Tag Archives: marijuana

Endocannabinoid signaling mediates oxytocin-driven social reward.

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“Marijuana exerts profound effects on human social behavior, but the neural substrates underlying such effects are unknown. Here we report that social contact increases, whereas isolation decreases, the mobilization of the endogenous marijuana-like neurotransmitter, anandamide, in the mouse nucleus accumbens (NAc), a brain structure that regulates motivated behavior. The results indicate that anandamide-mediated signaling at CB1 receptors, driven by oxytocin, controls social reward. Deficits in this signaling mechanism may contribute to social impairment in autism spectrum disorders and might offer an avenue to treat these conditions.”  http://www.ncbi.nlm.nih.gov/pubmed/26504214

“In conclusion, our results illuminate a mechanism underlying the prosocial actions of oxytocin, and provide unexpected insights on possible neural substrates involved in the social facilitation caused by marijuana. Pharmacological modulation of oxytocin-driven anandamide signaling (by using, for example, FAAH inhibitors) might open new avenues to treat social impairment in autism spectrum disorders.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653148/

Controlled downregulation of the cannabinoid CB1 receptor provides a promising approach for the treatment of obesity and obesity-derived type 2 diabetes.

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“Increased activity of the endocannabinoid system has emerged as a pathogenic factor in visceral obesity, which is a risk factor for type 2 diabetes mellitus (T2DM).

The endocannabinoid system is composed of at least two G-protein-coupled receptors (GPCRs), the cannabinoid receptor type 1 (CB1), and the cannabinoid receptor type 2 (CB2).

Downregulation of CB1 activity in rodents and humans has proven efficacious to reduce food intake, abdominal adiposity, fasting glucose levels, and cardiometabolic risk factors.

Unfortunately, downregulation of CB1 activity by universally active CB1 inverse agonists has been found to elicit psychiatric side effects, which led to the termination of using globally active CB1 inverse agonists to treat diet-induced obesity.

Interestingly, preclinical studies have shown that downregulation of CB1 activity by CB1 neutral antagonists or peripherally restricted CB1 inverse agonists provided similar anorectic effects and metabolic benefits without psychiatric side effects seen in globally active CB1 inverse agonists.

Furthermore, downregulation of CB1 activity may ease endoplasmic reticulum and mitochondrial stress which are contributors to obesity-induced insulin resistance and type 2 diabetes.

This suggests new approaches for cannabinoid-based therapy in the management of obesity and obesity-related metabolic disorders including type 2 diabetes.”

http://www.ncbi.nlm.nih.gov/pubmed/26498013

Peripherally Restricted Cannabinoids for the Treatment of Pain.

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“The use of cannabinoids for the treatment of chronic diseases has increased in the United States, with 23 states having legalized the use of marijuana.

Although currently available cannabinoid compounds have shown effectiveness in relieving symptoms associated with numerous diseases, the use of cannabis or cannabinoids is still controversial mostly due to their psychotropic effects (e.g., euphoria, laughter) or central nervous system (CNS)-related undesired effects (e.g., tolerance, dependence).

A potential strategy to use cannabinoids for medical conditions without inducing psychotropic or CNS-related undesired effects is to avoid their actions in the CNS.

This approach could be beneficial for conditions with prominent peripheral pathophysiologic mechanisms (e.g., painful diabetic neuropathy, chemotherapy-induced neuropathy).

In this article, we discuss the scientific evidence to target the peripheral cannabinoid system as an alternative to cannabis use for medical purposes, and we review the available literature to determine the pros and cons of potential strategies that can be used to this end.”

http://www.ncbi.nlm.nih.gov/pubmed/26497478

Head and neck cancer among marijuana users: A meta-analysis of matched case-control studies.

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“The scientific literature presents conflicting data on a possible causal relationship between marijuana users and the development of head and neck cancer.

This study performed a systematic review with meta-analysis.

The meta-analysis found no association between exposure and disease.

No association between lifetime marijuana use and the development of head and neck cancer was found.”

http://www.ncbi.nlm.nih.gov/pubmed/26433192

http://www.aobjournal.com/article/S0003-9969(15)30041-8/abstract

Past 15-year trends in adolescent marijuana use: Differences by race/ethnicity and sex.

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“The potential for increases in adolescent marijuana use is an important concern given recent changes in marijuana policy.

The purpose of this study was to estimate trends in marijuana use from 1999 to 2013 among a national sample of US high school students…

Despite considerable changes in state marijuana policies over the past 15 years, marijuana use among high school students has largely declined. ”

http://www.ncbi.nlm.nih.gov/pubmed/26361714

The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells.

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“One of the most exciting areas of current research in the cannabinoid field is the study of the potential application of these compounds as antitumoral drugs. Here, we describe the signaling pathway that mediates cannabinoid-induced apoptosis of tumor cells. By using a wide array of experimental approaches, we identify the stress-regulated protein p8 (also designated as candidate of metastasis 1) as an essential mediator of cannabinoid antitumoral action and show that p8 upregulation is dependent on de novo-synthesized ceramide. We also observe that p8 mediates its apoptotic effect via upregulation of the endoplasmic reticulum stress-related genes ATF-4, CHOP, and TRB3. Activation of this pathway may constitute a potential therapeutic strategy for inhibiting tumor growth.”

http://www.ncbi.nlm.nih.gov/pubmed/16616335

“Marijuana has been used in medicine for many centuries, and nowadays there is a renaissance in the study of the therapeutic effects of cannabinoids. One of the most active areas of research in the cannabinoid field is the study of the potential antitumoral application of these drugs. Our results unravel the mechanism of cannabinoid antitumoral action by demonstrating the proapoptotic role of the stress protein p8 via its downstream targets ATF-4, CHOP, and TRB3.

