Endocannabinoid signaling in social functioning: an RDoC perspective.

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“Core deficits in social functioning are associated with various neuropsychiatric and neurodevelopmental disorders, yet biomarker identification and the development of effective pharmacological interventions has been limited.

Recent data suggest the intriguing possibility that endogenous cannabinoids, a class of lipid neuromodulators generally implicated in the regulation of neurotransmitter release, may contribute to species-typical social functioning.

Systematic study of the endogenous cannabinoid signaling could, therefore, yield novel approaches to understand the neurobiological underpinnings of atypical social functioning.

This article provides a critical review of the major components of the endogenous cannabinoid system (for example, primary receptors and effectors-Δ9-tetrahydrocannabinol, cannabidiol, anandamide and 2-arachidonoylglycerol) and the contributions of cannabinoid signaling to social functioning.

Data are evaluated in the context of Research Domain Criteria constructs (for example, anxiety, chronic stress, reward learning, motivation, declarative and working memory, affiliation and attachment, and social communication) to enable interrogation of endogenous cannabinoid signaling in social functioning across diagnostic categories.

The empirical evidence reviewed strongly supports the role for dysregulated cannabinoid signaling in the pathophysiology of social functioning deficits observed in brain disorders, such as autism spectrum disorder, schizophrenia, major depressive disorder, posttraumatic stress disorder and bipolar disorder.

Moreover, these findings indicate that the endogenous cannabinoid system holds exceptional promise as a biological marker of, and potential treatment target for, neuropsychiatric and neurodevelopmental disorders characterized by impairments in social functioning.”

https://www.ncbi.nlm.nih.gov/pubmed/27676446

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Cannabinoids biology: the search for new therapeutic targets.

“Cannabinoids, in the form of marijuana plant extracts, have been used for thousands of years for a wide variety of medical conditions, ranging from general malaise and mood disorders to more specific ailments, such as pain, nausea, and muscle spasms.

The discovery of tetrahydrocannabinol, the active principal in marijuana, and the identification and cloning of two cannabinoid receptors (i.e., CB1 and CB2) has subsequently led to biomedical appreciation for a family of endocannabinoid lipid transmitters.

The biosynthesis and catabolism of the endocannabinoids and growing knowledge of their broad physiological roles are providing insight into potentially novel therapeutic targets.

Compounds directed at one or more of these targets may allow for cannabinoid-based therapeutics with limited side effects and abuse liability.”

http://www.ncbi.nlm.nih.gov/pubmed/16809476

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Cannabinoids in bipolar affective disorder: a review and discussion of their therapeutic potential.

“Bipolar affective disorder is often poorly controlled by prescribed drugs.

Cannabis use is common in patients with this disorder and anecdotal reports suggest that some patients take it to alleviate symptoms of both mania and depression.

We undertook a literature review of cannabis use by patients with bipolar disorder and of the neuropharmacological properties of cannabinoids suggesting possible therapeutic effects in this condition.

No systematic studies of cannabinoids in bipolar disorder were found to exist, although some patients claim that cannabis relieves symptoms of mania and/or depression.

The cannabinoids Delta(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) may exert sedative, hypnotic, anxiolytic, antidepressant, antipsychotic and anticonvulsant effects.

Pure synthetic cannabinoids, such as dronabinol and nabilone and specific plant extracts containing THC, CBD, or a mixture of the two in known concentrations, are available and can be delivered sublingually.

Controlled trials of these cannabinoids as adjunctive medication in bipolar disorder are now indicated.”

http://www.ncbi.nlm.nih.gov/pubmed/15888515

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Joint Effects: A Pilot Investigation of the Impact of Bipolar Disorder and Marijuana Use on Cognitive Function and Mood.

“The current study aimed to determine the impact of marijuana on mood in bipolar patients and to examine whether marijuana confers an additional negative impact on cognitive function.

Findings suggest that for some bipolar patients, marijuana may result in partial alleviation of clinical symptoms. Moreover, this improvement is not at the expense of additional cognitive impairment.”

