Medical Cannabis in the Palliation of Malignant Wounds—A Case Report

“Anecdotal accounts of the use of topical extracts from the cannabis plant being used on open wounds date back to antiquity. In modern times, cannabinoid therapies have demonstrated efficacy as analgesic agents in both pharmaceutical and botanical formats. Medical cannabis (MC), also known as medical marijuana,… The endogenous cannabinoid system, consisting of cannabinoid receptors and their endogenous ligands, is ubiquitous throughout the human bodyAvailable research shows that cancer cells express higher levels of the cannabinoid receptors, CB1 and CB2, relative to their noncancer counterparts, while also demonstrating an overall state of upregulationHuman in vitro studies, using nonmelanoma skin lines, have demonstrated direct induction of tumor cell apoptosis and inhibition of tumor-related angiogenesis, both by way of activation of cannabinoid receptors.

The analgesic outcomes observed in this case are supported by the results of a recent systematic review and meta-analysis of cannabinoids for medical useUnlike intact skin, which is polar and hydrophilic, wounds lack epithelial coverage and are nonpolar and lipophilic. Therefore, lipophilic compounds such as the THC and CBD cannabinoids may be readily absorbed through cutaneous wounds.

Before the use of topical MC oil, the patient’s wound was growing rapidly. Yet, after a few weeks, a modest regression of his malignant wound was observed while the patient used topical MC. This secondary outcome suggests that topical MC may promote antineoplastic activity as per the findings of Casanova et al.

In summary, this is the first case report to demonstrate the potential for MC to provide effective pain and symptom management in the setting of malignant wounds. The rapid onset of analgesia after topical placement suggests that the effects were mediated through absorption of the THC and CBD cannabinoids that subsequently interacted with peripheral nociceptors, immune cells, and cancer cells. The postapplication analgesia may be because of the gastrointestinal absorption of ingested residual MC oil. This case suggests that MC delivered in vaporized and topical oil formats warrants further investigation in human malignancy, including randomized controlled trials capable of establishing long-term efficacy, optimal dosage, schedules of administration, mixture composition, and safety.”

http://www.jpsmjournal.com/article/S0885-3924(16)30328-1/fulltext “Can Cannabis Oil Help Heal Wounds?”                              http://www.livescience.com/57500-can-medical-cannabis-help-heal-wounds.html “Oral cancer patient, 44, claims cannabis oil helped to shrink a hole in his cheek that was caused by the disease” http://www.dailymail.co.uk/health/article-4124752/Oral-cancer-patient-44-claims-cannabis-oil-helped-shrink-hole-cheek-caused-disease.html

“Miracle plant: Can medical marijuana heal wounds?” http://www.nydailynews.com/life-style/medical-marijuana-heal-wounds-article-1.3384572

“Cannabis Oil Shows Potential To Heal Cancer Wounds Fast”  http://www.healthaim.com/cannabis-oil-shows-potential-heal-cancer-wounds-fast/71395]]>

Synergistic attenuation of chronic pain using mu opioid and cannabinoid receptor 2 agonists.

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“The misuse of prescription opiates is on the rise with combination therapies (e.g. acetaminophen or NSAIDs) resulting in severe liver and kidney damage. In recent years, cannabinoid receptors have been identified as potential modulators of pain and rewarding behaviors associated with cocaine, nicotine and ethanol in preclinical models. Yet, few studies have identified whether mu opioid agonists and CB2 agonists act synergistically to inhibit chronic pain while reducing unwanted side effects including reward liability.

We determined if analgesic synergy exists between the mu-opioid agonist morphine and the selective CB2 agonist, JWH015, in rodent models of acute and chronic inflammatory, post-operative, and neuropathic pain using isobolographic analysis. We also investigated if the MOR-CB2 agonist combination decreased morphine-induced conditioned place preference (CPP) and slowing of gastrointestinal transit. Co-administration of morphine with JWH015 synergistically inhibited preclinical inflammatory, post-operative and neuropathic-pain in a dose- and time-dependent manner; no synergy was observed for nociceptive pain. Opioid-induced side effects of impaired gastrointestinal transit and CPP were significantly reduced in the presence of JWH015.

Here we show that MOR + CB2 agonism results in a significant synergistic inhibition of preclinical pain while significantly reducing opioid-induced unwanted side effects.

