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

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

Cannabis and its Constituents for Cancer: History, Biogenesis, Chemistry and Pharmacological Activities

Pharmacological Research “Cannabis has long been used for healing and recreation in several regions of the world. Over 400 bioactive constituents, including more than 100 phytocannabinoids, have been isolated from this plant. The non-psychoactive cannabidiol (CBD) and the psychoactive Δ9-tetrahydrocannabinol (Δ9-THC) are the major and widely studied constituents from this plant.

Cannabinoids exert their effects through the endocannabinoid system (ECS) that comprises cannabinoid receptors (CB1, CB2), endogenous ligands, and metabolizing enzymes. Several preclinical studies have demonstrated the potential of cannabinoids against leukemia, lymphoma, glioblastoma, and cancers of the breast, colorectum, pancreas, cervix and prostate.

Cannabis and its constituents can modulate multiple cancer related pathways such as PKB, AMPK, CAMKK-β, mTOR, PDHK, HIF-1α, and PPAR-γ. Cannabinoids can block cell growth, progression of cell cycle and induce apoptosis selectively in tumour cells. Cannabinoids can also enhance the efficacy of cancer therapeutics. These compounds have been used for the management of anorexia, queasiness, and pain in cancer patients.

Cannabinoid based products such as dronabinol, nabilone, nabiximols, and epidyolex are now approved for medical use in cancer patients. Cannabinoids are reported to produce a favourable safety profile. However, psychoactive properties and poor bioavailability limit the use of some cannabinoids. The Academic Institutions across the globe are offering training courses on cannabis. How cannabis and its constituents exert anticancer activities is discussed in this article. We also discuss areas that require attention and more extensive research.”

https://pubmed.ncbi.nlm.nih.gov/33246167/

https://www.sciencedirect.com/science/article/abs/pii/S1043661820316108?via%3Dihub

Use of Cannabinoids to Treat Acute Respiratory Distress Syndrome and Cytokine Storm Associated with Coronavirus Disease-2019

Frontiers in Pharmacology (@FrontPharmacol) | Twitter“Coronavirus disease 2019 (COVID-19) is a highly infectious respiratory disease caused by the severe acute respiratory syndrome coronavirus 2. A significant proportion of COVID-19 patients develop Acute Respiratory Distress Syndrome (ARDS) resulting from hyperactivation of the immune system and cytokine storm, which leads to respiratory and multi-organ failure, and death. Currently, there are no effective treatments against hyperimmune syndrome and ARDS.

We propose that because immune cells express cannabinoid receptors and their agonists are known to exhibit potent anti-inflammatory activity, targeting cannabinoid receptors, and endocannabinoids deserve intense investigation as a novel approach to treat systemic inflammation, cytokine storm, and ARDS in patients with COVID-19.”

https://pubmed.ncbi.nlm.nih.gov/33240092/

“The fact that cells of the immune system produce endocannabinoids and express both CB1 and CB2 cannabinoid receptors provides unique opportunities into investigating how the cannabinoid system can be engineered to suppress inflammation using both exogenous and endogenous cannabinoids. Because cannabinoids are potent suppressors of inflammation as evidenced by their ability to suppress cytokine storm in animal models, they may serve as novel therapeutic agents to treat cytokine storm and ARDS that are seen in patients with or without COVID-19. There is a dire need for novel anti-inflammatory agents that exert broad spectrum cytokine suppression associated with ARDS considering that currently up to 40% of such patients, including those with COVID-19, die because currently there are no FDA-approved drugs that are highly effective against cytokine storm and ARDS.”

https://www.frontiersin.org/articles/10.3389/fphar.2020.589438/full

Cannabis in Parkinson’s Disease: The Patients’ View

IOS Press | Impacting the World of ScienceLittle is known about the patients’ view on treatment with medical cannabis (MC) for Parkinson’s disease (PD).

Objective: To assess the PD community’s perception of MC and patients’ experience with MC.

