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Scientific articles

• Cannabis in Parkinson's Disease: The Patients' View

  This study consists of a cross-sectional survey based on the application of structured questionnaires in Germany, whose main objective was to map the general perception, level of knowledge, therapeutic interest and real-world practical experiences of the Parkinson's Disease (PD) patient community in relation to the use of medicinal cannabis. Although the endocannabinoid system has been gaining prominence in the literature as a potential route to alleviating neurological symptoms, controlled clinical evidence remains scarce and little was known, in a statistically representative way, about the direct perspective and consumption habits of patients themselves. To collect these data and mitigate possible sampling biases, the authors distributed the questionnaires nationally through the German Parkinson Association's membership journal and locally in a specialized neurological clinic, gathering a substantial total of 1,348 validated responses for analysis.

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• Effects of Cannabis in Parkinson's Disease: A Systematic Review and Meta-Analysis

  This study consists of a systematic review and comprehensive meta-analysis whose main objective was to compile, analyze and rigorously evaluate the best scientific evidence available in the medical literature on the efficacy, safety and clinical benefits of the use of cannabis and cannabinoids in the management of Parkinson's Disease (PD). As the relaxation of laws and regulation of cannabis advances worldwide, an increasing number of Parkinson's patients have turned to products derived from the plant in search of therapeutic alternatives. Given this, the authors structured this research to map existing data and serve as a robust informative guide for patients, caregivers, clinicians and researchers when making decisions. The structured literature search, carried out until June 2021, identified and selected 5 randomized, placebo-controlled clinical trials (RCTs) and 18 non-randomized studies evaluating cannabinoid treatment in humans.

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• Use of Cannabidiol in the Treatment of Epilepsy: Efficacy and Security in Clinical Trials

  This article consists of a comprehensive review of the scientific literature that mapped and evaluated the efficacy data, safety profiles and pharmacological interactions resulting from the use of cannabidiol (CBD) — a non-psychotropic and terpenogenic phytocannabinoid extracted from Cannabis sativa — in the adjuvant treatment of severe and drug-resistant epilepsy (Treatment-Resistant Epilepsy - TRE). It is estimated that epilepsy affects more than 50 million people worldwide, with around 30% of this contingent not responding satisfactorily to therapies with conventional first-line antiepileptic drugs (AEDs). Faced with this debilitating scenario, the authors conducted a detailed survey focused on consolidating the results of pivotal Phase III clinical trials (registered on ClinicalTrials.gov) and data indexed on PubMed that investigated CBD for severe seizure disorders.

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• Cannabidiol prescription in New Zealand: real-world data

  This real-world, prospective, observational study was conducted with the objective of evaluating the safety, tolerability, usage patterns, and clinical outcomes of patients receiving cannabidiol (CBD) prescriptions in primary healthcare. Although clinical interest in cannabinoids has expanded substantially, most of the available data comes from highly controlled and restricted clinical trials, generating a lack of empirical evidence on the impact of CBD on the daily practice of a heterogeneous population of patients in general medicine. To address this gap, the research conducted a prospective clinical audit following a consecutive series of 400 patients who were prescribed oral CBD by a single family doctor in New Zealand between December 2017 and December 2018. Participants' medical indications were divided into four main categories: chronic pain, neurological symptoms, mental health symptoms (such as anxiety and depression) and cancer-related symptoms. Well-being and health-related quality of life outcomes were quantified using the validated EuroQol 5-dimensional, 5-level questionnaire (EQ-5D-5L) at baseline and after 4 weeks of follow-up.

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• Add-On Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex: A Placebo-Controlled Randomized Clinical Trial

  This article consists of an international Phase III, randomized, double-blind, placebo-controlled clinical trial (known as the GWPCARE6 protocol), which established pivotal evidence of efficacy and safety for the use of highly purified cannabidiol (CBD) in the treatment of difficult-to-control seizures associated with Tuberous Sclerosis Complex (TSC). TSC is a rare multisystemic genetic disorder characterized by the growth of benign tumors in multiple organs, including the brain, which often results in severe focal and multifocal epilepsy, severely resistant to traditional anti-seizure medications (ASMs). Although CBD was already approved for efficacy in seizures associated with Lennox-Gastaut and Dravet syndromes, its benefit in conditions dominated by focal seizures such as TSC had yet to be rigorously established. The research recruited and randomized 224 patients (with a median age of 11.4 years, ranging from 1.1 to 56.8 years) who had uncontrolled seizures despite being on a stable therapeutic regimen of concomitant medications. Subjects were randomly assigned to three parallel treatment arms for 16 weeks: CBD at a dose of 25 mg/kg/day (n = 75), CBD at a dose of 50 mg/kg/day (n = 73), or matching placebo (n = 76).

