Cannabinoids, Blood–Brain Barrier, and Brain Disposition

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Cannabinoids, Blood–Brain Barrier, and Brain Disposition

by Fabrizio Calapai ¹, Luigi Cardia ², Emanuela Elisa Sorbara ¹, Michele Navarra ³, Sebastiano Gangemi ⁴, Gioacchino Calapai ^1,* and Carmen Mannucci ¹

¹

Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, 98125 Messina, Italy

²

Anesthesia, Intensive Care and Pain Therapy, A.O.U.G. Martino Messina, University of Messina, 98125 Messina, Italy

³

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy

⁴

School and Division of Allergy and Clinical Immunology, Department of Experimental Medicine, University of Messina, 98125 Messina, Italy

^*

Author to whom correspondence should be addressed.

Pharmaceutics 2020, 12(3), 265; https://doi.org/10.3390/pharmaceutics12030265

Received: 28 January 2020 / Revised: 21 February 2020 / Accepted: 12 March 2020 / Published: 15 March 2020

(This article belongs to the Special Issue Drug Delivery to the Brain)

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Abstract

Potential therapeutic actions of the cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are based on their activity as analgesics, anti-emetics, anti-inflammatory agents, anti-seizure compounds. THC and CBD lipophilicity and their neurological actions makes them candidates as new medicinal approaches to treat central nervous system (CNS) diseases. However, they show differences about penetrability and disposition in the brain. The present article is an overview about THC and CBD crossing the blood–brain barrier (BBB) and their brain disposition. Several findings indicate that CBD can modify the deleterious effects on BBB caused by inflammatory cytokines and may play a pivotal role in ameliorating BBB dysfunction consequent to ischemia. Thus supporting the therapeutic potential of CBD for the treatment of ischemic and inflammatory diseases of CNS. Cannabinoids positive effects on cognitive function could be also considered through the aspect of protection of BBB cerebrovascular structure and function, indicating that they may purchase substantial benefits through the protection of BBB integrity. Delivery of these cannabinoids in the brain following different routes of administration (subcutaneous, oral, and pulmonary) is illustrated and commented. Finally, the potential role of cannabinoids in drug-resistance in the clinical management of neurological or psychiatric diseases such as epilepsy and schizophrenia is discussed on the light of their crossing the BBB. View Full-Text