“The endocannabinoid system regulates neurite outgrowth and neurogenesis during development of the central nervous system.
Cannabinoid receptor 1 (CB1R) is expressed in neurons, including the somata and fibers, that innervate the endometrial ectopic cyst in rats.
This finding may provide a new therapeutic target for patients with endometriosis.”
“In the adult mammalian brain, new neurons are born throughout life, and these new cells may influence learning, memory, olfaction, and even mood. The putative function of these new neurons suggests that manipulation of adult neurogenesis could be used therapeutically in the future, and emphasizes the importance of understanding how neurogenesis is regulated. Voluntary exercise and antidepressants are examples of factors that increase neurogenesis, while stress and drugs of abuse – alcohol, nicotine, psychostimulants, opiates – decrease neurogenesis. In contrast to the clear negative influence of these drugs of abuse, cannabinoids have mixed influence, with some marijuana-like compounds actually enhancing neurogenesis.” https://www.researchgate.net/publication/264424221_Regulation_of_Adult_Neurogenesis_by_Cannabinoids
“Alzheimer’s disease (AD) is a debilitating neurodegenerative disease that is affecting an increasing number of people. It is characterized by the accumulation of amyloid-β and tau hyperphosphorylation as well as neuroinflammation and oxidative stress.
Current AD treatments do not stop or reverse the disease progression, highlighting the need for new, more effective therapeutics.
Cannabidiol (CBD) is a non-psychoactive phytocannabinoid that has demonstrated neuroprotective, anti-inflammatory and antioxidant properties in vitro. Thus, it is investigated as a potential multifunctional treatment option for AD.
Here, we summarize the current status quo of in vivo effects of CBD in established pharmacological and transgenic animal models for AD.
The studies demonstrate the ability of CBD to reduce reactive gliosis and the neuroinflammatory response as well as to promote neurogenesis.
Importantly, CBD also reverses and prevents the development of cognitive deficits in AD rodent models.
Interestingly, combination therapies of CBD and Δ9-tetrahydrocannabinol (THC), the main active ingredient of cannabis sativa, show that CBD can antagonize the psychoactive effects associated with THC and possibly mediate greater therapeutic benefits than either phytocannabinoid alone.
The studies provide “proof of principle” that CBD and possibly CBD-THC combinations are valid candidates for novel AD therapies.” https://www.ncbi.nlm.nih.gov/pubmed/28217094
“As a consequence of an increasingly aging population, the number of people affected by neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease, is rapidly increasing. Although the etiology of these diseases has not been completely defined, common molecular mechanisms including neuroinflammation, excitotoxicity and mitochondrial dysfunction have been confirmed and can be targeted therapeutically.
Moreover, recent studies have shown that endogenous cannabinoid signaling plays a number of modulatory roles throughout the central nervous system (CNS), including the neuroinflammation and neurogenesis.
In particular, the up-regulation of type-2 cannabinoid (CB2) receptors has been found in a number of neurodegenerative disorders. Thus, the modulation of CB2 receptor signaling may represent a promising therapeutic target with minimal psychotropic effects that can be used to modulate endocannabinoid-based therapeutic approaches and to reduce neuronal degeneration.
For these reasons this review will focus on the CB2 receptor as a promising pharmacological target in a number of neurodegenerative diseases.”
https://www.ncbi.nlm.nih.gov/pubmed/28210207
“Neuroimmune networks and the brain endocannabinoid system contribute to the maintenance of neurogenesis.
Activation of cannabinoid receptors suppresses chronic inflammatory responses through the attenuation of pro-inflammatory mediators. Moreover, the endocannabinoid system directs cell fate specification of NSCs (neural stem cells) in the CNS (central nervous system).
The aim of our work is to understand better the relationship between the endocannabinoid and the IL-1β (interleukin-1β) associated signalling pathways and NSC biology, in order to develop therapeutical strategies on CNS diseases that may facilitate brain repair.
NSCs express functional CB1 and CB2 cannabinoid receptors, DAGLα (diacylglycerol lipase α) and the NSC markers SOX-2 and nestin. We have investigated the role of CB1 and CB2 cannabinoid receptors in the control of NSC proliferation and in the release of immunomodulators [IL-1β and IL-1Ra (IL-1 receptor antagonist)] that control NSC fate decisions. Pharmacological blockade of CB1 and/or CB2 cannabinoid receptors abolish or decrease NSC proliferation, indicating a critical role for both CB1 and CB2 receptors in the proliferation of NSC via IL-1 signalling pathways.
