TY - JOUR
T1 - Phytocannabinoids in Neurological Diseases
T2 - Could They Restore a Physiological GABAergic Transmission?
AU - Cifelli, P.
AU - Ruffolo, G.
AU - De Felice, E.
AU - Alfano, V.
AU - van Vliet, E.A.
AU - Aronica, E.
AU - Palma, E.
PY - 2020/1/22
Y1 - 2020/1/22
N2 - γ-Aminobutyric acid type A receptors (GABAARs) are the main inhibitory mediators in the central nervous system (CNS). GABAARs are pentameric ligand gated ion channels, and the main subunit composition is usually 2α2βγ, with various isotypes assembled within a set of 19 different subunits. The inhibitory function is mediated by chloride ion movement across the GABAARs, activated by synaptic GABA release, reducing neuronal excitability in the adult CNS. Several studies highlighted the importance of GABA-mediated transmission during neuro-development, and its involvement in different neurological and neurodevelopmental diseases, from anxiety to epilepsy. However, while it is well known how different classes of drugs are able to modulate the GABAARs function (benzodiazepines, barbiturates, neurosteroids, alcohol), up to now little is known about GABAARs and cannabinoids interaction in the CNS. Endocannabinoids and phytocannabinoids are lately emerging as a new class of promising drugs for a wide range of neurological conditions, but their safety as medication, and their mechanisms of action are still to be fully elucidated. In this review, we will focus our attention on two of the most promising molecules (Δ9-tetrahydrocannabinol; Δ9-THC and cannabidiol; CBD) of this new class of drugs and their possible mechanism of action on GABAARs.
AB - γ-Aminobutyric acid type A receptors (GABAARs) are the main inhibitory mediators in the central nervous system (CNS). GABAARs are pentameric ligand gated ion channels, and the main subunit composition is usually 2α2βγ, with various isotypes assembled within a set of 19 different subunits. The inhibitory function is mediated by chloride ion movement across the GABAARs, activated by synaptic GABA release, reducing neuronal excitability in the adult CNS. Several studies highlighted the importance of GABA-mediated transmission during neuro-development, and its involvement in different neurological and neurodevelopmental diseases, from anxiety to epilepsy. However, while it is well known how different classes of drugs are able to modulate the GABAARs function (benzodiazepines, barbiturates, neurosteroids, alcohol), up to now little is known about GABAARs and cannabinoids interaction in the CNS. Endocannabinoids and phytocannabinoids are lately emerging as a new class of promising drugs for a wide range of neurological conditions, but their safety as medication, and their mechanisms of action are still to be fully elucidated. In this review, we will focus our attention on two of the most promising molecules (Δ9-tetrahydrocannabinol; Δ9-THC and cannabidiol; CBD) of this new class of drugs and their possible mechanism of action on GABAARs.
KW - Cannabinoids
KW - Endocannabinoid system
KW - GABAARS
KW - Neurotransmission
UR - http://www.scopus.com/inward/record.url?scp=85078277720&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/ijms21030723
DO - https://doi.org/10.3390/ijms21030723
M3 - Review article
C2 - 31979108
SN - 1661-6596
VL - 21
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 3
M1 - 723
ER -