Anti-Inflammatory Drugs and Herbs with Special Emphasis on Herbal Medicines for Countering Inflammatory Diseases and Disorders – A Review.

“Diseases with inflammatory etiopathology have increased in incidence in recent times. Drugs used for therapeutic management of such inflammatory diseases are relieving the ailment but at the same time also countering serious life-threatening consequences. Moreover, they are costly and rarely available at all places. In this context, research and development on medicinal herbs have opened a new era in the prophylactic and therapeutic management of inflammatory diseases.

OBJECTIVE:

To highlight the importance of anti-inflammatory medicine-synthetic drugs and natural herbs, their constituents, mechanism of action, benefits, side effects and future prospects. The overall aim is to provide better health services to patiens regardless of their background on equality basis.

RESULTS:

Anti-inflammatory herbs have proven beneficial by combating inflammatory responses that lead to severe abnormality in body systems. Inflammation though a protective response to infection or injury and may result in pathological outcome when aggravated or of severe degree thus needs an early intervention for proper resolution. Medicinal plants or their constituents are considered beneficial due to the properties i.e., satisfactory potency, ease of availability, cheapness, less or no side effects, safer and efficient as compared to the synthetic counterparts. These medicinal herbs contain phytoconstituents that can prevent undesirable inflammatory processes and also posses anti-inflammatory activity. Steroids, glycosides, phenolics, flavonoids, alkaloids, polysaccharides, terpenoids, cannabinoids, fatty acids are common phytoconstituents present in these plants. Different mechanisms have been explored for the anti-inflammatory action of these active ingredients. They may synergize the anti-inflammatory pathway enzymes, factors, proteins or interfere with these in the inflammatory pathway like lipooxygenases, cyclooxygenases, tumor necrosis factors, interleukins, prostaglandin, nitric oxide, mitogen-activated protein, nuclear factor, etc. Considering all the above-mentioned factors, further research from molecular to cellular level will enable a better understanding of the mechanisms. Common anti-inflammatory herbal plants are Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, Urtica dioica, Uncaria tomentosa, Vaccinium myrtillus, Olea europaea and much more. They are believed to be without side effects unlike the chemical counterparts or synthetic anti-inflammatory agents e.g. steroids, nonsteroid anti-inflammatory drugs, and immunosuppressant used for controlling and suppressing inflammatory crisis. A proper phytochemical, pharmacological and physiological evaluation will enable their safe and effective use in inflammatory conditions. Many of these anti-inflammatory drugs and herbal preparations have been patented with some under consideration.

CONCLUSION:

Natural herbs are safe, effective and better options as anti-inflammatory agents than synthetic ones. The phytoconstituents are as effective with the comparable mechanism of action as synthetic molecules. Future research should focus on molecular mechanisms of different beneficial applications of these herbal plants in various diseases. Recent patents on anti-inflammatory drugs and herbal plants have been covered which provide insight into the current status and future prospects in this field.”

https://www.ncbi.nlm.nih.gov/pubmed/29336271  http://www.eurekaselect.com/159064/article

“Cannabinoids as novel anti-inflammatory drugs”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828614/

“Cannabinoids for the treatment of inflammation.” http://www.ncbi.nlm.nih.gov/pubmed/17520866

“Cannabis-based drugs have been shown to be effective in inflammatory diseases.” https://www.ncbi.nlm.nih.gov/pubmed/29110674

http://www.thctotalhealthcare.com/tag/anti-inflammatory/

Practical considerations in medical cannabis administration and dosing.

European Journal of Internal Medicine

“Cannabis has been employed medicinally throughout history, but its recent legal prohibition, biochemical complexity and variability, quality control issues, previous dearth of appropriately powered randomised controlled trials, and lack of pertinent education have conspired to leave clinicians in the dark as to how to advise patients pursuing such treatment.

With the advent of pharmaceutical cannabis-based medicines (Sativex/nabiximols and Epidiolex), and liberalisation of access in certain nations, this ignorance of cannabis pharmacology and therapeutics has become untenable.

In this article, the authors endeavour to present concise data on cannabis pharmacology related to tetrahydrocannabinol (THC), cannabidiol (CBD) et al., methods of administration (smoking, vaporisation, oral), and dosing recommendations. Adverse events of cannabis medicine pertain primarily to THC, whose total daily dose-equivalent should generally be limited to 30mg/day or less, preferably in conjunction with CBD, to avoid psychoactive sequelae and development of tolerance.

CBD, in contrast to THC, is less potent, and may require much higher doses for its adjunctive benefits on pain, inflammation, and attenuation of THC-associated anxiety and tachycardia. Dose initiation should commence at modest levels, and titration of any cannabis preparation should be undertaken slowly over a period of as much as two weeks.

Suggestions are offered on cannabis-drug interactions, patient monitoring, and standards of care, while special cases for cannabis therapeutics are addressed: epilepsy, cancer palliation and primary treatment, chronic pain, use in the elderly, Parkinson disease, paediatrics, with concomitant opioids, and in relation to driving and hazardous activities.”

