“The endocannabinoid system is located throughout the central and peripheral nervous systems, endocrine system, gastrointestinal system, and within inflammatory cells. The use of medical cannabinoids has been gaining traction as a viable treatment option for varying illnesses in recent years. Research is ongoing looking at the effect of cannabinoids for treatment of common otolaryngologic pathologies. This article identifies common otolaryngologic pathologies where cannabinoids may have benefit, discusses potential drawbacks to cannabinoid use, and suggests future directions for research in the application of medical cannabinoids.”
“The use of medical cannabis (MC) to treat cancer-related symptoms is rising. However, there is a lack of long-term trials to assess the benefits and safety of MC treatment in this population. In this work, we followed up prospectively and longitudinally on the effectiveness and safety of MC treatment.
Oncology patients reported on multiple symptoms before and after MC treatment initiation at one-, three-, and 6-month follow-ups. Oncologists reported on the patients’ disease characteristics. Intention-to-treat models were used to assess changes in outcomes from baseline. MC treatment was initiated by 324 patients and 212, 158 and 126 reported at follow-ups.
Most outcome measures improved significantly during MC treatment for most patients (p < 0.005). Specifically, at 6 months, total cancer symptoms burden declined from baseline by a median of 18%, from 122 (82–157) at baseline to 89 (45–138) at endpoint (−18.98; 95%CI= −26.95 to −11.00; p < 0.001). Reported adverse effects were common but mostly non-serious and remained stable during MC treatment.
The results of this study suggest that MC treatment is generally safe for oncology patients and can potentially reduce the burden of associated symptoms with no serious MC-related adverse effects.
The main finding of the current study is that most cancer comorbid symptoms improved significantly during 6 months of MC treatment.
Additionally, we found that MC treatment in cancer patients was well tolerated and safe.”
“Cancer Pain Treatment Using Marijuana Safe and Effective, Large Study Finds”
“Cannabinoid-based therapies offer a safer, non-opioid alternative for the management of chronic pain. While most studies focus on the analgesic potential of the main psychoactive component of marijuana, Δ9-tetrahydrocannabinol, fewer studies have investigated the role of the non-psychoactive component, cannabidiol (CBD). CBD has been purported to have analgesic, anti-inflammatory, anticonvulsant, and anxiolytic effects. In addition to having actions at both cannabinoid receptors (CB1 and CB2 ), CBD has been shown to interact with both the transient receptor potential vanilloid-1 (TRPV1) and serotonergic (5-HT) receptors. Clinically, CBD’s lack of psychoactivity and decreased abuse liability make it an appealing pharmacotherapeutic for the management of chronic pain. Therefore, the purpose of the current study was to determine whether CBD sex- or dose-dependently reverses antinociception in an acute model of thermal pain and/or mechanical allodynia in a model of cisplatin-induced chronic neuropathic pain. Furthermore, we observed the degree to which CB1 , CB2 , 5-HT, and TRPV1 receptors may be mediating these anti-allodynic responses. Male and female wild-type mice were assessed for either the anti-allodynic effects of 0, 1, 3, 10, and 30 mg/kg CBD in a cisplatin-induced model of neuropathic pain or the antinociceptive effects of 0, 1, 3, 10, 30, and 100 mg/kg CBD in a model of acute thermal (tail-flick) pain 60 minutes following CBD administration. To determine the relative contributions of each receptor subtype in mediating the anti-allodynic effects of CBD, male and female mice were pretreated with either: vehicle, the CB1 inverse agonist SR141716A (10 mg/kg), the CB2 antagonist SR144528 (10 mg/kg), the TRPV1 antagonist capsazepine (10 mg/kg), or the 5-HT2 antagonist methysergide (4 mg/kg) 30 minutes prior to treatment with CBD. Mice were assessed for the effects of the pretreatment alone and in combination with CBD. CBD at a dose of 3 mg/kg was able to partially reverse cisplatin-induced allodynia in male and female mice, while doses of 10 and 30 mg/kg resulted in nearly complete reversal. Our preliminary findings showed that the anti-allodynic effects of 30 mg/kg CBD were completely blocked following pretreatment with SR141716A and SR144528, and partially blocked by capsazepine in both male and female mice. Interestingly, pretreatment with methysergide partially attenuated the anti-allodynic effects of CBD in females alone. In contrast, CBD (0-100 mg/kg) failed to induce antinociception on the tail-flick assay. CBD did induce mild hypothermia with males showing a greater degree of CBD-mediated hypothermia than female mice. Taken together, these findings suggest that CBD may be a more effective treatment option for the management of chronic pain. This study highlights the therapeutic potential of CBD in a model of neuropathic pain and suggests that these effects may have clinical implications for the use of cannabinoids in chronic pain management.”