Results: Overall, 1.348 questionnaires (1.123 nationwide, 225 local) were analysed. 51% of participants were aware of the legality of MC application, 28% of various routes of administration (ROA) and 9% of the difference between delta9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). PD-related cannabis use was reported by 8.4% of patients and associated with younger age, living in large cities and better knowledge about the legal and clinical aspects of MC. Reduction of pain and muscle cramps was reported by more than 40% of cannabis users. Stiffness/akinesia, freezing, tremor, depression, anxiety and restless legs syndrome subjectively improved for more than 20% and overall tolerability was good. Improvement of symptoms was reported by 54% of users applying oral CBD and 68% inhaling THC-containing cannabis. Compared to CBD intake, inhalation of THC was more frequently reported to reduce akinesia and stiffness (50.0% vs. 35.4%; p < 0.05). Interest in using MC was reported by 65% of non-users.

Conclusion: MC is considered as a therapeutic option by many PD patients. Nevertheless, efficacy and different ROA should further be investigated.”

https://pubmed.ncbi.nlm.nih.gov/33216043/

https://content.iospress.com/articles/journal-of-parkinsons-disease/jpd202260

CB2 receptor-selective agonists as candidates for targeting infection, inflammation, and immunity in SARS-CoV-2 infections

“The COVID-19 pandemic caused by SARS-CoV-2 is a deadly disease afflicting millions. The pandemic continues affecting population due to nonavailability of drugs and vaccines. The pathogenesis and complications of infection mainly involve hyperimmune-inflammatory responses. Thus, therapeutic strategies rely on repurposing of drugs aimed at reducing infectivity and inflammation and modulate immunity favourably.

Among, numerous therapeutic targets, the endocannabinoid system, particularly activation of cannabinoid type-2 receptors (CB2R) emerged as an important one to suppress the hyperimmune-inflammatory responses. Recently, potent antiinflammatory, antiviral and immunomodulatory properties of CB2R selective ligands of endogenous, plant, and synthetic origin were showed mediating CB2R selective functional agonism.

CB2R activation appears to regulate numerous signaling pathways to control immune-inflammatory mediators including cytokines, chemokines, adhesion molecules, prostanoids, and eicosanoids. Many CB2R ligands also exhibit off-target effects mediating activation of PPARs, opioids, and TRPV, suggestive of adjuvant use with existing drugs that may maximize efficacy synergistically and minimize therapeutic doses to limit adverse/ side effects.

We hypothesize that CB2R agonists, due to immunomodulatory, antiinflammatory, and antiviral properties may show activity against COVID-19. Based on the organoprotective potential, relative safety, lack of psychotropic effects, and druggable properties, CB2R selective ligands might make available promising candidates for further investigation.”

https://pubmed.ncbi.nlm.nih.gov/33190277/

https://onlinelibrary.wiley.com/doi/10.1002/ddr.21752

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The endocannabinoidome as a substrate for noneuphoric phytocannabinoid action and gut microbiome dysfunction in neuropsychiatric disorders

“The endocannabinoid (eCB) system encompasses the eCBs anandamide and 2-arachidonoylglycerol, their anabolic/catabolic enzymes, and the cannabinoid CB1 and CB2 receptors. Its expansion to include several eCB-like lipid mediators, their metabolic enzymes, and their molecular targets, forms the endocannabinoidome (eCBome).

This complex signaling system is deeply involved in the onset, progress, and symptoms of major neuropsychiatric disorders and provides a substrate for future therapeutic drugs against these diseases. Such drugs may include not only THC, the major psychotropic component of cannabis, but also other, noneuphoric plant cannabinoids.

