Category Archives: Uncategorized

The emerging role of the cannabinoid receptor family in peripheral and neuro-immune interactions.

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“The classical endogenous cannabinoid (CB) system is composed of the endocannabinoid signalling molecules, 2-arachidonoyl glycerol (2-AG) and anandamide (AEA) and their G-protein coupled receptors (GPCR), CB1 and CB2 which together constitutes the endocannabinoid system (ECS).

However, putative, novel lipid-sensing CB receptors have recently been identified, including the orphan GPR55 and GPR18 receptors that are regulated by cannabinoid-like molecules and interact with CB system.

CB receptors and associated orphan GPCRs are expressed at high levels in the immune and/or central nervous systems (CNS) and regulate a number of neurophysiological processes, including key events involved in neuroinflammation.

As such, these receptors have been identified as emerging therapeutic targets for a number of brain disorders in which neuroinflammation is a key feature, including multiple sclerosis (MS) and Alzheimer’s disease (AD).

This review will consider the role of the widercannabinoid receptor superfamily in mediating immune function with a focus on the immune processes that contribute to neuroinflammatory conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/26758668

Marijuana: A Fifty-Year Personal Addiction Medicine Perspective.

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“As of September 2015, the cultivation, possession, and/or use of marijuana is illegal under U.S. federal law as a Schedule I narcotic; however, it is legal in four states and Washington, D.C. Forty-six states allow some form of medicinal marijuana or decriminalization.

Marijuana has been used medicinally for thousands of years; Marijuana’s regulation by law enforcement in the U.S., rather than the medical community, led to an almost complete halt to academic and scientific research after the 1930s.

The late 1960s saw an upsurge in recreational marijuana use by middle-class youth, the majority of whom experienced minimal adverse effects aside from arrest and attendant legal complications.

Since the mid-1990s, the use of medicinal marijuana for certain conditions has gained increasing acceptance.

In the East, the feeling is primarily that marijuana continue to be proscribed. In the West, where clinicians must face the realities of medicalization, decriminalization, and/or legalization, as well as widespread recreational use, there is more of a movement to minimize adverse effects, particularly on youth.”

http://www.ncbi.nlm.nih.gov/pubmed/26757396

Are IQ and educational outcomes in teenagers related to their cannabis use? A prospective cohort study.

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“We investigated associations between adolescent cannabis use and IQ and educational attainment in a sample of 2235 teenagers from the Avon Longitudinal Study of Parents and Children.

After full adjustment, those who had used cannabis ⩾50 times did not differ from never-users on either IQ or educational performance.

Adjusting for group differences in cigarette smoking dramatically attenuated the associations between cannabis use and both outcomes, and further analyses demonstrated robust associations between cigarette use and educational outcomes, even with cannabis users excluded.

These findings suggest that adolescent cannabis use is not associated with IQ or educational performance once adjustment is made for potential confounds, in particular adolescent cigarette use.

Modest cannabis use in teenagers may have less cognitive impact than epidemiological surveys of older cohorts have previously suggested.”

http://www.ncbi.nlm.nih.gov/pubmed/26739345

The effect of cannabis on regular cannabis consumers’ ability to ride a bicycle.

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“To assess the effects of cannabis on the ability required to ride a bicycle, repetitive practical cycling tests and medical examinations were carried out before and after inhalative consumption of cannabis.

A maximum of three joints with body weight-adapted THC content (300 μg THC per kg body weight) could be consumed by each test subject.

Fourteen regular cannabis-consuming test subjects were studied (12 males, 2 females).

In summary, only a few driving faults were observed even under the influence of very high THC concentrations. A defined THC concentration that leads to an inability to ride a bicycle cannot be presented.

The test subjects showed only slight distinctive features that can be documented using a medical test routinely run for persons under suspicion of driving under the influence of alcohol or drugs.” http://www.ncbi.nlm.nih.gov/pubmed/26739323

“Alcohol-related deficits were already identifiable at very low blood alcohol concentrations (BAC)s. A significant increase in gross motoric disturbances compared to the soberness state did not regularly occur until a BAC of at least 0.8 g/kg was reached. At the BAC of 1.4 g/kg and above, no test subjects were able to achieve or surpass their sober driving results.”  http://www.ncbi.nlm.nih.gov/pubmed/25428289

“The practical ability to ride a bicycle was significantly reduced in the postalcoholic state… The relative cycling performance in the postalcoholic state was comparable to the rides under the influence of BAC of around 0.30 g/kg… it can be assumed that the direct influence of residual blood alcohol levels plays a minor role for the ability to ride a bicycle in the postalcoholic state. Instead, the side effects of the high amounts of alcohol that were consumed the night before are crucial.” http://www.ncbi.nlm.nih.gov/pubmed/25940454

“A defined THC concentration that leads to an inability to ride a bicycle cannot be presented.” http://www.ncbi.nlm.nih.gov/pubmed/26739323

Human rights, public health and medicinal cannabis use.

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“This paper explores the interplay between the human rights and drug control frameworks and critiques case law on medicinal cannabis use to demonstrate that a bona fide human rights perspective allows for a broader conception of ‘health’.

This broad conception, encompassing both medicalised and social constructionist definitions, can inform public health policies relating to medicinal cannabis use.

The paper also demonstrates how a human rights lens can alleviate a core tension between the State and the individual within the drug policy field.

The leading medicinal cannabis case in the UK highlights the judiciary’s failure to engage with an individual’s human right to health as they adopt an arbitrary, externalist view, focussing on the legality of cannabis to the exclusion of other concerns.

