Topical Medical Cannabis (TMC): A new treatment for wound pain-Three cases of Pyoderma Gangrenosum.

Cover image volume 54, Issue 2

“Pain associated with integumentary wounds is highly prevalent yet it remains an area of significant unmet need within healthcare. Currently, systemically administered opioids are the mainstay of treatment. However, recent publications are casting opioids in a negative light given their high side effect profile, inhibition of wound healing, and association with accidental overdose, incidents that are frequently fatal. Thus, novel analgesic strategies for wound-related pain need to be investigated.

The ideal methods of pain relief for wound patients are modalities that are topical, lack systemic side effects, non-invasive, self-administered, and display rapid onset of analgesia.

Extracts derived from the cannabis plant have been applied to wounds for thousands of years. The discovery of the human endocannabinoid system and its dominant presence throughout the integumentary system provides a valid and logical scientific platform to consider the use of topical cannabinoids for wounds.

We are reporting a prospective case series of 3 patients with Pyoderma Gangrenosum (PG) that were treated with Topical Medical Cannabis (TMC) compounded in non-genetically modified organic sunflower oil.

Clinically significant analgesia that was associated with reduced opioid utilization was noted in all 3 cases. TMC has the potential to improve pain management in patients suffering from wounds of all classes.”

https://www.ncbi.nlm.nih.gov/pubmed/28818631

http://www.jpsmjournal.com/article/S0885-3924(17)30351-2/fulltext

How Does Marijuana Effect Outcomes After Trauma in ICU Patients? A Propensity Matched Analysis

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“Unlike several studies that focus on the effects of marijuana on the outcomes of diseases, our aim was to assess the relationship between a positive toxicology screen for marijuana and mortality in such patients.

A positive marijuana screen is associated with decreased mortality in adult trauma patients admitted to the ICU.

This association warrants further investigation of the possible physiological effects of marijuana in trauma patients.”

https://insights.ovid.com/pubmed?pmid=28787375

GPR55 – a putative “type 3” cannabinoid receptor in inflammation.

“G protein-coupled receptor 55 (GPR55) shares numerous cannabinoid ligands with CB1 and CB2 receptors despite low homology with those classical cannabinoid receptors. The pharmacology of GPR55 is not yet fully elucidated; however, GPR55 utilizes a different signaling system and downstream cascade associated with the receptor. Therefore, GPR55 has emerged as a putative “type 3” cannabinoid receptor, establishing a novel class of cannabinoid receptor. Furthermore, the recent evidence of GPR55-CB1 and GPR55-CB2 heteromerization along with its broad distribution from central nervous system to peripheries suggests the importance of GPR55 in various cellular processes and pathologies and as a potential therapeutic target in inflammation.”

GPR55 G protein-coupled receptor 55 [ Homo sapiens (human) ]

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“This gene belongs to the G-protein-coupled receptor superfamily. The encoded integral membrane protein is a likely cannabinoid receptor. It may be involved in several physiological and pathological processes by activating a variety of signal transduction pathways. ” https://www.ncbi.nlm.nih.gov/gene/9290

“The orphan receptor GPR55 is a novel cannabinoid receptor”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095107/

The orphan receptor GPR55 is a novel cannabinoid receptor

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“Preparations of Cannabis sativa have been used for medicinal and recreational purposes for at least 4000 years and extracts of C. sativa contain over 60 different pharmacologically active components the most prominent being Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol

Ligands such as cannabidiol and abnormal cannabidiol which exhibit no CB1or CB2 activity and are believed to function at a novel cannabinoid receptor, also showed activity at GPR55.

These data suggest that GPR55 is a novel cannabinoid receptor, and its ligand profile with respect to CB1and CB2 described here will permit delineation of its physiological function(s).”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095107/

Cannabis Roots: A Traditional Therapy with Future Potential for Treating Inflammation and Pain

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“The cannabis plant is known for its multiple uses: the leaves, flowers, seeds, stalks, and resin glands have all been exploited for food, fuel, fiber, medicine, and other uses.

The roots of the cannabis plant have a long history of medical use stretching back millennia. However, the therapeutic potential of cannabis roots has been largely ignored in modern times.

In the first century, Pliny the Elder described in Natural Histories that a decoction of the root in water could be used to relieve stiffness in the joints, gout, and related conditions. By the 17th century, various herbalists were recommending cannabis root to treat inflammation, joint pain, gout, and other conditions.

