Phytocannabinoids CBD, CBG, and their Derivatives CBD-HQ and CBG-A Induced In Vitro Cytotoxicity in 2D and 3D Colon Cancer Cell Models.

Phytocannabinoids, compounds found in Cannabis sativa L., are used in oncology and palliative care to reduce the adverse reactions of standard therapies. Cancer patients use formulations of Cannabis sativa L. to manage the anxiety, pain, and nausea associated with cancer treatment, and there is growing evidence that some of them may exhibit anticancer properties. In this study, we tested the anticancer potential of selected cannabinoids CBD (cannabidiol) and its quinone derivative CBD-HQ (cannabidiol hydroquinone), CBG (cannabigerol) and its acid derivative CBG-A (cannabigerolic acid), as well as a combination of CBD+CBG on the colon cancer cell line SW-620. The MTT assay was used to determine the cannabinoids' ability to induce colon cancer cell death. All cannabinoids were cytotoxic at the lowest concentration (3 µg/mL). The half maximal inhibitory concentration (IC50) ranged from 3.90 to 8.24 µg/mL, depending on the substance. Cytotoxicity was confirmed in a 3D spheroidal cell culture with calcein and propidium iodide staining. The amount of intracellular reactive oxygen species (ROS) was examined using a DCF-DA assay. CBG showed the lowest antioxidant activity of all the cannabinoids tested. The level of intracellular ROS decreased only by 0.7-18%. However, CBG-A induced the strongest reduction in ROS level by 31-39%. Our results suggest that cannabinoids represent an interesting research direction with great implementation potential. These preliminary results represent the beginning of research into the potential of these substances for anticancer treatment and underscore the potential for further research.

Genotype-by-diagnosis interaction influences self-control in human cocaine addiction.

Not everyone who uses drugs loses control over their intake, which is a hallmark of addiction. Although familial risk studies suggest significant addiction heritability, the genetic basis of vulnerability to drug addiction remains largely unknown. In the present study, we investigate the relationship between self-control, cocaine use, and the rs36024 single nucleotide polymorphism of the noradrenaline transporter gene (SLC6A2). We hypothesize that C-allele-carrying adults show impaired self-control, as measured by the stop-signal task and demonstrated previously in adolescents, and further exacerbated by chronic cocaine use. Patients with cocaine use disorder (CUD, n = 79) and healthy unrelated participants with no history of drug abuse (n = 54) completed the stop-signal task. All participants were genotyped for rs36024 allelic variants (CC/TT homozygotes, CT heterozygotes). We measured mean stop-signal reaction time, reflecting the ability to inhibit ongoing motor responses, reaction times to go stimuli, and the proportion of successful stops. CUD patients showed prolonged stop-signal reaction time, however, there was no main effect of rs36024 genotype. Importantly, there was a significant genotype-by-diagnosis interaction such that CUD patients with CC genotype had longer stop-signal reaction time and fewer successful stops compared with CC healthy controls and TT CUD patients. CT CUD patients showed an intermediate performance. Self-control deficits were associated with cocaine use disorder diagnosis, which interacts with the noradrenaline transporter rs36024 polymorphism. Our findings suggest that rs36024 may represent a potential genetic vulnerability marker, which facilitates the transition from first cocaine use to addiction by weakening the inhibitory control over behavior.

Cannabinoids-Perspectives for Individual Treatment in Selected Patients: Analysis of the Case Series.

Cannabinoids can be successfully used in the treatment of many symptoms and diseases; however, most often they are not the drugs of first choice. They can be added to the primary therapy, which can improve its effectiveness, or be introduced as the basic treatment when the conventional methods have failed. Small clinical trials and case reports prove the benefits of applying medicinal cannabis in various indications; however, clinical trials in larger groups of patients are scarce and often controversial. Due to limited scientific evidence, it is essential to conduct further experimental trials. Understanding the role of endocannabinoids, as well as the composition of cannabis containing both phytocannabinoids and terpenes plays an important role in their clinical use. The clinical effects of cannabinoids depend, among other things, on the activity of the endocannabinoid system, the proportion of phytocannabinoids, such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), and the dosage used. The article discusses the role of phytocannabinoids and the potential of using them in different clinical cases in patients suffering from chronic pain, opioid dependence, depression and migraine, who did not respond to the conventional therapeutic methods. In each of the presented cases, the implementation of cannabinoids altered the course of the disease and resulted in symptom relief. Every decision to introduce cannabinoids to the treatment should be made individually with careful attention paid to details. Additionally, it is worth taking care of good clinical communication and education so that the implemented therapy is safe, effective and properly perceived by the patient.

Anti-Inflammatory and Antiviral Effects of Cannabinoids in Inhibiting and Preventing SARS-CoV-2 Infection.

