Tag Archives: treatment

Δ8 -Tetrahydrocannabivarin has potent anti-nicotine effects in multiple rodent models of nicotine dependence.

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British Journal of Pharmacology banner“Both types of cannabinoid receptors – CB1 and CB2 – regulate brain functions relating to addictive drug-induced reward and relapse. CB1 receptor antagonists and CB2 receptor agonists have anti-addiction efficacy, in animal models, against a broad range of addictive drugs.

Δ9 -Tetrahydrocannabivarin (Δ9 -THCV) – a cannabis constituent – acts as a CB1 antagonist and a CB2 agonist. Δ8 -Tetrahydrocannabivarin (Δ8 -THCV) is a Δ9 -THCV analogue with similar combined CB1 antagonist/CB2agonist properties.

KEY RESULTS:

Δ8 -THCV significantly attenuated intravenous nicotine self-administration, and both cue-induced and nicotine-induced relapse to nicotine-seeking behavior in rats. Δ8 -THCV also significantly attenuated nicotine-induced conditioned place preference and nicotine withdrawal in mice.

CONCLUSIONS AND IMPLICATIONS:

We conclude that Δ8 -THCV may have therapeutic potential for the treatment of nicotine dependence. We also suggest that tetrahydrocannabivarins should be tested for possible anti-addiction efficacy in a broader range of preclinical animal models, against other addictive drugs, and eventually in humans.”

https://www.ncbi.nlm.nih.gov/pubmed/31454413

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14844

Therapeutic potential of cannabinoid receptor 2 in the treatment of diabetes mellitus and its complications.

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European Journal of Pharmacology“The biological effects of endocannabinoid system are mediated by two types of receptors, cannabinoid 1 (CB1) and cannabinoid 2 receptor (CB2). They play a pivotal role in the management of pain, inflammation, cancer, obesity and diabetes mellitus.

CB2 receptor activity downregulation is hallmark of inflammation and oxidative stress. Strong evidence display the relation between activation of CB2 receptors with decrease in the pro-inflammatory cytokines and pro-apoptotic factors. Numerous in vitro and in vivo studies have been validated to confirm the role of CB2 receptor in the management of obesity, hyperlipidemia and diabetes mellitus by regulating glucose and lipid metabolism.

Activation of CB2 receptor has led to reduction of inflammatory cytokines; tumor necrosis factor-alpha (TNF-α), Interleukin 6 (IL-6), Nuclear factor kappa beta (NF-κβ) and also amelioration of reactive oxygen species and reactive nitrogen species playing role in apoptosis. Many studies confirmed the role of CB2 receptors in the insulin secretion via facilitating calcium entry into the pancreatic β-cells. CB2 receptors also displayed improvement in the neuronal and renal functions by decreasing the oxidative stress and downregulating inflammatory cascade.

The present review addresses, potential role of CB2 receptor activation in management of diabetes and its complications. It also includes the role of CB2 receptors as an anti-oxidant, anti-apoptotic and anti-inflammatory for the treatment of DM and its complications. Also, an informative summary of CB2 receptor agonist drugs is provided with their potential role in the reduction of glucose levels, increment in the insulin levels, decrease in the hyperglycaemic oxidative stress and inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/31461639

https://www.sciencedirect.com/science/article/pii/S0014299919305801?via%3Dihub

Cannabinoids and Mental Health, Part 1: The Endocannabinoid System and Exogenous Cannabinoids.

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Image result for j psychosoc nurs ment health serv“The increasing public acceptance of cannabis and the proliferation of cannabis products in the marketplace has coincided with more patients using the drug as a substitute for psychiatric medications or as an adjunctive treatment modality for psychiatric conditions, despite limited evidence of efficacy. With a goal of furthering harm-reduction efforts in psychiatric nursing, the current article reviews the fundamentals of the endocannabinoid system in humans and the exogenous phytocannabinoids that act on this regulatory neurotransmitter system. The basics of cannabis botany are also reviewed to help nurse clinicians understand the heterogeneous nature of cannabis products. This foundational knowledge will help improve clinical interactions with patients who use cannabis and provide the necessary understanding of cannabinoids needed to undertake further scientific query into their purported benefits in psychiatric disease states.”

https://www.ncbi.nlm.nih.gov/pubmed/31461513

Use of Medicinal Cannabis and Synthetic Cannabinoids in Post-Traumatic Stress Disorder (PTSD): A Systematic Review.

