Author Archives: David Worrell

Comparison of outcome expectancies for synthetic cannabinoids and botanical marijuana.

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“Although initially developed for medical purposes, synthetic cannabinoids have also been consumed for recreational purposes.

To evaluate whether agreement with positive and negative outcome expectancies differed for synthetic cannabinoids versus botanical marijuana, and assess reported reasons for using synthetic cannabinoids.

A significant interaction revealed that participants who had used both synthetic cannabinoids and botanical marijuana indicated lower agreement with positive expectancies for synthetic cannabinoids, and higher agreement with positive expectancies for botanical marijuana, than did those participants who used only botanical marijuana.

There was no interaction between type of drug and use history on agreement with negative expectancies, and participants agreed more strongly with negative outcome expectancies for synthetic cannabinoids than for botanical marijuana whether they had used one or both types of these drugs.

The most frequently provided reasons for using synthetic cannabinoids included availability, perceived legality, cost, curiosity, and social interaction.

Given growing public acceptance of recreational and medical marijuana, coupled with negative perceptions and increasing regulation of synthetic cannabinoid compounds, botanical marijuana is likely to remain more available and more popular than synthetic cannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/26910181

The endogenous cannabinoid system protects against colonic inflammation

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“Excessive inflammatory responses can emerge as a potential danger for organisms’ health.

Our results indicate that the endogenous cannabinoid system represents a promising therapeutic target for the treatment of intestinal disease conditions characterized by excessive inflammatory responses.

The major active constituent of the plant Cannabis sativa (marijuana), Δ9-tetrahydrocannabinol, and a variety of natural and synthetic cannabinoids have been shown to possess antinociceptive and anti-inflammatory activities.

For millennia, Cannabis preparations have been used in folk medicine for the treatment of a wide variety of disorders, including those affecting the gastrointestinal tract. A century ago, extracts of Cannabis were used in the US to treat gastrointestinal pain of different origins, gastroenteritis, and diarrhea. There are also anecdotal reports suggesting that marijuana may be effective in alleviating symptoms of Crohn disease.

In conclusion, this study shows that the endogenous cannabinoid system is physiologically involved in the protection against excessive inflammation in the colon, both by dampening smooth muscular irritation caused by inflammation and by controlling cellular pathways leading to inflammatory responses.

These results strongly suggest that modulation of the physiological activity of the endogenous cannabinoid system during colonic inflammation might be a promising therapeutic tool for the treatment of several diseases characterized by inflammation of the gastrointestinal tract.”

https://www.jci.org/articles/view/19465

“A mouse study demonstrated that endogenous cannabinoid system signaling is likely to provide intrinsic protection against colonic inflammation. As a result, a hypothesis that phytocannabinoids and endocannabinoids may be useful in the risk reduction and treatment of colorectal cancer has been developed.” http://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq#section/_7

Driving the need to feed: Insight into the collaborative interaction between ghrelin and endocannabinoid systems in modulating brain reward systems.

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“Independent stimulation of either the ghrelin or endocannabinoid system promotes food intake and increases adiposity. Given the similar distribution of their receptors in feeding associated brain regions and organs involved in metabolism, it is not surprising that evidence of their interaction and its importance in modulating energy balance has emerged. This review documents the relationship between ghrelin and endocannabinoid systems within the periphery and hypothalamus (HYP) before presenting evidence suggesting that these two systems likewise work collaboratively within the ventral tegmental area (VTA) to modulate non-homeostatic feeding. Mechanisms, consistent with current evidence and local infrastructure within the VTA, will be proposed.”

http://www.ncbi.nlm.nih.gov/pubmed/27136126

Getting into the weed: the role of the endocannabinoid system in the brain-gut axis.

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“The actions of cannabis are mediated by receptors that are part of an endogenous cannabinoid system.

The endocannabinoid system (ECS) consists of the naturally occurring ligands N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG), their biosynthetic and degradative enzymes, and the cannabinoid receptors CB1 and CB2.

The ECS is a widely distributed transmitter system that controls gut functions peripherally and centrally. It is an important physiologic regulator of gastrointestinal motility.

Polymorphisms in the gene encoding CB1 (CNR1) have been associated with some forms of irritable bowel syndrome. The ECS is involved in the control of nausea and vomiting and visceral sensation. The homeostatic role of the ECS also extends to the control of intestinal inflammation.

We review the mechanisms by which the ECS links stress and visceral pain. CB1 in sensory ganglia controls visceral sensation, and transcription of CNR1 is modified through epigenetic processes under conditions of chronic stress. These processes might link stress with abdominal pain.

The ECS is also involved centrally in the manifestation of stress, and endocannabinoid signaling reduces the activity of hypothalamic-pituitary-adrenal pathways via actions in specific brain regions-notably the prefrontal cortex, amygdala, and hypothalamus.

Agents that modulate the ECS are in early stages of development for treatment of gastrointestinal diseases. Increasing our understanding of the ECS will greatly advance our knowledge of interactions between the brain and gut and could lead to new treatments for gastrointestinal disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/27133395

New review sheds light on cannabinoids anticancer mechanisms

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cannabinoids, cancer

“The palliative effects of cannabinoids on cancer-related symptoms are well established.

In fact, many drugs comprised of delta-9-tetrahydrocannabinol (THC) or its synthetic analogues are currently approved in Canada for use in the management of chemotherapy-induced nausea and vomiting, pain relief, and appetite stimulation.

