Tag Archives: Cannabinoids

Using cannabis for pain management after spinal cord injury: a qualitative study.

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Image result for spinal cord series and cases

“OBJECTIVES:

To explore why individuals with spinal cord injury (SCI) choose to use cannabis to manage their pain and their experiences in doing so.

RESULTS:

Eight individuals participated in this study. We interpreted six themes that captured the participants’ perspectives regarding their choice to, and perceptions of, using cannabis to manage SCI pain. Participants were motivated to use cannabis when other pain management strategies had been ineffective and were well-informed, knowledgeable cannabis consumers. Participants reported cannabis reduced their pain quickly and enabled them to engage in activities of daily living and participate in life roles without the drowsiness of traditional prescribed pain medication. Despite the positive aspects, participants were concerned about the irregularity of supply and inconsistent dosage.

CONCLUSIONS:

Findings show that cannabis is used to reduce pain after SCI and enable increased community participation. Findings suggest that future studies examining the efficacy of cannabinoids in managing pain include function and participation outcome measures rather than solely focusing on measuring pain intensity. Focusing on meaningful outcomes may contribute to a greater understanding of the experiences of people with SCI.”

https://www.ncbi.nlm.nih.gov/pubmed/31632740

https://www.nature.com/articles/s41394-019-0227-3

“Cannabis helps those with spinal cord injuries escape pain”  https://medicalxpress.com/news/2019-10-cannabis-spinal-cord-injuries-pain.html

The endocannabinoid system: Novel targets for treating cancer induced bone pain.

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Biomedicine & Pharmacotherapy“Treating Cancer-induced bone pain (CIBP) continues to be a major clinical challenge and underlying mechanisms of CIBP remain unclear.

Recently, emerging body of evidence suggested the endocannabinoid system (ECS) may play essential roles in CIBP. Here, we summarized the current understanding of the antinociceptive mechanisms of endocannabinoids in CIBP and discussed the beneficial effects of endocannabinoid for CIBP treatment.

Targeting non-selective cannabinoid 1 receptors or selective cannabinoid 2 receptors, and modulation of peripheral AEA and 2-AG, as well as the inhibition the function of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have produced analgesic effects in animal models of CIBP.

Management of ECS therefore appears to be a promising way for the treatment of CIBP in terms of efficacy and safety. Further clinical studies are encouraged to confirm the possible translation to humans of the very promising results already obtained in the preclinical studies.”

https://www.ncbi.nlm.nih.gov/pubmed/31627091

“Thus, cannabinoids may be clinically useful for treating chronic pain and CIBP.”

https://www.sciencedirect.com/science/article/pii/S075333221933731X?via%3Dihub

Neuropeptide Y and cannabinoids interaction in the amygdala after exposure to shock and reminders model of PTSD.

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Neuropharmacology“Modulation of cannabinoid and neuropeptide Y (NPY) receptors may offer therapeutic benefits for post-traumatic stress disorder (PTSD).

In this study, we aimed to investigate the functional interaction between these systems in the basolateral amygdala (BLA) in a rat model of PTSD.

The findings suggest that the functional interaction between the eCB and NPY1 systems is complex and provide a rationale for exploring novel therapeutic strategies that target the cannabinoid and NPY systems for stress-related diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/31622603

https://www.sciencedirect.com/science/article/pii/S0028390819303661?via%3Dihub

Systematic Affinity Purification Coupled to Mass Spectrometry Identified p62 as Part of the Cannabinoid Receptor CB2 Interactome.

