Endocannabinoid Signaling in Autism.

“Autism spectrum disorder (ASD) is a complex behavioral condition with onset during early childhood and a lifelong course in the vast majority of cases. To date, no behavioral, genetic, brain imaging, or electrophysiological test can specifically validate a clinical diagnosis of ASD. However, these medical procedures are often implemented in order to screen for syndromic forms of the disorder (i.e., autism comorbid with known medical conditions).

In the last 25 years a good deal of information has been accumulated on the main components of the “endocannabinoid (eCB) system”, a rather complex ensemble of lipid signals (“endocannabinoids”), their target receptors, purported transporters, and metabolic enzymes.

It has been clearly documented that eCB signaling plays a key role in many human health and disease conditions of the central nervous system, thus opening the avenue to the therapeutic exploitation of eCB-oriented drugs for the treatment of psychiatric, neurodegenerative, and neuroinflammatory disorders.

Here we present a modern view of the eCB system, and alterations of its main components in human patients and animal models relevant to ASD. This review will thus provide a critical perspective necessary to explore the potential exploitation of distinct elements of eCB system as targets of innovative therapeutics against ASD.”

http://www.ncbi.nlm.nih.gov/pubmed/26216231#

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

Mitochondrial CB1 receptor is involved in ACEA-induced protective effects on neurons and mitochondrial functions.

“Mitochondrial dysfunction contributes to cell death after cerebral ischemia/reperfusion (I/R) injury.

Cannabinoid CB1 receptor is expressed in neuronal mitochondrial membranes (mtCB1R) and involved in regulating mitochondrial functions under physiological conditions…

In purified neuronal mitochondria, mtCB1R activation attenuated Ca(2+)-induced mitochondrial injury.

In conclusion, mtCB1R is involved in ACEA-induced protective effects on neurons and mitochondrial functions, suggesting mtCB1R may be a potential novel target for the treatment of brain ischemic injury.”

http://www.ncbi.nlm.nih.gov/pubmed/26215450

An Overview of Products and Bias in Research.

“Cannabis is a genus of annual flowering plant.

Cannabis is often divided into 3 species-Cannabis sativa, Cannabis indica, and Cannabis ruderalis-but there is significant disagreement about this, and some consider them subspecies of the same parent species.

Cannabis sativa can grow to 5-18 feet or more, and often has a few branches.

Cannabis indica typically grows 2-4 feet tall and is compactly branched.

Cannabis ruderalis contains very low levels of Δ-9-tetrahyocannabinol so is rarely grown by itself. Cannabis ruderalis flowers as a result of age, not light conditions, which is called autoflowering. It is principally used in hybrids, to enable the hybrid to have the autoflowering property.

There are > 700 strains of cannabis, often with colorful names.

Some are strains of 1 of the 3 subspecies. Many are crossbred hybrids.

The strains can be named in a variety of ways: smell or lineage are common ways of naming. There are only a few rules about how the strains are named, and most strains’ names do not follow the rules.

There are 4 basic preparations of marijuana: bhang, hasish, oil (or hash oil), and leaves and/or buds.

In medical marijuana trials, subjective outcomes are frequently used but blind breaking can introduce significant bias. Blind breaking occurs when patients figure out if they are in the control or the treatment group. When this occurs, there is significant overestimation of treatment effect.”

http://www.ncbi.nlm.nih.gov/pubmed/26202343

Cannabinoids blocks tactile allodynia in diabetic mice without attenuation of its antinociceptive effect.

“Diabetic neuropathic pain is one of the most commonly encountered neuropathic pain syndromes.

It is well known that diabetic animals are less sensitive to the analgesic effect of morphine, and opioids are found to be ineffective in the treatment of diabetic neuropathic pain.

Cannabinoids are promising drugs and they share a similar pharmacological properties with opioids.

It has been reported that cannabinoid analgesia remained intact and to be effective in some models of nerve injury.

Thus, we investigated antinociceptive efficacy and the effects of cannabinoids on behavioral sign of diabetic neuropathic pain in diabetic mice by using WIN 55, 212-2, a cannabinoid receptor agonist.

This study suggests that cannabinoids have a potential beneficial effect on experimental diabetic neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/15342139

Synergistic anti-allodynic effects of nociceptin/orphanin FQ and cannabinoid systems in neuropathic mice.

“Combinations of analgesics from different classes are commonly used in the management of chronic pain. The goal is to enhance pain relief together with the reduction of side effects.

The present study was undertaken to examine the anti-allodynic synergy resulting from the combination of WIN 55,212-2, a cannabinoid CB1 receptor agonist, and JTC-801, a nociceptin/orphanin FQ receptor antagonist, on neuropathic pain…

In conclusion, co-administration of acannabinoid with a nociceptin/orphanin FQ receptor antagonist resulted in a synergistic interaction, which may have utility in the pharmacological treatment of neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/21664922

Analysis of the anti-allodynic effects of combination of a synthetic cannabinoid and a selective noradrenaline re-uptake inhibitor in nerve injury-induced neuropathic mice.

