Antineoplastic properties of cannabinoids

The potential role of phytocannabinoids and the endocannabinoid system (ECS) in confining malignant tumours is among the most discussed topics in the field of medical cannabis.

There are countless anecdotes from patients and even clinical studies (usually small ones) about the effect of cannabinoids on controlling different types of cancer. Many patients also believe that cannabis and its derivatives are effective tools for fighting against cancer. Hence, many cancer patients want to use cannabis for treating their disease.

The state of evidence

It should be noted that there is not enough clinical evidence about the efficacy of cannabinoids on cancer in humans, however, there is plenty of evidence from preclinical studies indicating that cannabinoids and ECS can potentially play a role in treating cancers.

A review by Dr. Hinz and Dr. Ramer published in the British Journal of Pharmacology has summarized the current state of evidence about the interactions (and possible therapeutic effects) between the ECS and tumours as the followings:

Source: Hinz B, Ramer R. Anti-tumour actions of cannabinoids. Br J Pharmacol. 2019;176(10):1384-1394.

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The prevalence of problematic use of prescription opioids and Cannabis-Based Medications (CBMs) among chronic pain patients

The concerns about the problematic use of CBMs is one of the most heated debates among healthcare practitioners about integrating CBMs in the treatment protocols of patients suffering from chronic pain. Healthcare Practitioners would like to know how common the problematic use is and if there is any way to detect patients with higher risks for the problematic use.

Although there is no published controlled study, a cross-sectional study conducted in Israel tries to answer these questions.

In a cross-sectional study in two pain clinics in Israel, 888 chronic pain patients were assessed for problematic use of their pain medications (i.e. prescription opioids and CBMs). Researchers used DSM-IV, Portenoy’s Criteria (PC) and Current Opioid Misuse Measure (COMM) to detect the problematic use of opioids and CBMs.

471 patients (53.4%) were treated with opioids and 329 patients (37.3%) were treated with Medical Cannabis exclusively. 77 patients (8.7%) of patients have received both opioids and cannabinoids. The problematic use of opioids or CBMs has been demonstrated in the below chart.

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Health professional beliefs, knowledge, and concerns surrounding medicinal cannabis – A systematic review

The result of this systematic review indicated that while HCPs (Healthcare Professionals) believed that medical cannabis is a viable useful therapeutic option for patients, they do not have enough knowledge and formal education to make the best decision for their patients. Consequently, they reject to prescribe or support patients to use medical cannabis or they get the information from unreliable sources such as media/news. The result of this systematic review highlights the importance of education for HCPs to ensure to offer the best possible care for patients.

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Cannabis-Based Medications (CBMs) for managing weight loss in patients with advanced cancer

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

Loss of appetite and weight among cancer patients are among the most challenging symptoms to be managed by physicians. Moreover, there are not effective appetite stimulant medications in the market and physicians are reluctant to add another medication to highly medicated (chemotherapeutic agents, painkillers, sleep medications, …) advanced cancer patients if they have any doubt about its efficacy or safety profile.

Cannabis has been very well-known for its appetite stimulant effect and pharmaceutical preparations such as Dronabinol were successfully tested for improving appetite in HIV patients.

In this study, Dr. Bar-Sela and his colleagues assessed the effect of Cannabis capsules (THC: CBD 20:1 ratio) for the first time among patients with advanced cancer. The planned starting dose was 20 mg of cannabinoids (19 mg THC, 1 mg CBD) per day for six months, however, if patients could not tolerate it, the dose was reduced to 10 mg per day. In total, 24 patients were enrolled for the trial, however, only 6 of them received the capsules for more than 6 months.

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What do we know about CBD dosing for medicinal purposes?

Although CBD is one of the most used cannabinoids for medicinal purposes, the evidence about the dosing of CBD-based products (starting dose, up-titration protocol) is scarce. Following the approval of Epidiolex by FDA, we have a better understanding of the effective dose and up-titration schedule for epileptic patients, however, it seems that Epidiolex dosing schedule cannot be applied to other therapeutic areas such as pain, inflammation, and psychiatric disorders.Continue reading

The use of Cannabis-based Medications (CBMs) to manage psychological and behavioral issues in patients with dementia

The majority of patients with dementia will develop psychological and behavioral issues such as agitation, delusion, and hallucination during the course of their disease. These symptoms are very important because they will impact the communication between patients and caregivers, interfere in providing optimum care to patients and impact the quality of life of patients and their caregivers.Continue reading

β-Caryophyllene (BCP) and Neurodegenerative Disorders

Neurodegenerative disorders such as dementia, multiple sclerosis (MS) and Alzheimer’s disease (AD) share neuroinflammatory characterization.
CB2 receptor agonists have shown neuromodulatory and immunomodulatory effects in the immune system.
β-Caryophyllene (BCP) is a CB2 agonist found in natural products such as cannabis, black pepper, Thai basil and cloves. It has displayed anti-inflammatory and antioxidant effects through activation of the CB2 receptors.
Askari and Shafiee-Nick 2019,  investigated the protective effects of a broad range concentration of BCP against LPS-induced primary microglia cells inflammation and M1/M2 imbalance as well as the involvement of related signaling pathways. β-Caryophyllene (BCP) as a CB2 agonist in neuroprotection

They found that” The protective effects of BCP on LPS-induced microglia imbalance is provided by the M2 healing phenotype of microglia, releasing the anti-inflammatory (IL-10, Arg-1, and urea) and anti-oxidant (GSH) parameters and reducing the inflammatory (IL-1β, TNF-α, PGE2, iNOS and NO) and oxidative (ROS) biomarkers”.
It is important to note that middle to higher concentrations of BCP reduced the protective activity of BCP and resulted in the activation of the PPAR-γ pathway by SMase induction. It has also been found that SMase inhibitors imipramine (IMP) and fluoxetine (FLX) synergistically increase the protective effects of BCP.

SMase inhibitors synergistically increase the neuroprotective effects of β-Caryophyllene
Lindsey et al. 2019, showed that IL-23 levels are most strongly associated with aging in mice. They assessed changes in circulating cytokines in young and aged mice, and the effects of BCP on memory function and cytokine load.
They found that BCP improved working memory and decreased IL-23 levels in aged mice. BCP appears to reverse age-associated impairments in memory in this animal study.
Further research is needed to determine whether CB2 agonists can play a role as novel anti- neurodegenerative disorders medications.

Manipulation of the endocannabinoid system could be a promising therapy to control Parkinson’s disease and l-DOPA-induced dyskinesia symptoms

According to a literature review published in the journal of Neurotoxicity Research, cannabinoids, provide a potential multi-targeted treatment strategy for patients with Parkinson’s disease and dyskinesia.

Picture Source : WebMD/3D4 Medical

https://link.springer.com/article/10.1007%2Fs12640-019-00109-8