**5. Conclusions**

Overall, our results indicate both similarities and differences between the impact of CBD- and THC-based drugs. Although all the tested treatments had an anti-inflammatory effect, their specific effects (for example, on phenotype of the cells and on cytokine production) differed. These differences may influence the clinical outcome of the treatment. We were surprised to find very similar anti-inflammatory results for the two cannabis extracts, which had diverse content of THC and CBD. This could sugges<sup>t</sup> that THC/CBD content may not be the best indicator for anti-inflammatory properties of a cannabis-based drug. These results highlight the need to expand the research on the interplay between cannabinoids and other phytochemicals in the cannabis extracts. A better understanding of the effects of each molecule and the synergism between these molecules on the immune response will assist physicians to provide the best possible individually targeted treatment for their patients and will allow the design of new treatments.

**Supplementary Materials:** The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/biomedicines10081793/s1, Figure S1: Dose dependent inhibition of nitric oxide production by peritoneal macrophages treated with pure CBD/THC or cannabis extracts. Figure S2: MTT viability assay. Figure S3: Combination of THC and CBD (2.5 μg/mL of each) is less effective than the pure cannabinoids. Figure S4: IL12p40, CCL22, and IL18 secretion from activated peritoneal macrophages.

**Author Contributions:** Conceptualization, O.A.-H. and R.O.; methodology, Z.Y. and I.K.; validation, O.A.-H., D.M. and R.O.; formal analysis, O.A.-H., Z.Y., D.M. and I.K.; investigation, O.A.-H. and R.O.; resources, R.O.; data curation, O.A.-H.; writing—original draft preparation, O.A.-H.; writing—review and editing, R.O.; supervision, O.A.-H.; funding acquisition, R.O. All authors have read and agreed to the published version of the manuscript.

**Funding:** This study was supported (in part) by the Gassner Fund for Medical Research. The sponsors of this study are public or nonprofit organizations that support science in general. They had no role in gathering, analyzing, or interpreting the data.

**Institutional Review Board Statement:** The animal study protocol was approved by the Institutional Animal Care and Use Committee of the Hebrew University of Jerusalem in accordance with national laws and regulations for the protection of animals (MD-22-16868-4, MD-20-16432-4, and MD-18-15565-5).

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Acknowledgments:** We thank Raphael Mechoulam and Aviva Brener for the THC and for their helpful advice. We thank Cannabliss Ltd. for providing cannabis extracts. Cannabliss Ltd. had no role in study design, the collection, analysis and interpretation of results. We thank Zichron Menachem nonprofit organization for their support. We thank Norman Grover for his help with statistical analysis. We thank Tamara Silberberg for her help in editing the manuscript.

**Conflicts of Interest:** The authors declare no conflict of interest.
