“Resveratrol is a polyphenolic compound with antioxidant, anti-inflammatory, and neuroprotective effects. It has also shown antidepressant-like effects in the behavioral studies; however, its mechanism(s) of action merit further evaluation.
Resveratrol like the classical antidepressant, amitriptyline, affects brain NGF and eCB signaling under the regulatory drive of CB1receptors.”
“Evidence has accumulated over the last few years suggesting that endocannabinoid-based drugs may potentially be useful to reduce the effects of neurodegeneration. In fact, exogenous and endogenous cannabinoids were shown to exert neuroprotection in a variety of in vitro and in vivo models of neuronal injury via different mechanisms,”
“Cannabinoids have been proposed as clinically promising neuroprotective molecules, based on their capability to normalize glutamate homeostasis, reducing excitotoxicity, to inhibit calcium influx, lowering intracellular levels and the subsequent activation of calcium-dependent destructive pathways, and to reduce the generation of reactive oxygen intermediates or to limit their toxicity, decreasing oxidative injury.
Cannabinoids are also able to decrease local inflammatory events by acting on glial processes that regulate neuronal survival, and to restore blood supply by reducing vasocontriction produced by several endothelium-derived factors.
Treatment of neurodegenerative disorders is a challenge for neuroscientists and neurologists. Unhappily, the efficacy of available medicines is still poor and there is an urgent need for novel neuroprotective agents. Cannabinoids can serve this purpose given their recognized antiexcitotoxic, antioxidant and anti-inflammatory properties.”
“Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques.
Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques.
Our results indicate that Δ9-THC modulates miRs that regulate mRNAs of proteins involved in 1) neurotrophin signaling, 2) MAPK signaling, and 3) cell cycle and immune response thus promoting an overall neuroprotective environment in the striatum of SIV-infected macaques.
This is also reflected by increased Brain Derived Neurotrophic Factor (BDNF) and decreased proinflammatory cytokine expression compared to the VEH/SIV group.”
“Exogenously administered cannabinoids are neuroprotective in several different cellular and animal models.
In the current study, two cannabinoid CB1 receptor ligands (WIN 55,212-2, CP 55,940) markedly reduced hippocampal cell death, in a time-dependent manner, in cultured neurons subjected to high levels of NMDA…
The results suggest that cannabinoids prevent cell death by initiating a time and dose dependent inhibition of adenylyl cyclase, that outlasts direct action at the CB1 receptor and is capable of reducing [Ca2+](i) via a cAMP/PKA-dependent process during the neurotoxic event.”
“This review focuses on the role of the endocannabinoid signaling system in controlling neuronal survival, an extremely important issue to be considered when developing new therapies for neurodegenerative disorders.
First, we will describe the cellular and molecular mechanisms, and the signaling pathways, underlying these neuroprotective properties, including the control of glutamate homeostasis, calcium influx, the toxicity of reactive oxygen species, glial activation and other inflammatory events; and the induction of autophagy.
We will then concentrate on the preclinical studies and the few clinical trials that have been carried out targeting endocannabinoid signaling in three important chronic progressive neurodegenerative disorders (Parkinson’s disease, Huntington’s chorea, and Alzheimer’s disease), as well as in other less well-studied disorders.
We will end by offering some ideas and proposals for future research that should be carried out to optimize endocannabinoid-based treatments for these disorders.
Such studies will strengthen the possibility that these therapies will be investigated in the clinical scenario and licensed for their use in specific disorders.”
“Epilepsy is the most common chronic neurological disease, affecting about 1% of the world’s population during their lifetime. Most people with epilepsy can attain a seizure-free life upon treatment with antiepileptic drugs (AEDs).
Unfortunately, seizures in up to 30% do not respond to treatment. It is estimated that 90% of people with epilepsy live in developing countries, and most of them receive no drug treatment for the disease. This treatment gap has motivated investigations into the effects of plants that have been used by traditional healers all over the world to treat seizures.
Extracts of hundreds of plants have been shown to exhibit anticonvulsant activity in phenotypic screens performed in experimental animals.
