The volume of research on the therapeutic use of psychedelic drugs has been increasing during the last decades. Partly because of the need of innovative treatments in psychiatry, several studies have ...assessed the safety and efficacy of drugs like psilocybin or ayahuasca for a wide range of mental disorders, including major depression. The first section of this chapter will offer an introduction to psychedelic research, including a brief historical overview and discussions about appropriate terminology. In the second section, the recently published clinical trials in which psychedelic drugs were administered to patients will be analysed in detail. Then, in the third section, the main neurobiological mechanisms of these drugs will be described, noting that while some of these mechanisms could be potentially associated with their therapeutic properties, they are commonly used as adjuvants in psychotherapeutic processes. The last section suggests future challenges for this groundbreaking field of research and therapy.
Harmine is a natural β-carboline alkaloid found in several botanical species, such as the Banisteriopsis caapi vine used in the preparation of the hallucinogenic beverage ayahuasca and the seeds of ...Syrian rue (Peganum harmala). Preclinical studies suggest that harmine may have neuroprotective and cognitive-enhancing effects, and retrospective/observational investigations of the mental health of long-term ayahuasca users suggest that prolonged use of this harmine-rich hallucinogen is associated with better neuropsychological functioning. Thus, in order to better investigate these possibilities, we performed a systematic literature review of preclinical studies analyzing the effects of harmine on hippocampal neurons and in memory-related behavioral tasks in animal models. We found two studies involving hippocampal cell cultures and nine studies using animal models. Harmine administration was associated with neuroprotective effects such as reduced excitotoxicity, inflammation, and oxidative stress, and increased brain-derived neurotrophic factor (BDNF) levels. Harmine also improved memory/learning in several animal models. These effects seem be mediated by monoamine oxidase or acetylcholinesterase inhibition, upregulation of glutamate transporters, decreases in reactive oxygen species, increases in neurotrophic factors, and anti-inflammatory effects. The neuroprotective and cognitive-enhancing effects of harmine should be further investigated in both preclinical and human studies.
Celotno besedilo
Dostopno za:
DOBA, IJS, NUK, SIK, UILJ, UKNU, UL, UM, UPUK
Posttraumatic stress disorder (PTSD) is characterized by alterations in emotional and cognitive processing. The current neurobiological model of PTSD posits that amygdala and prefrontal cortex ...functioning impairment underpins symptoms, such as altered emotional and cognitive processing. Additionally, these structures are key components of emotional and attention regulation.
This review sought to evaluate studies comparing PTSD group to non-PTSD controls performance in affective attention tasks during neuroimaging.
PTSD group behavioral performance when responding to affective stimuli differed from controls only in stroop-based tasks. However, neuroimaging techniques were able to identify brain activation differences even when behavioral differences were not present. Amygdala hyperactivation in PTSD patients was confirmed in most cases, but cortical networks results were not as consistent. More than a general reduction in activity, PTSD group data points out to impaired recruitment of ventral cortical structures and increased reliance on dorsal cortical structures during task performance.
Stroop-based tasks seem to be better at identifying differences in behavioral performance of PTSD individuals. PTSD individuals seems to present an altered brain activation pattern in affective attention tasks when compared to controls, where PTSD individuals seem to present enhanced amygdala activation and rely more on dorsal anterior cingulate cortex and posterior insula activation during tasks. The PROSPERO ID for this study is CRD42022355471.
•Stroop-based tasks are more efficient to unveil behavioral differences.•Neural activation can differ even in the absence of behavioral differences.•Trauma-exposed and unexposed controls diverge in brain activity during tasks.
Cannabinoid signaling, mainly via CB1 and CB2 receptors, plays an essential role in oligodendrocyte health and functions. However, the specific molecular signals associated with the activation or ...blockade of CB1 and CB2 receptors in this glial cell have yet to be elucidated. Mass spectrometry-based shotgun proteomics and in silico biology tools were used to determine which signaling pathways and molecular mechanisms are triggered in a human oligodendrocytic cell line (MO3.13) by several pharmacological stimuli: the phytocannabinoid cannabidiol (CBD); CB1 and CB2 agonists ACEA, HU308, and WIN55, 212–2; CB1 and CB2 antagonists AM251 and AM630; and endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG). The modulation of cannabinoid signaling in MO3.13 was found to affect pathways linked to cell proliferation, migration, and differentiation of oligodendrocyte progenitor cells. Additionally, we found that carbohydrate and lipid metabolism, as well as mitochondrial function, were modulated by these compounds. Comparing the proteome changes and upstream regulators among treatments, the highest overlap was between the CB1 and CB2 antagonists, followed by overlaps between AEA and 2-AG. Our study opens new windows of opportunities, suggesting that cannabinoid signaling in oligodendrocytes might be relevant in the context of demyelinating and neurodegenerative diseases. Proteomics data are available at ProteomeXchange (PXD031923).
