Synergy between cannabidiol, cannabidiolic acid, and Δ⁹-tetrahydrocannabinol in the regulation of emesis in the Suncus murinus (house musk shrew).

“Smoked marijuana contains over 100 different cannabinoids, including the psychoactive compound Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD).

THC, CBD, and its acidic precursor, cannabidiolic acid (CBDA), have all been shown to have antiemetic properties in the Suncus murinus.

Here we show that when subthreshold antiemetic doses of CBD or CBDA are combined with a subthreshold antiemetic dose of THC in the S. murinus, both lithium-chloride-induced vomiting and abdominal retching are dramatically suppressed.

These results suggest that combined effects of these compounds may lead to better control of vomiting with fewer side effects.”

http://www.ncbi.nlm.nih.gov/pubmed/26030435

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

High prevalence of cannabis use among Aka foragers of the Congo Basin and its possible relationship to helminthiasis

Cover image for Vol. 27 Issue 3

“Little is known about cannabis use in hunter-gatherers. Therefore, we investigated cannabis use in the Aka, a population of foragers of the Congo Basin.

Because cannabis contains anthelminthic compounds,” http://medical-dictionary.thefreedictionary.com/anthelmintic ” and the Aka have a high prevalence of helminthiasis, we also tested the hypothesis that cannabis use might be an unconscious form of self-medication against helminths.

THCA levels were negatively correlated with parasite infection and reinfection, supporting the self-medication hypothesis.

This, to our knowledge, is the first biomarker-validated study of cannabis use in a hunting-gathering population, and also the first to explore the relationship between the use of cannabis, which is toxic to helminths, and intestinal helminth infection.

Although the conventional view is that drug abuse impairs immunity, thus increasing susceptibility to infection, if recreational drug use is explained by the drugs’ antiparasitic properties, this would suggest that the immune system plays a key role in regulating drug use.”  

http://onlinelibrary.wiley.com/doi/10.1002/ajhb.22740/full

“Medical Marijuana Smoking Linked to Parasite Prevention. Scientists from Washington State University have suggested that smoking cannabis may have a beneficial effect with regard to the avoidance of intestinal parasite infections, which could explain why the drug has such a long history of recreational use… those who smoked cannabis had a lower rate of infection.” http://www.newhistorian.com/medical-marijuana-smoking-linked-to-parasite-prevention/3936/

Maternal marijuana use and neonatal morbidity.

“Marijuana use is becoming increasingly common in the obstetric population, however it is unknown whether it is associated with poor neonatal outcomes. We sought to determine the prevalence and risk factors for marijuana use in pregnancy, and to evaluate whether marijuana use is independently associated with poor neonatal outcomes.

CONCLUSION:

Marijuana use is common in pregnancy, but may not be an independent risk factor for poor neonatal outcomes in term pregnancies.”

http://www.ncbi.nlm.nih.gov/pubmed/26026918

Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It’s Been ….

“The use of cannabis, or marijuana, for medicinal purposes is deeply rooted though history, dating back to ancient times. It once held a prominent position in the history of medicine, recommended by many eminent physicians for numerous diseases, particularly headache and migraine.

Through the decades, this plant has taken a fascinating journey from a legal and frequently prescribed status to illegal, driven by political and social factors rather than by science.

However, with an abundance of growing support for its multitude of medicinal uses, the misguided stigma of cannabis is fading, and there has been a dramatic push for legalizing medicinal cannabis and research.

Almost half of the United States has now legalized medicinal cannabis, several states have legalized recreational use, and others have legalized cannabidiol-only use, which is one of many therapeutic cannabinoids extracted from cannabis.

Physicians need to be educated on the history, pharmacology, clinical indications, and proper clinical use of cannabis, as patients will inevitably inquire about it for many diseases, including chronic pain and headache disorders for which there is some intriguing supportive evidence…

The literature suggests that the medicinal use of cannabis may have a therapeutic role for a multitude of diseases, particularly chronic pain disorders including headache.

Supporting literature suggests a role for medicinal cannabis and cannabinoids in several types of headache disorders including migraine and cluster headache, although it is primarily limited to case based, anecdotal, or laboratory-based scientific research.

Cannabis contains an extensive number of pharmacological and biochemical compounds, of which only a minority are understood, so many potential therapeutic uses likely remain undiscovered.

Cannabinoids appear to modulate and interact at many pathways inherent to migraine, triptan mechanisms ofaction, and opiate pathways, suggesting potential synergistic or similar benefits.

