Cannabidiol improves behavioural and neurochemical deficits in adult female offspring of the maternal immune activation (poly I:C) model of neurodevelopmental disorders.

Brain, Behavior, and Immunity“Cognitive impairment is a major source of disability in schizophrenia and current antipsychotic drugs (APDs) have minimal efficacy for this symptom domain.

Cannabidiol (CBD), the major non-intoxicating component of Cannabis sativa L., exhibits antipsychotic and neuroprotective properties.

We recently reported the effects of CBD on cognition in male offspring of a maternal immune activation (polyinosinic-polycytidilic acid (poly I:C)) model relevant to the aetiology of schizophrenia; however, the effects of CBD treatment in females are unknown. Sex differences are observed in the onset of schizophrenia symptoms and response to APD treatment.

Furthermore, the endogenous cannabinoid system, a direct target of CBD, is sexually dimorphic in humans and rodents. Therefore, the present work aimed to assess the therapeutic impact of CBD treatment on behaviour and neurochemical signalling markers in female poly I:C offspring.

Overall, the findings of this study support the therapeutic benefits of CBD on recognition memory and sociability in female poly I:C offspring, and provide insight into the neurochemical changes that may underlie the therapeutic benefits of CBD in the poly I:C model.”

https://www.ncbi.nlm.nih.gov/pubmed/31326506

“These findings suggest that CBD is an efficacious treatment for behavioural and neurochemical changes in a female rodent model relevant to schizophrenia.”

https://www.sciencedirect.com/science/article/pii/S0889159119302806?via%3Dihub

Allostatic load and the cannabinoid system: implications for the treatment of physiological abnormalities in post-traumatic stress disorder (PTSD).

Image result for cns spectrums“It is becoming clear that post-traumatic stress disorder (PTSD) is not simply a psychiatric disorder, but one that involves pervasive physiological impairments as well. These physiological disturbances deserve attention in any attempt at integrative treatment of PTSD that requires a focus beyond the PTSD symptoms themselves. The physiological disturbances in PTSD range over many systems, but a common thread thought to underlie them is that the chronic effects of PTSD involve problems with allostatic control mechanisms that result in an excess in what has been termed “allostatic load” (AL).

A pharmacological approach to reducing AL would be valuable, but, because of the large range of physiological issues involved – including metabolic, inflammatory, and cardiovascular systems – it is unclear whether there exists a simple comprehensive way to address the AL landscape. In this paper, we propose that the cannabinoid system may offer just such an approach, and we outline evidence for the potential utility of cannabinoids in reducing many of the chronic physiological abnormalities seen in PTSD which are thought to be related to excess AL.” https://www.ncbi.nlm.nih.gov/pubmed/31303187
https://www.cambridge.org/core/journals/cns-spectrums/article/allostatic-load-and-the-cannabinoid-system-implications-for-the-treatment-of-physiological-abnormalities-in-posttraumatic-stress-disorder-ptsd/F85D2588638C20BE9DD86DEC2F768242

Potential Mechanisms Influencing the Inverse Relationship Between Cannabis and Nonalcoholic Fatty Liver Disease: A Commentary.

Image result for Nutrition and Metabolic Insights“Nonalcoholic fatty liver disease (NAFLD) develops when the liver is unable to oxidize or export excess free fatty acids generated by adipose tissue lipolysis, de novo lipogenesis, or dietary intake. Although treatment has generally been centered on reversing metabolic risk factors that increase the likelihood of NAFLD by influencing lifestyle modifications, therapeutic modalities are being studied at the cellular and molecular level.

The endocannabinoid system has been of recent focus. The agonism and antagonism of cannabinoid receptors play roles in biochemical mechanisms involved in the development or regression of NAFLD. Exocannabinoids and endocannabinoids, the ligands which bind cannabinoid receptors, have been studied in this regard.

Exocannabinoids found in cannabis (marijuana) may have a therapeutic benefit. Our recent study demonstrated an inverse association between marijuana use and NAFLD among adults in the United States.

This commentary combines knowledge on the role of the endocannabinoid system in the setting of NAFLD with the findings in our article to hypothesize different potential mechanisms that may influence the inverse relationship between cannabis and NAFLD.” https://www.ncbi.nlm.nih.gov/pubmed/31308686

https://journals.sagepub.com/doi/10.1177/1178638819847480

Overcoming the psychiatric side effects of the cannabinoid CB1 receptor antagonists: Current approaches for therapeutics development.

