Medicinal cannabis.

Posted on February 5, 2016 by David

“A number of therapeutic uses of cannabis and its derivatives have been postulated from preclinical investigations.

Possible clinical indications include spasticity and pain in multiple sclerosis, cancer-associated nausea and vomiting, cancer pain and HIV neuropathy.

Controversies lie in how to produce, supply and administer cannabinoid products.

Introduction of cannabinoids therapeutically should be supported by a regulatory and educational framework that minimises the risk of harm to patients and the community.

The Regulator of Medicinal Cannabis Bill 2014 is under consideration in Australia to address this.

Nabiximols is the only cannabinoid on the Australian Register of Therapeutic Goods at present, although cannabidiol has been recommended for inclusion in Schedule 4.”

http://www.ncbi.nlm.nih.gov/pubmed/26843715

“There is some evidence of therapeutic benefit for cannabis products in defined patient populations.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674028/

Cannabinoids for the Treatment of Schizophrenia: An Overview.

Posted on February 5, 2016 by David

“Δ9-tetrahydrocannabinol and its analogues are found to have particular application in psychiatry because of their antipsychotic properties suggesting a therapeutic use as neuroleptic agents in limiting psychotic diseases.

These treatments should not only aim to alleviate specific symptoms but also attempt to delay/arrest disease progression.

In the present review, we reported recent studies supporting the view that the cannabinoid signalling system is a key modulatory element in the activity of the striatum and temporal cortex that has been traditionally associated with psychosis and schizophrenia.

This idea is supported by different anatomical, electrophysiological, pharmacological and biochemical data.

Furthermore, these studies indicate that the cannabinoid system is impaired in different psychotic disorders, supporting the idea of developing novel pharmacotherapies with compounds that selectively target specific elements of the cannabinoid system.”

http://www.ncbi.nlm.nih.gov/pubmed/26845552

http://www.thctotalhealthcare.com/category/schizophrenia/

Expression and Function of the Endocannabinoid System in the Retina and the Visual Brain.

Posted on February 4, 2016 by David

“Endocannabinoids are important retrograde modulators of synaptic transmission throughout the nervous system.

Cannabinoid receptors are seven transmembrane G-protein coupled receptors favoring Gi/o protein. They are known to play an important role in various processes, including metabolic regulation, craving, pain, anxiety, and immune function.

In the last decade, there has been a growing interest for endocannabinoids in the retina and their role in visual processing.

The purpose of this review is to characterize the expression and physiological functions of the endocannabinoid system in the visual system, from the retina to the primary visual cortex, with a main interest regarding the retina, which is the best-described area in this system so far.

It will show that the endocannabinoid system is widely present in the retina, mostly in the through pathway where it can modulate neurotransmitter release and ion channel activity, although some evidence also indicates possible mechanisms via amacrine, horizontal, and Müller cells.

The presence of multiple endocannabinoid ligands, synthesizing and catabolizing enzymes, and receptors highlights various pharmacological targets for novel therapeutic application to retinal diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/26839718

Cannabidiol disrupts the reconsolidation of contextual drug-associated memories in Wistar rats.

Posted on February 3, 2016 by David

“In addicts, craving and relapse are frequently induced by the recall of memories related to a drug experience. Several studies have demonstrated that drug-related memories are reactivated after exposure to environmental cues and may undergo reconsolidation, a process that can strengthen memories. Thus, reactivation of mnemonic traces provides an opportunity for disrupting memories that contribute to the pathological cycle of addiction.

Here we used drug-induced conditioned place preference (CPP) to investigate whether cannabidiol (CBD), a phytocannabinoid, given just after reactivation sessions, would affect reconsolidation of drug-reward memory, reinstatement of morphine-CPP, or conditioned place aversion precipitated by naltrexone in Wistar rats.

We found that CBD impaired the reconsolidation of preference for the environment previously paired with both morphine and cocaine. This disruption seems to be persistent, as the preference did not return after further reinstatement induced by priming drug and stress reinstatement.

Moreover, in an established morphine-CPP, an injection of CBD after the exposure to a conditioning session led to a significant reduction of both morphine-CPP and subsequent conditioned place aversion precipitated by naltrexone in the same context.

Thus, established memories induced by a drug of abuse can be blocked after reactivation of the drug experience.

Taken together, these results provide evidence for the disruptive effect of CBD on reconsolidation of contextual drug-related memories and highlight its therapeutic potential to attenuate contextual memories associated with drugs of abuse and consequently to reduce the risk of relapse.”

http://www.ncbi.nlm.nih.gov/pubmed/26833888

Regulation of Stem Cells by the Endocannabinoid System

Posted on January 30, 2016 by David

“The endocannabinoids, endogenous lipid mediators of related chemical structure to the prototype exogenous cannabinoid Δ⁹-THC found in marijuana, have emerged as important mediators that regulate central and peripheral neural functions as well as immune responses.

Endogenous and exogenous cannabinoid ligands bind to cannabinoid receptors: the predominant central cannabinoid receptor type 1 (CB₁) and the peripheral cannabinoid receptor type 2 (CB₂). CB₁ and CB₂ are members of the G-protein coupled receptor family.

