Abstract
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.
Highlights
GABA is the main inhibitory neurotransmitter in the central nervous system (CNS), able to bind three different classes of γ-Aminobutyric acid type A receptors (GABARs): GABAARs, GABABRs, and GABACRs
We present and discuss the latest published data regarding the GABAARs modulation by pCBs, in order to better understand how other pathological conditions could be treated with these compounds
The pCBs action on GABAARs could open the way to the development of new therapeutic approaches for different pathological conditions
Summary
GABA is the main inhibitory neurotransmitter in the central nervous system (CNS), able to bind three different classes of γ-Aminobutyric acid type A receptors (GABARs): GABAARs, GABABRs, and GABACRs. GABAAR impairment seems to be involved in the pathogenesis of several neurodevelopmental diseases, epileptic syndromes, and cognitive dysfunctions [3], conditions that can often coexist Both benzodiazepines (BDZ) and barbiturates (BBT) target GABAARs and are used in the treatment of anxiety, sleep disorders, and seizures, especially during status epilepticus. CBD is a non-psychoactive compound with a better safety profile if compared with ∆9-THC: it seems to be well tolerated at high doses in both animal models and humans, it does not alter heart rate, blood pressure, or body temperature and has no effects on locomotor activity or superior cognitive functions [9] This good safety profile is probably related to its pharmacodynamics, since it binds with low affinity both to CB1Rs and CB2Rs [10,11,12]. This last detail, though, paved the way for an intensive investigation of the possible alternative targets of this compound but, at the current state of the art, none of the proposed mechanisms seem to fully explain its clinical efficacy [13]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
