Targeting Cannabinoid Receptor 2 on Peripheral Leukocytes to Attenuate Inflammatory Mechanisms Implicated in HIV-Associated Neurocognitive Disorder.

 SpringerLink“HIV infection affects an estimated 38 million people. Approximately 50% of HIV patients exhibit neurocognitive dysfunction termed HIV-Associated Neurocognitive Disorder (HAND). HAND is a consequence of chronic low-level neuroinflammation due to HIV entry into the brain. Initially, monocytes become activated in circulation and traffic to the brain. Monocytes, when activated, become susceptible to infection by HIV and can then carry the virus across the blood brain barrier. Once in the brain, activated monocytes secrete chemokines, which recruit virus-specific CD8+ T cells into the brain to further promote neuroinflammation. HAND is closely linked to systemic inflammation driven, in part, by HIV but is also due to persistent translocation of microorganisms across the GI tract. Persistent anti-viral responses in the GI tract compromise microbial barrier integrity. Indeed, HIV patients can exhibit remarkably high levels of activated (CD16+) monocytes in circulation.

Recent studies, including our own, show that HIV patients using medical marijuana exhibit lower levels of circulating CD16+ monocytes than non-cannabis using HIV patients. Cannabis is a known immune modulator, including anti-inflammatory properties, mediated, in part, by ∆9-tetrahydrocannabinol (THC), as well as less characterized minor cannabinoids, such as cannabidiol (CBD), terpenes and presumably other cannabis constituents. The immune modulating activity of THC is largely mediated through cannabinoid receptors (CB) 1 and 2, with CB1 also responsible for the psychotropic properties of cannabis.

Here we discuss the anti-inflammatory properties of cannabinoids in the context of HIV and propose CB2 as a putative therapeutic target for the treatment of neuroinflammation. Graphical Abstract HIV-associated neurocognitive disorder is a systemic inflammatory disease leading to activation of plasmacytoid dendritic cells, monocytes and T cells. Monocyte and CD8 T cell migration across the BBB and interaction with astrocytes promotes neurotoxic inflammatory mediators release. CB2 ligands are proposed as therapeutics capable of suppressing systemic and localized inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/32409991

https://link.springer.com/article/10.1007%2Fs11481-020-09918-7

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The impact of naturalistic cannabis use on self-reported opioid withdrawal.

A Case of Mutism Subsequent to Cocaine Abuse - Journal of ...“Four states have legalized medical cannabis for the purpose of treating opioid use disorder. It is unclear whether cannabinoids improve or exacerbate opioid withdrawal. A more thorough examination of cannabis and its impact on specific symptoms of opioid withdrawal is warranted.

METHOD:

Two hundred individuals recruited through Amazon Mechanical Turk with past month opioid and cannabis use and experience of opioid withdrawal completed the survey. Participants indicated which opioid withdrawal symptoms improved or worsened with cannabis use and indicated the severity of their opioid withdrawal on days with and without cannabis.

RESULTS:

62.5% (n = 125) of 200 participants had used cannabis to treat withdrawal. Participants most frequently indicated that cannabis improved: anxiety, tremors, and trouble sleeping. A minority of participants (6.0%, n = 12) indicated cannabis worsened opioid withdrawal, specifically symptoms of yawning, teary eyes, and runny nose. Across all symptoms, more participants indicated that symptoms improved with cannabis compared to those that indicated symptoms worsened with cannabis. Women reported greater relief from withdrawal with cannabis use than men.

DISCUSSION:

These results show that cannabis may improve opioid withdrawal symptoms and that the size of the effect is clinically meaningful. It is important to note that symptoms are exacerbated with cannabis in only a minority of individuals. Prospectively designed studies examining the impact of cannabis and cannabinoids on opioid withdrawal are warranted.”

https://www.ncbi.nlm.nih.gov/pubmed/32359667

“Cannabis alleviates self-reported opioid withdrawal symptoms.”

https://www.journalofsubstanceabusetreatment.com/article/S0740-5472(19)30564-1/pdf

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Cannabidiol and Other Non-Psychoactive Cannabinoids for Prevention and Treatment of Gastrointestinal Disorders: Useful Nutraceuticals?

ijms-logo“Cannabis sativa is an aromatic annual flowering plant with several botanical varieties, used for different purposes, like the production of fibers, the production of oil from the seeds, and especially for recreational or medical purposes.

Phytocannabinoids (terpenophenolic compounds derived from the plant), include the well-known psychoactive cannabinoid Δ9-tetrahydrocannabinol, and many non-psychoactive cannabinoids, like cannabidiol.

