Emerging role of cannabinoids and synthetic cannabinoid receptor 1/cannabinoid receptor 2 receptor agonists in cancer treatment and chemotherapy-associated cancer management

 Journal of Cancer Research and Therapeutics“Cannabis was extensively utilized for its medicinal properties till the 19th century. A steep decline in its medicinal usage was observed later due to its emergence as an illegal recreational drug. Advances in technology and scientific findings led to the discovery of delta-9-tetrahydrocannabinol (THC), the primary psychoactive compound of cannabis, that further led to the discovery of endogenous cannabinoids system consisting of G-protein-coupled receptors – cannabinoid receptor 1 and cannabinoid receptor 2 along with their ligands, mainly anandamide and 2-arachidonoylglycerol. Endocannabinoid (EC) is shown to be a modulator not only for physiological functions but also for the immune system, endocrine network, and central nervous system. Medicinal research and meta-data analysis over the last few decades have shown a significant potential for both THC and cannabidiol (CBD) to exert palliative effects. People suffering from many forms of advanced stages of cancers undergo chemotherapy-induced nausea and vomiting followed by severe and chronic neuropathic pain and weight loss. THC and CBD exhibit effective analgesic, anxiolytic, and appetite-stimulating effect on patients suffering from cancer. Drugs currently available in the market to treat such chemotherapy-induced cancer-related ailments are Sativex (GW Pharmaceutical), Dronabinol (Unimed Pharmaceuticals), and Nabilone (Valeant Pharmaceuticals). Apart from exerting palliative effects, THC also shows promising role in the treatment of cancer growth, neurodegenerative diseases (multiple sclerosis and Alzheimer’s disease), and alcohol addiction and hence should be exploited for potential benefits. The current review discusses the nature and role of CB receptors, specific applications of cannabinoids, and major studies that have assessed the role of cannabinoids in cancer management.”

https://pubmed.ncbi.nlm.nih.gov/33723124/

“Specific targeting of cannabinoid receptors can be used to manage severe side effects during chemotherapy, palliative care, and overall cancer management. Furthermore, research evidences on cannabinoids have suggested tumor inhibiting and suppressing properties which warrant reconsidering legality of the substance. Studies on CB1 and CB2 receptors, in case of cancers, have demonstrated the psychoactive constituents of cannabinoids to be potent against tumor growth. Interestingly, studies have also shown that activation of CB1 and CB2 cannabinoid receptors by their respective synthetic agonists tends to limit human cancer cell growth, suggesting the role of the endocannabinoid system as a novel target for treatment of cancers.”

https://www.cancerjournal.net/article.asp?issn=0973-1482;year=2021;volume=17;issue=1;spage=1;epage=9;aulast=Shah

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Cannabinoids in Dermatologic Surgery

JAAD Journals on Twitter: "Have questions for JAAD authors? Join the new  JAAD Virtual Journal Club and start engaging with authors today:  https://t.co/KWSzvAEPd5… https://t.co/ip6aG4d2fm"“Though known as a medicinal herb for centuries, the recent legalization of cannabinoids across many states has ushered in a new era where cannabinoids have become a popular treatment option amongst clinicians and patients alike. Cannabinoids have demonstrated efficacy in wound healing, reducing inflammation, ameliorating pain, and have shown potential as an anti-tumor agent. As a result, cannabinoids have been rapidly woven into the fabric of modern medicine. However, the utility of cannabinoids in dermatologic surgery has not been explored to date. In this paper, we review the current literature to discuss the potential impact of cannabinoid use in dermatologic surgery.”

https://pubmed.ncbi.nlm.nih.gov/33422628/

https://www.jaad.org/article/S0190-9622(21)00104-3/pdf

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A Survey on the Effect That Medical Cannabis Has on Prescription Opioid Medication Usage for the Treatment of Chronic Pain at Three Medical Cannabis Practice Sites

Cureus | LinkedIn“Objective: The opioid epidemic continues to claim thousands of lives every year without an effective strategy useful in mitigating mortality. The use of medical cannabis has been proposed as a potential strategy to decrease opioid usage. The objective of this study was to determine how the use of medical cannabis affects prescribed opioid usage in chronic pain patients.

Methods: We conducted an online convenience sample survey of patients from three medical cannabis practice sites who had reported using opioids. A total of 1181 patients responded, 656 were excluded for not using medical cannabis in combination with opioid use or not meeting the definition of chronic pain, leaving 525 patients who had used prescription opioid medications continuously for at least three months to treat chronic pain and were using medical cannabis in combination with their prescribed opioid use.

