Cannabis in medicine: a national educational needs assessment among Canadian physicians.

“There is increasing global awareness and interest in the use of cannabis for therapeutic purposes (CTP).

It is clear that health care professionals need to be involved in these decisions, but often lack the education needed to engage in informed discussions with patients. This study was conducted to determine the educational needs of Canadian physicians regarding CTP…

 We have identified several key educational needs among Canadian physicians regarding CTP. These data can be used to develop resources and educational programs to support clinicians in this area, as well as to guide further research to inform these gaps.”
“History of cannabis as a medicine: a review” 

Pure cannabidiol in the treatment of malignant migrating partial seizures in infancy: a case report.

“Malignant migrating partial seizures in infancy is a devastating pharmacoresistent epileptic encephalopathy of unknown etiology characterized by onset in the first 6 months of life, continuous migrating focal seizures with corresponding multifocal electroencephalographic discharges, developmental deterioration, and early mortality.

Recent widespread interest in the nonpsychoactive component of the cannabis plant, cannabidiol, as a potential treatment for refractory devastating epilepsies has led to individual trials initiated by families or physicians in states that have legalized medical marijuana with anecdotal success.

We describe a now 10-month-old boy with malignant migrating partial seizures in infancy who made developmental gains and demonstrated sustained seizure reduction with the addition of cannabidiol to his antiepileptic regimen.

This report supports a role for cannabidiol in the treatment of malignant migrating partial seizures in infancy.”

http://www.ncbi.nlm.nih.gov/pubmed/25882081

http://www.thctotalhealthcare.com/category/epilepsy-2/

The biology that underpins the therapeutic potential of cannabis-based medicines for the control of spasticity in multiple sclerosis.

“Cannabis-based medicines have recently been approved for the treatment of pain and spasticity in multiple sclerosis (MS).

This supports the original perceptions of people with MS, who were using illegal street cannabis for symptom control and pre-clinical testing in animal models of MS.

This activity is supported both by the biology of the disease and the biology of the cannabis plant and the endocannabinoid system.

MS results from disease that impairs neurotransmission and this is controlled by cannabinoid receptors and endogenous cannabinoid ligands. This can limit spasticity and may also influence the processes that drive the accumulation of progressive disability.”

http://www.ncbi.nlm.nih.gov/pubmed/25876933

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Cannabidiol, a non-psychoactive cannabinoid, leads to EGR2-dependent anergy in activated encephalitogenic T cells.

“Cannabidiol (CBD), the main non-psychoactive cannabinoid, has been previously shown by us to ameliorate clinical symptoms and to decrease inflammation in myelin oligodendrocyte glycoprotein (MOG)35-55-induced mouse experimental autoimmune encephalomyelitis model of multiple sclerosis as well as to decrease MOG35-55-induced T cell proliferation and IL-17 secretion. However, the mechanisms of CBD anti-inflammatory activities are unclear.

We found that CBD leads to upregulation of CD69 and lymphocyte-activation gene 3 (LAG3) regulatory molecules on CD4+CD25-accessory T cells. This subtype of CD4+CD25-CD69+LAG3+ T cells has been recognized as induced regulatory phenotype promoting anergy in activated T cells.

Indeed, we observed that CBD treatment results in upregulation of EGR2 (a key T cell anergy inducer) mRNA transcription in stimulated TMOG cells. This was accompanied by elevated levels of anergy promoting genes such as IL-10 (anti-inflammatory cytokine), STAT5 (regulatory factor), and LAG3 mRNAs, as well as of several enhancers of cell cycle arrest (such as Nfatc1, Casp4, Cdkn1a, and Icos).

Moreover, CBD exposure leads to a decrease in STAT3 and to an increase in STAT5 phosphorylation in TMOG cells, positive and negative regulators of Th17 activity, respectively. In parallel, we observed decreased levels of major histocompatibility complex class II (MHCII), CD25, and CD69 on CD19+ B cells following CBD treatment, showing diminished antigen presenting capabilities of B cells and reduction in their pro-inflammatory functions.

CONCLUSIONS:

Our data suggests that CBD exerts its immunoregulatory effects via induction of CD4+CD25-CD69+LAG3+ cells in MOG35-55-activated APC/TMOG co-cultures. This is accompanied by EGR2-dependent anergy of stimulated TMOG cells as well as a switch in their intracellular STAT3/STAT5 activation balance leading to the previously observed decrease in Th17 activity.”

http://www.ncbi.nlm.nih.gov/pubmed/25880134

Full-text: http://www.jneuroinflammation.com/content/12/1/52

The dopamine theory of addiction: 40 years of highs and lows.

“For several decades, addiction has come to be viewed as a disorder of the dopamine neurotransmitter system; however, this view has not led to new treatments. In this Opinion article, we review the origins of the dopamine theory of addiction and discuss the ability of addictive drugs to elicit the release of dopamine in the human striatum.