Oral cannabis extracts as a promising treatment for the core symptoms of autism spectrum disorder: Preliminary experience in Chilean patients

Cover image volume 384, Issue

“Preclinical studies and several anecdotal case reports suggest a dysfunctional endocannabinoid system implicated in Autism Spectrum Disorder (ASD).

Objective: To report our preliminary findings in patients with ASD treated with oral cannabis extracts.

Most cases improved at least one of the core symptoms of ASD, including social communication, language, or repetitive behaviors. Additionally, sensory difficulties, food acceptance, feeding and sleep disorders, and/or seizures were improved in most cases.

71,5% of patients received balanced CBD:THC extracts; 19,0% high-CBD; and 9,5% high-THC extracts.

Oral cannabis extracts were well tolerated.

Two patients had more agitation and one had more irritability, effects that were solved by changing the strain.

Conclusion: In this small series of ASD patients, oral cannabis extracts were dramatically more effective than conventional medicines. Large randomized controlled trials are needed to establish efficacy and safety of medicinal cannabis in ASD.”

http://www.jns-journal.com/article/S0022-510X(17)33120-9/fulltext

Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial

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“Research in both animals and humans indicates that cannabidiol (CBD) has antipsychotic properties.

The authors assessed the safety and effectiveness of CBD in patients with schizophrenia.

After 6 weeks of treatment, compared with the placebo group, the CBD group had lower levels of positive psychotic symptoms and were more likely to have been rated as improved and as not severely unwell by the treating clinician.

These findings suggest that CBD has beneficial effects in patients with schizophrenia. As CBD’s effects do not appear to depend on dopamine receptor antagonism, this agent may represent a new class of treatment for the disorder.”

Extract of Fructus Cannabis Ameliorates Learning and Memory Impairment Induced by D-Galactose in an Aging Rats Model.

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“Hempseed (Cannabis sativa L.) has been used as a health food and folk medicine in China for centuries.

In the present study, we sought to define the underlying mechanism by which the extract of Fructus Cannabis (EFC) protects against memory impairment induced by D-galactose in rats.

To accelerate aging and induce memory impairment in rats, D-galactose (400 mg/kg) was injected intraperitoneally once daily for 14 weeks. EFC (200 and 400 mg/kg) was simultaneously administered intragastrically once daily in an attempt to slow the aging process.

We found that EFC significantly increased the activity of superoxide dismutase, while lowering levels of malondialdehyde in the hippocampus. Moreover, EFC dramatically elevated the organ indices of some organs, including the heart, the liver, the thymus, and the spleen. In addition, EFC improved the behavioral performance of rats treated with D-galactose in the Morris water maze. Furthermore, EFC inhibited the activation of astrocytes and remarkably attenuated phosphorylated tau and suppressed the expression of presenilin 1 in the brain of D-galactose-treated rats.

These findings suggested that EFC exhibits beneficial effects on the cognition of aging rats probably by enhancing antioxidant capacity and anti-neuroinflammation, improving immune function, and modulating tau phosphorylation and presenilin expression.”

Standardized Cannabis sativa extract attenuates tau and stathmin gene expression in the melanoma cell line.

Iranian Journal of Basic Medical Sciences

“Metastasis is the main cause of death in patients with melanoma.

Cannabis-based medicines are effective adjunctive drugs in cancer patients.

Tau and Stathmin proteins are the key proteins in cancer metastasis. Here we have investigated the effect of a standardized Cannabis sativa extract on cell migration and Tau and Stathmin gene expression in the melanoma cell line.

RESULTS:

Tau and stathmin gene expression was significantly decreased compared to the control group. Cell migration was also significantly reduced compared to controls.

CONCLUSION:

C. sativa decreased tau and stathmin gene expression and cancer metastasis. The results may have some clinical relevance for the use of cannabis-based medicines in patients with metastatic melanoma.”

https://www.ncbi.nlm.nih.gov/pubmed/29147495

Multiple sclerosis symptoms and spasticity management: new data.

Future Medicine Logo

“Spasticity, perceived by patients as muscle rigidity and spasms, is a common symptom in multiple sclerosis (MS). It is associated with functional impairment that can exacerbate other MS symptoms and reduce quality of life.

Pharmacological treatment options are limited and frequently ineffective. Treatment adherence is a key issue to address in these patients.

The efficacy and safety of 9-delta-tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray for treatment of MS spasticity were demonstrated in four Phase III trials.

Observational studies and registry data subsequently confirmed the effectiveness and tolerability of THC:CBD oromucosal spray under everyday practice conditions.

Among patients who respond to treatment, THC:CBD oromucosal spray has been shown to produce positive improvements in gait parameters and to normalize muscle fibers.”

Availability and approval of cannabis-based medicines for chronic pain management and palliative/supportive care in Europe: A survey of the status in the chapters of the European Pain Federation.

