Antonio Zuardi

• University of São Paulo

Background: Emerging evidence supports cannabidiol (CBD) as a promising therapeutic compound for various health conditions, despite its approval as a medication (product for medical purposes) remaining restricted to a limited range of clinical indications. Simultaneously, the regulation of cannabis-derived products for medicinal and recreational us...

Introduction Even though the long-term effects of the COVID-19 pandemic on healthcare workers’ mental health remain unknown, such effects might negatively impact health services and patient safety, especially in countries like Brazil, where there is little investment in public health policies. Objectives To assess how the mental health indicators...

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...

Introduction: Diabetic neuropathies are the most prevalent chronic complications of diabetes, characterized by pain and substantial morbidity. Although many drugs have been approved for the treatment of this type of pain, including gabapentin, tramadol (TMD), and classical opioids, it is common to report short-term results or potentially severe sid...

This study aimed to: (a) monitor the progression of symptoms of mental health burden among frontline workers caring for COVID-19 patients in Brazil during the two waves of the pandemic, considering the number of new cases and deaths, and; (b) to verify the different mental health outcomes and potential associations with current burnout symptoms. A...

Background Cannabidiol (CBD) is a non-intoxicating substance present in the extract of Cannabis sativa popularised by its therapeutic potential. A limited number of neuroimaging studies have investigated CBD effects on brain function primarily in healthy individuals, people with early/ clinical high risk of psychosis, and social anxiety disorder. A...

The neurobiological mechanisms underlying the effects of delta-9-tetrahydrocannabinol (THC) remain unclear. Here, we examined the spatial acute effect of THC on human on regional brain activation or blood flow (hereafter called ‘activation signal’) in a ‘core’ network of brain regions from 372 participants, tested using a within-subject repeated me...

Background: Cannabidiol (CBD) is one of the main nonpsychoactive components of Cannabis sativa and may represent an alternative treatment for Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) in patients with Parkinson's disease (PD) and REM (Rapid Eye Movement) sleep behavior disorder (RBD). Objective: Our purpose was a post hoc exploratory a...

Studies with cannabidiol (CBD) suggest that this compound has anxiolytic properties and may mediate the reconsolidation and extinction of aversive memories. The objective of this study was to test whether the administration of CBD 300 mg before the recall of traumatic events attenuated symptoms usually induced by recall in subjects diagnosed with p...

Health care workers from low- and middle-income countries have been playing a critical role in overcoming the challenges related to the COVID-19 pandemic; yet little is known about the relationship between workplace protections and wellbeing of Brazilian health care workers during the pandemic. This study aimed to evaluate whether Brazilian health...

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 pa...

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). M...

Oxaliplatin-induced neurotoxicity is expressed as a dose-limiting peripheral sensory neuropathy (PSN). Cannabinoid substances have been investigated for the analgesic effect. This study aimed to investigate the role of cannabinoid receptors in oxaliplatin-associated PSN. Swiss male mice received nine oxaliplatin injections (2 mg/kg, i.v.). Mechanic...

Clinical and preclinical evidence has indicated that estrogen depletion leads to memory impairments and increases the susceptibility to neural damage. Here, we have sought to investigate the effects of Cannabidiol (CBD) a non-psychotomimetic compound from Cannabis sativa, on memory deficits induced by estrogen depletion in rats, and its underlying...

The objective was to compare the mental health indicators of health workers providing care to individuals with COVID-19 in Brazil, considering sociodemographic and occupational variables and the risk perception of contamination by the Sars-CoV-2 of workers from different professions, identifying risk and protective factors. A sample of 916 health w...

Antidepressants such as serotonin uptake inhibitors are the first-line pharmacological treatment for chronic stress-related psychiatric disorders. However, their late-onset therapeutic action and frequent side effects, however, are important challenges for clinicians and patients. Besides, around 30% of major depression patients are considered trea...

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria are a major worldwide public health problem. In the last decades, resistance to last-resort antibiotics such as polymyxin B (PB) have been increasingly observed among these superbugs, compromising the effectiveness of antimicrobial therapy. The present study aimed (i) to assess...

