Tag Archives: Cannabinoids

Cannabinoid Receptor Type 1 Agonist ACEA Protects Neurons from Death and Attenuates Endoplasmic Reticulum Stress-Related Apoptotic Pathway Signaling.

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Neurotoxicity Research

“Neurodegeneration is the result of progressive destruction of neurons in the central nervous system, with unknown causes and pathological mechanisms not yet fully elucidated. Several factors contribute to neurodegenerative processes, including neuroinflammation, accumulation of neurotoxic factors, and misfolded proteins in the lumen of the endoplasmic reticulum (ER).

Endocannabinoid signaling has been pointed out as an important modulatory system in several neurodegeneration-related processes, inhibiting the inflammatory response and increasing neuronal survival. Thus, we investigated the presumptive protective effect of the selective cannabinoid type 1 (CB1) receptor agonist) against inflammatory (lipopolysaccharide, LPS) and ER stress (tunicamycin) stimuli in an in vitro neuronal model (Neuro-2a neuroblastoma cells). Cell viability analysis revealed that ACEA was able to protect against cell death induced by LPS and tunicamycin.

This neuroprotective effect occurs via the CB1 receptor in the inflammation process and via the transient receptor potential of vanilloid type-1 (TRPV1) channel in ER stress. Furthermore, the immunoblotting analyses indicated that the neuroprotective effect of ACEA seems to involve the modulation of eukaryotic initiation factor 2 (eIF2α), transcription factor C/EBP homologous protein (CHOP), and caspase 12, as well as the survival/death p44/42 MAPK, ERK1/2-related signaling pathways.

Together, these data suggest that the endocannabinoid system is a potential therapeutic target in neurodegenerative processes, especially in ER-related neurodegenerative diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/29134561

https://link.springer.com/article/10.1007%2Fs12640-017-9839-1

Hypoxia-induced inhibition of the endocannabinoid system in glioblastoma cells.

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Journal Cover

“The endocannabinoid system plays an important role in the regulation of physiological and pathological conditions, including inflammation and cancer.

Hypoxia is a fundamental phenomenon for the establishment and maintenance of the microenvironments in various physiological and pathological conditions. However, the influence of hypoxia on the endocannabinoid system is not fully understood. In the present study, we investigated the effects of hypoxia on the endocannabinoid system in malignant brain tumors.

Although cannabinoid receptor (CB) engagement induces cell death in U-87 MG cells in normoxic conditions, CB agonist-induced death was attenuated in hypoxic conditions. These results suggest that hypoxia modifies the endocannabinoid system in glioblastoma cells.

Hypoxia-induced inhibition of the endocannabinoid system may aid the development of glioblastoma.”

https://www.ncbi.nlm.nih.gov/pubmed/29130103

https://www.spandidos-publications.com/10.3892/or.2017.6048

ACPA and JWH-133 modulate the vascular tone of superior mesenteric arteries through cannabinoid receptors, BKCa channels, and nitric oxide dependent mechanisms.

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Pharmacological Reports

“Some cannabinoids, a family of compounds derived from Cannabis sativa (marijuana), have previously shown vasodilator effects in several studies, a feature that makes them suitable for the generation of a potential treatment for hypertension.

The mechanism underlying this vasodilator effect in arteries is still controversial. In this report, we explored how the synthetic cannabinoids ACPA (CB1-selective agonist) and JWH-133 (CB2-selective agonist) regulate the vascular tone of rat superior mesenteric arteries.

CB1 and CB2 receptor activation in superior mesenteric artery causes vasorelaxation by mechanisms involving BKCachannels and NO release.”

https://www.ncbi.nlm.nih.gov/pubmed/29128791

http://www.sciencedirect.com/science/article/pii/S1734114017300361?via%3Dihub

Pharmacotherapy of Apnea by Cannabimimetic Enhancement, the PACE Clinical Trial: Effects of Dronabinol in Obstructive Sleep Apnea.

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Oxford University Press

“There remains an important and unmet need for fully effective and acceptable treatments in obstructive sleep apnea (OSA). At present, there are no approved drug treatments. Dronabinol has shown promise for OSA pharmacotherapy in a small dose-escalation pilot study.