There is robust evidence that stimulants increase striatal dopamine levels and some evidence that alcohol may have such an effect, but little evidence, if any, that cannabis and opiates increase dopamine levels.

Moreover, there is good evidence that striatal dopamine receptor availability and dopamine release are diminished in individuals with stimulant or alcohol dependence but not in individuals with opiate, nicotine or cannabis dependence. These observations have implications for understanding reward and treatment responses in various addictions.”

http://www.ncbi.nlm.nih.gov/pubmed/25873042

http://www.thctotalhealthcare.com/category/addiction/

 

Cannabis and cardiotoxicity.

“Cannabis is the most commonly consumed illicit drug… Despite the drug’s extreme popularity, reports of cannabis-related stroke and myocardial infarction are so rare as to still be reportable… The observation that cardiotoxicity has never been reported in cancer patients taking dronabinol, the synthetic form of THC, tends to suggest that animal studies may have overstated the cardiovascular risk,” http://www.ncbi.nlm.nih.gov/pubmed/25868498

http://www.thctotalhealthcare.com/category/cardiovascular-disease/

Drug repurposing and emerging adjunctive treatments for schizophrenia.

“Schizophrenia is a frequent disorder, which substantially impairs patients’ quality of life. Moreover, the burden of illness for patients, their families and for the society, in general, is substantial.

Given the current failure of a number of mechanistically new drugs, repurposed compounds may serve as alternative and/or adjunctive agents for schizophrenic patients and for treatment refractory patients in particular. Anti-inflammatory drugs, as well as N-acetylcysteine, a precursor of the major antioxidant glutathione, hormones, glutamatergic and nicotinergic compounds, ‘nutraceuticals’ (e.g., ω-3 fatty acids) and cannabidiol, an endocannabinoid modulator, represent promising agents in this field.”

http://www.ncbi.nlm.nih.gov/pubmed/25866122

Sequence heterogeneity of cannabidiolic- and tetrahydrocannabinolic acid-synthase in Cannabis sativa L. and its relationship with chemical phenotype.

“Sequence variants of THCA- and CBDA-synthases were isolated from different Cannabis sativa L. strains expressing various wild-type and mutant chemical phenotypes (chemotypes). Expressed and complete sequences were obtained from mature inflorescences. Each strain was shown to have a different specificity and/or ability to convert the precursor CBGA into CBDA and/or THCA type products. The comparison of the expressed sequences led to the identification of different mutations, all of them due to SNPs. These SNPs were found to relate to the cannabinoid composition of the inflorescence at maturity and are therefore proposed to have a functional significance. The amount of variation was found to be higher within the CBDAS sequence family than in the THCAS family, suggesting a more recent evolution of THCA-forming enzymes from the CBDAS group. We therefore consider CBDAS as the ancestral type of these synthases.”

http://www.ncbi.nlm.nih.gov/pubmed/25865737

Gonadal hormones do not alter the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol in adult rats.

“The purpose of this study was to determine whether sex differences in the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol (THC) are due to activational effects of gonadal hormones…

These results suggest that greater antinociceptive tolerance in females, which occurred despite females receiving 40% less THC than males, is not due to activational effects of gonadal hormones.”

The multidrug transporter ABCG2 (BCRP) is inhibited by plant-derived cannabinoids.

“Multiple drug resistance (MDR) is one of the principal causes of chemotherapeutic treatment failure in malignant disease…

Cannabinoids are used therapeutically for the palliation of the adverse side effects associated with cancer chemotherapy. However, cannabinoids also inhibit both the activity and expression of the multidrug transporter…

Cannabinoids are novel Abcg2/ABCG2 inhibitors, reversing the Abcg2-mediated multidrug-resistant phenotype in vitro. This finding may have implications for the co-administration of cannabinoids with pharmaceuticals that are ABCG2 substrates…

Cannabis and cannabinoid preparations are used as therapeutic agents.

One of the many applications of cannabinoids is in the palliation of cancer chemotherapy-induced nausea, vomiting and anorexia. Indeed, the commercial preparations, Marinol and Cesamet, containing the synthetic Δ9-tetrahydrocannabinol (THC) analogue, dronabinol (or nabilone), are approved in some countries for this use.

Interestingly, in the future, cannabinoids might be co-administered with conventional cancer chemotherapies not only in a palliative capacity but also as primary anticancer medications. Accordingly, cannabinoids have demonstrated antiproliferative actions on cancer cells in vitro and in vivo…

To conclude, this is the first study to address the interaction of cannabinoids with the multidrug transporter ABCG2/Abcg2. The results presented here indicate that plant-derived cannabinoids are a novel class of ABCG2/Abcg2 inhibitors. Our results may have important implications for the use of cannabinoid compounds with therapeutic drugs that are substrates for ABCG2.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190019/