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Image result for frontiers in molecular neuroscience“The endocannabinoid system (ECS) consists particularly of cannabinoid receptors 1 and 2 (CB1 and CB2), their endogenous ligands, and enzymes that synthesize and degrade their ligands. It acts in a variety of organs and disease states ranging from cancer progression over neuropathic pain to neurodegeneration. Protein components engaged in the signaling, trafficking, and homeostasis machinery of the G-protein coupled CB2, are however largely unknown. It is therefore important to identify further interaction partners to better understand CB2 receptor functions in physiology and pathophysiology. For this purpose, we used an affinity purification and mass spectrometry-based proteomics approach of Strep-HA-CB2 receptor in HEK293 cells. After subtraction of background interactions and protein frequency library assessment we could identify 83 proteins that were classified by the identification of minimally 2 unique peptides as highly probable interactors. A functional protein association network analysis obtained an interaction network with a significant enrichment of proteins functionally involved in protein metabolic process, in endoplasmic reticulum, response to stress but also in lipid metabolism and membrane organization. The network especially contains proteins involved in biosynthesis and trafficking like calnexin, Sec61A, tubulin chains TUBA1C and TUBB2B, TMED2, and TMED10. Six proteins that were only expressed in stable CB2 expressing cells were DHC24, DHRS7, GGT7, HECD3, KIAA2013, and PLS1. To exemplify the validity of our approach, we chose a candidate having a relatively low number of edges in the network to increase the likelihood of a direct protein interaction with CB2 and focused on the scaffold/phagosomal protein p62/SQSTM1. Indeed, we independently confirmed the interaction by co-immunoprecipitation and immunocytochemical colocalization studies. 3D reconstruction of confocal images furthermore showed CB2 localization in close proximity to p62 positive vesicles at the cell membrane. In summary, we provide a comprehensive repository of the CB2 interactome in HEK293 cells identified by a systematic unbiased approach, which can be used in future experiments to decipher the signaling and trafficking complex of this cannabinoid receptor. Future studies will have to analyze the exact mechanism of the p62-CB2 interaction as well as its putative role in disease pathophysiology.”

https://www.ncbi.nlm.nih.gov/pubmed/31616248

https://www.frontiersin.org/articles/10.3389/fnmol.2019.00224/full

The Endocannabinoid System as a Window Into Microglial Biology and Its Relationship to Autism.

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Image result for frontiers in cellular neuroscience“Microglia are the resident, innate immune cells of the central nervous system (CNS) and are critical in managing CNS injuries and infections. Microglia also maintain CNS homeostasis by influencing neuronal development, viability, and function. However, aberrant microglial activity and phenotypes are associated with CNS pathology, including autism spectrum disorder (ASD). Thus, improving our knowledge of microglial regulation could provide insights into the maintenance of CNS homeostasis as well as the prevention and treatment of ASD.

Control of microglial activity is in part overseen by small, lipid-derived molecules known as endogenous cannabinoids (endocannabinoids). Endocannabinoids are one component of the endocannabinoid system (ECS), which also includes the enzymes that metabolize these ligands, in addition to cannabinoid receptor 1 (CB1) and 2 (CB2).

Interestingly, increased ECS signaling leads to an anti-inflammatory, neuroprotective phenotype in microglia. Here, we review the literature and propose that ECS signaling represents a largely untapped area for understanding microglial biology and its relationship to ASD, with special attention paid to issues surrounding the use of recreational cannabis (marijuana). We also discuss major questions within the field and suggest directions for future research.”

https://www.ncbi.nlm.nih.gov/pubmed/31619967

“Microglial activity can be modulated by eCB signaling, which makes the ECS a potentially forceful tool in the prevention and management of CNS dysfunction.”

https://www.frontiersin.org/articles/10.3389/fncel.2019.00424/full

Cannabinoid effects on responses to quantitative sensory testing among individuals with and without clinical pain: a systematic review.

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Image result for wolters kluwer“There has been an explosion of interest in the utility of cannabinoids as potential analgesics.

This systematic review critically synthesizes the evidence for cannabinoid analgesic effects on quantitative sensory testing outcomes in both healthy adults and patients with chronic non-cancer pain (CNCP).