Modulation of the endocannabinoid system through agonism or antagonism of its receptors, targeting its metabolic pathways, or combining cannabinoids with other analgesics for synergistic effects, may provide the foundation for many new classes of medications.”

http://www.ncbi.nlm.nih.gov/pubmed/26015168

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

Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine.

“Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate.

Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid, cannabidiol (CBD), protects against cocaine toxicity.

URB597 (1.0 mg/kg) abolished cocaine-induced seizure, yet it did not protect against acute liver injury.

Using confocal liver intravital microscopy, we observed that CBD reduced acute liver inflammation and damage induced by cocaine and prevented associated seizure.

Additionally, we showed that previous liver damage induced by another hepatotoxic drug (acetaminophen) increased seizure and lethality induced by cocaine intoxication, linking hepatotoxicity to seizure dynamics.

These findings suggest that activation of cannabinoid system may have protective actions on both liver and brain induced by cocaine, minimizing inflammatory injury promoted by cocaine, supporting its further clinical application in the treatment of cocaine abuse.”

http://www.ncbi.nlm.nih.gov/pubmed/25999668

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427116/

[Cannabinoids in medicine].

“Cannabinoids have been known for many centuries because of their various effects in healthcare. They are primarily effective in reducing nausea, vomiting, pain, anorexia, spasticity and depression. Some other effects are known, all seem to be mediated by cannabinoid receptors in the central nervous system. In the past years, medical use has been proven in several studies. Today, the therapeutical use of cannabinoids in medicine is increasing, and access was made easier. Especially in pain-management and palliative care, they seem to be a valuable therapeutic option.”

http://www.ncbi.nlm.nih.gov/pubmed/19165445

Hemp (Cannabis sativa L.).

“Hemp (Cannabis sativa L.) suspension culture cells were transformed with Agrobacterium tumefaciens strain EHA101 carrying the binary plasmid pNOV3635. The plasmid contains a phosphomannose isomerase (PMI) selectable marker gene. Cells transformed with PMI are capable of metabolizing the selective agent mannose, whereas cells not expressing the gene are incapable of using the carbon source and will stop growing. Callus masses proliferating on selection medium were screened for PMI expression using a chlorophenol red assay. Genomic DNA was extracted from putatively transformed callus lines, and the presence of the PMI gene was confirmed using PCR and Southern hybridization. Using this method, an average transformation frequency of 31.23% ± 0.14 was obtained for all transformation experiments, with a range of 15.1-55.3%.”

http://www.ncbi.nlm.nih.gov/pubmed/25416268

Id-1 is a key transcriptional regulator of glioblastoma aggressiveness and a novel therapeutic target.

Figure 2

“Glioblastoma (GBM) is the most common form of primary adult brain tumors…

It is, therefore, essential to discover master regulators that control GBM invasiveness and target them therapeutically.

We demonstrate here that the transcriptional regulator Id-1 plays a critical role in modulating the invasiveness of GBM cell lines and primary GBM cells.

Furthermore, we show that a non-toxic compound, cannabidiol, significantly down-regulates Id-1 gene expression and associated glioma cell invasiveness…

Our results suggest that Id-1 regulates multiple tumor-promoting pathways in GBM, and that drugs targeting Id-1 represent a novel and promising strategy for improving the therapy and outcome of GBM patients.

We previously showed a strong correlation between Id-1 expression and the invasive and metastatic behavior of breast cancer cells.”

“Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells… CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells…  Moreover, reducing Id-1 expression with cannabinoids could also provide a therapeutic strategy for the treatment of additional aggressive cancers because Id-1 expression was found to be up-regulated during the progression of almost all types…”  http://mct.aacrjournals.org/content/6/11/2921.long

“In this report, we show that Id-1 is a key regulator of brain tumor cell invasiveness and neurosphere growth, and that Id-1 expression is specifically up-regulated in tissues from patients with high-grade gliomas. Importantly, we demonstrate that targeting Id-1 expression using either genetic approaches or the non-toxic cannabinoid, cannabidiol (CBD), leads to a significant reduction in the invasion of both GBM cell lines and patient-derived primary GBM cultures. CBD also significantly inhibits GBM dispersal ex vivo, and reduces tumor growth and Id-1 expression in vivo.

Consistent with the breast cancer study, we found that the non-psychoactive cannabinoid CBD significantly down-regulated Id-1 expression in serum-derived and primary GBM cells. As expected, we observed robust inhibition of glioma cell invasiveness.

In conclusion, our results establish Id-1 as a key regulator of both invasion and stemness in GBM cells and demonstrate that the non-toxic cannabinoid compound CBD down-regulates Id-1 expression and tumor aggressiveness in culture and in vivo.

