Tag Archives: therapeutic

Cannabis and Mood Disorders.

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 “The present review will provide an overview of the neurobiology, epidemiology, clinical impact, and treatment of cannabis use disorder (CUD) in mood disorders.

Patients with mood disorders including major depressive disorder (MDD) and bipolar disorder (BD) have higher rates of cannabis use, and CUD compared to the general population. Reasons for this association are not clear, nor are the putative therapeutic effects of cannabis use, or its components delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), in these illnesses.

Cannabis use may be associated mood disorders, but more research is needed to increase our understanding of the mechanisms for this association, and to develop more effective treatments for this comorbidity.”

https://www.ncbi.nlm.nih.gov/pubmed/30643708

https://link.springer.com/article/10.1007%2Fs40429-018-0214-y

“Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. Results of this study show that Delta(9)-THC and other cannabinoids exert antidepressant-like actions, and thus may contribute to the overall mood-elevating properties of cannabis.”   https://www.ncbi.nlm.nih.gov/pubmed/20332000

Cannabis and Turmeric as Complementary Treatments for IBD and Other Digestive Diseases.

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 “Complementary therapies for inflammatory bowel disease (IBD) have earned growing interest from patients and investigators alike, with a dynamic landscape of research in this area. In this article, we review results of the most recent studies evaluating the role of cannabis and turmeric for the treatment of IBD and other intestinal illnesses.

RECENT FINDINGS:

Cannabinoids are well-established modulators of gut motility and visceral pain and have demonstrated anti-inflammatory properties. Clinical trials suggest that there may be a therapeutic role for cannabinoid therapy in the treatment of IBD, irritable bowel syndrome (IBS), nausea and vomiting, and GI motility disorders. Recent reports of serious adverse effects from synthetic cannabinoids highlight the need for additional investigation of cannabinoids to establish their efficacy and safety. Turmeric trials have demonstrated some promise as adjuvant treatment for IBD, though not in other GI disease processes. Evidence suggests that the use of cannabis and turmeric is potentially beneficial in IBD and IBS; however, neither has been compared to standard therapy in IBD, and thus should not be recommended as alternative treatment for IBD. For cannabis in particular, additional investigation regarding appropriate dosing and timing, given known adverse effects of its chronic use, and careful monitoring of potential bleeding complications with synthetic cannabinoids are imperative.”

https://www.ncbi.nlm.nih.gov/pubmed/30635796

https://link.springer.com/article/10.1007%2Fs11894-019-0670-0

Preclinical safety and efficacy of cannabidivarin for early life seizures.

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Neuropharmacology

“A significant proportion of neonatal and childhood seizures are poorly controlled by existing anti-seizure drugs (ASDs), likely due to prominent differences in ionic homeostasis and network connectivity between the immature and mature brain. In addition to the poor efficacy of current ASDs, many induce apoptosis, impair synaptic development, and produce behavioral deficits when given during early postnatal development.

There is growing interest in new targets, such as cannabidiol (CBD) and its propyl analog cannabidivarin (CBDV) for early life indications. While CBD was recently approved for treatment of refractory childhood epilepsies, little is known about the efficacy or safety of CBDV.

Here, we addressed this gap through a systematic evaluation of CBDV against multiple seizure models in postnatal day (P) 10 and 20 animals. We also evaluated the impact of CBDV on acute neurotoxicity in immature rats.

CBDV (50-200 mg/kg) displayed an age and model-specific profile of anticonvulsant action.

Finally, CBDV treatment generally avoided induction of neuronal degeneration in immature rats.

Together, the efficacy and safety profile of CBDV suggest it may have therapeutic value for early life seizures.”

https://www.ncbi.nlm.nih.gov/pubmed/30633929

https://www.sciencedirect.com/science/article/pii/S0028390818306786?via%3Dihub

The protective effects of β-caryophyllene on LPS-induced primary microglia M1/M2 imbalance: A mechanistic evaluation.

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Life Sciences

“Neuroinflammation is observed as a routine characterization of neurodegenerative disorders such as dementia, multiple sclerosis (MS) and Alzheimer’s diseases (AD). Scientific evidence propounds both of the neuromodulatory and immunomodulatory effects of CB2 in the immune system. β-Caryophyllene (BCP) is a dietary selective CB2 agonist, which deserves the anti-inflammatory and antioxidant effects at both low and high doses through activation of the CB2 receptor.

METHODS:

In this study, we investigated the protective effects of a broad range concentration of BCP against LPS-induced primary microglia cells inflammation and M1/M2 imbalance and identifying the portion of the involvement of related signaling pathways on BCP effects using pharmacological antagonists of CB2, PPAR-γ, and sphingomyelinase (SMase).

