cannabis products that differ substantially in their THC–CBD ratio: Indica-THC dominant (I-THC; 16–22% THC) and Sativa-CBD dominant (S-CBD; 13–19% CBD). We demonstrate that this smoke exposure regime not only delivers physiologically relevant levels of THC to the bloodstream, but that acute inhalation of cannabis smoke modulates the pulmonary immune response. Cannabis smoke decreased the percentage of lung alveolar macrophages but increased lung interstitial macrophages (IMs). There was also a decrease in lung dendritic cells as well as Ly6C intermediate and Ly6C low monocytes, but an increase in lung neutrophils and CD8 + T cells. These immune cell changes were paralleled with changes in several immune mediators. These immunological modifications were more pronounced when mice were exposed to S-CBD compared to the I-THC variety. Thus, we show that acute cannabis smoke differentially affects lung immunity based on the THC:CBD ratio, thereby providing a foundation to further explore the effect of chronic cannabis smoke exposures on pulmonary health. Supplementary Information The online version contains supplementary material available at 10.1007/s00204-023-03514-3.

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Section: Resultsmentioning

confidence: 99%

Differential inflammatory profile in the lungs of mice exposed to cannabis smoke with varying THC:CBD ratio

et al. 2023

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“…Notably, THC also decreased the T cell activation caused by activated moDCs, which mirrors our results on LPS-activated CBD-treated moDCs ( 40 ). Importantly, although CBD acting directly on T cells can induce Treg responses ( 82 ), and has generally immunosuppressive effects by downregulating CD25 expression ( 83 ), in our experiments CBD was used only during the differentiation of moDCs, and was not applied during moDC-T cell cocultures. This also highlights the fact that care should be taken when administering CBD to cancer patients, who can receive cannabinoids to help stimulate their appetite ( 84 ), since its immunosuppressive effects ( 34 ) can help tumors escape immune surveillance, and can also interfere with immune checkpoint therapy ( 85 ).…”

Section: Discussionmentioning

confidence: 99%

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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“…Auch Cannabis wird von CED-Patienten immer wieder eingesetzt, um Symptome zu lindern oder auch einfach zur Entspannungsförderung. Cannabidiol, ein nicht psychotroper Bestandteil von Cannabis, kann die überschießende Aktivierung von Lymphozyten hemmen 17 . Bei M. Crohn hatte ein Cannabispräparat mit CBD und THC (dem psychotrop wirkenden Tetrahydrocannabinol) im Verhältnis 4:1 keine überzeugende Wirkung auf den Symptomscore im Vergleich mit Placebo 18 .…”

Section: Morbus Crohnunclassified

Phytotherapie bei chronisch entzündlichen Darmerkrankungen*

Huber

2023

Zeitschrift für Phytotherapie

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Immunosuppressive activity of non-psychoactive Cannabis sativa L. extract on the function of human T lymphocytes

Cited by 13 publications

References 39 publications

Differential inflammatory profile in the lungs of mice exposed to cannabis smoke with varying THC:CBD ratio

Differential inflammatory profile in the lungs of mice exposed to cannabis smoke with varying THC:CBD ratio

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

Phytotherapie bei chronisch entzündlichen Darmerkrankungen*

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