A possible role for the endocannabinoid system in the neurobiology of depression

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“The present review synthetically describes the currently advanced hypotheses for a neurobiological basis of depression, ranging from the classical monoaminergic to the more recent neurotrophic hypothesis. Moreover, the Authors review the available preclinical and clinical evidence suggesting a possible role for the endocannabinoid system in the physiopathology of depression. Indeed, in spite of the reporting of conflicting results, the pharmacological enhancement of endocannabinoid activity at the CB1 cannabinoid receptor level appears to exert an antidepressant-like effect in some animal models of depression. On the contrary, a reduced activity of the endogenous cannabinoid system seems to be associated with the animal model of depression, namely the chronic mild stress model. Moreover, a few studies have reported an interaction of antidepressants with the endocannabinoid system. “

“The endocannabinoid system”

“A detailed description of the endocannabinoid system is beyond the scope of this paper. Thus, in this section we briefly describe those components of the endocannabinoid system that act as targets for the pharmacological interventions aimed at determining the activity of the endocannabinoid system.”

“The term “endocannabinoid system” refers to the recently discovered neuromodulator system comprising cannabinoid receptors (which represent the receptors of Tetrahydrocannabinol (THC), the major active component of cannabis) and their endogenous ligands.”

“To date, two types of cannabinoid receptors have been identified: CB1 and CB2 receptors. These receptors belong to the superfamily of G protein coupled receptors, the CB1 receptor is widely distributed in the terminals of neurons, while the CB2 receptor is extensively expressed throughout the immune system. However, it has recently been reported that these receptors are present also in the brain.”

“No clinical trials carried out using cannabinoids in the treatment of affective disorders have been published to date, although anecdotal reports have described both antidepressant and antimanic properties of cannabis.”

“Indeed, pharmacological manipulations of the endocannabinoid system have elicited antidepressant-like effects in animal models of depression. Moreover, some animal models of depression seem to be associated to alterations in the endocannabinod system.”

“Although no clinical trials performed using cannabinoids in the treatment of affective disorders have been published to date, anecdotal reports have described both antidepressant and antimanic properties of cannabis”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169225/

The endocannabinoid system as a target for novel anxiolytic and antidepressant drugs.

“Observational studies in humans suggest that exposure to marijuana and other cannabis-derived drugs produces a wide range of subjective effects on mood tone and emotionality. These observations have their counterpart in animal studies, showing that cannabinoid agonists strongly affect emotional reactivity in directions that vary depending on dose and context. Based on these evidence, the activation of central CB(1) receptor has emerged as potential target for the development of antianxiety and antidepressant therapies…”

http://www.ncbi.nlm.nih.gov/pubmed/19607961

 

Role of cannabinoids in the regulation of bone remodeling

Abstract

“The endocannabinoid system plays a key role in regulating a variety of physiological processes such as appetite control and energy balance, pain perception, and immune responses. Recent studies have implicated the endocannabinoid system in the regulation of bone cell activity and bone remodeling. These studies showed that endogenous cannabinoid ligands, cannabinoid receptors, and the enzymes responsible for ligand synthesis and breakdown all play important roles in bone mass and in the regulation of bone disease. These findings suggest that the endocannabinoid pathway could be of value as a therapeutic target for the prevention and treatment of bone diseases. Here, we review the role of the skeletal endocannabinoid system in the regulation of bone remodeling in health and disease.”

http://www.ncbi.nlm.nih.gov/pubmed/23181053

CB1 and CB2 receptor agonists promote analgesia through synergy in a murine model of tumor pain

“Pain associated with cancer and tumor growth is often difficult to manage.”

“Cannabis sativa has a long history of use for management of pain.”

“In light of the adverse side effects of opioids, cannabinoid (CB) receptor agonists may provide an effective alternative for the treatment of cancer pain. The present study examined the potency and efficacy of synthetic CB1 and CB2 receptor agonists in a murine model of tumor pain.”

“Co-administering both CB receptor agonists attenuated mechanical hyperalgesia through a synergistic mechanism.”

 

“Together these data support the use of combined CB1 and CB2 receptor agonists in the development of strategies for the treatment of tumor related pain.”