Schizophrenia and autism spectrum disorders (ASD) are psychiatric neurodevelopmental disorders that cause high levels of functional disabilities. Also, the currently available therapies for these disorders are limited. Therefore, the search for treatments that could be beneficial for the altered course of the neurodevelopment associated with these...

Objective: To investigate associations between the percentage and severity of mental disorders (MD) and three different primary health care (PHC) strategies in Brazil: traditional care (TC), the Family Health Strategy (FHS), and FHS with shared mental health care (FHS+SC). Methods: Random samples were selected from three different areas of a Brazi...

Background Cannabidiol (CBD) is one of the main components of Cannabis sativa and has anxiolytic properties, but no study has been conducted to evaluate the effects of CBD on anxiety signs and symptoms in patients with Parkinson’s disease (PD). This study aimed to evaluate the impacts of acute CBD administration at a dose of 300 mg on anxiety measu...

Introduction Previous studies have shown attenuated cortisol awakening response in patients with posttraumatic stress disorder (PTSD). Case Presentation A 15-year-old girl, a survivor of acute sexual violence, received a 7-day oral treatment with cannabidiol. She was followed-up from the first 24 hours after the event for 6 months, for assessment...

Social anxiety disorder (SAD), or social phobia, is one of the most common types of anxiety disorder, with a lifetime prevalence that can reach 15%. Pharmacological treatments for SAD have moderate efficacy and are associated with significant adverse reactions. Therefore, recent studies have focused on searching for new treatments for this disorder...

Introduction: Recent studies have suggested that cannabidiol (CBD) could interconvert into Delta-8- and Delta-9- tetrahydrocannabinol. Materials and Methods: Thus, we tested the plasma samples of 120 healthy human subjects (60 male and 60 female), 60 in fasting and the other 60 under normal feeding conditions after acute administration of an oral s...

Reconsolidation is the return of a memory to a transient state of lability, following memory consolidation, that can occur when memories are evoked. During the process of reconsolidation, memories may be modified by different means, including the administration of drugs, during a period called the ''reconsolidation window”. This process has been wi...

Objective: Current pharmacotherapy of Parkinson's disease (PD) is palliative and unable to modify the progression of neurodegeneration. Treatments that can improve patients' quality of life with fewer side effects are needed, but not yet available. Cannabidiol (CBD), the major non-psychotomimetic constituent of cannabis, has received considerable...

Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by motor symptoms such as bradykinesia, rest tremor, postural disturbances, and rigidity. PD is also characterized by non-motor symptoms such as sleep disturbances, cognitive deficits, and psychiatric disorders such as psychosis, depression, and anxiety. The pharmacologi...

Asthma is characterized by chronic lung inflammation and airway hyperresponsiveness. Asthma remains a major public health problem and, at present, there are no effective interventions capable of reversing airway remodelling. Cannabidiol (CBD) is known to exert immunomodulatory effects through the activation of cannabinoid-1 and − 2 (CB1 and CB2) re...

Objective: Cannabidiol (CBD), one of the non-psychotomimetic compounds of Cannabis sativa, causes anxiolytic-like effects in animals, with typical bell-shaped dose-response curves. No study, however, has investigated whether increasing doses of this drug would also cause similar curves in humans. The objective of this study was to compare the acut...

Background: Among the many cannabinoids in the cannabis plant, cannabidiol (CBD) is a compound that does not produce the typical subjective effects of marijuana. Objectives: The aim of the present review is to describe the main advances in the development of the experimental and clinical use of cannabidiol CBD in neuropsychiatry. Methods: A non-sys...

Iron accumulation in the brain has been recognized as a common feature of both normal aging and neurodegenerative diseases. Cognitive dysfunction has been associated to iron excess in brain regions in humans. We have previously described that iron overload leads to severe memory deficits, including spatial, recognition, and emotional memory impairm...

The endocannabinoid retrograde signaling pathway is widely expressed in the central nervous system, where it plays major roles in regulating synaptic plasticity (excitatory and inhibitory) through long-term potentiation and long-term depression. The endocannabinoid system (ECS) components—cannabinoid receptors, endocannabinoids and synthesis/degrad...