Results: Overall, 40.4% (n=204) reported that they stopped all opioids, 45.2% (n=228) reported some decrease in their opioid usage, 13.3% (n=67) reported no change in opioid usage, and 1.1% (n=6) reported an increase in opioid usage. The majority (65.3%, n=299) reported that they sustained the opioid change for over a year. Almost half (48.2%, n=241) reported a 40-100% decrease in pain while 8.6% (n=43) had no change in pain and 2.6% (n=13) had worsening pain. The majority reported improved ability to function (80.0%, n=420) and improved quality of life (87.0%, n=457) with medical cannabis. The majority (62.8%, n=323) did not want to take opioids in the future. While the change in pain level was not affected by age and gender, the younger age group had improved ability to function compared with the middle and older age groups.

Conclusions: Patients in this study reported that cannabis was a useful adjunct and substitute for prescription opioids in treating their chronic pain and had the added benefit of improving the ability to function and quality of life.”

https://pubmed.ncbi.nlm.nih.gov/33409086/

“Our results show a remarkable percentage of patients both reporting complete cessation of opioids and decreasing opioid usage by the addition of medical cannabis, with results lasting for over a year for the majority. Additional benefits of medical cannabis included improved ability to function and improved quality of life, especially for the younger age group. We believe our results lend further support that medical cannabis provided in a standardized protocol can lead to decreased pain and opioid usage, improved function, and quality of life measures, and even complete cessation of opioids in patients with chronic pain treated by opioids.”

https://www.cureus.com/articles/41928-a-survey-on-the-effect-that-medical-cannabis-has-on-prescription-opioid-medication-usage-for-the-treatment-of-chronic-pain-at-three-medical-cannabis-practice-sites

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Cannabis use is associated with reduced risk of exposure to fentanyl among people on opioid agonist therapy during a community-wide overdose crisis

Drug and Alcohol Dependence “Background: The ongoing opioid overdose crisis is driven largely by exposure to illicitly-manufactured fentanyl. Preliminary observational and experimental research suggests that cannabis could potentially play a role in reducing use of prescription opioids among individuals with chronic pain. However, there is limited data on the effects of cannabis on illicit opioid consumption, particularly fentanyl, especially among individuals on opioid agonist therapy (OAT). We sought to assess the longitudinal association between cannabis use and exposure to fentanyl among people on OAT.

Results: Among the 819 participants on OAT who contributed 1989 observations over the study period, fentanyl exposure was common. At the baseline interview, fentanyl was detected in a majority of participants (431, 53 %), with lower prevalence among individuals with urine drug tests positive for tetrahydrocannabinol (47 vs. 56 %, p = 0.028). Over all study interviews, cannabis use was independently associated with reduced likelihood of being recently exposed to fentanyl (Adjusted Prevalence Ratio = 0.91, 95 % Confidence Interval: 0.83 – 0.99).

Conclusions: Participants on OAT using cannabis had significantly lower risk of being exposed to fentanyl. Our findings reinforce the need for experimental trials to investigate the potential benefits and risks of controlled cannabinoid administration for people on OAT.”

https://pubmed.ncbi.nlm.nih.gov/33342591/

“Opioid agonist therapies (OAT) are the primary treatments for opioid use disorder. Exposure to fentanyl is driving mortality risk in the overdose crisis. Among 819 participants on OAT, cannabis was negatively associated with fentanyl. Experimental trials are needed to evaluate cannabis use during OAT.”

https://www.sciencedirect.com/science/article/abs/pii/S0376871620305858?via%3Dihub

“Cannabis could reduce fentanyl use, reduce overdose risk: study” https://www.bccsu.ca/blog/news-release/cannabis-could-reduce-fentanyl-use-reduce-overdose-risk-study/

“Cannabis could reduce fentanyl use, reduce overdose risk” https://www.med.ubc.ca/news/cannabis-could-reduce-fentanyl-use-reduce-overdose-risk/

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Cannabinoid control of neurogenic inflammation

