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MDMA-assisted psychotherapy for post-traumatic stress disorder The devil is in the detail.

Recent years have seen escalating media, public and scientific interest in psychedelic medicine. Australia and New Zealand have been late to this research however, in the past 2 years, rapid developments suggest that this is changing. Here, we argue for the need to critically review existing evidence in this field to guide future directions. We focus on (±)3,4-methylenedioxymethamphetamine-assisted psychotherapy for post-traumatic stress disorder, currently the most advanced area of clinical psychedelic research. Food and Drug Administration approval of this approach is likely in 2023, based on a series of promising findings. We provide a detailed overview of Phase 2 and 3 studies published to date. We identify several concerns related to this body of evidence, including methodologicaldesign limitations and broader factors - such as robust involvement of advocacy groups in research and reliance on non-government financing leading to simplistic public messaging - that compound the methodological issues identified. We propose steps for future improvement, including the need for large, high-quality, independent efficacy trials with design enhancements, effectiveness trials and for researchers to consider their own engagement with media and public messaging around these modalities. We argue that, notwithstanding promising findings to date, rigorous and dispassionate science is needed to move the field forward and safeguard the welfare of participants.

Immunological Modulation and Control of Parasitaemia by Ayahuasca Compounds Therapeutic Potential for Chagass Disease.

Ayahuasca is a psychoactive and psychedelic decoct composed mainly of Banisteriopsis caapi and Psychotria viridis plant species. The beverage is rich in alkaloids and it is ritualistically used by several indigenous communities of South America as a natural medicine. There are also reports in the literature indicating the prophylaxis potential of Ayahuasca alkaloids against internal parasites. In the present study, Ayahuasca exhibited moderate in vitro activity against Trypanosoma cruzi trypomastigotes (IC

Anadenanthera colubrina (Vell) Brenan Ethnobotanical, phytochemical, pharmacological and toxicological aspects.

Anadenanthera colubrina (Vell.) Brenan is an endemic tree to South America and different parts of it are used by the population for the treatment of various diseases, as well as in indigenous rituals. This species has high pharmacological potential but may present toxic potential due to the presence of psychotropic compounds. To review published studies with the species A. colubrina regarding ethnobotanical, phytochemical, pharmacological and toxicological aspects, as well as discuss perspectives for new research and protection of this species. A literature review was performed by accessing published articles on databases such as PubMed, Science Direct, Scielo, Scopus, Taylor and Francis online, Springer Link, National Center for Biotechnology Information (NCBI), ACS Publications, Chemspider and Google Scholar. The keywords used were Anadenanthera colubrina or Mimosa colubrina or Piptadenia colubrina or Piptadenia macrocarpa or Piptadenia grata or Anadenanthera macrocarpa and medicinal plants or pharmacological or phytochemicals or traditional use or toxicological or ethnobotanical or pre-clinical trial or clinical. Articles found by database searches and search engines were screened at four stages (i) title screening, (ii) locality screening, (iii) abstract screening, and (iv) full text. Other articles found through supplementary searches were screened in the full text whenever available. Each article was assessed by three reviewers at the title and abstract screening stages, except for those found in Portuguese databases that were assessed by the native reviewer. This robust tree has been popularly useful for agroeconomic, medicinal and as a hallucinogen in religious rituals. According to the published studies, the main parts of the plant are the bark and seeds that are mostly used for respiratory conditions and as entheogens, respectively. It is a rich traditional herbal medicine with many pharmacological properties such as anti-inflammatory, antinociceptive, antidiarrheal, wound healing, antimicrobial, antitumoral, antioxidant, antiaddictive, insecticide and allelopathic that were described in in vitro and in vivo assays, and approximately 56 compounds were identified, suggesting a therapeutic potential for this species. Although most relate to medicinal uses, these are preliminaries and do not show the mechanism of action. The phytochemical assays showed the presence of phenolic compounds, flavonoids, triterpenes, steroids and alkaloids. Some of the compounds are anadanthoflavone, which is exclusive to this species, and no pharmacological or toxicological studies have yet demonstrated this compound. Another important compound is bufotenine which was isolated from seeds and is related to hallucinogenic and antiviral activity. The extracts made from leaves, bark, gum, and fruits appear to be safe, according to both in vivo and in vitro toxicology testing, which all shown low toxicity. Due to the presence of bufotenine in the seeds, it can be toxic, however, it was not found in toxicological assays with the seed extracts. Therefore, part of the studies confirms the popular use of A. colubrina, however, more assays with isolated compounds and with the different extracts are necessary to corroborate other uses and the mechanism of action of their pharmacological effects needs to discuss in more detail. Therefore, the present review would be identified the gaps and suggests further studies oriented to validate the popular use. Thus, it must be noted that the use of this species must be controlled in order to minimize the environmental impact, as most of the pharmacological potential was shown with the bark and seeds. Due to its wide use in folk medicine, it is part of the Brazilian medicinal species with priority for conservation.

A critical review on the synthesis of NH

Nowadays, emerging hazardous pollutants have caused many harmful effects on the environment and human health, calling for the state of the art methods for detection, qualification, and treatment. Metal-organic frameworks are porous, flexible, and versatile materials with unique structural properties, which can solve such problems. In this work, we reviewed the synthesis, activation, and characterization, and potential applications of NH

An evidence-based approach to psychopharmacology for posttraumatic stress disorder (PTSD) - 2022 update.

Algorithms for posttraumatic stress disorder were published by this team in 1999 and 2011. Developments since then warrant revision. New studies and review articles from January 2011 to November 2021 were identified via PubMed and analyzed for evidence supporting changes. Following consideration of variations required by special patient populations, treatment of sleep impairments remains as the first recommended step. Nightmares and non-nightmare disturbed awakenings are best addressed with the anti-adrenergic agent prazosin, with doxazosin and clonidine as alternatives. First choices for difficulty initiating sleep include hydroxyzine and trazodone. If significant non-sleep PTSD symptoms remain, an SSRI should be tried, followed by a second SSRI or venlafaxine as a third step. Second generation antipsychotics can be considered, particularly for SSRI augmentation when PTSD-associated psychotic symptoms are present, with the caveat that positive evidence is limited and side effects are considerable. Anti-adrenergic agents can also be considered for general PTSD symptoms if not already tried, though evidence for daytime use lags that available for sleep. Regarding other pharmacological and procedural options, e.g., transcranial magnetic stimulation, cannabinoids, ketamine, psychedelics, and stellate ganglion block, evidence does not yet support firm inclusion in the algorithm. An interactive version of this work can be found at www.psychopharm.mobi.

Development and initial validation of an MDMAEcstasy motives assessment.

MDMAEcstasy motives differ from those of other substances such as alcohol, cannabis, and methamphetamine. Previous literature on alcohol and cannabis use identified social, expansion, enhancement, coping, and conformism as primary motives for use. MDMAEcstasy users also report using the drug for increases in self-awareness and energy. The development of an MDMAEcstasy use motives assessment has potential to inform treatment interventions and public policy on harm reduction. An MDMAEcstasy use motives assessment was developed from alcohol and cannabis motives measures and qualitative feedback from MDMAEcstasy users. Participants included an international sample of adults (N 1754) who completed an online questionnaire regarding their motives for using recreational MDMAEcstasy. Exploratory and confirmatory factor analysis supported a 4-factor MDMAEcstasy motives scale. The four motive scales showed good internal consistency reliabilitySocial (α 0.88) Expansion (α 0.81), Coping (α 0.82), and Energy (α 0.75). Conformity and Enhancement did not emerge as significant factors. Analyses demonstrated convergent and discriminant validity with relevant constructs including quantityfrequency of use, MDMA use disorder, sensation seeking personality, and positive and negative consequences of use. MDMAEcstasy use motives differ from those of other substances due to the distinctly stimulating, emotional, and empathic effects sought by users. By identifying salient MDMAEcstasy motives, this study highlights the unique aspects of recreational MDMAEcstasy use. This research has utility for informing clinical practice and contributing to public health harm reduction efforts.

In vitro and in vivo pharmacology of nine novel synthetic cannabinoid receptor agonists.

Synthetic cannabinoid receptor agonists (SCRAs) are novel psychoactive substances that bind to and activate CB

Differential Enantiomer-Specific Signaling of Cannabidiol at CB

The two main constituents of

Trace determination of tetrahydrocannabinol (THC) in cosmetic products by stir bar sorptive dispersive microextraction followed by liquid chromatography-tandem mass spectrometry.

An analytical method for the determination of tetrahydrocannabinol (THC) at trace level in cosmetics is presented. As psychoactive compound, the presence of THC in consumer products should be avoided. However, it might be unintentionally present in cannabidiol-rich or hemp-based products by contamination or isomerization of cannabidiol. Due to the low concentrations expected, a sensitive and selective method is necessary for the analytical control of these products. In this sense, the presented method is based on stir bar sorptive dispersive microextraction (SBSDME) followed by liquid chromatography-tandem mass spectrometry (LC-MSMS). In this work, a magnetic composite made of CoFe

Accumulation and risk prioritization of psychoactive substances in the critically endangered Yangtze finless porpoise.

Psychoactive substances have been identified as a kind of emerging contaminants in aquatic environment and pose potential adverse effects on aquatic animals. Yangtze finless porpoise, a critically endangered species in China, is also facing the threat of psychoactive substances. In this study, the accumulation characteristics and risk prioritization of psychoactive substances were investigated in Yangtze finless porpoise collected from Poyang Lake (PYL) and Tian-E-Zhou Oxbow (TZO) in Yangtze River basin. The levels of psychoactive substances were detected in the range of below method detection limits (MDLs) to 98.4 ngmL in the serum of Yangtze finless porpoise. Codeine (COD) and methamphetamine were identified as the major substances due to the highest residual levels with a median concentration of 0.72 ngmL and 0.33 ngmL, respectively. The total concentrations of psychoactive substances in the porpoise collected from TZO was significantly higher than those from PYL. Risk analysis based on effect ratio derived from the ratio of steady-state psychoactive substance serum concentration in the porpoise and human therapeutic plasma concentration revealed that COD was the substance with the highest risk among the psychoactive substances detected, followed by lysergic acid diethylamide (LSD), morphine, alprazolam (ALPZ) and lormetazepam. Location-specific risk prioritization of psychoactive substances found that the top 3 substances are LSD, lorazepam (LORZ) and ALPZ in PYL, and COD, LSD and LORZ in TZO. The results disclose the accumulation of psychoactive substances in Yangtze finless porpoise and suggest that the potential adverse effects should be concerned.

Need for Methods to Investigate Endocannabinoid Signaling.

Endocannabinoids (eCBs) are endogenous lipids able to bind to cannabinoid receptors, the primary molecular targets of the cannabis (Cannabis sativa) active principle Δ

Substance-Specific Risk Factors among Young Adults Potential Prevention Targets across Cannabis-Permissive Environments.

