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

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Dark Classics in Chemical Neuroscience: Δ9-Tetrahydrocannabinol.

 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

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Cannabinoids as a Potential New and Novel Treatment for Melanoma: A Pilot Study in a Murine Model.

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

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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.”

“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

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Indazolylketones as new multitarget cannabinoid drugs.

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

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

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

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Attitudes toward and knowledge of medical cannabis among individuals with spinal cord injury.

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“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

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Some Prospective Alternatives for Treating Pain: The Endocannabinoid System and Its Putative Receptors GPR18 and GPR55.

Image result for frontiers in pharmacology“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

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Cannabis, cannabinoid receptors, and endocannabinoid system: yesterday, today, and tomorrow

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“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.”
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Cannabinoid Receptor as a potential therapeutic target for Parkinson’s Disease.

Brain Research Bulletin

“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

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