“Combining drugs not only reduces specific adverse effects of each of the drug at a higher dose but also may lead to enhanced efficacy.

Taking into consideration, the pharmacological similarities between opioids and cannabinoids, we assumed that combination of cannabinoids with noradrenaline re-uptake inhibitors might also be effective…

Overall, our data suggest that combination of a cannabinoid with a selective noradrenaline re-uptake inhibitor may offer a beneficial treatment option for neuropathic pain.”

Cannabinoids for the Treatment of Movement Disorders.

“Use of cannabinoids as medications has a long history.

Unfortunately, the prohibition of cannabis and its classification in 1970 as a schedule 1 drug has been a major obstacle in studying these agents in a systematic, controlled manner.

The number of class 1 studies (randomized, double-blind, placebo-controlled) in patients with movement disorders is limited. Hence, it is not possible to make recommendations on the use of these cannabinoids as primary treatments for any of the movement disorders at this time.

Fortunately, there is an expanding body of research in animal models of age-dependent and disease-related changes in the endocannabinoid system that is providing new targets for drug development.

Moreover, there is growing evidence of a “cannabinoid entourage effect” in which a combination of cannabinoids derived from the plant are more effective than any single cannabinoid for a number of conditions.

Cannabis preparations may presently offer an option for compassionate use in severe neurologic diseases, but at this point, only when standard-of-care therapy is ineffective.

As more high-quality clinical data are gathered, the therapeutic application of cannabinoids will expand.”

http://www.ncbi.nlm.nih.gov/pubmed/26206230

Cross-tolerance to cannabinoids in morphine-tolerant rhesus monkeys.

“Opioids remain the drugs of choice for treating moderate to severe pain, although adverse effects limit their use. Therapeutic utility might be improved by combining opioids with other drugs to enhance analgesic effects, but only if adverse effects are not similarly changed.

Cannabinoids have been shown to enhance the antinociceptive potency of opioids without increasing other effects; this study examined whether the effectiveness of cannabinoids is altered in morphine-dependent monkeys.

Tolerance developed to the antinociceptive effects of morphine and cross-tolerance developed to cannabinoids under conditions that produced modest physical dependence.

Compared with the doses examined in this study, much smaller doses of opioids have antinociceptive effects when given with cannabinoids; it is possible that tolerance will not develop to chronic treatment with opioid/cannabinoid mixtures.”

http://www.ncbi.nlm.nih.gov/pubmed/26202613

Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist.

“Cannabinoid receptor 2 agonists and inverse agonists are emerging as new therapeutic options for a spectrum of autoimmune-related disease.

Of particular interest, is the ability of CB2 ligands to regulate microglia function in neurodegenerative diseases and traumatic brain injury.

We have previously reported the receptor affinity of 3′,5′-dichloro-2,6-dihydroxy-biphenyl-4-yl)-phenyl-methanone (SMM-189) and the characterization of the beneficial effects of SMM-189 in the mouse model of mild traumatic brain injury.

Herein, we report the further characterization of SMM-189 as a potent and selective CB2 inverse agonist, which acts as a noncompetitive inhibitor of CP 55,940.

The ability of SMM-189 to regulate microglial activation, in terms of chemokine expression and cell morphology, has been determined.

Finally, we have determined that SMM-189 possesses acceptable biopharmaceutical properties indicating that the triaryl class of CB2 inverse agonists are viable compounds for continued preclinical development for the treatment of neurodegenerative disorders and traumatic brain injury.”

http://www.ncbi.nlm.nih.gov/pubmed/26196013

Use and effects of cannabinoids in military veterans with posttraumatic stress disorder.

“Published evidence regarding the use of cannabis and cannabis derivatives by military veterans with posttraumatic stress disorder (PTSD) is reviewed.

SUMMARY:

When inhaled or delivered orally or transdermally, cannabinoids (the psychoactive components of unrefined marijuana and various derivative products) activate endogenous cannabinoid receptors, modulating neurotransmitter release and producing a wide range of central nervous system effects, including increased pleasure and alteration of memory processes. Those effects provide a pharmacologic rationale for the use of cannabinoids to manage the three core PTSD symptom clusters: reexperiencing, avoidance and numbing, and hyperarousal.

Cross-sectional studies have found a direct correlation between more severe PTSD symptomatology and increased motivation to use cannabis for coping purposes, especially among patients with difficulties in emotional regulation or stress tolerance. Data from 4 small studies suggested that cannabinoid use was associated with global improvements in PTSD symptoms or amelioration of specific PTSD symptoms such as insomnia and nightmares.

CONCLUSION:

While further research into cannabinoid treatment effects on PTSD symptoms is required, the evaluated evidence indicates that substantial numbers of military veterans with PTSD use cannabis or derivative products to control PTSD symptoms, with some patients reporting benefits in terms of reduced anxiety and insomnia and improved coping ability.”

http://www.ncbi.nlm.nih.gov/pubmed/26195653