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The use of cannabis as a mood stabilizer in bipolar disorder: anecdotal evidence and the need for clinical research.

“The authors present case histories indicating that a number of patients find cannabis (marihuana) useful in the treatment of their bipolar disorder.

Some used it to treat mania, depression, or both. They stated that it was more effective than conventional drugs, or helped relieve the side effects of those drugs.

One woman found that cannabis curbed her manic rages; she and her husband have worked to make it legally available as a medicine. Others described the use of cannabis as a supplement to lithium (allowing reduced consumption) or for relief of lithium’s side effects.

Another case illustrates the fact that medical cannabis users are in danger of arrest, especially when children are encouraged to inform on parents by some drug prevention programs.

An analogy is drawn between the status of cannabis today and that of lithium in the early 1950s, when its effect on mania had been discovered but there were no controlled studies.

In the case of cannabis, the law has made such studies almost impossible, and the only available evidence is anecdotal. The potential for cannabis as a treatment for bipolar disorder unfortunately can not be fully explored in the present social circumstances.”

http://www.ncbi.nlm.nih.gov/pubmed/9692379

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ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.

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“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

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Endocannabinoids and Mental Disorders.

“Preclinical and clinical data fully support the involvement of the endocannabinoid system in the etiopathogenesis of several mental diseases.

In this review we will briefly summarize the most common alterations in the endocannabinoid system, in terms of cannabinoid receptors and endocannabinoid levels, present in mood disorders (anxiety, posttraumatic stress disorder, depression, bipolar disorder, and suicidality) as well as psychosis (schizophrenia) and autism.

The arising picture for each pathology is not always straightforward; however, both animal and human studies seem to suggest that pharmacological modulation of this system might represent a novel approach for treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/26408164

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Cannabis Enhances Bipolar Patients’ Neurocognitive Performance

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“According to a study published online in the journal Psychiatry Research, individuals with bipolar disorder who used cannabis showed higher neurocognitive performance than patients who did not use cannabis.

Researchers at The Zucker Hillside Hospital in Long Island, NY, in collaboration with a team at the Mount Sinai School of Medicine and the Albert Einstein College of Medicine in New York City, examined the difference in cognitive performance among 50 individuals with bipolar disorder who had a history of cannabis use, with 150 bipolar patients who had no history of cannabis use.

The team discovered that patients who used cannabis showed superior neurocognitive performance than those who did not…

“These data could be interpreted to suggest that cannabis use may have a beneficial effect on cognitive functioning in patients with severe psychiatric disorders…””

http://www.medicalnewstoday.com/articles/249006.php

“Cognitive and clinical outcomes associated with cannabis use in patients with bipolar I disorder”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408776/

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Study: Pot May Improve Cognitive Functioning in Bipolar Disorder

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“Patients with severe psychiatric disorders actually function better in neurocognitive assessments when they have a history of marijuana use.

Patients with bipolar I disorder performed better in neurocognitive assessments when they had a history of marijuana use.”

http://www.theatlantic.com/health/archive/2012/08/study-pot-may-improve-cognitive-functioning-in-bipolar-disorder/261140/

“Cognitive and clinical outcomes associated with cannabis use in patients with bipolar I disorder”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408776/

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Cognitive and clinical outcomes associated with cannabis use in patients with bipolar I disorder.

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“The objective of the present study was to compare clinical and neurocognitive measures in individuals with bipolar disorder with a history of cannabis use disorder (CUD) versus those without a history of CUD…

We compared the groups on clinical and demographic variables, as well as on performance on neurocognitive tests…

CUD+ subjects demonstrated significantly better performance on measures of attention, processing speed, and working memory…

Interestingly, bipolar patients with history of CUD had better neurocognitive performance as compared to patients with no history of CUD.

…these analyses indicate an interesting pattern suggesting superior neurocognitive performance among bipolar patients with comorbid CUD when compared to bipolar patients with no history of cannabis use.”

http://www.ncbi.nlm.nih.gov/pubmed/22818174

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408776/

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