This study examined levels of substance-specific risk factors such as perception of harm from substance use among young adults in a range of cannabis-permissive environments. The main objective was to inform future preventive interventions aimed at reducing cannabis use in the context of increasingly permissive environments. Data came from the Community Youth Development Study (CYDS) collected in 2016 when participants were about 23 years old ( Young adults in more permissive cannabis contexts reported higher levels of all cannabis-specific risk factors (e.g., greater access to and more favorable attitudes about cannabis use), except for perception of harm from regular cannabis use. However, permissiveness of the cannabis environment was not associated with heightened levels of risk factors for other substance use (such as alcohol, cigarettes, and opioids). Future preventive interventions for young adults living in more permissive cannabis contexts may need to focus on cannabis-specific risk factors in particular and go beyond considerations of harm from regular use. Future studies should replicate these findings with other samples.

Investigating the two-hit hypothesis Effects of prenatal maternal immune activation and adolescent cannabis use on neurodevelopment in mice.

Prenatal exposure to maternal immune activation (MIA) and chronic adolescent cannabis use are both risk factors for neuropsychiatric disorders. However, exposure to a single risk factor may not result in major mental illness, indicating that multiple exposures may be required for illness onset. Here, we examine whether combined exposure to prenatal MIA and adolescent delta-9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, lead to enduring neuroanatomical and behavioural changes in adulthood. Mice were prenatally exposed to viral mimetic, poly IC (5 mgkg), or vehicle at gestational day (GD) 9, and postnatally exposed to chronic THC (5 mgkg, intraperitoneal) or vehicle during adolescence (postnatal day PND28-45). Longitudinal magnetic resonance imaging (MRI) was performed pre-treatment, PND 25, post-treatment, PND 50, and in adulthood, PND85, followed by behavioural tests for anxiety-like, social, and sensorimotor gating. Post-mortem assessment of cannabinoid (CB)1 and 2 receptor expressing cells was performed in altered regions identified by MRI (anterior cingulate and somatosensory cortices, striatum, and hippocampus). Subtle deviations in neurodevelopmental trajectory and subthreshold anxiety-like behaviours were observed in mice exposed to both risk factors. Sex-dependent effects were observed in patterns of shared brain-behaviour covariation, indicative of potential sex differences in response to MIA and THC. Density of CB1 and CB2 receptor positive cells was significantly decreased in all mice exposed to MIA, THC, or both. These findings suggest that there may be a cumulative effect of risk factor exposure on gross neuroanatomical development, and that the endocannabinoid system may be sensitive to both prenatal MIA, adolescent THC, or the combination.

Triangulating Amsterdams illicit stimulant use trends by wastewater analysis and recreational drug use monitoring.

Drug consumption estimates are of relevance because of public health effects as well as associated criminal activities. Wastewater analysis of drug residues enables the estimation of drug consumption and drug markets. Short-term and long-term trends of cocaine, MDMA (ecstasy), amphetamine (speed) and methamphetamine (crystal meth), were studied for the city of Amsterdam. MDMA (41%) and cocaine (26%) showed significantly higher weekend vs. week consumption, while no differences were observed for the other drugs. The consumption of MDMA, cocaine, amphetamine and methamphetamine significantly increased between 2011 and 2019. Weekly trends emerging from wastewater analyses were supported by qualitative and quantitative data from a recreational drug use monitoring scheme. However, information collected in panel interviews within nightlife networks and surveys among visitors of pubs, clubs and festivals only partially reflected the long term increase in consumption as registered from wastewater analysis. Furthermore, methamphetamine use was not well presented in survey data, panel studies and test service samples, but could be monitored trough wastewater analysis. This illustrates that wastewater analysis can function as an early warning if use and user groups are small or difficult to reach trough other forms of research. All in all, this study illustrates that wastewater-based epidemiology is complementary to research among user groups, and vice versa. These different types of information enable to connect observed trends in total drug consumption to behaviour of users and the social context in which the use takes place as well as validate qualitative signals about (increased) consumption of psychoactive substances. Such a multi angular approach to map the illicit drug situation on local or regional scale can provide valuable information for public health.

Application of experimental design in HPLC method optimisation for the simultaneous determination of multiple bioactive cannabinoids.

The scientific interest in Cannabis sativa L. analysis has been rapidly increasing in recent years, especially for what concerns cannabinoids, plant secondary metabolites which are well known for having many biological properties. High-performance liquid chromatography (HPLC) is frequently used for both the qualitative and quantitative analysis of cannabinoids in plant extracts from C. sativa and its derived products. Many studies have been focused on the main cannabinoids, such as ∆

Pooled Urine Analysis at a Belgian Music Festival Trends in Alcohol Consumption and Recreational Drug Use.

Recreational drug use has become more and more accepted in society. Availability and purity are rising and new psychoactive substances (NPS) are popping up.The aim of this study was to provide objective data on illicit drug use at a Belgian festival in order to report on arising trends. This may provide additional information to help develop preventive strategies. A cross-sectional study took place during a music festival in the summer of 2019, where 43 samples of pooled urine were collected at four different locations and at different moments of the day. Analysis was performed using gas chromatography with a flame ionization detector (GC-FID) to determine ethanol concentrations. Drugs of abuse were quantified using liquid chromatography-tandem mass spectrometry. A qualitative analysis was performed using high-resolution mass spectrometry. Median ethanol concentration was 0.88gL. Cocaine, 3,4-methylenedioxymethamphetamine (MDMA), amphetamines, ketamine, and cannabis were detected in almost every sample and often in high concentrations. Furthermore, two NPS were detected and a variety of over-the-counter medication and adulterants were also found. The findings were largely in-line with trends outlined in the European Drug Report. Striking were the relatively high concentrations of MDMA and ketamine and detection of two synthetic cathinones. Two possible adulterants of cocaine were detected, namely flecainide and amlodipine. Music festivals are considered a high-risk setting for alcohol consumption and illicit drug use. Analysis of pooled urine samples at a festival therefore provides a valuable method to evaluate trends and to screen for new substances. Wide-spread use of classical drugs and identification of two NPS were observed during a major international music festival in Belgium. Results need to be interpreted carefully, taking into account the possibilities and limitations of the used techniques and a standardized sampling is required.

Analysis of Anti-Cancer and Anti-Inflammatory Properties of 25 High-THC Cannabis Extracts.

Simple Extraction of Cannabinoids from Female Inflorescences of Hemp (

The high interest in non-psychoactive cannabidiol increases the need for efficient and straightforward cannabidiol (CBD) extraction methods. The research aimed to compare simple methods of cannabinoid extraction that do not require advanced laboratory equipment. This work assesses the content of total CBD and Δ

Evaluation of the In Vitro Wound-Healing Potential of Ayahuasca.

Ayahuasca is an Amazonian drink, which contains β-carboline alkaloids and

Association between Lifetime Classic Psychedelic Use and Sick Leave in a Population-Based Sample.

Absenteeism from work due to illness, and related costs, has increased steadily during the past decades. In recent years, there has been a reemergence of research on the therapeutic effects of classic psychedelics showing associations with both physical and mental health. However, the association between classic psychedelics and sick leave remains unknown. The aim of this study is to investigate the association between lifetime classic psychedelic use and sick leave in the past 30 days among adults in the United States ( The primary analysis was conducted using multiple linear regression, controlling for sociodemographic characteristics, risky behavior, and use of other substances. There was a significant and negative association between lifetime classic psychedelic use and sick leave in the past 30 days (B -0.09, These findings suggest that classic psychedelics could potentially lead to reduced sick leave and associated costs in the general population, but more research is needed to investigate potential causal pathways of classic psychedelics on sick leave and evaluate possible mechanisms.

Cannabis- and Substance-Related Epidemiological Patterns of Chromosomal Congenital Anomalies in Europe Geospatiotemporal and Causal Inferential Study.

Laboratory data link cannabinoid exposure to chromosomal mis-segregation errors. Recent epidemiological reports confirm this link and raise concern that elevated chromosomal congenital anomaly rates (CCAR) may be occurring in Europe which is experiencing increased cannabis use, daily intensity of use and cannabinoid potency. CCAR data from Eurocat. Drug use data from the European Monitoring Centre for Drugs and Drug Addiction. Income from World Bank. Bivariate, multivariate, panel and geotemporospatial regressions analyzed. Inverse probability weighting of panel models and E-values used as major quantitative causal inferential methodologies. In countries where daily cannabis use was rising the trend for CCAs was upwards whereas in those where daily use was declining it was usually downwards ( Data indicate that, consistent with reports from Hawaii, Canada, Colorado, Australia and USA, CCARs are causally and spatiotemporally related to metrics and intensity of cannabis exposure, directly impact 645 MB (21.5%) of the human genome and may implicate epigenomic-centrosomal mechanisms.

Genetic Instability among Hitnü People Living in Colombian Crude-Oil Exploitation Areas.

Oil exploitation, drilling, transportation, and processing in refineries produces a complex mixture of chemical compounds, including polycyclic aromatic hydrocarbons (PAHs), which may affect the health of populations living in the zone of influence of mining activities (PZOI). Thus, to better understand the effects of oil exploitation activities on cytogenetic endpoint frequency, we conducted a biomonitoring study in the Hitnü indigenous populations from eastern Colombia by using the cytokinesis micronucleus cytome assay (CBMN-cyt). PAH exposure was also measured by determine urine 1-hydroxypyrene (1-OHP) using HPLC. We also evaluated the relationship between DNA damage and 1-OHP levels in the oil exploitation area, as well as the modulating effects of community health factors, such as Chagas infection nutritional status and consumption of traditional hallucinogens, tobacco, and wine from traditional palms. The frequencies of the CBMN-cyt assay parameters were comparable between PZOI and Hitnü populations outside the zone of influence of mining activities (POZOI) however, a non-significant incremental trend among individuals from the PZOI for most of the DNA damage parameters was also observed. In agreement with these observations, levels of 1-OHP were also identified as a risk factor for increased MN frequency (PR 1.20) compared to POZOI (PR 0.7). Proximity to oil exploitation areas also constituted a risk factor for elevated frequencies of nucleoplasmic bridges (NPBs) and APOP-type cell death. Our results suggest that genetic instability and its potential effects among Hitnü individuals from PZOI and POZOI could be modulated by the combination of multiple factors, including the levels of 1-OHP in urine, malnutrition, and some traditional consumption practices.