These compounds, unlike THC, possess a wide therapeutic window, possibly due to their capability of hitting several eCBome and non-eCBome receptors. This is particularly true for cannabidiol, which is one of the most studied cannabinoids and shows promise for the treatment of a wide range of mental and mood disorders. The eCBome plays a role also in the microbiota-gut-brain axis, which is emerging as an important actor in the control of affective and cognitive functions and in their pathological alterations.”

https://pubmed.ncbi.nlm.nih.gov/33162769/

https://www.dialogues-cns.org/dialoguesclinneurosci-22-259/

History of cannabis and the endocannabinoid system

“This article retraces the story of cannabis from the earliest contacts of humans with the plant to its subsequent global expansion, its medicinal uses, and the discovery of the endocannabinoid system in the 20th century. Cannabis was attested to around 12 000 years ago near the Altai Mountains in Central Asia, and since then, cannabis seeds have accompanied the migration of nomadic peoples. Records of the medicinal use of cannabis appear before the Common Era in China, Egypt, and Greece (Herodotus), and later in the Roman empire (Pliny the Elder, Dioscorides, Galen). In the 19th century, orientalists like Silvestre de Sacy, and Western physicians coming into contact with Muslim and Indian cultures, like O’Shaughnessy and Moreau de Tours, introduced the medicinal use of cannabis into Europe. The structure of the main psychoactive phytocannabinoid, tetrahydrocannabinol (THC), was determined in Israel by Mechoulam and Gaoni in 1964. This discovery opened the gate for many of the subsequent developments in the field of endocannabinoid system (ECS) research. The advances in the scientific knowledge of the ECS place the debate on cannabis liberalization in a new context.”

https://pubmed.ncbi.nlm.nih.gov/33162765/

https://www.dialogues-cns.org/dialoguesclinneurosci-22-223/

The Effects of Cannabis Use on Cognitive Function in Healthy Aging: A Systematic Scoping Review

Archives of Clinical Neuropsychology“Background: Older adults (≥50 years) represent the fastest-growing population of people who use cannabis, potentially due to the increasing promotion of cannabis as medicine by dispensaries and cannabis websites. Given healthy aging and cannabis use are both associated with cognitive decline, it is important to establish the effects of cannabis on cognition in healthy aging.

Objective: This systematic scoping review used preferred reporting items for systematic reviews and meta-analyses guidelines to critically examine the extent of literature on this topic and highlight areas for future research.

Results: Six articles reported findings for older populations (three human and three rodent studies), highlighting the paucity of research in this area. Human studies revealed largely null results, likely due to several methodological limitations. Better-controlled rodent studies indicate that the relationship between ∆9-tetrahydrocannabinol (THC) and cognitive function in healthy aging depends on age and level of THC exposure. Extremely low doses of THC improved cognition in very old rodents. Somewhat higher chronic doses improved cognition in moderately aged rodents. No studies examined the effects of cannabidiol (CBD) or high-CBD cannabis on cognition.

Conclusions: This systematic scoping review provides crucial, timely direction for future research on this emerging issue. Future research that combines neuroimaging and cognitive assessment would serve to advance understanding of the effects of age and quantity of THC and CBD on cognition in healthy aging.”

https://pubmed.ncbi.nlm.nih.gov/33159510/

“THC; the main psychoactive cannabis compound; exerted pro-cognitive effects on memory and learning in older populations.”

https://academic.oup.com/acn/advance-article/doi/10.1093/arclin/acaa105/5960018

Calling for Openness to the Study of Cannabis Use in Chronic Pelvic Pain

JOGC (@JOGC_Social) | Twitter“Chronic pelvic pain affects women across all demographics. Its management is complex and requires a multimodal approach.

Cannabis has been legal for medical purposes for many years; however, its pharmacokinetics are just beginning to be understood, as are its analgesic effects and other benefits, such as improved sleep quality and reduced nausea and vomiting.

Given the recent Canada-wide legalization of cannabis for non-medical use, patients may be more willing to disclose cannabis use and use it for pain management. Given the complexity of chronic pain management, physicians must be open to cannabis as an analgesic option.

Cannabis use may decrease the need for opioids, a phenomenon that could reduce opioid dependency. Now is the ideal time to study patients’ use of and perspectives on cannabis for pain relief in order to establish its effectiveness and safety.

Cannabis shows potential to be a key player in a multimodal approach to chronic pelvic pain.”

https://pubmed.ncbi.nlm.nih.gov/33132057/

https://www.jogc.com/article/S1701-2163(20)30791-X/fulltext