Monthly Archives: January 2019

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.

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“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.

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 ACS Chemical Neuroscience

“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.”

https://www.ncbi.nlm.nih.gov/pubmed/30689342

https://pubs.acs.org/doi/10.1021/acschemneuro.8b00651

Targeting CB1 and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease.

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 “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.

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Journal of Surgical Research Home

“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.

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“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

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“Cannabidiol (CBD), the nonpsychoactive compound in cannabis, may help normalize function in brain regions associated with psychosis, found a study in JAMA Psychiatry.”

https://www.ncbi.nlm.nih.gov/pubmed/30694318
https://jamanetwork.com/journals/jama/article-abstract/2722769

“Effect of Cannabidiol on Medial Temporal, Midbrain, and Striatal Dysfunction in People at Clinical High Risk of Psychosis A Randomized Clinical Trial. Cannabidiol (CBD) has antipsychotic effects in humans. Cannabidiol may partially normalize alterations in parahippocampal, striatal, and midbrain function associated with the CHR state. As these regions are critical to the pathophysiology of psychosis, the influence of CBD at these sites could underlie its therapeutic effects on psychotic symptoms.” https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2697762

Oral Cannabidiol Use in Children With Autism Spectrum Disorder to Treat Related Symptoms and Co-morbidities.

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“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.”

 https://www.ncbi.nlm.nih.gov/pubmed/30687090
https://www.frontiersin.org/articles/10.3389/fphar.2018.01521/full

Indazolylketones as new multitarget cannabinoid drugs.

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European Journal of Medicinal Chemistry

“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

Cannabinoid type-1 receptor blockade restores neurological phenotypes in two models for Down syndrome.

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Neurobiology of Disease“Intellectual disability is the most limiting hallmark of Down syndrome, for which there is no gold-standard clinical treatment yet.

The endocannabinoid system is a widespread neuromodulatory system involved in multiple functions including learning and memory processes.

Our results identify CB1R as a novel druggable target potentially relevant for the improvement of cognitive deficits associated with Down syndrome.”

https://www.ncbi.nlm.nih.gov/pubmed/30685352

https://www.sciencedirect.com/science/article/pii/S0969996118306855?via%3Dihub

“Endocannabinoid system, a target to improve cognitive disorders in models of Down syndrome” https://www.sciencedaily.com/releases/2019/02/190206115550.htm

“Endocannabinoid system, a target to improve cognitive disorders in models of Down syndrome” https://medicalxpress.com/news/2019-02-endocannabinoid-cognitive-disorders-syndrome.html

Cannabidiol modulates phosphorylated rpS6 signalling in a zebrafish model of Tuberous Sclerosis Complex.

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Behavioural Brain Research

“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