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• Adjunctive Transdermal Cannabidiol for Adults With Focal Epilepsy: A Randomized Clinical Trial

  This study consists of a multicenter, randomized, double-blind, placebo-controlled clinical trial (Phase II) that investigated the efficacy, safety and tolerability of cannabidiol (CBD) administered transdermally as adjuvant therapy in adults with drug-resistant focal epilepsy. Although the oral use of cannabidiol has robust and proven efficacy in the treatment of severe epileptic syndromes that predominantly affect children (such as Dravet and Lennox-Gastaut syndromes), oral formulations often cause significant gastrointestinal adverse events (such as diarrhea and loss of appetite), suffer from hepatic first-pass metabolism and can elevate transaminase enzymes. In view of this, the purified and synthetic transdermal gel formulation (ZYN002) was developed to mitigate these limitations, bypassing the digestive tract and providing a continuous, stable and spike-free plasma release. The trial was conducted at 14 specialist epilepsy centers in Australia and New Zealand, recruiting adults with uncontrolled focal seizures even on a stable therapeutic regimen of up to three anti-seizure medications (ASMs).

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• Efficacy, Tolerability, and Safety of Cannabis-Based Medicines for Chronic Pain Management

  This study consists of a comprehensive systematic review (a review of reviews) conducted with the aim of critically evaluating the efficacy, tolerability, and safety of cannabis-based medicines (CBMs) in the treatment of chronic pain syndromes in adults. The management of chronic pain — divided into neuropathic pain, cancer pain, and musculoskeletal/rheumatic pain (such as fibromyalgia) — remains a global clinical challenge, given that conventional analgesic therapies often offer limited relief or cause intolerable side effects. To establish evidence-based guidelines for medical practice, the authors synthesized data from multiple systematic reviews and meta-analyses of randomized controlled clinical trials.

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• Cannabidiol and epilepsy in Brazil: a current review

  This article consists of a narrative and critical review of the literature that summarizes the main pharmacological aspects, evidence of efficacy and safety, the regulatory panorama and the practical application of cannabidiol (CBD) in the management of drug-resistant epilepsy, specifically contextualizing the health scenario and current legislation in Brazil. It is estimated that epilepsy affects around 50 million people worldwide, with up to 30% of these individuals presenting the refractory form of the disease (persistence of seizures despite the correct use of two appropriate anti-seizure medications). Faced with this therapeutic challenge, CBD has gained prominence for exerting potent systemic anticonvulsant effects without manifesting the typical psychotropic properties of THC.

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• Effect of Cannabidiol on Interictal Epileptiform Activity and Sleep Architecture in Children with Intractable Epilepsy: A Prospective Open-Label Study

  This prospective, open-label clinical study was conducted with the aim of filling a critical gap in the neuropharmacological literature: evaluating the impact of cannabidiol (CBD) on reducing interictal epileptiform activity (discharges observed on the electroencephalogram between seizures) and modulating the microstructure of sleep. Although the effectiveness of CBD in reducing gross seizures was already established in pathologies such as Dravet and Lennox-Gastaut syndromes and the tuberous sclerosis complex, its effect on interictal electrical abnormalities and objective sleep patterns remained very little explored. The research prospectively followed a cohort of 35 children (mean age 10.1 years) diagnosed with drug-resistant epilepsy between November 2019 and January 2021. Patients received CBD associated with their stable regimen of conventional anti-seizure medications, starting with a dose of 5 mg/kg/day and progressing up to a standard dose of 20 mg/kg/day (with a maximum allowable ceiling of up to 50 mg/kg/day). Electroencephalogram (EEG) exams were performed at baseline (T0) and after 3 months of treatment (T1). To ensure freedom from bias, two independent evaluators blinded to the patients' clinical outcomes analyzed the records.

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• Cannabidiol in the Treatment of Epilepsy

  This article consists of a comprehensive scientific review focused on consolidating and analyzing the efficacy data, safety parameters, neurobiological mechanisms and practical management of the use of pharmaceutical-grade cannabidiol (CBD) in the treatment of epilepsy. While historical anecdotal reports have generated enormous public appeal, controlled Phase III clinical trials have scientifically validated that CBD acts robustly in reducing severe seizures. The article details the regulatory milestones for approval of the compound (such as the drug Epidiolex) by the FDA and EMA, while warning about the commercial confusion generated by the over-the-counter market (unregulated CBD supplements), whose labels and purities are inaccurate and whose clinical results cannot simply be equated with purified pharmaceutical CBD.

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• Medical Cannabis, Headaches, and Migraines: A Review of the Current Literature

  This article consists of a narrative literature review whose main objective was to evaluate the scientific validity, efficacy and safety of the use of medicinal cannabis as an alternative and adjuvant therapy for the management of headaches and migraine attacks. The study contextualizes that, due to the fact that cannabis is federally classified in the United States as a "Schedule I" drug (with no accepted medical use and high potential for abuse), the performance of large-scale randomized controlled clinical trials has historically been limited, generating a scenario in which most of the current evidence rests on case studies, retrospective chart reviews, and "real-world" observational research. To fill this information gap, the authors carried out a careful screening of the PubMed and Google Scholar databases, selecting 34 relevant scientific articles published between 1987 and 2020.

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• Cannabis‐based medicines for chronic neuropathic pain in adults

  This study consists of a robust and comprehensive systematic review published by the prestigious Cochrane Collaboration (Cochrane Database of Systematic Reviews) to evaluate the efficacy, tolerability and safety of cannabis-based medicines compared to placebo or conventional drugs in the treatment of chronic neuropathic pain in adults. Chronic neuropathic pain (resulting from damage to the somatosensory system) affects between 6% and 10% of the world's population and represents a major clinical challenge, given that current first-line pharmacological treatments offer real benefits to only a minority of patients, often generating disabling adverse effects. To compile the evidence, the authors carried out structured searches in international reference databases until November 2017, selecting randomized, double-blind, parallel-group controlled clinical trials with a minimum duration of two weeks and at least 10 participants per treatment arm. The level of certainty of the evidence was measured according to the GRADE methodology.

