The Effects of Dosage-Controlled Cannabis Capsules on Cancer-Related Cachexia and Anorexia Syndrome in Advanced Cancer Patients: Pilot Study.

Image result for integrative cancer therapies“Cancer-related cachexia and anorexia syndrome (CACS) is a common phenomenon in cancer patients. Cannabis has been suggested to stimulate appetite but research on this issue has yielded mixed results. The current study aimed to evaluate the effect of dosage-controlled cannabis capsules on CACS in advanced cancer patients.

Methods: The cannabis capsules used in this study contained two fractions of oil-based compounds. The planned treatment was 2 × 10 mg per 24 hours for six months of tetrahydrocannabinol (THC) 9.5 mg and cannabidiol (CBD) 0.5 mg. If patients suffered from side effects, dosage was reduced to 5 mg × 2 per day (THC 4.75 mg, CBD 0.25 mg). Participants were weighed on every physician visit. The primary objective of the study was a weight gain of ≥10% from baseline.

Results: Of 24 patients who signed the consent form, 17 started the cannabis capsules treatment, but only 11 received the capsules for more than two weeks. Three of six patients who completed the study period met the primary end-point. The remaining three patients had stable weights. In quality of life quaternaries, patients reported less appetite loss after the cannabis treatment (p=0.05). Tumor necrosis factor-α (TNF-α) levels decreased after the cannabis treatment but without statistical significance. According to patients’ self-reports, improvement in appetite and mood as well as a reduction in pain and fatigue was demonstrated.

Conclusions: Despite various limitations, this preliminary study demonstrated a weight increase of ≥10% in 3/17 (17.6%) patients with doses of 5mgx1 or 5mgx2 capsules daily, without significant side effects. The results justify a larger study with dosage-controlled cannabis capsules in CACS.”

https://www.ncbi.nlm.nih.gov/pubmed/31595793

“The primary objective of the study was a weight gain of ≥10% from baseline. Despite various limitations, the current preliminary study demonstrated a weight increase of ≥10% in 3/17 (17.6%) of the patients with doses of 5 mg × 1 or 5 mg × 2 capsules daily, without significant side effects.”

https://journals.sagepub.com/doi/10.1177/1534735419881498

The evaluation of Cannabidiol’s effect on the immunotherapy of Burkitt lymphoma.

Biochemical and Biophysical Research Communications

“AF1q has a precise oncogenic function.

The purpose of this study is to investigate whether CBD has an effect on the AF1q/ICAM-1 regulatory axis in Burkitt’s lymphoma (BL), and thus has potential to enhance immunotherapy and reduce side effects.

 

RESULTS:

AF1q increased oncogenic growth and colony formation, and induced resistance against cell-mediated cytotoxic chemotherapy through attenuation of ICAM-1 expression in BL. CBD was able to reverse the acquired resistance mediated by AF1q/ICAM-1 regulatory axis.

CONCLUSION:

CBD holds potential to enhance the efficacy of immunotherapy for BL with hyperactive AF1q/ICAM-1 regulatory axis, and warrants further study.”

https://www.ncbi.nlm.nih.gov/pubmed/31587870

“Non-psychoactive CBD could potentially enhance the efficacy of immunotherapy in cancer treatment, especially against aggressive B.”

https://www.sciencedirect.com/science/article/pii/S0006291X1931890X?via%3Dihub

How does cannabidiol (CBD) influence the acute effects of delta-9-tetrahydrocannabinol (THC) in humans? A systematic review.

