THC Total Health Care

A comprehensive research archive dedicated to the science of cannabis

Mechanisms of action of cannabidiol in adoptively transferred experimental autoimmune encephalomyelitis.

Posted on September 5, 2017 by David Worrell

“Cannabidiol (CBD) is one of the most important compounds in Cannabis sativa, lacks psychotropic effects, and possesses a high number of therapeutic properties including the amelioration of experimental autoimmune encephalomyelitis (EAE). The aim of this study was to analyse the relative efficacy of CBD in adoptively transferred EAE (at-EAE), a model that allows better delineation of the effector phase of EAE. Preventive intraperitoneal treatment with CBD ameliorated the clinical signs of at-EAE. CBD markedly improved the clinical signs of at-EAE and reduced infiltration, demyelination and axonal damage. The CBD-mediated decrease in the viability of encephalitogenic cells involves ROS generation, apoptosis and a decrease in IL-6 production and may contribute to the therapeutic effect of this compound.” https://www.ncbi.nlm.nih.gov/pubmed/28867485 http://www.sciencedirect.com/science/article/pii/S0014488617302212]]>

Cannabinoid CB1 and CB2 Receptor Signaling and Bias.

Posted on September 2, 2017 by David Worrell

“An agonist that acts through a single receptor can activate numerous signaling pathways. Recent studies have suggested that different ligands can differentially activate these pathways by stabilizing a limited range of receptor conformations, which in turn preferentially drive different downstream signaling cascades. This concept, termed “biased signaling” represents an exciting therapeutic opportunity to target specific pathways that elicit only desired effects, while avoiding undesired effects mediated by different signaling cascades. The cannabinoid receptors CB₁ and CB₂ each activate multiple pathways, and evidence is emerging for bias within these pathways. This review will summarize the current evidence for biased signaling through cannabinoid receptor subtypes CB₁ and CB₂.” https://www.ncbi.nlm.nih.gov/pubmed/28861504

http://online.liebertpub.com/doi/10.1089/can.2016.0037

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Cannabinoids in Parkinson's Disease.

Posted on September 2, 2017 by David Worrell

“The endocannabinoid system plays a regulatory role in a number of physiological processes and has been found altered in different pathological conditions, including movement disorders. The interactions between cannabinoids and dopamine in the basal ganglia are remarkably complex and involve both the modulation of other neurotransmitters (γ-aminobutyric acid, glutamate, opioids, peptides) and the activation of different receptors subtypes (cannabinoid receptor type 1 and 2). In the last years, experimental studies contributed to enrich this scenario reporting interactions between cannabinoids and other receptor systems (transient receptor potential vanilloid type 1 cation channel, adenosine receptors, 5-hydroxytryptamine receptors). The improved knowledge, adding new interpretation on the biochemical interaction between cannabinoids and other signaling pathways, may contribute to develop new pharmacological strategies. A number of preclinical studies in different experimental Parkinson’s disease (PD) models demonstrated that modulating the cannabinoid system may be useful to treat some motor symptoms. Despite new cannabinoid-based medicines have been proposed for motor and nonmotor symptoms of PD, so far, results from clinical studies are controversial and inconclusive. Further clinical studies involving larger samples of patients, appropriate molecular targets, and specific clinical outcome measures are needed to clarify the effectiveness of cannabinoid-based therapies.” https://www.ncbi.nlm.nih.gov/pubmed/28861502

“Cannabis is a psychoactive compound widely used along history for recreational and therapeutic purposes. Although many open questions remain, cannabis-based therapies have become increasingly common raising considerable interest in politics as well as in general public for legalization of medical cannabis.” http://online.liebertpub.com/doi/10.1089/can.2017.0002

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Cannabinoids in Parkinson’s Disease.

Posted on September 2, 2017 by David Worrell

Mary Ann Liebert, Inc. publishers

In the last years, experimental studies contributed to enrich this scenario reporting interactions between cannabinoids and other receptor systems (transient receptor potential vanilloid type 1 cation channel, adenosine receptors, 5-hydroxytryptamine receptors). The improved knowledge, adding new interpretation on the biochemical interaction between cannabinoids and other signaling pathways, may contribute to develop new pharmacological strategies.

