Splendor in the Grass? A Pilot Study Assessing the Impact of Medical Marijuana on Executive Function

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“To date, few studies have investigated the potential impact of MMJ use on cognitive performance, despite a well-documented association between recreational marijuana (MJ) use and executive dysfunction. The current study assessed the impact of 3 months of MMJ treatment on executive function, exploring whether MMJ patients would experience improvement in cognitive functioning, perhaps related to primary symptom alleviation.

Results suggest that in general, MMJ patients experienced some improvement on measures of executive functioning, including the Stroop Color Word Test and Trail Making Test, mostly reflected as increased speed in completing tasks without a loss of accuracy.

On self-report questionnaires, patients also indicated moderate improvements in clinical state, including reduced sleep disturbance, decreased symptoms of depression, attenuated impulsivity, and positive changes in some aspects of quality of life. Additionally, patients reported a notable decrease in their use of conventional pharmaceutical agents from baseline, with opiate use declining more than 42%.

Data from the current investigation provide preliminary evidence that after 3 months of treatment, MMJ users did not experience executive functioning deficits, which are often observed in regular, recreational MJ users. In fact, MMJ patients evidenced improvement in certain aspects of performance on these measures, particularly with regard to time required to complete tasks.”

http://journal.frontiersin.org/article/10.3389/fphar.2016.00355/full

Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report.

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“Anxiety and sleep disorders are often the result of posttraumatic stress disorder and can contribute to an impaired ability to focus and to demonstration of oppositional behaviors.

CASE PRESENTATION:

These symptoms were present in our patient, a ten-year-old girl who was sexually abused and had minimal parental supervision as a young child under the age of five. Pharmaceutical medications provided partial relief, but results were not long-lasting, and there were major side effects. A trial of cannabidiol oil resulted in a maintained decrease in anxiety and a steady improvement in the quality and quantity of the patient’s sleep.

DISCUSSION:

Cannabidiol oil, an increasingly popular treatment of anxiety and sleep issues, has been documented as being an effective alternative to pharmaceutical medications. This case study provides clinical data that support the use of cannabidiol oil as a safe treatment for reducing anxiety and improving sleep in a young girl with posttraumatic stress disorder.”

https://www.ncbi.nlm.nih.gov/pubmed/27768570

Experimental cannabidiol treatment reduces early pancreatic inflammation in type 1 diabetes.

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“Destruction of the insulin-producing beta cells in type 1 diabetes (T1D) is induced by invasion of immune cells causing pancreatic inflammation.

Cannabidiol (CBD), a phytocannabinoid, derived from the plant, Cannabis sativa, was shown to lower the incidence of diabetes in non-obese diabetic (NOD) mice, an animal model of spontaneous T1D development.

The goal of this study was to investigate the impact of experimental CBD treatment on early pancreatic inflammation in T1D by intravital microscopy (IVM) in NOD mice.

CBD-treated NOD mice developed T1D later and showed significantly reduced leukocyte activation and increased FCD in the pancreatic microcirculation.

Experimental CBD treatment reduced markers of inflammation in the microcirculation of the pancreas studied by intravital microscopy.”

https://www.ncbi.nlm.nih.gov/pubmed/27767974

Effect of cannabis smoking on lung function and respiratory symptoms: a structured literature review.

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“As cannabis use increases, physicians need to be familiar with the effects of both cannabis and tobacco on the lungs. However, there have been very few long-term studies of cannabis smoking, mostly due to legality issues and the confounding effects of tobacco.

It was previously thought that cannabis and tobacco had similar long-term effects as both cause chronic bronchitis. However, recent large studies have shown that, instead of reducing forced expiratory volume in 1 s and forced vital capacity (FVC), marijuana smoking is associated with increased FVC.

The cause of this is unclear, but acute bronchodilator and anti-inflammatory effects of cannabis may be relevant.”

https://www.ncbi.nlm.nih.gov/pubmed/27763599

Cannabinoid Receptor 2 Activation Restricts Fibrosis and Alleviates Hydrocephalus after Intraventricular Hemorrhage.

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“Fibrosis in ventricular system has a role in hydrocephalus following intraventricular hemorrhage (IVH).

The cannabinoid receptor 2 (CB2) has been reported to participate in alleviating the fibrosis process of many diseases.

However, its role in fibrosis after IVH was unclear so far, and we hypothesized that CB2 activation has potential to attenuate hydrocephalus after IVH via restricting fibrosis. So the present study was designed to investigate this hypothesis in a modified rat IVH model.

In conclusion, CB2 may have anti-fibrogenic effects after IVH. CB2 agonist suppressed fibrosis of ventricular system and alleviated hydrocephalus following IVH, which is partly mediated by inhibiting TGF-β1.”

https://www.ncbi.nlm.nih.gov/pubmed/27769788

Targeting cannabinoid receptor-2 pathway by phenylacetylamide suppresses the proliferation of human myeloma cells through mitotic dysregulation and cytoskeleton disruption.

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“Cannabinoid receptor-2 (CB2) is expressed dominantly in the immune system, especially on plasma cells.

Cannabinergic ligands with CB2 selectivity emerge as a class of promising agents to treat CB2-expressing malignancies without psychotropic concerns.

In this study, we found that CB2 but not CB1 was highly expressed in human multiple myeloma (MM) and primary CD138+ cells.