Active compounds identified and measured in cannabis roots include triterpenoids, friedelin (12.8 mg/kg) and epifriedelanol (21.3 mg/kg); alkaloids, cannabisativine (2.5 mg/kg) and anhydrocannabisativine (0.3 mg/kg); carvone and dihydrocarvone; N-( p-hydroxy-b-phenylethyl)-p-hydroxy-trans-cinnamamide (1.6 mg/kg); various sterols such as sitosterol (1.5%), campesterol (0.78%), and stigmasterol (0.56%); and other minor compounds, including choline. Of note, cannabis roots are not a significant source of D9 – tetrahydrocannabinol (THC), cannabidiol, or other known phytocannabinoids.

Conclusion: The current available data on the pharmacology of cannabis root components provide significant support to the historical and ethnobotanical claims of clinical efficacy. Certainly, this suggests the need for reexamination of whole root preparations on inflammatory and malignant conditions employing modern scientific techniques.”

http://online.liebertpub.com/doi/full/10.1089/can.2017.0028

Antidote to cannabinoid intoxication: Inverse cannabinoid receptor one (CB1) agonism by N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidse (AM251) reverses the hypothermic effects of cannabinoid receptor one agonism by 1-Naphthalenyl [4-(pentyloxy)-1-naphthalenyl] methanone (CB13) in mice.

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“Cannabis is a recreational drug leading to intoxication, due to cannabinoid receptor one (CB1 ) stimulation.

The aim of the study was to determine whether CB1 antagonism could reverse physical cannabimimetic effects.

In this study, the pre-existing, central nervous system-related cannabimimetic effects, measured via the hypothermic effect, induced by CB1 receptor agonism where therapeutically treated and were rapidly reversed by CB1 receptor antagonism/inverse agonism. There was also a subjective reversal of visually-evident sedation.

CONCLUSIONS & IMPLICATIONS:

Cannabinoid receptor antagonists have been used in thousands of people and so may provide a single-dose antidote to cannabinoid intoxication, which may save human life,”

https://www.ncbi.nlm.nih.gov/pubmed/28800377

Cannabis phenolics and their bioactivities.

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“Although Cannabis sativa L. is one of the most versatile plant species with multipurpose use both as medical, alimentary source and as psychoactive abuse, its biomedical relevance focused the attention on major cannabinoids. Phytochemical characterization of cannabis highlights the presence of various non-cannabinoids constituents including flavonoids, spiroindans, dihyrostilbenes, dihydrophenanthrenes, lignanamides, steroids and alkaloids. Cannabis is a plant with high pharmacological and nutrition values, its potentialities and applications are not only circumscribed to cannabinoids biological activities, but also defined by non-cannabinoid compounds. This review deals with polyphenols present in this plant, their biosynthesis, their bioactivities and their synthesis, when this occurred.”

https://www.ncbi.nlm.nih.gov/pubmed/28799497

Neuroprotective activity of cannabinoid receptor-2 against oxidative stress and apoptosis in rat pups having experimentally-induced congenital hypothyroidism.

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“In this study, it was aimed to show the cannabinoid receptor-2 (CB2) role, which is a part of neuroprotective endocannabinoidal system, against increasing nitric oxide synthetase (iNOS, eNOS) levels and the apoptotic activity (caspase-3, caspase-9 and DNA in situ fragmentation) within the postnatal critical period in pups of pregnant rats with artificially induced maternal thyroid hormone (TH) deficiency.

In conclusion, apoptosis was triggered via oxidative stress in hypothyroid pups. Accordingly, neuroprotective activity of CB2 receptors were motivated spontaneously to resist to CNS lesions during the first 3 weeks of postnatal period.”

https://www.ncbi.nlm.nih.gov/pubmed/28799288

Perioperative Patient Beliefs Regarding Potential Effectiveness of Marijuana (Cannabinoids) for Treatment of Pain: A Prospective Population Survey.

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“Cannabinoids have an expanding presence in medicine.

Perioperative patients’ perceptions of the effectiveness of these compounds, and acceptance if prescribed for pain, have not been previously described. Our primary objective was to describe patients’ beliefs regarding the potential effectiveness of cannabinoids for the treatment of acute and chronic pain, as well as gauge patient acceptance of these compounds if prescribed by a physician.

More than 80% of this cohort of preoperative patients believed that marijuana could be at least somewhat effective for the treatment of pain after surgery and would be willing to use cannabinoid compounds if prescribed by their physician.

Patients generally believe that marijuana could be at least somewhat effective for the management of pain and are willing to use cannabinoid compounds for this indication, if prescribed by a physician.”