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• Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain

  This experimental and laboratory study carried out in vivo with rodents pioneered the investigation into the neurobiological bases and exact electrophysiological mechanisms through which cannabidiol (CBD) — the main non-psychoactive and non-addictive component of cannabis — acts to simultaneously control pain and mood disorders. The researchers' central objective was to decipher the impact of CBD on the firing rate and signaling of serotonergic neurons (5-HT) located in the dorsal raphe nucleus (DRN), as chronic pain often degrades serotonin pathways in the brain, triggering serious secondary anxiety. Initially, using single-unit extracellular recordings, the study demonstrated that acute and increasing intravenous doses of CBD temporarily decrease the electrical firing of these neurons, an effect that was completely prevented by the use of the drug WAY 100635 (a selective 5-HT1A receptor antagonist).

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• Dronabinol Is a Safe Long-Term Treatment Option for Neuropathic Pain Patients

  This article consists of a Phase III, multicenter clinical trial that evaluated the efficacy and, primarily, the long-term safety and tolerability of dronabinol in the management of central neuropathic pain (CND). Chronic neuropathic pain is a highly prevalent and debilitating comorbidity in patients with Multiple Sclerosis (MS), and current first-line therapies (such as tricyclic antidepressants and anticonvulsants) often fail to provide satisfactory relief or induce intolerable adverse reactions. The study was divided into two sequential stages: a 16-week, randomized, double-blind, placebo-controlled initial phase (involving 240 MS patients), followed by a 32-week open-label extension period, in which a subcohort of 100 patients extended continuous use of the cannabinoid for up to 119 weeks. The daily dosage was adjusted individually during a 4-week titration period, ranging between 7.5 mg and 15.0 mg orally.

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• Anti‐seizure medications for Lennox‐Gastaut syndrome

  This article consists of a comprehensive systematic review of high methodological relevance, published by the prestigious Cochrane Collaboration (Cochrane Database of Systematic Reviews). The primary objective of the study was to rigorously evaluate the efficacy, safety, and tolerability of anti-seizure medications (ASMs) used to treat Lennox-Gastaut Syndrome (LGS), a severe, drug-resistant, childhood-onset form of epileptic encephalopathy characterized by multiple seizure types and severe cognitive delay. To compile the data, the authors carried out structured searches in international reference databases (such as MEDLINE and Cochrane Register of Studies), including randomized controlled clinical trials (RCTs) without language restrictions. In total, the review included 11 clinical trials that totaled 1,277 participants (children, adolescents and adults).

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• Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study of the Efficacy, Safety, and Tolerability of THC:CBD Extract and THC Extract in Patients with Intractable Cancer-Related Pain

  This renowned Phase II, multicenter, double-blind, randomized, placebo-controlled clinical trial was structured to directly compare the efficacy, safety and tolerability of a combined THC:CBD oromucosal extract (commercially known as nabiximols or Sativex) and an extract containing only isolated THC versus placebo in the relief of cancer pain. The study focused on a high clinical challenge population: 177 adult patients with advanced-stage cancer who suffered from intractable and severe pain, which persisted in a refractory manner even with the continuous use of chronic and potent doses of first-line opioid analgesics. Participants were randomly assigned to three parallel treatment arms over a two-week period: the THC:CBD group (n = 60), the THC alone group (n = 58), and the placebo group (n = 59).

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• A selective review of medical cannabis in cancer pain management

  This article consists of a selective review of the scientific literature whose objective was to analyze and synthesize data from historically conducted clinical studies (published between 1975 and 2017) that investigated the efficacy, safety and dosage of medicinal cannabis in controlling chronic and neuropathic pain in patients with advanced cancer. The treatment of end-stage cancer pain relies heavily on the use of potent opioid analgesics; however, variability in biological response and the occurrence of severe adverse effects (such as severe constipation, sedation, risk of tolerance, dependence or overdose) often limit its clinical application at sufficient analgesic doses. Given this, the search for alternative classes of adjuvant analgesics, such as cannabinoids, has become of great relevance for palliative medicine. To compile the evidence, the authors systematically reviewed five representative clinical trials indexed in the Medline database.

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• UK Medical Cannabis Registry: Assessment of clinical outcomes in patients with insomnia

  This observational study (a case series) used data from the UK Medical Cannabis Registry (UKMCR) to evaluate the safety, tolerability and clinical efficacy of cannabis-based medicinal products (CBMPs) in the treatment of patients diagnosed with chronic primary insomnia. The objective was to measure changes in specific sleep and overall quality of life outcomes reported directly by individuals who had not achieved satisfactory response to conventional licensed first-line therapies and medications. The analyzed cohort included 61 patients followed for a period of up to 6 months after the start of adjuvant treatment.