“The cannabinoid receptor 1 (CBR1) is involved in a variety of physiological pathways and has long been considered a golden target for therapeutic manipulation. A large body of evidence in both animal and human studies suggests that CB1R antagonism is highly effective for the treatment of obesity, metabolic disorders and drug addiction. However, the first-in-class CB1R antagonist/inverse agonist, rimonabant, though demonstrating effectiveness for obesity treatment and smoking cessation, displays serious psychiatric side effects, including anxiety, depression and even suicidal ideation, resulting in its eventual withdrawal from the European market. Several strategies are currently being pursued to circumvent the mechanisms leading to these side effects by developing neutral antagonists, peripherally restricted ligands, and allosteric modulators. In this review, we describe the progress in the development of therapeutics targeting the cannabinoid receptor 1 in the last two decades.”

https://www.ncbi.nlm.nih.gov/pubmed/31284863

http://www.eurekaselect.com/173316/article

Diet, endocannabinoids, and health.

Nutrition Research“Healthy aging includes freedom from disease, ability to engage in physical activity, and maintenance of cognitive skills for which diet is a major lifestyle factor. Aging, diet, and health are at the forefront of well-being for the growing population of older adults with the caveat of reducing and controlling pain. Obesity and diabetes risk increase in frequency in adults, and exercise is encouraged to control weight, reduce risk of type II diabetes, and maintain muscle mass and mobility.

One area of research that appears to integrate many aspects of healthy aging is focused on understanding the endocannabinoid system (ECS) because of its role in systemic energy metabolism, inflammation, pain, and brain biology. Physical activity is important for maintaining health throughout the life cycle. The benefits of exercise facilitate macronutrient use, promote organ health, and augment the maintenance of metabolic activity and physiological functions. One outcome of routine exercise is a generalized well-being, and perhaps, this is linked to the ECS.

The purpose of this review is to briefly present the current knowledge of key components of the ECS that contribute to appetite and influence systemic energy metabolism, and dietary factors that alter the responses of ligand binding and activation of cannabinoidreceptors and its role in the brain. Herein, the objectives are to (1) explain the role of the ECS in the body, (2) describe the relationship between dietary polyunsaturated fatty acids and macronutrient intake and systemic metabolism, and (3) present areas of promising research where exercise induces endocannabinoid production in the brain to benefit well-being. There are many gaps in the knowledge of how the ECS participates in controlling pain through exercise; however, emerging research will reveal key relationships to understand this system in the brain and body.”

https://www.ncbi.nlm.nih.gov/pubmed/31280882

https://www.sciencedirect.com/science/article/pii/S027153171930572X?via%3Dihub

Distinct Functions of Endogenous Cannabinoid System in Alcohol Abuse Disorders.

British Journal of Pharmacology banner

“Δ9-tetrahydrocannabinol (Δ9 -THC), the principal active component in Cannabis sativa extracts such as marijuana, participates in cell signaling by binding to cell surface receptors. CB1 receptors (CB1 s) are present in both inhibitory and excitatory presynaptic terminals. CB2 receptors (CB2 s) found in neuronal subpopulations in addition to microglial cells and astrocytes and are present in both pre- and postsynaptic terminals.

Subsequent to endocannabinoid (eCB) system discoveries, studies have suggested that alcohol alters the eCB system and that the eCB system plays a major role in the motivation to abuse alcohol.

Preclinical studies have provided evidence that chronic alcohol consumption modulates eCBs and CB1 expression in brain addiction circuits. In addition, studies have further established the distinct function of the eCB system in the development of fetal alcohol spectrum disorders. This review provides a recent and comprehensive assessment of the literature related to the function of the eCB system in alcohol abuse disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31265740

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14780

“Cannabis and Alcohol: From Basic Science to Public Policy.”  https://www.ncbi.nlm.nih.gov/pubmed/31265135

[Topical cannabinoid agonists. An effective new possibility for treating chronic pruritus].

“Chronic, therapy-resistant pruritus often fails to respond to standard measures so new therapeutic approaches are needed.

Recently, the expression of cannabinoid receptors on cutaneous sensory nerve fibers was described, so cannabinoid agonists seem a rational therapeutic option for pruritus.

