Cannabis-like chemical combats chief genetic cause of autism

“Natural cannabis-like chemicals in the brain may help combat the leading genetic cause of autism, research has shown.

Scientists linked blockages in a signalling pathway dependent on the compounds, called 2-AG endocannabinoid transmitters, with symptoms of Fragile X syndrome.

Correcting the fault with drugs led to dramatic behavioural improvements in mice with a version of the condition.

Fragile X syndrome is the most common known genetic cause of autism.

It results from a mutation in the FMR1 gene on the female X chromosome. Men possess one copy of the chromosome, paired with a male Y chromosome, and women two.

Boys are much more likely to be born with Fragile X than girls. This is thought to be because with two X chromosomes, a defect in one may be compensated for by the other.

People with the syndrome suffer mental impairment, learning difficulties, and may be hyperactive or impulsive. They also possess notable physical characteristics such as an elongated face, flat feet and large ears.

“What we hope is to one day increase the ability of people with Fragile X syndrome to socialise and engage in normal cognitive functions,” said lead researcher Professor Daniele Piomelli, from the University of California at Irvine in the United States.

The study was the first to identify the role of endocannabinoids in the neurobiology of Fragile X, she said.

About endocannabinoids

Endocannabinoid compounds are created naturally in the body and share a similar chemical structure with THC, the primary psychoactive component of the marijuana plant, Cannabis.

Endocannabinoids are distinctive because they link with protein molecule receptors — called cannabinoid receptors — on the surface of cells. For instance, when a person smokes marijuana, the cannabinoid THC activates these receptors. And because the body’s natural cannabinoids control a variety of factors — such as pain, mood and appetite — they’re attractive targets for drug discovery and development.”

Read more: http://www.belfasttelegraph.co.uk/news/health/cannabis-chemical-combats-chief-genetic-cause-of-autism-16216090.html#ixzz2DRLsbjJO

Consequences of Cannabinoid and Monoaminergic System Disruption in a Mouse Model of Autism Spectrum Disorders

“Autism is a behaviorally defined neurodevelopmental disorder characterized by impairments in social interaction and communication and repetitive/stereotyped behaviors . The cause of autism is not completely understood and there is no effective cure. However, genetic and environmental factors and the interaction between genes and environment are known to play a role in Autism Spectrum Disorders (ASDs)…

Our data provides a basis for further studies in evaluating the role of the cannabinoid and monoaminergic systems in the etiology of ASDs.

It is tempting to suggest the evaluation of Δ9-THC or other cannabinoids with reduced psychoactivity in irritability, tantrums and self-injurious behavior associated with autistic individuals.

 The rationale for this novel hypothesis arises from the discovery that the endocannabinoid system is one of the most abundant physiological control systems in animals and humans.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3137184/

Would some cannabinoids ameliorate symptoms of autism?

“Cannabidiol (CBD) is a major nonpsychotropic constituent of cannabis sativa, which unlike the other major constituent delta9-tetrahydrocannabinol (delta9-THC), is virtually inactive at both of its central nervous system receptors. In one study, cell-based calcium mobilization and electrophysiological assays were used to identify and characterize several novel cannabinoid TRPV2 agonists in cultured rat dorsal root ganglion neurons. Among these, CBD was found to be the most robust and potent, followed by delta9-THC and cannabinol. Those cannabinoids may, accordingly, possess the ability, due to their action as TRPV2 agonists, to increase the release of both oxytocin and vasopressin enhancing the stimulation of oxytocin receptor and V1a receptors at the same time. CBD displays a plethora of other actions including anticonvulsive, sedative, hypnotic, antipsychotic, anti-inflammatory and neuroprotective properties. CBD and delta9-THC are components of drugs commercialized, in certain countries, as treatments for neuropathic pain, overactive bladder, and spasticity in patients suffering from multiple sclerosis. Thus, despite their action on oxytocin and vasopressin release, CBD and delta9-THC may help in improving symptoms of ASD by their sedative, antipsychotic, anticonvulsant and tranquilizing effects. In addition, the cannabinoid system has already been shown to be implicated in social behavior in rats.
 
The administration of cannabinoids for children and adolescents suffering from ASD is a controversial legal and ethical issue. Instead, those cannabinoids may be tested when administered to animals presenting autistic symptoms. Animal models of autistic symptoms exist especially in rodents that have their oxytocin and/or vasopressin function impaired such as mice or rats lacking the oxytocin or vasopressin gene or one of their receptors]. Whenever cannabinoids were found efficient in animal models of autism, the rationale supporting their efficacy may outweigh their legal and ethical adversities, when administered to children in the setting of randomized controlled studies.”
 

[Cannabinoids in the control of pain].

Abstract

“Hemp (Cannabis sativa L.) has been used since remotes ages as a herbal remedy. Only recently the medical community highlighted the pharmacological scientific bases of its effects. The most important active principle, Delta-9-tetrahydrocannabinol, was identified in the second half of the last century, and subsequently two receptors were identified and cloned: CB1 that is primarily present in the central nervous system, and CB2 that is present on the cells of the immune system. Endogenous ligands, called endocannabinoids, were characterized. The anandamide was the first one to be discovered. The effectiveness of the cannabinoids in the treatment of nausea and vomit due to anti-neoplastic chemotherapy and in the wasting-syndrome during AIDS is recognized. Moreover, the cannabinoids are analgesic, and their activity is comparable to the weak opioids. Furthermore, parallels exist between opioid and cannabinoid receptors, and evidence is accumulating that the two systems sometimes may operate synergistically. The interest of the pharmaceutical companies led to the production of various drugs, whether synthetic or natural derived. The good ratio between the polyunsatured fatty acids omega-3 and omega-6 of the oil of Cannabis seeds led to reduction of the phlogosis and an improvement of the pain symptoms in patients with chronic musculo-skeletal inflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/19388223

An analgesic role for cannabinoids.