A Multidisciplinary Hypothesis about Serotonergic Psychedelics. Is it Possible that a Portion of Brain Serotonin Comes From the Gut

Here we present a complex hypothesis about the psychosomatic mechanism of serotonergic psychedelics. Serotonergic psychedelics affect gut microbes that produce a temporary increase of 5-HT by their host enterochromaffin cells (ECs). This increased 5-HT production-which is taken up and distributed by platelets-may work as a hormone-like regulatory signal that could influence membrane permeability in the host organs and tissues and in the brain. Increased plasma 5-HT levels could enhance permeability of the blood-brain barrier (BBB). Transiently increased permeability of the BBB allows for plasma 5-HT to enter the central nervous system (CNS) and be distributed by the volume transmission. Next, this gut-derived 5-HT could modulate excitatory and inhibitory neurotransmission and produce special network disintegration in the CNS. This transient perturbation of the normal neural hierarchy allows patients access to suppressed fear information and perform an emotional reset, in which the amygdale may have a key role.

Potent Marijuana Strains Are Making Teens Sick.

Despite fewer restrictive laws, cannabis products still carry risk.

The Emerging Field of Psychedelic Psychotherapy.

Few treatments are available for patients with mood disorders or post-traumatic stress disorder (PTSD) who have already failed multiple interventions. After several decades when research into psychedelics was effectively halted by federal legislation, the past several years have shown the re-emergence of thoughtful investigations studying the utility of compounds such as 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin. Several studies have coupled the safe administration of psychedelic compounds in a controlled environment after several hours of preparation of study participants and followed by multiple sessions to integrate the psychedelic experience. The improvement participants experience appear related to the often profound perspective changes experienced and seem unlike the improvements seen in the currently available care paradigms. Studies cited include treatment resistant depression, end of life despair, and PTSD. Psychedelic psychotherapy, a unique remarriage of biological therapy and psychotherapy, has the potential to transform mental health care.

Scoping Review of Experiential Measures from Psychedelic Research and Clinical Trials.

Subjective responses to psychoactive drugs have served as intriguing windows into consciousness as well as useful predictors. Subjective reactions to psychedelic molecules are particularly interesting given how they covary with subsequent improvements associated with psychedelic-assisted treatments. Although links between subjective reactions and decreases in treatment-resistant clinical depression, end-of-life anxiety, and maladaptive consumption of alcohol and nicotine appear in the empirical literature, the measurement of these subjective responses has proven difficult. Several scales developed over many decades show reasonable internal consistency. Studies suggest that many have a replicable factor structure and other good psychometric properties, but samples are often small and self-selected. We review the psychometric properties of some of the most widely used scales and detail their links to improvement in response to psychedelic-assisted treatments. Generally, assessments of mystical experiences or oceanic boundlessness correlate with improvements. Challenging subjective experiences, psychological insight, and emotional breakthroughs also show considerable promise, though replication would strengthen conclusions. We suggest a collaborative approach where investigators can focus on key responses to ensure that the field will eventually have data from many participants who report their subjective reactions to psychedelic molecules in a therapeutic setting. This may aid in predicting improvement amongst targeted conditions and wellbeing.

Screening microbially produced Δ

Microbial production of cannabinoids promises to provide a consistent, cheaper, and more sustainable supply of these important therapeutic molecules. However, scaling production to compete with traditional plant-based sources is challenging. Our ability to make strain variants greatly exceeds our capacity to screen and identify high producers, creating a bottleneck in metabolic engineering efforts. Here, we present a yeast-based biosensor for detecting microbially produced Δ

Hours high as a proxy for marijuana use quantity in intensive longitudinal designs.

Measuring marijuana use quantity in survey research is complicated due to wide variation in the types (e.g., flower, edibles) and potency of marijuana products and in the modes (e.g., smoking, dabbing) used to consume products. There is currently no gold standard marijuana use quantity measure for survey research. This study examined whether number of hours high can be used as a proxy for marijuana use quantity in survey research, particularly in intensive longitudinal designs. Participants came from a community sample of young adults participating in a longitudinal study on simultaneous alcohol and marijuana use that used a longitudinal measurement-burst design in which participants completed surveys on up to 14 consecutive days in up to five bursts across nearly two calendar years. Those who reported using marijuana on at least one sampled day were included in present analyses (N 379 M Within persons, mode-specific marijuana use quantity variables predicted same-day number of hours high indicating evidence of initial criterion validity. In turn, hours high predicted same-day negative marijuana-related consequences indicating evidence of proximal predictive validity. Between persons, participants average number of hours high was positively associated with their odds of possible cannabis use disorder following the last burst demonstrating distal predictive validity. Number of hours high may be a parsimonious proxy for measuring marijuana use quantity (regardless of mode of use) in survey research, particularly in intensive longitudinal designs.

White matter alterations in chronic MDMA use Evidence from diffusion tensor imaging and neurofilament light chain blood levels.

3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy) is a serotonin- and noradrenaline-releasing substance, currently among the most widely used illicit substances worldwide. In animal studies, repeated exposure to MDMA has been associated with dendritic but also axonal degeneration in the brain. However, translation of the axonal findings, specifically, to humans has been repeatedly questioned and the few existing studies investigating white matter alterations in human chronic MDMA users have yielded conflicting findings. In this study, we combined whole-brain diffusion tensor imaging and neurofilament light chain (NfL) analysis in blood to reveal potential MDMA-induced axonal neuropathology. To this end, we assessed 39 chronic MDMA users and 39 matched MDMA-naïve healthy controls. MDMA users showed increased fractional anisotropy in several white matter tracts, most prominently in the corpus callosum as well as corticospinal tracts, with these findings partly related to MDMA use intensity. However, the NfL levels of MDMA users were not significantly different from those of controls. We conclude that MDMA use is not associated with significant white matter lesions due to the absence of reduced fractional anisotropy and increased NfL levels commonly observed in conditions associated with white matter lesions, including stimulant and ketamine use disorders. Hence, the MDMA-induced axonal degradation demonstrated in animal models was not observed in this human study of chronic MDMA users.

Impact of emulsifiers for the nanoencapsulation with maltodextrin of cannabis oil by spray drying on the physicochemical properties and bioaccessibility of cannabinoids.

Our study aimed to investigate the impact of various emulsifiers, namely whey protein isolate (WPI), soy protein isolate (SPI), and Tween 80 (Tw), on their ability to encapsulate cannabis oil with maltodextrin as the wall material. The physicochemical properties of the powder, the stability of the cannabinoids, and their bioaccessibility during static

Animal evidence considered in determination of cannabis smoke and Δ

This review summarizes the most common potential pathways of neurodevelopmental toxicity due to perinatal exposure to Δ

Towards an understanding of psychedelic-induced neuroplasticity.

Classic psychedelics, such as LSD, psilocybin, and the DMT-containing beverage ayahuasca, show some potential to treat depression, anxiety, and addiction. Importantly, clinical improvements can last for months or years after treatment. It has been theorized that these long-term improvements arise because psychedelics rapidly and lastingly stimulate neuroplasticity. The focus of this review is on answering specific questions about the effects of psychedelics on neuroplasticity. Firstly, we review the evidence that psychedelics promote neuroplasticity and examine the cellular and molecular mechanisms behind the effects of different psychedelics on different aspects of neuroplasticity, including dendritogenesis, synaptogenesis, neurogenesis, and expression of plasticity-related genes (e.g., brain-derived neurotrophic factor and immediate early genes). We then examine where in the brain psychedelics promote neuroplasticity, particularly discussing the prefrontal cortex and hippocampus. We also examine what doses are required to produce this effect (e.g., hallucinogenic doses vs. microdoses), and how long purported changes in neuroplasticity last. Finally, we discuss the likely consequences of psychedelics effects on neuroplasticity for both patients and healthy people, and we identify important research questions that would further scientific understanding of psychedelics effects on neuroplasticity and its potential clinical applications.

Cannabidiol and Delta-9-Tetrahydrocannabinol Interactions in Male and Female Rats With Persistent Inflammatory Pain.

Cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), 2 of the primary constituents of cannabis, are used by some individuals to self-treat chronic pain. It is unclear whether the pain-relieving effects of CBD alone and in combination with THC are consistent across genders and among types of pain. The present study compared the effects of CBD and THC given alone and in combination in male and female rats with Complete Freunds adjuvant-induced inflammatory pain. After induction of hindpaw inflammation, vehicle, CBD (0.05-2.5 mgkg), THC (0.05-2.0 mgkg), or a CBDTHC combination (31, 11, or 13 dose ratio) was administered i.p. twice daily for 3 days. Then on day 4, mechanical allodynia, thermal hyperalgesia, weight-bearing, and locomotor activity were assessed 0.5 to 4 hours after administration of the same dose combination. Hindpaw edema and open field (anxiety-like) behaviors were measured thereafter. THC alone was anti-allodynic and anti-hyperalgesic, and decreased paw thickness, locomotion, and open field behaviors. CBD alone was anti-allodynic and anti-hyperalgesic. When combined with THC, CBD tended to decrease THC effects on pain-related behaviors and exacerbate THC-induced anxiety-like behaviors, particularly in females. These results suggest that at the doses tested, CBD-THC combinations may be less beneficial than THC alone for the treatment of chronic inflammatory pain. PERSPECTIVE The present study compared CBD and THC effects alone and in combination in male and female rats with persistent inflammatory pain. This study could help clinicians who prescribe cannabis-based medicines for inflammatory pain conditions determine which cannabis constituents may be most beneficial.

Assessment of delta-9-tetrahydrocannabinol (THC) in saliva and blood after oral administration of medical cannabis with respect to its effect on driving abilities.

Medical cannabis has recently been legalized in many countries, and it is currently prescribed with increasing frequency, particularly for treatment of chronic pain resistant to conventional therapy. The psychoactive substance delta-9-tetrahydro-cannabinol (THC) contained in cannabis may affect driving abilities. Therefore, the aims of this study (open-label, monocentric, nonrandomized) were to evaluate blood and saliva concentrations of THC after oral administration of medical cannabis and to assess the time needed for THC levels to decline below a value ensuring legal driving. The study involved 20 patients with documented chronic pain using long-term medical cannabis therapy. They were divided into two groups and treated with two different doses of cannabis in the form of gelatin capsules (62.5 mg or 125 mg). In all patients, the amount of THC was assessed in saliva and in blood at pre-defined time intervals before and after administration. THC levels in saliva were detected at zero in all subjects following administration of both doses at all-time intervals after administration. Assessment of THC levels in blood, however, showed positive findings in one subject 9 h after administration of the lower dose and in one patient who had been given a higher dose 7 h after administration. Our finding suggested that for an unaffected ability to drive, at least 9-10 h should elapse from the last cannabis use.

Use of plant-based hallucinogens and dissociative agents U.S. Time Trends, 2002-2019.