“Despite the long history of cannabinoid use for medicinal and ritual purposes, an endogenous system of cannabinoid-controlled receptors, as well as their ligands and the enzymes that synthesise and degrade them, was only discovered in the 1990s. Since then, the endocannabinoid system has attracted widespread scientific interest regarding new pharmacological targets in cancer treatment among other reasons.
Meanwhile, extensive preclinical studies have shown that cannabinoids have an inhibitory effect on tumour cell proliferation, tumour invasion, metastasis, angiogenesis, chemoresistance and epithelial-mesenchymal transition (EMT) and induce tumour cell apoptosis and autophagy as well as immune response. Appropriate cannabinoid compounds could moreover be useful for cancer patients as potential combination partners with other chemotherapeutic agents to increase their efficacy while reducing unwanted side effects.
In addition to the direct activation of cannabinoid receptors through the exogenous application of corresponding agonists, another strategy is to activate these receptors by increasing the endocannabinoid levels at the corresponding pathological hotspots. Indeed, a number of studies accordingly showed an inhibitory effect of blockers of the endocannabinoid-degrading enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) on tumour development and spread.
This review summarises the relevant preclinical studies with FAAH and MAGL inhibitors compared to studies with cannabinoids and provides an overview of the regulation of the endocannabinoid system in cancer.”
“Cannabinoids have been shown to suppress tumour cell proliferation, tumour invasion, metastasis, angiogenesis, chemoresistance and epithelial-mesenchymal transition and to induce tumour cell apoptosis, autophagy and immune response. This review focuses on the current status of investigations on the impact of inhibitors of endocannabinoid-degrading enzymes on tumour growth and spread in preclinical oncology research.”
“Substantial preclinical evidence demonstrates the antiproliferative, cytotoxic, and antimetastatic properties of plant-derived cannabinoids (phytocannabinoids) such as cannabidiol and tetrahydrocannabinol. The cumulative body of research into the intracellular mechanisms and phenotypic effects of these compounds supports a logical, judicious progression to large-scale phase II/III clinical trials in certain cancer types to truly assess the efficacy of phytocannabinoids as anticancer agents.”
“Drugs that target the endocannabinoid system are of interest as pharmacological options to combat cancer and to improve the life quality of cancer patients. From this perspective, cannabinoid compounds have been successfully tested as a systemic therapeutic option in a number of preclinical models over the past decades. As a result of these efforts, a large body of data suggests that the anticancer effects of cannabinoids are exerted at multiple levels of tumour progression via different signal transduction mechanisms. Accordingly, there is considerable evidence for cannabinoid-mediated inhibition of tumour cell proliferation, tumour invasion and metastasis, angiogenesis and chemoresistance, as well as induction of apoptosis and autophagy. Further studies showed that cannabinoids could be potential combination partners for established chemotherapeutic agents or other therapeutic interventions in cancer treatment. Research in recent years has yielded several compounds that exert promising effects on tumour cells and tissues in addition to the psychoactive Δ9-tetrahydrocannabinol, such as the non-psychoactive phytocannabinoid cannabidiol and inhibitors of endocannabinoid degradation. This review provides an up-to-date overview of the potential of cannabinoids as inhibitors of tumour growth and spread as demonstrated in preclinical studies.”
