This study establishes a fetal cannabinoid syndrome model to evaluate the effects of high doses of dronabinol (synthetic THC) during pregnancy and lactation on behavioral and brain changes in male ...and female progeny and their susceptibility to alcohol consumption. Female C57BL/6J mice received dronabinol (10 mg/kg/12 h, p.o.) from gestational day 5 to postnatal day 21. On the weaning day, the offspring were separated by sex, and on postnatal day 60, behavioral and neurobiological changes were analyzed. Mice exposed to dronabinol exhibited increased anxiogenic and depressive-like behaviors and cognitive impairment. These behaviors were associated with neurodevelopment-related gene and protein expression changes, establishing, for the first time, an association among behavioral changes, cognitive impairment, and neurobiological alterations. Exposure to dronabinol during pregnancy and lactation disrupted the reward system, leading to increased motivation to consume alcohol in the offspring. All these modifications exhibited sex-dependent patterns. These findings reveal the pronounced adverse effects on fetal neurodevelopment resulting from cannabis use during pregnancy and lactation and strongly suggest the need to prevent mothers who use cannabis in this period from the severe and permanent side effects on behavior and brain development that may occur in their children.
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.
The potential therapeutic use of some
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 (CB
r and CB
r), 5-HT
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.
This study evaluated the effects of cannabidiol (CBD) and/or sertraline (STR) on behavioral and gene expression alterations induced by a new chronic animal model of post-traumatic stress disorder ...(PTSD). C57BL/6J male mice were repeatedly exposed to physical and psychogenic alternate stressful stimuli. Fear-related memory and anxiety-like behaviors were evaluated. The effects of the administration of CBD (20 mg/kg, i.p.) and/or STR (10 mg/kg, p.o.) were analyzed on behavioral and gene expression changes induced by the model of PTSD. Gene expression alterations of targets related with stress regulation, endocannabinoid and serotonergic systems were analyzed by real-time PCR. The results revealed an increased and long-lasting fear-related memory and anxiety-like behaviors in mice exposed to the animal model of PTSD. Treatment with CBD improved these behaviors in PTSD animals, effects that were significantly potentiated when combined with STR. Gene expression analyses revealed a long-term increase of corticotropin releasing factor (
Crf
) that was significantly normalized with the combination CBD plus STR. Cannabinoid receptors (
Cnr1
and
Cnr2
) were up regulated in PTSD mice whereas the serotonin transporter (
Slc6a4
) was reduced. Interestingly, CBD and STR alone or combined induced a significant and marked increase of
Slc6a4
gene expression. These results point out the cooperative action of the combination CBD plus STR to enhance fear extinction and reduce anxiety-like behaviors, normalizing gene expression alterations in this animal model of PTSD and suggesting that the combination of CBD with STR deserves to be further explored for the treatment of patients with PTSD.
The high heterogeneity of psychiatric disorders leads to a lack of diagnostic precision. Therefore, the search of biomarkers is a fundamental aspect in psychiatry to reach a more personalized ...medicine. The endocannabinoid system (ECS) has gained increasing interest due to its involvement in many different functional processes in the brain, including the regulation of emotions, motivation, and cognition. This article reviews the role of the main components of the ECS as biomarkers in certain psychiatric disorders. Studies carried out in rodents evaluating the effects of pharmacological and genetic manipulation of cannabinoid receptors or endocannabinoids (eCBs) degrading enzymes were included. Likewise, the ECS-related alterations occurring at the molecular level in animal models reproducing some behavioral and/or neuropathological aspects of psychiatric disorders were reviewed. Furthermore, clinical studies evaluating gene or protein alterations in
brain tissue or
blood, plasma, and cerebrospinal fluid (CSF) samples were analyzed. Also, the results from neuroimaging studies using positron emission tomography (PET) or functional magnetic resonance (fMRI) were included. This review shows the close involvement of cannabinoid receptor 1 (CB1r) in stress regulation and the development of mood disorders anxiety, depression, bipolar disorder (BD), in post-traumatic stress disorder (PTSD), as well as in the etiopathogenesis of schizophrenia, attention deficit hyperactivity disorder (ADHD), or eating disorders (
anorexia and bulimia nervosa). On the other hand, recent results reveal the potential therapeutic action of the endocannabinoid tone manipulation by inhibition of eCBs degrading enzymes, as well as by the modulation of cannabinoid receptor 2 (CB2r) activity on anxiolytic, antidepressive, or antipsychotic associated effects. Further clinical research studies are needed; however, current evidence suggests that the components of the ECS may become promising biomarkers in psychiatry to improve, at least in part, the diagnosis and pharmacological treatment of psychiatric disorders.