Information on time trends in use of different plant-based hallucinogens is lacking. The current study used nationally representative U.S. data to assess overall and age-specific time trends in the prevalence of lifetime and 12-month use of plant-based hallucinogens and dissociative agents. Participants were respondents aged ≥ 12 years (N 1,006,051) from the National Survey on Drug Use and Health, 2002-2019. Predictors were continuous years. Outcomes included illicit use of peyote, mescaline, psilocybin, ketamine, salvia, and tryptamine. Sociodemographic variables (gender age raceethnicity educational level family income) were modeled as covariates. Trends were estimated overall and by age (12-17, 18-25, 26). Prevalence differences PDs were obtained for each category, along with 95 % confidence intervals CI. Increases in lifetime use were observed for psilocybin (2002-2019 PD1.61), tryptamine (2006-2014 PD0.55 2015-2019 PD0.44), and ketamine (2006-2014 PD0.27 2015-2019 PD0.21). Mescaline use decreased (PD -0.89). While overall lifetime salvia use increased between 2006 and 2014 (PD1.81), prevalence did not change between 2015 and 2019. Twelve-month use of tryptamine and ketamine increased between 2006 and 2014 (PD0.14 0.03, respectively). Twelve-month ketamine use also increased from 2015 to 2019 (PD0.03). By age, participants aged 12-17 and 18-25 showed decreases in use of most types of hallucinogens, but those age 26 generally showed increases. While use of plant-based hallucinogens and dissociative agents remains rare, lifetime use of ketamine, tryptamine, and psilocybin is increasing in adults. Considering these increases alongside concerns about unsupervised use of illicit products whose dose and composition is uncertain, clinicians and policymakers should remain mindful of the rising rates of illicit use in the general population.

Deficiency of kynurenine 3-monooxygenase exacerbates impairment of prepulse inhibition induced by phencyclidine.

Phencyclidine (PCP) causes mental symptoms that closely resemble schizophrenia through the inhibition of the glutamatergic system. The kynurenine (KYN) pathway (KP) generates metabolites that modulate glutamatergic systems such as kynurenic acid (KA), quinolinic acid (QA), and xanthurenic acid (XA). Kynurenine 3-monooxygenase (KMO) metabolizes KYN to 3-hydroxykynurenine (3-HK), an upstream metabolite of QA and XA. Clinical studies have reported lower KMO mRNA and higher KA levels in the postmortem brains of patients with schizophrenia and exacerbation of symptoms in schizophrenia by PCP. However, the association between KMO deficiency and PCP remains elusive. Here, we demonstrated that a non-effective dose of PCP induced impairment of prepulse inhibition (PPI) in KMO KO mice. KA levels were increased in the prefrontal cortex (PFC) and hippocampus (HIP) of KMO KO mice, but 3-HK levels were decreased. In wild-type C57BL6 N mice, the PPI impairment induced by PCP is exacerbated by KA, while attenuated by 3-HK, QA and XA. Taken together, KMO KO mice were vulnerable to the PPI impairment induced by PCP through an increase in KA and a decrease in 3-HK, suggesting that an increase in the ratio of KA to 3-HK (QA and XA) may play an important role in the pathophysiology of schizophrenia.

Perceived Substance Use Risks Among Never Users Sexual Identity Differences in a Sample of U.S. Young Adults.

Lower perceived risk is a well-established risk factor for initiating substance use behaviors and an integral component of many health behavior theories. Established literature has shown that many substance use behaviors are more prevalent among individuals who identify as lesbian, gay, or bisexual than among those who identify as heterosexual. However, potential differences in perceived risk by sexual identity among individuals with no lifetime use have not been well characterized to date. Data on 111,785 adults aged 18-34 years (including 11,377 lesbian, gay, and bisexual adults) were from the 2015-2019 National Survey on Drug Use and Health. Perceived risks (classified as great risk versus less than great risk) were assessed with 11 National Survey on Drug Use and Health survey items regarding 6 different substances (alcohol, cigarettes, marijuana, cocaine, lysergic acid diethylamide, and heroin). Survey-weighted and sex-stratified logistic regression models were used to estimate sexual identity differences regarding perceived great risk among those reporting no lifetime use. Analyses were conducted in 2021-2022. Gay men, bisexual men, lesbiangay women, and bisexual women were all significantly less likely than heterosexual peers to perceive great risk associated with specific marijuana, cocaine, lysergic acid diethylamide, and heroin use behaviors. Bisexual men and women were also significantly less likely than heterosexual peers to perceive great risk associated with binge drinking behaviors and smoking ≥1 packs of cigarettes daily. This novel investigation among never users provides evidence that lesbian, gay, and bisexual adults perceive significantly lower risks associated with multiple substance use behaviors than heterosexual adults, which may indicate important sexual identity differences in susceptibility to substance use initiation.

Self-Entropic Broadening Theory Toward a New Understanding of Self and Behavior Change Informed by Psychedelics and Psychosis.

The extremes of human experiences, such as those occasioned by classic psychedelics and psychosis, provide a rich contrast for understanding how components of these experiences impact well-being. In recent years, research has suggested that classic psychedelics display the potential to promote positive enduring psychologic and behavioral changes in clinical and nonclinical populations. Paradoxically, classic psychedelics have been described as psychotomimetics. This review offers a putative solution to this paradox by providing a theory of how classic psychedelics often facilitate persistent increases in well-being, whereas psychosis leads down a darker path. This will be done by providing an overview of the overlap between the states (i.e., entropic processing) and their core differences (i.e., self-focus). In brief, entropic processing can be defined as an enhanced overall attentional scope and decreased predictability in processing stimuli facilitating a hyperassociative style of thinking. However, the outcomes of entropic states vary depending on level of self-focus, or the degree to which the associations and information being processed are evaluated in a self-referential manner. We also describe potential points of overlap with less extreme experiences, such as creative thinking and positive emotion-induction. Self-entropic broadening theory offers a heuristically valuable perspective on classic psychedelics and their lasting effects and relation to other states by creating a novel synthesis of contemporary theories in psychology. SIGNIFICANCE STATEMENT Self-entropic broadening theory provides a novel theory examining the psychedelic-psychotomimetic paradox, or how classic psychedelics can be therapeutic, yet mimic symptoms of psychosis. It also posits a framework for understanding the transdiagnostic applicability of classic psychedelics. We hope this model invigorates the field to provide more rigorous comparisons between classic psychedelic-induced states and psychosis and further examinations of how classic psychedelics facilitate long-term change. As a more psychedelic future of psychiatry appears imminent, a model that addresses these long-standing questions is crucial.

Heating of consumer cannabis oils can lead to free radical initiated degradation, causing CBD and THC depletion.

Commercial cannabis oil products are widely available in Canada even though there is a significant gap in scientific information regarding them. Oils, such as vegetable oils, are known to undergo oxidative changes through free radical mechanisms when they are heated or aged, but the cannabis oils used in this study did not have expiry dates or best-before usage dates. This led to the question of how these products would be affected with time. We hypothesized that cannabis oils would produce increased concentrations of free radicals in aging-simulated conditions, which would be related to a decrease in cannabidiol (CBD) or Δ

Deepening our understanding of psychedelics by expanding psychedelic data collection in the United States National Survey on Drug Use and Health.

Amid a reappraisal of the medicinal and societal worth of psychedelics in many countries, regulatory and financial barriers to conducting clinical research with these compounds appear to be receding. Still, there remains a strong need for a clearer understanding of naturalistic psychedelic use and its associated epidemiology, since this type of psychedelic use, which is growing in many places, will almost certainly always exceed clinical use. Furthermore, psychedelics behave differently depending on the settings in which they are used, meaning many research findings on their effects may significantly differ depending on the contexts in which they are observed. Therefore, improving the collection of data on real-world psychedelic use should be of higher priority for the public health community. Expanding data collection on psychedelic use in the United States National Survey on Drug Use and Health, an already vital tool for researchers examining naturalistic psychedelic use, could address this important public health need, helping ensure the general public, the scientific community, and regulators have access to high-quality information as peoples across the world reevaluate what psychedelics place in medicine and society should be.

Changes in Emergency Department Visits for Cannabis Hyperemesis Syndrome Following Recreational Cannabis Legalization and Subsequent Commercialization in Ontario, Canada.

Prior research suggests that the legalization of recreational cannabis is associated with increases in cannabis hyperemesis syndrome (CHS), but it is unclear how cannabis commercialization (ie, greater retail store access as well as increased variety and potency of cannabis products) may be associated with these changes. To examine changes in the number and characteristics of CHS emergency department (ED) visits from before to after legalization of cannabis in Ontario, Canada. This repeated cross-sectional study used interrupted time-series analyses to examine immediate and gradual changes in ED visits for CHS in Ontario, Canada, during 3 time periods prelegalization (January 2014-September 2018), legalization with product and retail store restrictions (October 2018-February 2020), and commercialization with new products and expanded stores, which coincided with the COVID-19 pandemic (March 2020-June 2021). Data were obtained from routinely collected and linked health administrative databases. All individuals aged at least 15 years and who were eligible for Ontarios Universal Health Coverage were included. Data were analyzed between March and July 2022. Monthly counts of ED visits for CHS per capita. There were 12 866 ED visits for CHS from 8140 individuals during the study. Overall, the mean (SD) age was 27.4 (10.5) years, with 2834 individuals (34.8%) aged 19 to 24 years, 4163 (51.5%) females, and 1353 individuals (16.6%) with a mental health ED visit or hospitalization in the 2 years before their first CHS ED visit. Nearly 10% of visits (1135 visits 8.8%) led to hospital admissions. Monthly rates of CHS ED visits increased 13-fold during the 7.5-year study period, from 0.26 visits per 100 000 population in January 2014 to 3.43 visits per 100 000 population in June 2021. Legalization was not associated with an immediate or gradual change in rates of ED visits for CHS however, commercialization during the COVID-19 pandemic period was associated with an immediate increase in rates of CHS ED visits (incidence rate ratio IRR, 1.49 95% CI, 1.31-1.70). During commercialization, rates of CHS ED visits increased more in women (IRR, 1.49 95% CI, 1.16-1.92) and individuals older than the legal age of cannabis purchase (eg, age 19-24 years IRR, 1.60 95% CI, 1.19-2.16) than men (IRR, 1.08 95% CI, 0.85-1.37) and individuals younger than the legal age of purchase (IRR, 0.78 95% CI, 0.42-1.45). This cross-sectional study found large increases in CHS ED visits during the period of time when the market commercialized and the COVID-19 pandemic occurred. Greater awareness of CHS symptoms by ED staff in regions where legal commercialized cannabis markets exist is indicated.

Animal evidence considered in determination of cannabis smoke and Δ

This review focuses on neurodevelopmental effects observed in animal studies of cannabis smoke and Δ

Two new 22-membered macrolides from Streptomyces sp. HU210.

Two new 22-membered macrolide metabolites, phthoramycins B (1) and C (2), were isolated from the fermentation broth of Streptomyces sp. HU210. Their structures were elucidated based on extensive spectroscopic techniques including 1D, 2D NMR and HRESIMS data. Compounds 1 and 2 showed moderate cytotoxic activity against human leukemia cell line K562 and lung carcinoma cell line A549.

