The potential therapeutic use of some Cannabis sativa plant compounds has been attracting great interest, especially for managing neuropsychiatric disorders due to the relative lack of efficacy of the current treatments. Numerous studies have been carried out using the main phytocannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD). CBD displays an interesting pharmacological profile without the potential for becoming a drug of abuse, unlike THC. In this review, we focused on the anxiolytic, antidepressant, and antipsychotic effects of CBD found in animal and human studies. In rodents, results suggest that the effects of CBD depend on the dose, the strain, the administration time course (acute vs. chronic), and the route of administration. In addition, certain key targets have been related with these CBD pharmacological actions, including cannabinoid receptors (CB1r and CB2r), 5-HT1A receptor and neurogenesis factors. Preliminary clinical trials also support the efficacy of CBD as an anxiolytic, antipsychotic, and antidepressant, and more importantly, a positive risk-benefit profile. These promising results support the development of large-scale studies to further evaluate CBD as a potential new drug for the treatment of these psychiatric disorders.

During the last years, an extraordinary effort has been made to identify biomarkers as potential tools for improving prevention, diagnosis, drug response and drug development in psychiatric disorders. Contrary to other diseases, mental illnesses are classified by diagnostic categories with a broad variety list of symptoms. Consequently, patients diagnosed from the same psychiatric illness present a great heterogeneity in their clinical presentation. This fact together with the incomplete knowledge of the neurochemical alterations underlying mental disorders, contribute to the limited efficacy of current pharmacological options. In this respect, the identification of biomarkers in psychiatry is becoming essential to facilitate diagnosis through the developing of markers that allow to stratify groups within the syndrome, which in turn may lead to more focused treatment options. In order to shed light on this issue, this review summarizes the concept and types of biomarkers including an operational definition for therapeutic development. Besides, the advances in this field were summarized and sorted into five categories, which include genetics, transcriptomics, proteomics, metabolomics, and epigenetics. While promising results were achieved, there is a lack of biomarker investigations especially related to treatment response to psychiatric conditions. This review includes a final conclusion remarking the future challenges required to reach the goal of developing valid, reliable and broadly-usable biomarkers for psychiatric disorders and their treatment. The identification of factors predicting treatment response will reduce trial-and-error switches of medications facilitating the discovery of new effective treatments, being a crucial step towards the establishment of greater personalized medicine.

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Drug treatments available for the management of substance use disorders (SUD) present multiple limitations in efficacy, lack of approved treatments or alarming relapse rates. These facts hamper the clinical outcome and the quality of life of the patients supporting the importance to develop new pharmacological agents. Lately, several reports suggest that cannabidiol (CBD) presents beneficial effects relevant for the management of neurological disorders such as epilepsy, multiple sclerosis, Parkinson’s, or Alzheimer’s diseases. Furthermore, there is a large body of evidence pointing out that CBD improves cognition, neurogenesis and presents anxiolytic, antidepressant, antipsychotic, and neuroprotective effects suggesting potential usefulness for the treatment of neuropsychiatric diseases and SUD. Here we review preclinical and clinical reports regarding the effects of CBD on the regulation of the reinforcing, motivational and withdrawal-related effects of different drugs of abuse such as alcohol, opioids (morphine, heroin), cannabinoids, nicotine, and psychostimulants (cocaine, amphetamine). Furthermore, a special section of the review is focused on the neurobiological mechanisms that might be underlying the ‘anti-addictive’ action of CBD through the regulation of dopaminergic, opioidergic, serotonergic, and endocannabinoid systems as well as hippocampal neurogenesis. The multimodal pharmacological profile described for CBD and the specific regulation of addictive behavior-related targets explains, at least in part, its therapeutic effects on the regulation of the reinforcing and motivational properties of different drugs of abuse. Moreover, the remarkable safety profile of CBD, its lack of reinforcing properties and the existence of approved medications containing this compound (Sativex®, Epidiolex®) increased the number of studies suggesting the potential of CBD as a therapeutic intervention for SUD. The rising number of publications with substantial results on the valuable therapeutic innovation of CBD for treating SUD, the undeniable need of new therapeutic agents to improve the clinical outcome of patients with SUD, and the upcoming clinical trials involving CBD endorse the relevance of this review.

Nowadays, cannabis is the most consumed illicit drug. The global prevalence of the use of cannabis in 2017 was estimated in 188 million of people, 3.8% of worldwide population. Importantly, the legalization of cannabis in different countries, together with the increase in the apparent safety perception, may result in a great variety of health problems. Indeed, an important concern is the increase in cannabis use among pregnant and breastfeeding women, especially since the content of delta9-tetrahidrocannabinol (THC) is currently around 2-fold higher than it was 15-20 years ago. The purpose of this study was to review cannabis use during pregnancy and breastfeeding including epidemiological aspects, therapeutic or preventive strategies, and experimental considerations and results from animal models of perinatal cannabis exposure to analyze the underlying neurobiological mechanisms and to identify new therapeutic approaches. A recent report revealed that among pregnant women aged 15-44, last month cannabis use prevalence was over 4.9%, raising to 8.5% in the 18-25-year-old age range. Pre-and post-natal exposure to cannabis may be associated with critical alterations in the newborn infants that are prolonged throughout childhood and adolescence. Briefly, several reports revealed that perinatal cannabis exposure was associated with low birth weight, reduction in the head circumference, cognitive deficits (attention, learning, and memory), disturbances in emotional response leading to aggressiveness, high impulsivity, or affective disorders, and higher risk to develop a substance use disorder. Furthermore, important neurobiological alterations in different neuromodulatory and neurotransmission systems have been associated with cannabis consumption during pregnancy and lactation. In spite of the evidences pointing out the negative behavioral and neurobiological consequences of cannabis use in pregnant and breastfeeding women, there are still limitations to identify biomarkers that could help to establish preventive or therapeutic approaches. It is difficult to define the direct association specifically with cannabis, avoiding other confusing factors, co-occurrence of other drugs consumption (mainly nicotine and alcohol), lifestyle, or socioeconomic factors. Therefore, it is necessary to progress in the characterization of short-and long-term cannabis exposure-related disturbances.