Over the past 30 years, 'Aldea' (global village), the Education for Environmental and Sustainability (ESE) School Programme has been implemented in over one thousand public schools in Andalusia, ...Southern Spain. The present study analyses the beliefs of a group of teacher coordinators who have experience of implementing the Aldea programme in their schools with the aim of improving awareness of sustainability. Using data from 13 teachers who participated in regional focus groups, we analysed their beliefs towards the programme, their views of the perceived impact of the programme, and the common drivers and barriers related to the programme. Findings point to the need for a Whole School Approach in order to avoid the typical challenges associated with the implementation of such a programme, in particular teacher burnout. Finally, implications for the successful incorporation of ESE school programmes and subsequent effective practices are discussed.
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.
An educational innovation experience developed as part of the curriculum for the Early Childhood Education degree is presented within the framework of the scientific dissemination project entitled ...'INFA-CIENCIA: From the girls of today to the scientists of tomorrow', which pursues two objectives: (1) To bolster future teachers' knowledge of women scientists and (2) To improve their didactic skills so that they can adapt the research carried out by women to children's capacities. The key findings are a high level of satisfaction amongst teachers with the interventions by university students; the need to continue implementing this innovation, due to the scant knowledge of women scientists amongst students; and the advisability of the students voluntarily choosing the woman scientist they want to work on, in order to boost their motivation and interest.
Spinal opioids have mixed efficacy and their adverse effects force treatment cessation of postoperative pain. Consequently, there is an ongoing search for new therapeutic strategies. Here, we ...evaluated the analgesic efficacy of intrathecal UCM707, an anandamide reuptake inhibitor, and morphine combination. Firstly, we assessed the effects of morphine (1, 5 and 10 μg), UCM707 (75 μg) and its combination in the hot plate. Then, morphine + UCM707 at sub-effective doses was evaluated in a rat post-incisional pain model. In addition, μ-, CB1r-, CB2r- and TRPV1-antagonists were pre-administered before the combination. Activation of μ-opioid and CB1r, and Cnr1, Cnr2, Oprm1 and TRPV1 expressions were evaluated in the lumbar sacra and periaqueductal grey by 35 S-GTPγS binding autoradiography and qPCR studies. In the hot plate, morphine (1 μg) and UCM707 (75 μg) induced a more robust analgesic effect than each drug alone. Morphine plus UCM707 did not modify μ-opioid nor CB1 receptor function in the PAG or LS. Cnr1 and TRPV1 expression increased in the lumbar sacra (LS). Morphine plus UCM707 significantly reduced post-incisional pain at 1 and 4 days after surgery. Cnr1, Cnr2 and TRPV1 expressions increased in the LS. Blockade of μ-opioid receptor reduced combination effects on days 1 and 4. CB1r- and CB2r-antagonism reduced morphine + UCM707 effects on days 1 and 4, respectively. CB1r and TRPV1-antagonism improved their antinociceptive effects on day 4. These results revealed a synergistic/additive analgesic effect of UCM707 and morphine combination controlling postincisional pain. CB1r, CB2r and TRPV1 contribute differently as central sensitization occurs.
•Intrathecal UCM707 has synergistic/additive analgesic effects with morphine.•μ-opioid, cannabinoid and TPRV1 receptors contribute to UCM707 + morphine effects.•UCM707 may be acting as a co-adjuvant drug with opioids for relief of POP.
PDF
