Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series.

The Journal of Alternative and Complementary Medicine cover image

“Cannabidiol (CBD) is a non-psychotomimetic cannabinoid compound that is found in plants of the genus Cannabis. Preclinical research has suggested that CBD may have a beneficial effect in rodent models of post-traumatic stress disorder (PTSD). This effect is believed to be due to the action of CBD on the endocannabinoid system. CBD has seen a recent surge in research regarding its potential value in a number of neuro-psychiatric conditions. This is the first study to date examining the clinical benefit of CBD for patients with PTSD.

RESULTS:

From the total sample of 11 patients, 91% (n = 10) experienced a decrease in PTSD symptom severity, as evidenced by a lower PCL-5 score at 8 weeks than at their initial baseline. The mean total PCL-5 score decreased 28%, from a mean baseline score of 51.82 down to 37.14, after eight consecutive weeks of treatment with CBD. CBD was generally well tolerated, and no patients discontinued treatment due to side effects.

CONCLUSIONS:

Administration of oral CBD in addition to routine psychiatric care was associated with PTSD symptom reduction in adults with PTSD. CBD also appeared to offer relief in a subset of patients who reported frequent nightmares as a symptom of their PTSD. Additional clinical investigation, including double-blind, placebo-controlled trials, would be necessary to further substantiate the response to CBD that was observed in this study.”

https://www.ncbi.nlm.nih.gov/pubmed/30543451

https://www.liebertpub.com/doi/10.1089/acm.2018.0437

Cannabinoids: Potential Role in Inflammatory and Neoplastic Skin Diseases.

 

“The endocannabinoid system is a complex and nearly ubiquitous network of endogenous ligands, enzymes, and receptors that can also be stimulated by exogenous compounds such as those derived from the marijuana plant, Cannabis sativa.

Recent data have shown that the endocannabinoid system is fully functional in the skin and is responsible for maintaining many aspects of skin homeostasis, such as proliferation, differentiation, and release of inflammatory mediators. Because of its role in regulating these key processes, the endocannabinoid system has been studied for its modulating effects on both inflammatory disorders of the skin and skin cancer.

Although legal restrictions on marijuana as a Schedule I drug in the USA have made studying cannabinoid compounds unfavorable, an increasing number of studies and clinical trials have focused on the therapeutic uses of cannabinoids. This review seeks to summarize the current, and rapidly expanding field of research on the broad potential uses of cannabinoids in inflammatory and neoplastic diseases of the skin.”

https://www.ncbi.nlm.nih.gov/pubmed/30542832

An Analysis of Endocannabinoid Concentrations and Mood Following Singing and Exercise in Healthy Volunteers.

Image result for frontiers in behavioral neuroscience “The euphoric feeling described after running is, at least in part, due to increased circulating endocannabinoids (eCBs). eCBs are lipid signaling molecules involved in reward, appetite, mood, memory and neuroprotection.

The aim of this study was to investigate whether activities other than running can increase circulating eCBs.

Nine healthy female volunteers (mean 61 years) were recruited from a local choir. Circulating eCBs, haemodynamics, mood and hunger ratings were measured before and immediately after 30 min of dance, reading, singing or cycling in a fasted state.

Singing increased plasma levels of anandamide (AEA) by 42% (P < 0.05), palmitoylethanolamine (PEA) by 53% (P < 0.01) and oleoylethanolamine (OEA) by 34% (P < 0.05) and improved positive mood and emotions (P < 0.01), without affecting hunger scores.

Dancing did not affect eCB levels or hunger ratings, but decreased negative mood and emotions (P < 0.01).

Cycling increased OEA levels by 26% (P < 0.05) and tended to decrease how hungry volunteers felt, without affecting mood.

Reading increased OEA levels by 28% (P < 0.01) and increased the desire to eat.

Plasma AEA levels were positively correlated with how full participants felt (P < 0.05). Plasma OEA levels were positively correlated with positive mood and emotions (P < 0.01). All three ethanolamines were positively correlated with heart rate (HR; P < 0.0001).

These data suggest that activities other than running can increase plasma eCBs associated with changes in mood or appetite. Increases in eCBs may underlie the rewarding and pleasurable effects of singing and exercise and ultimately some of the long-term beneficial effects on mental health, cognition and memory.”

https://www.ncbi.nlm.nih.gov/pubmed/30534062

https://www.frontiersin.org/articles/10.3389/fnbeh.2018.00269/full

Cannabinoid 2 receptor attenuates inflammation during skin wound healing by inhibiting M1 macrophages rather than activating M2 macrophages.

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“The anti-inflammatory properties of the cannabinoid 2 receptor (CB2R) in injury and inflammatory diseases have been widely substantiated. Specifically, the anti-inflammatory effect of CB2R may be achieved by regulating macrophage polarisation.

Several research findings suggested that the activation of CB2R could attenuate inflammation by reducing pro-inflammatory M1 macrophage polarisation and promoting anti-inflammatory M2 polarisation.

However, considering CB2R inhibits fibrosis and M2 promotes fibrosis, that the activation of CB2R may lead to an increase in M2 macrophages seems contradictory. Therefore, we hypothesised that the activation of CB2R to attenuate inflammation is not achieved by up-regulating M2 macrophages.