Combined alcohol and cannabinoid exposure leads to synergistic toxicity by affecting cerebellar Purkinje cells.

Combined use of cannabis and alcohol results in greater psychoactive toxicity than either substance alone, but the underlying central mechanisms behind this worsened outcome remain unclear. Here we show that the synergistic effect of Δ

Psychedelics and schizophrenia Distinct alterations to Bayesian inference.

Schizophrenia and states induced by certain psychotomimetic drugs may share some physiological and phenomenological properties, but they differ in fundamental ways one is a crippling chronic mental disease, while the others are temporary, pharmacologically-induced states presently being explored as treatments for mental illnesses. Building towards a deeper understanding of these different alterations of normal consciousness, here we compare the changes in neural dynamics induced by LSD and ketamine (in healthy volunteers) against those associated with schizophrenia, as observed in resting-state MEEG recordings. While both conditions exhibit increased neural signal diversity, our findings reveal that this is accompanied by an increased transfer entropy from the front to the back of the brain in schizophrenia, versus an overall reduction under the two drugs. Furthermore, we show that these effects can be reproduced via different alterations of standard Bayesian inference applied on a computational model based on the predictive processing framework. In particular, the effects observed under the drugs are modelled as a reduction of the precision of the priors, while the effects of schizophrenia correspond to an increased precision of sensory information. These findings shed new light on the similarities and differences between schizophrenia and two psychotomimetic drug states, and have potential implications for the study of consciousness and future mental health treatments.

Cannabis dosing and administration for sleep a systematic review.

As cannabis is increasingly used to treat sleep disorders, we performed a systematic review to examine the effects of cannabis on sleep and to guide cannabis prescribers in their recommendations to patients, specifically focusing on dosing. We searched EMBASE, Medline, and Web of Science and identified 4550 studies for screening. Five hundred sixty-eight studies were selected for full-text review and 31 were included for analysis. Study results were considered positive based on improvements in sleep architecture or subjective sleep quality. Bias in randomized controlled trials was assessed using Cochrane Risk of Bias tool 2.0. Sleep improvements were seen in 7 out of 19 randomized studies and in 7 out of 12 uncontrolled trials. There were no significant differences between the effects of tetrahydrocannabinol and cannabidiol. Cannabis showed most promise at improving sleep in patients with pain-related disorders, as compared to those with neurologic, psychiatric, or sleep disorders, and showed no significant effects on healthy participants sleep. While subjective improvements in sleep quality were often observed, diagnostic testing showed no improvements in sleep architecture. Adverse events included headaches, sedation, and dizziness, and occurred more frequently at higher doses, though no serious adverse events were observed. High-quality evidence to support cannabis use for sleep remains limited. Heterogeneity in cannabis types, doses, timing of administration, and sleep outcome measures limit the ability to make specific dosing recommendations.

Combined Use of Flubromazepam and Stimulants Blood and Oral Fluid Concentrations and Impact on Driving Ability.

Designer benzodiazepines (DBZDs) are becoming increasingly available in Europe, with the European Monitoring Centre of Drugs and Drug Addiction currently monitoring ∼30 new benzodiazepines. The following driving under the influence of drug (DUID) case describes the oral fluid (OF) and blood concentrations, as well as the observed effects after the combined use of stimulants and flubromazepam. Both OF, collected via the Intercept i2 collector (Immunalysis, Pomona, CA, USA), and blood (collected in containers with various stabilizers) were screened using a liquid chromatographic (LC) time-of-flight (TOF) mass spectrometric (MS-MS) method. In addition, various LC-MS-MS methods in multi-reaction monitoring mode were applied for confirmation and quantification. The OF and blood samples were taken 2 h 25 min and 9 h 19 min after the accident, respectively. OF contained 789 ngmL amphetamine, 5,173 ngmL MDMA, 168 ngmL benzoylecgonine, 492 ngmL cocaine, 134 ngmL 4-methylmethcathinone (4-MMC) and traces of flubromazepam (less than limit of quantification (LLOQ) 2 ngmL). The sodium-fluoride blood samples contained 19 ngmL amphetamine, 284 ngmL MDMA, 20 ngmL MDA, 38 ngmL benzoylecgonine, 4 ngmL methylecgonine, 161 ngmL flubromazepam and traces of 4-MMC (<LLOQ 2.5 ngmL). The driver was observed to have an irregular speed driving pattern and could not keep his lane. He demonstrated the following effects after the accident bloodshot eyes, red face, sweating, fatigue, disorientation in time and space and mental confusion. Even 24 h after the accident, the driver was confused, disoriented, had red spots on his face and could not keep his balance. The effects of flubromazepam combined with several stimulants are demonstrated. Moreover, this case illustrates well the pros and cons of the different biological matrices applied in a DUID context. Differences between the biological matrices are not only observed concerning the easepracticality of (on-site) collection, but also in the final drug detectability due to the large variations in OFblood drug concentration ratios and metabolismelimination rates as a result of the different chemical entities of the compounds.

Contrasting effects of DOI and lisuride on impulsive decision-making in delay discounting task.

The 5-HT The current study aims to compare the effects of DOI and lisuride on impulsive decision-making and further to investigate the possible receptor mechanisms responsible for the actions of the two drugs. Impulsive decision-making was evaluated in male Sprague-Dawley rats by the percentage of choice for the LR in delay discounting task (DDT). Delay to the LR changed in an ascending order (0, 4, 8, 16, and 32 s) across one session. DOI (0.5 and 1.0 mgkg) increased impulsive decision-making, and the effects of DOI (1.0 mgkg) were blocked by the 5-HT DOI and lisuride have contrasting effects on impulsive decision-making via distinct receptors. DOI-induced increase of impulsivity is mediated by the 5-HT

Fingolimod ameliorates schizophrenia-like cognitive impairments induced by phencyclidine in male rats.

Improvement of cognitive deficits in schizophrenia remains an unmet need owing to the lack of new therapies and drugs. Recent studies have reported that fingolimod, an immunomodulatory drug for treating multiple sclerosis, demonstrates anti-inflammatory and neuroprotective effects in several neurological disease models. This suggests its usefulness for ameliorating cognitive dysfunction in schizophrenia. Herein, we assessed the efficacy profile and mechanism of fingolimod in a rat model of phencyclidine (PCP)-induced schizophrenia. Male Sprague-Dawley rats were treated with PCP for 14 days. The therapeutic effect of fingolimod on cognitive function was assessed using the Morris water maze and fear conditioning tests. Hippocampal neurogenesis and the expression of astrocytes and microglia were evaluated using immunostaining. Cytokine expression was quantified using multiplexed flow cytometry. Brain-derived neurotrophic factor expression and phosphorylation of extracellular signal-regulated kinase were determined using western blot analysis. Fingolimod attenuated cognitive deficits and restored hippocampal neurogenesis in a dose-dependent manner in PCP-treated rats. Fingolimod treatment exerted anti-inflammatory effects by inhibiting microglial activation and IL-6 and IL-1β pro-inflammatory cytokine expression. The underlying mechanism involves the upregulation of brain-derived neurotrophic factor protein expression and activation of the ERK signalling pathway. This is the first preclinical assessment of the effects of fingolimod on cognitive function in a model for schizophrenia. Our results suggest the immune system plays an crucial role in cognitive alterations in schizophrenia and highlight the potential of immunomodulatory strategies to improve cognitive deficits in schizophrenia.

Ecstasy metabolites and monoamine neurotransmitters upshift the Na

3,4-Methylenedioximethamphetamine (MDMA ecstasy) is a psychotropic drug with well-known neurotoxic effects mediated by hitherto not fully understood mechanisms. The Na

Psychosocial and Integrative Oncology Interventions Across the Disease Trajectory.

This article provides an overview of the fields of psychosocial and integrative oncology, highlighting common psychological reactions to being diagnosed with and treated for cancer, including distress, anxiety, depression, fear of cancer recurrence and caregiver burden, as well as symptoms of fatigue, pain, and sleep disturbance. Patterns of symptomatology across the disease continuum are also discussed. Interventions targeted at treating these symptoms are reviewed, including acceptance-based and mindfulness therapies, mind-body therapies, and meaning-based approaches designed for people with advanced stages of disease, including psychedelic therapy. Common methodological issues and shortcomings of the evidence base are summarized with design recommendations, and a discussion of trends in future research including pragmatic research design, digital health interventions, and implementation science completes the article.

Facile synthesis of CoFe

The global occurrence of textile dyes pollution has recently emerged, posing a serious threat to ecological systems. To abate dye contamination, we here developed a novel magnetic porous CoFe

A label-free electrochemical aptasensor based on NH

This study successfully developed a simple, specific, and ultrasensitive electrochemical aptasensor based on a label-free strategy for detecting citrinin (CIT). The NH

Increased identification of cannabis use among drivers involved in motor vehicle collisions using an expanded cannabis inventory.

The objectives of this study were to implement and examine the potential capture rate of a novel instrument, the Expanded Cannabis Inventory, in a population of emergency department (ED) patients presenting after motor vehicle collisions (MVC). Study participants who presented to the ED after MVC were recruited from three hospitals in cannabis-legal states (Denver, CO Portland, OR and Sacramento, CA). Research assistants (RAs) administered the Expanded Cannabis Inventory, which includes a wide variety of products that have become readily available in states where cannabis is legal, in addition to assessments related to patient demographic characteristics, general health, cannabis attitudes, and dependency measures. RAs also obtained blood samples for delta-9-THC and metabolites. Among 692 participants who provided responses to questions about cannabis use, 292 (42%) reported past-year use. Seventy-eight (27%) of those identified as using cannabis were only captured due to items in the expanded instrument. These patients were more likely to be White and were more likely to perceive daily use to be of high risk. Fewer had Cannabis Use Disorder Inventory Test (CUDIT) scores consistent with hazardous cannabis use. However, more of the patients only captured by the expanded instrument had high measured blood levels of delta-9-THC on samples obtained in the ED. Changing cannabis use patterns must be reflected in our measurements for clinical practice, research, and surveillance. Instruments that are the current standard in clinical practice capture limited data and may no longer perform well enough to identify a complete cohort or to provide insight into the health behaviors of patients.

Updates in the use of cannabis for insomnia.