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• Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report

  This article consists of a clinical case report that documents the efficacy and safety of using cannabidiol (CBD) oil in the treatment of severe symptoms of anxiety and insomnia in a 10-year-old pediatric patient diagnosed with Post-Traumatic Stress Disorder (PTSD) resulting from sexual abuse and family neglect suffered in early childhood. Prior to treatment with cannabinoids, conventional pharmacological attempts were made (with clonidine and imipramine), which provided only partial, temporary relief and were accompanied by serious side effects (such as hallucinations caused by clonidine). Given this, the family sought safer alternatives with less pharmacological burden to mitigate the child's self-destructive behaviors, tantrums, anxiety and chronic sleep disorders.

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• The Use of Cannabinoids for Insomnia in Daily Life: Naturalistic Study

  This real-world observational and retrospective study was conducted with the aim of mapping the usage profile and evaluating the perceived effectiveness of cannabis-based products in managing insomnia in patients' daily lives. Although sleep disorders are one of the main reasons that lead individuals to seek medical cannabis, most of the scientific evidence available on the subject derives from research whose primary outcome was another pathology (such as chronic pain or multiple sclerosis), generating a lack of robust data specifically focused on insomnia in natural conditions of daily use.

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• An investigation of cannabis use for insomnia in depression and anxiety in a naturalistic sample

  This retrospective cohort study investigated the use patterns and self-perceived effectiveness of medical cannabis in managing insomnia in patients diagnosed with depression, anxiety, or the comorbidity of both conditions. Disturbances in the sleep-wake cycle are central pathophysiological hallmarks of mood disorders, affecting 70% to 90% of this population. To evaluate these effects in a real-life environment ("real world"), researchers used data collected through the Strainprint® health tracking mobile app. The final sample totaled 677 voluntary participants — divided between the groups of isolated depression (n = 100), isolated anxiety (n = 463) and anxious-depressive comorbidity (n = 114) — whose interactions generated a robust database with 8,476 use sessions monitored between 2017 and 2020. Users recorded the initial severity of insomnia on a scale of 0 to 10 before consumption and reported the residual severity after a predetermined period.

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• The (Poly)Pharmacology of Cannabidiol in Neurological and Neuropsychiatric Disorders: Molecular Mechanisms and Targets

  This article consists of a comprehensive scientific review focused on mapping and updating the complex and versatile polypharmacological profile of cannabidiol (CBD) in the treatment of a wide range of neurological and neuropsychiatric disorders, such as anxiety, schizophrenia, depression, epilepsy and chemical dependency. The authors describe that the great therapeutic virtue of CBD arises from its ability to act in a multi-target manner, interacting with dozens of cellular receptors and ion channels that extend far beyond the classic endocannabinoid system. Unlike Δ9-THC, CBD does not have psychotropic effects, often functioning as a beneficial counterpoint to the adverse and anxiogenic effects of THC.

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• Cannabidiol in Neurological and Neoplastic Diseases: Latest Developments on the Molecular Mechanism of Action

  This article consists of a comprehensive scientific review focused on updating and detailing discoveries about the biochemical and molecular mechanisms of action of cannabidiol (CBD) — the main non-psychotropic phytocannabinoid from Cannabis sativa L. — in the treatment of serious chronic diseases. Due to the urgent need for more efficient pharmacological treatments, the authors discuss the potential beneficial effects of CBD for the management of Alzheimer's Disease (AD), epilepsy, multiple sclerosis and various types of cancer, including neoplasms that directly affect the nervous system. Due to its broad spectrum of activities (antioxidant, anti-inflammatory, antiepileptic, anxiolytic and neuroprotective), CBD is characterized as a multimodal drug.

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• Molecular Targets of Cannabidiol in Experimental Models of Neurological Disease

  This article consists of a detailed scientific review that compiles and analyzes in vitro and in vivo studies published over 15 years that describe the biochemical and molecular mechanisms associated with the therapeutic effects and efficacy of cannabidiol (CBD) in pathologies of the central nervous system. Given the complexity and incurability of neurodegenerative and psychiatric illnesses, CBD stands out as a promising pharmacological candidate as it presents a broad spectrum of anxiolytic, anticonvulsant, antidepressant, anti-inflammatory and antioxidant properties, in addition to having an excellent safety profile and low toxicity, without inducing the psychotropic effects characteristic of Δ9-THC.

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• Phytocannabinoids: General Aspects and Pharmacological Potential in Neurodegenerative Diseases

  This article consists of a comprehensive scientific review focused on mapping the state of the art, pharmacology and clinical potential of phytocannabinoids and new cannabis-based drug candidates for the treatment of chronic neurodegenerative diseases and dementias, with emphasis on Alzheimer's (AD), Parkinson's (PD) and Huntington's (HD). Currently, conventional clinical approaches to these pathologies are mostly limited to palliative and symptomatic control, which makes it imperative to search for innovative disease-modifying therapies that can effectively delay, mitigate or interrupt degenerative progression in the face of global demographic aging.

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• Cannabinoids for the treatment of dementia

  This article consists of a comprehensive systematic review conducted and published by the prestigious Cochrane Collaboration, whose main objective was to rigorously evaluate the efficacy and safety of the use of cannabinoid compounds in the treatment of dementia. Dementia represents a prevalent chronic condition that mostly affects the elderly and is characterized by the progressive decline in cognitive and functional capabilities, often accompanied by severe behavioral and psychological symptoms (such as agitation, anxiety and aggression). Given the modest efficacy and safety challenges associated with current conventional medicines, cannabinoids have begun to be investigated as a potential therapeutic alternative. To prepare the study, the authors carried out structured searches in multiple international health databases until July 2021, selecting randomized, placebo-controlled clinical trials (RCTs) without restrictions on age, dosage or route of administration.