In summary, our findings suggested that during incised skin wound healing in mice, increased levels of CB2R may affect inflammation by regulating M1 rather than M2 macrophage subtype polarisation.

These results offer a novel understanding of the molecular mechanisms involved in the inhibition of inflammation by CBR2 that may lead to new treatments for cutaneous inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/30534003

https://journal-inflammation.biomedcentral.com/articles/10.1186/s12950-018-0201-z

Behavioral effects of psychostimulants in mutant mice with cell-type specific deletion of CB2 cannabinoid receptors in dopamine neurons.

Behavioural Brain Research

“Activation of the endocannabinoid system modulate dopaminergic pathways that are involved in the effects of psychostimulants including amphetamine, cocaine, nicotine and other drugs of abuse. Genetic deletion or pharmacological activation of CB2 cannabinoid receptor is involved in the modulation of the effects of psychostimulants and their rewarding properties. Taken together, our data suggest that CB2Rs play a role in the modulation of dopamine-related effects of psychostimulants and could be exploited as therapeutic target in psychostimulant addiction and other psychiatric disorders associated with dopamine dysregulation.”

https://www.ncbi.nlm.nih.gov/pubmed/30508607

https://www.sciencedirect.com/science/article/pii/S0166432818311987?via%3Dihub

Cannabinoid receptor 2 agonist prevents local and systemic inflammatory bone destruction in rheumatoid arthritis.

Publication cover image

“Cannabinoid receptor 2 (CB2) has been implicated as an important clinical regulator of inflammation and malignant osteolysis. Here, we observed that CB2 expression was markedly higher in the collagen-induced arthritis (CIA) mice synovium and bone tissues than in the non-inflamed synovium and bone tissues. We found that JWH133 ameliorates pathologic bone destruction in CIA mice via the inhibition of osteoclastogenesis and modulation of inflammatory responses, thereby highlighting its potential as a treatment for human rheumatoid arthritis.”

https://www.ncbi.nlm.nih.gov/pubmed/30508319

https://onlinelibrary.wiley.com/doi/abs/10.1002/jbmr.3637

Cannabinoid-1 Receptor Antagonism Improves Glycemic Control and Increases Energy Expenditure via Sirt1/mTORC2 and AMPK Signaling.

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“Endocannabinoids promote energy conservation in obesity, whereas cannabinoid-1 receptor (CB1 R) blockade reverses body weight gain and insulin resistance and increases energy expenditure.

Here we investigated the molecular mechanisms of the catabolic effects of CB1 R blockade in the liver.

CONCLUSION: peripheral CB1 R blockade in obese mice improves glycemic control via the hepatic Sirt1/mTORC2/Akt pathway, whereas it increases fatty acid oxidation via LKB1/AMPK signaling.”

https://www.ncbi.nlm.nih.gov/pubmed/30506571

https://aasldpubs.onlinelibrary.wiley.com/doi/abs/10.1002/hep.30364

Disordered Peptides Looking for Their Native Environment: Structural Basis of CB1 Endocannabinoid Receptor Binding to Pepcans.

Image result for frontiers in molecular biosciences

“Endocannabinoid peptides, or “pepcans,” are endogenous ligands of the CB1 cannabinoid receptor. Depending on their length, they display diverse activity: For instance, the nona-peptide Pepcan-9, also known as hemopressin, is a powerful inhibitor of CB1, whereas the longer variant Pepcan-12, which extends by only three amino acid residues at the N-terminus, acts on both CB1 and CB2 as an allosteric modulator. These findings open the way to structure-driven design of selective peptide modulators of CB1.”

https://www.ncbi.nlm.nih.gov/pubmed/30505835

https://www.frontiersin.org/articles/10.3389/fmolb.2018.00100/full

Cannabinoid receptor type-1 partially mediates metabolic endotoxemia-induced inflammation and insulin resistance.

Physiology & Behavior

“Cannabinoid receptor type-1 partially mediates metabolic endotoxemia-induced inflammation and insulin resistance. Despite no significant differences in body weight among groups, chronic exposure to low-level LPS altered hepatic endocannabinoid signaling, increased inflammation, and impaired insulin sensitivity and insulin clearance. CB1 inhibition significantly attenuated LPS signaling, which attenuated LPS-induced metabolic alterations. Therefore, we concluded that CB1 contributes to LPS-mediated inflammation and insulin resistance, suggesting that blocking CB1 signaling may have therapeutic benefits in reducing inflammation-induced metabolic abnormalities.”

https://www.ncbi.nlm.nih.gov/pubmed/30502357

https://www.sciencedirect.com/science/article/abs/pii/S0031938418304190?via%3Dihub

Cannabis-based products for pediatric epilepsy: A systematic review.

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“Evidence from high-quality randomized controlled trials (RCTs) suggests that cannabidiol probably reduces seizures among children with drug-resistant epilepsy (moderate certainty).”

https://www.ncbi.nlm.nih.gov/pubmed/30515765 

https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.14608

“Phytocannabinoids produce anticonvulsant effects through the endocannabinoid system, with few adverse effects.” https://www.ncbi.nlm.nih.gov/pubmed/25475762