Differential transcriptional profiles mediated by exposure to the cannabinoids cannabidiol and Δ9-tetrahydrocannabinol in BV-2 microglial cells.

“Apart from their effects on mood and reward, cannabinoids exert beneficial actions such as neuroprotection and attenuation of inflammation. The immunosuppressive activity of cannabinoids has been well established. We previously showed that the psychoactive cannabinoid Δ(9) -tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD) differ in their anti-inflammatory signalling pathways.

CONCLUSIONS AND IMPLICATIONS:

These observations indicated that CBD, but much less than THC, induced a cellular stress response in microglial cells and suggested that this effect could underlie its anti-inflammatory activity.”

http://www.ncbi.nlm.nih.gov/pubmed/21542829

Cannabinoids Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Inhibit the Lipopolysaccharide-activated NF-κB and Interferon-β/STAT Proinflammatory Pathways in BV-2 Microglial Cells

“Cannabinoids have been shown to exert anti-inflammatory activities in various in vivo and in vitro experimental models as well as ameliorate various inflammatory degenerative diseases. Δ9-Tetrahydrocannabinol (THC)is a major constituent of Cannabis and serves as an agonist of the cannabinoid receptors CB1 and CB2.

The second major constituent of Cannabis extract is cannabidiol (CBD). CBD lacks the psychoactive effects that accompany the use of THC. Moreover, CBD was demonstrated to antagonize some undesirable effects of THC, including intoxication, sedation, and tachycardia, while sharing neuroprotective, anti-oxidative, anti-emetic, and anti-carcinogenic properties. Both THC and CBD have been shown to exert anti-inflammatory properties and to modulate the function of immune cells…

In summary, our results show that although both THC and CBD exert anti-inflammatory effects, the two compounds engage different, although to some extent overlapping, intracellular pathways. Both THC and CBD decrease the activation of proinflammatory signaling…

 The cannabinoids by moderating or disrupting these signaling networks may show promise as anti-inflammatory agents.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804319/

Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease.

“A placebo-controlled crossover design to investigate effects of dronabinol (THC) in patients with a diagnosis of probable Alzhemer’s disease who were refusing food. 

These results indicate that dronabinol is a promising novel therapeutic agent which may be useful not only for treatment of anorexia but also to improve disturbed behavior in patients with Alzheimer’s disease.”

http://www.ncbi.nlm.nih.gov/pubmed/9309469

Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia.

Psychopharmacology

“Nighttime agitation occurs frequently in patients with dementia and represents the number one burden on caregivers today. Current treatment options are few and limited due to substantial side effects.

OBJECTIVES:

The aim of the study was to measure the effect of the cannabinoid dronabinol (THC) on nocturnal motor activity.

RESULTS:

Compared to baseline, dronabinol led to a reduction in nocturnal motor activity. These findings were corroborated by improvements in Neuropsychiatric Inventory total score as well as in subscores for agitation, aberrant motor, and nighttime behaviors . No side effects were observed.

CONCLUSIONS:

The study suggests that dronabinol (THC) was able to reduce nocturnal motor activity and agitation in severely demented patients. Thus, it appears that dronabinol (THC) may be a safe new treatment option for behavioral and circadian disturbances in dementia.”

http://www.ncbi.nlm.nih.gov/pubmed/16521031

https://link.springer.com/article/10.1007%2Fs00213-006-0343-1

Regulation of cannabinoid CB1 receptors in the central nervous system by chronic cannabinoids.

“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.”

http://www.ncbi.nlm.nih.gov/pubmed/14977366

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. ”

http://www.jimmunol.org/content/187/12/6508.long

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.”

http://www.ncbi.nlm.nih.gov/pubmed/21034788

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.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069704/

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.”

http://www.ncbi.nlm.nih.gov/pubmed/19456285

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.”

http://www.ncbi.nlm.nih.gov/pubmed/19839933