Thus the endocannabinoid system, which has neuroprotective and immunomodulatory actions mediated by IL-1 signalling cascades in the brain, could assist the process of proliferation and differentiation of embryonic or adult NSCs, and this may be of therapeutic interest in the emerging field of brain repair.
In summary, cannabinoids and IL-1β seem to play antagonistic roles in neurogenesis: although cannabinoids increase proliferation and induce formation and maturation of new neurons, IL-1β blocks proliferation and formation of new neurons, inducing a shift towards a glial fate. This may be important in situations such as in aging, neurodegenerative diseases, and lesions of the brain and spinal cord.”
“Stroke is a leading cause of adult disability characterized by physical, cognitive, and emotional disturbances. Unfortunately, pharmacological options are scarce.
The cannabinoid type-2 receptor (CB2R) is neuroprotective in acute experimental stroke by anti-inflammatory mechanisms.
Our data support that CB2R is fundamental for driving neuroblast migration and suggest that an endocannabinoid tone is required for poststroke neurogenesis by promoting neuroblast migration toward the injured brain tissue, increasing the number of new cortical neurons and, conceivably, enhancing motor functional recovery after stroke.”
“This study investigated the effects of cannabidiol (CBD), a non-psychotomimetic phytochemical present in Cannabis sativa, on the cognitive and emotional impairments induced by bilateral common carotid artery occlusion (BCCAO) in mice.
Using a multi-tiered behavioral testing battery during 21days, we found that BCCAO mice exhibited long-lasting functional deficits reflected by increase in anxiety-like behavior (day 9), memory impairments (days 12-18) and despair-like behavior (day 21).
Short-term CBD 10mg/kg treatment prevented the cognitive and emotional impairments, attenuated hippocampal neurodegeneration and white matter (WM) injury, and reduced glial response that were induced by BCCAO.
In addition, ischemic mice treated with CBD exhibited an increase in the hippocampal brain derived neurotrophic factor (BDNF) protein levels.
CBD also stimulated neurogenesis and promoted dendritic restructuring in the hippocampus of BCCAO animals.
Collectively, the present results demonstrate that short-term CBD treatment results in global functional recovery in ischemic mice and impacts multiple and distinct targets involved in the pathophysiology of brain ischemic injury.”
“The endocannabinoid system has been implicated in the modulation of adult neurogenesis.
Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures.
There is an emerging consensus that endocannabinoid signaling plays a major role in adult neurogenesis.
Cannabinoids act on at least two types of receptors, the type 1 and type 2 cannabinoid receptors (CB1R and CB2R), which are, respectively, predominantly distributed in the central nervous system (CNS) and immune system, although some studies have described the presence of low levels of CB2R in the brain.
Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.
“The cannabinoid (CB) system is widespread in the central nervous system and is crucial for controlling a range of neurophysiological processes such as pain, appetite, and cognition. The endogenous CB molecules, anandamide, and 2-arachidonoyl glycerol, interact with the G-protein coupled CB receptors, CB(1) and CB(2).
These receptors are also targets for the phytocannabinoids isolated from the cannabis plant and synthetic CB receptor ligands.
The CB system is emerging as a key regulator of neuronal cell fate and is capable of conferring neuroprotection by the direct engagement of prosurvival pathways and the control of neurogenesis.
Many neurological conditions feature a neurodegenerative component that is associated with excitotoxicity, oxidative stress, and neuroinflammation, and certain CB molecules have been demonstrated to inhibit these events to halt the progression of neurodegeneration.
Such properties are attractive in the development of new strategies to treat neurodegenerative conditions of diverse etiology, such as Alzheimer’s disease, multiple sclerosis, and cerebral ischemia.
This article will discuss the experimental and clinical evidence supporting a potential role for CB-based therapies in the treatment of certain neurological diseases that feature a neurodegenerative component.”
“Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid derived from Cannabis sativa.
It has possible therapeutic effects over a broad range of neuropsychiatric disorders.
CBD attenuates brain damage associated with neurodegenerative and/or ischemic conditions.
It also has positive effects on attenuating psychotic-, anxiety- and depressive-like behaviors.
Moreover, CBD affects synaptic plasticity and facilitates neurogenesis.
The mechanisms of these effects are still not entirely clear but seem to involve multiple pharmacological targets.
In the present review, we summarized the main biochemical and molecular mechanisms that have been associated with the therapeutic effects of CBD, focusing on their relevance to brain function, neuroprotection and neuropsychiatric disorders.”