This review aims to summarize recent updates in the area of cannabis use for insomnia. Cannabis products have continued to become more potent, particularly in regard to delta-9- tetrahydrocannabinol (THC) concentration. Additionally, the use of cannabis has continued to become more accepted with less legal restrictions. The reported use of cannabis for relief of symptoms in sleep disorders appears to be increasing, however the specific effects of cannabinoids on sleep varies with cannabinoid type and concentration. Some evidence supports claims of efficacy of cannabinoids in sleep disorders such as insomnia, while other evidence is either lacking or in some cases contradictory. Regular cannabis use has been associated with withdrawal which can profoundly alter sleep. Also, clinicians should be aware of the potential effects of cannabis on the metabolism of other medications as well as the fact that cannabis use has been reported in a significant number of women in the periods before, during, and after pregnancy. Cannabis use has been becoming more and more prevalent in the setting of relaxed restrictions and easier consumer level access to cannabis and cannabis products. A relative paucity of high quality evidence regarding the effects of cannabis on sleep and the treatment of insomnia symptoms remains. The optimal type, concentration, ratio, and dosage form of cannabinoids in the treatment of insomnia symptoms needs further clarification. As the trend of acceptance and use of cannabis continues, more high quality evidence to help guide clinicians in their recommendations will hopefully become available.

Neuroprotective potential of Cannabis sativa-based oils in Caenorhabditis elegans.

Substances from the Cannabis sativa species, especially cannabidiol (CBD) and Delta-9-tetrahydrocannabinol (Δ9-THC), have attracted medical attention in recent years. The actions of these two main cannabinoids modulate the cholinergic nervous system (CholNS) involving development, synaptic plasticity, and response to endogenous and environmental damage, as a characteristic of many neurodegenerative diseases. The dynamics of these diseases are mediated by specific neurotransmitters, such as the GABAergic nervous system (GNS) and the CholNS. The nematode Caenorhabditis elegans is an important experimental model, which has different neurotransmitter systems that coordinate its behavior and has a transgene strain that encodes the human β-amyloid 1-42 peptide in body wall muscle, one of the main proteins involved in Alzheimer´s disease. Therefore, the objective of this study was to evaluate the protective potential of terpenoids found in C. sativa in the GNS and CholNS of C. elegans. The effect of two C. sativa oils with variations in CBD and THC concentrations on acetylcholinesterase (AChE) activity, lipid peroxidation, and behavior of C. elegans was evaluated. C. sativa oils were efficient in increasing pharyngeal pumping rate and reducing defecation cycle, AChE activity, and ROS levels in N2 strains. In the muscleAbeta1-42 strain, mainly when using CBD oil, worm movement, body bends, and pharyngeal pumping were increased, with a reduced AChE activity. Consequently, greater investments in scientific research are needed, in addition to breaking the taboo on the use of the C. sativa plant as an alternative for medicinal use, especially in neurodegenerative diseases, which have already shown positive initial results.

Discovery of β-Arrestin-Biased 25CN-NBOH-Derived 5-HT

The serotonin 2A receptor (5-HT

Assessing suicide risk in patients with Obsessive-Compulsive Disorder a dimensional approach.

Obsessive-Compulsive Disorder has recently been found to be associated with an increased risk of suicide however, prevalence rates of both suicidal ideation and attempts vary considerably, being the phenomenon mainly categorically evaluated. Our aims were to evaluate the prevalence of suicidal ideation (SI) and behaviors (SB) using a dimensional approach. 129 patients with OCD were enrolled. Suicidality was assessed through the administration of the Columbia-Suicide Severity Rating Scale. Logistic and linear regressions were used to examine predictors of SI, severe SI, and SB. Lifetime prevalence of SI and SB were 64.3% and 16.3%. Lifetime SI was associated with the number of stressful life events, the duration of illness, HAM-D scores, family history for mood disorders. A positive family history for OCD was associated with lower probability of lifetime SI. Severe SI was related to a greater severity of the highest stressful life event, HAM-D scores and a longer duration of untreated illness. The probability of lifetime SB was related to the HAM-A scores, symmetry obsessions, washing and checking compulsions. The probability of lifetime Non-Suicidal Self-Injurious Behaviors was related to HAM-A scores. The recognition of predictors of SISB is crucial to identify those patients at greater risk.

Cannabis and the heart unchartered territory.

Cannabis is one of the most commonly used illicit drugs. It is a psychoactive drug with tetrahydrocannabinol being the main active ingredient. With increasing decriminalization and legalization of marijuana use in the USA, it is essential to study its long-term effects on cardiovascular diseases, a leading cause of death in the USA. Cannabis can trigger acute myocardial infarction in otherwise healthy young individuals, affect atherogenesis, arrhythmia, develop Takotsubo cardiomyopathy and cannabis arteritis. The only definitive treatment for these pathologies is complete abstinence. In this review we focus on discussing the long-term effects of tetrahydrocannabinol on cardiovascular pathologies, its pathophysiology and a brief discussion on its clinical features and definitive management. Cannabis is one of the most commonly abused drugs. It is a stimulant with tetrahydrocannabinol being the main active ingredient. With increasing decriminalization and legalization of marijuana use in the USA, it is essential to study its long-term effects on heart diseases, a leading cause of death in the USA. Cannabis can trigger heart attacks in otherwise healthy young individuals, affect normal beating of the heart and heart muscle functions and also play a role in narrowing of the blood vessels reducing the blood to distant parts of the body. The only definitive treatment for these marijuana induced heart and blood vessel diseases is completely restricting the use of the drug. In this review, we focus on discussing the long-term effects of tetrahydrocannabinol on development of certain heart and blood vessel diseases and briefly discuss its clinical features and definitive treatment options for complete restrain from marijuana.

Impact of cannabis-infused edibles on public safety and regulation.

Popularity of cannabis-infused products has bloomed since legalization for recreational use of marijuana started. Consumption of cannabis edibles has steadily increased, as restrictions on recreational cannabis smoking have become tighter. This phenomenon enhanced the possibility of these products crossing the state line. The most psychoactive component of cannabis, ∆9-tetrahydrocannabinol (THC) is infused in edibles and linked to physiological and psychological effects. Consumers unfamiliar with these edibles may mistake them for non-THC containing products, causing unintended use or overconsumption. In addition, these cannabis-infused edibles are posing significant health risks. The FDA has recognized the potential dangers and recommended that cannabis remain as a Schedule I substance and illegal at the federal level. However, states maintain control of determining the legality of cannabis related products, and creating guidelines distinguishing cannabis edibles from the non-cannabis containing products. Recently, the State of Maine offers a blueprint for edible regulation that should be implemented in all states that are considering or have legalized marijuana.

A Research Domain Criteria (RDoC)-Guided Dashboard to Review Psilocybin Target Domains A Systematic Review.

Preliminary results from randomized controlled studies as well as identified molecular, cellular, and circuit targets of select psychedelics (e.g., psilocybin) suggest that their effects are transdiagnostic. In this review, we exploit the Research Domain Criteria (RDoC) transdiagnostic framework, to synthesize extant literature on psilocybin. We aimed to identify RDoC-based effects of psilocybin and vistas for future mechanistic and interventional research. A systematic search in electronic databases (i.e., PubMed, Scopus, PsycINFO, and Web of Science) performed in January and February 2021 identified English articles published between 1990 and 2020 reporting the effects of psilocybin on mental health measures. Data from included articles were retrieved and organized according to the RDoC bio-behavioral matrix and its constituent six main domains, namely positive valence systems, negative valence systems, cognitive systems, social processes, sensorimotor systems, and arousal and regulatory systems. The preponderance of research with psilocybin has differentially reported beneficial effects on positive valence systems, negative valence system, and social process domains. The data from the included studies support both short-term (23 assessments) and long-term (15 assessments) beneficial effects of psilocybin on the positive valence systems. While 12 of the extracted outcome measures suggest that psilocybin use is associated with increases in the fear construct of the negative valence systems domain, 19 findings show no significant effects on this construct, and seven parameters show lowered levels of the sustained threat construct in the long term. Thirty-four outcome measures revealed short-term alterations in the social systems construct namely, perception and understanding of self, and social communications as well as enhancements in perception and understanding of others and affiliation and attachment. The majority of findings related to the cognitive systems domain reported dyscognitive effects. There have been relatively few studies reporting outcomes of psilocybin on the remaining RDoC domains. Moreover, seven of the included studies suggest the transdiagnostic effects of psilocybin. The dashboard characterization of RDoC outcomes with psilocybin suggests beneficial effects in the measures of reward, threat, and arousal, as well as general social systems. Psilocybin possesses a multi-domain effectiveness. The field would benefit from highly rigorous proof-of-mechanism research to assess the effects of psilocybin using the RDoC framework. The combined effect of psilocybin with psychosocial interventions with RDoC-based outcomes is a priority therapeutic vista.

Chronic delta-9-tetrahydrocannabinol (THC) treatment counteracts SIV-induced modulation of proinflammatory microRNA cargo in basal ganglia-derived extracellular vesicles.

Early invasion of the central nervous system (CNS) by human immunodeficiency virus (HIV) (Gray et al. in Brain Pathol 61-15, 1996 An et al. in Ann Neurol 40611-6172, 1996), results in neuroinflammation, potentially through extracellular vesicles (EVs) and their micro RNAs (miRNA) cargoes (Sharma et al. in FASEB J 325174-5185, 2018 Hu et al. in Cell Death Dis 3e381, 2012). Although the basal ganglia (BG) is a major target and reservoir of HIV in the CNS (Chaganti et al. in Aids 331843-1852, 2019 Mintzopoulos et al. in Magn Reson Med 812896-2904, 2019), whether BG produces EVs and the effect of HIV andor the phytocannabinoid-delta-9-tetrahydrocannabinol (THC) on BG-EVs and HIV neuropathogenesis remain unknown. We used the simian immunodeficiency virus (SIV) model of HIV and THC treatment in rhesus macaques (Molina et al. in AIDS Res Hum Retroviruses 27585-592, 2011) to demonstrate for the first time that BG contains EVs (BG-EVs), and that BG-EVs cargo and function are modulated by SIV and THC. We also used primary astrocytes from the brains of wild type (WT) and CX3CR1 Significant changes in BG-EV-associated miRNA specific to SIV infection and THC treatment were observed. BG-EVs from SIV-infected rhesus macaques (SIV EVs) contained 11 significantly downregulated miRNAs. Remarkably, intervention with THC led to significant upregulation of 37 miRNAs in BG-EVs (SIV-THC EVs). Most of these miRNAs are predicted to regulate pathways related to inflammationimmune regulation, TLR signaling, Neurotrophin TRK receptor signaling, and cell deathresponse. BG-EVs activated WT and CX3CR1 Our findings reveal a role for BG-EVs as a vehicle with potential to disseminate HIV- and THC-induced changes within the CNS.

A Cannabinoid Fuel Cell Capable of Producing Current by Oxidizing Δ

We report the development of a current-producing H-Cell that relies on the oxidation of Δ

Different degradation mechanisms of low-concentration ozone for MIL-100(Fe) and MIL-100(Mn) over wide humidity fluctuation.