Schizophrenia is considered a debilitating neurodevelopmental psychiatric disorder and its pharmacotherapy remains problematic without recent major advances. The development of interventions able to prevent the emergence of schizophrenia would therefore represent an enormous progress. Here, we investigated whether treatment with cannabidiol (CBD –...

Cannabidiol (CBD) is a non-psychotomimetic compound of the Cannabis sativa that has been used for the treatment of severe epilepsy as well as other diseases of nervous system. However, toxicity studies of CBD have great relevance to guarantee the patients safety. In this context, morphological analyses of zebrafish can contribute to evaluate the te...

Objective: To evaluate whether a short compilation of screening tools for specific disorders could identify Mental or Emotional Disorders (MEDs) in the general population. Methods: We selected validated screening tools for the most prevalent MEDs. In order to be selected, these tools should maintain the psychometric properties of the complete instr...

Cannabidiol (CBD) is a component of Cannabis sativa that has a broad spectrum of potential therapeutic effects in neuropsychiatric and other disorders. However, few studies have investigated the possible interference of CBD on the sleep-wake cycle. The aim of the present study was to evaluate the effect of a clinically anxiolytic dose of CBD on the...

Background Laboratory rodents and human studies have demonstrated that cannabidiol (CBD) presents antipsychotic effects. Several mechanisms of action have been associated to CBD effects. Most of the studies that have investigated these mechanisms have been performed in vitro and their relevance for the in vivo effects of this drug is still uncertai...

Background Preclinical and clinical studies have suggested the involvement of the endocannabinoid system in schizophrenia pathobiology. In addition, in vitro studies have shown the molecular pathways and biological processes associated with cannabinoids’ effects in some cell types, such as glial cell cultures. Thus, the effects of cannabinoid drugs...

Evidence has demonstrated iron accumulation in specific brain regions of patients suffering from neurodegenerative disorders, and this metal has been recognized as a contributing factor for neurodegeneration. Using an experimental model of brain iron accumulation, we have shown that iron induces severe memory deficits that are accompanied by oxidat...

Aim To compare the impact of three different approaches to primary care mental health on the prevalence of mental disorders. Background Millions of people suffer from mental disorders. As entry point into the health service, primary healthcare plays an important role in providing mental health prevention and treatment. Methods Random sample of ho...

Background: Recent evidence has shown improvements in schizophrenia symptoms after the infusion of sodium nitroprusside (SNP), a nitric oxide (NO) donor. In the rat model of schizophrenia using ketamine injection, pretreatment with SNP seems to prevent behavioral changes associated with positive symptoms for up to one week. Objective: We investiga...

Background: Pain involves different brain regions and is critically determined by emotional processing. Among other areas, the rostral anterior cingulate cortex (rACC) is implicated in the processing of affective pain. Drugs that interfere with the endocannabinoid system are alternatives for the management of clinical pain. Cannabidiol (CBD), a phy...

The purpose of this study was to investigate whether the anxiolytic effect of cannabidiol (CBD) in humans follows the same pattern of an inverted U-shaped dose-effect curve observed in many animal studies. Sixty healthy subjects of both sexes aged between 18 and 35 years were randomly assigned to five groups that received placebo, clonazepam (1 mg)...

Cannabidiol (CBD), a major cannabinoid of hemp, does not bind to CB1 receptors and is therefore devoid of psychotomimetic properties. Under acidic conditions, CBD can be transformed to delta9-tetrahydrocannabinol (THC) and other cannabinoids. It has been argued that this may occur also after oral administration in humans. However, the experimental...

The present study reports the behavioral, electrophysiological, and neuropathological effects of cannabidiol (CBD), a major non-psychotropic constituent of Cannabis sativa, in the intrahippocampal pilocarpine-induced status epilepticus (SE) rat model. CBD was administered before pilocarpine-induced SE (group SE+CBDp) or before and after SE (group S...

Representative photo of a rat inside the open field apparatus (A). Rat movement is detected by a series of infrared sensors (arrows), being three lower sensors that detect horizontal movement (white arrows) and one high sensor (black arrow) that detects vertical movements (i.e., rises). The apparatus is attached to a computer, and the software prov...

