BACKGROUND No therapeutics have yet been proven effective for the treatment of mild-illness caused by SARS-CoV-2. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be more efficacious than no-treatment for outpatients with mild Covid-19. METHODS We conducted a multicenter, open label, randomized controlled trial in Catalonia (Spain) between March 17, and May 26, 2020. Eligible Covid-19 cases were non-hospitalized adult patients with recently confirmed SARS-CoV-2 infection and less than five days of symptoms. Patients were assigned to receive HCQ (800 mg on day 1, followed by 400 mg once daily for 6 days) or no antiviral treatment (not-placebo controlled). Study outcomes were the reduction of viral RNA load in nasopharyngeal swabs up to 7 days after treatment start, patient disease progression using the WHO scale up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days. RESULTS A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD 12.6), mean viral load at baseline was 7.90 (SD 1.82) Log10 copies/mL, and median time from symptom onset to randomization was 3 days. No significant differences were found in the mean reduction of viral load at day 3 (-1.41 vs. -1.41 Log10 copies/mL in the control and intervention arm, respectively; difference 0.01 [95% CI -0.28;0.29]) or at day 7 (-3.37 vs. -3.44; d –0.07 [-0.44;0.29]). This treatment regimen did not reduce risk of hospitalization (7.1%, control vs. 5.9%, intervention; RR 0.75 [0.32;1.77]) nor shortened the time to complete resolution of symptoms (12 days, control vs. 10 days, intervention; p = 0.38). No relevant treatment-related AEs were reported. CONCLUSIONS In patients with mild Covid-19, no benefit was observed with HCQ beyond the usual care.

BackgroundThe growing concern about cannabis use, the most commonly used illicit drug worldwide, has led to a significant increase in the number of human studies using neuroimaging techniques to determine the effect of cannabis on brain structure and function. We conducted a systematic review to assess the evidence of the impact of chronic cannabis use on brain structure and function in adults and adolescents.MethodsPapers published until August 2012 were included from EMBASE, Medline, PubMed and LILACS databases following a comprehensive search strategy and pre-determined set of criteria for article selection. Only neuroimaging studies involving chronic cannabis users with a matched control group were considered.ResultsOne hundred and forty-two studies were identified, of which 43 met the established criteria. Eight studies were in adolescent population. Neuroimaging studies provide evidence of morphological brain alterations in both population groups, particularly in the medial temporal and frontal cortices, as well as the cerebellum. These effects may be related to the amount of cannabis exposure. Functional neuroimaging studies suggest different patterns of resting global and brain activity during the performance of several cognitive tasks both in adolescents and adults, which may indicate compensatory effects in response to chronic cannabis exposure.LimitationsHowever, the results pointed out methodological limitations of the work conducted to date and considerable heterogeneity in the findings.ConclusionChronic cannabis use may alter brain structure and function in adult and adolescent population. Further studies should consider the use of convergent methodology, prospective large samples involving adolescent to adulthood subjects, and data-sharing initiatives.

rug addiction is a chronic, relapsing disorder in which compulsive drug-seeking and drug-taking behavior persists despite serious negative consequences. Addictive substances induce pleasant states (euphoria in the initiation phase) or relieve distress. Continued use induces adaptive changes in the central nervous system that lead to tolerance, physical dependence, sensitization, craving, and relapse (Table 1). The addictive drugs discussed here are opioids, cannabinoids, ethanol, cocaine, amphetamines, and nicotine. The World Health Organization 1 and the American Psychiatric Association 2 use the term "substance dependence" rather than "drug addiction." "Drug addiction," however, emphasizes the behavioral connotation of the term and is less likely to be confused with physical dependence. 3 We use both terms interchangeably in this review. The American Psychiatric Association's definition of substance dependence 2 requires a patient to meet at least three of the seven criteria listed in Table 1. Tolerance and physical dependence reflect physiological adaptation to the effects of a drug, whereas the remaining criteria define uncontrollable drug consumption. However, tolerance and physical dependence are neither necessary nor sufficient for a diagnosis of substance dependence. Substance abuse 2 or harmful use, 1 a less severe disorder, may result in dependence. Theories of addiction have mainly been developed from neurobiologic evidence and data from studies of learning behavior and memory mechanisms. They overlap in some aspects and are not mutually exclusive. None of them alone can explain all aspects of addiction. It is not our purpose to present a detailed assessment of these theories, especially because of the complexity of the problem. Generally, addictive drugs can act as positive reinforcers (producing euphoria) or as negative reinforcers (alleviating symptoms of withdrawal or dysphoria). Environmental stimuli (cues) associated with drug use itself can also induce a conditioned response (withdrawal or craving) in the absence of the drug. 4,5 Koob and Le Moal 6,7 have proposed that the organism tries to counteract the effects of a given drug through a vicious circle in which the hedonic set point (the point at which pleasure is achieved) continually changes in response to the administration of the substance. They argue that drug addiction results from dysregulation of the reward mechanism and subsequent allostasis, the ability to achieve stability through change. Robinson and Berridge 8,9 emphasize the dissociation between the incentive value of the drug ("wanting") and its pleasurable or hedonic effects ("liking"), so that the brain system involved in the reward mechanism becomes hypersensitized to both the direct effects of the drug and associated stimuli that are not directly attributable to the drug. This hypersensitization causes pathologic wanting, or craving, independently of the presence of withdrawal symptoms and leads to compulsive drug-seeking and drug-taking behavior. Although liking progressivel...