Targeted proteomics of cannabinoid receptor CB1 and the CB1b isoform.

Posted on December 5, 2016 by David

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“Cannabinoid receptors (CBR), including CB1 and CB2 have been therapeutic targets for a number of conditions.

Recently, splice variants of the CB1R have been identified in humans.

The isoforms differ in their N-terminus sequence and pharmacological activity relative to the CB1R, as a result, the differentiation between the CB1 receptor and its isoform is required.

As a result, a selected reaction monitoring mass spectrometry (SRM-MS) method was developed for the quantitation of CB1 and the CB1b isoform in CHO cells transduced with CB1 and CB1b.

The SRM-MS protocol was assessed with isotopically labeled peptide standards and had high reproducibility of intra-day assay (CVs from 1.9 to 4.3% for CB1 and 0.5 to 5.9% for CB1b) and inter-day assay (CVs from 1.2 to 5.2% for CB1 and 1.2 to 6.1% for CB1b).”

https://www.ncbi.nlm.nih.gov/pubmed/27914737

What is THC?

Posted on December 4, 2016 by David

“THC, or tetrahydrocannabinol, is the chemical responsible for most of marijuana’s psychological effects. It acts much like the cannabinoid chemicals made naturally by the body, according to the National Institute on Drug Abuse (NIDA).

Cannabinoid receptors are concentrated in certain areas of the brain associated with thinking, memory, pleasure, coordination and time perception. THC attaches to these receptors and activates them and affects a person’s memory, pleasure, movements, thinking, concentration, coordination, and sensory and time perception, according to NIDA.

THC is one of many compounds found in the resin secreted by glands of the marijuana plant. More of these glands are found around the reproductive organs of the plant than on any other area of the plant. Other compounds unique to marijuana, called cannabinoids, are present in this resin.

One cannabinoid, CBD is nonpsychoactive, according to the National Center for Biotechnology Information, and actually blocks the high associated with THC.”

http://www.livescience.com/24553-what-is-thc.html

http://www.thctotalhealthcare.com/category/thc-delta-9-tetrahydrocannabinol/

Δ9-THC-Caused Synaptic and Memory Impairments Are Mediated through COX-2 Signaling

Posted on December 4, 2016 by David

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“Marijuana has been used for thousands of years as a treatment for medical conditions.

However, untoward side effects limit its medical value. Here, we show that synaptic and cognitive impairments following repeated exposure to Δ⁹-tetrahydrocannabinol (Δ⁹-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids in the brain. COX-2 induction by Δ⁹-THC is mediated via CB1 receptor-coupled G protein βγ subunits.

Pharmacological or genetic inhibition of COX-2 blocks downregulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ⁹-THC exposures. Ablation of COX-2 also eliminates Δ⁹-THC-impaired hippocampal long-term synaptic plasticity, spatial, and fear memories.

Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ⁹-THC in Alzheimer’s disease animals are retained in the presence of COX-2 inhibition.

These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2.”

http://www.cell.com/cell/abstract/S0092-8674(13)01360-3

“Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis.” https://www.ncbi.nlm.nih.gov/pubmed/18556441

Smoking cannabis ‘helps addicts give up heroin’, study finds

Posted on December 3, 2016 by David

Smoking cannabis ‘helps addicts give up heroin’, study finds

“Smoking weed helps patients give up opiates such as heroin, a new study has found.

Researchers at Columbia University monitored patients undergoing treatment for opiate addiction – and found that patients who smoked weed were more able to sleep, less anxious, and more likely to complete their course.

The researchers also found that dosing patients with dronabinol – a drug consisting of the ‘active’ ingredient in cannabis, THC – helped with withdrawal symptoms.”

http://metro.co.uk/2015/12/02/smoking-cannabis-helps-addicts-give-up-heroin-study-finds-5538896/

Cannabis-induced Moto-Cognitive Dysfunction in Wistar Rats: Ameliorative Efficacy of Nigella Sativa.

