“The review represents the analysis of works about role of endogenous cannabinoid (EC) system in the neuro- degenerate diseases (ND), in which the cellular death and disturbances of neuronal functions of the hippo- campus, neocortex and striatum are observed. Here, the diseases.ofAlzheimer, of Parkinson, of Hangtington, and the temporal lobe epilepsy are considered. In recent years the fundamental role of EC system in regu- lation of neuroexcitability, energy metabolism, inflammatory and many other processes has been opened in ND pathogenesis. It points to possibility of development of therapeutic approaches which use the prepara- tions for activation of EC system. In the review various mechanisms of cellular survival and their reparations provided to EC system during action of pathological factors are stated.”
Author Archives: David Worrell
Cannabisin F from Hemp (Cannabis sativa) Seed Suppresses Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglia as SIRT1 Modulator.
“Hemp seed (Fructus cannabis) is rich in lignanamides, and initial biological screening tests showed their potential anti-inflammatory and anti-oxidative capacity.
This study investigated the possible effects and underlying mechanism of cannabisin F, a hempseed lignanamide, against inflammatory response and oxidative stress in lipopolysaccharide (LPS)-stimulated BV2 microglia cells.
Cannabisin F suppressed the production and the mRNA levels of pro-inflammatory mediators such as interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in a concentration-dependent manner in LPS-stimulated BV2 microglia cell. Furthermore, cannabisin F enhanced SIRT1 expression and blocked LPS-induced NF-κB (Nuclear factor kappa B) signaling pathway activation by inhibiting phosphorylation of IκBα (Inhibit proteins of nuclear factor kappaB) and NF-κB p65. And the SIRT1 inhibitor EX527 significantly inhibited the effect of cannabisin F on pro-inflammatory cytokines production, suggesting that the anti-inflammatory effects of cannabisin F are SIRT1-dependent. In addition, cannabisin F reduced the production of cellular reactive oxygen species (ROS) and promoted the expression of Nrf2 (Nuclear factor erythroid-2 related factor 2) and HO-1 (Heme Oxygenase-1), suggesting that the anti-oxidative effects of cannabisin F are related to Nrf2 signaling pathway.
Collectively, these results suggest that the neuro-protection effect of cannabisin F against LPS-induced inflammatory response and oxidative stress in BV2 microglia cells involves the SIRT1/NF-κB and Nrf2 pathway.”
Pills to pot: observational analyses of cannabis substitution among medical cannabis users with chronic pain.
“Chronic pain is common, costly and challenging to treat. Many individuals with chronic pain have turned to cannabis as an alternative form of pain management.
We report results from an ongoing, online survey of medical cannabis users with chronic pain nationwide about how cannabis affects pain management, health, and pain medication use. We also examined whether and how these parameters were affected by concomitant recreational use, and duration of use (novice: <1 year vs. experienced: ≥1 year). 1,321 participants (59% female, 54% ≥50 years old) completed the survey.
Consistent with other observational studies, ∼80% reported substituting cannabis for traditional pain medications (53% for opioids, 22% for benzodiazepines), citing fewer side effects and better symptom management as their rationale for doing so. Medical only users were older (52 vs. 47, p<0.0001), less likely to drink alcohol (66% vs. 79%, p<0.0001), and more likely to be currently taking opioids (21% vs. 11%, p<0.0001) than users with a combined recreational + medical history. Compared to novice users, experienced users were more likely to be male (64% vs. 58%, p<0.0001), take no concomitant pain medications (43% vs. 30%), and report improved health (74% vs. 67%, p=0.004) with use.
Given that chronic pain is the most common reason for obtaining a medical cannabis license, these results highlight clinically important differences among the changing population of medical cannabis users. More research is needed to better understand effective pain management regimens for medical cannabis users.
PERSPECTIVE: This article presents results that confirm previous clinical studies suggesting that cannabis may be an effective analgesic and potential opioid substitute. Participants reported improved pain, health, and fewer side effects as rationale for substituting. This article highlights how use duration and intentions for use affect reported treatment and substitution effects.”
https://www.ncbi.nlm.nih.gov/pubmed/30690169
https://www.jpain.org/article/S1526-5900(18)30735-1/fulltext
Medical cannabis patterns of use and substitution for opioids & other pharmaceutical drugs, alcohol, tobacco, and illicit substances; results from a cross-sectional survey of authorized patients.
“The findings provide a granular view of patient patterns of medical cannabis use, and the subsequent self-reported impacts on the use of opioids, alcohol, and other substances, adding to a growing body of academic research suggesting that increased regulated access to medical and recreational cannabis can result in a reduction in the use of and subsequent harms associated with opioids, alcohol, tobacco, and other substances.”
https://www.ncbi.nlm.nih.gov/pubmed/30691503
https://harmreductionjournal.biomedcentral.com/articles/10.1186/s12954-019-0278-6
Dark Classics in Chemical Neuroscience: Δ9-Tetrahydrocannabinol.
“Cannabis (Cannabis sativa) is the most widely used illicit drug in the world, with an estimated 192 million users globally.
The main psychoactive component of cannabis is (-)-trans-Δ9-tetrahydrocannabinol (Δ9-THC), a molecule with a diverse range of pharmacological actions. The unique and distinctive intoxication caused by Δ9-THC primarily reflects partial agonist action at central cannabinoid type 1 (CB1) receptors.
