[Cannabinoids in multiple sclerosis — therapeutically reasonable?].

“For centuries extracts from the Cannabis sativa plant have been used for recreational use and as remedies.

Anecdotal reports from patients with multiple sclerosis (MS) experiencing relief of their spasticity and pain after smoking marihuana have prompted discussions about a potential therapeutic application of cannabis preparations in MS.

Only recently the first large, multicenter, double-blind, placebo controlled study was conducted evaluating the use of cannabinoids for treatment of spasticity and other symptoms related to MS.

Based on this trial and previous uncontrolled observations together with insights from basic research and animal experiments there is reasonable evidence for the therapeutical employment of cannabinoids in the treatment of MS related symptoms.

Furthermore, data are arising that cannabinoids have immunomodulatory and neuroprotective properties.

This article summarizes the present knowledge of clinical and experimental research regarding the therapeutic potential of cannabinoids for the treatment of MS.”

http://www.ncbi.nlm.nih.gov/pubmed/16052440

Decreased depression in marijuana users.

“Over 4400 adult internet users completed The Center for Epidemiologic Studies Depression scale and measures of marijuana use.

We employed an internet survey in an effort to recruit the most depressed and marijuana-involved participants, including those who might prove unwilling to travel to the laboratory or discuss drug use on the phone or in person.

We compared those who consumed marijuana daily, once a week or less, or never in their lives.

Despite comparable ranges of scores on all depression subscales, those who used once per week or less had less depressed mood, more positive affect, and fewer somatic complaints than non-users.

Daily users reported less depressed mood and more positive affect than non-users.

These data suggest that adults apparently do not increase their risk for depression by using marijuana.”

http://www.ncbi.nlm.nih.gov/pubmed/15964704

Opposite Cannabis-Cognition Associations in Psychotic Patients Depending on Family History.

“The objective of this study is to investigate cognitive performance in a first-episode psychosis sample, when stratifying the interaction by cannabis use and familial or non-familial psychosis.

We found that cannabis use was associated with worse working memory, regardless of family history. However, cannabis use was clearly associated with worse cognitive performance in patients with no family history of psychosis, in cognitive domains including verbal memory, executive function and global cognitive index, whereas cannabis users with a family history of psychosis performed better in these domains.

The main finding of the study is that there is an interaction between cannabis use and a family history of psychosis in the areas of verbal memory, executive function and global cognition: that is, cannabis use is associated with a better performance in patients with a family history of psychosis and a worse performance in those with no family history of psychosis.

In order to confirm this hypothesis, future research should explore the actual expression of the endocannabinoid system in patients with and without a family history of psychosis.”

http://www.ncbi.nlm.nih.gov/pubmed/27513670

Synthesis and Biological Evaluation of Thiophene-Based Cannabinoid Receptor Type 2 Radiotracers for PET Imaging.

“Over the past two decades, our understanding of the endocannabinoid system has greatly improved due to the wealth of results obtained from exploratory studies. Currently, two cannabinoid receptor subtypes have been well-characterized. The cannabinoid receptor type 1 (CB1) is widely expressed in the central nervous system, while the levels of the cannabinoid receptor type 2 (CB2) in the brain and spinal cord of healthy individuals are relatively low.”

http://www.ncbi.nlm.nih.gov/pubmed/27512365

The inhibitory effect of combination treatment with leptin and cannabinoid CB1 receptor agonist on food intake and body weight gain is mediated by serotonin 1B and 2C receptors.

“Previous studies reported that the co-injection of leptin and cannabinoid CB1 receptor antagonists reduces food intake and body weight in rats, and this effect is more profound than that induced by these compounds individually. Additionally, serotonin mediates the effects of numerous anorectic drugs.

To investigate whether serotonin interacts with leptin and endocannabinoids to affect food intake and body weight, we administered 5-hydroxytryptamine(HT)1B and 5-hydroxytryptamine(HT)2C serotonin receptor antagonists (3 mg/kg GR 127935 and 0.5 mg/kg SB 242084, respectively) to male Wistar rats treated simultaneously with leptin (100 μg/kg) and the CB1 receptor inverse agonist AM 251 (1 mg/kg) for 3 days.

In accordance with previous findings, the co-injection of leptin and AM 251, but not the individual injection of each drug, resulted in a significant decrease in food intake and body weight gain. Blockade of the 5-HT1B and 5-HT2C receptors completely abolished the leptin- and AM 251-induced anorectic and body-weight-reducing effects.

These results suggest that serotonin mediates the leptin- and AM 251-dependent regulation of feeding behavior in rats via the 5-HT1B and 5-HT2C receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27512006

Cross-validated stable-isotope dilution GC-MS and LC-MS/MS assays for monoacylglycerol lipase (MAGL) activity by measuring arachidonic acid released from the endocannabinoid 2-arachidonoyl glycerol.

“2-Arachidonoyl glycerol (2AG) is an endocannabinoid that activates cannabinoid (CB) receptors CB1 and CB2. Monoacylglycerol lipase (MAGL) inactivates 2AG through hydrolysis to arachidonic acid (AA) and glycerol, thus modulating the activity at CB receptors.” http://www.ncbi.nlm.nih.gov/pubmed/27511795

Acute Stress Suppresses Synaptic Inhibition and Increases Anxiety via Endocannabinoid Release in the Basolateral Amygdala.

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“Stress and glucocorticoids stimulate the rapid mobilization of endocannabinoids in the basolateral amygdala (BLA).

Cannabinoid receptors in the BLA contribute to anxiogenesis and fear-memory formation. We tested for rapid glucocorticoid-induced endocannabinoid regulation of synaptic inhibition in the rat BLA.

Together, these findings suggest that acute stress causes a long-lasting suppression of synaptic inhibition in BLA neurons via a membrane glucocorticoid receptor-induced release of 2-AG at GABA synapses, which contributes to stress-induced anxiogenesis.

We show that acute stress increases anxiety-like behavior via an endocannabinoid-dependent mechanism centered in the BLA.

The stress-induced endocannabinoid modulation of synaptic transmission in the BLA contributes, therefore, to the stress regulation of anxiety, and may play a role in anxiety disorders of the amygdala.”

http://www.ncbi.nlm.nih.gov/pubmed/27511017

Medical Marijuana-Opportunities and Challenges

“Over the recent years, public and political opinions have demonstrated increasing support for the legalization of medical marijuana.

To date, 24 states as well as the District of Columbia have legalized cannabis for medical use, 4 states have legalized the recreational use of Marijuana.

Marijuana is derived from the hemp plant Cannabis sativa. Δ-9-tetrahydrocannabinol (THC) is the major psychoactive constituent of cannabis, while cannabidiol (CBD) is the major non-psychoactive constituent. THC is a partial agonist at CB1 and CB2 receptors, while CBD at high levels is an antagonist CB1 and CB2.

CB1 is abundantly expressed in the brain, and CB2 is expressed on immune cells (expression of CB2 on neurons remains controversial). The brain also produces endogenous cannabis-like substances (endocannabinoids) that bind and activate the CB1/CB2 receptors.

There is tremendous interest in harnessing the therapeutic potential of plant-derived and synthetic cannabinoids.

This Editorial provides an overview of diseases that may be treated by cannabinoids.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948749/

Marijuana users do not have increased healthcare utilization: A National Health and Nutrition Examination Survey (NHANES) study

“There is paucity of data on healthcare utilization due to marijuana use on a national scale.

Our study found no significant association exists between marijuana use and healthcare utilization.

The frequency of marijuana use also does not have significant impact on healthcare utilization.”

http://www.ejinme.com/article/S0953-6205(16)30231-X/fulltext