An ultra-low dose of tetrahydrocannabinol provides cardioprotection.

“Tetrahydrocannabinol (THC), the major psychoactive component of marijuana, is a cannabinoid agonist that exerts its effects by activating at least two specific receptors (CB1 and CB2) that belong to the seven transmembrane G-protein coupled receptor (GPCR) family.

Both CB1 and CB2 mRNA and proteins are present in the heart.

THC treatment was beneficial against hypoxia in neonatal cardiomyocytes in vitro.

We also observed a neuroprotective effect of an ultra low dose of THC when applied to mice before brain insults.

The present study was aimed to test and characterize the cardioprotective effects of a very low dose of THC…

All protocols of THC administration were found to be beneficial.

CONCLUSION:

A single ultra low dose of THC before ischemia is a safe and effective treatment that reduces myocardial ischemic damage.”

http://www.ncbi.nlm.nih.gov/pubmed/23537701

Effects of cannabinoids and their receptors on viral infections.

“Cannabinoids, the active ingredient in marijuana, and their derivatives have received remarkable attention in the last two decades because they can affect tumor growth and metastasis.

There is a large body of evidence from in vivo and in vitro models showing that cannabinoids and their receptors influence the immune system, viral pathogenesis, and viral replication.

The present study reviews current insights into the role of cannabinoids and their receptors on viral infections.

The results reported here indicate that cannabinoids and their receptors have different sequels for viral infection.

Although activation or inhibition of cannabinoid receptors in the majority of viral infections are proper targets for development of safe and effective treatments, caution is required before using pharmaceutical cannabinoids as a treatment agent for patients with viral infections.”

[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

Neuroprotective effect of (-)Delta9-tetrahydrocannabinol and cannabidiol in N-methyl-D-aspartate-induced retinal neurotoxicity: involvement of peroxynitrite.

“In glaucoma, the increased release of glutamate is the major cause of retinal ganglion cell death. Cannabinoids have been demonstrated to protect neuron cultures from glutamate-induced death.

In this study, we test the hypothesis that glutamate causes apoptosis of retinal neurons via the excessive formation of peroxynitrite, and that the neuroprotective effect of the psychotropic Delta9-tetrahydroxycannabinol (THC) or nonpsychotropic cannabidiol (CBD) is via the attenuation of this formation.

These results suggest the potential use of CBD as a novel topical therapy for the treatment of glaucoma.

“Cannabinoid components of marijuana, such as (−)Δ9-tetrahydrocannabinol (THC), or the synthetic cannabinoid WIN55,212-2, have been shown to prevent glutamate- or NMDA-induced neurotoxicity in isolated neurons or in the brain via activation of the cannabinoid receptor subtype CB1.

…the nonpsychotropic component of marijuana, cannabidiol (CBD), and the synthetic nonpsychotropic cannabinoid, HU-211, as well as THC have been demonstrated as potent antioxidants and/or NMDA receptor antagonists that protect neuron cultures from glutamate-induced death or from oxidative stress.

… we demonstrated that THC and CBD are neuroprotective against NMDA-induced retinal injury and that their protective actions are in part because of an effect in reducing formation of lipid peroxides, nitrite/nitrate, and nitrotyrosine.

In addition to possessing neuroprotective or retinal neuroprotective activity as demonstrated here and elsewhere, cannabinoids such as THC, WIN55,212-2, endogenous cannabinoid 2-arachidonoylglycerol, as well as nonpsychotropic HU-211 have been demonstrated to induce dose-related reductions in intraocular pressure in human and in animal models.

 This suggests that cannabinoids may offer a multifaceted therapy for glaucoma.

In conclusion, our results indicate that lipid peroxidation and ONOO− formation play an important role in NMDA-induced retinal neurotoxicity and cell loss in the retina, and that THC and CBD, by reducing the formation of these compounds, are effective neuroprotectants.

The present studies could form the basis for the development of new topical therapies for the treatment of glaucoma.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892413/

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

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

Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome.

