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

Use of marijuana for medical purposes.

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“Cannabis is the most popular illicit drug on the European market. Over 16 million young Europeans have used it at least once in the last few years. The recent trends in the consumption of marihuana differ between countries. Some countries face an increase in the prevalence of cannabis use, including Poland, where the level cannabis use has been systematically increasing since the 1990’s. According to a recent ESPAD study, 19% of Polish adolescents aged 15-16 have used cannabis in the last year. Marihuana is also a leading substance when analyzing the data of seizures and crimes. The recent EMCDDA Annual report on the drug situation in Europe notes the increasing potency in cannabis available on the market. Some countries face an increasing number of emergencies caused by marihuana, which was unlikely to have happened previously. In almost all European countries there is an ongoing discussion about loosening marijuana laws or its complete legalization. There is also ongoing discussion on the use of marihuana in therapy as a medicine. Many scientific studies are being conducted in this field. Some of the results are promising; however, there is no well-designed human trial which would unequivocally confirm that medical cannabis is effective as a medicine, or more effective than other medicines on the market. The problem is that the debate on the medical use of marihuana becomes more ideological and less professional. The medical use of marihuana is strongly supported by organizations lobbying for the legalization of cannabis use. Research on the medical use of cannabis should be continued, as there are some promising results supporting therapy in different medical conditions. However, the use of cannabis as a medicine should be discussed only among professionals. If marihuana is to be used for medical purposes, the fact that it is the most popular illicit drug in Europe is irrelevant.”

http://www.ncbi.nlm.nih.gov/pubmed/27660881

Medical Marijuana: Just the Beginning of a Long, Strange Trip?

Physical Therapy Journal

“Medical marijuana continues to gain acceptance and become legalized in many states. Various species of the marijuana plant have been cultivated, and this plant can contain up to 100 active compounds known as cannabinoids.

Two cannabinoids seem the most clinically relevant: Δ9-tetrahydrocannabinol (THC), which tends to produce the psychotropic effects commonly associated with marijuana, and cannabidiol (CBD), which may produce therapeutic effects without appreciable psychoactive properties.

Smoking marijuana, or ingesting extracts from the whole plant orally (in baked goods, teas, and so forth), introduces variable amounts of THC, CBD, and other minor cannabinoids into the systemic circulation where they ultimately reach the central and peripheral nervous systems.

Alternatively, products containing THC, CBD, or a combination of both compounds, can also be ingested as oral tablets, or via sprays applied to the oral mucosal membranes. These products may provide a more predictable method for delivering a known amount of specific cannabinoids into the body.

Although there is still a need for randomized controlled clinical trials, preliminary studies have suggested that medical marijuana and related cannabinoids may be beneficial in treating chronic pain, inflammation, spasticity, and other conditions seen commonly in physical therapist practice.

Physical therapists should therefore be aware of the options that are available for patients considering medical marijuana, and be ready to provide information for these patients.”

http://www.ncbi.nlm.nih.gov/pubmed/27660328

Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines

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“Cannabis sativa, commonly called hemp, has thousands of years-long history of medical use. Cannabis extracts were widely used in Europe and North America for their therapeutic value as sedatives, hypnotics, analgesics, muscle relaxants, and anticonvulsant agents. However, cannabis was removed from British and American Pharmacopoeias in 20th century, partially due to politic bias. Although prohibited, many patients were nevertheless self-medicating to obtain therapeutic benefits from cannabis for various conditions, including AIDS wasting syndrome, multiple sclerosis (MS) and spinal injuries. More recently, a growing interest in the therapeutic effects of cannabis has developed following the isolation of cannabinoids, the principal chemical compounds of cannabis, as well as the discovery of endocannabinoids and their cognate receptors in humans. These advances supported legalisation and wide-spread use of cannabis for therapeutic purposes in many countries.

There has been an escalating interest in the medicinal use of Cannabis sativa in recent years. Cannabis is often administered orally with fat-containing foods, or in lipid-based pharmaceutical preparations. However, the impact of lipids on the exposure of patients to cannabis components has not been explored. Therefore, the aim of this study is to elucidate the effect of oral co-administration of lipids on the exposure to two main active cannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). In this study, oral co-administration of lipids enhanced the systemic exposure of rats to THC and CBD by 2.5-fold and 3-fold, respectively, compared to lipid-free formulations. In vitro lipolysis was conducted to explore the effect of lipids on the intestinal solubilisation of cannabinoids. More than 30% of THC and CBD were distributed into micellar fraction following lipolysis, suggesting that at least one-third of the administered dose will be available for absorption following co-administration with lipids. Both cannabinoids showed very high affinity for artificial CM-like particles, as well as for rat and human CM, suggesting high potential for intestinal lymphatic transport. Moreover, comparable affinity of cannabinoids for rat and human CM suggests that similar increased exposure effects may be expected in humans. In conclusion, co-administration of dietary lipids or pharmaceutical lipid excipients has the potential to substantially increase the exposure to orally administered cannabis and cannabis-based medicines. The increase in patient exposure to cannabinoids is of high clinical importance as it could affect the therapeutic effect, but also toxicity, of orally administered cannabis or cannabis-based medicines.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009397/

State Medical Marijuana Laws and the Prevalence of Opioids Detected Among Fatally Injured Drivers.