The identification of this pathway may contribute to the design of therapeutic strategies for inhibiting tumor growth. In particular, our findings can help to improve the efficiency and selectivity of potential antitumoral therapies with cannabinoids.

Our results also support that cannabinoid treatment does not activate this pathway in nontransformed cells, in line with the belief that cannabinoid proapoptotic action is selective for tumor versus nontumor cells, and that cannabinoids act in a synergic fashion with ER stress inducers as well as with other antitumoral agents.

The identification of the p8-regulated pathway described here may contribute to the design of therapeutic strategies for inhibiting tumor growth. In particular, our findings can help to improve the efficiency and selectivity of a potential cannabinoid-based antitumoral therapy.”

http://www.sciencedirect.com/science/article/pii/S1535610806000857

Medical Marijuana: Reducing Spasticity in Multiple Sclerosis Patients

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“Medical marijuana is a justifiable treatment for spasticity in patients with MS.

Interviews indicate that many patients choose marijuana over other medicines because they experience minimal side effects and rapid improvements in motor functioning…

Compared to the steroids, tranquilizers, and sedatives usually prescribed for MS patients, marijuana is remarkably safe and benign…

There is a lack of evidence for long-term risks associated with marijuana use. The short-term risks are minimal and short-lived.

Studies verify the positive relationship between medical marijuana use and reduced spasticity.

Voters are realizing the cruelty associated with robbing a terminally or chronically ill patient from the medicine that most relieves their pain.

MS is a chronic disease that can lead to severe pain and disability if untreated. For these reasons, medical marijuana should be available to patients who understand the risks associated with its use.

Until medical research develops an equally effective oral drug, marijuana will remain a reasonable option for patients suffering from MS.”

http://www.vanderbilt.edu/AnS/psychology/health_psychology/medicalmarijuana.htm

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

High dosage of cannabidiol (CBD) alleviates pentylenetetrazole-induced epilepsy in rats by exerting an anticonvulsive effect.

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“The study was designed to investigate the effect of various concentrations of cannabidiol (CBD) in rats with chronic epilepsy.

The results revealed a significant decrease in the daily average grade of epileptic seizures on treatment with CBD (50 mg/kg).

The neuronal loss and astrocyte hyperplasia in the hippocampal area were also decreased.

CBD treatment did not affect the expression of iNOS in the hippocampus; however, the expression of NR1 was decreased significantly.

Thus, CBD administration inhibited the effect of pentylenetetrazole in rats, decreased the astrocytic hyperplasia, decreased neuronal damage in the hippocampus caused by seizures and selectively reduced the expression of the NR1 subunit of NMDA.

Therefore, CBD exhibits an anticonvulsive effect in the rats with chronic epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/26309534

“Epilepsy is one of the most common diseases of the brain, affecting at least 50 million people globally… Despite development of a number of new antiepileptic drugs, epilepsy could not be significantly reduced and is a challenge to the clinicians… Many plants, known for their anticonvulsant activity are subjected to phytochemical and pharmacological studies. Cannabidiol (CBD) a constituent of the hemp seed exhibits potent anticonvulsant activity…  The CBD possess anticonvulsive, anti-epileptic, and antimicrobial properties… The present study was performed to examine the anticonvulsive effects of CBD in pentylenetetrazole-induced chronic epilepsy rat models… The present study demonstrates that CBD protects against pentylenetetrazole-induced chronic seizures, decreases astrocytic hyperplasia, decreases neuronal cell loss and selectively suppresses NMDA1 receptor in the hippocampus… Therefore, CBD exhibits an anticonvulsive effect in the rats with chronic epilepsy.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537971/

The Genetic Structure of Marijuana and Hemp.

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“Despite its cultivation as a source of food, fibre and medicine, and its global status as the most used illicit drug, the genus Cannabis has an inconclusive taxonomic organization and evolutionary history.

Drug types of Cannabis (marijuana), which contain high amounts of the psychoactivecannabinoid Δ9-tetrahydrocannabinol (THC), are used for medical purposes and as a recreational drug.

Hemp types are grown for the production of seed and fibre, and contain low amounts of THC.

Two species or gene pools (C. sativa and C. indica) are widely used in describing the pedigree or appearance of cultivated Cannabis plants.

Using 14,031 single-nucleotide polymorphisms (SNPs) genotyped in 81 marijuana and 43 hemp samples, we show that marijuana and hemp are significantly differentiated at a genome-wide level, demonstrating that the distinction between these populations is not limited to genes underlying THC production.

We find a moderate correlation between the genetic structure of marijuana strains and their reported C. sativa and C. indica ancestry and show that marijuana strain names often do not reflect a meaningful genetic identity.

We also provide evidence that hemp is genetically more similar to C. indica type marijuana than to C. sativa strains.”

http://www.ncbi.nlm.nih.gov/pubmed/26308334

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0133292