Abstract 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 objective of this study was to evaluate the effects of intranasal oxytocin in a facial emotion matching task in patients with schizophrenia and healthy volunteers. Twenty patients and 20 healthy volunteers received 48 IU intranasal oxytocin and placebo in a double-blind, randomized, placebo-controlled, within subjects design. Fifty minutes after treatment, subjects completed a facial emotion matching task and three control tests. Oxytocin failed to improve facial affect processing, in contrast with previous results. Possible explanations are the fact that we used a facial emotion matching paradigm instead of emotion labeling tasks and a higher dose of oxytocin than the one used in most similar studies.
The interest in psychedelic substances as potential treatments for psychiatric disorders is increasing. The β-carboline harmine, an Ayahuasca component, presents hallucinogenic and antidepressant ...effects. Although Ayuahuasca-and consequently harmine-is usually consumed in rituals, the role of social contexts in the behavioral effects of harmine has not been investigated yet. In this sense, affective states may modulate cohabitants' behavior, including learning/memory. This work investigates the effects of harmine on the learning/memory performance of rats evaluated on the contextual and tone fear conditioning (CFC and TFC) and on the plus-maze discriminative avoidance (PMDAT) tasks. The possible influence of a harmine-treated cohabitant was assessed by evaluating rats housed in homogeneous cages-where all the animals were acutely administered with the same treatment (vehicle, 5, 10, or 15 mg/kg harmine), and in heterogeneous cages-where each animal received a different drug treatment. The main results are: (a) harmine impaired CFC (10 mg/kg) and PMDAT discrimination (all doses); and (b) harmine caused a memory deficit in CFC, TFC, and PMDAT of untreated rats kept in heterogeneous cages. Our results show that harmine induces a memory deficit in tasks with emotional contexts. Further, the cohabitation with animals treated with this drug also seems to impair memory performance of untreated animals.
Public Health Significance
Harmine, one of the components of the Ayahuasca beverage, presents hallucinogenic and antidepressant effects. Here, we demonstrate that harmine induces memory deficits, and the cohabitation with harmine-treated animals impairs memory performance of untreated animals. The investigation of the effects of harmine per se and on the emotions/behaviors of others is of great importance considering the potential of psychedelic agents as an alternative for the treatment of psychiatric disorders.
The number of patients using cannabis for therapeutic purposes is growing worldwide. While research regarding the treatment of certain diseases/disorders with cannabis and cannabinoids is also ...expanding, only a few longitudinal studies have assessed the mid‐term impacts of medical cannabis use on psychological variables and quality of life (QoL). The aim of the study was to assess the psychological safety and QoL of patients with chronic diseases who self‐medicate with cannabis over time. We recruited patients with various chronic diseases who use cannabis and collected data regarding patterns of cannabis use as well as mental health, personality and QoL. Participants were followed‐up at baseline, 4, 8 and 12 months. Hair analysis was conducted to confirm the presence of cannabinoids. Personality assessment showed a consistent decrease in self‐transcendence and self‐directedness scores. Neither cognitive nor psychopathological deterioration was found. There were also no variations in QoL. Mid‐term use of medical cannabis seems to show adequate tolerability regarding cognitive and psychopathological abilities, and it may help patients with chronic diseases to maintain an acceptable QoL.
Cannabidiol (CBD) is one of the main components of Cannabis sativa and has a wide spectrum of action, including effects in the sleep-wake cycle.
Objective:
The objective of this paper is to assess ...the effects on sleep of acute systemic administration of CBD.
Method:
Adult male Wistar rats were randomly distributed into four groups that received intraperitoneal injections of CBD 2.5 mg/kg, CBD 10 mg/kg, CBD 40 mg/kg or vehicle (n=seven animals/group). Sleep recordings were made during light and dark periods for four days: two days of baseline recording, one day of drug administration (test), and one day after drug (post-test).
Results:
During the light period of the test day, the total percentage of sleep significantly increased in the groups treated with 10 and 40 mg/kg of CBD compared to placebo. REM sleep latency increased in the group injected with CBD 40 mg/kg and was significantly decreased with the dose of 10 mg/kg on the post-test day. There was an increase in the time of SWS in the group treated with CBD 40 mg/kg, although this result did not reach statistical significance.
Conclusion:
The systemic acute administration of CBD appears to increase total sleep time, in addition to increasing sleep latency in the light period of the day of administration.
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