Could cannabidiol be used as an alternative to antipsychotics?

“Schizophrenia is a mental disorder that affects close to 1% of the population. Individuals with this disorder often present signs such as hallucination, anxiety, reduced attention, and social withdrawal. Although antipsychotic drugs remain the cornerstone of schizophrenia treatment, they are associated with severe side effects.

Recently, the endocannabinoid system (ECS) has emerged as a potential therapeutic target for pharmacotherapy that is involved in a wide range of disorders, including schizophrenia.

Since its discovery, a lot of effort has been devoted to the study of compounds that can modulate its activity for therapeutic purposes.

Among them, cannabidiol (CBD), a non-psychoactive component of cannabis, shows great promise for the treatment of psychosis, and is associated with fewer extrapyramidal side effects than conventional antipsychotic drugs.

The overarching goal of this review is to provide current available knowledge on the role of the dopamine system and the ECS in schizophrenia, and to discuss key findings from animal studies and clinical trials investigating the antipsychotic potential of CBD.”

http://www.ncbi.nlm.nih.gov/pubmed/27267317

Variability in Seed Traits in a Collection of Cannabis sativa L. Genotypes.

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“Cannabis sativa L. (hemp) is a wind-pollinated annual plant that originated in central Asia. Hemp, naturally, is a dioecious crop, but some monoecious cultivars have been obtained as a result of earlier breeding efforts.

Hemp is an ancient crop that has been cultivated worldwide until the early twentieth century, after which its cultivation declined.

Recently, interest in this multipurpose crop delivering fibers, shives, and seeds, has been renewed by an increasing demand not only for natural fibers but also for the high content and quality of seed protein and oil. Hemp seed contains 25–35% oil, 20–25% protein, 20–30% carbohydrates, 10–15% insoluble fiber, vitamins, and minerals such as phosphorus, potassium, magnesium, sulfur, and calcium.

The increasing demand for vegetable oils and proteins, along with current awareness about their nutritional and functional role in human diet, has made indispensable to characterize new plant sources. In this regard, hemp seed contains all the essential amino acids and fatty acids necessary to maintain healthy human life, and it might be a new good source of nutrients for both humans and livestock.

The principal value of hemp seed oil resides in its fatty acid composition. It contains the two dietary essential fatty acids: linoleic acid (LA; 18:2ω6) and the α-linolenic acid (ALA; 18:3ω3) in the ratio of 2.5–3:1, which has been claimed as ideal for human nutrition.

The seed of Cannabis sativa L. is an expanding source of proteins and oil for both humans and animals.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873519/

Proteomic characterization of hempseed (Cannabis Sativa L.).

“Hempseed is an underexploited non-legume protein-rich seed. Although its protein is well-known for its digestibility, essential amino acid composition, and useful techno-functional properties, a comprehensive proteome characterization is still lacking. The objective of this work was to fill this knowledge gap and provide information useful for a better exploitation of this seed in different food products.”

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“This paper presents an investigation on hempseed proteome.

The experimental approach, based on combinatorial peptide ligand libraries (CPLLs), SDS-PAGE separation, nLC-ESI-MS/MS identification, and database search, permitted identifying in total 181 expressed proteins. This very large number of identifications was achieved by searching in two databases: Cannabis sativa L. (56 gene products identified) and Arabidopsis thaliana(125 gene products identified). By performing a protein-protein association network analysis using the STRING software, it was possible to build the first interactomic map of all detected proteins, characterized by 137 nodes and 410 interactions. Finally, a Gene Ontology analysis of the identified species permitted to classify their molecular functions: the great majority is involved in the seed metabolic processes (41%), responses to stimulus (8%), and biological process (7%).”

http://www.sciencedirect.com/science/article/pii/S1874391916302354

Comparing adults who use cannabis medically with those who use recreationally: Results from a national sample.

“There were no significant differences between those who used medically versus recreationally in race, education, past year depression and prevalence of cannabis use disorders. In adjusted analyses, those with medical cannabis use were more likely to have poorer health and lower levels of alcohol use disorders and non-cannabis drug use. A third of those who reported medical cannabis use endorsed daily cannabis use compared to 11% in those who reported recreational use exclusively.”

http://www.ncbi.nlm.nih.gov/pubmed/27262964

Sativex Associated With Behavioral-Relapse Prevention Strategy as Treatment for Cannabis Dependence: A Case Series.

“The current lack of pharmacological treatments for cannabis dependence warrants the use of novel approaches and further investigation of promising pharmacotherapy.

In this case series, we assessed the use of self-titrated dosages of Sativex (1:1, Δ-tetrahydrocannabinol [THC]/cannabidiol [CBD] combination) and motivational enhancement therapy and cognitive behavioral therapy (MET/CBT) for the treatment of cannabis dependence among 5 treatment-seeking community-recruited cannabis-dependent subjects.

THC/CBD metabolite concentration indicated reduced cannabis use and compliance with medication.

CONCLUSIONS:

In summary, this pilot study found that with Sativex in combination with MET/CBT reduced cannabis use while preventing increases in craving and withdrawal in the 4 participants completing the study. Further systematic exploration of Sativex as a pharmacological treatment option for cannabis dependence should be performed.”

http://www.ncbi.nlm.nih.gov/pubmed/27261670

Gastric acid inhibitory and gastric protective effects of Cannabis and cannabinoids.

