RESUMO

OBJECTIVE: The treatment of bipolar depression remains challenging due to the limited effective and safe therapeutic options available; thus, developing newer treatments that are effective and well tolerable is an urgent unmet need. The objective of the present trial was to test 150 to 300 mg/day of cannabidiol as an adjunctive treatment for bipolar depression. METHOD: A randomized, double-blind, placebo-controlled pilot study to assess the efficacy of adjunctive cannabidiol in bipolar depression was used. Efficacy parameters were changes in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 8. Secondary outcomes included response and remission rates, changes in anxiety and psychotic symptoms, and changes in functioning. Patients continued double-blind treatment until week 12 to monitor for adverse effects, laboratory analysis, and manic symptoms. Study registry: NCT03310593. RESULTS: A total of 35 participants were included. MADRS scores significantly decreased from baseline to the endpoint (placebo, -14.56; cannabidiol, -15.38), but there was no significant difference between the groups. Similarly, there were no other significant effects on the secondary outcomes. However, an exploratory analysis showed a significant effect of cannabidiol 300 mg/day in reducing MADRS scores from week 2 to week 8 (placebo, -6.64; cannabidiol, -13.72). There were no significant differences in the development of manic symptoms or any other adverse effects. CONCLUSION: Cannabidiol did not show significantly higher adverse effects than placebo. Despite the negative finding on the primary outcome, an exploratory analysis suggested that cannabidiol should be further studied in bipolar depression in higher doses of at least 300 mg/day and under research designs that could better control for high placebo response.

Assuntos

RESUMO

Introduction: The effects of cannabidiol (CBD) on cognition has been investigated in recent years to determine the therapeutic potential of this cannabinoid for a broad gamut of medical conditions, including neuropsychiatric disorders. The aim of the present study was to perform a systematic review of studies that analyzed the effects of the acute and chronic administration of CBD on cognition in humans and animals both to assess the cognitive safety of CBD and to determine a beneficial potential of CBD on cognition. Methods: The PubMed, Web of Science, PsycINFO, and Scopus databases were searched in December of 2022 for relevant articles using the following combinations of keywords: ("cannabidiol" OR "CBD") AND ("cognition" OR "processing cognitive" OR "memory" OR "language" OR "attention" OR "executive function" OR "social cognition" OR "perceptual motor ability" OR "processing speed"). Results: Fifty-nine articles were included in the present review (36 preclinical and 23 clinical trials). CBD seems not to have any negative effect on cognitive processing in rats. The clinical trials confirmed these findings in humans. One study found that repeated dosing with CBD may improve cognitive in people who use cannabis heavily but not individuals with neuropsychiatric disorders. Considering the context of neuropsychiatric disorders in animal models, CBD seems to reverse the harm caused by the experimental paradigms, such that the performance of these animals becomes similar to that of control animals. Conclusions: The results demonstrate that the chronic and acute administration of CBD seems not to impair cognition in humans without neuropsychiatric disorders. In addition, preclinical studies report promising results regarding the effects of CBD on the cognitive processing of animals. Future double-blind, placebo-controlled, randomized clinical trials with larger, less selective samples, with standardized tests, and using different doses of CBD in outpatients are of particular interest to elucidate the cognitive effects of CBD.

Assuntos

RESUMO

Background: The concept of an "entourage" effect in the cannabis and cannabinoids' field was first introduced in the late 1990s, during a period when most research on medical cannabinoids focused on the effects of isolated cannabinoids, such as cannabidiol and Δ9-tetrahydrocannabinol. Over the past decade, however, with the increased understanding of the endocannabinoid system, the discovery of other phytocannabinoids and their potential therapeutic uses, the term has gained widespread use in scientific reviews and marketing campaigns. Objective: Critically review the application of the term "entourage effect (EE)" in the literature and its endorsement by certain sectors of the cannabis market. Also, explore the perspectives for further interpretation and elaboration of the term based on current evidence, aiming to contribute to a more nuanced understanding of the concept and its implications for cannabinoid-based medicine. Methods: A comprehensive review of the literature was conducted to evaluate the current state of knowledge regarding the entourage effect. Relevant studies and scientific reviews were analyzed to assess the evidence of clinical efficacy and safety, as well as the regulation of cannabinoid-containing product production. Results: The EE is now recognized as a synergistic phenomenon in which multiple components of cannabis interact to modulate the therapeutic actions of the plant. However, the literature provides limited evidence to support it as a stable and predictable phenomenon. Hence, there is also limited evidence to support clinical efficacy, safety, and appropriate regulation for cannabinoid-containing products based on a "entourage" hypothesis. Conclusion: The EE has significant implications for the medical use of cannabinoid-containing products and their prescription. Nevertheless, a critical evaluation of the term's application is necessary. Further research and evidence are needed to establish the clinical efficacy, safety, and regulatory framework for these products. It's crucial that regulators, the pharmaceutical industry, the media, and health care providers exercise caution and avoid prematurely promoting the entourage effect hypothesis as a scientific proven phenomenon for cannabinoids and other cannabis-derived compound combinations.