Here, we present initial findings of the Phase II PACE (Pharmacotherapy of Apnea by Cannabimimetic Enhancement) trial, a fully-blinded parallel groups, placebo-controlled randomized trial of dronabinol in patients with moderate or severe OSA.

These findings support the therapeutic potential of cannabinoids in patients with OSA. In comparison to placebo, dronabinol was associated with lower AHI, improved subjective sleepiness and greater overall treatment satisfaction. Larger scale clinical trials will be necessary to clarify the best potential approach(es) to cannabinoid therapy in OSA”   https://www.ncbi.nlm.nih.gov/pubmed/29121334

“These findings support the therapeutic potential of cannabinoids in patients with obstructive sleep apnea (OSA).” https://academic.oup.com/sleep/article-abstract/doi/10.1093/sleep/zsx184/4600041?redirectedFrom=fulltext

“Cannabinoid May Be First Drug for Sleep Apnea” https://www.medscape.com/viewarticle/891821

The positive link between executive function and lifetime cannabis use in schizophrenia is not explained by current levels of superior social cognition.

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Psychiatry Research Home

“There has been a growing link between a history of cannabis use and neurocognitive performance in patients with schizophrenia. Fewer neurocognitive deficits may be a marker of the superior social cognition needed to obtain illicit substances, or cannabis use may indicate a distinct path to schizophrenia with less neurocognitive vulnerability. This study sought to determine whether the relationship of cannabis use and executive function exists independently of social cognition.

Eighty-seven patients with schizophrenia were administered measures of social cognition and executive function. Social cognition was assessed using the Bell-Lysaker Emotion Recognition Test to measure affect recognition, and the Eyes and Hinting Tests to measure theory of mind. Executive function was assessed by the Mental Flexibility component of the Delis-Kaplan Executive Functioning Scale. The relations between the variables were examined with structural equation modeling.

Cannabis use positively related to executive function, negatively related to affect recognition, and had no relationship with theory of mind. There were no indirect effects of other illicit substances on amount of regular cannabis use. Alcohol use was related to worse affect recognition. The relationship between cannabis use and better executive function was supported and was not explained by superior social cognition.”

https://www.ncbi.nlm.nih.gov/pubmed/28152399

http://www.psy-journal.com/article/S0165-1781(16)31861-3/fulltext

Efficacy and safety of cannabis for treating children with refractory epilepsy.

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Nursing Children and Young People

“The aim of this literature review was to examine the evidence base for the safety and efficacy of cannabis in treating children with refractory epilepsy. Clinical and medical databases were searched and four articles were included in the final analysis, which included retrospective reviews and open-label trials with a total sample size of 424. One clinical trial included administration of cannabidiol, the non-psychoactive compound of cannabis, while the other three articles stated that the compound administered to participants contained tetrahydrocannabidiol, the psychoactive constituent of cannabis.

Cannabis may reduce seizures in some children and young people with refractory epilepsy, however, its success may be affected by aetiology of the epilepsy or concomitant anti-epileptic drug use, and a therapeutic dose has not been found. Positive side effects were also found including improved sleep, alertness and mood. More research is needed on this subject, including randomised controlled trials. Nurses who are aware of patients and families wishing to trial cannabis for refractory epilepsy should have full and frank discussions.”

https://www.ncbi.nlm.nih.gov/pubmed/29115760

https://journals.rcni.com/nursing-children-and-young-people/efficacy-and-safety-of-cannabis-for-treating-children-with-refractory-epilepsy-ncyp.2017.e907

Cannabinoids offer alternatives to opioids for pain relief, experts say.

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“Alternatives to opioids can be used alone or in combination with opioids for pain relief, to help prevent medical exposure to narcotics being an entry point to misuse, said experts at a medical education forum in Washington, DC on 3 November.

Endocannabinoid compounds found in marijuana can greatly enhance the potency of opioids in relieving pain.

The synergy from using these drugs together can result in more effective pain relief from lower doses of opioids,”

https://www.ncbi.nlm.nih.gov/pubmed/29113969

http://www.bmj.com/content/359/bmj.j5140.full

Anti-migraine effect of ∆9-tetrahydrocannabinol in the female rat.