A number of preclinical studies in different experimental Parkinson’s disease (PD) models demonstrated that modulating the cannabinoid system may be useful to treat some motor symptoms. Despite new cannabinoid-based medicines have been proposed for motor and nonmotor symptoms of PD, so far, results from clinical studies are controversial and inconclusive. Further clinical studies involving larger samples of patients, appropriate molecular targets, and specific clinical outcome measures are needed to clarify the effectiveness of cannabinoid-based therapies.” https://www.ncbi.nlm.nih.gov/pubmed/28861502

Even High Doses of Oral Cannabidol Do Not Cause THC-Like Effects in Humans

Posted on September 2, 2017 by David Worrell

“Cannabidiol (CBD) is a cannabinoid of the cannabis plant devoid of intoxicating effects. It may be of therapeutic value in a large number of diseases, including epilepsy, anxiety disorders, depression, schizophrenic psychosis, inflammatory diseases, dystonia, nausea, and vomiting without causing relevant or severe side effects. No biosynthetic enzyme or pathway exists in the human body to convert CBD to THC. This short communication examines the question whether the experimental data presented in a study by Merrick et al. are of clinical relevance. These authors found that cannabidiol (CBD), a major cannabinoid of the cannabis plant devoid of psychotropic effects and of great interest for therapeutic use in several medical conditions, may be converted in gastric fluid into the psychoactive cannabinoids delta-8-THC and delta-9-THC to a relevant degree. They concluded that “the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a positive physiological response.” They issued a warning concerning oral use of CBD and recommend the development of other delivery methods. However, the available clinical data do not support this conclusion and recommendation, since even high doses of oral CBD do not cause psychological, psychomotor, cognitive, or physical effects that are characteristic for THC or cannabis rich in THC. On the contrary, in the past decades and by several groups, high doses of oral CBD were consistently shown to cause opposite effects to those of THC in clinical studies. In addition, administration of CBD did not result in detectable THC blood concentrations. Thus, there is no reason to avoid oral use of CBD, which has been demonstrated to be a safe means of administration of CBD, even at very high doses.” https://www.ncbi.nlm.nih.gov/pubmed/28861499 http://online.liebertpub.com/doi/full/10.1089/can.2016.0036 “A Conversion of Oral Cannabidiol to Delta9-Tetrahydrocannabinol Seems Not to Occur in Humans.” https://www.ncbi.nlm.nih.gov/pubmed/28861507]]>

Immunolocalization of cannabinoid receptor type 1 and CB2 cannabinoid receptors, and transient receptor potential vanilloid channels in pterygium.

Posted on August 31, 2017 by David Worrell

“Cannabinoids, as multi‑target mediators, activate cannabinoid receptors and transient receptor potential vanilloid (TRPV) channels. There is evidence to support a functional interaction of cannabinoid receptors and TRPV channels when they are coexpressed. Human conjunctiva demonstrates widespread cannabinoid receptor type 1 (CB1), CB2 and TRPV channel localization. The aim of the present study was to investigate the expression profile for cannabinoid receptors (CB1 and CB2) and TRPV channels in pterygium, an ocular surface lesion originating from the conjunctiva. The differentiated expression of cannabinoid receptors in combination with the presence of TRPV channels, in primary and recurrent pterygia, imply a potential role of these cannabinoidtargets in the underlying mechanisms of pterygium.”

https://www.ncbi.nlm.nih.gov/pubmed/28849159

https://www.spandidos-publications.com/10.3892/mmr.2017.7246

“A pterygium is a pinkish, triangular tissue growth on the cornea of the eye.” https://en.wikipedia.org/wiki/Pterygium_(conjunctiva)

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Is the Cannabinoid CB2 Receptor a Major Regulator of the Neuroinflammatory Axis of the Neurovascular Unit in Humans?

Posted on August 23, 2017 by David Worrell

“The central nervous system (CNS) is an immune privileged site where the neurovascular unit (NVU) and the blood-brain barrier (BBB) act as a selectively permeable interface to control the passage of nutrients and inflammatory cells into the brain parenchyma. However, in response to injury, infection, or disease, CNS cells become activated, and release inflammatory mediators to recruit immune cells to the site of inflammation. Increasing evidence suggests that cannabinoids may have a neuroprotective role in CNS inflammatory conditions. For many years, it was widely accepted that cannabinoid receptor type 1 (CB₁) modulates neurological function centrally, while peripheral cannabinoid receptor type 2 (CB₂) modulates immune function. As knowledge about the physiology and pharmacology of the endocannabinoid system advances, there is increasing interest in targeting CB₂ as a potential treatment for inflammation-dependent CNS diseases (Ashton & Glass, 2007), where recent rodent and human studies have implicated intervention at the level of the NVU and BBB. These are incredibly important in brain health and disease. Therefore, this review begins by explaining the cellular and molecular components of these systems, highlighting important molecules potentially regulated by cannabinoid ligands and then takes an unbiased look at the evidence in support (or otherwise) of cannabinoid receptor expression and control of the NVU and BBB function in humans.” https://www.ncbi.nlm.nih.gov/pubmed/28826541 http://www.sciencedirect.com/science/article/pii/S1054358917300376?via%3Dihub]]>

The Role of Nuclear Hormone Receptors in Cannabinoid Function.