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• The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review

  This study consists of a comprehensive systematic review conducted with the aim of evaluating the efficacy and benefits of herbal cannabis preparations for the treatment of chronic pain in adults, as well as synthesizing global evidence on the physical and mental harms associated with their use, both in populations with persistent pain and in the general adult population. The survey involved rigorous analysis of data from 27 clinical trials on chronic pain, complemented by safety information extracted from 11 systematic reviews and 32 primary studies focused on adverse events.

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• Cannabis-Based Products for Chronic Pain: A Systematic Review

  This study consists of a comprehensive systematic review, funded by the Agency for Healthcare Research and Quality (AHRQ) in the United States, which rigorously evaluated the benefits and harms of the use of cannabinoids in the management of chronic pain. To establish a robust picture, the authors reviewed data from 18 randomized placebo-controlled trials (totaling 1,740 patients) and 7 cohort studies (encompassing 13,095 patients). Most of the research analyzed evaluated short-term treatments (lasting 1 to 6 months) and focused on relieving chronic neuropathic pain.

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• The Effectiveness of Cannabis and Cannabis Derivatives in Treating Lower Back Pain in the Aged Population: A Systematic Review

  This article consists of a systematic review of the scientific literature whose main objective was to evaluate the role and clinical efficacy of cannabis and its pharmaceutical derivatives in the management of chronic low back pain (Lower Back Pain - LBP) specifically in the elderly population, in addition to mapping the impact of treatment on common comorbidities, such as anxiety and insomnia. The study was motivated by the progressive reduction in social stigma and the consequent increase in interest in the use of medicinal cannabinoids, contrasting with the chronic lack of evidence-based guidelines aimed at geriatric patients. To compile the data, three independent researchers conducted structured searches that resulted in the selection and in-depth analysis of 23 articles that met the strict inclusion criteria.

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• Tetrahydrocannabinol and cannabidiol medicines for chronic pain and mental health conditions

  This article consists of a detailed review of the literature focused on the efficacy, safety and pharmacology of medicines based on the combination of THC and CBD or containing only isolated CBD for the management of chronic pain, stress, anxiety, depression and insomnia. The authors describe that THC and CBD act by increasing the signaling of the body's cannabinoid receptors, generating a reduction in synaptic transmission at strategic points in the central and peripheral nervous system, in addition to repressing the secretion of inflammatory cytokines by immune and glial cells. The great usefulness of combining CBD with formulations with THC is based on CBD's ability to enhance the analgesic effects and, at the same time, counteract and mitigate the adverse and psychoactive reactions of THC.

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• Values and preferences towards medical cannabis among people living with chronic pain: a mixed-methods systematic review

  This study consists of a systematic review of mixed methods (bringing together quantitative and qualitative approaches) whose objective was to explore and map global scientific evidence on the values, attitudes and preferences of patients affected by chronic pain in relation to the use of medicinal cannabis. To this end, the researchers carried out careful searches in reference databases (such as MEDLINE, EMBASE and PsycINFO) since the beginning of their records, identifying 1,838 initial records, of which 15 studies met all eligibility criteria. The degree of certainty of the evidence was assessed using the GRADE methodological approach.

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• Chronic Pain and the Endocannabinoid System: Smart Lipids – A Novel Therapeutic Option?

  This article consists of a scientific review focused on the relationship between chronic pain and the modulation of the endocannabinoid system (ECS), highlighting a biotechnological innovation in drug delivery called "Smart Lipids". The authors propose a new conceptual perspective, suggesting that chronic pain acts as a failure in the brain's ability to extinguish traces of aversive associative memory ("pain memory"), being strongly aggravated by comorbidities of stress and anxiety. The SEC plays a central role in controlling these emotional and sensory circuits through its CB1 and CB2 receptors.

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• A Survey on the Effect That Medical Cannabis Has on Prescription Opioid Medication Usage for the Treatment of Chronic Pain at Three Medical Cannabis Practice Sites

  This study consists of a cross-sectional survey (observational study based on questionnaires) whose objective was to determine how the beginning of the use of medicinal cannabis influences the consumption of prescribed opioids in patients with chronic pain. The research collected data through a convenience sample obtained online from three affiliated medical cannabis clinics in the United States (located in the states of Maine and Massachusetts). Of the 1,181 patients who responded to the survey, 525 met the inclusion criteria: they suffered from chronic pain and had been using prescription opioids continuously for at least three months before introducing adjuvant cannabis therapy.

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• Medicinal Cannabis for the Treatment of Chronic Refractory Pain: An Investigation of the Adverse Event Profile and Health-Related Quality of Life Impact of an Oral Formulation

  This observational, cross-sectional study investigated the safety, tolerability, and clinical efficacy of an oral oil formulation containing a balanced ratio of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). The research analyzed real-world data collected from 151 adult patients in Australia who had suffered from refractory chronic pain for at least 3 months and who had not had success with conventional first-line analgesic treatments. The study collected clinical data on physician-documented adverse events (AEs) and tracked metrics of health-related quality of life (HRQoL), sleep quality, and fatigue scores reported directly by participants.