Drawing on some international comparisons, the paper considers how a human rights perspective can lead to an approach to medicinal cannabis use which facilitates a holistic understanding of public health.”

http://www.ncbi.nlm.nih.gov/pubmed/26692654

The cross-talk between electrophiles, antioxidant defence and the endocannabinoid system in fibroblasts and keratinocytes after UVA and UVB irradiation.

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“UV, including UVA and UVB radiation, is one of the most ubiquitous environmental stress factors to human skin and leads to redox imbalance and, consequently, photoaging and cancer development. The aim of the study was to verify which skin cells, keratinocytes or fibroblasts, were more susceptible to UVA or UVB irradiation.

The results presented in this paper demonstrate a strong relationship between UV-induced oxidative stress and changes in the endocannabinoid system.

The differences demonstrated in the response of the tested cells to UV irradiation allow for a better understanding of the mechanisms occurring in the human skin, which may be exploited for future therapies in dermatology.”

http://www.ncbi.nlm.nih.gov/pubmed/26674123

GPR55 – a putative “type 3” cannabinoid receptor in inflammation.

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“G protein-coupled receptor 55 (GPR55) shares numerous cannabinoid ligands with CB1 and CB2 receptors despite low homology with those classical cannabinoid receptors. The pharmacology of GPR55 is not yet fully elucidated; however, GPR55 utilizes a different signaling system and downstream cascade associated with the receptor.

Therefore, GPR55 has emerged as a putative “type 3″ cannabinoid receptor, establishing a novel class of cannabinoid receptor.

Furthermore, the recent evidence of GPR55-CB1 and GPR55-CB2 heteromerization along with its broad distribution from central nervous system to peripheries suggests the importance of GPR55 in various cellular processes and pathologies and as a potential therapeutic target in inflammation.”

 http://www.ncbi.nlm.nih.gov/pubmed/26669245

Small Molecules from Nature Targeting G-Protein Coupled Cannabinoid Receptors: Potential Leads for Drug Discovery and Development.

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“The cannabinoid molecules are derived from Cannabis sativa plant which acts on the cannabinoid receptors types 1 and 2 (CB1 and CB2) which have been explored as potential therapeutic targets for drug discovery and development.

Currently, there are numerous cannabinoid based synthetic drugs used in clinical practice like the popular ones such as nabilone, dronabinol, and Δ9-tetrahydrocannabinol mediates its action through CB1/CB2receptors.

In recent years, many phytocannabinoids have been isolated from plants other than Cannabis. Several studies have shown that these phytocannabinoids show affinity, potency, selectivity, and efficacy towards cannabinoid receptors and inhibit endocannabinoid metabolizing enzymes, thus reducing hyperactivity of endocannabinoid systems.

Also, these naturally derived molecules possess the least adverse effects opposed to the synthetically derived cannabinoids. Therefore, the plant based cannabinoid molecules proved to be promising and emerging therapeutic alternative.

The present review provides an overview of therapeutic potential of ligands and plants modulating cannabinoid receptors that may be of interest to pharmaceutical industry in search of new and safer drug discovery and development for future therapeutics.”

Differential physiological and behavioral cues observed in individuals smoking botanical marijuana versus synthetic cannabinoid drugs.

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“Synthetic cannabinoid use has increased in many states, and medicinal and/or recreational marijuana use has been legalized in some states. These changes present challenges to law enforcement drug recognition experts (DREs) who determine whether drivers are impaired by synthetic cannabinoids or marijuana, as well as to clinical toxicologists who care for patients with complications from synthetic cannabinoids and marijuana.

Our goal was to compare what effects synthetic cannabinoids and marijuana had on performance and behavior, including driving impairment, by reviewing records generated by law enforcement DREs who evaluated motorists arrested for impaired driving.

 Drivers under the influence of synthetic cannabinoids were more frequently impaired with confusion, disorientation, and incoherent, slurred speech than drivers under the influence of marijuana in this population evaluated by DREs.”

Determination of 11 Cannabinoids in Biomass and Extracts of Different Varieties of Cannabis Using High-Performance Liquid Chromatography.

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“An HPLC single-laboratory validation was performed for the detection and quantification of the 11 major cannabinoids in most cannabis varieties, namely, cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), cannabigerol (CBG), cannabidiol (CBD), tetrahydrocannabivarin (THCV), cannabinol (CBN), Δ9-trans-tetrahydrocannabinol (Δ9-THC), Δ8- trans-tetrahydrocannabinol (Δ8-THC), cannabicyclol (CBL), cannabichromene (CBC), and Δ9-tetrahydrocannabinolic acid-A (THCAA). The analysis was carried out on the biomass and extracts of these varieties. Methanol-chloroform (9:1, v/v) was used for extraction, 4-androstene-3,17-dione was used as the internal standard, and separation was achieved in 22.2 min on a C18 column using a two- step gradient elution. The method was validated for the 11 cannabinoids. The concentration-response relationship of the method indicated a linear relationship between the concentration and peak area with r2 values of >0.99 for all 11 cannabinoids. Method accuracy was determined through a spike study, and recovery ranged from 89.7 to 105.5% with an RSD of 0.19 to 6.32% for CBDA, CBD, THCV, CBN, Δ9-THC, CBL, CBC, and THCAA; recovery was 84.7, 84.2, and 67.7% for the minor constituents, CBGA, CBG, and Δ8-THC, respectively, with an RSD of 2.58 to 4.96%. The validated method is simple, sensitive, and reproducible and is therefore suitable for the detection and quantification of these cannabinoids in different types of cannabis plant materials.”