The data also shed light on some of the key pathways that control GBM cell dispersal and progression. A greater understanding of these pathways may lead to more effective therapies for cancer patients including the additional refinement of cannabinoid analogs targeting Id-1.

We expect our efforts to ultimately translate to the development of future clinical trials with nontoxic compounds that target the expression of Id-1, a master regulator of GBM aggressiveness.

With its lack of systemic toxicity and psychoactivity, CBD is an ideal candidate agent in this regard and may prove useful in combination with front-line agents for the treatment of patients with aggressive and high-grade GBM tumors.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594064/

“McAllister Lab… Cannabidiol inhibits tumor (glioblastoma) progression in mouse models of brain cancer. Mice bearing human brain tumors derived from glioblastoma were treated with the naturally occurring cannabinoid, cannabidiol (CBD).”  http://www.cpmcri-currents.org/our-people/discovery-investigators/mcallister-lab

“New Study Finds Cannabis Compound Could Have Even Greater Reach in Inhibiting Aggressive Cancer than Previously Thought. Researchers at California Pacific Medical Center Research Institute (CPMCRI, a Sutter Health affiliate) have found that a compound in cannabis previously shown to decrease metastatic breast cancer now shows promise in stopping aggressive brain cancer as well. The findings are particularly important given the safety of the cannabis compound and the fact that patients with advanced brain cancer have few options for treatment.”  http://www.cpmc.org/about/press/news2012/cannabis-brain.html

http://www.thctotalhealthcare.com/category/brain-cancer/

Glioblastoma progression in mouse models of brain cancer, after treatment with CBD

A novel hemp seed meal protein hydrolysate reduces oxidative stress factors in spontaneously hypertensive rats.

Logo of nutrients

“This report shows the antioxidant effects of a hemp seed meal protein hydrolysate (HMH) in spontaneously hypertensive rats (SHR)…

The results suggest that HMH contained antioxidant peptides that reduced the rate of lipid peroxidation in SHRs with enhanced antioxidant enzyme levels and total antioxidant capacity.”

http://www.ncbi.nlm.nih.gov/pubmed/25493943

“Cannabis sativa L., also commonly called industrial hemp seed, is historically an important source of food, fibre, dietary oil and medicine; the seed contains about 30% oil and 25% protein…

Proteins from both plant and animal sources, including those of hemp seed, have been isolated and recognized as essential sources of bioactive peptides capable of exerting various in vitro and in vivo activities, such as antioxidant, antihypertensive, antimicrobial, opioid, antithrombotic, hypocholesterolemic, appetite-reducing, mineral-binding, immunomodulatory and cytomodulatory…

HMH may serve as an important ingredient to formulate antioxidant diets with potential therapeutic effects.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276990/

http://www.thctotalhealthcare.com/category/hypertension-high-blood-pressure/

The cannabinoid CB₂ receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain.

European Neuropsychopharmacology Home

“The widespread plant volatile beta-caryophyllene (BCP) was recently identified as a natural selective agonist of the peripherally expressedcannabinoid receptor 2 (CB₂).

…the natural plant product BCP may be highly effective in the treatment of long lasting, debilitating pain states. Our results have important implications for the role of dietary factors in the development and modulation of chronic pain conditions.

Cannabis preparations, which have been used since thousands of years for the treatment of pain have recently come again into the focus as potential therapeutics for inflammatory and neuropathic pain conditions. Currently, cannabis extracts and synthetic preparations of the psychoactive cannabis compound Δ9-tetrahydrocannabinol (THC) have been approved in many countries for clinical pain management at doses and formulations that show on only minor central side effects…

A natural selective agonist for CB2 receptors is the plant volatile BCP, which represents a dietary phytocannabinoid. BCP is found in large amounts in the essential oils of many common spices and food plants… Several health effects have been attributed to BCP or medicinal plants containing BCP, including anti-inflammatory, local anesthetic, anti-carcinogenic, anti-fibrotic and anxiolytic-like activity.

In the present study, we investigated the analgesic effects of BCP in formalin-induced inflammation model and in a model of neuropathic pain, which involves the partial ligation of the sciatic nerve… BCP is the first natural CB2 receptor agonist, which could orally reduce inflammatory responses in different animal models of pain.

Thus, it is likely that BCP belongs to a group of common plant natural products with major potential impact on human health.

The oral intake of this dietary cannabinoid with vegetable food could be advantageous in the daily routine clinical practice over synthetic cannabinoid agonists.”

http://www.europeanneuropsychopharmacology.com/article/S0924-977X(13)00302-7/fulltext

http://www.thctotalhealthcare.com/category/neuropathic-pain/