Ingestion of a THC-Rich Cannabis Oil in People with Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Issue Cover “Objective: To determine the benefit of a tetrahydrocannabinol (THC)-rich cannabis oil on symptoms and quality of life of fibromyalgia patients.

Conclusions: Phytocannabinoids can be a low-cost and well-tolerated therapy to reduce symptoms and increase the quality of life of patients with fibromyalgia. Future studies are still needed to assess long-term benefits, and studies with different varieties of cannabinoids associated with a washout period must be done to enhance our knowledge of cannabis action in this health condition.”

https://pubmed.ncbi.nlm.nih.gov/33118602/

“To our knowledge, this is the first randomized controlled trial to demonstrate the benefit of cannabis oil—a THC-rich whole plant extract—on symptoms and on quality of life of people with fibromyalgia. We conclude that phytocannabinoids can be a low-cost and well-tolerated therapy for symptom relief and quality of life improvement in these patients, and we suggest that this therapy could be included as an herbal medicine option for the treatment of this condition”

https://academic.oup.com/painmedicine/article/21/10/2212/5942556

Update on cannabis and cannabinoids for cancer pain

Current Issue Cover Image “The prevalence of cancer pain will continue to rise as pain is common among the survivorship and general cancer population. As interest in cannabis and cannabinoids for medicinal use including pain management continues to rise, there is growing need to update and review the current state of evidence for their use. The literature was searched for articles in English with key words cannabis, cannabinoids, and cancer pain. The sources of articles were PubMed, Embase, and open Google search.

Recent findings: In a double-blind randomized placebo-controlled trial including a 3-week treatment period of nabiximol for advanced cancer patients with pain refractory to optimized opiate therapy, improvements in average pain were seen in the intention to treat population (P = 0.0854) and per- protocol population (P = 0.0378).

Summary: To date, preclinical data has demonstrated evidence to suggest promising potential for cancer pain and the urgent need to translate this into clinical practice. Unfortunately, due to limited data, for adults with advanced cancer being treated with opiate therapy, the addition of cannabis or cannabinoids is not currently supported to address cancer pain effectively.”

https://pubmed.ncbi.nlm.nih.gov/33110020/

https://journals.lww.com/co-anesthesiology/Abstract/2020/12000/Update_on_cannabis_and_cannabinoids_for_cancer.19.aspx

Attenuation of Oxidative Stress by Cannabinoids and Cannabis Extracts in Differentiated Neuronal Cells

pharmaceuticals-logo“In this proof-of-concept study, the antioxidant activity of phytocannabinoids, namely cannabidiol (CBD) and Δ9- tetrahydrocannabinol (THC), were investigated using an in vitro system of differentiated human neuronal SY-SH5Y cells.

We showed that THC had a high potency to combat oxidative stress in both in vitro models, while CBD did not show a remarkable antioxidant activity. The cannabis extracts also exhibited a significant antioxidant activity, which depended on the ratio of the THC and CBD. However, our results did not suggest any antagonist effect of the CBD on the antioxidant activity of THC. The effect of cannabis extracts on the cell viability of differentiated human neuronal SY-SH5Y cells was also investigated, which emphasized the differences between the bioactivity of cannabis extracts due to their composition.

Our preliminary results demonstrated that cannabis extracts and phytocannabinoids have a promising potential as antioxidants, which can be further investigated to develop novel pharmaceuticals targeting oxidative stress therapy.”

https://pubmed.ncbi.nlm.nih.gov/33105840/

https://www.mdpi.com/1424-8247/13/11/328

Cancer patients’ experiences with medicinal cannabis-related care

 “Background: Little is known about medical cannabis (MC)-related care for patients with cancer using MC.

Methods: Semistructured telephone interviews were conducted in a convenience sample of individuals (n = 24) with physician-confirmed oncologic diagnoses and state/district authorization to use MC (Arizona, California, Florida, Illinois, Massachusetts, Oregon, New York, and Washington, DC) from April 2017 to March 2019. Standard qualitative techniques were used to assess the degree of MC-related health care oversight, MC practices, and key information sources.

Results: Among 24 participants (median age, 57 years; range, 30-71 years; 16 women [67%]), MC certifications were typically issued by a professional new to a patient’s care after a brief, perfunctory consultation. Patients disclosed MCuse to their established medical teams but received little medical advice about whether and how to use MC. Patients with cancer used MC products as multipurpose symptom management and as cancer-directed therapy, sometimes in lieu of standard-of-care treatments. Personal experimentation, including methodical self-monitoring, was an important source of MC know-how. Absent formal advice from medical professionals, patients relied on nonmedical sources for MC information.

