Potential for endocannabinoid system modulation in ocular pain and inflammation: filling the gaps in current pharmacological options

Posted on April 15, 2019 by David

Neuronal Signaling

“Challenges in the management of ocular pain are an underappreciated topic. Currently available therapeutics lack both efficacy and clear guidelines for their use, with many also possessing unacceptable side effects. Promising novel agents would offer analgesic, anti-inflammatory, and possibly neuroprotective actions; have favorable ocular safety profiles; and show potential in managing neuropathic pain.

Growing evidence supports a link between the endocannabinoid system (ECS) and a range of physiological and disease processes, notably those involving inflammation and pain. Both preclinical and clinical data suggest analgesic and anti-inflammatory actions of cannabinoids and ECS-modifying drugs in chronic pain conditions, including those of neuropathic origin.

The ECS is present ubiquitously through the body, including a range of ocular tissues, and represents a promising target in the treatment of several physiological and pathophysiologic processes in the eye including, but not limited to, pain, inflammation, and neuronal damage. ”

http://www.neuronalsignaling.org/content/2/4/NS20170144

Δ9-tetrahydrocannabinol attenuates oxycodone self-administration under extended access conditions.

Posted on April 14, 2019 by David

Neuropharmacology

“Growing nonmedical use of prescription opioids is a global problem, motivating research on ways to reduce use and combat addiction.

Medical cannabis (“medical marijuana”) legalization has been associated epidemiologically with reduced opioid harms and cannabinoids have been shown to modulate effects of opioids in animal models.

This study was conducted to determine if Δ⁹-tetrahydrocannabinol (THC) enhances the behavioral effects of oxycodone.

Together these data demonstrate additive effects of THC and oxycodone and suggest the potential use of THC to enhance therapeutic efficacy, and to reduce the abuse, of opioids.”

https://www.ncbi.nlm.nih.gov/pubmed/30980837

“Δ⁹-tetrahydrocannabinol (THC) enhances the antinociceptive effects of oxycodone. Vaporized and injected THC reduces oxycodone self-administration. Cannabinoids may reduce opioid use for analgesia. Cannabinoids may reduce nonmedical opioid use.”

https://www.sciencedirect.com/science/article/pii/S0028390819301212?via%3Dihub

The Potential of Cannabinoid-Based Treatments in Tourette Syndrome.

Posted on April 13, 2019 by David

“Novel pharmacological treatments are needed for Tourette syndrome.

Our goal was to examine the current evidence base and biological rationale for the use of cannabis-derived medications or medications that act on the cannabinoid system in Tourette syndrome.

There is a strong biological rationale regarding how cannabis-derived medications could affect tic severity. Anecdotal case reports and series have noted that many patients report that their tics improve after using cannabis. However, only two small randomized, placebo-controlled trials of Δ⁹-tetrahydrocannabinol have been published; these suggested possible benefits of cannabis-derived agents for the treatment of tics.

Trials examining other agents active on the cannabinoid system for tic disorders are currently ongoing.

Cannabinoid-based treatments are a promising avenue of new research for medications that may help the Tourette syndrome population.”

https://www.ncbi.nlm.nih.gov/pubmed/30977108

https://link.springer.com/article/10.1007%2Fs40263-019-00627-1

AM-1241 CB2 Receptor Agonist Attenuates Inflammation, Apoptosis and Stimulate Progenitor Cells in Bile Duct Ligated Rats.

Posted on April 13, 2019 by David

“The cannabinoid receptor 2 (CB2) plays a pleiotropic role in the innate immunity and is considered a crucial mediator of liver disease.

Cannabinoid CB2 receptor activation has been reported to attenuate liver fibrosis in CCl4 exposed mice and also plays a potential role in liver regeneration in a mouse model of I/R and protection against alcohol-induced liver injury.

AIM:

In this study, we investigated the impact of CB2 receptors on the antifibrotic and regenerative process associated with cholestatic liver injury.

RESULTS:

Following bile duct ligation (BDL) for 3 weeks, there was increased aminotransferase levels, marked inflammatory infiltration and hepatocyte apoptosis with induced oxidative stress, as reflected by increased lipid peroxidation. Conversely, following treatment with the CB2 agonist, AM-1241, BDL rats displayed a reduction in liver injury and attenuation of fibrosis as reflected by expression of hydroxyproline and α-smooth muscle actin. AM1241 treatment also significantly attenuated lipid peroxidation end-products, p53-dependent apoptosis and also attenuated inflammatory process by stimulating IL-10 production. Moreover, AM1241 treated rats were associated with significant expression of hepatic progenitor/oval cell markers.