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• Cannabidiol for Pain Treatment: Focus on Pharmacology and Mechanism of Action

  This article consists of a detailed scientific review focused on mapping the intricate molecular mechanisms and pharmacodynamic profile by which cannabidiol (CBD) acts as an analgesic and anti-inflammatory agent. The authors highlight that, unlike Δ9-THC (the most abundant component of the plant), CBD does not induce intoxication or the psychotropic behavioral effects characteristic of drugs of abuse, which makes it highly attractive for clinical pain management.

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• Cannabigerol (CBG): A Comprehensive Review of Its Molecular Mechanisms and Therapeutic Potential

  This article consists of a comprehensive scientific review focused on mapping the pharmacological properties, molecular signaling mechanisms and broad clinical potential of cannabigerol (CBG), a phytocannabinoid of growing medical interest derived from the Cannabis sativa plant. The main advantage of CBG is the fact that it is a non-psychotropic compound, which means that, unlike the well-known Δ9-tetrahydrocannabinol (THC), it does not induce inebriating or intoxicating effects, qualifying it as a highly safe alternative for the clinical environment.

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• A novel phytocannabinoid isolated from Cannabis sativa L. with an in vivo cannabimimetic activity higher than Δ9-tetrahydrocannabinol: Δ9-Tetrahydrocannabiphorol

  This study describes the discovery, isolation and complete chemical characterization of a previously unknown natural phytocannabinoid, extracted from a variety of medicinal cannabis, named (-)-trans-Δ9-tetrahydrocannabiphorol (Δ9-THCP). Structurally, Δ9-THCP shares the same molecular structure as traditional Δ9-THC, however, it has an extended seven-carbon alkyl side chain (as opposed to THC's five-carbon chain). The length of this side chain is crucial in determining the affinity and biological activity of the compound towards the body's receptors. In addition to THCP, researchers were able to isolate and identify the corresponding homologue of cannabidiol with seven carbons in the side chain, called cannabidiphorol (CBDP).

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• Potential role of cannabidiol in Parkinson's disease by targeting the WNT/β-catenin pathway, oxidative stress and inflammation

  This article consists of a scientific review focused on detailing the neuroprotective properties of cannabidiol (CBD) in the context of Parkinson's Disease (PD). PD is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars Compacta, a process intimately driven by neuroinflammation and oxidative stress.

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• Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) for chronic insomnia disorder ('CANSLEEP' trial): protocol for a randomised, placebo-controlled, double-blinded, proof-of-concept trial

  This article presents the description and structural methodology (clinical protocol) of a pilot trial called the "CANSLEEP" trial. The aim of the research project was to establish a rigorous method for evaluating the safety and short-term acute effects of a single dose of an oral oil solution (termed 'ETC120', containing 10 mg THC and 200 mg CBD) on sleep and daytime functions in patients diagnosed with chronic insomnia disorder.

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• Treating insomnia symptoms with medicinal cannabis: a randomized, crossover trial of the efficacy of a cannabinoid medicine compared with placebo

  This study consists of a pioneering crossover, double-blind, randomized, placebo-controlled clinical trial designed to evaluate the safety and efficacy of a specific formulation of medicinal cannabis (ZTL-101) in relieving symptoms in adults diagnosed with chronic insomnia. During the protocol, 24 eligible participants sublingually self-administered nightly doses of active medication or placebo for two consecutive weeks for each condition.

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• Cannabidiol is a partial agonist at dopamine D2High receptors, predicting its antipsychotic clinical dose

  This laboratory study investigated the neurobiological mechanisms behind the antipsychotic properties of cannabidiol (CBD). Historically, all antipsychotic medications used in the management of schizophrenia act by interfering with the action of dopamine at D2 receptors. However, landmark clinical trials demonstrated that the administration of 800 to 1000 mg of CBD daily was able to alleviate the signs and symptoms of psychosis in a manner equivalent to traditional antipsychotics, even without CBD being known to interact with dopaminergic pathways. To unravel this paradox, the author carried out pharmacological competition tests using tritiated domperidone to mark D2 receptors in tissues of the cerebral striatum of rats.

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• Role of Cannabidiol for Improvement of the Quality of Life in Cancer Patients: Potential and Challenges

  This comprehensive scientific review analyzes the molecular mechanisms, antitumor properties and clinical efficacy of cannabidiol (CBD) in mitigating severe symptoms caused by cancer and aggressive oncological treatments, such as pain, sleep disorders and anxiety. The work compiles evidence obtained from in vitro (cell cultures) and in vivo (mouse animal models) assays to uncover the cellular signaling pathways and molecular targets that underlie the antitumor action of CBD.

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• Synergistic Interactions of Cannabidiol with Chemotherapeutic Drugs in MCF7 Cells: Mode of Interaction and Proteomics Analysis of Mechanisms

  This in vitro study evaluated the potential of cannabidiol (CBD) as a cytotoxic agent and its ability to act synergistically with five chemotherapy drugs widely used in the treatment of breast cancer: docetaxel (DOC), doxorubicin (DOX), paclitaxel (PTX), vinorelbine (VIN) and 7-ethyl-10-hydroxycamptothecin (SN-38). The experiments were conducted on human breast adenocarcinoma cell lines (MCF7 cells), applying different mathematical models to quantify pharmacological synergy.