The synergistic control of ozone and fine particulate matter is a research hotspot in the current environmental fields. Among the ozone removal, wide humidity fluctuation and low concentration dynamic adsorption are two thorny problems. In this work, MIL-100(Fe) and MIL-100(Mn), synthesized by hydrothermal and solvothermal methods respectively, were selected to investigate the degradation of flowing ozone pollutants. The samples showed different ozone degradation mechanisms, namely photocatalytic degradation and normal temperature degradation. Notably, MIL-100(Fe) exhibited more outstanding photocatalytic activity than MIL-100(Mn), while the normal temperature catalytic efficiency of MIL-100(Mn) was much superior to MIL-100(Fe). For different humidity conditions, MIL-100(Fe) has the optimal photocatalytic performance at 10% humidity, which is 38%, while MIL-100(Mn) has basically no change in normal temperature catalytic degradation efficiency at different humidity levels of 10-90%. Furthermore, the degradation mechanism was proposed by in-situ DRIFTS and ESR, which was significantly correlated with oxygen vacancy and photogenerated electron efficiency. By the aid of Temperature Programmed Desorption (TPD), a large quantity of Lewis acid sites was detected in MIL-100(Mn), which was the critical factor that the selected materials could maintain excellent normal temperature degradation performance under high humidity. This work will expand the practical application of ozone removal and improve the degradation efficiency.

Population pharmacokineticpharmacodynamic modeling of the psychedelic experience induced by N,N-dimethyltryptamine - Implications for dose considerations.

N,N-dimethyltryptamine (DMT) is a psychedelic compound that is believed to have potential as a therapeutic option in several psychiatric disorders. The number of clinical investigations with DMT is increasing. However, very little is known about the pharmacokinetic properties of DMT as well as any relationship between its exposure and effects. This study aimed to characterize population pharmacokinetics of DMT as well as the relationship between DMT plasma concentrations and its psychedelic effects as measured through subjective intensity ratings. Data were obtained from 13 healthy subjects after intravenous administration of DMT. The data were analyzed using nonlinear mixed-effects modeling in NONMEM. DMT plasma concentrations were described by a two-compartment model with first-order elimination leading to formation of the major metabolite indole 3-acetic acid. The relationship between plasma concentrations and psychedelic intensity was described by an effect site compartment model with a sigmoid maximum effect (E

Why Otolaryngologists Should Be Interested in Psychedelic Medicine.

As psychedelic medicine is becoming mainstream, physicians need to know something about these medications, their indications, contraindications, and potential for research. This article is a brief overview of the subject with some ideas of how psychedelic medicines can impact the practice of Otolaryngology-Head and Neck Surgery.

Signaling snapshots of a serotonin receptor activated by the prototypical psychedelic LSD.

Serotonin (5-hydroxytryptamine 5-HT) 5-HT2-family receptors represent essential targets for lysergic acid diethylamide (LSD) and all other psychedelic drugs. Although the primary psychedelic drug effects are mediated by the 5-HT

Toward a typology of driving under the influence of alcohol and drugs.

Most research on driving under the influence (DUI) has relied upon variable-centered methods that examine predictorscorrelates of DUI. In the present study, we utilize a person-level approach-latent class analysis (LCA)-to model a typology of individuals reporting DUI. This allows us to understand the degree to which individuals drive under the influence of a particular substance or do so across multiple substance types. We use public-use data collected between 2016 and 2019 from the National Survey on Drug Use and Health. The analytic sample was 189,472 participants with a focus on those reporting DUI of psychoactive substances in the past-year (n 24,619). LCA was conducted using self-reported DUI of past-year alcohol, cannabis, cocaine, heroin, hallucinogens, and methamphetamine as indicator variables. More than 1 in 10 Americans reported a DUI within the past-year. One in five people who reported DUI of one substance also reported DUI of at least one additional substance. Using LCA to model heterogeneity among individuals reporting DUI, four classes emerged Alcohol Only (55%), Cannabis and Alcohol (36%), Polydrug (5%), and Methamphetamine (3%). Rates of risk propensity, drug involvement, illicit drug use disorders, and criminal justice system involvement were highest among members of the Polydrug and Methamphetamine classes. Drug treatment centers should take care to include discussions of the dangers and decision-making processes related to DUI of the full spectrum of illicit substances. Greater investment in drug treatment across the service continuum, including the justice system, could preventreduce future DUI episodes.

Children and adolescents with ASD treated with CBD-rich cannabis exhibit significant improvements particularly in social symptoms an open label study.

In recent years there has been growing interest in the potential benefits of CBD-rich cannabis treatment for children with ASD. Several open label studies and one double-blind placebo-controlled study have reported that CBD-rich cannabis is safe and potentially effective in reducing disruptive behaviors and improving social communication. However, previous studies have mostly based their conclusions on parental reports without the use of standardized clinical assessments. Here, we conducted an open label study to examine the efficacy of 6 months of CBD-rich cannabis treatment in children and adolescents with ASD. Longitudinal changes in social communication abilities and restricted and repetitive behaviors (RRB) were quantified using parent report with the Social Responsiveness Scale and clinical assessment with the Autism Diagnostic Observation Schedule (ADOS). We also quantified changes in adaptive behaviors using the Vineland, and cognitive abilities using an age-appropriate Wechsler test. Eighty-two of the 110 recruited participants completed the 6-month treatment protocol. While some participants did not exhibit any improvement in symptoms, there were overall significant improvements in social communication abilities as quantified by the ADOS, SRS, and Vineland with larger improvements in participants who had more severe initial symptoms. Significant improvements in RRB were noted only with parent-reported SRS scores and there were no significant changes in cognitive scores. These findings suggest that treatment with CBD-rich cannabis can yield improvements, particularly in social communication abilities, which were visible even when using standardized clinical assessments. Additional double-blind placebo-controlled studies utilizing standardized assessments are highly warranted for substantiating these findings.

Bimetallic Metal-Organic Framework FeCo-MIL-88(NH

Metal-organic frameworks (MOFs) have many attractive features, including tunable composition, rigid structure, controllable pore size, and large specific surface area, and thus are highly applicable in molecular analysis. Depending on the MOF structure, a high number of unsaturated metal sites can be exposed to catalyze chemical reactions. In the present work, we report that using both Co(II) and Fe(III) to prepare the MIL-88(NH

A Critical Evaluation of Terpenoid Signaling at Cannabinoid CB1 Receptors in a Neuronal Model.

In addition to phytocannabinoids, cannabis contains terpenoids that are claimed to have a myriad of effects on the body. We tested a panel of five common cannabis terpenoids, myrcene, linalool, limonene, α-pinene and nerolidol, in two neuronal models, autaptic hippocampal neurons and dorsal root ganglion (DRG) neurons. Autaptic neurons express a form of cannabinoid CB1 receptor-dependent retrograde plasticity while DRGs express a variety of transient receptor potential (TRP) channels. Most terpenoids had little or no effect on neuronal cannabinoid signaling. The exception was nerolidol, which inhibited endocannabinoid signaling. Notably, this is not via inhibition of CB1 receptors but by inhibiting some aspect of 2-arachidonoylglycerol (2-AG) productiondelivery the mechanism does not involve reducing the activity of the 2-AG-synthesizing diacylglycerol lipases (DAGLs). Nerolidol was also the only terpenoid that activated a sustained calcium response in a small (7%) subpopulation of DRGs. In summary, we found that only one of five terpenoids tested had notable effects on cannabinoid signaling in two neuronal models. Our results suggest that a few terpenoids may indeed interact with some components of the cannabinoid signaling system and may therefore offer interesting insights upon further study.

In the Swim of Cannabis Developmental Toxicity and Metabolomic Pathway Alterations of Zebrafish Larvae Exposed to THC for the Assessment of Its Potential Environmental and Human Health Impact.

As the pharmacological properties and therapeutic applications of

The Determination of Cannabinoids in Urine Samples Using Microextraction by Packed Sorbent and Gas Chromatography-Mass Spectrometry.

Cannabis is the most consumed illicit drug worldwide, and its legal status is a source of concern. This study proposes a rapid procedure for the simultaneous quantification of Δ

Bufotenines-loaded liposome exerts anti-inflammatory, analgesic effects and reduce gastrointestinal toxicity through altering lipid and bufotenines metabolism.

Bufotenines, a natural component from toad venom, showed great potential for development as a novel anti-inflammation and analgesia agent, but the potential toxicity limited its clinic use. In this paper, bufotenines-loaded liposome was prepared and optimized. Then, the therapeutic effects and drug safety of bufotenines-liposome were investigated against inflammation and pain on animal models, with a focus on gastrointestinal toxicity. Bufotenines and its liposome significantly increased paw withdrawal mechanical threshold (PWMT) in Von Frey test and hot paw withdrawal latency (HPWL) in hot-plate test. Moreover, intestinal absorption in vitro and pathological analysis in vivo showed that total bufotenines-loaded liposome significantly reduced the gastrointestinal irritation through reducing exposure of total bufotenines on intestinal tissue. High-sensitivity lipidomics analysis revealed the effect of total bufotenines-loaded liposome were be related to the down-regulation of inflammatory mediators from cyclooxygenase (COX) and lipoxygenase (LOX), the up-regulation of cytochrome P450 (CYP450), and other pathways, thus regulating lipid metabolism pathway and ultimately reducing gastrointestinal irritation. This study shows that liposome-loaded bufotenines has anti-inflammatory, analgesic effects and achieves toxicity reduction. These results provide systematic evidences for efficacy and safety of toad venom active ingredients.

NAbiximols Clinical Translation To the treatment of Pain and Agitation In Severe Dementia (NACTOPAISD) Clinical trial protocol.

Up to 80 % nursing home residents with dementia experiences chronic pain. Contextually, 97 % presents fluctuant neuropsychiatric symptoms (NPS). Among the most challenging is agitation, connected with undertreated pain and managed through neuroleptics doubling death risk. Evidence is accumulating in favor of the involvement of the endocannabinoid system in nociception and NPS. This double-blind, placebo-controlled, randomized trial (NAbiximols Clinical Translation To the treatment of Pain and Agitation In Severe Dementia NACTOPAISD) aims at investigating efficacy and safety of oral spray nabiximols, containing Δ9-tetrahydrocannabinol and cannabidiol (Sativex®), for pain and agitation treatment in severe dementia patients (Mini-Mental State Examination ≤ 12) over 65. The coprimary endpoints are efficacy on pain and agitation, assessed through the recently validated Italian Mobilization-Observation-Behavior-Intensity-Dementia and the Cohen-Mansfield Agitation Inventory. The secondary endpoint is the evaluation of efficacy duration after wash-out and the assessment of quality of life through the DEMQOL. Any adverse events will be reported. The results undergo statistical analysis plan. NACTOPAISD might provide rationale for a translational safer pain and agitation treatment in severe dementia. It is approved by Calabria Region Ethics Committee and follows the Standard Protocol Items Recommendations for Interventional Trials (SPIRIT) and the Consolidated Standards of Reporting Trials (CONSORT) statements.