CONCLUSION:

In conclusion, this study points out that CB2 receptors reduce liver injury and promote liver regeneration via distinct mechanisms including IL-10 dependent inhibition of inflammation, reduction of p53-reliant apoptosis and through stimulation of oval/progenitor cells. These results suggest that CB2 agonists display potent hepatoregenrative properties, in addition to their antifibrogenic effects.”

https://www.ncbi.nlm.nih.gov/pubmed/30976335

https://www.id-press.eu/mjms/article/view/oamjms.2019.194

The onus of cannabinoids in interrupting the molecular odyssey of breast cancer: A critical perspective on UPRER and beyond.

Posted on April 13, 2019 by David

Saudi Pharmaceutical Journal

“Cannabinoids, commonly used for medicinal and recreational purposes, consist of various complex hydrophobic molecules obtained from Cannabis sativa L. Acting as an inhibitory molecule; they have been investigated for their antineoplastic effect in various breast tumor models. Lately, it was found that cannabinoid treatment not only stimulates autophagy-mediated apoptotic death of tumor cells through unfolded protein response (UPR^ER) activated downstream effectors, but also imposes cell cycle arrest. The exploitation of UPR^ER tumors as such is believed to be a major molecular event and is therefore employed in understanding the development and progression of breast tumor. Simultaneously, the data on clinical trials following administration of cannabinoid is currently being explored to find its role not only in palliation but also in the treatment of breast cancer. The present study summarizes new achievements in understanding the extent of therapeutic progress and highlights recent developments in cannabinoid biology towards achieving a better cure of breast cancer through the exploitation of different cannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/30976189

https://www.sciencedirect.com/science/article/pii/S1319016419300064?via%3Dihub

Ketamine-induced antidepressant like effects in mice: A possible involvement of cannabinoid system.

Posted on April 12, 2019 by David

Biomedicine & Pharmacotherapy

“The purpose of this study was to explore the possible interaction between ketamine and cannabinoid system in the modulation of depression-related responses.

It seems that possible interaction between ketamine and cannabinoid system may modulate depression-related behavior.”

https://www.ncbi.nlm.nih.gov/pubmed/30970516

https://www.sciencedirect.com/science/article/pii/S0753332218375309?via%3Dihub

“FDA Approves Ketamine Nasal Spray to Treat Depression” https://www.psychologytoday.com/us/blog/when-your-adult-child-breaks-your-heart/201903/fda-approves-ketamine-nasal-spray-treat

“Antidepressant-like effect of Δ9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866040/

http://www.thctotalhealthcare.com/category/depression-2/

Psychopathological symptoms associated with synthetic cannabinoid use: a comparison with natural cannabis.

Posted on April 11, 2019 by David

“Synthetic cannabinoids (SCs) are a class of new psychoactive substances that have been rapidly evolving around the world throughout recent years. Many different synthetic cannabinoid analogues are on the consumer market and sold under misleading names, like “spice” or “incense.”

A limited number of studies have reported serious health effects associated with SC use. In this study, we compared clinical and subclinical psychopathological symptoms associated with SC use and natural cannabis (NC) use.

SC users scored higher than NC users on all used psychometric measures, indicating a higher likelihood of drug abuse, sleep problems, (hypo)manic symptoms, and the nine dimensions comprising the BSI, somatization, obsessive-compulsive behavior, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism.

This study shows that SC use is associated with increased mental health symptomatology compared to NC use.”

https://www.ncbi.nlm.nih.gov/pubmed/30968175

https://link.springer.com/article/10.1007%2Fs00213-019-05238-8

“While cannabis use usually induces psychotropic effects such as euphoria, relaxation, and a general pleasant feeling, the use of Synthetic Cannabinoid drugs is associated with more undesired effects including; agitation, irritability, confusion, hallucinations, delusions, psychosis, and death.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999798/
“These side effects (including psychosis, tachyarrhythmia, and seizures) are not typically seen with marijuana (Cannabis sativa) use.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726077/

Prescription of a THC/CBD-Based Medication to Patients with Dementia: A Pilot Study in Geneva

Posted on April 10, 2019 by David

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“Dementia is increasing worldwide. No effective medication is currently available for the treatment of the underlying disease and accompanying behavioral symptoms. Cannabinoids might have a beneficial effect, but clinical studies with (low-dose) synthetic THC have not been conclusive.

