Author Archives: David Worrell

Practical Perspectives in the Treatment of Nausea and Vomiting.

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“Nausea and vomiting result from complex interactions between afferent and efferent pathways of the gastrointestinal tract, central nervous system, and autonomic nervous system. Afferent pathways from the vagus nerve, vestibular system, and chemoreceptor trigger zone project to nucleus tractus solitarius, which in turn relays signals to the central pattern generator to initiate multiple downstream pathways resulting in symptoms of nausea and vomiting. There is increasing evidence that the central pathway of chronic nausea is different from that of acute nausea and vomiting-and closely resembles that of neuropathic pain. This improved understanding of chronic nausea has resulted in a paradigm shift with regard to management strategy. Although conventional therapies such as antiemetics and prokinetics are commonly used to manage acute nausea and vomiting, they are historically not as effective in treating chronic nausea. Recently, neuromodulator agents, such as tricyclic antidepressants, gabapentin, olanzapine, mirtazapine, and benzodiazepines, and cannabinoids have been shown to be efficacious in the treatment of nausea and vomiting, and may be useful in the treatment of chronic symptoms. There is a need to study these agents, especially in the management of chronic functional nausea. Improved understanding of the central and peripheral circuitry of nausea and vomiting symptoms will allow for enhanced utilization of the currently available medications, and the development of novel therapeutic options.”

https://www.ncbi.nlm.nih.gov/pubmed/30614944

https://insights.ovid.com/crossref?an=00004836-900000000-97784

Progress in Brain Cannabinoid CB2 Receptor Research: From Genes to Behavior.

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Neuroscience & Biobehavioral Reviews

“The type 2 cannabinoid receptor (CB2R) was initially regarded as a peripheral cannabinoid receptor. However, recent technological advances in gene detection, alongside the availability of transgenic mouse lines, indicate that CB2Rs are expressed in both neurons and glial cells in the brain under physiological and pathological conditions, and are involved in multiple functions at cellular and behavioral levels. Brain CB2Rs are inducible and neuroprotective via up-regulation in response to various insults, but display species differences in gene and receptor structures, CB2R expression, and receptor responses to various CB2R ligands. CB2R transcripts also differ between the brain and spleen. In the brain, CB2A is the major transcript isoform, while CB2A and CB2B transcripts are present at higher levels in the spleen. These new findings regarding brain versus spleen CB2R isoforms may in part explain why early studies failed to detect brain CB2R gene expression. Here, we review evidence supporting the expression and function of brain CB2R from gene and receptor levels to cellular functioning, neural circuitry, and animal behavior.”

https://www.ncbi.nlm.nih.gov/pubmed/30611802

https://www.sciencedirect.com/science/article/pii/S0149763418308297?via%3Dihub

Successful cannabis derivatives oromucosal spray therapy for a seronegative stiff-person syndrome: a case report.

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“Stiff-person syndrome (SPS) is an uncommon and disabling disorder characterised by progressive rigidity and episodic painful spasms involving axial and limb musculature.

The authors report a patient with seronegative SPS successfully treated with THC-CBD oromucosal spray.

In conclusion cannabinoids can be a therapeutic option to treat spasticity associated with neurological diseases such as stiff-person syndrome.

Our patient’s quality of life has improved remarkably although more information is needed about this particular use.”

https://ejhp.bmj.com/content/19/2/219.2?fbclid=IwAR0PVg0GRQDmu_tXu_vYJmmKHo2MGnJ_EsnkdsR4HE7deFVUtqhAxziHQBc

http://dx.doi.org/10.1136/ejhpharm-2012-000074.352

A Review of Herbal Therapy in Multiple Sclerosis

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“Medicinal plants have opened a new horizon in curing neurodegenerative disorders such as Parkinson’s disease, AD and MS. literature data review indicated that herbal medicines could be effective in the treatment of MS disease and itsʼ related symptoms, by reducing the demyelination, improving remyelination and suppressing the inflammation in the CNS. On the basis of the above mentioned review, it can be concluded that the anti-inflammatory effect is the main reason of medicinal plants therapeutic effects in MS disease, through which medicinal plants ameliorate the severity of disease and reduce neuropathological changes. In addition to neuroprotective effect, medicinal plants have other beneficial effects for MS patients, such as sedation, improving sleep quality, anti-depressant effects, relief muscle stiffness and reducing bladder disturbance. The medicinal plants and their derivatives; Ginkgo biloba, Zingiber officinale, Curcuma longa, Hypericum perforatum, Valeriana officinalis, Vaccinium macrocarpon, Nigella sativa,Piper methysticum, Crocus sativus, Panax ginseng, Boswellia papyrifera, Vitis vinifera, Gastrodia elata, Camellia sinensis, Oenothera biennis, MS14 and Cannabis sativa have been informed to have several therapeutic effects in MS patients.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311642/

https://www.ncbi.nlm.nih.gov/pubmed/30607330

Adenosine A2A-Cannabinoid CB1 Receptor Heteromers in the Hippocampus: Cannabidiol Blunts Δ9-Tetrahydrocannabinol-Induced Cognitive Impairment

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“At present, clinical interest in the plant-derived cannabinoid compound cannabidiol (CBD) is rising exponentially, since it displays multiple therapeutic properties. In addition, CBD can counteract the undesirable effects of the psychoactive cannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) that hinder clinical development of cannabis-based therapies. Here, by combining in vivo and complementary molecular techniques, we demonstrate for the first time that CBD blunts the Δ9-THC-induced cognitive impairment in an adenosine A2A receptor (A2AR)-dependent manner. Overall, these data provide new evidence regarding the mechanisms of action of CBD and the nature of A2AR-CB1R interactions in the brain.”

https://www.ncbi.nlm.nih.gov/pubmed/30610611

https://link.springer.com/article/10.1007%2Fs12035-018-1456-3

The Cerebellum, THC, and Cannabis Addiction: Findings from Animal and Human Studies.