While this may provide adequate treatment to the symptoms endured by cancer patients, what if cannabis can all together treat and cure cancer?

Latest discoveries on cannabinoids and their anticancer properties focus on their molecular mechanisms of action and have been discussed in a recently published review article in Current Oncology, a peer-reviewed journal (Velasco, Sanchez, & Guzman, 2016).

It is important to begin by understanding that our body possesses an endogenous cannabinoid system.”

https://news.liftcannabis.ca/2016/04/21/new-review-sheds-light-cannabinoids-anticancer-mechanisms/

“Anticancer mechanisms of cannabinoids”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791144/

Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent

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“Cannabinoid compounds, both nonspecific as well as agonists selective for either cannabinoid receptor 1 (CB1) or cannabinoid receptor 2 (CB2), have been shown to modulate the tumor microenvironment by inducing apoptosis in tumor cells in several model systems.

The mechanism of this modulation remains only partially delineated, and activity induced via the CB1 and CB2 receptors may be distinct despite significant sequence homology and structural similarity of ligands.

The results of this work characterize the actions of a CB2-selective agonist on breast cancer cells in a syngeneic murine model representing how a clinical presentation of cancer progression and metastasis may be significantly modulated by a G-protein-coupled receptor.”

https://www.dovepress.com/modulation-of-breast-cancer-cell-viability-by-a-cannabinoid-receptor-2-peer-reviewed-article-BCTT

Neuroscientists discover previously unknown function of cannabinoid receptor

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Neuroscientists discover previously unknown function of cannabinoid receptor

“Previously Unknown Function of a Cannabinoid Receptor Identified.  Study could improve our insights into brain diseases.” http://neurosciencenews.com/cb2-cannabinoid-receptor-hippocampus-4147/

“In the brain, there is a delicate interplay of signaling substances and cellular activity. Scientists have now identified another key player within this ensemble. In a laboratory study they found that the ‘cannabinoid type 2 receptor’ influences information processing inside the hippocampus. The research results might help advance our understanding of schizophrenia and Alzheimer’s, say the authors.”  https://www.sciencedaily.com/releases/2016/05/160502111228.htm

“The cannabinoid type 2 receptor – also called “CB2 receptor” – is a special membrane protein. Its function is to receive chemical signals that control cellular activity. “Until now, this receptor was considered part of the immune system without function in nerve cells. However, our study shows that it also plays an important role in the signal processing of the brain,” explains Professor Dietmar Schmitz, Speaker for the DZNE-Site Berlin and Director of the Neuroscience Research Center of the Charité (NWFZ/NeuroCure).”  https://scienceblog.com/483935/neuroscientists-discover-previously-unknown-function-cannabinoid-receptor/

 

Cannabinoid Type 2 Receptors Mediate a Cell Type-Specific Plasticity in the Hippocampus

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“Endocannabinoids (eCBs) exert major control over neuronal activity by activating cannabinoid receptors (CBRs).

The functionality of the eCB system is primarily ascribed to the well-documented retrograde activation of presynaptic CB1Rs.

We find that action potential-driven eCB release leads to a long-lasting membrane potential hyperpolarization in hippocampal principal cells that is independent of CB1Rs.

The hyperpolarization, which is specific to CA3 and CA2 pyramidal cells (PCs), depends on the activation of neuronal CB2Rs, as shown by a combined pharmacogenetic and immunohistochemical approach.

Upon activation, they modulate the activity of the sodium-bicarbonate co-transporter, leading to a hyperpolarization of the neuron.

CB2R activation occurred in a purely self-regulatory manner, robustly altered the input/output function of CA3 PCs, and modulated gamma oscillations in vivo.

To conclude, we describe a cell type-specific plasticity mechanism in the hippocampus that provides evidence for the neuronal expression of CB2Rs and emphasizes their importance in basic neuronal transmission.”

http://www.cell.com/neuron/abstract/S0896-6273(16)30025-3

Cannabidiol attenuates catalepsy induced by distinct pharmacological mechanisms via 5-HT1A receptor activation in mice.

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“Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa plant that produces antipsychotic effects in rodents and humans.

It also reverses L-dopa-induced psychotic symptoms and improves motor function in Parkinson’s patients. This latter effect raised the possibility that CBD could have beneficial effects on motor related striatal disorders.

To investigate this possibility we evaluated if CBD would prevent catalepsy induced by drugs with distinct pharmacological mechanisms.

These findings indicate that CBD can attenuate catalepsy caused by different mechanisms (D2 blockade, NOS inhibition and CB1 agonism) via 5-HT1A receptor activation, suggesting that it could be useful in the treatment of striatal disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/23791616

Cannabidiol attenuates haloperidol-induced catalepsy and c-Fos protein expression in the dorsolateral striatum via 5-HT1A receptors in mice.

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“Cannabidiol (CBD) is a major non-psychoactive compound from Cannabis sativa plant.

Given that CBD reduces psychotic symptoms without inducing extrapyramidal motor side-effects in animal models and schizophrenia patients, it has been proposed to act as an atypical antipsychotic.

In addition, CBD reduced catalepsy induced by drugs with distinct pharmacological mechanisms, including the typical antipsychotic haloperidol.

Altogether, these results suggest that CBD acts in the dorsal striatum to improve haloperidol-induced catalepsy via postsynaptic 5-HT1A receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27131780