The opioid sparing effect of CB2 receptor agonism strongly supports the advancement of a MOR-CB2 agonist combinatorial pain therapy for clinical trials.”

https://www.ncbi.nlm.nih.gov/pubmed/28007501

Cannabis and epilepsy: An ancient treatment returns to the fore.

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“Cannabis has been associated with the treatment of epilepsy throughout history, and if ancient Assyrian sources referring to “hand of ghost” are considered credible, this relationship may span four millennia.

A tradition of usage continued in Arabic medicine and Ayurvedic practice in India, which led, in turn, to early experiments in Europe and North America with “Indian hemp.”

Lack of standardization, bioavailability issues, and ultimately prohibition were all factors in cannabis-based medicines failing to maintain mainstream usage in seizure treatment, but investigation was resumed in the 1970s with interesting signals noted in both laboratory and clinical settings.

Early case studies showed promise, but lacked sufficient rigor. Resumption of research coupled with mass experimentation by families of epilepsy patients has led to intense interest in cannabis-based medicines for its treatment once more, with greatest focus on cannabidiol, but additional investigation of tetrahydrocannabinol, tetrahydrocannabinolic acid, and other phytocannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/27989385

In vitro Antimicrobial and Antioxidant Activity of Extracts from Six Chemotypes of Medicinal Cannabis

“Nowadays, medicinal cannabis (Cannabis sativa L) is in the focus of the researches not only for its high content of tetrahydrocannabinol (THC), but for other cannabinoids as well.

It has been reported that some of the identified substances (e.g. cannabidiol, cannabinochromene) possess anti-inflammatory and antimicrobial properties, which corresponds to its traditional use as wound healing agent at Pakistan.

The aim of this study was to evaluate antimicrobial and antioxidant ability of extracts from high potent Cannabis sativa chemotypes.

The six ethanolic extracts prepared from dried inflorescence of five medicinal cannabis chemotypes (Nurse Jackie, Jilly Bean, Nordle, Jack Cleaner, Conspiracy Kush) were tested by standard microdilution method against Staphylococcus aureus (three strains), Streptococcus pyogenes and the yeast Candida albicans.

Those microbial strains are present on skin and can cause complication during wound healing process.

The antioxidative activity, which plays an important role in wound healing process, was tested by oxygen radical absorbance capacity test (ORAC).

All tested extracts demonstrated high antimicrobial activity against two strains of S. aureus and S. pyogenes (MIC ranged from 4 – 16 µg·mL-1), moreover high antioxidant capacity was observed (ORAC ranged from 800 – 1300 µg TE/mg of extract).

The results indicate that cannabis has high potential to be used in ointments and other material for wound healing.

However, further research on the identification of the active components is needed.”

https://www.thieme-connect.com/DOI/DOI?10.1055/s-0036-1596302

An observational postmarketing safety registry of patients in the UK, Germany, and Switzerland who have been prescribed Sativex® (THC:CBD, nabiximols) oromucosal spray.

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“The global exposure of Sativex®9-tetrahydrocannabinol [THC]:cannabidiol [CBD], nabiximols) is estimated to be above 45,000 patient-years since it was given marketing approval for treating treatment-resistant spasticity in multiple sclerosis (MS).

An observational registry to collect safety data from patients receiving THC:CBD was set up following its approval in the UK, Germany, and Switzerland, with the aim of determining its long-term safety in clinical practice.

Twice a year, the Registry was opened to prescribing physicians to voluntarily report data on patients’ use of THC:CBD, clinically significant adverse events (AEs), and special interest events. The Registry contains data from 941 patients with 2,213.98 patient-years of exposure.

Within this cohort, 60% were reported as continuing treatment, while 83% were reported as benefiting from the treatment. Thirty-two percent of patients stopped treatment, with approximately one third citing lack of effectiveness and one quarter citing AEs.

Psychiatric AEs of clinical significance were reported in 6% of the patients, 6% reported falls requiring medical attention, and suicidality was reported in 2%. Driving ability was reported to have worsened in 2% of patients, but improved in 7%.

AEs were more common during the first month of treatment. The most common treatment-related AEs included dizziness (2.3%) and fatigue (1.7%).

There were no signals to indicate abuse, diversion, or dependence.