“Cannabis sativa has long been known for its psychotropic effect. Only recently with the discovery of the cannabinoid receptors, their endogenous legends and the enzymes responsible for their synthesis and degradation, the role of this ‘endocannabinoid system’ in different pathophysiologic processes is beginning to be delineated.

There is evidence that CB1 receptor stimulation with synthetic cannabinoids or Cannabis sativa extracts rich in Δ9-tetrahydrocannabinol inhibit gastric acid secretion in humans and experimental animals.

This is specially seen when gastric acid secretion is stimulated by pentagastrin, carbachol or 2-deoxy-d-glucose.

Cannabis and/or cannabinoids protect the gastric mucosa against noxious challenge with non-steroidal anti-inflammatory drugs, ethanol as well as against stress-induced mucosal damage.

Cannabis/cannabinoids might protect the gastric mucosa by virtue of its antisecretory, antioxidant, anti-inflammatory, and vasodilator properties.”

http://www.ncbi.nlm.nih.gov/pubmed/27261847

Pathways and gene networks mediating the regulatory effects of cannabidiol, a nonpsychoactive cannabinoid, in autoimmune T cells.

“Our previous studies showed that the non-psychoactive cannabinoid, cannabidiol (CBD), ameliorates the clinical symptoms in mouse myelin oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune encephalomyelitis model of multiple sclerosis (MS) as well as decreases the memory MOG35-55-specific T cell (TMOG) proliferation and cytokine secretion including IL-17, a key autoimmune factor.

Microarray-based gene expression profiling demonstrated that CBD exerts its immunoregulatory effects in activated memory TMOG cells via (a) suppressing proinflammatory Th17-related transcription, (b) by promoting T cell exhaustion/tolerance, (c) enhancing IFN-dependent anti-proliferative program, (d) hampering antigen presentation, and (d) inducing antioxidant milieu resolving inflammation.

These findings put forward mechanism by which CBD exerts its anti-inflammatory effects as well as explain the beneficial role of CBD in pathological memory T cells and in autoimmune diseases.”

TRPV2 is a novel biomarker and therapeutic target in triple negative breast cancer.

Image result for Oncotarget.“Transient receptor potential vanilloid type-2 (TRPV2) is an ion channel that is triggered by agonists like cannabidiol (CBD). Triple negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Chemotherapy is still the first line for the treatment of TNBC patients; however, TNBC usually gains rapid resistance and unresponsiveness to chemotherapeutic drugs.

In this study, we found that TRPV2 protein is highly up-regulated in TNBC tissues compared to normal breast tissues. We also observed that TNBC and estrogen receptor alpha negative (ERα-) patients with higher TRPV2 expression have significantly higher recurrence free survival compared to patients with lower TRPV2 expression especially those who were treated with chemotherapy.

In addition, we showed that TRPV2 overexpression or activation by CBD significantly increased doxorubicin (DOX) uptake and apoptosis in TNBC cells. The induction of DOX uptake was abrogated by TRPV2 blocking or downregulation.

In vivo mouse model studies showed that the TNBC tumors derived from CBD+DOX treated mice have significantly reduced weight and increased apoptosis compared to those treated with CBD or DOX alone.

Overall, our studies for the first time revealed that TRPV2 might be a good prognostic marker for TNBC and ERα- breast cancer patient especially for those who are treated with chemotherapy. In addition, TRPV2 activation could be a novel therapeutic strategy to enhance the uptake and efficacy of chemotherapy in TNBC patients.”

http://www.ncbi.nlm.nih.gov/pubmed/27248470

Need for Methods to Investigate Endocannabinoid Signaling.

“Endocannabinoids (eCBs) are endogenous lipids able to activate cannabinoid receptors, the primary molecular targets of the cannabis (Cannabis sativa) active principle Δ(9)-tetrahydrocannabinol. During the last 20 years, several N-acylethanolamines and acylesters have been shown to act as eCBs, and a complex array of receptors, metabolic enzymes, and transporters (that altogether form the so-called eCB system) has been shown to finely tune their manifold biological activities. It appears now urgent to develop methods and protocols that allow to assay in a specific and quantitative manner the distinct components of the eCB system, and that can properly localize them within the cell. A brief overview of eCBs and of the proteins that bind, transport, and metabolize these lipids is presented here, in order to put in a better perspective the relevance of methodologies that help to disclose molecular details of eCB signaling in health and disease. Proper methodological approaches form also the basis for a more rationale and effective drug design and therapeutic strategy to combat human disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/27245886

Can Cannabinoids Modulate Fibrotic Progression in Systemic Sclerosis?

“Since ancient times, plants have been used for therapeutic purposes.

Cannabis sativa has been widely used as a medicinal herb by Ayurveda and traditional Chinese medicine for centuries.

According to our in vitro and in vivo experimental models, cannabinoids are able to modulate fibrosis.

The exact mechanism underlying this effect requires further investigation, but it seems to go beyond their anti-inflammatory and immunomodulatory properties.

Based on the above observations, we aimed to investigate the role of cannabinoids in systemic sclerosis (SSc), an autoimmune disease characterized by diffuse fibrosis.

Since preclinical data on cannabinoids show their capability to modulate fibrosis, inflammation and vasodilatation, these molecules could be ideal drugs for targeting SSc.”

http://www.ima.org.il/FilesUpload/IMAJ/0/193/96907.pdf