“These data extend our previous findings that the peripheral cannabinoid receptors are a promising target for the management of cancer pain and mixed cannabinoid receptor agonists may have a therapeutic advantage over selective agonists.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155626/

Cannabinoids and omega-3/6 endocannabinoids as cell death and anticancer modulators.

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“Cannabinoids-endocannaboids are possible preventatives of common diseases including cancers. Cannabinoid receptors (CB(½), TRPV1) are central components of the system. Many disease-ameliorating effects of cannabinoids-endocannabinoids are receptor mediated, but many are not, indicating non-CBR signaling pathways.

Cannabinoids-endocannabinoids are anti-inflammatory, anti-proliferative, anti-invasive, anti-metastatic and pro-apoptotic in most cancers, in vitro and in vivo in animals.

They signal through p38, MAPK, JUN, PI3, AKT, ceramide, caspases, MMPs, PPARs, VEGF, NF-κB, p8, CHOP, TRB3 and pro-apoptotic oncogenes (p53,p21 waf1/cip1) to induce cell cycle arrest, autophagy, apoptosis and tumour inhibition. Paradoxically they are pro-proliferative and anti-apoptotic in some cancers. Differences in receptor expression and concentrations of cannabinoids in cancer and immune cells can elicit anti- or pro-cancer effects through different signal cascades (p38MAPK or PI3/AKT).

Similarities between effects of cannabinoids-endocannabinoids, omega-3 LCPUFA and CLAs/CLnAs as anti-inflammatory, antiangiogenic, anti-invasive anti-cancer agents indicate common signaling pathways.

Evidence in vivo and in vitro shows EPA and DHA can form endocannabinoids that: (i) are ligands for CB(½) receptors and possibly TRPV-1, (ii) have non-receptor mediated bioactivity, (iii) induce cell cycle arrest, (iii) increase autophagy and apoptosis, and (iv) augment chemotherapeutic actions in vitro. They can also form bioactive, eicosanoid-like products that appear to be non-CBR ligands but have effects on PPARs and NF-kB transcription factors. The use of cannabinoids in cancer treatment is currently limited to chemo- and radio-therapy-associated nausea and cancer-associated pain apart from one trial on brain tumours in patients. Further clinical studies are urgently required to determine the true potential of these intriguing, low toxicity compounds in cancer therapy. Particularly in view of their synergistic effects with chemotherapeutic agents similar to that observed for n-3 LCPUFA.”  https://www.ncbi.nlm.nih.gov/pubmed/23103355

http://www.sciencedirect.com/science/article/pii/S0163782712000537

Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial.

 “Patients with advanced cancer who have pain that responds poorly to opioid therapy pose a clinical challenge. Nabiximols (Nabiximols is the U.S. Adopted Name [USAN] for Sativex [GW Pharma Ltd, Wiltshire, U.K.], which does not yet have an INN), a novel cannabinoid formulation, is undergoing investigation as add-on therapy…

This study supports the efficacy and safety of nabiximols at the 2 lower-dose levels and provides important dose information for future trials.

 PERSPECTIVE: Nabiximols, a novel cannabinoid formulation, may be a useful add-on analgesic for patients with opioid-refractory cancer pain. A randomized, double-blind, placebo-controlled, graded-dose study demonstrated efficacy and safety at low and medium doses.”

http://www.ncbi.nlm.nih.gov/pubmed/22483680

An Open-Label Extension Study to Investigate the Long-Term Safety and Tolerability of THC/CBD Oromucosal Spray and Oromucosal THC Spray in Patients With Terminal Cancer-Related Pain Refractory to Strong Opioid Analgesics.

  “Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group.

OBJECTIVES:

This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer.

CONCLUSION:

This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit.”

http://www.ncbi.nlm.nih.gov/pubmed/23141881

Treatment of Tourette syndrome with cannabinoids.