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“To assess the association between medical marijuana laws (MMLs) and the odds of a positive opioid test, an indicator for prior use.

State-specific estimates indicated a reduction in opioid positivity for most states after implementation of an operational MML,

CONCLUSIONS:

Operational MMLs are associated with reductions in opioid positivity among 21- to 40-year-old fatally injured drivers and may reduce opioid use and overdose.”

http://www.ncbi.nlm.nih.gov/pubmed/27631755

Preparation and Distribution of Cannabis and Cannabis-Derived Dosage Formulations for Investigational and Therapeutic Use in the United States.

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“Cannabis is classified as a schedule I controlled substance by the US Drug Enforcement Agency, meaning that it has no medicinal value. Production is legally restricted to a single supplier at the University of Mississippi, and distribution to researchers is tightly controlled. However, a majority of the population is estimated to believe that cannabis has legitimate medical or recreational value, numerous states have legalized or decriminalized possession to some degree, and the federal government does not strictly enforce its law and is considering rescheduling. The explosive increase in open sale and use of herbal cannabis and its products has occurred with widely variable and in many cases grossly inadequate quality control at all levels-growing, processing, storage, distribution, and use. This paper discusses elements of the analytical and regulatory system that need to be put in place to ensure standardization for the researcher and to reduce the hazards of contamination, overdosing, and underdosing for the end-user.”

http://www.ncbi.nlm.nih.gov/pubmed/27630566

Evaluation of Two Commercially Available Cannabidiol Formulations for Use in Electronic Cigarettes.

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“Since 24 states and the District of Columbia have legalized marijuana in some form, suppliers of legal marijuana have developed Cannabis sativa products for use in electronic cigarettes (e-cigarettes).

Personal battery powered vaporizers, or e-cigarettes, were developed to deliver a nicotine vapor such that smokers could simulate smoking tobacco without the inherent pathology of inhaled tobacco smoke. The liquid formulations used in these devices are comprised of an active ingredient such as nicotine mixed with vegetable glycerin (VG) and/or propylene glycol (PG) and flavorings.

A significant active ingredient of C. sativa, cannabidiol (CBD), has been purported to have anti-convulsant, anti-nociceptive, and anti-psychotic properties. These properties have potential medical therapies such as intervention of addictive behaviors, treatments for epilepsy, management of pain for cancer patients, and treatments for schizophrenia.

However, CBD extracted from C. sativa remains a DEA Schedule I drug since it has not been approved by the FDA for medical purposes.

Two commercially available e-cigarette liquid formulations reported to contain 3.3 mg/mL of CBD as the active ingredient were evaluated. These products are not regulated by the FDA in manufacturing or in labeling of the products and were found to contain 6.5 and 7.6 mg/mL of CBD in VG and PG with a variety of flavoring agents. Presently, while labeled as to content, the quality control of manufacturers and the relative safety of these products is uncertain.”

http://www.ncbi.nlm.nih.gov/pubmed/27621706

Maternal Marijuana Use and Adverse Neonatal Outcomes: A Systematic Review and Meta-analysis.

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“To estimate whether marijuana use in pregnancy increases risks for adverse neonatal outcomes and clarify if any increased risk is attributable to marijuana use itself or to confounding factors such as tobacco use.

CONCLUSION:

Maternal marijuana use during pregnancy is not an independent risk factor for adverse neonatal outcomes after adjusting for confounding factors.

Thus, the association between maternal marijuana use and adverse outcomes appears attributable to concomitant tobacco use and other confounding factors.”

http://www.ncbi.nlm.nih.gov/pubmed/27607879

“Using Pot While Pregnant Not Tied to Birth Risks. Smoking marijuana during pregnancy doesn’t appear to increase the risk of preterm birth or other harmful birth outcomes, a new review study suggests.” http://www.livescience.com/56036-marijuana-pregnant-preterm-birth-risk.html

“Marijuana Is Safe During pregnancy, Experts Do Not Encourage. Marijuana does not increase pregnancy risk according to new research. It does not have a negative outcome when it comes to premature birth and low birth weight. Still, experts do not encourage marijuana use during pregnancy.” http://www.scienceworldreport.com/articles/47194/20160910/marijuana-safe-during-pregnancy-experts-encourage.htm