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

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

Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders

biomolecules-logo“The potential therapeutic use of some Cannabis sativa plant compounds has been attracting great interest, especially for managing neuropsychiatric disorders due to the relative lack of efficacy of the current treatments.

Numerous studies have been carried out using the main phytocannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD). CBD displays an interesting pharmacological profile without the potential for becoming a drug of abuse, unlike THC.

In this review, we focused on the anxiolytic, antidepressant, and antipsychotic effects of CBD found in animal and human studies. In rodents, results suggest that the effects of CBD depend on the dose, the strain, the administration time course (acute vs. chronic), and the route of administration. In addition, certain key targets have been related with these CBD pharmacological actions, including cannabinoid receptors (CB1r and CB2r), 5-HT1A receptor and neurogenesis factors.

Preliminary clinical trials also support the efficacy of CBD as an anxiolytic, antipsychotic, and antidepressant, and more importantly, a positive risk-benefit profile. These promising results support the development of large-scale studies to further evaluate CBD as a potential new drug for the treatment of these psychiatric disorders.”

https://pubmed.ncbi.nlm.nih.gov/33228239/

https://www.mdpi.com/2218-273X/10/11/1575

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

In search of preventative strategies: novel high-CBD cannabis sativa extracts modulate ACE2 expression in COVID-19 gateway tissues

 Archive of "Aging (Albany NY)".“With the current COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent need for new therapies and prevention strategies that can help curtail disease spread and reduce mortality.

The inhibition of viral entry and thus spread is a plausible therapeutic avenue. SARS-CoV-2 uses receptor-mediated entry into a human host via the angiotensin-converting enzyme 2 (ACE2), which is expressed in lung tissue as well as the oral and nasal mucosa, kidney, testes and gastrointestinal tract. The modulation of ACE2 levels in these gateway tissues may be an effective strategy for decreasing disease susceptibility.

Cannabis sativa, especially those high in the anti-inflammatory cannabinoid cannabidiol (CBD), has been found to alter gene expression and inflammation and harbour anti-cancer and anti-inflammatory properties. However, its effects on ACE2 expression remain unknown.

Working under a Health Canada research license, we developed over 800 new C. sativa cultivars and hypothesized that high-CBD C. sativa extracts may be used to down-regulate ACE2 expression in target COVID-19 tissues. Using artificial 3D human models of oral, airway and intestinal tissues, we identified 13 high-CBD C. sativa extracts that decrease ACE2 protein levels. Some C. sativa extracts down-regulate serine protease TMPRSS2, another critical protein required for SARS-CoV-2 entry into host cells.

While our most effective extracts require further large-scale validation, our study is important for future analyses of the effects of medical cannabis on COVID-19. The extracts of our most successful novel high-CBD C. sativa lines, pending further investigation, may become a useful and safe addition to the prevention/treatment of COVID-19 as an adjunct therapy.”

https://pubmed.ncbi.nlm.nih.gov/33221759/

Preliminary assessment of medical cannabis consumption by cancer survivors

Complementary Therapies in Medicine “Objectives: To assess the motivation of cancer survivors to consume medical cannabis and to assess the patterns of use, perceived efficacy, as well as side and adverse effects.

Results: The mean monthly dosage of cannabis consumed was 42.4 grams; 95.8% of respondents reported not consuming cannabis regularly before being diagnosed with cancer; the most common way of administration was smoking, and most of the participants reported taking cannabis throughout the day. The most common symptoms for which participants took medical cannabis were pain (n = 169, 88.9%), sleeping disorder (n = 144, 75.8%) and anxiety (n = 79, 41.6%). Twenty patients (10.5%) reported on mild side (or adverse) effects.

Conclusions: This study indicates that cancer survivors may indeed consume cannabis for symptom relief, and not merely for recreational purposes. Although our findings point to perceived safety and efficacy of medical cannabis for cancer survivors, more research is needed to study the adequate role that cannabis may have for treating symptoms associated with cancer survivorship.”

https://pubmed.ncbi.nlm.nih.gov/33197667/

“In conclusion, despite the many challenges and uncertainties, cannabis is being slowly diffused into healthcare. Survivors who have ongoing symptoms as a result of their prior treatments should be carefully assessed as to whether there is a medical need for which cannabis may be helpful. Indeed, patients and physicians should establish and maintain a therapeutic alliance in which medical needs and potential treatments, including medical cannabis, are honestly discussed and mutually considered and agreed upon.”

https://www.sciencedirect.com/science/article/pii/S0965229920318598?via%3Dihub

Cannabinoids in the management of frontotemporal dementia: a case series

 “Background: Frontotemporal dementia (FTD) is characterized by progressive deterioration in behaviors, executive function and/or language. The behavioral variant (Bv) is characterized by disinhibition and obsessive/compulsive behaviors. These symptoms are sometimes resistant to medications. This series examines patients suffering with treatment-resistant Bv-FTD who were prescribed cannabinoid and related compounds for other indications.