Δ9-THC is an approved therapeutic treatment for a range of conditions, including chronic pain, chemotherapy-induced nausea and vomiting, and is being investigated in indications such as anorexia nervosa, agitation in dementia, and Tourette’s syndrome.
It is available as a regulated pharmaceutical in products such as Marinol®, Sativex®, and Namisol®, as well as in an ever-increasing range of unregistered medicinal and recreational cannabis products.
While cannabis is an ancient medicament, contemporary use is embroiled in legal, scientific, and social controversy, much of which relates to the potential hazards and benefits of Δ9-THC itself.
Robust contemporary debate surrounds the therapeutic value of Δ9-THC in different diseases, its capacity to produce psychosis and cognitive impairment, and the addictive and “gateway” potential of the drug.
This review will provide a profile of the chemistry, pharmacology, toxicology, and recreational and therapeutic uses of Δ9-THC, as well as the historical and societal importance of this unique, distinctive, and ubiquitous psychoactive substance.”
Targeting CB1 and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease.
“Cannabinoid CB1 receptors (CB1R) and the GPR55 receptor are expressed in striatum and are potential targets in the therapy of Parkinson’s disease (PD), one of the most prevalent neurodegenerative diseases in developed countries.
The aim of this paper was to address the potential of ligands acting on those receptors to prevent the action of a neurotoxic agent, MPP+, that specifically affects neurons of the substantia nigra due to uptake via the dopamine DAT transporter.
These results show that neurons expressing heteromers are more resistant to cell death but question the real usefulness of CB1R, GPR55, and their heteromers as targets to afford PD-related neuroprotection.”
https://www.ncbi.nlm.nih.gov/pubmed/30687889
https://link.springer.com/article/10.1007%2Fs12035-019-1495-4
Cannabinoids as a Potential New and Novel Treatment for Melanoma: A Pilot Study in a Murine Model.
“Malignant melanoma is a complex malignancy with significant morbidity and mortality. The incidence continues to rise, and despite advances in treatment, the prognosis is poor. Thus, it is necessary to develop novel strategies to treat this aggressive cancer. Synthetic cannabinoids have been implicated in inhibiting cancer cell proliferation, reducing tumor growth, and reducing metastasis. We developed a unique study focusing on the effects of treatment with a cannabinoid derivative on malignant melanoma tumors in a murine model.
RESULTS:
A significant decrease in tumor size was detected in mice treated with CBD when compared with the control group (P = 0.01). The survival curve of melanoma tumors treated with CBD increased when compared with the control group and was statistically significant (P = 0.04). The growth curve and survival curve of melanoma tumors treated with Cisplatin were significantly decreased and increased, respectively, when compared with the control and CBD-treated groups. Mice treated with Cisplatin demonstrated the longest survival time, but the quality of life and movement of CBD-treated mice were observed to be better.
CONCLUSIONS:
We demonstrate a potential beneficial therapeutic effect of cannabinoids, which could influence the course of melanoma in a murine model. Increased survival and less tumorgenicity are novel findings that should guide research to better understand the mechanisms by which cannabinoids could be utilized as adjunctive treatment of cancer, specifically melanoma. Further studies are necessary to evaluate this potentially new and novel treatment of malignant melanoma.”
https://www.ncbi.nlm.nih.gov/pubmed/30691796
https://www.journalofsurgicalresearch.com/article/S0022-4804(18)30626-7/fulltext
US Veterinarians’ Knowledge, Experience, and Perception Regarding the Use of Cannabidiol for Canine Medical Conditions.
“Due to the myriad of laws concerning cannabis, there is little empirical research regarding the veterinary use of cannabidiol (CBD).
This study used the Veterinary Information Network (VIN) to gauge US veterinarians’ knowledge level, views and experiences related to the use of cannabinoids in the medical treatment of dogs.
Most participants agreed that both marijuana and CBD products offer benefits for humans and expressed support for use of CBD products for animals.”
https://www.ncbi.nlm.nih.gov/pubmed/30687726
https://www.frontiersin.org/articles/10.3389/fvets.2018.00338/full
Cannabidiol May Help Normalize Brain Function in Psychosis
“Cannabidiol (CBD), the nonpsychoactive compound in cannabis, may help normalize function in brain regions associated with psychosis, found a study in JAMA Psychiatry.”
Oral Cannabidiol Use in Children With Autism Spectrum Disorder to Treat Related Symptoms and Co-morbidities.
“Children with autism spectrum disorder (ASD) commonly exhibit comorbid symptoms such as aggression, hyperactivity and anxiety. Several studies are being conducted worldwide on cannabidiol use in ASD; however, these studies are still ongoing, and data on the effects of its use is very limited.
In this study we aimed to report the experience of parents who administer, under supervision, oral cannabinoids to their children with ASD.
Results: 53 children at a median age of 11 (4-22) year received cannabidiol for a median duration of 66 days (30-588). Self-injury and rage attacks (n = 34) improved in 67.6% and worsened in 8.8%. Hyperactivity symptoms (n = 38) improved in 68.4%, did not change in 28.9% and worsened in 2.6%. Sleep problems (n = 21) improved in 71.4% and worsened in 4.7%. Anxiety (n = 17) improved in 47.1% and worsened in 23.5%. Adverse effects, mostly somnolence and change in appetite were mild.
Conclusion: Parents’ reports suggest that cannabidiol may improve ASD comorbidity symptoms; however, the long-term effects should be evaluated in large scale studies.”