Abstract

“Cannabinoids have significant analgesic properties in animal models, particularly for chronic pain states, but there are few human studies. An endogenous cannabinoid system, with specific receptors and transmitters, has recently been discovered. This discovery has led pharmacologists to explore the potential of synthetic cannabinoids to selectively target chronic pain disorders without producing the side effects associated with cannabis. Well-controlled clinical trials on cannabinoids, and cannabinoid delivery systems, are now required.”

http://www.ncbi.nlm.nih.gov/pubmed/11130354

Reassessment of the role of cannabinoids in the management of pain.

“The aim of this article is to assess the role of cannabinoids in the treatment of acute and chronic pain in humans.

 …to date there is increasing evidence that cannabinoids are safe and effective for refractory chronic pain conditions including neuropathic pain associated with multiple sclerosis, rheumatoid arthritis, and peripheral neuropathy associated with HIV/AIDS.

SUMMARY:

The precise role of cannabinoids in pain treatment still needs further evaluation. Cannabinoid compounds may be more effective in the context of chronic neuropathic pain than for the management of acute pain.”

http://www.ncbi.nlm.nih.gov/pubmed/17873600

Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials.

“Effective therapeutic options for patients living with chronic pain are limited. The pain relieving effect of cannabinoids remains unclear. A systematic review of randomized controlled trials (RCTs) examining cannabinoids in the treatment of chronic non-cancer pain was conducted according to the PRISMA statement update on the QUORUM guidelines for reporting systematic reviews that evaluate health care interventions. Cannabinoids studied included smoked cannabis, oromucosal extracts of cannabis based medicine, nabilone, dronabinol and a novel THC analogue. Chronic non-cancer pain conditions included neuropathic pain, fibromyalgia, rheumatoid arthritis, and mixed chronic pain. Overall the quality of trials was excellent. Fifteen of the eighteen trials that met the inclusion criteria demonstrated a significant analgesic effect of cannabinoid as compared with placebo and several reported significant improvements in sleep. There were no serious adverse effects. Adverse effects most commonly reported were generally well tolerated, mild to moderate in severity and led to withdrawal from the studies in only a few cases. Overall there is evidence that cannabinoids are safe and modestly effective in neuropathic pain with preliminary evidence of efficacy in fibromyalgia and rheumatoid arthritis. The context of the need for additional treatments for chronic pain is reviewed. Further large studies of longer duration examining specific cannabinoids in homogeneous populations are required.

In conclusion this systematic review of 18 recent good quality randomized trials demonstrates that cannabinoids are a modestly effective and safe treatment option for chronic non-cancer (predominantly neuropathic) pain. Given the prevalence of chronic pain, its impact on function and the paucity of effective therapeutic interventions, additional treatment options are urgently needed. More large scale trials of longer duration reporting on pain and level of function are required.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243008/

Cannabinoids for pain management.

Abstract

“Cannabinoids have been used for thousands of years to provide relief from suffering, but only recently have they been critically evaluated in clinical trials. This review provides an in-depth examination of the evidence supporting cannabinoids in various pain states, along with an overview of potential adverse effects. In summary, there is strong evidence for a moderate analgesic effect in peripheral neuropathic and central pain conditions, and conflicting evidence for their use in nociceptive pain. For spasticity, most controlled studies demonstrate significant improvement. Adverse effects are not uncommon with cannabinoids, though most are not serious and self-limiting. In view of the limited effect size and low but not inconsequential risk of serious adverse events, cannabinoids should be employed as analgesics only when safer and more effective medication trials have failed, or as part of a multimodal treatment regimen.”

http://www.ncbi.nlm.nih.gov/pubmed/21508629

Cannabinoids for the treatment of neuropathic pain: clinical evidence.

Abstract

“Neuropathic pain is a worldwide epidemic that occurs in 3 to 8% of individuals in industrialized countries and is often refractory to existing treatments. Drugs currently available to target neuropathic pain are, at best, moderately effective and include antidepressants, gabapentin, NMDA receptor antagonists, as well as other anticonvulsants, all of which are limited by their adverse-effect profiles. Cannabinoid drugs are emerging as a promising class of drugs to treat neuropathic pain and have been tested for analgesic effects in a range of chronic pain conditions. Data show that cannabinoids are often effective in individuals with refractory pain receiving concomitant analgesic drugs. Clinical studies on cannabinoids for the treatment of neuropathic pain are reviewed, focusing on clinical trials published within the last five years. Data from large, well-controlled studies show that cannabinoids are moderately effective in reducing chronic pain and that side effects are comparable to existing treatments, suggesting that cannabinoids can play a useful role in the management of chronic pain. Like other drugs for neuropathic pain, cannabinoids have a dose titration that is limited by psychoactive side effects. The development of cannabinoid drugs to target neuropathic pain with improved therapeutic ratios will depend upon the development of cannabinoid treatments with reduced psychoactivity.”

http://www.ncbi.nlm.nih.gov/pubmed/18183533

Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain.

“OBJECTIVE:

Debilitating pain, occurring in 50-70% of multiple sclerosis (MS) patients, is poorly understood and infrequently studied. We summarized efficacy and safety data of cannabinoid-based drugs for neuropathic pain.

CONCLUSION:

Cannabinoids including the cannabidiol/THC buccal spray are effective in treating neuropathic pain in MS.”

http://www.ncbi.nlm.nih.gov/pubmed/17257464