Our systematic review protocol is pre-registered on PROSPERO (CRD42018117367). An electronic search was made in PsycINFO, Cochrane, Google Scholar, Embase, and Pubmed of all literature published until August 2018. Of the 1,217 studies found from the search, a total 39 placebo-controlled studies that met the eligibility criteria were synthesized for the present study. Due to substantial heterogeneity of study designs, populations, cannabinoid compounds, and quantitative sensory testing outcomes, meta-analysis was not conducted.

More consistent evidence of cannabinoid analgesia was observed for inhaled cannabis than synthetic cannabinoids.

Analgesic effects were most commonly observed in tests of cold pain sensitivity, and hyperalgesic effects were most commonly observed in tests of electrical stimulation. Patterns of findings from studies with healthy subjects did not substantively differ from those with CNCP. However, these observations are qualified by the high degree of inconsistency across studies and methodological heterogeneity. We offer recommendations for future studies to improve study rigor and reproducibility.”

 https://www.ncbi.nlm.nih.gov/pubmed/31613869
https://insights.ovid.com/crossref?an=00006396-900000000-98577

Antitumor Activity of Abnormal Cannabidiol and Its Analog O-1602 in Taxol-Resistant Preclinical Models of Breast Cancer.

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Image result for frontiers in pharmacology“Cannabinoids exhibit anti-inflammatory and antitumorigenic properties.

Contrary to most cannabinoids present in the Cannabis plant, some, such as O-1602 and abnormal cannabidiol, have no or only little affinity to the CB1 or CB2 cannabinoid receptors and instead exert their effects through other receptors.

Here, we investigated whether the synthetic regioisomers of cannabidiol, abnormal cannabidiol, and a closely related compound, O-1602, display antitumorigenic effects in cellular models of breast cancer and whether it could reduce tumorigenesis in vivo.

Several studies have shown the effects of cannabinoids on chemotherapy-sensitive breast cancer cell lines, but less is known about the antitumorigenic effects of cannabinoids in chemotherapy-resistant cell lines.

Paclitaxel-resistant MDA-MB-231 and MCF-7 breast cancer cell lines were used to study the effect of O-1602 and abnormal cannabidiol on viability, apoptosis, and migration. The effects of O-1602 and abnormal cannabidiol on cell viability were completely blocked by the combination of GPR55 and GPR18-specific siRNAs. Both O-1602 and abnormal cannabidiol decreased viability in paclitaxel-resistant breast cancer cells in a concentration-dependent manner through induction of apoptosis. The effect of these cannabinoids on tumor growth in vivo was studied in a zebrafish xenograft model. In this model, treatment with O-1602 and abnormal cannabidiol (2 µM) significantly reduced tumor growth.

Our results suggest that atypical cannabinoids, like O-1602 and abnormal cannabidiol, exert antitumorigenic effects on paclitaxel-resistant breast cancer cells. Due to their lack of central sedation and psychoactive effects, these atypical cannabinoids could represent new leads for the development of additional anticancer treatments when resistance to conventional chemotherapy occurs during the treatment of breast and possibly other cancers.”

https://www.ncbi.nlm.nih.gov/pubmed/31611800

“Our results suggest that some cannabinoids acting through the GPR55 and/or GPR18 receptors can be helpful in inducing apoptosis in breast cancer cell lines that are unresponsive to paclitaxel. The effects of O-1602 and Abn-CBD on cell viability were observed both in vitro and in a zebrafish xenograft model. These drugs were also reducing cell migration. Taken together, even if no synergistic antitumor effect is always observed when cannabinoids and chemotherapeutic agents are combined as an anticancer treatment, cannabinoids can still provide anticancer benefits on top of their palliative effects. This is particularly important in the context of cancers that have developed resistance to current chemotherapies.”

https://www.frontiersin.org/articles/10.3389/fphar.2019.01124/full

‘Standard THC Units’: a proposal to standardise dose across all cannabis products and methods of administration.