Cannabidiol (CBD) plasma levels. CBD plasma concentration pre- and post-SE induction, measured with liquid phase gas chromatography. At day 0 (pre-SE), all rats injected with CBD (groups CBD, SE+CBDp, and SE+CBDt) had detectable CBD plasma 90 min post infusion. At days 1 and 3, CBD levels decreased in the pretreatment group (SE+CBDp, medium green b...

Local field potential (LFP) register equipment. In A is shown a rat attached to the register cable inside the register box, which in turn is attached to an analogic-digital converter connected to a computer (B). Inside the box there is a webcam, a light and a cooler (A).

The prefrontal cortex (PFC), amygdala and hippocampus display a coordinated activity during acquisition of associative fear memories. Evidence indicates that PFC engagement in aversive memory formation does not progress linearly as previously thought. Instead, it seems to be recruited at specific time windows after memory acquisition, which has imp...

Background Secondary interventions are implemented within a short interval following the occurrence of traumatic events with the purpose of preventing the onset of PTSD. Objective Analyze the results of studies that assessed post-trauma interventions in adults aimed at preventing the onset of PTSD or symptoms related to PTSD. Methods We performed...

Objectives: To compare outcomes from Brazilian patients with anxiety and/or depression followed by primary care teams working with and without access to mental health integrated care. Method: The study was conducted with patients from 4 Brazilian Family Health Strategy teams. Only 2 of these teams had access to an integrated care model. A psychiatr...

Animal studies and preliminary clinical trials have shown that cannabidiol (CBD)-enriched extracts may have beneficial effects for children with treatment-resistant epilepsy. However, these compounds are not yet registered as medicines by regulatory agencies. We describe the cases of two children with treatment-resistant epilepsy (Case A with left...

Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects. In Parkinson’s disease patients, CBD is able to attenuate the psychotic symptoms induced by L-DOPA and to improve quality of life. Repeated administration of reserpine in rodents induces m...

Schizophrenia is a severe psychiatric disorder that involves positive, negative and cognitive symptoms. Prepulse inhibition of startle reflex (PPI) is a paradigm that assesses the sensorimotor gating functioning and is impaired in schizophrenia patients as well as in animal models of this disorder. Recent data point to the participation of the endo...

[This corrects the article DOI: 10.1371/journal.pone.0158779.].

Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects i...

To date, pharmacological treatments for mood and anxiety disorders and for drug dependence show limited efficacy, leaving a large number of patients suffering severe and persistent symptoms. Preliminary studies in animals and humans suggest that ayahuasca, psilocybin and lysergic acid diethylamide (LSD) may have antidepressive, anxiolytic, and anti...

Background: Structural brain abnormalities in schizophrenia have been repeatedly demonstrated in magnetic resonance imaging (MRI) studies, but it remains unclear whether these are static or progressive in nature. While longitudinal MRI studies have been traditionally used to assess the issue of progression of brain abnormalities in schizophrenia, i...

Purpose This study aims to verify the impact that the length of stay has on the rates of readmission for patients who were first admitted to various inpatient psychiatric units in a large catchment area in a middle-income country. Methods The study included all patients who were first admitted to the 108 acute psychiatric beds available in the catc...

Since most patients with schizophrenia do not respond properly to treatment, scientific effort has been driven to the development of new compounds acting on pharmacological targets beyond the dopaminergic system. Therefore, the aim is to review basic and clinical research findings from studies evaluating the effects of cannabidiol (CBD), an inhibit...

Cannabidiol (CBD) has been investigated in a wide spectrum of clinical approaches due to its psychopharmacological properties. CBD has low affinity for cannabinoid neuroreceptors and agonistic properties to 5-HT receptors. An interaction between cannabinoid and purinergic receptor systems has been proposed. The purpose of this study is to evaluate...

Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the major constituents of the Cannabis sativa plant, which is frequently consumed by subjects exposed to life-threatening situations to relief their symptomatology. It is still unknown, however, whether THC could also affect the maintenance of an aversive memory formed at that time when take...