“Preclinical models provided ample evidence that cannabinoids are cytotoxic against cancer cells. Among the best studied phytocannabinoids, cannabidiol (CBD) is most promising for the treatment of cancer as it lacks the psychotomimetic properties of delta-9-tetrahydrocannabinol (THC). In vitro studies and animal experiments point to a concentration- (dose-)dependent anticancer effect. The effectiveness of pure compounds versus extracts is the subject of an ongoing debate. Actual results demonstrate that CBD-rich hemp extracts must be distinguished from THC-rich cannabis preparations. Whereas pure CBD was superior to CBD-rich extracts in most in vitro experiments, the opposite was observed for pure THC and THC-rich extracts, although exceptions were noted. The cytotoxic effects of CBD, THC and extracts seem to depend not only on the nature of cannabinoids and the presence of other phytochemicals but also largely on the nature of cell lines and test conditions. Neither CBD nor THC are universally efficacious in reducing cancer cell viability. The combination of pure cannabinoids may have advantages over single agents, although the optimal ratio seems to depend on the nature of cancer cells; the existence of a ‘one size fits all’ ratio is very unlikely. As cannabinoids interfere with the endocannabinoid system (ECS), a better understanding of the circadian rhythmicity of the ECS, particularly endocannabinoids and receptors, as well as of the rhythmicity of biological processes related to the growth of cancer cells, could enhance the efficacy of a therapy with cannabinoids by optimization of the timing of the administration, as has already been reported for some of the canonical chemotherapeutics. Theoretically, a CBD dose administered at noon could increase the peak of anandamide and therefore the effects triggered by this agent. Despite the abundance of preclinical articles published over the last 2 decades, well-designed controlled clinical trials on CBD in cancer are still missing. The number of observations in cancer patients, paired with the anticancer activity repeatedly reported in preclinical in vitro and in vivo studies warrants serious scientific exploration moving forward.”
“Various preclinical and clinical studies exhibited the potential of cannabis against various diseases, including cancer and related pain. Subsequently, many efforts have been made to establish and develop cannabis-related products and make them available as prescription products. Moreover, FDA has already approved some cannabis-related products, and more advancement in this aspect is still going on. However, the approved product of cannabis is in oral dosage form, which exerts various limitations to achieve maximum therapeutic effects. A considerable translation is on a hike to improve bioavailability, and ultimately, the therapeutic efficacy of cannabis by the employment of nanotechnology. Besides the well-known psychotropic effects of cannabis upon the use at high doses, literature has also shown the importance of cannabis and its constituents in minimising the lethality of cancer in the preclinical models. This review discusses the history of cannabis, its legal aspect, safety profile, the mechanism by which cannabis combats with cancer, and the advancement of clinical therapy by exploiting nanotechnology. A brief discussion related to the role of cannabinoid in various cancers has also been incorporated. Lastly, the information regarding completed and ongoing trials have also been elaborated.”
“The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems.
In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development.
The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development.
The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases.
This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.”
“Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment”
“Cannabidiol (CBD) has anti-tumorigenic activity. However, the anti-cancer effect of CBD on head and neck squamous cell carcinoma (HNSCC) remains unclear. The cytotoxicity of CBD on HNSCC was analyzed using cell survival and colony-forming assays in vitro.
CBD treatment significantly reduced migration/invasion and viability of HNSCC cells in a dose- and time-dependent manner. HNSCC mouse xenograft models revealed anti-tumor effects of CBD. Furthermore, combinational treatment with CBD enhanced the efficacy of chemotherapy drugs.
We identified CBD as a new potential anti-cancer compound for single or combination therapy of HNSCC.”
In conclusion, our study determined the anti-tumorigenic potential of CBD. In addition, single treatment of CBD or co-treatment with chemotherapeutic agents promoted HNSCC cell death along with apoptosis and autophagy processes. Therefore, our study suggests that CBD can be an excellent therapeutic agent against HNSCC. Cannabidiol (CBD) is one of the components in the Cannabis sativa L. (marijuana) family of plants.”