“The potential therapeutic benefits of certain cannabinoid-mediated effects, as well as the use of marijuana for its psychoactive properties, has raised interest in understanding the cellular adaptations produced by chronic administration of this class of drugs.”
Category Archives: Endocannabinoid System
Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation
“The present in vivo and in vitro findings clearly indicate that the CB1 receptor possesses anti-inflammatory properties and inhibits microglia-mediated oxidative stress.
Our results collectively suggest that the cannabinoid system is beneficial for the treatment of Parkinson’s disease and other disorders associated with neuroinflammation and microglia-derived oxidative damage.
CB1 receptor is a useful pharmacological target for treating PD and other disorders associated with neuroinflammation and microglia-derived oxidative damage. ”
Intact cannabinoid CB1 receptors in the Alzheimer’s disease cortex.
“The cannabinoid CB1 receptor has gained much attention as a potential pharmacotherapeutic target in various neurodegenerative diseases including Alzheimer’s disease (AD). Our study suggests that CB1 receptors are intact in AD and may play a role in preserving cognitive function.
Therefore, CB1 receptors should be further assessed as a potential therapeutic target in AD.”
Molecular reorganization of endocannabinoid signalling in Alzheimer’s disease
“CB1 cannabinoid receptor expression is unchanged in Alzheimer’s disease
Therefore, endocannabinoid signalling networks may represent novel targets to reinstate the precision of synaptic communication under neurodegenerative conditions associated with cognitive deficit.”
Cannabinoid system in neurodegeneration: new perspectives in Alzheimer’s disease.
“Alzheimer’s disease is a chronic and progressive neurodegenerative disorder. The presence of functional cannabinoid CB2 receptors in central nervous system (CNS) has provoked that this receptor and its agonist ligands are now considered as promising pharmacological targets for neurological diseases. Herein, we review the evidences supporting the potential role of the ECS as a therapeutic target, focused on CB2 receptor and its ligands, for the treatment of Alzheimer’s disease.”
Cannabinoids and neurodegenerative diseases.
“Although significant advances have taken place in recent years on our understanding of the molecular mechanisms of different neurodegenerative diseases, its translation into effective therapeutic treatments has not been as successful as could be expected. There is still a dramatic lack of curative treatments for the most frequent disorders and only symptomatic relief for many others. Under this perspective, the search for novel therapeutic approaches is demanding and significant attention and efforts have been directed to studying additional neurotransmission systems including the endocannabinoid system (ECS).
The neuroprotective properties of exogenous as well as endogenous cannabinoids have been known for years and the underlying molecular mechanisms have been recently unveiled. As discussed later, antioxidative, antiglutamatergic and antiinflammatory effects are now recognized as derived from cannabinoid action and are known to be of common interest for many neurodegenerative processes.
Thus, these characteristics make cannabinoids attractive candidates for the development of novel therapeutic strategies.
The present review will focus on the existing data regarding the possible usefulness of cannabinoid agents for the treatment of relevant neurological pathologies for our society such as Alzheimer’s disease, multiple sclerosis, Huntington’s disease and amyotrophic lateral sclerosis.”
New pathways in drug discovery for Alzheimer’s disease.
Abstract
“Specific treatments for Alzheimer’s disease (AD) were first introduced in the 1990s using the acetyl-cholinesterase inhibitors. More recently, the N-methyl-D-aspartate (NMDA) antagonist memantine has become available. Although these treatments do provide a modest improvement in the cognitive abnormalities present in AD, their pharmacology is based on manipulation of neurotransmitter systems, and there is no compelling evidence that they interfere with the underlying pathogenic process. Pathologic and genetic data have led to the hypothesis that a peptide called amyloid ss(Abeta) plays a primary role in the pathophysiology of AD. Several investigational therapies targeting Abeta are now undergoing clinical trials. This paper reviews the available data regarding Abeta-directed therapies that are in the clinic and summarizes the approach to biomarkers and clinical trial designs that can provide evidence of modification of the underlying disease process.”
Cannabinoid CB1 receptor stimulation affords neuroprotection in MPTP-induced neurotoxicity by attenuating S100B up-regulation in vitro.
“…the involvement of the endocannabinoid system was investigated by using selective inhibitors of endocannabinoid inactivation (cellular re-uptake or enzymatic hydrolysis) and selective cannabinoid CB1 and CB2 receptor antagonists and by silencing the CB1 receptor…
Our data suggest that selective activation of CB1 receptors by either exogenous or endogenous cannabinoids might afford neuroprotection…”
CB1 agonist ACEA protects neurons and reduces the cognitive impairment of AβPP/PS1 mice.
“The present study shows that chronic administration of the cannabinoid receptor type 1 (CB1) receptor agonist arachidonyl-2-chloroethylamide (ACEA) at pre-symptomatic or at early symptomatic stages, at a non-amnesic dose, reduces the cognitive impairment observed in double AβPP(swe)/PS1(1dE9) transgenic mice from 6 months of age onwards…
… targeting the CB1 receptor could offer a versatile approach for the treatment of Alzheimer’s disease.”
Contrasting protective effects of cannabinoids against oxidative stress and amyloid-β evoked neurotoxicity in vitro.
“Cannabinoids have been widely reported to have neuroprotective properties in vitro and in vivo. In this study we compared the effects of CB1 and CB2 receptor-selective ligands, the endocannabinoid anandamide and the phytocannabinoid cannabidiol, against oxidative stress and the toxic hallmark Alzheimer’s protein, β-amyloid (Aβ)…
…the endocannabinoid anandamide protects neuronal cells from Aβ exposure via a pathway unrelated to CB1 or CB2 receptor activation…protective effect of cannabidiol against oxidative stress…
…divergent pathways for neuroprotection of these two cannabinoids.”