Objective: To test the acceptability, practical aspects, and clinical outcomes of the introduction of a THC/CBD-based oral medication in severely demented patients in a specialized nursing home in Geneva.

Methods: This was a prospective observational study.

Results: Ten female demented patients with severe behavior problems received oral medication with on average 7.6 mg THC/13.2 mg CBD daily after 2 weeks, 8.8 mg THC/17.6 mg CBD after 1 month, and 9.0 mg THC/18.0 mg CBD after 2 months. The THC/CBD-based oil was preferred. Neuropsychiatric Inventory, Cohen-Mansfield Agitation Inventory score, and a behavior problem visual analog scale decreased by 40% after 2 months, rigidity score by 50%. Half of the patients decreased or stopped other psychotropic medications. The staff appreciated the decrease in rigidity, making daily care and transfers easier, the improved direct contact with the patients, the improvement in behavior, and the decrease in constipation with less opioids. There was no withholding of the medication for reasons of side effects, and the effects persisted after 2 months.

Conclusions: An oral cannabis extract with THC/CBD, in higher dosages than in other studies, was well tolerated and greatly improved behavior problems, rigidity, and daily care in severely demented patients.”

https://www.karger.com/Article/Abstract/498924

Circulating endocannabinoid concentrations and sexual arousal in women.

Posted on April 10, 2019 by David

“Several lines of evidence point to the potential role of the endocannabinoid system in female sexual functioning. These include results from studies describing the subjective effects of exogenous cannabinoids on sexual functioning in humans and the observable effects of exogenous cannabinoids on sexual functioning in other species, as well as results from studies investigating the location of cannabinoid receptors in the brain and periphery, and the effects of cannabinoid receptor activation on neurotransmitters implicated in sexual functioning. While these lines of research suggest a role for the endocannabinoid system in female sexual functioning, no studies investigating the relationship between concentrations of endogenous cannabinoids (i.e., arachidonoylethanolamide [AEA] and 2-arachidonoylglycerol [2-AG]) and sexual functioning have been conducted in any species.

AIM:

To measure circulating endocannabinoid concentrations in relation to subjective and physiological indices of sexual arousal in women (N = 21).

METHODS:

Serum endocannabinoid (AEA and 2-AG) concentrations were measured immediately prior to, and immediately following, viewing of neutral (control) and erotic (experimental) film stimuli in a repeated measures design. Physiological sexual arousal was measured via vaginal photoplethysmography. Subjective sexual arousal was measured both continuously and noncontinuously. Pearson’s correlations were used to investigate the relationships between endocannabinoid concentrations and sexual arousal.

MAIN OUTCOME MEASURES:

Changes in AEA and 2-AG concentrations from pre- to post-film and in relation to physiological and subjective indices of sexual arousal.

RESULTS:

Results revealed a significant relationship between endocannabinoid concentrations and female sexual arousal, whereby increases in both physiological and subjective indices of sexual arousal were significantly associated with decreases in AEA, and increases in subjective indices of sexual arousal were significantly associated with decreases in 2-AG.

CONCLUSIONS:

These findings support the hypothesis that the endocannabinoid system is involved in female sexual functioning, with implications for furthering understanding of the biological mechanisms underlying female sexual functioning.”

https://www.ncbi.nlm.nih.gov/pubmed/22462722

https://www.jsm.jsexmed.org/article/S1743-6095(15)33996-5/fulltext

[Significance of the endocannabinoid system in migraine].

Posted on April 10, 2019 by David

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“Based on the traditional pain-relieving effect of Cannabis species an endogenous cannabinoid like system was discovered in the human body. Endocannabinoids have important role in the homeostasis of the body, such as stress response and mood control, feeding behaviour, energy balance and metabolism, immunological processes, and also play important role in controlling pain processing. Previous studies suggested that an endocannabinoid dysfunction, namely endocannabinoid deficit, might contribute to the development of migraine and its chronification. Although, the exact nature of the relationship between migraine and endocannabinoid system is not fully understood yet, in this brief review we summarise research results suggesting that the endocannabinoid system may be a potential drug target in the migraine therapy.”

https://www.ncbi.nlm.nih.gov/pubmed/30962405