Entries by Michelle Smith

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Tetrahydrocannabinol and Cannabidiol for Pain Treatment—An Update on the Evidence

In light of the current International Association for the Study of Pain (IASP) clinical practice guidelines (CPGs) and the European Society for Medical Oncology (ESMO) guidelines, the topic of cannabinoids in relation to pain remains controversial, with insufficient research presently available. Cannabinoids are an attractive pain management option due to their synergistic effects when administered with opioids, thereby also limiting the extent of respiratory depression. On their own, however, cannabinoids have been shown to have the potential to relieve specific subtypes of chronic pain in adults, although controversies remain. Among these subtypes are neuropathic, musculoskeletal, cancer, and geriatric pain. Another interesting feature is their effectiveness in chemotherapy-induced peripheral neuropathy (CIPN). Analgesic benefits are hypothesized to extend to HIV-associated neuropathic pain, as well as to lower back pain in the elderly. The aim of this article is to provide an up-to-date review of the existing preclinical as well as clinical studies, along with relevant systematic reviews addressing the roles of various types of cannabinoids in neuropathic pain settings.

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Cannabidiol and brain function: current knowledge and future perspectives

Cannabidiol (CBD) is a naturally occurring non-psychoactive cannabinoid found in Cannabis sativa, commonly known as cannabis or hemp. Although currently available CBD products do not meet the safety standards of most food safety authorities to be approved as a dietary supplement or food additive, CBD has been gaining widespread attention in recent years due to its various potential health benefits. While primarily known for its therapeutic effects in managing epileptic seizures, psychosis, anxiety, (neuropathic) pain, and inflammation, CBD’s influence on brain function has also piqued the interest of researchers and individuals seeking to enhance cognitive performance. The primary objective of this review is to gather, synthesize, and consolidate scientifically proven evidence on the impact of CBD on brain function and its therapeutic significance in treating neurological and mental disorders. First, basic background information on CBD, including its biomolecular properties and mechanisms of action is presented. Next, evidence for CBD effects in the human brain is provided followed by a discussion on the potential implications of CBD as a neurotherapeutic agent.

Immunotherapy and Cannabis: A Harmful Drug Interaction or Reefer Madness?

A retrospective (N=140) and a prospective (N=102) observational Israeli study by Bar-Sela and colleagues about cannabis potentially adversely impacting the response to immunotherapy have together been cited 191 times including by clinical practice guidelines. There have also been re-ports on PubPeer outlining unverifiable information in their statistics and numerous discrepan-cies calculating percentages. This report attempted to replicate the data-analysis including non-parametric statistics. Table 1 of the corrected prospective report contained 22 p-values but only one (4.5%) could be verified, despite the authors being transparent about the N and statistics employed. Cannabis users were significantly (p < .0025) younger than non-users but this was not reported in the retrospective report. There were also errors in percentage calculations (e.g. 13/34 reported as 22.0% instead of 38.2%). Overall, these observational investigations, and especially the prospective, appear to contain gross inaccuracies which could impact the statistical decisions (i.e. significant findings reported as non-significant or vice-versa). Although it is mechanistically plausible that cannabis could have immunosuppressive effects which inhibit the response to immunotherapy, these two reports should be viewed cautiously. Larger prospective studies of this purported drug interaction that account for potential confounds (e.g. greater nicotine smok-ing among cannabis users) may be warranted.

Overview: Chronic Pain and Cannabis-Based Medicines

Chronic pain is primarily conceptualized as a disease in its own right when it is associated with emotional distress and functional impairment. Pathophysiologically, dysfunction of the cortico-mesolimbic connectome is of major importance, with overlapping signals in the nociceptive and stress systems. The endocannabinoid system plays an important role in the central processing of nociceptive signals and regulates the central stress response. Clinically, there is moderate evidence that cannabis-based medicines (CBM) can contribute to a significant reduction in pain, especially the associated pain affect, and improvement in physical function and sleep quality in a proportion of patients with chronic pain. The analgesic effect appears to be largely independent of the cause of pain. In this context, CBM preferentially regulates stress-associated pain processing

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Cannabis by any name does not smell as sweet: potential cardiovascular events with medical cannabis

