ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.

Posted on April 19, 2016 by David

Image result for Curr Clin Pharmacol.

“Cannabis sativa is also popularly known as marijuana. It is being cultivated and used by man for recreational and medicinal purposes from many centuries.

Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries.

The research of drugs acting on endocannabinoid system has seen many ups and down in recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve “protective role” in many medical conditions.

Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and Tourette’s syndrome could possibly be treated by drugs modulating endocannabinoid system.

Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures. Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008.

Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse events in the participating subjects could be discouraging for the research fraternity. Despite of some mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and antagonists.

One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that acts selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted.

Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids.

In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as “protective” and “disease inducing substance”, time-dependent changes in the expression of cannabinoid receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27086601

Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?

Posted on March 30, 2016 by David

“The Cannabis sativa plant has been used to treat various physiological and psychiatric conditions for millennia.

Current research is focused on isolating potentially therapeutic chemical constituents from the plant for use in the treatment of many central nervous system disorders.

Of particular interest is the primary nonpsychoactive constituent cannabidiol (CBD).

Unlike Δ9-tetrahydrocannabinol (THC), CBD does not act through the cannabinoid type 1 (CB1) receptor but has many other receptor targets that may play a role in psychiatric disorders.

Here we review preclinical and clinical data outlining the therapeutic efficacy of CBD for the treatment of motivational disorders such as drug addiction, anxiety, and depression.

Across studies, findings suggest promising treatment effects and potentially overlapping mechanisms of action for CBD in these disorders and indicate the need for further systematic investigation of the viability of CBD as a psychiatric pharmacotherapy.”

http://www.ncbi.nlm.nih.gov/pubmed/27023732

Study the Effect of Endocannabinoid System on Rat Behavior in Elevated Plus-Maze.

Posted on February 24, 2016 by David

“Previous studies have shown that cannabinoidergic system is involved in anxiety.

The aim of this study is to evaluate the effect of pharmacological stimulation or blocking of CB1 receptors and inhibition of endocannabinoid degradation in anxiety like behavior in elevated plus-maze (EPM) test in rat.

It is concluded that activation of cannabinoid receptor exert anxiolytic effect while blocking of cannabinoid receptor resulted in anxiety behavior. The locomotor activity was not significantly changed by cannabinoid system.

It is suggested that potentiation of cannabinoid system may be therapeutic strategy for the anxiety behavior.”

http://www.ncbi.nlm.nih.gov/pubmed/26904171

http://www.thctotalhealthcare.com/category/anxiety-2/

Cannabis use and symptoms of anxiety in adolescence and the moderating effect of the serotonin transporter gene.

Posted on February 11, 2016 by David

“Prior studies have concluded that cannabis use alone is not sufficient for the development of long-term anxiety, and it has been suggested that cannabis is simply a risk factor that operates in conjunction with other risk factors.

One such risk factor may be an individuals’ genetic vulnerability.

The present study examines the relationship between cannabis use and symptoms of anxiety by taking a developmental molecular-genetic perspective with a focus on a polymorphism involved in the regulation of serotonin.

The findings of the present study show first evidence that the links between cannabis use and symptoms of anxiety are conditional on the individuals’ genetic make-up.”

http://www.ncbi.nlm.nih.gov/pubmed/26860734

Cannabidiol, neuroprotection and neuropsychiatric disorders.

Posted on February 5, 2016 by David

“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.”

http://www.ncbi.nlm.nih.gov/pubmed/26845349

A systematic review of plant-derived natural compounds for anxiety disorders.

Posted on February 5, 2016 by David

“Anxiety disorders are the most common mental illnesses affecting human beings. They range from panic to generalized anxiety disorders upsetting the well-being and psychosocial performance of patients. Several conventional anxiolytic drugs are being used which in turn result in several adverse effects. Therefore, studies to find suitable safe medicines from natural sources are being conducted by researchers.

The aim of the present study is to comprehensively review phytochemical compounds with well-established anxiolytic activities and their structure-activity relationships as well as neuropsychopharmacological aspects. Results showed that phytochemicals like; alkaloids, flavonoids, phenolic acids, lignans, cinnamates, terpenes and saponins possess anxiolytic effects in a wide range of animal models of anxiety.

