Remote Ischemia Preconditioning Attenuates Blood-Spinal Cord Barrier Breakdown in Rats Undergoing Spinal Cord Ischemia Reperfusion Injury: Associated with Activation and Upregulation of CB1 and CB2 Receptors.

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“Remote ischemic preconditioning (RIPC) has protective effects on spinal cord ischemia reperfusion (I/R) injury, but the potential mechanisms remain unclear. In our study, the effects and underlying mechanisms of RIPC on blood-spinal cord barrier (BSCB) breakdown following I/R injury were investigated.

RIPC attenuated the motor dysfunction, BSCB disruption and downregulation of occludin after I/R injury, which were impaired by blocking CB1 and CB2 receptors. Moreover, RIPC upregulated the elevated perivascular expression of CB1 and CB2 receptors following I/R injury.

CONCLUSIONS:

These results indicated that RIPC, through activation and upregulation of CB1 and CB2 receptors, was involved in preserving the integrity of BSCB after spinal cord I/R injury.”

https://www.ncbi.nlm.nih.gov/pubmed/29130941

https://www.karger.com/Article/FullText/484460

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

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“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

Pharmacokinetic and behavioural profile of THC, CBD, and THC+CBD combination after pulmonary, oral, and subcutaneous administration in rats and confirmation of conversion in vivo of CBD to THC.

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European Neuropsychopharmacology Home

“Of central importance was the novel finding that THC can be detected in serum and brain after administration of CBD alone which, if confirmed in humans and given the increasing medical use of CBD-only products, might have important legal and forensic ramifications.” https://www.ncbi.nlm.nih.gov/pubmed/29129557  http://www.europeanneuropsychopharmacology.com/article/S0924-977X(17)30983-5/fulltext

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

Cannabidiol as a treatment for epilepsy

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Journal of Neurology

“Despite an increasing number of anti-epileptic drugs (AEDs), the proportion of drug-resistant cases of epilepsy has remained fairly static at around 30% and the search for new and improved AEDs continues.

Cannabis has been used as a medical treatment for epilepsy for thousands of years; it contains many active compounds, the most important being tetrahydrocannabinol, which has psychoactive properties, and cannabidiol, which does not.

Animal models and clinical data to date have suggested that cannabidiol is more useful in treating epilepsy; there is limited evidence that tetrahydrocannabinol has some pro-convulsant effects in animal models. The mechanism by which cannabidiol exerts its anti-convulsant properties is currently unclear.

Conclusion. The evidence is increasing that cannabidiol is an effective treatment option for childhood onset severe treatment-resistant epilepsies with a tolerable side effect and safety profile. Further evidence is needed before cannabidiol can be considered in more common or adult onset epilepsies. Longer-term safety data for cannabidiol, particularly considering its effects on the developing brain, are also required.”

https://link.springer.com/article/10.1007%2Fs00415-017-8663-0

Single-Dose Pharmacokinetics of Oral Cannabidiol Following Administration of PTL101: A New Formulation Based on Gelatin Matrix Pellets Technology.

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Clinical Pharmacology in Drug Development

“Cannabidiol (CBD) is the main nonpsychoactive component of the cannabis plant. It has been associated with antiseizure, antioxidant, neuroprotective, anxiolytic, anti-inflammatory, antidepressant, and antipsychotic effects.

PTL101 is an oral gelatin matrix pellets technology-based formulation containing highly purified CBD embedded in seamless gelatin matrix beadlets. Study objectives were to evaluate the safety and tolerability of PTL101 containing 10 and 100 mg CBD, following single administrations to healthy volunteers and to compare the pharmacokinetic profiles and relative bioavailability of CBD with Sativex oromucosal spray (the reference product) in a randomized, crossover study design.

Administration of PTL101 containing 10 CBD, led to a 1.7-fold higher Cmax and 1.3-fold higher AUC compared with the oromucosal spray. Tmax following both modes of delivery was 3-3.5 hours postdosing. CBD exhibited about a 1-hour lag in absorption when delivered via PTL101. A 10-fold increase in the dose resulted in an ∼15-fold increase in Cmax and AUC. Bioavailability of CBD in the 10-mg PTL101 dose was 134% relative to the reference spray.

PTL101 is a pharmaceutical-grade, user-friendly oral formulation that demonstrated safe and efficient delivery of CBD and therefore could be an attractive candidate for therapeutic indications.”

https://www.ncbi.nlm.nih.gov/pubmed/29125702

http://onlinelibrary.wiley.com/doi/10.1002/cpdd.408/abstract

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