Recently, attitudes towards cannabis and its use have changed dramatically and continue to evolve worldwide. In 2014, many states in the USA started legalizing cannabis, thus increasing the availability of medical and recreational cannabis and creating an entire cannabis industry with dispensaries on many street corners.1 Within most of the European Union (EU), cannabis remains illegal; however, recently many countries have begun to legalize cannabis for limited therapeutic purposes. Countries such as Germany, the Czech Republic, Denmark, Germany, Italy, and Poland now permit the cultivation of cannabis for medical purposes, with the cultivation and subsequent processing taking place under the usually strict rules applicable to agricultural, manufacturing, distribution, security, and clinical good practice.2 Close pharmacovigilance of cannabis, as well as its safety and efficacy, have been limited by decades of worldwide illegality and by the ongoing classification of cannabis as a Schedule 1 controlled substance in the USA. Nonetheless, with increased cannabis decriminalization and legalization across the globe, the association between cannabis exposure and incident cardiovascular (CV) events has emerged as an important safety signal.

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Terpenes and Cannabidiol against Human Corona and Influenza Viruses – Anti-Inflammatory and Antiviral in Vitro Evaluation

The activity of the terpenes and Cannabidiol (CBD) against human coronavirus (HCoV) strain OC43 and influenza A (H1N1) was evaluated in human lung fibroblasts (MRC-5 cells). Also, we examined whether these ingredients inhibit pro-inflammatory cytokines in peripheral blood mononuclear cells (PBMC). The tested preparations exhibited both anti-inflammatory and antiviral effects. The combination of terpenes was effective against both HCoV-OC43 and influenza A (H1N1) virus. The addition of CBD improved the antiviral activity in some, but not all cases. This variation in activity may suggest an antiviral mechanism. In addition, there was a strong correlation between the quantitative results from a cell-viability assay and the cytopathic effect after 72 h, as observed under a microscope. The anti-inflammatory properties of terpenes were demonstrated using a pro-inflammatory cytokine-inhibition assay, which revealed significant cytokine inhibition and enhanced by the addition of CBD.

Exploring the Therapeutic Potential of Domestic Marijuana (Bong) Uses for Common Diseases in Booni Chitral Upper, Khyber Pakhtunkhwa

Cannabis (marijuana) based medicines have been used for medicinal purposes in many cultures for centuries. Traditional herbal medicine continues to serve as the most cost-effective and readily available form of treatment within the primary healthcare system for communities that do not have access to modern medicine. This study investigated the indigenous knowledge of folk healing among tribal minorities at selected sites in Booni Upper Chitral, Khyber Pakhtunkhwa . In this study, researcher explored the effects of using cannabis (bong) for medicinal purposes. This study intends to shed light on the cultural and domestic contexts of locally grown marijuana in order to discover its possible therapeutic uses for common ailments. In order to study the household utilization of marijuana for common ailments, a qualitative research approach is to conduct in-depth interviews with people who have first-hand experience using marijuana for health purposes in the comfort of their own homes. The researcher interviewed 10 dwellers for which 3 were females and 7 were males in Booni Upper Chitral selected through a snowball sampling technique.

An Overview of Cannabidiol as a Multifunctional Drug: Pharmacokinetics and Cellular Effects

Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis Sativa, has garnered increasing attention for its diverse therapeutic potential. This comprehensive review delves into the complex pharmacokinetics of CBD, including factors such as bioavailability, distribution, safety profile, and dosage recommendations, which contribute to the compound’s pharmacological profile. CBD’s role as a pharmacological inhibitor is explored, encompassing interactions with the endocannabinoid system and ion channels. The compound’s anti-inflammatory effects, influencing the Interferon-beta and NF-κB, position it as a versatile candidate for immune system regulation and interventions in inflammatory processes. The historical context of Cannabis Sativa’s use for recreational and medicinal purposes adds depth to the discussion, emphasizing CBD’s emergence as a pivotal phytocannabinoid. As research continues, CBD’s integration into clinical practice holds promise for revolutionizing treatment approaches and enhancing patient outcomes. The evolution in CBD research encourages ongoing exploration, offering the prospect of unlocking new therapeutic utility.