The COVID-19 pandemic caused by the SARS-CoV-2 virus made it necessary to search for new options for both causal treatment and mitigation of its symptoms. Scientists and researchers around the world are constantly looking for the best therapeutic options. These difficult circumstances have also spurred the re-examination of the potential of natural substances contained in Cannabis sativa L. Cannabinoids, apart from CB1 and CB2 receptors, may act multifacetedly through a number of other receptors, such as the GPR55, TRPV1, PPARs, 5-HT1A, adenosine and glycine receptors. The complex anti-inflammatory and antiviral effects of cannabinoids have been confirmed by interactions with various signaling pathways. Considering the fact that the SARS-CoV-2 virus causes excessive immune response and triggers an inflammatory cascade, and that cannabinoids have the ability to regulate these processes, it can be assumed that they have potential to be used in the treatment of COVID-19. During the pandemic, there were many publications on the subject of COVID-19, which indicate the potential impact of cannabinoids not only on the course of the disease, but also their role in prevention. It is worth noting that the anti-inflammatory and antiviral potential are shown not only by well-known cannabinoids, such as cannabidiol (CBD), but also secondary cannabinoids, such as cannabigerolic acid (CBGA) and terpenes, emphasizing the role of all of the plant's compounds and the entourage effect. This article presents a narrative review of the current knowledge in this area available in the PubMed, Scopus and Web of Science medical databases.

Relationship between breakthrough cancer pain, background cancer pain and analgesic treatment - case series and review of the literature.

The assessment and treatment of breakthrough cancer pain (BTcP) remain a major challenge in medicine due to its high impact on several aspects of health-related quality of life. BTcP should be carefully monitored in all cancer care settings by a multidisciplinary team to provide an appropriate and personalized clinical approach. The aim of this paper is to provide healthcare professionals involved in cancer pain management with a review of the relevant literature on the relationship between background cancer pain and BTcP which, by definition, occurs despite adequately controlled background cancer pain. The clinical cases presented contribute to a better understanding of this issue and underline its impact in daily clinical practice. This article is part of the Management of breakthrough cancer pain Special Issue: https://www.drugsincontext.com/special_issues/management-of-breakthrough-cancer-pain.

The Therapeutic Potential of Cannabis in Counteracting Oxidative Stress and Inflammation.

Significant growth of interest in cannabis (Cannabis sativa L.), especially its natural anti-inflammatory and antioxidative properties, has been observed recently. This narrative review aimed to present the state of the art of research concerning the anti-inflammatory activity of all classes of cannabinoids published in the last five years. Multimodal properties of cannabinoids include their involvement in immunological processes, anti-inflammatory, and antioxidative effects. Cannabinoids and non-cannabinoid compounds of cannabis proved their anti-inflammatory effects in numerous animal models. The research in humans is missing, and the results are unconvincing. Although preclinical evidence suggests cannabinoids are of value in treating chronic inflammatory diseases, the clinical evidence is scarce, and further well-designed clinical trials are essential to determine the prospects for using cannabinoids in inflammatory conditions.

Prospects for the Use of Cannabinoids in Psychiatric Disorders.

Increasing evidence suggests an essential role of the endocannabinoid system in modulating cognitive abilities, mood, stress, and sleep. The psychoactive effects of cannabis are described as euphoric, calming, anxiolytic, and sleep-inducing and positively affect the mood, but can also adversely affect therapy. The responses to cannabinoid medications depend on the patient's endocannabinoid system activity, the proportion of phytocannabinoids, the terpenoid composition, and the dose used. There is some evidence for a therapeutic use of phytocannabinoids in psychiatric conditions. THC and CBD may have opposing effects on anxiety. Current guidelines recommend caution in using THC in patients with anxiety or mood disorders. In a small number of clinical trials, cannabinoids used to treat cancer, HIV, multiple sclerosis, hepatitis C, Crohn's disease, and chronic neuropathic pain report decreases in anxiety or depression symptoms and presented sedative and anxiolytic effects. Several studies have investigated the influence of potential genetic factors on psychosis and schizophrenia development after cannabis use. THC may increase the risk of psychosis, especially in young patients with an immature central nervous system. There is limited evidence from clinical trials that cannabinoids are effective therapy for sleep disorders associated with concomitant conditions. There is evidence for a possible role of cannabis as a substitute for alcohol and drugs, also in the context of the risks of opioid use (e.g., opioid-related mortality). In this narrative review of the recent evidence, we discuss the prospects of using the psychoactive effects of cannabinoids in treating mental and psychiatric disorders. However, this evidence is weak for some clinical conditions and well-designed randomized controlled trials are currently lacking. Furthermore, some disorders may be worsened by cannabis use.

Why patients are afraid of opioid analgesics: a study on opioid perception in patients with chronic pain.

INTRODUCTION    Opiophobia is deemed one of the key barriers in effective pain management. OBJECTIVES    The study aimed to assess the overall perception of opioids in cancer patients treated for chronic pain, as well as to determine the nature of their most common related fears. PATIENTS AND METHODS     The study included 100 palliative care patients who suffered from chronic cancer or noncancer pain. Initially, they had to complete a survey exploring their knowledge on analgesics and potential fear of using opioids. The second phase was based on in­depth interviews with 10 palliative care patients suffering from cancer pain who were reluctant to use opioids. RESULTS     Of the 100 patients, 43 expressed concerns over commencing the treatment with opioids. Fear was reported more often in patients already on strong opioids, who either overtly expressed it (group C) or not (group B), as compared with patients treated with weak opioids (group A) (50%, 48%, and 19% of groups C, B, and A, respectively). The main concerns were drug addiction, fear of death or dying, and undesirable side effects. A qualitative study revealed similar types of fear among patients expressing concerns prior to being put on strong opioids. CONCLUSIONS    Opiophobia seems to be common among palliative care patients (up to 50%) treated with strong opioids. They mainly fear drug addiction, undesirable effects, and death or dying. Better awareness of patients' preconceptions about opioids may become instrumental to alleviating their suffering through enhanced pain management.