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Publication cover image“Cannabis products are becoming increasingly diverse, and they vary considerably in concentrations of ∆9 -tetrahydrocannabinol (THC) and cannabidiol (CBD). Higher doses of THC can increase the risk of harm from cannabis, while CBD may partially offset some of these effects. Lower Risk Cannabis Use Guidelines currently lack recommendations based on quantity of use, and could be improved by implementing standard units. However, there is currently no consensus on how units should be measured or standardised across different cannabis products or methods of administration.

ARGUMENT:

Existing proposals for standard cannabis units have been based on specific methods of administration (e.g. joints) and these may not capture other methods including pipes, bongs, blunts, dabbing, vaporizers, vape pens, edibles and liquids. Other proposals (e.g. grams of cannabis) cannot account for heterogeneity in THC concentrations across different cannabis products. Similar to alcohol units, we argue that standard cannabis units should reflect the quantity of active pharmacological constituents (dose of THC). On the basis of experimental and ecological data, public health considerations, and existing policy we propose that a ‘Standard THC Unit’ should be fixed at 5 milligrams of THC for all cannabis products and methods of administration. If supported by sufficient evidence in future, consumption of Standard CBD Units might offer an additional strategy for harm reduction.

CONCLUSIONS:

Standard THC Units can potentially be applied across all cannabis products and methods of administration to guide consumers and promote safer patterns of use.”

https://www.ncbi.nlm.nih.gov/pubmed/31606008

https://onlinelibrary.wiley.com/doi/abs/10.1111/add.14842

Disease associated polymorphisms within the conserved ECR1 enhancer differentially regulate the tissue specific activity of the cannabinoid-1 receptor gene promoter; implications for cannabinoid pharmacogenetics.

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Publication cover image“Cannabinoid receptor-1 (CB1) represents a potential drug target against conditions that include obesity and substance abuse. However, drug trials targeting CB1 (encoded by the CNR1 gene) have been compromised by differences in patient response.

Towards addressing the hypothesis that genetic changes within the regulatory regions controlling CNR1 expression contribute to these differences, we characterised the effects of disease associated allelic variation within a conserved regulatory sequence (ECR1) in CNR1 intron 2 that had previously been shown to modulate cannabinoid response, alcohol intake and anxiety-like behaviour.

We used primary cell analysis of reporters carrying different allelic variants of the human ECR1 and found that human specific C-allele variants of ECR1 (ECR1(C)) drove higher levels of CNR1prom activity in primary hippocampal cells than did the ancestral T-allele and demonstrated a differential response to CB1 agonism.

We further demonstrate a role for the AP-1 transcription factor in driving higher ECR1(C) activity and evidence that the ancestral t-allele variant of ECR1 interacted with higher affinity with the insulator binding factor CTCF. The cell-specific approaches used in our study represent an important step in gaining a mechanistic understanding the roles of non-coding polymorphic variation in disease and in the increasingly important field of cannabinoid pharmacogenetics.”

https://www.ncbi.nlm.nih.gov/pubmed/31608546

https://onlinelibrary.wiley.com/doi/abs/10.1002/humu.23931

The potential role of cannabinoids in dermatology.

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 Publication Cover“Cannabis is increasingly being used world-wide to treat a variety of dermatological conditions. Medicinal cannabis is currently legalized in Canada, 31 states in America and 19 countries in Europe. The authors reviewed the literature on the pharmacology and use of cannabinoids in treating a variety of skin conditions including acne, atopic dermatitis, psoriasis, skin cancer, pruritus, and pain. Cannabinoids have demonstrated anti-inflammatory, antipruritic, anti-ageing, and antimalignancy properties by various mechanisms including interacting with the newly found endocannabinoid system of the skin thereby providing a promising alternative to traditional treatments.”

https://www.ncbi.nlm.nih.gov/pubmed/31599175

https://www.tandfonline.com/doi/abs/10.1080/09546634.2019.1675854?journalCode=ijdt20