European Journal of Pain

“There is considerable public and political interest in the use of cannabis products for medical purposes.

METHODS:

The task force of the European Pain Federation (EFIC) conducted a survey with its national chapters representatives on the status of approval of all types of cannabis-based medicines, the covering of costs and the availability of a position paper of a national medical association on the use of medical cannabis for chronic pain and for symptom control in palliative/supportive care.

RESULTS:

Thirty-one out of 37 contacted councillors responded. Plant-derived tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray is approved for spasticity in multiple sclerosis refractory to conventional treatment in 21 EFIC chapters. Plant-derived THC (dronabinol) is approved for some palliative care conditions in four EFIC chapters. Synthetic THC analogue (nabilone) is approved for chemotherapy-associated nausea and vomiting refractory to conventional treatment in four EFIC chapters’. Eight EFIC chapters’ countries have an exceptional and six chapters an expanded access programme for medical cannabis. German and Israeli pain societies recommend the use of cannabis-based medicines as third-line drug therapies for chronic pain within a multicomponent approach. Conversely, the German medical association and a team of finish experts and officials do not recommend the prescription of medical cannabis due to the lack of high-quality evidence of efficacy and the potential harms.

CONCLUSIONS:

There are marked differences between the countries represented in EFIC in the approval and availability of cannabis-based products for medical use. EFIC countries are encouraged to collaborate with the European Medicines Agency to publish a common document on cannabis-based medicines.

SIGNIFICANCE:

There are striking differences between European countries in the availability of plant-derived and synthetic cannabinoids and of medical cannabis for pain management and for symptom control in palliative care and in the covering of costs by health insurance companies or state social security systems.”

https://www.ncbi.nlm.nih.gov/pubmed/29134767

http://onlinelibrary.wiley.com/doi/10.1002/ejp.1147/abstract

Characterization of endocannabinoids and related acylethanolamides in the synovial fluid of dogs with osteoarthritis: a pilot study.

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“Cannabis-based drugs have been shown to be effective in inflammatory diseases.

A number of endocannabinoids including N- arachidonoylethanolamide (anandamide, AEA) and 2-arachidonyl glycerol (2-AG) with activity at the cannabinoidreceptors (CBR) CBR1 and CBR2, have been identified. Other structurally related endogenous fatty acid compounds such as oleoylethanolamide (OEA) and palmitoyl ethanolamide (PEA) have been identified in biological tissues.

These compounds do not bind to CBR but might be involved in facilitating the actions of directly acting endocannabinoids and thus are commonly termed “entourage” compounds due to their ability to modulate the endocannabinoid system.

The aim of this study was to evaluate the presence of endocannabinoids and entourage compounds in the synovial fluid of dogs with osteoarthritis subjected to arthrotomy of the knee joint. Cytokines and cytology were studied as well.

AEA, 2-AG, OEA and PEA were all present in the synovial fluid of arthritic knees and in the contralateral joints; in addition, a significant increase of OEA and 2AG levels were noted in SF from OA knees when compared to the contralateral joints.

The identification and quantification of endocannabinoids and entourage compounds levels in synovial fluids from dogs with OA of the knee is reported for the first time. Our data are instrumental for future studies involving a greater number of dogs. Cannabinoids represent an emerging and innovative pharmacological tool for the treatment of OA and further studies are warranted to evaluate the effectiveness of cannabinoids in veterinary medicine.”

https://www.ncbi.nlm.nih.gov/pubmed/29110674

“The ECS can be exploited as a potential therapeutic option for OA. We have demonstrated the presence of AEA, 2-AG, OEA and PEA in the SF of dogs with OA. Our data open the avenue to future studies involving a higher number of dogs and aimed at defining the role played by these compounds in OA of the dogs. Both plant-derived and synthetic agonists of CBRs represent an emerging and innovative pharmacological tool for the treatment of OA. ” https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-017-1245-7

Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation.

 

 

“Cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC) have well documented immunomodulatory effects in vitro, but not following oral administration in humans. Here we show that oral co-administration of cannabinoids with lipids can substantially increase their intestinal lymphatic transport in rats. Moreover, immune cells from MS patients were more susceptible to the immunosuppressive effects of cannabinoids than those from healthy volunteers or cancer patients. Therefore, administering cannabinoids with a high-fat meal or in lipid-based formulations has the potential to be a therapeutic approach to improve the treatment of MS, or indeed other autoimmune disorders.”  https://www.ncbi.nlm.nih.gov/pubmed/29109461

“Cannabis sativa has a very long history of medical use. In summary, it has been demonstrated in this work that oral co-administration of cannabis or cannabis-based medicines with lipids results in extremely high levels of lipophilic cannabinoids in the intestinal lymphatic system and prominent immunomodulatory effects. Therefore, administering cannabinoids with a high-fat meal, as cannabis-containing food, or in lipid-based formulations has the potential to be a therapeutic approach to improve the treatment of MS, or indeed other autoimmune disorders.”  https://www.nature.com/articles/s41598-017-15026-z