Abstract

“Cannabinoids have been used for hundred of years for medical purposes. To day, the cannabinoid delta-9-tetrahydrocannabinol (THC) and the cannabis extract nabiximols are approved for the treatment of nausea, anorexia and spasticity, respectively. In Tourette syndrome (TS) several anecdotal reports provided evidence that marijuana might be effective not only in the suppression of tics, but also in the treatment of associated behavioural problems. At the present time there are only two controlled trials available investigating the effect of THC in the treatment of TS. Using both self and examiner rating scales, in both studies a significant tic reduction could be observed after treatment with THC compared to placebo, without causing significant adverse effects. Available data about the effect of THC on obsessive-compulsive symptoms are inconsistent. According to a recent Cochrane review on the efficacy of cannabinoids in TS, definite conclusions cannot be drawn, because longer trials including a large number of patients are missing. Notwithstanding this appraisal, by many experts THC is recommended for the treatment of TS in adult patients, when first line treatments failed to improve the tics. In treatment resistant adult patients, therefore, treatment with THC should be taken into consideration.”

http://www.ncbi.nlm.nih.gov/pubmed/23187140

Marijuana- Like Compound in Brain Reduces Anxiety Associated With Fragile X Syndrome

“Increasing levels of a marijuana-like compound in the brain may help reduce some behavioral problems seen in people with Fragile X Syndrome.
Researchers say that the marijuana-like compound may help reduce some of the anxiety and learning-related issues in people with this condition. The compound, called 2-AG, falls under a class of chemicals in the brain called endocannabinoids transmitters.

 Fragile X syndrome is a genetic disorder that causes learning disabilities. Children with this condition have characteristic physical features like long and narrow face, large forehead and ears, flexible fingers and flat feet that become more apparent as the child ages. The condition is caused by a change in the FMR1 gene that codes for a protein that helps the brain grow properly.”

Read more at http://www.medicaldaily.com/articles/12334/20120926/marijuana-compound-brain-reduces-anxiety-associated-fragile.htm#tFdDDvKazcBZ1gFG.99

  • mike

    “YES, finally its time… i have autistic spectrum and i have incorrect behaviors that cannot be fixed unless you tell yourself 24/7 and behaviors and thought process that is incorrect that you will never even know is incorrect. Ive tried marijuana before and the first time ive tried it ive done some self explaining to myself that was very different and i didnt know why. after using marijuana several times which i find relaxing if not used too much at once, i started realizing the difference in thought process and realizing the off things that i do and it got to the point where i actually started figuring out my problems with cannabis and i cant believe the correction in thought process when using this significant plant. there was never a cure for autism but this is the CLOSEST to it. i have a lot more things to say about this but it would take too long to write but all i have to say is this is THE best medication for personality disorders and autistic behaviors and correction to the thought process of such.”

Marijuana cannabinoids found to help combat autism

“(NaturalNews) The cannabinoid compounds naturally found in many varieties of cannabis, also known more commonly as marijuana, may help children with autism spectrum disorders experience dramatic behavioral improvements, and potentially even full recovery from their symptoms. These are the findings of a new study published in the journal Nature Communications that help reinforce the growing body of evidence which shows that medicinal cannabinoids hold incredible potential in both treating and potentially curing chronic illness.

Daniele Piomelli from the University of California, Irvine (UCI) and her colleague Olivier Manzoni from Inserm, a French research agency, observed that marijuana cannabinoids are very closely related to the endocannabinoid transmitters naturally found in the brain that facilitate the transport of electrical signals between neurons. Known as 2-AG, these transmitters are responsible for regulating a whole host of important bodily processes, which include things like telling the body when it is hungry or when it is experiencing pain.

Children with autism spectrum disorders; however, including those who developed these disorders as a result of Fragile X syndrome, which is said to be the most commonly-known genetic cause of autism, often have poorly or non-functioning 2-AG, which necessitates chronic synaptic failure in the brain. Many children with Fragile X-induced autism end up becoming mentally disabled as a result of this synaptic failure, and have trouble developing basic motor skills like walking and talking, or learning how to behave in various social situations.

But taking marijuana cannabinoids, which as we pointed out in an earlier article are not psychoactive in the same way that tetrahydrocannabinol (THC) is (http://www.naturalnews.com/035759_cannabis_juicing_health.html), can help effectively block the enzymes that inhibit the proper function of 2-AG. In essence, marijuana cannabinoids essentially restore synaptic communication by feeding an ailing body the cannabinoids it lacks, which are absolutely vital for proper cell function and communication.

“Endocannabinoid compounds are created naturally in the body and share a similar chemical structure with THC … (and) are distinctive because they link with protein molecule receptors — called cannabinoid receptors — on the surface of cells,” explains the UCI report. “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.””

Learn more: http://www.naturalnews.com/037445_marijuana_cannabinoids_autism.html#ixzz2DRNu5iDg