Author Archives: David Worrell

GPR55 promotes migration and adhesion of colon cancer cells indicating a role in metastasis.

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“Tumor cell migration and adhesion constitute essential features of metastasis. G protein-coupled receptor 55 (GPR55), a lysophospholipid receptor, has been shown to play an important role in carcinogenesis. Here, we investigated the involvement of GPR55 in migration and metastasis of colon cancer cells.

GPR55 antagonist CID16020046, cannabidiol, a putative GPR55 antagonist, and GPR55 siRNA were used to block GPR55 activity in HCT116 colon cancer cells.

In a mouse model of metastasis, the arrest of HCT116 cancer cells in the liver was reduced after treatment with CID16020046 or cannabidiol.

CONCLUSIONS AND IMPLICATIONS:

GPR55 is involved in the migratory behavior of colon carcinoma cells and may serve as a pharmacological target for the prevention of metastasis.”

http://www.ncbi.nlm.nih.gov/pubmed/26436760

“Pharmacological Characterization of GPR55, A Putative Cannabinoid Receptor”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874616/ 

Polypharmacology Shakes Hands with Complex Aetiopathology.

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“Chronic diseases are due to deviations of fundamental physiological systems, with different pathologies being characterised by similar malfunctioning biological networks.

The ensuing compensatory mechanisms may weaken the body’s dynamic ability to respond to further insults and reduce the efficacy of conventional single target treatments.

The multitarget, systemic, and prohomeostatic actions emerging for plant cannabinoids exemplify what might be needed for future medicines.

Indeed, two combined cannabis extracts were approved as a single medicine (Sativex®), while pure cannabidiol, a multitarget cannabinoid, is emerging as a treatment for paediatric drug-resistant epilepsy.

Using emerging cannabinoid medicines as an example, we revisit the concept of polypharmacology and describe a new empirical model, the ‘therapeutic handshake’, to predict efficacy/safety of compound combinations of either natural or synthetic origin.”

http://www.ncbi.nlm.nih.gov/pubmed/26434643

A comparison of cannabidiolic acid with other treatments for anticipatory nausea using a rat model of contextually elicited conditioned gaping.

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“The effectiveness of cannabidiolic acid (CBDA) was compared with other potential treatments for anticipatory nausea (AN), using a rat model of contextually elicited conditioned gaping reactions.

The potential of ondansetron (OND), Δ(9)-tetrahydrocannabinol (THC), chlordiazepoxide (CDP), CBDA, and co-administration of CBDA and tetrahydrocannabinolic acid (THCA) to reduce AN and modify locomotor activity was evaluated…

CBDA has therapeutic potential as a highly potent and selective treatment for AN without psychoactive or locomotor effects.”

http://www.ncbi.nlm.nih.gov/pubmed/24595502

The phytocannabinoid, Δ⁹-tetrahydrocannabivarin, can act through 5-HT₁A receptors to produce antipsychotic effects.

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“This study aimed to address the questions of whether Δ(9)-tetrahydrocannabivarin (THCV) can (i) enhance activation of 5-HT1 A receptors in vitro and (ii) induce any apparent 5-HT₁A receptor-mediated antipsychotic effects in vivo…

Our findings suggest that THCV can enhance 5-HT₁A receptor activation, and that some of its apparent antipsychotic effects may depend on this enhancement.

We conclude that THCV has therapeutic potential for ameliorating some of the negative, cognitive and positive symptoms of schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/25363799

Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation.

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“The cannabis plant is a natural source of at least 70 compounds known collectively as phytocannabinoids, and there is convincing evidence that one of these, cannabidiol (CBD), can suppress nausea and vomiting.

To evaluate the ability of cannabidiolic acid (CBDA) to reduce nausea and vomiting and enhance 5-HT(1A) receptor activation in animal models…

Compared with cannabidiol, CBDA displays significantly greater potency at inhibiting vomiting in shrews and nausea in rats, and at enhancing 5-HT(1A) receptor activation, an action that accounts for its ability to attenuate conditioned gaping in rats.

Consequently, CBDA shows promise as a treatment for nausea and vomiting, including anticipatory nausea for which no specific therapy is currently available.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596650/

Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a phytocannabinoid with therapeutic potential for anticipatory nausea.

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“Anticipatory nausea (AN) is a poorly controlled side effect experienced by chemotherapy patients. Currently, pharmacotherapy is restricted to benzodiazepine anxiolytics, which have limited efficacy, have significant sedative effects and induce dependency.