Case presentation: Three FTD cases from a dementia clinic were identified. These patients had disability due to behavior despite typical pharmacologic management. These patients were prescribed marijuana for comorbidities (anxiety, insomnia and pain). In all cases, use of cannabinoid products showed significant improvements in behavior and in the primary indication for prescription.

Conclusion: Review of these cases demonstrates potential for the use of cannabinoids in the management of treatment-resistant Bv-FTD.”

https://pubmed.ncbi.nlm.nih.gov/33190583/

“Frontotemporal dementia is a complicated and difficult disease that can be challenging to manage and often leads to significant burden on caregivers. Sometimes management of behavioral changes is difficult even with medications. In this case series, we report three cases of patients with behavior that was resistant to typical treatment who showed improvement in behavior when they were prescribed medical marijuana for other reason.”

https://www.futuremedicine.com/doi/10.2217/nmt-2020-0048

The Therapeutic Potential of Cannabinoids for Integumentary Wound Management

“The increasing legalization of Cannabis for recreational and medicinal purposes in the United States has spurred renewed interest in the therapeutic potential of cannabinoids (CBs) for human disease.

The skin has its own endocannabinoid system (eCS) which is a key regulator of various homeostatic processes, including those necessary for normal physiologic wound healing.

Data on the use of CBs for wound healing is scarce. Compelling pre-clinical evidence supporting the therapeutic potential of CBs to improve wound healing by modulating key molecular pathways is herein reviewed.

These findings merit further exploration in basic science, translational and clinical studies.”

https://pubmed.ncbi.nlm.nih.gov/33205468/

https://onlinelibrary.wiley.com/doi/10.1111/exd.14241

Antioxidant Effects of Hemp ( Cannabis sativa L.) Inflorescence Extract in Stripped Linseed Oil

antioxidants-logo“The ability of hemp (Cannabis sativa L.) inflorescence extract to counteract lipid oxidation was studied in stripped linseed oil.

This study demonstrates that hemp inflorescences can be used as a source of natural antioxidants in vegetable oils and lipid products to retard their oxidation, especially those characterized by a high degree of unsaturation.”

https://pubmed.ncbi.nlm.nih.gov/33202647/

https://www.mdpi.com/2076-3921/9/11/1131

Cannabis: are there any benefits?

“Cannabis has been used as a medicine for millennia. Prohibition in the mid-20th century precluded early scientific investigation.

‘Cannabis’ describes three separate forms – herbal cannabis, ‘hemp’ products, pharmaceutical-grade regulated cannabinoid-based medical products (CBMP).

The endocannabinoid system (ECS), delineated in the late 1990s, has increased the understanding and interest in research for appropriate clinical indications. The ubiquitous ECS has homeostatic and anti-inflammatory effects and comprises cannabinoid receptors, endocannabinoids and degrading enzymes.

Phytocannabinoids are partial agonists of the ECS. In pre-clinical studies, THC and CBD produce beneficial effects in chronic pain, anxiety, sleep and inflammation. Systematic reviews often conflate herbal cannabis and CBMP, confusing the evidence. Currently large randomised controlled trials are unlikely to be achieved. Other methodologies with quality end-points are required. Rich, valuable high-quality real-world evidence for the safe and effective use of CBMP provides an opportunity to examine benefits and potential harms.

Evidence demonstrates benefit of CBMP in multiple sclerosis, chronic neuropathic pain, chemotherapy induced nausea and vomiting, resistant paediatric epilepsy, anxiety and insomnia. CBMP are well tolerated with few serious adverse events. Additional clinical benefits are promising in many other resistant chronic conditions. Pharmaceutical grade prescribed CBMP has proven clinical benefits and provides another clinical option in the physician’s pharmacopeia.”

https://pubmed.ncbi.nlm.nih.gov/33215831/

“Medical use of cannabis has been practiced for millennia and pre‐dates recorded human history.”

https://onlinelibrary.wiley.com/doi/10.1111/imj.15052