Assuntos

RESUMO

Objective: To assess whether the effects of oral administration of 300 mg of Cannabidiol (CBD) for 28 days on mental health are maintained for a period after the medication discontinuation. Methods: This is a 3-month follow-up observational and clinical trial study. The data were obtained from two studies performed simultaneously by the same team in the same period and region with Brazilian frontline healthcare workers during the COVID-19 pandemic. Scales to assess emotional symptoms were applied weekly, in the first month, and at weeks eight and 12. Results: The primary outcome was that, compared to the control group, a significant reduction in General Anxiety Disorder-7 Questionnaire (GAD-7) from baseline values was observed in the CBD group on weeks two, four, and eight (Within-Subjects Contrasts, time-group interactions: F1-125 = 7.67; p = 0.006; ηp 2 = 0.06; F1-125 = 6.58; p = 0.01; ηp 2 = 0.05; F1-125 = 4.28; p = 0.04; ηp 2 = 0.03, respectively) after the end of the treatment. Conclusions: The anxiolytic effects of CBD in frontline health care professionals during the COVID-19 pandemic were maintained up to 1 month after the treatment discontinuation, suggesting a persistent decrease in anxiety in this group in the real world. Future double-blind placebo-controlled clinical trials are needed to confirm the present findings and weigh the benefits of CBD therapy against potential undesired or adverse effects.

RESUMO

Cannabidiol (CBD) is a non-psychotomimetic constituent of the Cannabis plant, with potential therapeutic properties for many physical and neuropsychiatric conditions. Isolated CBD has been suggested to have favorable safety and tolerability. Although CBD-related rash is described, few case reports are well documented in the literature, and usually, CBD was used concomitantly with other medications. Thus, we report four women who presented a skin rash after ongoing CBD use. Other causes of these skin rashes were ruled out after conducting an extensive viral and serological detection panel, and three patients had their lesions biopsied. Two patients were re-exposed to the vehicle (MCT) without developing a new skin rash. Therefore, clinicians must be aware of this potential adverse effect of CBD use.

RESUMO

Objectives: We assessed whether administering cannabidiol (CBD) before recalling the traumatic event that triggered their disorder attenuates anxiety in patients with post-traumatic stress disorder (PTSD). As an exploratory pilot analysis, we also investigated whether this effect depends on the nature of the event (sexual vs. nonsexual trauma). Methods: Thirty-three patients of both sexes with PTSD were recruited and randomized 1:1 into two groups. One group received oral CBD (300 mg), and the other received a placebo before listening to a digital audio playback of their previously recorded report of the trigger event. Subjective and physiological measurements were taken before and after recall. We analyzed the data in two subsamples: trigger events involving sexual and nonsexual trauma. Results: In the nonsexual trauma group, the differences between measurements before and after recall were significantly smaller with CBD than placebo; this held true for anxiety and cognitive impairment. However, in the sexual trauma group, the differences were non-significant for both measurements. Conclusion: A single dose of CBD (300mg) attenuated the increased anxiety and cognitive impairment induced by recalling a traumatic event in patients with PTSD when the event involved nonsexual trauma.

RESUMO

Few longitudinal studies assessed the less immediate consequences of the COVID-19 pandemic on health workers' mental health, especially in less developed countries. The objective was to assess the evolution of mental health indicators of Brazilian health workers providing care to COVID-19 patients, considering the beginning and first wave of the pandemic, identifying risk and protective factors. A non-probabilistic sample of health professionals was assessed for 6 months at seven different points in time using standardized instruments to measure anxiety, depression, insomnia, posttraumatic stress, and burnout symptoms. Risk and protective factors were assessed using a questionnaire addressing socio-demographic, clinical, occupational variables, and COVID-19 risk perception. The results indicate high rates for all the indicators (>30%) throughout the follow-up; only anxiety symptoms decreased in the different phases compared to the baseline. Depression and insomnia symptoms showed a significant drop in isolated points of the assessment, which were not maintained at the final follow-up. Burnout indicators concerning emotional exhaustion and depersonalization remained stable (40 and 20%), while professional achievement decreased by approximately 19%. Occupational and personal characteristics (profession and work setting), perceptions regarding protective measures imposed by the institutions, and future professional prospects stood out as risk/protective factors in mental health. Unlike European and Asian countries, where mental distress symptoms tended to decrease over the pandemic, this study's results suggest alarming indicators of mental health problems remaining stable with burnout symptoms on the rise. Hence, the different contexts across countries, with different management resources and investments in health actions, seem to influence workers' mental health differently, demanding constant attention and monitoring and measures to minimize the impacts on individuals and collectives, especially in less developed countries like Brazil.

RESUMO

OBJECTIVES: We assessed whether administering cannabidiol (CBD) before recalling the traumatic event that triggered their disorder attenuates anxiety in patients with post-traumatic stress disorder (PTSD). As an exploratory pilot analysis, we also investigated whether this effect depends on the nature of the event (sexual vs. nonsexual trauma). METHODS: Thirty-three patients of both sexes with PTSD were recruited and randomized 1:1 into two groups. One group received oral CBD (300 mg), and the other received a placebo before listening to a digital audio playback of their previously recorded report of the trigger event. Subjective and physiological measurements were taken before and after recall. We analyzed the data in two subsamples: trigger events involving sexual and nonsexual trauma. RESULTS: In the nonsexual trauma group, the differences between measurements before and after recall were significantly smaller with CBD than placebo; this held true for anxiety and cognitive impairment. However, in the sexual trauma group, the differences were non-significant for both measurements. CONCLUSION: A single dose of CBD (300mg) attenuated the increased anxiety and cognitive impairment induced by recalling a traumatic event in patients with PTSD when the event involved nonsexual trauma.

Assuntos