 British Journal of Pharmacology“A significant number of cannabinoids are known to have analgesic and anti-inflammatory properties in various diseases. Due to their presynaptic/terminal location, cannabinoid receptors can inhibit synaptic transmission and have the potential to regulate neurogenic inflammation. Neurogenic inflammation occurs when a noxious signal is detected in the periphery initiating an antidromic axon reflex in the same sensory neurone leading to depolarization of the afferent terminal. Neuropeptides are subsequently released and contribute to vasodilation, plasma extravasation and modulation of immune cells. Endocannabinoids, synthetic cannabinoids and phytocannabinoids can reduce neuroinflammation by inhibiting afferent firing and inflammatory neuropeptide release. Thus, in addition to a direct effect on vascular smooth muscle and inflammatory cells, cannabinoids can reduce inflammation by silencing small diameter neurones. This review examines the neuropharmacological processes involved in regulating antidromic depolarization of afferent nerve terminals by cannabinoids and the control of neurogenic inflammation in different diseases.”

https://pubmed.ncbi.nlm.nih.gov/33289534/

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.15208

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Perioperative Cannabis as a Potential Solution for Reducing Opioid and Benzodiazepine Dependence

See the source image“Cannabis is increasingly being used for medicinal purposes but remains outside Western medical practice. Data on perioperative use and outcomes are scarce. Few surgeons receive training regarding legal endorsement, reported medicinal benefits, and potential risks, making it difficult to advise patients. Guidelines and additional research are needed.

Observations: It is legal to recommend cannabis, which can be obtained in states with medical cannabis programs. There are many methods of consumption, oral being the safest. Activity is primarily through Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) via cannabinoid receptors, which may be potentiated when taken together in the plant or plant extract. The known effects of cannabis on inflammation and malignancy are largely limited to laboratory experiments. However, there are higher-quality data to support adjunctive use of cannabis for relief of pain, nausea, and insomnia, which may be useful postoperatively and could potentially decrease reliance on opiates and benzodiazepines. There are prospective trials in surgical patients, but no reported data regarding surgical complications or other surgical outcomes. Currently, cannabis is regulated differently than other controlled substances, and there are issues with purity/homogeneity, making it difficult for surgeons to accept or significantly explore its medical benefits.

Conclusions and relevance: Recommendations are made for surgeons advising patients who use cannabis based on the limited existing data. While cannabis likely has some therapeutic benefits, it must be treated as other medical controlled substances to truly elucidate its role in surgical patient care.”

https://pubmed.ncbi.nlm.nih.gov/33263719/

https://jamanetwork.com/journals/jamasurgery/article-abstract/2773526

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Use of Cannabis for Self-Management of Chronic Pelvic Pain

 View details for Journal of Women's Health cover image“Chronic pelvic pain (CPP) affects up to 15% of women in the United States. The endocannabinoid system is a potential pharmacological target for pelvic pain as cannabinoid receptors are highly expressed in the uterus and other nonreproductive tissues.

We hypothesize that cannabis use is common for self-management of CPP, and our primary objective was to determine the prevalence of cannabis use in this population.

Results: A total of 240 patients were approached, with 113 responses (47.1% response rate). There were 26 patients who used cannabis (23%). The majority used at least once per week (n = 18, 72%). Most users (n = 24, 96%) reported improvement in symptoms, including pain, cramping, muscle spasms, anxiety, depression, sleep disturbances, libido, and irritability. Over one-third (35%) stated that cannabis use decreased the number of phone calls or messages sent to their provider, and 39% reported decreased number of clinical visits. Side effects, including dry mouth, sleepiness, and feeling “high,” were reported by 84% (n = 21).

Conclusions: Almost one-quarter of patients with CPP report regular use of cannabis as an adjunct to their prescribed therapy. Although side effects are common, most users report improvement in symptoms. Our study highlights the potential of cannabis as a therapeutic option for patients with CPP.”

https://pubmed.ncbi.nlm.nih.gov/33252316/

https://www.liebertpub.com/doi/10.1089/jwh.2020.8737

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Consensus-Based Recommendations for Titrating Cannabinoids and Tapering Opioids for Chronic Pain Control

International Journal of Clinical Practice“Opioid misuse and overuse has contributed to a widespread overdose crisis and many patients and physicians are considering medical cannabis to support opioid tapering and chronic pain control. Using a five-step modified Delphi process, we aimed to develop consensus-based recommendations on: 1) when and how to safely initiate and titrate cannabinoids in the presence of opioids, 2) when and how to safely taper opioids in the presence of cannabinoids, and 3) how to monitor patients and evaluate outcomes when treating with opioids and cannabinoids.

