**5. Conclusions**

In conclusion, we have demonstrated that CBD can be detected in the plasma and mPFC, following single or repeated injections. In both districts, CBD is detected following a specific dose −response profile. Further, we showed that CBD can modulate BDNF expression in a manner that depends upon the length of the treatment and following a specific anatomical pattern. Accordingly, our data are likely to reflect the targeting of specific neuroplastic processes in the cortico-striatal pathway rather than an interference with specific neurotrophic responses.

**Supplementary Materials:** The following supporting information can be downloaded at: https://www. mdpi.com/article/10.3390/biomedicines10081853/s1, Figures S1–S4: Western blot uncropped immunoblot representative images of the data shown in Figures 4, 5 and 7–10. Supplementary Tables S1–S4 show the normality of residuals calculation of data shown in Figures 1–10.

**Author Contributions:** Conceptualization, M.D., F.F. and L.C.; methodology, F.M., M.F., F.C.-D., S.P., G.T., E.S. and B.P.; software, F.M. and E.S.; investigation, F.M., M.F., F.C.-D., S.P., G.T. and E.S.; writing—original draft preparation, F.M. and M.F.; writing—review and editing, B.P., M.H.S. and M.D., F.F. and L.C.; supervision, M.D., F.F. and L.C.; funding acquisition, F.F. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by Curaleaf International, UK and by grants from MIUR Progetto Eccellenza.

**Institutional Review Board Statement:** All animal procedures were conducted in accordance with the ethical standards and according to national and international guidelines and were revised and approved by the authors' institutional review board (Organism for Animal Wellbeing—OPBA) and conducted at the Department of Pharmacological and Biomolecular Sciences at the University of Milan. The animal study protocol was approved and carried out in accordance with the principles set out in the following laws, regulations, and policies governing the care and use of laboratory animals: Italian Governing Law (D.lgs 26/2014; Authorization n.19/2008-A issued March 6, 2008, by Ministry of Health); the NIH Guide for the Care and Use of Laboratory Animals (2011 edition) [30]; and EU directives and guidelines (EEC Council Directive 2010/63/UE).

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Acknowledgments:** Francesca Mottarlini is the recipient of a postdoc fellowship from Zardi Gori Foundation.

**Conflicts of Interest:** Mikael Sodergren is a Clinical Senior Lecturer at Imperial College and Chief Medical Officer at Curaleaf International, from whom he receives payments as a consultant. The other authors declare no conflict of interests.