The endocannabinoid system (ECS) comprises of endocannabinoid ligands, enzymes for synthesis and degradation of such ligands, and receptors. This system is widely distributed in the gastrointestinal tract, where phytocannabinoids exert potent effects, particularly under pathological (i.e., inflammatory) conditions.

Herein, we will first look at the hemp plant as a possible source of new functional food ingredients and nutraceuticals that might be eventually useful to treat or even prevent gastrointestinal conditions.

Subsequently, we will briefly describe the ECS and the general pharmacology of phytocannabinoids. Finally, we will revise the available data showing that non-psychoactive phytocannabinoids, particularly cannabidiol, may be useful to treat different disorders and diseases of the gastrointestinal tract.

With the increasing interest in the development of functional foods for a healthy life, the non-psychoactive phytocannabinoids are hoped to find a place as nutraceuticals and food ingredients also for a healthy gastrointestinal tract function.”

https://www.ncbi.nlm.nih.gov/pubmed/32357565

https://www.mdpi.com/1422-0067/21/9/3067

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Innovative methods for the preparation of medical Cannabis oils with a high content of both cannabinoids and terpenes.

Journal of Pharmaceutical and Biomedical Analysis“Cannabis-based medications are being increasingly used for the treatment of different clinical conditions.

Among all galenic formulations, olive oil extracts from medical Cannabis are the most prescribed ones for their easy preparation and usage. A great variety of methods have been described so far for the extraction of medical Cannabis oils to reach a high yield of Δ9-tetrahydrocannabinol (Δ9-THC), but poor attention has been paid to the preservation of the terpene fraction from the plant, which may contribute to the overall bioactivity of the extracts.

In this context, the present study was aimed at the chemical characterization of different medical Cannabis oils prepared by following both innovative and existing extraction protocols, with particular attention to cannabinoids and terpenes, in order to set up a suitable method to obtain an extract rich in these chemical classes. In particular, six different extraction procedures were followed, based on different techniques, of which all but one included a decarboxylation of the plant material.

The profile of cannabinoids was studied in detail by means of HPLC-ESI-MS/MS, while terpenes were characterized by means both GC-MS and GC-FID techniques coupled with solid-phase microextraction operated in the head-space mode (HS-SPME). An innovative method that is based on the extraction of the oil by dynamic maceration at room temperature from plant inflorescences, which were partially decarboxylated in a closed system at a moderate temperature and partially pre-extracted with ethanol, produced similar yields of bioactive compounds as that obtained by using a microwave-assisted distillation of the essential oil from the plant material, in combination with a maceration extraction of the oil from the residue.

Both these new methods provided a higher efficiency over already existing extraction procedures of medical Cannabis oils and they can be applied to obtain a product with a high therapeutic value.”

https://www.ncbi.nlm.nih.gov/pubmed/32334134

“New methods were developed for the extraction of medical Cannabis oils.”

https://www.sciencedirect.com/science/article/abs/pii/S0731708520303897?via%3Dihub

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A Comprehensive Patient and Public Involvement Program Evaluating Perception of Cannabis-Derived Medicinal Products in the Treatment of Acute Postoperative Pain, Nausea, and Vomiting Using a Qualitative Thematic Framework.

View details for Cannabis and Cannabinoid Research cover image“Cannabis-derived medicinal products (CDMPs) have antiemetic properties and in combination with opioids have synergistic analgesic effects in part signaling through the delta and kappa opioid receptors.

The objective of this patient and public involvement program was to determine perception of perioperative CDMPs in our local population to inform design of a clinical trial.

Consensus was that potential benefits of CDMPs were attractive compared with the known risk profile of opioid use. Decrease in opioid dependence was agreed to be an appropriate clinical end-point for a randomized controlled clinical trial and there was concurrence of positive opinion of a therapeutic schedule of 5 days.

The perception of postoperative CDMP therapy was overwhelmingly positive in this West London population. The data from this thematic analysis will inform protocol development of clinical trials to determine analgesic and antiemetic efficacy of CDMPs.”

https://www.ncbi.nlm.nih.gov/pubmed/32322678

https://www.liebertpub.com/doi/10.1089/can.2019.0020

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A case study for the use of medical cannabis in generalized anxiety disorder.

logo“Despite the increasing prevalence and acceptance of the medical cannabis use among the general public, the evidence required by physicians to use cannabis as a treatment is generally lacking. Research on the health effects of cannabis and cannabinoids has been limited worldwide, leaving patients, health care professionals, and policymakers without the evidence they need to make sound decisions regarding the use of cannabis and cannabinoids.