The involved mechanisms include interaction with γ-aminobutyric acid (GABA)A receptors at benzodiazepine (BZD) and non-BZD sites with various affinity to different subunits, serotonergic 5-hydrodytryptamine (5-HT)1A and 5-HT2A/C receptors, noradrenergic and dopaminergic systems, glycine and glutamate receptors, and κ-opioid receptor as well as cannabinoid (CB)1 and CB2 receptors.

Phytochemicals also modulate the hypothalamo-pituitary-adrenal (HPA) axis, the levels of pro-inflammatory cytokines like interleukin (IL)-2, IL-6, IL-1β and tumor necrosis factor (TNF)-α, and improve brain derived neurotrophic factor (BDNF) levels. Transient receptor potential cation channel subfamily V (TRPV)3, nitric oxide cyclic guanosine monophosphate (NO-cGMP) pathway and monoamine oxidase enzymes are other targets of phytochemicals with anxiolytic activity.

Taking together, these phytochemicals may be considered as supplements to conventional anxiolytic therapies in order to improve efficacy and reduce adverse effects.

Further preclinical and clinical studies are still needed in order to recognize the structure-activity relationships, metabolism, absorption, and neuropsychopharmacological mechanisms of plant-derived natural agents.”

http://www.ncbi.nlm.nih.gov/pubmed/26845556

The association between cannabis use and anxiety disorders: Results from a population-based representative sample.

Posted on January 19, 2016 by David

“This study explored the association between cannabis use, cannabis use disorders (CUDs) and anxiety disorders in a 3-year prospective study.

Our findings suggest that cannabis use and CUDs are not associated with increased incidence of most anxiety disorders and inversely, most anxiety disorders are not associated with increased incidence of cannabis use or CUDs.”

http://www.ncbi.nlm.nih.gov/pubmed/26775742

Cannabis use, depression and anxiety: A 3-year prospective population-based study.

Posted on January 17, 2016 by David

“Whether or not cannabis use may increase the risk for depression and/or anxiety is not clear. For one thing, it has not been possible to draw a definitive conclusion regarding the direction of causality, i.e. whether cannabis use increases the risk for depression/anxiety or vice versa. This study aimed at examining possible associations between cannabis use, depression and anxiety, using all three measures as both exposure and outcome…

CONCLUSIONS:

We found no longitudinal associations between cannabis use and incidence of depression/anxiety, or between depression/anxiety and later cannabis use onset.”

http://www.ncbi.nlm.nih.gov/pubmed/26773900

Self-Medication of Somatic and Psychiatric Conditions Using Botanical Marijuana.

Posted on November 28, 2015 by David

“As a complement to research evaluating botanical marijuana as a medical therapy for various somatic and psychiatric conditions, there is a growing body of research assessing marijuana users’ self-reports of the symptoms and conditions for which they use marijuana without a physician’s recommendation.

As part of two larger web-based surveys and one in-situ survey at an outdoor marijuana festival, we asked regular marijuana users if they consumed the drug without a physician’s recommendation and, if so, to describe (or select from a checklist) the conditions for which they used marijuana as a medication.

Participants reported using marijuana to self-medicate a wide variety of both somatic conditions (such as pain, diabetes, and irritable bowel syndrome) and psychiatric conditions (such as depression, anxiety, and insomnia).

Because fewer than half of the American states, and only a few countries, allow physicians to recommend medicinal marijuana, these findings may be of interest to clinicians as they treat patients, to lawmakers and policymakers as they consider legislation allowing physicians to recommend botanical marijuana for somatic and psychiatric conditions, and to researchers evaluating conditions that individuals elect to self-medicate using botanical marijuana.”

http://www.ncbi.nlm.nih.gov/pubmed/26595140

The endocannabinoid system in guarding against fear, anxiety and stress.

Posted on November 21, 2015 by David

“The endocannabinoid (eCB) system has emerged as a central integrator linking the perception of external and internal stimuli to distinct neurophysiological and behavioural outcomes (such as fear reaction, anxiety and stress-coping), thus allowing an organism to adapt to its changing environment.

eCB signalling seems to determine the value of fear-evoking stimuli and to tune appropriate behavioural responses, which are essential for the organism’s long-term viability, homeostasis and stress resilience; and dysregulation of eCB signalling can lead to psychiatric disorders.

An understanding of the underlying neural cell populations and cellular processes enables the development of therapeutic strategies to mitigate behavioural maladaptation.”

http://www.ncbi.nlm.nih.gov/pubmed/26585799