Cannabinoids were shown to modulate the immune system and to affect the migration of blood cells, such as T-cells, monocytes and myeloid leukemia cells, through CB receptors.

Recent data indicate the potential role of cannabinoid ligands and receptors in the regulation of hematopoiesis and hematopoietic stem cell (HSC) migration and trafficking.

These studies may lead to clinical applications of cannabinoid-based compounds as new HSC-mobilizer agents for therapeutic intervention in bone marrow failure.”

http://link.springer.com/chapter/10.1007/978-94-007-2993-3_30

CB2 receptor activation prevents glial-derived neurotoxic mediator production, BBB leakage and peripheral immune cell infiltration and rescues dopamine neurons in the MPTP model of Parkinson’s disease

Posted on January 30, 2016 by David

“Parkinson’s disease (PD) is characterized by the degeneration of nigrostriatal dopamine neurons.

The endocannabinoid system consists of cannabinoid receptors, their ligands and enzymes for the synthesis and degradation of cannabinoids.

Our results suggest that targeting the cannabinoid system may be beneficial for the treatment of neurodegenerative diseases, such as PD, that are associated with glial activation, BBB disruption and peripheral immune cell infiltration.

In summary, we demonstrated that activation of the CB2 receptor inhibits BBB damage, the expression of iNOS and proinflammatory cytokines/chemokines in activated microglia, the infiltration of T cells and astroglial expression of MPO, resulting in the survival of dopamine neurons in vivo in the MPTP mouse model of PD.

Therefore, it is likely that targeting the CB2 receptor may have therapeutic value in the treatment of aspects of PD related to neuroinflammation.”

http://www.nature.com/emm/journal/v48/n1/full/emm2015100a.html

Clinical/Therapeutic Approaches for Cannabinoid Ligands in Central and Peripheral Nervous System Diseases: Mini Review.

Posted on January 29, 2016 by David

“Cannabinoids, the components of Cannabis sativa Linnaeus, interact with CB1 and CB2 receptors, which are located both in the central nervous system and in the periphery and thus may exert a widespread biological activity in the body.

The main medicinal properties of cannabinoids include analgesic, anti-inflammatory, antitumor, appetite stimulation, antiemesis, and muscle relaxation effects.

This mini review aims to explore existing clinical trials that investigated the use of cannabinoids in diseases affecting the nervous system.

There is evidence that cannabinoid-based drugs may effectively control some symptoms associated with nervous system dysfunction, especially various types of pain and neurologic disorders, although studies are limited.

The efficacy of cannabinoid drugs in the treatment of nervous system diseases should be verified in future large-scale randomized clinical trials.”

http://www.ncbi.nlm.nih.gov/pubmed/26818043

The endocannabinoid system and neuropathic pain.

Posted on January 20, 2016 by David

“The research of new therapeutic strategies for neuropathic pain represents a major current priority.

Important drawbacks to advance in the development of these therapies are the limited translational value of the animal models now available and the elucidation of the complex neuronal and immune pathophysiological mechanisms underlying neuropathic pain.

One of the neurotransmitter systems participating in neuropathic pain control that has recently raised a particular interest is the endocannabinoid system.

This system is highly expressed in neurons and immune cells, and it plays a crucial role in the development of neuropathic pain.

Preclinical studies have provided important findings, revealing the potential interest of the endocannabinoid system for the treatment of neuropathic pain.

These studies have reported the analgesic effects of cannabinoid agonists in multiple neuropathic pain models, and they have identified specific targets within this system to develop more effective and safe analgesic compounds.

Several clinical studies suggest that cannabinoids significantly reduced neuropathic pain…“

http://www.ncbi.nlm.nih.gov/pubmed/26785153

Role of hypothalamic cannabinoid receptors in post-stroke depression in rats.

Posted on January 19, 2016 by David

“One of the most common psychological consequences of stroke is post-stroke depression (PSD). While more than 30 percent of stroke patients eventually develop PSD, the neurobiological mechanisms underlying such a phenomenon have not been well investigated.

Given the critical involvement of hypothalamic-pituitary-adrenal axis and endocannabinoid system in response to stressful stimuli, we evaluated the hypothesis that cannabinoid receptors in the hypothalamus are critical for modulation of post-stroke depression-like behaviors in rats.

Taken together, these results suggest that decreased CB1 receptor expression is likely associated with the development of post-stroke depression, and CB2 receptor may be a potential therapeutic target for the treatment post-stroke depressive disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26778127

Cannabinoid receptor-2 agonist inhibits macrophage induced EMT in non-small cell lung cancer by downregulation of EGFR pathway.

Posted on January 12, 2016 by David

“JWH-015, a cannabinoid receptor 2 (CB2) agonist has tumor regressive property in various cancer types.

These data confer the impact of this cannabinoid on anti-proliferative and anti-tumorigenic effects, thus enhancing our understanding of its therapeutic efficacy in NSCLC.

Our findings open new avenues for cannabinoid receptor CB2 agonist-JWH-015 as a novel and potential therapeutic target based on EGFR downregulation mechanisms in NSCLC.”

http://www.ncbi.nlm.nih.gov/pubmed/26741322