“Neurodegeneration is associated with dysfunction of calcium buffering capacity and thereby sustained cellular and mitochondrial calcium overload. Paraneoplastic cerebellar degeneration (PCD), characterized by progressive Purkinje neuron degeneration following paraneoplastic Yo antibody internalisation and binding to cerebellar degeneration-related protein CDR2 and CDR2L, has been linked to intracellular calcium homeostasis imbalance due to calbindin D28k malfunction. Therefore, we hypothesized that Yo antibody internalisation affects not only calbindin calcium binding capacity but also calcium-sensitive mitochondrial-associated signalling, causing mitochondrial calcium overload and thereby Purkinje neuron death.
Category Archives: Uncategorized
Prolonged Cannabidiol Treatment Effects on Hippocampal Subfield Volumes in Current Cannabis Users.
“Chronic cannabis use is associated with neuroanatomical alterations in the hippocampus. While adverse impacts of cannabis use are generally attributed to Δ9-tetrahydrocannabinol, emerging naturalistic evidence suggests cannabidiol (CBD) is neuroprotective and may ameliorate brain harms associated with cannabis use, including protection from hippocampal volume loss. This study examined whether prolonged administration of CBD to regular cannabis users within the community could reverse or reduce the characteristic hippocampal harms associated with chronic cannabis use.
Results: No change was observed in left or right hippocampus as a whole. However, left subicular complex (parasubiculum, presubiculum, and subiculum) volume significantly increased from baseline to post-treatment (p=0.017 uncorrected) by 1.58% (Cohen’s d=0.63; 2.83% in parasubiculum). Heavy cannabis users demonstrated marked growth in the left subicular complex, predominantly within the presubiculum, and right cornu ammonis (CA)1 compared to lighter users. Associations between greater right subicular complex and total hippocampal volume and higher plasma CBD concentration were evident, particularly in heavy users.
Conclusions: Our findings suggest a restorative effect of CBD on the subicular and CA1 subfields in current cannabis users, especially those with greater lifetime exposure to cannabis. While replication is required in a larger, placebo-controlled trial, these findings support a protective role of CBD against brain structural harms conferred by chronic cannabis use. Furthermore, these outcomes suggest that CBD may be a useful adjunct in treatments for cannabis dependence and may be therapeutic for a range of clinical disorders characterized by hippocampal pathology (e.g., schizophrenia, Alzheimer’s disease, and major depressive disorder).”
https://www.ncbi.nlm.nih.gov/pubmed/29682609
“In conclusion, our findings are the first to demonstrate an ameliorating effect of CBD treatment upon brain structural harms characteristic of regular cannabis use. Furthermore, these results speak to the potential for CBD treatment to restore hippocampal pathology in a range of clinical populations (e.g., schizophrenia, Alzheimer’s disease, and major depressive disorder).” https://www.liebertpub.com/doi/10.1089/can.2017.0047Marijuana Use by Adolescents and Young Adults with Inflammatory Bowel Disease.
“Marijuana use by adolescents and young adults with IBD is common and perceived as beneficial.” https://www.ncbi.nlm.nih.gov/pubmed/29673723 http://www.jpeds.com/article/S0022-3476(18)30388-3/fulltext]]>
Association of Cannabis With Cognitive Functioning in Adolescents and Young Adults: A Systematic Review and Meta-analysis
“Question Is frequent or heavy cannabis use associated with cognitive dysfunction in adolescents and young adults? Findings This systematic review and meta-analysis of 69 cross-sectional studies of 2152 cannabis users and 6575 comparison participants showed a small but significant overall effect size for reduced cognitive functioning in adolescents and young adults who reported frequent cannabis use. However, studies requiring abstinence from cannabis for longer than 72 hours had a very small, nonsignificant effect size. Meaning Although continued cannabis use may be associated with small reductions in cognitive functioning, results suggest that cognitive deficits are substantially diminished with abstinence. Conclusions and Relevance Associations between cannabis use and cognitive functioning in cross-sectional studies of adolescents and young adults are small and may be of questionable clinical importance for most individuals. Furthermore, abstinence of longer than 72 hours diminishes cognitive deficits associated with cannabis use. Although other outcomes (eg, psychosis) were not examined in the included studies, results indicate that previous studies of cannabis in youth may have overstated the magnitude and persistence of cognitive deficits associated with use.” https://www.ncbi.nlm.nih.gov/pubmed/29710074 https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2678214?redirect=true
“Cannabis harm to teenagers’ brains ‘overstated’, finds study” https://www.independent.co.uk/news/health/cannabis-marijuana-legalisation-harm-brain-intelligence-development-mental-health-a8311126.html
“Weed doesn’t make stoners permanently slow – study” http://www.newshub.co.nz/home/health/2018/04/weed-doesn-t-make-stoners-permanently-slow-study.html
“Marijuana’s effects on young brains diminish 72 hours after use, research says” https://www.cnn.com/2018/04/18/health/marijuana-cognitive-effects-study/index.html
]]>Medical Marijuana Use in Older Adults.
“Symptom management in older adults, including pain and distressing non-pain symptoms, can be challenging. Medications can cause side effects that worsen quality of life or create other symptoms, and polypharmacy itself can be detrimental in older adults.
Cannabinoids may offer a way of managing selected symptoms with fewer side effects.
Medical marijuana is an important area of study for older adults because of the side effects of other medications. It is also important for Baby Boomers, who are likely to have more experience with marijuana than older adults of previous generations. Therefore, geriatricians should understand medical marijuana’s clinical indications, adverse effects, and legal context.
This article reviews the evidence regarding indications for and risks of medical marijuana use in older adults.”
https://www.ncbi.nlm.nih.gov/pubmed/29668039
https://onlinelibrary.wiley.com/doi/abs/10.1111/jgs.15346
“Our study finds that the therapeutic use of cannabis is safe and efficacious in the elderly population.” https://www.ncbi.nlm.nih.gov/pubmed/29398248
“Medical cannabis significantly safer for elderly with chronic pain than Opioids” https://www.sciencedaily.com/releases/2018/02/180213111508.htm
]]>Ajulemic acid: potential treatment for chronic inflammation.
“Ajulemic acid (AJA, CT-3, IP-751, JBT-101, anabasum) is a first-in-class, synthetic, orally active, cannabinoid-derived drug that preferentially binds to the CB2 receptor and is nonpsychoactive.
In preclinical studies, and in Phase 1 and 2 clinical trials, AJA showed a favorable safety, tolerability, and pharmacokinetic profile. It also demonstrated significant efficacy in preclinical models of inflammation and fibrosis. It suppresses tissue scarring and stimulates endogenous eicosanoids that resolve chronic inflammation and fibrosis without causing immunosuppression.
AJA is currently being developed for use in 4 separate but related indications including systemic sclerosis (SSc), cystic fibrosis, dermatomyositis (DM), and systemic lupus erythematosus. Phase 2 clinical trials in the first 3 targets demonstrated that it is safe, is a potential treatment for these orphan diseases and appears to be a potent inflammation-resolving drug with a unique mechanism of action, distinct from the nonsteroidal anti-inflammatory drug (NSAID), and will be useful for treating a wide range of chronic inflammatory diseases.
It may be considered to be a disease-modifying drug unlike most NSAIDs that only provide symptomatic relief. AJA is currently being evaluated in 24-month open-label extension studies in SSc and in skin-predominant DM. A Phase 3 multicenter trial to demonstrate safety and efficacy in SSc has recently been initiated.”
“Research suggests that daily 