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Neurocognitive Impact of Exposure to Cannabis Concentrates and Cannabinoids Including Vaping in Children and Adolescents: A Systematic Review

During adolescence, significant changes unfold in the brain’s maturation process. The density of white matter increases, accompanied by the pruning back of gray matter. This critical and vulnerable period becomes especially noteworthy in the context of drug use, as adolescents are extensively exposed to substances such as tobacco, alcohol, and cannabis. The concern is heightened now that cannabis has been legalized for recreational use in many places, leading to increased exposure levels. Additionally, knowledge about the impact of cannabis on neurocognitive development during this stage is limited. This knowledge gap compounds the issue, making it even more concerning. Therefore, a systematic review was carried out based on the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using medical databases such as PubMed, PubMed Central (PMC), Medline, Cochrane Library, Internet Archive Scholar, and Embase-Elsevier for relevant medical literature. The identified articles were reviewed, eligibility criteria were applied, and 19 research articles were identified. The final papers explored the correlation between children’s and adolescents’ exposure to cannabis-containing compounds and subsequent changes in the central nervous system (CNS).

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Cannabis for chronic pain: cardiovascular safety in a nationwide Danish study

A rising number of countries allow physicians to treat chronic pain with medical cannabis. However, recreational cannabis use has been linked with cardiovascular side effects, necessitating investigations concerning the safety of prescribed medical cannabis. Using nationwide Danish registers, patients with chronic pain initiating first-time treatment with medical cannabis during 2018–21 were identified and matched 1:5 to corresponding control patients on age, sex, chronic pain diagnosis, and concomitant use of other pain medication. The absolute risks of first-time arrhythmia (atrial fibrillation/flutter, conduction disorders, paroxysmal tachycardias, and ventricular arrhythmias) and acute coronary syndrome were reported comparing medical cannabis use with no use.

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Role of Cannabinoids in Oral Cancer

Cannabinoids have incited scientific interest in different conditions, including malignancy, due to increased exposure to cannabis. Furthermore, cannabinoids are increasingly used to alleviate cancer-related symptoms. This review paper aims to clarify the recent findings on the relationship between cannabinoids and oral cancer, focusing on the molecular mechanisms that could link cannabinoids with oral cancer pathogenesis. In addition, we provide an overview of the current and future perspectives on the management of oral cancer patients using cannabinoid compounds. Epidemiological data on cannabis use and oral cancer development are conflicting. However, in vitro studies assessing the effects of cannabinoids on oral cancer cells have unveiled promising anti-cancer features, including apoptosis and inhibition of cell proliferation. Downregulation of various signaling pathways with anti-cancer effects has been identified in experimental models of oral cancer cells exposed to cannabinoids. Furthermore, in some countries, several synthetic or phytocannabinoids have been approved as medical adjuvants for the management of cancer patients undergoing chemoradiotherapy. Cannabinoids may improve overall well-being by relieving anxiety, depression, pain, and nausea. In conclusion, the link between cannabinoid compounds and oral cancer is complex, and further research is necessary to elucidate the potential risks or their protective impact on oral cancer.

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The Neurotherapeutic Arsenal in Cannabis sativa: Insights into Anti-Neuroinflammatory and Neuroprotective Activity and Potential Entourage Effects

Terpenes, aromatic compounds imbuing distinct flavours, not only contribute to cannabis’s sensory profile but also modulate cannabinoid effects through diverse molecular mechanisms. Flavonoids, another cannabis component, demonstrate anti-inflammatory, antioxidant, and neuroprotective properties, particularly relevant to neuroinflammation. The entourage hypothesis posits that combined cannabinoid, terpene, and flavonoid action yields synergistic or additive effects, surpassing individual compound efficacy. Recognizing the nuanced interactions is crucial for unravelling cannabis’s complete therapeutic potential. Tailoring treatments based on the holistic composition of cannabis strains allows optimization of therapeutic outcomes while minimizing potential side effects. This review underscores the imperative to delve into the intricate roles of cannabinoids, terpenes, and flavonoids, offering promising prospects for innovative therapeutic interventions and advocating continued research to unlock cannabis’s full therapeutic potential within the realm of natural plant-based medicine.