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medicina-logo“Post-traumatic stress disorder (PTSD) is a common psychiatric disorder resulting from a traumatic event, is manifested through hyperarousal, anxiety, depressive symptoms, and sleep disturbances.

Despite several therapeutic approaches being available, both pharmacological and psychological, recently a growing interest has developed in using cannabis and synthetic cannabinoids stems from their consideration as more efficient and better tolerated alternatives for the treatment of this condition.

The present paper aims to evaluate the clinical and therapeutic potentials of medical cannabis and synthetic cannabinoids in treating PTSD patients.

Present data show that cannabis and synthetic cannabinoids, both acting on the endocannabinoids system, may have a potential therapeutic use for improving PTSD symptoms, e.g., reducing anxiety, modulating memory-related processes, and improving sleep.”

https://www.ncbi.nlm.nih.gov/pubmed/31450833

https://www.mdpi.com/1010-660X/55/9/525

Cannabidivarin Treatment Ameliorates Autism-Like Behaviors and Restores Hippocampal Endocannabinoid System and Glia Alterations Induced by Prenatal Valproic Acid Exposure in Rats.

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 Image result for frontiers in cellular neuroscience“Autism spectrum disorder (ASD) is a developmental condition whose primary features include social communication and interaction impairments with restricted or repetitive motor movements. No approved treatment for the core symptoms is available and considerable research efforts aim at identifying effective therapeutic strategies.

Emerging evidence suggests that altered endocannabinoid signaling and immune dysfunction might contribute to ASD pathogenesis. In this scenario, phytocannabinoids could hold great pharmacological potential due to their combined capacities to act either directly or indirectly on components of the endocannabinoid system and to modulate immune functions.

Among all plant-cannabinoids, the phytocannabinoid cannabidivarin (CBDV) was recently shown to reduce motor impairments and cognitive deficits in animal models of Rett syndrome, a condition showing some degree of overlap with autism, raising the possibility that CBDV might have therapeutic potential in ASD.

Here, we investigated the ability of CBDV treatment to reverse or prevent ASD-like behaviors in male rats prenatally exposed to valproic acid (VPA; 500 mg/kg i.p.; gestation day 12.5).

CBDV in symptomatic rats recovered social impairments, social novelty preference, short-term memory deficits, repetitive behaviors and hyperlocomotion whereas preventative treatment reduced sociability and social novelty deficits, short-term memory impairments and hyperlocomotion, without affecting stereotypies.

As dysregulations in the endocannabinoid system and neuroinflammatory markers contribute to the development of some ASD phenotypes in the VPA model, neurochemical studies were performed after symptomatic treatment to investigate possible CBDV’s effects on the endocannabinoid system, inflammatory markers and microglia activation in the hippocampus and prefrontal cortex.

Prenatal VPA exposure increased CB1 receptor, FAAH and MAGL levels, enhanced GFAP, CD11b, and TNFα levels and triggered microglia activation restricted to the hippocampus. All these alterations were restored after CBDV treatment.

These data provide preclinical evidence in support of the ability of CBDV to ameliorate behavioral abnormalities resembling core and associated symptoms of ASD. At the neurochemical level, symptomatic CBDV restores hippocampal endocannabinoid signaling and neuroinflammation induced by prenatal VPA exposure.”

https://www.ncbi.nlm.nih.gov/pubmed/31447649

https://www.frontiersin.org/articles/10.3389/fncel.2019.00367/full

Clinicians’ Guide to Cannabidiol and Hemp Oils.