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“Despite being legally scheduled as a drug with high harm potential and no therapeutic utility in countries like the USA, evidence shows otherwise and legislative changes and reinterpretations of existing ambiguous laws make this drug increasingly available by legal means.”

https://www.ncbi.nlm.nih.gov/pubmed/30610540

https://link.springer.com/article/10.1007%2Fs12311-018-0993-7

Cannabinoid Receptor Type 1 Agonist ACEA Improves Cognitive Deficit on STZ-Induced Neurotoxicity Through Apoptosis Pathway and NO Modulation.

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“The cannabinoid system has the ability to modulate cellular and molecular mechanisms, including excitotoxicity, oxidative stress, apoptosis, and inflammation, acting as a neuroprotective agent, by its relationship with signaling pathways associated to the control of cell proliferation, differentiation, and survival. Recent reports have raised new perspectives on the possible role of cannabinoid system in neurodegenerative diseases like Alzheimer disease’s (AD).

Our study has demonstrated a participation of the cannabinoid system in cellular survival, involving the CB1 receptor, which occurs by positive regulation of the anti-apoptotic proteins, suggesting the participation of this system in neurodegenerative processes. Our data suggest that the cannabinoid system is an interesting therapeutic target for the treatment of neurodegenerative diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/30607903

https://link.springer.com/article/10.1007%2Fs12640-018-9991-2

Gender and the Politics of Marijuana

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“The objectives of this study were to understand why, even though women are more liberal than men on a broad range of issues, when it comes to the increasingly prominent issue of marijuana legalization, the direction of the gender gap is reversed, with women more conservative than men.

We find that women’s role as mothers cannot explain this gap, and that mothers are in fact no different from those without children in terms of their support for marijuana policy, as well as their reported use of marijuana. The greater religiosity of women does play a prominent role in the gender gap on marijuana policy, but does not account for the full difference of opinion between women and men. Our findings suggest that men’s greater propensity relative to women to use marijuana is a major driver behind the gender gap.

Conclusions

Not only are attitudes on marijuana legalization likely to continue to liberalize, but as marijuana legalization and marijuana use become normalized, rather than viewed as immoral and dangerous behavior, the existing gender gap should shrink.”

https://onlinelibrary.wiley.com/doi/abs/10.1111/ssqu.12558

“Drug use, religion explain ‘reverse gender gap’ on marijuana”  https://www.sciencedaily.com/releases/2018/11/181126134251.htm?fbclid=IwAR072Y-SGz0PElUfNtQCTe56kzRC5ZBDoBMmlW2oTagAOy-IOcT_8UxVCEI

Anti-inflammatory mechanisms of cannabinoids: an immunometabolic perspective.

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“A number of studies have implicated cannabinoids as potent anti-inflammatory mediators. However, the exact mechanism by which cannabinoids exert these effects remains to be fully explained.

The recent resurgence in interest regarding the metabolic adaptations undergone by activated immune cells has highlighted the intricate connection between metabolism and an inflammatory phenotype.

In this regard, evidence suggests that cannabinoids may alter cell metabolism by increasing AMPK activity. In turn, emerging evidence suggests that the activation of AMPK by cannabinoids may mediate an anti-inflammatory effect through a range of processes.

First, AMPK may promote oxidative metabolism, which have been shown to play a central role in immune cell polarisation towards a tolerogenic phenotype. AMPK activation may also attenuate anabolic processes which in turn may antagonise immune cell function. Furthermore, AMPK activity promotes the induction of autophagy, which in turn may promote anti-inflammatory effects through various well-described processes.

Taken together, these observations implicate cannabinoids to mediate part of their anti-inflammatory effects through alterations in immune cell metabolism and the induction of autophagy.”

https://www.ncbi.nlm.nih.gov/pubmed/30610735

https://link.springer.com/article/10.1007%2Fs10787-018-00560-7

Production, digestibility and allergenicity of hemp (Cannabis sativa L.) protein isolates.

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Food Research International

“Hemp (Cannabis sativa L.), traditionally cultivated for industrial use and harvested for fibers and seeds, has raised much interest as a sustainable crop in the last years.

Recently, hemp seeds and derived oil have started to be used in a variety of food products. Hemp-based food products are considered less allergenic than those from other edible seeds, although this statement has never been experimentally verified.

In this study high purity grade hemp flour (HF) and hemp protein isolate (HPI) were obtained through a fast and cheap process starting from defatted hemp cakes, a residue of hempseed oil extraction.

HPI resulted enriched at nearly 86% protein, mainly constituted by the storage protein edestin (accounting for 70% total protein). In vitro protein digestibility was determined using a static model of gastrointestinal digestion (GID), which included a final step with purified brush border membrane (BBM) enzyme preparations. HF and HPI showed a high degree of digestibility. The survival of potential bioactive and/or allergenic peptide sequences in digests was investigated by peptidomic analysis. Only a limited number of sequences survived GID. Among them, fragments from 12 seed proteins. These fragments were precursors of sequences with potential bioactive peptides, which might justify the bioactivity of HPI hydrolysates, reported in previous studies.

More importantly, all known hemp allergens, including the major thaumatin-like protein and LTP, were entirely eliminated by the HPI production process, neither fragments of the proteins were present after GID.

These data support the use of HPI as an ingredient for hypoallergenic foods.”

https://www.ncbi.nlm.nih.gov/pubmed/30599980

https://www.sciencedirect.com/science/article/pii/S0963996918307427?via%3Dihub