“Cannabidiol (CBD), the nonpsychoactive compound in cannabis, may help normalize function in brain regions associated with psychosis, found a study in JAMA Psychiatry.”
Cannabidiol May Help Normalize Brain Function in Psychosis
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Tag Archives: therapeutic
Indazolylketones as new multitarget cannabinoid drugs.
“Multitarget cannabinoids could be a promising therapeutic strategic to fight against Alzheimer’s disease.
In this sense, our group has developed a new family of indazolylketones with multitarget profile including cannabinoids, cholinesterase and BACE-1 activity. A medicinal chemistry program that includes computational design, synthesis and in vitro and cellular evaluation has allowed to us to achieve lead compounds.
In this work, the synthesis and evaluation of a new class of indazolylketones have been performed. Pharmacological evaluation includes functional activity for cannabinoid receptors on isolated tissue. In addition, in vitro inhibitory assays in AChE/BuChE enzymes and BACE-1 have been carried out. Furthermore, studies of neuroprotective effects in human neuroblastoma SH-SY5Y cells and studies of the mechanisms of survival/death in lymphoblasts of patients with Alzheimer’s disease have been achieved.
The results of pharmacological tests have revealed that some of these derivatives (5, 6) behave as CB2 cannabinoid agonists and simultaneously show BuChE and/or BACE-1 inhibition.”
https://www.ncbi.nlm.nih.gov/pubmed/30685536
https://www.sciencedirect.com/science/article/pii/S0223523419300406?via%3Dihub
Cannabidiol modulates phosphorylated rpS6 signalling in a zebrafish model of Tuberous Sclerosis Complex.
“Tuberous sclerosis complex (TSC) is a rare disease caused by mutations in the TSC1 or TSC2 genes and is characterized by widespread tumour growth, intractable epilepsy, cognitive deficits and autistic behaviour.
CBD has been reported to decrease seizures and inhibit tumour cell progression, therefore we sought to determine the influence of CBD on TSC pathology in zebrafish carrying a nonsense mutation in the tsc2 gene.
CBD treatment from 6 to 7 days post-fertilization (dpf) induced significant anxiolytic actions without causing sedation. Furthermore, CBD treatment from 3 dpf had no impact on tsc2-/- larvae motility nor their survival. CBD treatment did, however, reduce the number of phosphorylated rpS6 positive cells, and their cross-sectional cell size. This suggests a CBD mediated suppression of mechanistic target of rapamycin (mTOR) activity in the tsc2-/- larval brain.
Taken together, these data suggest that CBD selectively modulates levels of phosphorylated rpS6 in the brain and additionally provides an anxiolytic effect. This is pertinent given the alterations in mTOR signalling in experimental models of TSC. Additional work is necessary to identify upstream signal modulation and to further justify the use of CBD as a possible therapeutic strategy to manage TSC.”
https://www.ncbi.nlm.nih.gov/pubmed/30684511
https://www.sciencedirect.com/science/article/pii/S0166432818311215?via%3Dihub
Attitudes toward and knowledge of medical cannabis among individuals with spinal cord injury.
“An observational study based on an online survey addressing attitudes toward and knowledge of cannabis among people living with spinal cord injury (SCI).
Participants largely believed that cannabis use is safe, has potential therapeutic benefits, and ought to be legal.
This study is the first to assess beliefs about and attitudes toward cannabis use among a nationwide sample of people with SCI. While limited, it provides a roadmap for future research. It also offers medical providers an initial understanding of which factors may encourage or dissuade their patients with SCI from seeking medical cannabis treatment.”
https://www.ncbi.nlm.nih.gov/pubmed/30675390
https://www.nature.com/articles/s41394-019-0151-6
“Cannabis cures the spine.” https://www.ncbi.nlm.nih.gov/pubmed/30172587
Some Prospective Alternatives for Treating Pain: The Endocannabinoid System and Its Putative Receptors GPR18 and GPR55.
“Marijuana extracts (cannabinoids) have been used for several millennia for pain treatment.
Regarding the site of action, cannabinoids are highly promiscuous molecules, but only two cannabinoid receptors (CB1 and CB2) have been deeply studied and classified.
Thus, therapeutic actions, side effects and pharmacological targets for cannabinoids have been explained based on the pharmacology of cannabinoid CB1/CB2 receptors. However, the accumulation of confusing and sometimes contradictory results suggests the existence of other cannabinoid receptors.
Different orphan proteins (e.g., GPR18, GPR55, GPR119, etc.) have been proposed as putative cannabinoid receptors.
According to their expression, GPR18 and GPR55 could be involved in sensory transmission and pain integration.
This work summarized novel data supporting that, besides cannabinoid CB1 and CB2receptors, GPR18 and GPR55 may be useful for pain treatment.
Conclusion: There is evidence to support an antinociceptive role for GPR18 and GPR55.”
https://www.ncbi.nlm.nih.gov/pubmed/30670965
https://www.frontiersin.org/articles/10.3389/fphar.2018.01496/full
Cannabis, cannabinoid receptors, and endocannabinoid system: yesterday, today, and tomorrow
“Cannabis sativa, is also popularly known as marijuana, has been cultivated and used for recreational and medicinal purposes for many centuries.
The main psychoactive content in cannabis is Δ9-tetrahydrocannabinol (THC). In addition to plant cannabis sativa, there are two classes of cannabinoids—the synthetic cannabinoids (e.g., WIN55212–2) and the endogenous cannabinoids (eCB), anandamide (ANA) and 2-arachidonoylglycerol (2-AG).
The biological effects of cannabinoids are mainly mediated by two members of the G-protein-coupled receptor family, cannabinoid receptors 1 (CB1R) and 2 (CB2R). The endocannabinoids, cannabinoid receptors, and the enzymes/proteins responsible for their biosynthesis, degradation, and re-updating constitute the endocannabinoid system.
