Cannabidiolic acid-mediated selective down-regulation of c-fos in highly aggressive breast cancer MDA-MB-231 cells: possible involvement of its down-regulation in the abrogation of aggressiveness.

 

“The physiological activities of cannabidiolic acid (CBDA), a component of fiber-type cannabis plants, have been demonstrated and include its function as a protector against external invasion by inducing cannabinoid-mediated necrosis.

The biological activities of CBDA have been attracting increasing attention.

We previously identified CBDA as an inhibitor of the migration of MDA-MB-231 cells, a widely used human breast cancer cell line in cancer biology, due to its highly aggressive nature.

The chemical inhibition and down-regulation of cyclooxygenase-2 (COX-2), the expression of which has been detected in ~40 % of human invasive breast cancers, are suggested to be involved in the CBDA-mediated abrogation of cell migration.

In the present study, we describe a possible mechanism by which CBDA abrogates the expression of COX-2 via the selective down-regulation of c-fos, one component of the activator protein-1 (AP-1) dimer complex, a transcription factor for the positive regulation of the COX-2 gene.”

http://www.ncbi.nlm.nih.gov/pubmed/27530354

Modulation of Gut-Specific Mechanisms by Chronic Δ9-Tetrahydrocannabinol Administration in Male Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Systems Biology Analysis

 

“The major psychoactive cannabinoid in marijuana, Δ9-tetrahydrocannabinol (THC), exerts unique effects on the progression of simian immunodeficiency virus (SIV) infection.

Previous studies from our laboratory have shown that chronic THC administration ameliorates SIV disease progression and significantly reduces the morbidity and mortality of male SIV-infected macaques.

Our studies have demonstrated that chronic Δ9-tetrahydrocannabinol (THC) administration results in a generalized attenuation of viral load and tissue inflammation in simian immunodeficiency virus (SIV)-infected male rhesus macaques.

Gut-associated lymphoid tissue is an important site for HIV replication and inflammation that can impact disease progression.

Our results indicate that chronic THC administration modulated duodenal T cell populations, favored a pro-Th2 cytokine balance, and decreased intestinal apoptosis. These findings reveal novel mechanisms that may potentially contribute to cannabinoid-mediated disease modulation.

In summary, using a systems biology approach to understanding the impact of chronic cannabinoid treatment on gut-associated immunopathology, we identified relevant mechanisms that can potentially modulate disease progression.

Our results suggest that gut immunomodulation through changes in gene expression, cytokine profiles, and immune cell populations could potentially contribute to chronic THC modulation of SIV disease progression. Moreover, they reveal novel mechanisms that may potentially contribute to decreased morbidity and mortality.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046212/

Sex-dependent effects of cannabis-induced analgesia.

“Preclinical studies demonstrate that cannabinoid-mediated antinociceptive effects vary according to sex; it is unknown if these findings extend to humans.

These results indicate that in cannabis smokers, men exhibit greater cannabis-induced analgesia relative to women.

As such, sex-dependent differences in cannabis’s analgesic effects are an important consideration that warrants further investigation when considering the potential therapeutic effects of cannabinoids for pain relief.”

http://www.ncbi.nlm.nih.gov/pubmed/27522535

[Cannabinoids in multiple sclerosis — therapeutically reasonable?].

“For centuries extracts from the Cannabis sativa plant have been used for recreational use and as remedies.

Anecdotal reports from patients with multiple sclerosis (MS) experiencing relief of their spasticity and pain after smoking marihuana have prompted discussions about a potential therapeutic application of cannabis preparations in MS.

Only recently the first large, multicenter, double-blind, placebo controlled study was conducted evaluating the use of cannabinoids for treatment of spasticity and other symptoms related to MS.

Based on this trial and previous uncontrolled observations together with insights from basic research and animal experiments there is reasonable evidence for the therapeutical employment of cannabinoids in the treatment of MS related symptoms.

Furthermore, data are arising that cannabinoids have immunomodulatory and neuroprotective properties.

This article summarizes the present knowledge of clinical and experimental research regarding the therapeutic potential of cannabinoids for the treatment of MS.”

http://www.ncbi.nlm.nih.gov/pubmed/16052440

Decreased depression in marijuana users.

“Over 4400 adult internet users completed The Center for Epidemiologic Studies Depression scale and measures of marijuana use.

We employed an internet survey in an effort to recruit the most depressed and marijuana-involved participants, including those who might prove unwilling to travel to the laboratory or discuss drug use on the phone or in person.

We compared those who consumed marijuana daily, once a week or less, or never in their lives.

Despite comparable ranges of scores on all depression subscales, those who used once per week or less had less depressed mood, more positive affect, and fewer somatic complaints than non-users.

Daily users reported less depressed mood and more positive affect than non-users.

These data suggest that adults apparently do not increase their risk for depression by using marijuana.”

http://www.ncbi.nlm.nih.gov/pubmed/15964704

Opposite Cannabis-Cognition Associations in Psychotic Patients Depending on Family History.

“The objective of this study is to investigate cognitive performance in a first-episode psychosis sample, when stratifying the interaction by cannabis use and familial or non-familial psychosis.