RESULTS:

In 14/22 patients a good antipruritic effect could be documented. The average reduction in itch was 86.4%. The therapy was well-tolerated by all patients; neither burning burn nor contact dermatitis was observed.

CONCLUSIONS:

Topical cannabinoid agonists represent an new effective and well-tolerated therapy for refractory itching of various origins. Creams with a higher concentration may be even more effective with broader indications.”

https://www.ncbi.nlm.nih.gov/pubmed/16874533

https://link.springer.com/article/10.1007%2Fs00105-006-1180-1

“Cannabinoids for the treatment of chronic refractory pruritus.”  https://www.ncbi.nlm.nih.gov/pubmed/31264498

Cannabis sativa L. extract and cannabidiol inhibit in vitro mediators of skin inflammation and wound injury.

Publication cover image“The present study investigates the potential effect of a Cannabis sativa L. ethanolic extract standardized in cannabidiol as antiinflammatory agent in the skin. The extract inhibited the release of mediators of inflammation involved in wound healing and inflammatory processes occurring in the skin. Cannabis extract and cannabidiol showed different effects on the release of interleukin-8 and vascular endothelial growth factor, which are both mediators whose genes are dependent on NF-κB. Our findings provide new insights into the potential effect of Cannabis extracts against inflammation-based skin diseases.” https://www.ncbi.nlm.nih.gov/pubmed/31250491

https://onlinelibrary.wiley.com/doi/abs/10.1002/ptr.6400

“The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757311/

“The endocannabinoid system of the skin. A potential approach for the treatment of skin disorders” https://www.sciencedirect.com/science/article/abs/pii/S0006295218303484

Cannabinoid system in the skin – a possible target for future therapies in dermatology.”   https://www.ncbi.nlm.nih.gov/pubmed/19664006

“Extracts of the hemp plant cannabis are traditionally used as a popular remedy against inflammation.” https://medicalxpress.com/news/2007-06-cannabinoids-human-body-anti-inflammatory-effect.html

Cannabinoids reduce hyperalgesia and inflammation via interaction with peripheral CB1 receptors.

Image result for pain journal

“Central antinociceptive effects of cannabinoids have been well documented.

Our results indicate that cannabinoids produce antihyperalgesia via interaction with a peripheral CB1 receptor.

This hypothesis is supported by the finding that anandamide inhibited capsaicin-evoked release of calcitonin gene-related peptide from isolated hindpaw skin.

Collectively, these results indicate that cannabinoids reduce inflammation via interaction with a peripheral CB1 receptor.”

“The Endocannabinoid System and Pain. Cannabis has been used for more than twelve thousand years and for many different purposes (i.e. fiber, medicinal, recreational). However, the endocannabinoid signaling system has only recently been the focus of medical research and considered a potential therapeutic target. Cannabinoid receptors and their endogenous ligands are present at supraspinal, spinal and peripheral levels. Cannabinoids suppress behavioral responses to noxious stimulation and suppress nociceptive processing through activation of cannabinoid CB1 and CB2 receptor subtypes. These studies suggest that manipulation of peripheral endocannabinoids may be promising strategy for the management of pain.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834283/

“The Analgesic Potential of Cannabinoids. Historically and anecdotally cannabinoids have been used as analgesic agents. Moreover, cannabinoids act synergistically with opioids and act as opioid sparing agents, allowing lower doses and fewer side effects from chronic opioid therapy. Thus, rational use of cannabis based medications deserves serious consideration to alleviate the suffering of patients due to severe pain.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728280/

Cannabinoid receptor 1 (CB1R) expression in rat dental pulp

Oral Science International“Accumulating evidence supports the role of the cannabinoid system in providing an antinociceptive effect in various painful conditions.

This effect is mediated through the Cannabinoid receptor 1 (CB1R) expressed on nociceptive afferent nerve terminals.

To investigate whether this receptor plays a similar role in dental pain, we studied the presence and distribution of CB1R in rat dental pulp.

CB1R was present on nerve fibers in rat dental pulp and possibly plays a role in dental pain mechanisms.

Interestingly, CB1R has recently been demonstrated in human dental pulp.

This strongly suggests that CB1R could be a therapeutic target for dental pain management.”

https://www.sciencedirect.com/science/article/pii/S1348864312000031