Conclusions: Patients with cancer used MC with minimal medical oversight. Most received MC certifications through brief meetings with unfamiliar professionals. Participants desired but were often unable to access high-quality clinical information about MC from their established medical teams. Because many patients are committed to using MC, a product sustained by a growing industry, medical providers should familiarize themselves with the existing data for MM and its limitations to address a poorly met clinical need.”

https://pubmed.ncbi.nlm.nih.gov/32986266/

“Notably, oncology patients reported using medical cannabis (MC) for symptom management and as cancer‐directed therapy, sometimes instead of traditional treatments.”

https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.33202

Efficacy of combined therapy with fish oil and phytocannabinoids in murine intestinal inflammation

Phytotherapy Research“Fish oil (FO) and phytocannabinoids have received considerable attention for their intestinal anti-inflammatory effects.

We investigated whether the combination of FO with cannabigerol (CBG) and cannabidiol (CBD) or a combination of all three treatments results in a more pronounced intestinal antiinflammatory action compared to the effects achieved separately.

Colitis was induced in mice by 2,4-dinitrobenzenesulfonic acid (DNBS). CBD and CBG levels were detected and quantified by liquid chromatography coupled with time of flight mass spectrometry and ion trap mass spectrometry (LC-MS-IT-TOF). Endocannabinoids and related mediators were assessed by LC-MS. DNBS increased colon weight/colon length ratio, myeloperoxidase activity, interleukin-1β, and intestinal permeability.

CBG, but not CBD, given by oral gavage, ameliorated DNBS-induced colonic inflammation. FO pretreatment (at the inactive dose) increased the antiinflammatory action of CBG and rendered oral CBD effective while reducing endocannabinoid levels. Furthermore, the combination of FO, CBD, and a per se inactive dose of CBG resulted in intestinal anti-inflammatory effects. Finally, FO did not alter phytocannabinoid levels in the serum and in the colon.

By highlighting the apparent additivity between phytocannabinoids and FO, our preclinical data support a novel strategy of combining these substances for the potential development of a treatment of inflammatory bowel disease.”

https://pubmed.ncbi.nlm.nih.gov/32996187/

https://onlinelibrary.wiley.com/doi/10.1002/ptr.6831

Cannabidiol Ameliorates Monocrotaline-Induced Pulmonary Hypertension in Rats

ijms-logo“Cannabidiol (CBD) is known for its vasorelaxant (including in the human pulmonary artery), anti-proliferative and anti-inflammatory properties. The aim of our study was to examine the potential preventive effect of chronic CBD administration (10 mg/kg/day for three weeks) on monocrotaline (MCT)-induced pulmonary hypertension (PH) rats.

PH was connected with elevation of right ventricular systolic pressure; right ventricle hypertrophy; lung edema; pulmonary artery remodeling; enhancement of the vasoconstrictor and decreasing vasodilatory responses; increases in plasma concentrations of tissue plasminogen activator, plasminogen activator inhibitor type 1 and leukocyte count; and a decrease in blood oxygen saturation.

CBD improved all abovementioned changes induced by PH except right ventricle hypertrophy and lung edema. In addition, CBD increased lung levels of some endocannabinoids (anandamide, N-arachidonoyl glycine, linolenoyl ethanolamide, palmitoleoyl ethanolamide and eicosapentaenoyl ethanolamide but not 2-arachidonoylglycerol). CBD did not affect the cardiopulmonary system of control rats or other parameters of blood morphology in PH.

Our data suggest that CBD ameliorates MCT-induced PH in rats by improving endothelial efficiency and function, normalization of hemostatic alterations and reduction of enhanced leukocyte count determined in PH. In conclusion, CBD may be a safe, promising therapeutic or adjuvant therapy agent for the treatment of human pulmonary artery hypertension.”

https://pubmed.ncbi.nlm.nih.gov/32992900/

https://www.mdpi.com/1422-0067/21/19/7077

Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines

cancers-logo“Pancreatic cancer (PC) is related to lifestyle risks, chronic inflammation, and germline mutations in BRCA1/2ATMMLH1TP53, or CDKN2A. Surgical resection and adjuvant chemotherapy are the main therapeutic strategies but are less effective in patients with high-grade tumors.

Oxygen-ozone (O2/O3) therapy is an emerging alternative tool for the treatment of several clinical disorders. O2/O3 therapy has been found to ameliorate mechanisms promoting chronic pain and inflammation, including hypoxia, inflammatory mediators, and infection.

The advantages of using cannabinoids have been evaluated in vitro and in vivo models of several human cancers. Regarding PDAC, activation of cannabinoid receptors was found to induce pancreatic cancer cell apoptosis without affecting the normal pancreas cells.

In a murine model of PDAC, a combination of cannabidiol (CBD) and gemcitabine increased survival length by nearly three times. Herein, we evaluate the anticancer effect of CBD and O2/O3, alone or in combination, on two human PDAC cell lines, PANC-1 and MiaPaCa-2, examining expression profiles of 92 pancreatic adenocarcinoma associated genes, cytotoxicity, migration properties, and cell death. Finally, we assess the combination effects with gemcitabine and paclitaxel.