We found that cannabis use was associated with worse working memory, regardless of family history. However, cannabis use was clearly associated with worse cognitive performance in patients with no family history of psychosis, in cognitive domains including verbal memory, executive function and global cognitive index, whereas cannabis users with a family history of psychosis performed better in these domains.

The main finding of the study is that there is an interaction between cannabis use and a family history of psychosis in the areas of verbal memory, executive function and global cognition: that is, cannabis use is associated with a better performance in patients with a family history of psychosis and a worse performance in those with no family history of psychosis.

In order to confirm this hypothesis, future research should explore the actual expression of the endocannabinoid system in patients with and without a family history of psychosis.”

http://www.ncbi.nlm.nih.gov/pubmed/27513670

Medical Marijuana-Opportunities and Challenges

“Over the recent years, public and political opinions have demonstrated increasing support for the legalization of medical marijuana.

To date, 24 states as well as the District of Columbia have legalized cannabis for medical use, 4 states have legalized the recreational use of Marijuana.

Marijuana is derived from the hemp plant Cannabis sativa. Δ-9-tetrahydrocannabinol (THC) is the major psychoactive constituent of cannabis, while cannabidiol (CBD) is the major non-psychoactive constituent. THC is a partial agonist at CB1 and CB2 receptors, while CBD at high levels is an antagonist CB1 and CB2.

CB1 is abundantly expressed in the brain, and CB2 is expressed on immune cells (expression of CB2 on neurons remains controversial). The brain also produces endogenous cannabis-like substances (endocannabinoids) that bind and activate the CB1/CB2 receptors.

There is tremendous interest in harnessing the therapeutic potential of plant-derived and synthetic cannabinoids.

This Editorial provides an overview of diseases that may be treated by cannabinoids.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948749/

Effective treatment of spasticity using dronabinol in pediatric palliative care.

“Cannabis extracts have a wide therapeutic potential but in many countries they have not been approved for treatment in children so far.

We conducted an open, uncontrolled, retrospective study on the administration of dronabinol to determine the value, efficacy, and safety of cannabis-based medicines in the treatment of refractory spasticity in pediatric palliative care.

Sixteen children, adolescents and young adults having complex neurological conditions with spasticity (aged 1.3-26.6 years, median 12.7 years) were treated with dronabinol by our specialized pediatric palliative care team between 01.12.2010 and 30.04.2015 in a home-care setting. Therapeutic efficacy and side effects were closely monitored.

RESULTS:

Drops of the 2.5% oily tetrahydrocannabinol solution (dronabinol) were administered. A promising therapeutic effect was seen, mostly due to abolishment or marked improvement of severe, treatment resistant spasticity (n = 12). In two cases the effect could not be determined, two patients did not benefit. The median duration of treatment was 181 days (range 23-1429 days). Dosages to obtain a therapeutic effect varied from 0.08 to 1.0 mg/kg/d with a median of 0.33 mg/kg/d in patients with a documented therapeutic effect. When administered as an escalating dosage scheme, side effects were rare and only consisted in vomiting and restlessness (one patient each).

No serious and enduring side effects occurred even in young children and/or over a longer period of time.

CONCLUSIONS:

In the majority of pediatric palliative patients the treatment with dronabinol showed promising effects in treatment resistant spasticity.”

http://www.ncbi.nlm.nih.gov/pubmed/27506815

A new antipsychotic mechanism of action for cannabidiol

Totally dope! – A new antipsychotic mechanism of action for cannabidiol, by Anand Gururajan

“The pharmacological strategy for the treatment of schizophrenia has not changed in the six decades since chlorpromazine was introduced in 1952. Although several newer agents have recently gained approval, the mechanism of action of antipsychotics is still largely based on normalising dopaminergic neurotransmission which does not adequately address the symptomatology of a very complex disorder. Moreover, they cause side effects such as extrapyramidal motor symptoms and metabolic syndrome which can worsen the patient condition.

In this regard, preclinical and clinical studies since the ’90s have demonstrated the antipsychotic potential of cannabidiol (CBD), a derivative of the cannabis sativa plant which does not have the adverse psychoactive properties of tetrahydrocannabinol.

In particular, CBD has been shown to be effective in attenuating the positive symptoms of schizophrenia with a negligible side-effect profile.

Accumulating evidence implicates dysfunction of the mammalian target of rapamycin (mTOR) signaling cascade in the pathophysiology of schizophrenia. Thus, in a recent paper, Renard et al. (2016) used the amphetamine (AMPH)-sensitisation protocol in rats to investigate whether the antipsychotic effects of CBD were mediated by its effects on the mTOR cascade. Specifically, they focused on the nucleus accumbens shell (NASh) which has been implicated as a therapeutically relevant ‘hot-spot’ for antipsychotic action and is one of the brain regions targeted by CBD.

Thus, together with the fact that CBD alone had no behavioural effects, the behavioural findings reinforce the potential utility of this cannabinoid as an antipsychotic for the treatment of the positive symptoms of schizophrenia.”

http://medicalxpress.com/news/2016-08-antipsychotic-mechanism-action-cannabidiol.html