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Mayo Clinic“Cannabidiol (CBD) oils are low tetrahydrocannabinol products derived from Cannabis sativa that have become very popular over the past few years. Patients report relief for a variety of conditions, particularly pain, without the intoxicating adverse effects of medical marijuana.

In June 2018, the first CBD-based drug, Epidiolex, was approved by the US Food and Drug Administration for treatment of rare, severe epilepsy, further putting the spotlight on CBD and hemp oils.

There is a growing body of preclinical and clinical evidence to support use of CBD oils for many conditions, suggesting its potential role as another option for treating challenging chronic pain or opioid addiction.

Care must be taken when directing patients toward CBD products because there is little regulation, and studies have found inaccurate labeling of CBD and tetrahydrocannabinol quantities.

This article provides an overview of the scientific work on cannabinoids, CBD, and hemp oil and the distinction between marijuana, hemp, and the different components of CBD and hemp oil products.

We summarize the current legal status of CBD and hemp oils in the United States and provide a guide to identifying higher-quality products so that clinicians can advise their patients on the safest and most evidence-based formulations.

This review is based on a PubMed search using the terms CBD, cannabidiol, hemp oil, and medical marijuana. Articles were screened for relevance, and those with the most up-to-date information were selected for inclusion.”

https://www.ncbi.nlm.nih.gov/pubmed/31447137

https://www.mayoclinicproceedings.org/article/S0025-6196(19)30007-2/fulltext

The therapeutic role of cannabinoid receptors and its agonists or antagonists in Parkinson’s disease.

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Progress in Neuro-Psychopharmacology and Biological Psychiatry“Parkinson’s disease (PD) is a neurodegenerative disease and its characteristic is the progressive degeneration of dopaminergic neurons within the substantia nigra (SN) of the midbrain. There is hardly any clinically proven efficient therapeutics for its cure in several recent preclinical advances proposed to treat PD.

Recent studies have found that the endocannabinoid signaling system in particular the comprised two receptors, CB1 and CB2 receptors, has a significant regulatory function in basal ganglia and is involved in the pathogenesis of PD. Therefore, adding new insights into the biochemical interactions between cannabinoids and other signaling pathways may help develop new pharmacological strategies.

Factors of the endocannabinoid system (ECS) are abundantly expressed in the neural circuits of basal ganglia, where they interact interactively with glutamatergic, γ-aminobutyric acid-ergic (GABAergic), and dopaminergic signaling systems. Although preclinical studies on PD are promising, the use of cannabinoids at the clinical level has not been thoroughly studied.

In this review, we evaluated the available evidence and reviewed the involvement of ECS in etiologies, symptoms and treatments related to PD. Since CB1 and CB2 receptors are the two main receptors of endocannabinoids, we primarily put the focus on the therapeutic role of CB1 and CB2 receptors in PD. We will try to determine future research clues that will help understand the potential therapeutic benefits of the ECS in the treatment of PD, aiming to open up new strategies and ideas for the treatment of PD.”

https://www.ncbi.nlm.nih.gov/pubmed/31442553

https://www.sciencedirect.com/science/article/pii/S0278584619302210?via%3Dihub

Terpenoids and Phytocannabinoids Co-Produced in Cannabis Sativa Strains Show Specific Interaction for Cell Cytotoxic Activity.

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molecules-logo“Mixtures of different Cannabis sativa phytocannabinoids are more active biologically than single phytocannabinoids. However, cannabis terpenoids as potential instigators of phytocannabinoid activity have not yet been explored in detail.

Terpenoid groups were statistically co-related to certain cannabis strains rich in Δ9-tetrahydrocannabinolic acid (THCA) or cannabidiolic acid (CBDA), and their ability to enhance the activity of decarboxylase phytocannabinoids (i.e., THC or CBD) was determined.

Analytical HPLC and GC/MS were used to identify and quantify the secondary metabolites in 17 strains of C. sativa, and correlations between cannabinoids and terpenoids in each strain were determined. Column separation was used to separate and collect the compounds, and cell viability assay was used to assess biological activity.