Summarizing, for the first time the antitumoral effect of combined therapy with CBD and oxygen-ozone therapy in PDAC is evidenced.”

https://pubmed.ncbi.nlm.nih.gov/32992648/

https://www.mdpi.com/2072-6694/12/10/2774

Development of cannabidiol as a treatment for severe childhood epilepsies

“In recent years there has been a growing appreciation by regulatory authorities that cannabis-based medicines can play a useful role in disease therapy.

Although often conflagrated by proponents of recreational use, the legislative rescheduling of cannabis-derived compounds, such as cannabidiol (CBD), has been associated with the steady increase in the pursuit of use of medicinal cannabis.

One key driver in this interest has been the scientific demonstration of efficacy and safety of CBD in randomised, placebo-controlled clinical trials in children and young adults with difficult-to-treat epilepsies, which has encouraged increasing numbers of human trials of CBD for other indications and in other populations.

The introduction of CBD as the medicine Epidiolex in the US (in 2018) and as Epidyolex in the EU (in 2019) as the first cannabis-derived therapeutic for the treatment for seizures was underpinned by preclinical research performed at the University of Reading.

This work was awarded the British Pharmacological Society Sir James Black Award for Contributions to Drug Discovery 2019 and is discussed in the following review article.”

https://pubmed.ncbi.nlm.nih.gov/32986848/

https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15274

A pediatric patient with autism spectrum disorder and epilepsy using cannabinoid extracts as complementary therapy: a case report

 Journal of Medical Case Reports | Home page“The pharmacological treatment for autism spectrum disorders is often poorly tolerated and has traditionally targeted associated conditions, with limited benefit for the core social deficits.

We describe the novel use of a cannabidiol-based extract that incidentally improved core social deficits and overall functioning in a patient with autism spectrum disorder, at a lower dose than has been previously reported in autism spectrum disorder.

Case presentation: The parents of a 15-year-old boy, of South African descent, with autism spectrum disorder, selective mutism, anxiety, and controlled epilepsy, consulted a medical cannabis physician to trial cannabis extract to replace seizure medications. Incidentally, at a very low cannabidiol-based extract dose, he experienced unanticipated positive effects on behavioral symptoms and core social deficits.

Conclusion: This case report provides evidence that a lower than previously reported dose of a phytocannabinoid in the form of a cannabidiol-based extract may be capable of aiding in autism spectrum disorder-related behavioral symptoms, core social communication abilities, and comorbid anxiety, sleep difficulties, and weight control. Further research is needed to elucidate the clinical role and underlying biological mechanisms of action of cannabidiol-based extract in patients with autism spectrum disorder.”

https://pubmed.ncbi.nlm.nih.gov/32958062/

https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-020-02478-7

Add-on cannabidiol significantly decreases seizures in 3 patients with SYNGAP1 developmental and epileptic encephalopathy

“Mutations in SYNGAP1 are associated with developmental delay, epilepsy, and autism spectrum disorder (ASD). Epilepsy is often drug-resistant in this syndrome with frequent drop attacks.

In a prospective study of add-on cannabidiol (CBD), we identified three patients with SYNGAP1 mutations: two boys and one girl. Seizure onset was at 3.5, 8, and 18 months (M), respectively, with numerous atypical absences per day associated with eyelid myoclonia (2/3 patients), upper limb myoclonic jerks (2/3 patients), and drop attacks (all patients). Seizures were resistant to at least 5 antiepileptic drugs (AEDs).

After CBD introduction, two patients were responders since M2 and achieve a seizure reduction of 90% and 80%, respectively, at M9 with disappearance of drop attacks. EEGs showed an improvement regarding background activity and interictal anomalies. The last patient showed a late response at M7 of treatment with an 80% decrease in seizure frequency. Caregiver in all three evaluated as much improved the status of their children. Treatment was well-tolerated in all, and no major adverse events (AEs) were reported.

CBD showed efficacy in patients with drug-resistant epilepsy due to SYNGAP1 mutations. Other patients with rare genetic developmental and epileptic encephalopathies with drug-resistant epilepsies might benefit from CBD.”

https://pubmed.ncbi.nlm.nih.gov/32913957/

“CBD add‐on therapy in patients with SYNGAP1 encephalopathy showed a good response in three patients with a good safety profile and a late response in one patient. This therapy should be included in the treatment algorithm of patients with SYNGAP1 mutations presenting drug resistance epilepsy and might be expanded to other rare genetic epilepsies that might not be included in formal trials.”

https://onlinelibrary.wiley.com/doi/full/10.1002/epi4.12411