Some of those extracts appear to exhibit anticonvulsant efficacy similar to that of synthetic AEDs.
Dozens of plant-derived chemical compounds have similarly been shown to act as anticonvulsants in various in vivo and in vitro assays.
To a significant degree, anticonvulsant effects of plant extracts can be attributed to widely distributed flavonoids, (furano)coumarins, phenylpropanoids, and terpenoids.
Flavonoids and coumarins have been shown to interact with the benzodiazepine site of the GABAA receptor and various voltage-gated ion channels, which are targets of synthetic AEDs.
Modulation of the activity of ligand-gated and voltage-gated ion channels provides an explanatory basis of the anticonvulsant effects of plant secondary metabolites.
Many complex extracts and single plant-derived compounds exhibit antiinflammatory, neuroprotective, and cognition-enhancing activities that may be beneficial in the treatment of epilepsy.
Thus, botanicals provide a base for target-oriented antiepileptic drug discovery and development.
In the future, preclinical work should focus on the characterization of the effects of plant extracts and plant-derived compounds on well-defined targets rather than on phenotypic screening using in vivo animal models of acute seizures. At the same time, available data provide ample justification for clinical studies with selected standardized botanical extracts and plant-derived compounds.”
“Parkinson’s disease (PD) is a common chronic neurodegenerative disorder, usually of idiopathic origin. Symptoms including tremor, bradykinesia, rigidity and postural instability are caused by the progressive loss of dopaminergic neurons in the nigrostriatal region of the brain.
Symptomatic therapies are available but no treatment slows or prevents the loss of neurons.
Neuroinflammation has been implicated in its pathogenesis.
To this end, the present study utilises the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin to reproduce the pattern of cell death evident in PD patients.
Herein, the role of a potential regulator of an immune response, the endocannabinoid system (ECS), is investigated.
The most prevalent endocannabinoid, 2-arachidonoylglycerol (2-AG) (3 and 5mg/kg), was added exogenously and its enzymatic degradation inhibited to provide protection against MPTP-induced cell death.
Furthermore, the addition of DFU (25mg/kg), a selective inhibitor of inflammatory mediator cyclooxygenase-2 (COX-2), potentiated these effects.
Levels of 2-AG were shown to be upregulated in a time- and region-specific manner following MPTP administration, indicating that the ECS represents a natural defence mechanism against inflammation, potentiation of which could provide therapeutic benefits.
The results expand the current understanding of the role that this signalling system has and its potential influence in PD.”
“The endocannabinoid system has been implicated in psychosis both related and unrelated to cannabis exposure, and studying this system holds potential to increase understanding of the pathophysiology of schizophrenia.
Anandamide signaling in the central nervous system may be particularly important.
Δ9-Tetrahydrocannabinol in cannabis can cause symptoms of schizophrenia when acutely administered, and cannabidiol (CBD), another compound in cannabis, can counter many of these effects.
CBD may have therapeutic potential for the treatment of psychosis following cannabis use, as well as schizophrenia, possibly with better tolerability than current antipsychotic treatments. CBD may also have anti-inflammatory and neuroprotective properties.
Establishing the role of CBD and other CBD-based compounds in treating psychotic disorders will require further human research.”
“One of the most important causes of morbidity and mortality is neurologic dysfunction; its high incidence has led to an intense research of the mechanisms that protect the central nervous system from hypoxia and ischemia. The mayor challenge is to block the biochemical events leading to neuronal death.
This may be achieved by neuroprotective mechanisms that avoid the metabolic and immunologic cascades that follow a neurological damage. When it occurs, several pathophysiological events develop including cytokine release, oxidative stress and excitotoxicity.
Neuroprotective effects of cannabinoids to all those mechanisms have been reported in animal models of brain ischemia, excitotoxicity, brain trauma and neurodegenerative disorders.
Some endocannabinoid analogs are being tested in clinical studies (I-III phase) for acute disorders involving neuronal death (brain trauma and ischemia).
The study of the cannabinoid system may allow the discovery of effective neuroprotective drugs for the treatment of neurological disorders.”