Results: In patients with chronic pain taking opioids not reaching treatment goals, there was consensus that cannabinoids may be considered for patients experiencing or displaying opioid-related complications, despite psychological or physical interventions. There was consensus observed to initiate with a cannabidiol (CBD)-predominant oral extract in the daytime and consider adding tetrahydrocannabinol (THC). When adding THC, start with 0.5-3 mg, and increase by 1-2 mg once or twice weekly up to 30-40 mg/day. Initiate opioid tapering when the patient reports a minor/major improvement in function, seeks less as-needed medication to control pain, and/or the cannabis dose has been optimized. The opioid tapering schedule may be 5%-10% of the morphine equivalent dose (MED) every 1 to 4 weeks. Clinical success could be defined by an improvement in function/quality of life, a ≥ 30% reduction in pain intensity, a ≥ 25% reduction in opioid dose, a reduction in opioid dose to < 90 mg MED, and/or reduction in opioid-related adverse events.

Conclusions: This five-stage modified Delphi process led to the development of consensus-based recommendations surrounding the safe introduction and titration of cannabinoids in concert with tapering opioids.”

https://pubmed.ncbi.nlm.nih.gov/33249713/

https://onlinelibrary.wiley.com/doi/10.1111/ijcp.13871

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Antinociception mechanisms of action of cannabinoid-based medicine: an overview for anesthesiologists and pain physicians

 Pain Rounds“Cannabinoid-based medications possess unique multimodal analgesic mechanisms of action, modulating diverse pain targets.

Cannabinoids are classified based on their origin into three categories: endocannabinoids (present endogenously in human tissues), phytocannabinoids (plant derived) and synthetic cannabinoids (pharmaceutical). Cannabinoids exert an analgesic effect, peculiarly in hyperalgesia, neuropathic pain and inflammatory states.

Endocannabinoids are released on demand from postsynaptic terminals and travels retrograde to stimulate cannabinoids receptors on presynaptic terminals, inhibiting the release of excitatory neurotransmitters. Cannabinoids (endogenous and phytocannabinoids) produce analgesia by interacting with cannabinoids receptors type 1 and 2 (CB1 and CB2), as well as putative non-CB1/CB2 receptors; G protein-coupled receptor 55, and transient receptor potential vanilloid type-1. Moreover, they modulate multiple peripheral, spinal and supraspinal nociception pathways.

Cannabinoids-opioids cross-modulation and synergy contribute significantly to tolerance and antinociceptive effects of cannabinoids. This narrative review evaluates cannabinoids’ diverse mechanisms of action as it pertains to nociception modulation relevant to the practice of anesthesiologists and pain medicine physicians.”

https://pubmed.ncbi.nlm.nih.gov/33239391/

https://rapm.bmj.com/content/early/2020/11/24/rapm-2020-102114

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Prescribed medical cannabis in women with gynecologic malignancies: A single-institution survey-based study

Gynecologic Oncology Reports “Research within a gynecologic oncology population has lagged behind the uptake in use of medical cannabis for symptom control. This study seeks to evaluate patient experience with prescribed medical cannabis obtained through licensed dispensaries in women with gynecologic malignancies.

A 43-item survey exploring patient experience with medical cannabis was administered to women with gynecologic malignancies who used medical cannabis prescribed by a gynecologic oncologist. Thirty-six eligible patients were approached for consent, and 31 patients returned completed surveys (86%). Ninety-three percent had advanced or recurrent disease; 74% were receiving chemotherapy or immunotherapy.

Eighty-three percent reported medical cannabis provided relief from cancer or treatment-related symptoms including decreased appetite (41%), insomnia (41%), neuropathy (41%), anxiety (35%), nausea (29%), joint pain (29%), bone pain (29%), abdominal pain (25%), and depression (19%). Eighty percent of patients reported medical cannabis worked the same or better than other traditional medications for management of their cancer or treatment-related symptoms, and 83% reported medical cannabis had an equivalent or better side effect profile.

Of the subset of patients using medical cannabis for pain, 63% reported a reduction in opioid use. Patients perceive that medical cannabis was useful for relief of cancer and treatment-related symptoms, suggesting medical cannabis may be a reasonable alternative or adjunct therapy. Medical cannabis was well tolerated and may have the potential to improve neuropathic pain and decrease opioid use.”

https://pubmed.ncbi.nlm.nih.gov/33204797/

“Patients with gynecologic malignancies perceive medical cannabis relieves multiple cancer-related symptoms. Medical cannabis is well-tolerated and perceived to have a favorable side effect profile. Patients using medical cannabis for pain control report an associated reduction in opioid use.”

https://www.sciencedirect.com/science/article/pii/S2352578920301338?via%3Dihub

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