Neuroscience & Biobehavioral Reviews“The recent liberalisation of cannabis regulation has increased public and scientific debate about its potential benefits and risks. A key focus has been the extent to which cannabidiol (CBD) might influence the acute effects of delta-9-tetrahydrocannabinol (THC), but this has never been reviewed systematically. In this systematic review of how CBD influences the acute effects of THC we identified 16 studies involving 466 participants. Ten studies were judged at low risk of bias. The findings were mixed, although CBD was found to reduce the effects of THC in several studies. Some studies found that CBD reduced intense experiences of anxiety or psychosis-like effects of THC and blunted some of the impairments on emotion and reward processing. However, CBD did not consistently influence the effects of THC across all studies and outcomes. There was considerable heterogeneity in dose, route of administration and THC:CBD ratio across studies and no clear dose-response profile emerged. Although findings were mixed, this review suggests that CBD may interact with some acute effects of THC.”

https://www.ncbi.nlm.nih.gov/pubmed/31580839

“CBD influenced the effects of THC in some but not all studies. Several studies found that CBD reduced the acute effects of THC. CBD may reduce intense experiences of anxiety or psychosis-like effects of THC. CBD may blunt effects of THC on emotion and reward processing. CBD did not alter subjective intoxication or psychomotor effects of THC. CBD may influence the benefits and harms of cannabis”

https://www.sciencedirect.com/science/article/pii/S0149763419305615?via%3Dihub

Beyond THC and Endocannabinoids.

Image result for AR Annual Reviews“Research in the cannabinoid field, namely on phytocannabinoids, the endogenous cannabinoids anandamide and 2-arachidonoyl glycerol and their metabolizing and synthetic enzymes, the cannabinoid receptors, and anandamide-like cannabinoid compounds, has expanded tremendously over the last few years. Numerous endocannabinoid-like compounds have been discovered. The Cannabis plant constituent cannabidiol (CBD) was found to exert beneficial effects in many preclinical disease models ranging from epilepsy, cardiovascular disease, inflammation, and autoimmunity to neurodegenerative and kidney diseases and cancer. CBD was recently approved in the United States for the treatment of rare forms of childhood epilepsy. This has triggered the development of many CBD-based products for human use, often with overstated claims regarding their therapeutic effects. In this article, the recently published research on the chemistry and biological effects of plant cannabinoids (specifically CBD), endocannabinoids, certain long-chain fatty acid amides, and the variety of relevant receptors is critically reviewed. ”

https://www.ncbi.nlm.nih.gov/pubmed/31580774

https://www.annualreviews.org/doi/10.1146/annurev-pharmtox-010818-021441

Concomitant Treatment of Malignant Brain Tumours With CBD – A Case Series and Review of the Literature.

“Grade IV glioblastoma multiforme is a deadly disease, with a median survival of around 14 to 16 months. Maximal resection followed by adjuvant radiochemotherapy has been the mainstay of treatment since many years, although survival is only extended by a few months. In recent years, an increasing number of data from in vitro and in vivo research with cannabinoids, particularly with the non-intoxicating cannabidiol (CBD), point to their potential role as tumour-inhibiting agents. Herein, a total of nine consecutive patients with brain tumours are described as case series; all patients received CBD in a daily dose of 400 mg concomitantly to the standard therapeutic procedure of maximal resection followed by radiochemotherapy. By the time of the submission of this article, all but one patient are still alive with a mean survival time of 22.3 months (range=7-47 months). This is longer than what would have been expected.”

https://www.ncbi.nlm.nih.gov/pubmed/31570484

http://ar.iiarjournals.org/content/39/10/5797

Cannabidiol Counteracts the Psychotropic Side-Effects of Δ-9-Tetrahydrocannabinol in the Ventral Hippocampus Through Bi-Directional Control of ERK1-2 Phosphorylation