The non-psychoactive phytocannabinoid, cannabidiolic acid (CBDA), has shown considerable efficacy in pre-clinical AN models…:

This study aims to assess the tolerability of CBDA in locomotor activity, motor coordination and muscular strength tests, and additionally for ability to modulate feeding behaviours…

CBDA is very well tolerated and devoid of the sedative side effect profile of benzodiazepines, justifying its clinical investigation as a novel AN treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/26439367

A runner’s high depends on cannabinoid receptors in mice.

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“Exercise is rewarding, and long-distance runners have described a runner’s high as a sudden pleasant feeling of euphoria, anxiolysis, sedation, and analgesia.

A popular belief has been that endogenous endorphins mediate these beneficial effects. However, running exercise increases blood levels of both β-endorphin (an opioid) and anandamide (an endocannabinoid).

Using a combination of pharmacologic, molecular genetic, and behavioral studies in mice, we demonstrate that cannabinoid receptors mediate acute anxiolysis and analgesia after running.

We show that anxiolysis depends on intact cannabinoid receptor 1 (CB1) receptors on forebrain GABAergic neurons and pain reduction on activation of peripheral CB1 and CB2 receptors.

We thus demonstrate that the endocannabinoid system is crucial for two main aspects of a runner’s high. Sedation, in contrast, was not influenced by cannabinoid or opioid receptor blockage, and euphoria cannot be studied in mouse models.”

http://www.ncbi.nlm.nih.gov/pubmed/26438875

“Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the ‘runner’s high’”  http://jeb.biologists.org/content/215/8/1331.long

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

Control of Breast Cancer by the Endocannabinoid System

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“Activation of the endocannabinoid system through CB1, CB2 and additional receptor subtypes results in the inhibition of a broad range of cancers.

The endocannabinoid system was discovered through research focusing on the classical cannabinoid agonist, ?9-tetrahydrocannabinol (?9-THC), and other synthetic cannabinoids.

This proposal will focus on the potential treatment of human breast cancer using cannabinoids as selective antitumor agents.

We have found that cannabinoid compounds activating CB1, CB2 and additional receptor subtypes can inhibit breast cancer cell proliferation and invasiveness and we have discovered down-stream targets that potentially link cannabinoid receptor stimulation to these effects.

Furthermore, our preliminary studies provide evidence that endogenous endocannabinoid tone tonically inhibits metastatic breast cancer cell proliferation and invasiveness through the activation of cannabinoid receptors.

Our preliminary data also suggests that cannabinoid compounds possess selective efficacy, having less adverse effects on the normal human cells from which the breast cancers arise.

Since toxicity in healthy tissue limits the efficacy of current cancer treatments, discovering the mechanism behind selective efficacy in human tissues is of clinical importance.

Cannabinoids can inhibit multiple types of tumor growth in vivo…

Testing the hypotheses outlined in the application may lead to the development of effective inhibitors of breast, and perhaps other, cancers.

This research may also elucidate novel mechanisms related to the anticancer activity of cannabinoids, and will serve to develop the career of the candidate in the field of cancer biology.”

 http://grantome.com/grant/NIH/K01-CA111723-01A2

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

Targeting the endocannabinoid system to treat anxiety-related disorders.

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“The endocannabinoid system plays an important role in the control of emotions, and its dysregulation has been implicated in several psychiatric disorders.

The most common self-reported reason for using cannabis is rooted in its ability to reduce feelings of stress, tension, and anxiety.

Nevertheless, there are only few studies in controlled clinical settings that confirm that administration of cannabinoids can benefit patients with a post-traumatic stress disorder (PTSD).

There are considerable encouraging preclinical data to suggest that endocannabinoid-targeted therapeutics for anxiety disorders should continue.

In this review, we will describe data supporting a role for the endocannabinoid system in preventing and treating anxiety-like behavior in animal models and PTSD patients.

Cannabinoids have shown beneficial outcomes in rat and mouse models of anxiety and PTSD, but they also may have untoward effects that discourage their chronic usage, including anxiogenic effects.

Hence, clinical and preclinical research on the endocannabinoid system should further study the effects of cannabinoids on anxiety and help determine whether the benefits of using exogenous cannabinoids outweigh the risks.

In general, this review suggests that targeting the endocannabinoid system represents an attractive and novel approach to the treatment of anxiety-related disorders and, in particular, PTSD.”

http://www.ncbi.nlm.nih.gov/pubmed/26426887