Posted on August 23, 2017 by David Worrell

“Since the early 2000s, evidence has been accumulating that most cannabinoid compounds interact with the nuclear hormone family peroxisome proliferator-activated receptors (PPARs). This can be through direct binding of these compounds to PPARs, metabolism of cannabinoid to other PPAR-activating chemicals, or indirect activation of PPAR through cell signaling pathways. Delivery of cannabinoids to the nucleus may be facilitated by fatty acid-binding proteins and carrier proteins. All PPAR isoforms appear to be activated by cannabinoids, but the majority of evidence is for PPARα and γ. To date, little is known about the potential interaction of cannabinoids with other nuclear hormones. At least some (but not all) of the well-known biological actions of cannabinoids including neuroprotection, antiinflammatory action, and analgesic effects are partly mediated by PPAR-activation, often in combination with activation of the more traditional target sites of action. This has been best investigated for the endocannabinoid-like compounds palmitoylethanolamide and oleoylethanolamine acting at PPARα, and for phytocannabinoids or their derivatives activation acting at PPARγ. However, there are still many aspects of cannabinoid activation of PPAR and the role it plays in the biological and therapeutic effects of cannabinoids that remain to be investigated.” https://www.ncbi.nlm.nih.gov/pubmed/28826538 http://www.sciencedirect.com/science/article/pii/S1054358917300364?via%3Dihub]]>

Actions and Regulation of Ionotropic Cannabinoid Receptors.

Posted on August 23, 2017 by David Worrell

2+, Na⁺, and various type of K⁺ channels), ligand-gated ion channels (i.e., GABA, glycine), and ion-transporting membranes proteins such as transient potential receptor class (TRP) channels. The first direct, cannabinoid receptor-independent interaction was reported on the function of serotonin 5-HT₃ receptor-ion channel complex. Similar effects were reported also on the other above mentioned ion channels. In the early ninety, studies searching for endogenous modulators of L-type Ca²⁺ channels identified anandamide as ligand for L-type Ca²⁺ channel. Later investigations indicated that other types of Ca²⁺ currents are also affected by endocannabinoids, and, in the late ninety, it was discovered that endocannabinoids activate the vanilloid receptor subtype 1 (TRPV1), and nowadays, it is known that (endo)cannabinoids gate at least five distinct TRP channels. This chapter focuses on cannabinoid regulation of ion channels and lays special emphasis on their action at transient receptor channels.” https://www.ncbi.nlm.nih.gov/pubmed/28826537]]>

CB1 and CB2 Receptor Pharmacology.

Posted on August 23, 2017 by David Worrell

“The CB₁ and CB₂ cannabinoid receptors (CB₁R, CB₂R) are members of the G protein-coupled receptor (GPCR) family that were identified over 20 years ago. CB₁Rs and CB₂Rs mediate the effects of Δ⁹-tetrahydrocannabinol (Δ⁹-THC), the principal psychoactive constituent of marijuana, and subsequently identified endogenous cannabinoids (endocannabinoids) anandamide and 2-arachidonoyl glycerol. CB₁Rs and CB₂Rs have both similarities and differences in their pharmacology. Both receptors recognize multiple classes of agonist and antagonist compounds and produce an array of distinct downstream effects. Natural polymorphisms and alternative splice variants may also contribute to their pharmacological diversity. As our knowledge of the distinct differences grows, we may be able to target select receptor conformations and their corresponding pharmacological responses. This chapter will discuss their pharmacological characterization, distribution, phylogeny, and signaling pathways. In addition, the effects of extended agonist exposure and how that affects signaling and expression patterns of the receptors are considered.” https://www.ncbi.nlm.nih.gov/pubmed/28826534 http://www.sciencedirect.com/science/article/pii/S1054358917300340?via%3Dihub]]>