Asthma represents a public health problem and traditionally is classified as an atopic disease, where the allergen can induce clinical airway inflammation, bronchial hyperresponsiveness, and reversible obstruction of airways. Studies have demonstrated the presence of T-helper 2 lymphocytes in the lung of patients with asthma. These cells are involv...

Many studies suggest that the substantia nigra, pars reticulata (SNpr), a tegmental mesencephalic structure rich in γ-aminobutyric acid (GABA)- and endocannabinoid receptor-containing neurons, is involved in the complex control of defensive responses through the neostriatum-nigral disinhibitory and nigro-tectal inhibitory GABAergic pathways during...

Objetivo Realizar uma revisão sistemática sobre as características psicométricas de instrumentos breves para rastreamento de múltiplos transtornos mentais em cuidados primários de saúde. Métodos Revisão sistemática da literatura nas bases de dados PubMed, Lilacs, SciELO e ISI, de artigos publicados até abril de 2014, utilizando descritores sobre r...

B y modulating the "glutamate-NO (nitric oxide)-cGMP" pathway," a new paradigm for the treatment of schizophrenia seems to arise. Indeed, our group has recently pub-lished a double-blind placebo (PLB) con-trolled trial showing that an infusion of sodium nitroprusside (SNP), a nitric oxide donor, improved positive, negative, anxiety, and depressive...

Introduction: Parkinson's disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons. Although no neuroprotective treatments for PD have been found to date, the endocannabinoid system has emerged as a promising target. Methods: From a sample of 119 patients consecutively evaluated in a specialized move...

The neuropeptide oxytocin improves the performance in facial emotion recognition tests in healthy volunteers and in individuals with schizophrenia. Different paradigms are used in emotion recognition tasks, engaging different neurobiological bases. To date, the effects of oxytocin in facial emotion matching tasks have not been studied. The objectiv...

Despite decades of study, the etiology and physiopathology of schizophrenia remain unknown. Recent evidence suggests that nitric oxide (NO) may be implicated in schizophrenia. NO is a gas that mediates the release of neurotransmitters, learning, memory, and neurodevelopment. Studies investigating the role of NO in patients with schizophrenia found...

Studies have suggested that the endocannabinoid system is implicated in the pathophysiology of schizophrenia. We have recently reported that Spontaneously Hypertensive Rats (SHRs) present a deficit in social interaction that is ameliorated by atypical antipsychotics. In addition, SHRs display hyperlocomotion — reverted by atypical and typical antip...

Clinical and neurobiological findings suggest that the cannabinoids and the endocannabinoid system may be implicated in the pathophysiology and treatment of schizophrenia. We described that the spontaneously hypertensive rats (SHR) strain presents a schizophrenia behavioral phenotype that is specifically attenuated by antipsychotic drugs, and poten...

We investigated the hypothesis that rimonabant, a cannabinoid antagonist/inverse agonist, would increase anxiety in healthy subjects during a simulation of the public speaking test. Participants were randomly allocated to receive oral placebo or 90 mg rimonabant in a double-blind design. Subjective effects were measured by Visual Analogue Mood Scal...

Objective: To investigate the effects of cannabidiol (CBD) on mitochondrial complex and creatine kinase (CK) activity in the rat brain using spectrophotometry. Method: Male adult Wistar rats were given intraperitoneal injections of vehicle or CBD (15, 30, or 60 mg/kg) in an acute (single dose) or chronic (once daily for 14 consecutive days) regi...

Objectives: a) To perform a systematic and meta-analytic review to verify whether the Simulated Public Speaking Task (SPST) leads to a greater increase in self-rated anxiety than in physiological correlates of anxiety; and b) to compare the results obtained with the SPST with an actual public speaking task involving healthy volunteers. Methods:...

We have recently shown that chronic treatment with cannabidiol (CBD) was able to recover memory deficits induced by brain iron loading in a dose-dependent manner in rats. Brain iron accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson's and Alzheimer's, and has been related to cognitive deficits in anima...

Objective: Anxiety disorders represent an important part of mental health problems in primary care. This literature review seeks to find out whether collaborative care (called “matrix support” in Brazil) assists the treatment of anxiety disorders and/or anxiety symptoms. Methods: We performed a literature search with no time period restriction usin...