KEY FINDINGS:

The protective effects of BCP on LPS-induced microglia imbalance is provided by the M2 healing phenotype of microglia, releasing the anti-inflammatory (IL-10, Arg-1, and urea) and anti-oxidant (GSH) parameters and reducing the inflammatory (IL-1β, TNF-α, PGE2, iNOS and NO) and oxidative (ROS) biomarkers. Moreover, we showed that BCP exerts its effects through CB2receptors which overproduction of ceramides by SMase at middle to higher concentrations of BCP reduce the protective activity of BCP and results in the activation of the PPAR-γ pathway.

SIGNIFICANCE:

In conclusion, the low concentration of BCP has higher selective anti-inflammatory effects rather than high levels. On this occasion, BCP by modulating the microglia is able to have potential therapeutic effects in neuro-inflammation conditions and microglia cells such as MS and AD.”

https://www.ncbi.nlm.nih.gov/pubmed/30620895

https://www.sciencedirect.com/science/article/abs/pii/S0024320518308610?via%3Dihub

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”  https://www.ncbi.nlm.nih.gov/pubmed/18574142

The effects of cannabinoids on the endocrine system.

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“Cannabinoids are the derivatives of the cannabis plant, the most potent bioactive component of which is tetrahydrocannabinol (THC). The most commonly used drugs containing cannabinoids are marijuana, hashish, and hashish oil.

These compounds exert their effects via interaction with the cannabinoid receptors CB1 and CB2. Type 1 receptors (CB1) are localised mostly in the central nervous system and in the adipose tissue and many visceral organs, including most endocrine organs. Type 2 cannabinoid receptors (CB2) are positioned in the peripheral nervous system (peripheral nerve endings) and on the surface of the immune system cells.

Recently, more and more attention has been paid to the role that endogenous ligands play for these receptors, as well as to the role of the receptors themselves. So far, endogenous cannabinoids have been confirmed to participate in the regulation of food intake and energy homeostasis of the body, and have a significant impact on the endocrine system, including the activity of the pituitary gland, adrenal cortex, thyroid gland, pancreas, and gonads.

Interrelations between the endocannabinoid system and the activity of the endocrine system may be a therapeutic target for a number of drugs that have been proved effective in the treatment of infertility, obesity, diabetes, and even prevention of diseases associated with the cardiovascular system.”

 https://www.ncbi.nlm.nih.gov/pubmed/30618031
https://journals.viamedica.pl/endokrynologia_polska/article/view/58487

Blood-brain barrier disturbances in diabetes-associated dementia: Therapeutic potential for cannabinoids.

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Pharmacological Research

“Type-2 diabetes (T2D) increases the risk of dementia by ˜5-fold, however the mechanisms by which T2D increases dementia risk remain unclear. Evidence suggests that the heightened inflammation and oxidative stress in T2D may lead to disruption of the blood-brain barrier (BBB), which precedes premature cognitive decline. Studies show that vascular-targeted anti-inflammatory treatments protect the BBB by attenuating neuroinflammation, and in some studies attenuate cognitive decline. Yet, this potential pathway is understudied in T2D-associated cognitive impairment.

In recent years, therapeutic potential of cannabinoids has gained much interest. The two major cannabinoids, cannabidiol and tetrahydrocannabinol, exert anti-inflammatory and vascular protective effects, however few studies report their potential for reversing BBB dysfunction, particularly in T2D. Therefore, in this review, we summarize the current findings on the role of BBB dysfunction in T2D-associated dementia and consider the potential therapeutic use of cannabinoids as a protectant of cerebrovascular BBB protection.”

https://www.ncbi.nlm.nih.gov/pubmed/30616019

https://www.sciencedirect.com/science/article/abs/pii/S1043661818314634?via%3Dihub

Cannabinoids-induced peripheral analgesia depends on activation of BK channels.

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 Brain Research“The endogenous cannabinoid system is involved in the physiological inhibitory control of pain and is of particular interest for the development of therapeutic approaches for pain management.

Selective activation of the peripheral CB1 cannabinoid receptor has been shown to suppress the heightened firing of primary afferents, which is the peripheral mechanism underlying neuropathic pain after nerve injury. However, the mechanism underlying this effect of CB1 receptor remains unclear.

The large-conductance calcium-activated potassium (BK) channels have been reported to participate in anticonvulsant and vasorelaxant effects of cannabinoids. We asked whether BK channels participate in cannabinoids-induced analgesia and firing-suppressing effects in primary afferents after nerve injury.

Here, using mice with chronic constriction injury(CCI)-induced neuropathic pain, antinociception action and firing-suppressing effect of HU210 were measured before and after BK channel blocker application. We found that local peripheral application of HU210 alleviated CCI-induced pain behavior and suppressed the heightened firing of injured fibers. Co-administration of IBTX with HU210 significantly reversed the analgesia and the firing-suppressing effect of HU210.

This result indicated that the peripheral analgesic effects of cannabinoids depends on activation of BK channels.”

https://www.ncbi.nlm.nih.gov/pubmed/30615887

https://www.sciencedirect.com/science/article/pii/S0006899319300071?via%3Dihub

Practical Perspectives in the Treatment of Nausea and Vomiting.

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Image result for J Clin Gastroenterol.

“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

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