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• Cannabidiol—from Plant to Human Body: A Promising Bioactive Molecule with Multi-Target Effects in Cancer

  This article consists of a comprehensive scientific review developed with the aim of compiling and updating evidence on the antitumor properties and multi-target effects of cannabidiol (CBD) in various types of cancer. The authors highlight that although the Cannabis sativa L. plant harbors more than 100 phytocannabinoids, medical attention focuses on THC and CBD. The great advantage of CBD compared to THC is the absence of psychotropic properties, which enables its safe application in the oncology clinical environment.

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• Repurposing Cannabidiol as a Potential Drug Candidate for Anti-Tumor Therapies

  This study consists of a review article that compiles the growing scientific evidence on the potential of cannabidiol (CBD) — the main non-psychoactive compound of the Cannabis sativa plant — as a promising therapeutic agent against cancer. The work synthesizes the results of multiple preclinical and translational studies, detailing the diverse molecular pathways by which CBD is capable of targeting cancer cells.

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• Cannabidiol rather than Cannabis sativa extracts inhibit cell growth and induce apoptosis in cervical cancer cells

  This in vitro study aimed to compare the antiproliferative and cytotoxic effects of the crude extract of the Cannabis sativa plant (prepared with solvents such as hexane and butanol) in relation to its main isolated compound, cannabidiol (CBD), in human cervical cancer cell lines (specifically the SiHa, HeLa and ME-180 cell lines). Cervical cancer is one of the most lethal neoplasms among black women, which demands the urgent development of new therapeutic strategies.

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• Cannabidiol Exerts a Neuroprotective and Glia-Balancing Effect in the Subacute Phase of Stroke

  This experimental preclinical study investigated the neuroprotective efficacy and anti-inflammatory properties of cannabidiol (CBD) on glial cells during the subacute phase of focal cerebral ischemia (CVA). Using transgenic mice and advanced in vivo two-photon laser scanning microscopy techniques, researchers performed real-time monitoring of astroglial calcium (Ca²+) signaling and microglial dynamics in the somatosensory cortex of animals after stroke.

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• Safety and Efficacy of Cannabis in Autism Spectrum Disorder

  This article consists of a scientific commentary and critical analysis of a previous observational study conducted in Israel, which evaluated the safety and efficacy of medical cannabis treatment in 188 patients with Autism Spectrum Disorder (ASD) over six months.

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• Cannabinoid treatment for autism: a proof-of-concept randomized trial

  This randomized, double-blind, placebo-controlled clinical trial (proof-of-concept study) evaluated the efficacy and safety of two oral cannabinoid solutions in managing symptoms in 150 children and adolescents (aged 5 to 21 years) diagnosed with Autism Spectrum Disorder (ASD) who presented moderate to severe behavioral problems. Volunteers were divided to receive for 12 weeks: a whole plant extract with a CBD/THC ratio of 20:1; purified cannabinoids (pure CBD and THC) in the same ratio of 20:1; or placebo.

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• CBD-enriched cannabis for autism spectrum disorder: an experience of a single center in Turkey and reviews of the literature

  This study combined observational clinical follow-up and a detailed literature review to evaluate the efficacy and safety of using CBD-rich Cannabis extracts in the management of Autism Spectrum Disorder (ASD). The practical part of the research followed 33 children and adolescents (27 boys and 6 girls) diagnosed with autism in Turkey over a two-year period (between 2018 and 2020). Patients used medicinal cannabis preparations in a ratio of 20 parts CBD to 1 part THC, with an average dosage of 3.8 mg/kg per day.

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• Oral Cannabidiol Use in Children With Autism Spectrum Disorder to Treat Related Symptoms and Co-morbidities

  This observational and prospective clinical study aimed to evaluate the efficacy and safety of administering cannabidiol (CBD) oil orally for the management of comorbidities and behavioral symptoms in children and adolescents diagnosed with Autism Spectrum Disorder (ASD).

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• Cannabidiol as a Potential Treatment for Anxiety and Mood Disorders: Molecular Targets and Epigenetic Insights from Preclinical Research

  This article consists of a review of the preclinical literature focused on mapping the molecular targets and neurobiological mechanisms that support the anxiolytic and antidepressant properties of cannabidiol (CBD). The authors summarize a series of research based on animal models, directly connecting the molecular pharmacology of the compound to the behavioral improvements observed in anxiety and depression.

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• Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients

  This pioneering, double-blind, randomized clinical trial investigated the acute effects of cannabidiol (CBD) on anxiety generated by stressful performance situations in humans. The study specifically evaluated patients with Social Anxiety Disorder (SAD / Social Phobia) who had never undergone previous psychiatric treatment. To do this, participants underwent a Public Speaking Simulation Test (TSFP). A total of 24 patients with SAD were divided to receive a single dose of CBD (600 mg) or placebo, while a group of 12 healthy volunteers performed the same test as controls, without receiving any medication.