This case study outlines an intervention that involved a patient integrating medical cannabis into her treatment to better manage a generalized anxiety disorder and the debilitating symptoms of vertigo. This case demonstrates how the patient drastically improved her quality of life and reinforces the need for more rigorous testing on the use of medical cannabis to support patients and better manage the symptoms associated with their medical conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/32309610

https://www.discoveriesjournals.org/discoveries/D.2019.02.OACS-Walkaden.DOI

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Beneficial Effects of Cannabis on Blood Brain Barrier Function in HIV.

“HIV infection leads to blood-brain barrier (BBB) dysfunction that does not resolve despite viral suppression on antiretroviral therapy and is associated with adverse clinical outcomes.

In preclinical models, cannabis restores BBB integrity.

Cannabis may have a beneficial impact on HIV-associated BBB injury.

Since BBB disruption may permit increased entry of toxins such as microbial antigens and inflammatory mediators, with consequent CNS injury, these results support a potential therapeutic role of cannabis among PWH and may have important treatment implications for ART effectiveness and toxicity.”

https://www.ncbi.nlm.nih.gov/pubmed/32296832

https://academic.oup.com/cid/article-abstract/doi/10.1093/cid/ciaa437/5820626?redirectedFrom=fulltext

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The effect of attitudes, subjective norms and stigma on health-care providers’ intention to recommend medicinal cannabis to patients.

International Journal of Nursing Practice“The aim of this study was to explore the effect of health-care providers’ attitudes towards the medical use of cannabis, subjective norms and perceived stigma towards medicinal cannabis users on health-care providers’ intention to recommend medicinal cannabis for patients with qualifying conditions.

RESULTS:

More positive attitudes towards the medical use of cannabis were associated with lower stigma towards medicinal cannabis users, which, in turn, was associated with a higher intention of recommending medicinal cannabis for patients with qualifying conditions. The relationship between attitudes towards the medical use of cannabis and the intention to recommend medicinal cannabis varies according to subjective norms.

CONCLUSIONS:

Among nurses and physicians, stigma towards medicinal cannabis users mediated the relationship between attitudes towards the medical use of cannabis and the intention to recommend medicinal cannabis for patients with qualifying conditions, whereas subjective norms moderated this relationship.

Effective treatment with medicinal cannabis might be compromised by health-care providers’ negative attitudes, stigma and subjective norms.”

https://www.ncbi.nlm.nih.gov/pubmed/32237017

https://onlinelibrary.wiley.com/doi/abs/10.1111/ijn.12836

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High expectations: The landscape of clinical trials of medical marijuana in oncology.

Complementary Therapies in Medicine“Given the infancy and evolving complexity of medicinal marijuana, an evolving political landscape, and the growing frequency of its use in cancer care, it is important for oncologists to be actively engaged in developing and successfully implementing clinical trials focusing on medical marijuana.

The purpose of this study was to analyze and evaluate trends in clinical trials focused on medical marijuana in oncology.

CONCLUSION:

Our results indicate that across oncology, there is growing interest in clinical research in the use of medical marijuana.”

https://www.ncbi.nlm.nih.gov/pubmed/32147080

https://www.sciencedirect.com/science/article/abs/pii/S0965229919309306?via%3Dihub

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Medical Cannabis in Children.

 Logo of rmmj“The use of medical cannabis in children is rapidly growing.

While robust evidence currently exists only for pure cannabidiol (CBD) to treat specific types of refractory epilepsy, in most cases, artisanal strains of CBD-rich medical cannabis are being used to treat children with various types of refractory epilepsy or irritability associated with autism spectrum disorder (ASD).

Other common pediatric disorders that are being considered for cannabis treatment are Tourette syndrome and spasticity.

As recreational cannabis use during youth is associated with serious adverse events and medical cannabis use is believed to have a relatively high placebo effect, decisions to use medical cannabis during childhood and adolescence should be made with caution and based on evidence.

This review summarizes the current evidence for safety, tolerability, and efficacy of medical cannabis in children with epilepsy and in children with ASD. The main risks associated with use of Δ9-tetrahydrocannabinol (THC) and CBD in the pediatric population are described, as well as the debate regarding the use of whole-plant extract to retain a possible “entourage effect” as opposed to pure cannabinoids that are more standardized and reproducible.”

https://www.ncbi.nlm.nih.gov/pubmed/32017680

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