We found that in “high THC” or “high CBD” strains, phytocannabinoids are produced alongside certain sets of terpenoids. Only co-related terpenoids enhanced the cytotoxic activity of phytocannabinoids on MDA-MB-231 and HCT-116 cell lines.

This was found to be most effective in natural ratios found in extracts of cannabis inflorescence. The correlation in a particular strain between THCA or CBDA and a certain set of terpenoids, and the partial specificity in interaction may have influenced the cultivation of cannabis and may have implications for therapeutic treatments.”

https://www.ncbi.nlm.nih.gov/pubmed/31438532

https://www.mdpi.com/1420-3049/24/17/3031

“Anticancer Terpenoids” https://link.springer.com/chapter/10.1007/978-3-319-14027-8_5

“Anticancer effects of phytocannabinoids” https://www.ncbi.nlm.nih.gov/pubmed/28560402

Cannabidiol attenuates the rewarding effects of cocaine in rats by CB2, 5-TH1A and TRPV1 receptor mechanisms.

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Neuropharmacology“Cocaine abuse continues to be a serious health problem worldwide. Despite intense research there is currently no FDA-approved medication to treat cocaine use disorder. The recent search has been focused on agents targeting primarily the dopamine system, while limited success has been achieved at the clinical level.

Cannabidiol (CBD) is a U.S. FDA-approved cannabinoid for the treatment of epilepsy and recently was reported to have therapeutic potential for other disorders. Here we systemically evaluated its potential utility for the treatment of cocaine addiction and explored the underlying receptor mechanisms in experimental animals.

These findings suggest that CBD may have certain therapeutic utility by blunting the acute rewarding effects of cocaine via a DA-dependent mechanism.”

https://www.ncbi.nlm.nih.gov/pubmed/31437433

https://www.sciencedirect.com/science/article/pii/S0028390819302990?via%3Dihub

The effectiveness of self-directed medical cannabis treatment for pain

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Complementary Therapies in Medicine“The prior medical literature offers little guidance as to how pain relief and side effect manifestation may vary across commonly used and commercially available cannabis product types. We used the largest dataset in the United States of real-time responses to and side effect reporting from patient-directed cannabis consumption sessions for the treatment of pain under naturalistic conditions in order to identify how cannabis affects momentary pain intensity levels and which product characteristics are the best predictors of therapeutic pain relief.

Between 06/06/2016 and 10/24/2018, 2987 people used the ReleafApp to record 20,513 cannabis administration measuring cannabis’ effects on momentary pain intensity levels across five pain categories: musculoskeletal, gastrointestinal, nerve, headache-related, or non-specified pain. The average pain reduction was –3.10 points on a 0–10 visual analogue scale (SD = 2.16, d = 1.55, p < .001).

Whole Cannabis flower was associated with greater pain relief than were other types of products, and higher tetrahydrocannabinol (THC) levels were the strongest predictors of analgesia and side effects prevalence across the five pain categories. In contrast, cannabidiol (CBD) levels generally were not associated with pain relief except for a negative association between CBD and relief from gastrointestinal and non-specified pain.

These findings suggest benefits from patient-directed, cannabis therapy as a mid-level analgesic treatment; however, effectiveness and side effect manifestation vary with the characteristics of the product used.

The results suggest that Cannabis flower with moderate to high levels of tetrahydrocannabinol is an effective mid-level analgesic.”

https://www.ncbi.nlm.nih.gov/pubmed/31519268

https://www.sciencedirect.com/science/article/abs/pii/S0965229919308040

“UNM study confirms cannabis flower is an effective mid-level analgesic medication for pain treatment. Cannabis likely has numerous constituents that possess analgesic properties beyond THC, including terpenes and flavonoids, which likely act synergistically for people that use whole dried cannabis flower, Cannabis offers the average patient an effective alternative to using opioids for general use in the treatment of pain with very minimal negative side effects for most people.”  https://news.unm.edu/news/unm-study-confirms-cannabis-flower-is-an-effective-mid-level-analgesic-medication-for-pain-treatment