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• The role of tetrahydrocannabivarin (THCV) in metabolic disorders: A promising cannabinoid for diabetes and weight management

  This article is a scientific review focused on the pharmacological properties and therapeutic potential of Δ9-tetrahydrocannabivarin (Δ9-THCV), a non-psychotropic cannabinoid derived from the Cannabis sativa plant, in the management of metabolic disorders such as obesity and type 2 diabetes. Unlike classic THC, which strongly binds to CB1 receptors and stimulates appetite and fat storage, THCV presents a differentiated dual action, acting mainly as a neutral receptor antagonist type 1 cannabinoid (CB1) and type 2 receptor partial agonist (CB2).

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• Δ9-Tetrahydrocannabivarin (THCV): a commentary on potential therapeutic benefit for the management of obesity and diabetes

  This article is a commentary and literature review focused on the unique pharmacological properties of Δ9-tetrahydrocannabivarin (Δ9-THCV), highlighting it as a viable alternative for the control of obesity and type 2 diabetes. The main advantage of THCV over common THC is that it does not present unwanted psychotropic effects.

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• The cannabinoid Δ9-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity

  This preclinical study investigated the metabolic effects of the phytocannabinoid Δ9-tetrahydrocannabivarin (Δ9-THCV) using two animal models of obesity: diet-induced obese (DIO) mice and genetically obese (ob/ob) mice. THCV acts as a neutral antagonist of the cannabinoid receptor type 1 (CB1), which differentiates it from older synthetic compounds (such as rimonabant) that caused serious psychiatric side effects.

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• Effects of ∆9-tetrahydrocannabinol on aversive memories and anxiety: a review from human studies

  This study consists of a systematic review of the scientific literature that brought together and analyzed multiple clinical trials and previous experimental research carried out strictly on human beings (healthy volunteers and patients diagnosed with Post-Traumatic Stress Disorder - PTSD). The objective was to map and discuss the impacts of THC on anxiety and the extinction of aversive or traumatic memories.

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• Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders

  This work is a broad review of scientific literature focused on the neuropsychiatric properties of cannabidiol (CBD). The authors systematically analyze the anxiolytic, antidepressant and antipsychotic properties demonstrated by the compound both in animal models (rodents) and in preliminary clinical trials with humans. The study highlights that, unlike THC, CBD exhibits a highly safe pharmacological profile and is devoid of any potential for abuse or chemical dependency.

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• Cannabidiol in Anxiety and Sleep: A Large Case Series

  This retrospective clinical study evaluated whether the use of cannabidiol (CBD) can help improve anxiety and sleep quality in a real clinical population. The research consisted of analyzing the medical records of 103 adult patients in a psychiatric clinic, who received CBD as a complementary treatment to their usual therapies. From this group, the final sample focused on 72 adults whose main complaints were anxiety (47 patients) or poor quality sleep (25 patients). The most common dose administered was 25 mg of CBD capsules per day.

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• Cannabidiol Prevents Spontaneous Fear Recovery after Extinction and Ameliorates Stress-Induced Extinction Resistance

  This preclinical study investigated the effects of systemic cannabidiol (CBD) treatment on fear memory in rats subjected to Pavlov's auditory classical conditioning. The objective was to analyze the action of CBD against two of the main barriers found in the treatment of anxiety and post-traumatic stress disorders (PTSD) via exposure therapies: the return of fear over time (spontaneous recovery) and resistance to extinction caused by stress (immediate extinction deficit - IED).

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• Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration–effect relations using the IB-de-risk tool

  This study consists of a systematic review designed with the aim of predicting the optimal therapeutic window for the anxiolytic effects of CBD in humans from translational data. The authors conducted a rigorous screening integrating pharmacokinetic (absorption and levels in the body) and pharmacodynamic (biological effects) data from 87 previous studies that evaluated isolated CBD in humans, mice and rats.

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• Cannabidiol as a Potential Treatment for Anxiety Disorders

  This work is a comprehensive review of the scientific literature that evaluated both preclinical studies (with laboratory animals) and clinical studies (with humans) to determine the potential of CBD in treating a wide range of anxiety disorders.

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• Overview of cannabidiol (CBD) and its analogues: Structures, biological activities, and neuroprotective mechanisms in epilepsy and Alzheimer's disease

  This article is a comprehensive review of medicinal chemistry. Its main objective was to compile the chemical structures, biological activities and hidden molecular mechanisms that make CBD and its analogues strong drug candidates against epilepsy and neurodegenerative diseases, with a main focus on Alzheimer's Disease (AD).

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• Effects of ∆9-tetrahydrocannabinol on aversive memories and anxiety: a review from human studies

  Unlike the first article (which was a practical experiment with animals), this work is a review of the scientific literature. The authors gathered, analyzed and discussed the results of multiple clinical trials and previous experimental studies carried out exclusively on humans (healthy volunteers and patients with Post-Traumatic Stress Disorder - PTSD). The objective was to map how THC influences anxiety and the extinction of aversive or traumatic memories.

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• Cannabidiol Treatment Improves Glucose Metabolism and Memory in Streptozotocin-Induced Alzheimer's Disease Rat Model: A Proof-of-Concept Study

  The objective of this proof-of-concept study was to evaluate the effect of Cannabidiol (CBD) treatment on cerebral glucose metabolism and memory, using an animal model (male Wistar rats) for Alzheimer's Disease (AD) induced by intracerebroventricular injection of streptozotocin (STZ).

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