“There is a great need for safe and effective therapies for treatment of infantile spasms (IS) and Lennox-Gastaut syndrome (LGS). Based on anecdotal reports and limited experience in an open-label trial, cannabidiol (CBD) has received tremendous attention as a potential treatment for pediatric epilepsy, especially Dravet syndrome.

We sought to document the experiences of children with IS and/or LGS who have been treated with CBD-enriched cannabis preparations.

Perceived efficacy and tolerability were similar across etiologic subgroups.

Eighty-five percent of all parents reported a reduction in seizure frequency, and 14% reported complete seizure freedom.

Reported side effects were far less common during CBD exposure, with the exception of increased appetite (30%).

A high proportion of respondents reported improvement in sleep (53%), alertness (71%), and mood (63%) during CBD therapy… this study suggests a potential role for CBD in the treatment of refractory childhood epilepsy including IS and LGS…”

http://www.ncbi.nlm.nih.gov/pubmed/25935511

“Safety and side effects of cannabidiol, a Cannabis sativa constituent.”  http://www.ncbi.nlm.nih.gov/pubmed/22129319

“Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa…” http://www.ncbi.nlm.nih.gov/pubmed/19690824

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

Responsible and controlled use: Older cannabis users and harm reduction.

“Cannabis use is becoming more accepted in mainstream society. In this paper, we use Zinberg’s classic theoretical framework of drug, set, and setting to elucidate how older adult cannabis users managed health, social and legal risks in a context of normalized cannabis use…

Interviewees made harm reduction choices based on preferred cannabis derivatives and routes of administration, as well as why, when, where, and with whom to use. Most interviewees minimized cannabis-related harms so they could maintain social functioning in their everyday lives. Responsible and controlled use was described as moderation of quantity and frequency of cannabis used, using in appropriate settings, and respect for non-users. Users contributed to the normalization of cannabis use through normification.

Participants followed rituals or cultural practices, characterized by sanctions that helped define “normal” or “acceptable” cannabis use. Users contributed to cannabis normalization through their harm reduction methods.

These cultural practices may prove to be more effective than formal legal prohibitions in reducing cannabis-related harms.

Findings also suggest that users with access to a regulated market (medical cannabis dispensaries) were better equipped to practice harm reduction.

More research is needed on both cannabis culture and alternative routes of administration as harm reduction methods.”

http://www.ncbi.nlm.nih.gov/pubmed/25911027

Self-reported efficacy of cannabis and other complementary medicine modalities by Parkinson’s disease patients in colorado.

“Complementary and alternative medicine (CAM) is frequently used by Parkinson’s disease (PD) patients. We sought to provide information on CAM use and efficacy in PD patients in the Denver metro area with particular attention to cannabis use given its recent change in legal status.

Self-reported improvement related to the use of CAM was highest for massage, art therapy, music therapy, and cannabis.

While only 4.3% of our survey responders reported use of cannabis, it ranked among the most effective CAM therapies.

Conclusions. Overall, our cross-sectional study was notable for a high rate of CAM utilization amongst PD patients and high rates of self-reported efficacy across most CAM modalities.

Cannabis was rarely used in our population but users reported high efficacy, mainly for nonmotor symptoms.”

http://www.ncbi.nlm.nih.gov/pubmed/25821504

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363882/

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

Cannabinoids for the Treatment of Chronic Non-Cancer Pain: An Updated Systematic Review of Randomized Controlled Trials.

“An updated systematic review of randomized controlled trials examining cannabinoids in the treatment of chronic non-cancer pain was conducted according to PRISMA guidelines for systematic reviews reporting on health care outcomes.

Eleven trials published since our last review met inclusion criteria.

The quality of the trials was excellent.

Seven of the trials demonstrated a significant analgesic effect.

Several trials also demonstrated improvement in secondary outcomes (e.g., sleep, muscle stiffness and spasticity).

Adverse effects most frequently reported such as fatigue and dizziness were mild to moderate in severity and generally well tolerated.

This review adds further support that currently available cannabinoids are safe, modestly effective analgesics that provide a reasonable therapeutic option in the management of chronic non-cancer pain.”

http://www.ncbi.nlm.nih.gov/pubmed/25796592

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