Posted on December 3, 2016 by David

“Cannabis is a widely used illicit drug with various threats of personality syndrome, and Nigella sativa has been widely implicated as having therapeutic efficacy in many neurological diseases.

The present study investigates the ameliorative efficacy of Nigella sativa oil (NSO) on cannabis-induced moto-cognitive defects.

CONCLUSIONS:

The observed ameliorative effects of NSO make it a promising agent against moto-cognitive dysfunction and cerebelo-hippocampal alterations induced by cannabis.”

https://www.ncbi.nlm.nih.gov/pubmed/27904421

Targeting the endocannabinoid/CB1 receptor system for treating obesity in Prader-Willi syndrome.

Posted on December 3, 2016 by David

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“Extreme obesity is a core phenotypic feature of Prader-Willi syndrome (PWS).

Among numerous metabolic regulators, the endocannabinoid (eCB) system is critically involved in controlling feeding, body weight, and energy metabolism, and a globally acting cannabinoid-1 receptor (CB₁R) blockade reverses obesity both in animals and humans.

The first-in-class CB₁R antagonist rimonabant proved effective in inducing weight loss in adults with PWS. However, it is no longer available for clinical use because of its centrally mediated, neuropsychiatric, adverse effects.

CONCLUSIONS:

Dysregulation of the eCB/CB₁R system may contribute to hyperphagia and obesity in Magel2-null mice and in individuals with PWS. Our results demonstrate that treatment with peripherally restricted CB₁R antagonists may be an effective strategy for the management of severe obesity in PWS.”

https://www.ncbi.nlm.nih.gov/pubmed/27900261

Cannabinoid Type-2 Receptor Drives Neurogenesis and Improves Functional Outcome After Stroke.

Posted on December 3, 2016 by David

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“Stroke is a leading cause of adult disability characterized by physical, cognitive, and emotional disturbances. Unfortunately, pharmacological options are scarce.

The cannabinoid type-2 receptor (CB2R) is neuroprotective in acute experimental stroke by anti-inflammatory mechanisms.

CONCLUSIONS:

Our data support that CB2R is fundamental for driving neuroblast migration and suggest that an endocannabinoid tone is required for poststroke neurogenesis by promoting neuroblast migration toward the injured brain tissue, increasing the number of new cortical neurons and, conceivably, enhancing motor functional recovery after stroke.”

https://www.ncbi.nlm.nih.gov/pubmed/27899748

Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males.

Posted on December 3, 2016 by David

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“Preclinical research demonstrates that cannabinoids have differing effects in adolescent and adult animals. Whether these findings translate to humans has not yet been investigated. Here we believe we conducted the first study to compare the acute effects of cannabis in human adolescent (n=20; 16-17 years old) and adult (n=20; 24-28 years old) male cannabis users, in a placebo-controlled, double-blind cross-over design.

After inhaling vaporized active or placebo cannabis, participants completed tasks assessing spatial working memory, episodic memory and response inhibition, alongside measures of blood pressure and heart rate, psychotomimetic symptoms and subjective drug effects (for example, ‘stoned’, ‘want to have cannabis’).

Results showed that on active cannabis, adolescents felt less stoned and reported fewer psychotomimetic symptoms than adults. Further, adults but not adolescents were more anxious and less alert during the active cannabis session (both pre- and post-drug administration). Following cannabis, cognitive impairment (reaction time on spatial working memory and prose recall following a delay) was greater in adults than adolescents. By contrast, cannabis impaired response inhibition accuracy in adolescents but not in adults.