Thus, targeting CB2 may represent an attractive approach to treat cancers of immune origin.”

https://www.ncbi.nlm.nih.gov/pubmed/25640641

The effects of cannabidiol and its synergism with bortezomib in multiple myeloma cell lines. A role for transient receptor potential vanilloid type-2.

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“Multiple myeloma (MM) is a plasma cell (PC) malignancy characterised by the accumulation of a monoclonal PC population in the bone marrow (BM).

Cannabidiol (CBD) is a non-psychoactive cannabinoid with antitumoural activities, and the transient receptor potential vanilloid type-2 (TRPV2) channel has been reported as a potential CBD receptor.

TRPV2 activation by CBD decreases proliferation and increases susceptibility to drug-induced cell death in human cancer cells.

However, no functional role has been ascribed to CBD and TRPV2 in MM. In this study, we identified the presence of heterogeneous CD138+TRPV2+ and CD138+TRPV2- PC populations in MM patients, whereas only the CD138+ TRPV2- population was present in RPMI8226 and U266 MM cell lines.

Because bortezomib (BORT) is commonly used in MM treatment, we investigated the effects of CBD and BORT in CD138+TRPV2- MM cells and in MM cell lines transfected with TRPV2 (CD138+TRPV2+).

These results showed that CBD by itself or in synergy with BORT strongly inhibited growth, arrested cell cycle progression and induced MM cells death by regulating the ERK, AKT and NF-κB pathways with major effects in TRPV2+ cells.

These data provide a rationale for using CBD to increase the activity of proteasome inhibitors in MM.”

https://www.ncbi.nlm.nih.gov/pubmed/24293211

Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration.

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“Several studies showed a potential anti-tumor role for cannabinoids, by modulating cell signaling pathways involved in cancer cell proliferation, chemo-resistance and migration.

Cannabidiol (CBD) was previously noted in multiple myeloma (MM), both alone and in synergy with the proteasome inhibitor bortezomib, to induce cell death.

In other type of human cancers, the combination of CBD with Δ9-tetrahydrocannabinol (THC) was found to act synergistically with other chemotherapeutic drugs suggesting their use in combination therapy.

In the current study, we evaluated the effects of THC alone and in combination with CBD in MM cell lines.

We found that CBD and THC, mainly in combination, were able to reduce cell viability by inducing autophagic-dependent necrosis.

Moreover, we showed that the CBD-THC combination was able to reduce MM cells migration by down-regulating expression of the chemokine receptor CXCR4 and of the CD147 plasma membrane glycoprotein.

Furthermore, since the immuno-proteasome is considered a new target in MM and also since carfilzomib (CFZ) is a new promising immuno-proteasome inhibitor that creates irreversible adducts with the β5i subunit of immuno-proteasome, we evaluated the effect of CBD and THC in regulating the expression of the β5i subunit and their effect in combination with CFZ.

Herein, we also found that the CBD and THC combination is able to reduce expression of the β5i subunit as well as to act in synergy with CFZ to increase MM cell death and inhibits cell migration.

In summary, these results proved that this combination exerts strong anti-myeloma activities.”

 https://www.ncbi.nlm.nih.gov/pubmed/27769052

Crystal Structure of the Human Cannabinoid Receptor CB1.

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“Cannabinoid receptor 1 (CB1) is the principal target of Δ9-tetrahydrocannabinol (THC), a psychoactive chemical from Cannabis sativa with a wide range of therapeutic applications and a long history of recreational use.

CB1 is activated by endocannabinoids and is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders.

Here, we present the 2.8 Å crystal structure of human CB1 in complex with AM6538, a stabilizing antagonist, synthesized and characterized for this structural study.

The structure of the CB1-AM6538 complex reveals key features of the receptor and critical interactions for antagonist binding.

In combination with functional studies and molecular modeling, the structure provides insight into the binding mode of naturally occurring CB1 ligands, such as THC, and synthetic cannabinoids.

This enhances our understanding of the molecular basis for the physiological functions of CB1 and provides new opportunities for the design of next-generation CB1-targeting pharmaceuticals.”

https://www.ncbi.nlm.nih.gov/pubmed/27768894

Therapeutic potential of fatty acid amide hydrolase, monoacylglycerol lipase, and N-acylethanolamine acid amidase inhibitors.

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“Fatty acid ethanolamides (FAEs) and endocannabinoids (ECs) have been shown to alleviate pain and inflammation, regulate motility and appetite, and produce anti-cancer, anxiolytic, and neuroprotective efficacies via cannabinoid receptor type 1 (CB1) or type 2 (CB2), or via peroxisome proliferator-activated receptor α (PPAR-α) stimulation.

FAEs and ECs are synthesized by a series of endogenous enzymes, including N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD), diacylglycerol lipase (DAGL), or phospholipase C (PLC), and their metabolism is mediated by several metabolic enzymes, including fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), N-acylethanolamine acid amidase (NAAA), or cyclooxygenase-2 (COX-2).

Over the last decades, increasing the concentration of FAEs and ECs through the inhibition of degrading enzymes has been considered to be a viable therapeutic approach to enhance their anti-nociceptive and anti-inflammatory effects, as well as protecting the nervous system.”

 https://www.ncbi.nlm.nih.gov/pubmed/27766867