Journal of Neuroscience“Evidence suggests that the phytocannabinoids Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) differentially regulate salience attribution and psychiatric risk. The ventral hippocampus (vHipp) relays emotional salience via control of dopamine (DA) neuronal activity states, which are dysregulated in psychosis and schizophrenia. Using in-vivo electrophysiology in male Sprague Dawley rats, we demonstrate that intra-vHipp THC strongly increases ventral tegmental area (VTA) DA neuronal frequency and bursting rates, decreases GABA frequency, and amplifies VTA beta, gamma and epsilon oscillatory magnitudes via modulation of local extracellular signal-regulated kinase phosphorylation (pERK1-2). Remarkably, whereas intra-vHipp THC also potentiates salience attribution in morphine place-preference and fear conditioning assays, CBD co-administration reverses these changes by down-regulating pERK1-2 signaling, as pharmacological re-activation of pERK1-2 blocked the inhibitory properties of CBD. These results identify vHipp pERK1-2 signaling as a critical neural nexus point mediating THC-induced affective disturbances and suggest a potential mechanism by which CBD may counteract the psychotomimetic and psychotropic side-effects of THC.

SIGNIFICANCE STATEMENT

Strains of marijuana with high levels of delta-9-tetrahydrocannabinol (THC) and low levels of cannabidiol (CBD) have been shown to underlie neuropsychiatric risks associated with high potency cannabis use. However, the mechanisms by which CBD mitigates the side effects of THC have not been identified. We demonstrate that THC induces cognitive and affective abnormalities resembling neuropsychiatric symptoms directly in the hippocampus, while dysregulating dopamine activity states and amplifying oscillatory frequencies in the ventral tegmental area via modulation of the extracellular signal-regulated kinase (ERK) signaling pathway. In contrast, CBD co-administration blocked THC-induced ERK phosphorylation, and prevented THC-induced behavioural and neural abnormalities. These findings identify a novel molecular mechanism that may account for how CBD functionally mitigates the neuropsychiatric side-effects of THC.”

https://www.ncbi.nlm.nih.gov/pubmed/31570536

https://www.jneurosci.org/content/early/2019/09/27/JNEUROSCI.0708-19.2019

“Western University researchers show how CBD blocks side-effects of THC in cannabis. Research out of Western University is showing for the first time how cannabidiol (CBD) helps to lessen negative psychiatric side effects of tetrahydrocannabinol (THC) in cannabis.”  https://globalnews.ca/news/5970908/western-university-research-cbd-thc-cannabis/

“Cannabis study reveals how CBD offsets the psychiatric side-effects of THC”  https://neurosciencenews.com/cbd-thc-psychosis-15002/

Medical cannabis for inflammatory bowel disease: real-life experience of mode of consumption and assessment of side-effects.

 

Image result for ovid journal“Use of medical cannabis for improving symptoms of inflammatory bowel disease is increasing. However, reports on long-term outcomes are lacking. This prospective, observational study assessed the effects of licensed cannabis use among patients with inflammatory bowel disease.

METHODS:

Dose and mode of consumption, adverse events, use of other medications, and long-term effects were evaluated among 127 patients with inflammatory bowel disease using legalized medical cannabis. Blood count, albumin, and C-reactive protein were assessed before, 1 month, and at least 1 year after medical cannabis therapy was initiated. Questionnaires on disease activity, patient function, and signs of addiction were completed by patients and by a significant family member to assess its effects.

RESULTS:

The average dose used was 31 ± 15 g/month. The average Harvey-Bradshaw index improved from 14 ± 6.7 to 7 ± 4.7 (P < 0.001) during a median follow-up of 44 months (interquartile range, 24-56 months). There was a slight, but statistically significant, average weight gain of 2 kg within 1 year of cannabis use. The need for other medications was significantly reduced. Employment among patients increased from 65 to 74% (P < 0.05). We conclude that the majority of inflammatory bowel disease patients using cannabis are satisfied with a dose of 30 g/month. We did not observe negative effects of cannabis use on the patients’ social or occupational status.

CONCLUSIONS:

Cannabis use by inflammatory bowel disease patients can induce clinical improvement and is associated with reduced use of medication and slight weight gain. Most patients respond well to a dose of 30 g/month, or 21 mg Δ9-tetra- hydrocannabinol (THC) and 170 mg Cannabidiol (CBD) per day.”