Moreover, following drug administration, the adolescents did not show satiety; instead they wanted more cannabis regardless of whether they had taken active or placebo cannabis, while the opposite was seen for adults. These contrasting profiles of adolescent resilience (blunted subjective, memory, physiological and psychotomimetic effects) and vulnerability (lack of satiety, impaired inhibitory processes) show some degree of translation from preclinical findings, and may contribute to escalated cannabis use by human adolescents.” https://www.ncbi.nlm.nih.gov/pubmed/27898071

“Developmental observations suggest further that CB1 receptors develop only gradually during the postnatal period, which correlates with an insensitivity to the psychoactive effects of cannabinoid treatment in the young organism. Therefore, it is suggested that children may respond positively to medicinal applications of cannabinoids without undesirable central effects.” https://www.ncbi.nlm.nih.gov/pubmed/15159678

Treatment with tetrahydrocannabinol (THC) prevents infertility in male cystic fibrosis mice.

Posted on December 1, 2016 by David

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“Cystic fibrosis (CF) is a hereditary disease caused by mutations of the gene encoding a channel protein CFTR, conducting Cl- and HCO3 – ions. The disease is characterized by disturbances in most physiological systems, and more than 95% of men are infertile. The mechanism underlying the etiology of CF is associated with an imbalance of fatty acids.

It has been suggested that the function of the endocannabinoid system is also disturbed in CF, because endocannabinoids are derivatives of fatty acids. We assumed, therefore, that endocannabinoid activity, which plays an important role in fertility, is disrupted in CF and could be one of the causes of infertility.

The aim of the present study was to test the hypothesis that stimulation of endocannabinoid receptors in infancy would normalize their function and prevent infertility in adulthood.

Knockout male mice (cftr-/-) were treated with tetrahydrocannabinol (THC), endocannabinoid receptors agonist, in infancy from days 7 until 28, daily.

CF males treated with THC were fully fertile, producing offspring comparable by the number of litters and the number of pups with wild-type mice. CF males that were not treated with THC were completely infertile.

The present study shows that (i) endocannabinoid function is impaired in CF mice, as evidenced by the regenerating effect of its stimulation on the fertility of otherwise infertile males, (ii) endocannabinoid system dysfunction is apparently the determining factor causing infertility in CF, and (iii) mild stimulation of the endocannabinoid system in infancy and adolescence appears to normalize many reproductive processes and thereby prevent infertility in CF males.”

https://www.ncbi.nlm.nih.gov/pubmed/22865360

Behavioral alterations in cystic fibrosis mice are prevented by cannabinoid treatment in infancy.

Posted on December 1, 2016 by David

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“Substantial data have been accumulated regarding the molecular basis of cystic fibrosis (CF) pathogenesis, whereas the influence of biochemical impairments on brain processes has been the focus of much less attention. We have studied some behavioral parameters, such as motor activity and anxiety level, in a mice model of CF.

We have assumed that functioning of the endocannabinoid system could be impaired in CF (endocannabinoids are fatty acid derivatives, and fatty acid deficiency is considered a major factor in CF etiology). We have suggested that chronic treatment with cannabinoid receptors agonist during infancy would balance cannabinoid levels and prevent CF-related behavioral alterations.

Motor activity and anxiety level were studied in naïve adult CF mice (cftr-deficient mice) and compared with wild-type mice and to CF mice treated chronically with Δ9-tetrahydrocannabinol (Δ9-THC; endocannabinoid receptor agonist) during infancy (from days 7 to 28). Motor activity was tested in the tetrad, and level of anxiety in the plus maze, a month after cessation of treatment.

Motor activity decrease and elevated anxiety level were found in adult naïve CF mice compared with wild-type mice. CF mice treated with THC in infancy showed normal motor activity and anxiety levels in adulthood. Motor function alteration and elevated anxiety levels in CF can result from lack of CFTR-channel in neurons and disturbed activity of various brain areas, as well as being secondary and mediated by fatty acids deficiency, altered levels of endocannabinoids and their receptors.

It can be suggested that chronic treatment during infancy restores endocannabinoid function and thus prevents behavioral alterations.”

https://www.ncbi.nlm.nih.gov/pubmed/22865361