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European Journal of Pharmacology

“Current anti-migraine treatments have limited efficacy and many side effects. Although anecdotal evidence suggests that marijuana is useful for migraine, this hypothesis has not been tested in a controlled experiment. Thus, the present study tested whether administration of ∆9-tetrahydrocannabinol (THC) produces anti-migraine effects in the female rat.

These data suggest that: 1) THC reduces migraine-like pain when administered at the right dose (0.32mg/kg) and time (immediately after AITC); 2) THC’s anti-migraine effect is mediated by CB1 receptors; and 3) Wheel running is an effective method to assess migraine treatments because only treatments producing antinociception without disruptive side effects will restore normal activity.

These findings support anecdotal evidence for the use of cannabinoids as a treatment for migraine in humans and implicate the CB1 receptor as a therapeutic target for migraine.”

https://www.ncbi.nlm.nih.gov/pubmed/29111112

http://www.sciencedirect.com/science/article/pii/S0014299917307239?via%3Dihub

Characterization of endocannabinoids and related acylethanolamides in the synovial fluid of dogs with osteoarthritis: a pilot study.

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“Cannabis-based drugs have been shown to be effective in inflammatory diseases.

A number of endocannabinoids including N- arachidonoylethanolamide (anandamide, AEA) and 2-arachidonyl glycerol (2-AG) with activity at the cannabinoidreceptors (CBR) CBR1 and CBR2, have been identified. Other structurally related endogenous fatty acid compounds such as oleoylethanolamide (OEA) and palmitoyl ethanolamide (PEA) have been identified in biological tissues.

These compounds do not bind to CBR but might be involved in facilitating the actions of directly acting endocannabinoids and thus are commonly termed “entourage” compounds due to their ability to modulate the endocannabinoid system.

The aim of this study was to evaluate the presence of endocannabinoids and entourage compounds in the synovial fluid of dogs with osteoarthritis subjected to arthrotomy of the knee joint. Cytokines and cytology were studied as well.

AEA, 2-AG, OEA and PEA were all present in the synovial fluid of arthritic knees and in the contralateral joints; in addition, a significant increase of OEA and 2AG levels were noted in SF from OA knees when compared to the contralateral joints.

The identification and quantification of endocannabinoids and entourage compounds levels in synovial fluids from dogs with OA of the knee is reported for the first time. Our data are instrumental for future studies involving a greater number of dogs. Cannabinoids represent an emerging and innovative pharmacological tool for the treatment of OA and further studies are warranted to evaluate the effectiveness of cannabinoids in veterinary medicine.”

https://www.ncbi.nlm.nih.gov/pubmed/29110674

“The ECS can be exploited as a potential therapeutic option for OA. We have demonstrated the presence of AEA, 2-AG, OEA and PEA in the SF of dogs with OA. Our data open the avenue to future studies involving a higher number of dogs and aimed at defining the role played by these compounds in OA of the dogs. Both plant-derived and synthetic agonists of CBRs represent an emerging and innovative pharmacological tool for the treatment of OA. ” https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-017-1245-7

Radioligands for Positron Emission Tomography Imaging of Cannabinoid type 2 Receptor.

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Journal of Labelled Compounds and Radiopharmaceuticals

“The cannabinoid type 2 (CB2) receptor is an immunomodulatory receptor mainly expressed in peripheral cells and organs of the immune system. The expression level of CB2 in the central nervous system under physiological conditions is negligible, however under neuroinflammatory conditions an upregulation of CB2 protein or mRNA mainly co-localized with activated microglial cells has been reported.

Consequently, CB2 agonists have been confirmed to play a role in neuroprotective and anti-inflammatory processes.

A suitable PET radioligand for imaging CB2 would provide an invaluable research tool to explore the role of CB2 receptor expression in inflammatory disorders. In this review, we provide a summary of so far published CB2 radioligands as well as their in vitro and in vivo binding characteristics.”

https://www.ncbi.nlm.nih.gov/pubmed/29110331

http://onlinelibrary.wiley.com/doi/10.1002/jlcr.3579/abstract