In recent decades, the endocannabinoid system has attracted considerable attention as a potential therapeutic target in numerous physiological conditions, such as in energy balance, appetite stimulation, blood pressure, pain modulation, embryogenesis, nausea and vomiting control, memory, learning and immune response, as well as in pathological conditions such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, and multiple sclerosis.
The major goal of this Special Issue is to discuss and evaluate the current progress in cannabis and cannabinoid research in order to increase our understanding about cannabinoid action and the underlying biological mechanisms and promote the development cannabinoid-based pharmacotherapies.
Overall, the present special issue provides an overview and insight on pharmacological mechanisms and therapeutic potentials of cannabis, cannabinoid receptors, and eCB system. I believe that this special issue will promote further efforts to apply cannabinoid ligands as the therapeutic strategies for treating a variety of diseases.”
Cannabinoid Receptor as a potential therapeutic target for Parkinson’s Disease.
“Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease, characterized by the loss of dopaminergic neurons from substantia nigra pars compacta of basal ganglia caused due to gene mutation, misfolded protein aggregation, reactive oxygen species generation and inflammatory stress. Degeneration of dopaminergic neurons results in muscle stiffness, uncoordinated body movements, sleep disturbance, fatigue, amnesia and impaired voice.
Currently, levodopa (L-DOPA) administration is the most widely used therapy for PD. But prolonged administration of L-DOPA is associated with the symptoms of dyskinesia.
However, emerging evidences suggest the role of cannabinoid receptors (CBRs) in curtailing the progression of PD by activating neuroprotective pathways. Hence, cannabinoid therapy could be a promising alternative to combat PD in future.
In the present review we have discussed the potential role of CBRs in attenuating the key mechanisms of PD and how the existing research gaps needs to be bridged in order to understand the molecular mechanism of CBRs in detail.”
https://www.ncbi.nlm.nih.gov/pubmed/30664919
https://www.sciencedirect.com/science/article/abs/pii/S0361923018306208?via%3Dihub
Real life Experience of Medical Cannabis Treatment in Autism: Analysis of Safety and Efficacy.
“There has been a dramatic increase in the number of children diagnosed with autism spectrum disorders (ASD) worldwide. Recently anecdotal evidence of possible therapeutic effects of cannabis products has emerged.
The aim of this study is to characterize the epidemiology of ASD patients receiving medical cannabis treatment and to describe its safety and efficacy.
We analysed the data prospectively collected as part of the treatment program of 188 ASD patients treated with medical cannabis between 2015 and 2017. The treatment in majority of the patients was based on cannabis oil containing 30% CBD and 1.5% THC. Symptoms inventory, patient global assessment and side effects at 6 months were primary outcomes of interest and were assessed by structured questionnaires.
After six months of treatment 82.4% of patients (155) were in active treatment and 60.0% (93) have been assessed; 28 patients (30.1%) reported a significant improvement, 50 (53.7%) moderate, 6 (6.4%) slight and 8 (8.6%) had no change in their condition. Twenty-three patients (25.2%) experienced at least one side effect; the most common was restlessness (6.6%).
Cannabis in ASD patients appears to be well tolerated, safe and effective option to relieve symptoms associated with ASD.”
https://www.ncbi.nlm.nih.gov/pubmed/30655581
https://www.nature.com/articles/s41598-018-37570-y
“Medical cannabis is an effective, well-tolerated, and most importantly, a safe treatment for autism in children, helping to reduce a range of symptoms in those with the condition, a new study finds.” https://www.studyfinds.org/cannabis-safe-effective-treatment-autism-young-children/
The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No “Strain,” No Gain
“The current wave of excitement in Cannabis commerce has translated into a flurry of research on alternative sources, particularly yeasts, and complex systems for laboratory production have emerged, but these presuppose that single compounds are a desirable goal. Rather, the case for Cannabis synergy via the “entourage effect” is currently sufficiently strong as to suggest that one molecule is unlikely to match the therapeutic and even industrial potential of Cannabis itself as a phytochemical factory.
These studies and others provide a firm foundation for Cannabis synergy, and support for botanical drug development vs. that of single components, or production via fermentation methods in yeast or other micro-organisms.
This article has briefly outlined recently technological attempts to “reinvent the phytocannabinoid wheel.” Cogent arguments would support that it can be done, but should it be done? The data supporting the existence of Cannabis synergy and the astounding plasticity of the Cannabis genome suggests a reality that obviates the need for alternative hosts, or even genetic engineering of Cannabis sativa, thus proving that, “The plant does it better.””
Crystal Structure of the Human Cannabinoid Receptor CB2.
“The cannabinoid receptor CB2 is predominately expressed in the immune system, and selective modulation of CB2 without the psychoactivity of CB1 has therapeutic potential in inflammatory, fibrotic, and neurodegenerative diseases.
Here, we report the crystal structure of human CB2 in complex with a rationally designed antagonist, AM10257, at 2.8 Å resolution. The CB2-AM10257 structure reveals a distinctly different binding pose compared with CB1. However, the extracellular portion of the antagonist-bound CB2 shares a high degree of conformational similarity with the agonist-bound CB1, which led to the discovery of AM10257’s unexpected opposing functional profile of CB2 antagonism versus CB1 agonism.
Further structural analysis using mutagenesis studies and molecular docking revealed the molecular basis of their function and selectivity for CB2 and CB1. Additional analyses of our designed antagonist and agonist pairs provide important insight into the activation mechanism of CB2. The present findings should facilitate rational drug design toward precise modulation of the endocannabinoid system.”
https://www.ncbi.nlm.nih.gov/pubmed/30639103
https://linkinghub.elsevier.com/retrieve/pii/S0092867418316258