The long-term risk profile from the Registry is consistent with the known (labeled) safety profile of THC:CBD, and therefore supports it being a well-tolerated and beneficial medication for the treatment of MS spasticity.

No evidence of new long-term safety concerns has emerged.”

https://www.ncbi.nlm.nih.gov/pubmed/27956834

Cannabinoid 2 Receptor Agonist Improves Systemic Sensitivity to Insulin in High-Fat Diet/Streptozotocin-Induced Diabetic Mice.

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“The endocannabinoid signalling (ECS) system has been known to regulate glucose homeostasis.

Previous studies have suggested that the cannabinoid 2 (CB2) receptor may play a regulatory role on insulin secretion, immune modulation and insulin resistance.

Given that diabetes and insulin resistance are attributable to elevated inflammatory tone, we investigated the role of CB2 receptor on glucose tolerance and insulin sensitivity in high-fat diet (HFD)/streptozotocin (STZ)-induced mice.

Our data suggest a lipolytic role of SER601 in HFD/STZ-induced diabetic mice, which results in significant improvement of systemic insulin sensitivity.

Thus, the CB2 receptor may be considered a promising target for therapeutic development against insulin resistance and obesity-related diabetes.”

https://www.ncbi.nlm.nih.gov/pubmed/27960161

Tolerability of dronabinol alone, ondansetron alone and the combination of dronabinol plus ondansetron in delayed chemotherapy-induced nausea and vomiting.

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“Dronabinol (Marinol), the synthetic version of tetrahydrocannabinol, is used to treat nausea and vomiting following cancer chemotherapy (CINV).

It has a unique mechanism of action (cannabinoid receptor binding) compared to the more frequently used serotonin receptor antagonists. Tolerability of dronabinol versus ondansetron and the combination of dronabinol plus ondansetron was explored in subjects with delayed CINV.

Dronabinol was well tolerated and resulted in few terminations due to adverse events. The low rate of CNS-related adverse events following D treatment may make it a suitable alternative to serotonin antagonist therapy for delayed CINV.”

https://www.ncbi.nlm.nih.gov/pubmed/27946950

Dronabinol treatment of delayed chemotherapy-induced nausea and vomiting (CINV).

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“Dronabinol (MARINOL), synthetic tetrahydrocannabinol, binds to cannabinoid receptors and has antiemetic activity. To explore if this novel mechanism would be of benefit in delayed CINV, dronabinol was added to the prophylactic regimen for acute CINV and continued after chemotherapy.

Efficacy at Endpoint (LOCF) Conclusions: Dronabinol (D) was comparable to ondansetron (O) in total response and but was more effective in reducing nausea intensity and vomiting/retching. Results for the combination of DO were similar to either agent alone.

These results support conducting a larger study since D could become an attractive alternative to serotonin receptor antagonists in treating delayed CINV.”

https://www.ncbi.nlm.nih.gov/pubmed/27946578

Compensatory activation of cannabinoid CB2 receptor inhibition of GABA release in the rostral ventromedial medulla (RVM) in inflammatory pain.

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“The rostral ventromedial medulla (RVM) is a relay in the descending pain modulatory system and an important site of endocannabinoid modulation of pain.

These studies demonstrate that endocannabinoid signaling to CB1- and CB2-receptors in adult RVM is altered in persistent inflammation.

The emergence of CB2 receptor function in the RVM provides additional rationale for the development of CB2 receptor-selective agonists as useful therapeutics for chronic inflammatory pain.”

https://www.ncbi.nlm.nih.gov/pubmed/27940994

Anti-inflammatory effect of cannabinoid agonist WIN55, 212 on mouse experimental colitis is related to inhibition of p38MAPK.

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“To investigate the anti-inflammatory effect and the possible mechanisms of an agonist of cannabinoid (CB) receptors, WIN55-212-2 (WIN55), in mice with experimental colitis, so as to supply experimental evidence for its clinical use in future.

These results confirmed the anti-inflammatory effect and protective role of WIN55 on the mice with experimental colitis, and revealed that this agent exercises its action at least partially by inhibiting p38MAPK.

Furthermore, the results showed that SB203580, affected the expression of CB1 and CB2 receptors in the mouse colon, suggesting a close linkage and cross-talk between the p38MAPK signaling pathway and the endogenous CB system.”

https://www.ncbi.nlm.nih.gov/pubmed/27920472