Molecular mechanism of TRPV2 channel modulation by cannabidiol.

eLife logo

“Transient receptor potential vanilloid 2 (TRPV2) plays a critical role in neuronal development, cardiac function, immunity, and cancer.

Cannabidiol (CBD), the non-psychotropic therapeutically active ingredient of Cannabis sativa, is an activator of TRPV2 and also modulates other transient receptor potential (TRP) channels.

We show that CBD interacts with TRPV2 through a hydrophobic pocket located between S5 and S6 helices of adjacent subunits, which differs from known ligand and lipid binding sites in other TRP channels. CBD-bound TRPV2 structures revealed that the S4-S5 linker plays a critical role in channel gating upon CBD binding. Additionally, nanodiscs permitted us to visualize two distinct TRPV2 apo states in a lipid environment.

Together these results provide a foundation to further understand TRPV channel gating, their divergent physiological functions, and to accelerate structure-based drug design.”

https://www.ncbi.nlm.nih.gov/pubmed/31566564

https://elifesciences.org/articles/48792

Enhancing Breast Cancer Treatment Using a Combination of Cannabidiol and Gold Nanoparticles for Photodynamic Therapy.

ijms-logo“Indisputably, cancer is a global crisis that requires immediate intervention. Despite the use of conventional treatments over the past decades, it is acceptable to admit that these are expensive, invasive, associated with many side effects and, therefore, a reduced quality of life.

One of the most possible solutions to this could be the use of gold nanoparticle (AuNP) conjugated photodynamic therapy (PDT) in combination with cannabidiol (CBD), a Cannabis derivative from the Cannabis sativa.

Since the use of Cannabis has always been associated with recreation and psychoactive qualities, the positive effects of Cannabis or its derivatives on cancer treatment have been misunderstood and hence misinterpreted.

On the other hand, AuNP-PDT is the most favoured form of treatment for cancer, due to its augmented specificity and minimal risk of side effects compared to conventional treatments. However, its use requires the consideration of several physical, biologic, pharmacologic and immunological factors, which may hinder its effectiveness if not taken into consideration.

In this review, the role of gold nanoparticle mediated PDT combined with CBD treatment on breast cancer cells will be deliberated.”

https://www.ncbi.nlm.nih.gov/pubmed/31561450

https://www.mdpi.com/1422-0067/20/19/4771

Preclinical and Clinical Evidence Supporting Use of Cannabidiol in Psychiatry.

Image result for hindawi “Cannabidiol (CBD) is a major chemical compound present in Cannabis sativa.

CBD is a nonpsychotomimetic substance, and it is considered one of the most promising candidates for the treatment of psychiatric disorders.

The aim of this review is to illustrate the state of art about scientific research and the evidence of effectiveness of CBD in psychiatric patients.

RESULTS:

Preclinical and clinical studies on potential role of CBD in psychiatry were collected and further discussed. We found four clinical studies describing the effects of CBD in psychiatric patients: two studies about schizophrenic patients and the other two studies carried out on CBD effects in patients affected by generalized social anxiety disorder (SAD).

CONCLUSION:

Results from these studies are promising and suggest that CBD may have a role in the development of new therapeutic strategies in mental diseases, and they justify an in-depth commitment in this field. However, clinical evidence we show for CBD in psychiatric patients is instead still poor and limited to schizophrenia and anxiety, and it needs to be implemented with further studies carried out on psychiatric patients.”

https://www.ncbi.nlm.nih.gov/pubmed/31558911

“Results of our research, enriched in assessment of methodological quality of the studies, confirm the view of this cannabinoid as a promising molecule especially in particular sectors of psychiatry such as schizophrenia, anxiety, depression, and autism. CBD is considered a safe substance and is one of the most promising candidates for the treatment of psychiatric disorders”.

https://www.hindawi.com/journals/ecam/2019/2509129/