Chromatographic analysis of CBD and THC after their acylation with blockade of compound transformation.

for the analysis of cannabinoids in bio-matrices are continually improved to achieve best possible sensitivity in their detection and accurate quantification. It has been well documented that CBD cyclizes to Δ9-THC and Δ9-THC isomerizes to Δ8-THC under acidic conditions by means of a Lewis-acid-catalyzed process, causing difficulty in accurate quantification of Δ9-THC in the presence of CBD, of CBD itself and of Δ9-THC itself when these compounds have to be derivatized by acylation. The present paper shows that CBD cyclization and Δ9-THC isomerization can be blocked by tertiary amines or azines, which capture protons appearing in the derivatizing mixture during acylation. The efficiency of the described acylation of CBD depends on the time and temperature of the derivatizing process, whereas the degree of CBD acylation, i.e. the synthesis of mono- or di-acylate CBD derivative, depends on the mutual ratio of the cannabinoid, the acylating agent and the proton binding compound. The way of mono- and di-acyl CBD derivatives formation described in the paper has not been reported yet. The paper contains a comprehensive analytical characterization of two types of CBD acyl derivatives, CBD-TFA and CBD-Ac, obtained by NMR, GC-MS and LC-MS.

Evidence on the impairing effects of Ayahuasca on fear memory reconsolidation.

To uncover whether psychedelic drugs attenuate fear memory responses would advance the development of better psychedelic-based treatments for posttraumatic stress disorder (PTSD). Ayahuasca (AYA), a psychedelic brew containing indolamine N, N-dimethyltryptamine (DMT) and β-carbolines, facilitates fear extinction and improves neural plasticity. Upon retrieval, fear memory undergoes labilization and reconsolidation however, the effects of AYA on this memory stabilization phase are unknown. We aimed to investigate the effects of AYA treatment on fear memory reconsolidation. Fear-conditioned Wistar rats received AYA (60, 120, or 240 mgkg) or H AYA impaired fear memory reconsolidation when given 20 min before or 3 h after memory retrieval, with the dose of 60 mgkg being effective at both moments. This dose of AYA was devoid of anxiolytic effect. Importantly, during retrieval, AYA did not change fear expression. The lack of retrieval abolished the reconsolidation impairing effect of AYA. The effects of AYA treatment 20 min before or 3 h after memory retrieval lasted at least 22 days, suggesting no spontaneous recovery of fear memory. Fear memory impairments induced by AYA treatment, at both moments, do not show reinstatement. Our findings support the view that a low dose of AYA treatment impairs early and late stages of memory reconsolidation instead of facilitating fear extinction.

An ultrasensitive cathodic electrochemiluminescence immunoassay for thrombomodulin based on Ru(bpy)

The rapid and reliable determination of thrombomodulin (TM) is of great significance for the diagnosis of disseminated intravascular coagulation, thrombosis and others. This work exhibits an electrochemiluminescent (ECL) sensor, which was prepared using Ru(bpy)

Transdiagnostic connectome signatures from resting-state fMRI predict individual-level intellectual capacity.

Medication and other therapies for psychiatric disorders show unsatisfying efficacy, in part due to the significant clinical biological heterogeneity within each disorder and our over-reliance on categorical clinical diagnoses. Alternatively, dimensional transdiagnostic studies have provided a promising pathway toward realizing personalized medicine and improved treatment outcomes. One factor that may influence response to psychiatric treatments is cognitive function, which is reflected in ones intellectual capacity. Intellectual capacity is also reflected in the organization and structure of intrinsic brain networks. Using a large transdiagnostic cohort (n 1721), we sought to discover neuroimaging biomarkers by developing a resting-state functional connectome-based prediction model for a key intellectual capacity measure, Full-Scale Intelligence Quotient (FSIQ), across the diagnostic spectrum. Our cross-validated model yielded an excellent prediction accuracy (r 0.5573, p < 0.001). The robustness and generalizability of our model was further validated on three independent cohorts (n 2641). We identified key transdiagnostic connectome signatures underlying FSIQ capacity involving the dorsal-attention, frontoparietal and default-mode networks. Meanwhile, diagnosis groups showed disorder-specific biomarker patterns. Our findings advance the neurobiological understanding of cognitive functioning across traditional diagnostic categories and provide a new avenue for neuropathological classification of psychiatric disorders.

Magnetic restricted-access carbon nanotubes for SPME to determine cannabinoids in plasma samples by UHPLC-MSMS.

This manuscript describes the development of magnetic restricted-access carbon nanotubes (M-RACNTs) for use as SPME sorbent to determine cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) in human plasma samples by UHPLC-MSMS. The adsorptive phase was immobilized on an SPME device by electromagnetic interactions between the M-RACNTs and a cylindrical neodymium magnet (3-mm diameter x 8-mm height) attached to a stainless-steel rod (3-mm diameter x 40-mm height). The M-RACNTs were synthesized by incorporating Fe

Simultaneous quantification of 106 drugs or their metabolites in nail samples by UPLC-MSMS with high-throughput sample preparation Application to 294 real cases.

The nail is an alternative matrix to complement hair analysis in proving drug intake over several months in forensic toxicology investigations. However, because of the high hardness and toughness of nails, the existing pretreatment procedures for nails have the disadvantages of either a high degree of time consumption (from hours to days), or low extraction recoveries. This study aims to propose a high-throughput nail sample preparation method and provide a quantitative analytical method for 106 drugs and their metabolites present in nail. We developed cryogenic grinding, coupled with high-speed grinding in the extraction solvent method, which could improve the extraction recovery by thoroughly destroying the nail keratin for approximately 18 min. Subsequently, an ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed for the identification and quantification of 34 synthetic cannabinoids, 26 fentanyls, 18 synthetic cathinones, 10 phenylethylamines, eight opioids, three phencyclidine, two tryptamines, two piperazine, cocaine, benzoylecgonine, and tetrahydrocannabinol (THC). Nail samples were collected from people with a history of drug abuse from five different regions of China. The analysis of 294 authentic samples resulted in 213 detected samples, and showed a broad concentration range including 5.04-67.26 pgmg for nine synthetic cannabinoids, 109.29-250.29 pgmg for a synthetic cathinone, 5.06-434291 pgmg for four phenylethylamines, 5.06-464278 pgmg for three phencyclidine, 5.50-192195 pgmg for six opioids, 19.44-36.11 pgmg for cocaine, and 50.53 pgmg for THC in nail. Furthermore, up to 10 different compounds were detected in a single nail sample. This nail analysis method serves as a useful tool for the large-scale surveillance of illicit drugs abuse.

Microdosing psilocybin for chronic pain a case series.

Psychedelic serotonergic agonists such as psilocybin have recently been shown to produce sustained benefit in refractory depression, end of life anxiety, and addiction when administered in hallucinogenic doses and coupled with psychotherapy. Although it has been suggested that similar high-dose protocols may help chronic pain conditions, there are few published clinical trials of psychedelics for pain. The use of these agents in subpsychedelic doses for chronic pain management has received even less attention. This case series details the experiences of 3 individuals who have used low-dose psilocybin to manage chronic neuropathic pain. Although the nature and etiology of each patients pain vary, they share a common experience, including inefficacy of current therapeutics and decreased quality of life. Through self-administration of psilocybin, these patients have achieved robust pain relief with decreased reliance on traditional analgesic medications. Despite varying preparations and uncertain potencies, the analgesic effects for all 3 patients occurred at doses without a psychedelic experience and with minimal cognitive or somatic adverse effects. Furthermore, the efficacy of pain relief and, in some cases, the duration of the effect were magnified when coupled with functional exercise. In addition, in 1 case, repeated dosing seemed to produce increased relief, suggesting a possible long-term plasticity-mediated effect. These commonalities highlight psilocybins therapeutic potential in the treatment of chronic pain that warrants further investigation.

Effects of psilocybin versus escitalopram on rumination and thought suppression in depression.

Major depressive disorder is often associated with maladaptive coping strategies, including rumination and thought suppression. To assess the comparative effect of the selective serotonin reuptake inhibitor escitalopram, and the serotonergic psychedelic psilocybin (COMP360), on rumination and thought suppression in major depressive disorder. Based on data derived from a randomised clinical trial ( A time×condition interaction was found for rumination (F(1, 56) 4.58, These data provide further evidence on the therapeutic mechanisms of psilocybin and escitalopram in the treatment of depression.

Illicit drugs and their metabolites in urban wastewater Analysis, occurrence and consumption in Xinjiang, China.

The use of illicit drugs has increased considerably across the world. Wastewater-based epidemiology (WBE) of illicit drugs might help determine the types and quantity of illicit drugs consumed in a region. In this study, WBE was applied to analyze illicit drugs in five representative urban wastewater treatment plants (WWTPs) in Xinjiang, China. The collected samples were pretreated under optimized solid-phase extraction conditions and then analyzed using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MSMS). The results revealed the presence of 9 of the 11 evaluated drugs among them, the concentrations of these substances ranged as follows METH (2.60-10.02 ngL), MDMA (0.49-6.87 ngL), MOR (4.53-44.75 ngL), COD (2.24-8.30 ngL), MTD (1.36-3.75 ngL), COC (0.48 ngL), THC (5.98-18.89 ngL), BE (1.12-2.45 ngL) and KET (1.50 ngL). And an estimate of the per capita consumption revealed morphine (10.2 mgd1000inhabitants), cannabis (3.9 mgd1000inhabitants), 3,4-methylenedioxymethamphetamine (3.9 mgd1000 inhabitants), and methamphetamine (2.2 mgd1000 inhabitants) as the main substances of abuse in Xinjiang, China. The results of this study might be taken as a reference for future studies on the continuous monitoring of such drugs.

Harm reduction in the hospital An overdose prevention site (OPS) at a Canadian hospital.

Substance use management in hospitals can be challenging. In response, a Canadian hospital opened an overdose prevention site (OPS) where community members and hospital inpatients can inject pre-obtained illicit drugs under supervision. This study aims to (1) describe program utilization patterns (2) characterize OPS visits and (3) evaluate overdose events and related outcomes. A retrospective chart review was completed at one hospital in Vancouver, Canada. All community members and hospital inpatients who visited the OPS between May 2018 and July 2019 were included. Client measures included hospital inpatient status, use of intravenous access line for drug injection, and substances used. Program measures included number of visits (dailymonthly), overdose (fatalnon-fatal) events and overdose-related outcomes. Overall, 11,673 OPS visits were recorded. Monthly visits increased from 306 to 1198 between May 2018 and July 2019 respectively. On average, 26 visits occurred daily. Among all visits, 20% reported being a hospital inpatient, and 5% reported using a hospital intravenous access line for drug injection. Opioids (56%) and stimulants (24%) were the most common substances used. Overall 39 overdose events occurred - 82% required naloxone reversal, 28% required transfer to the hospitals emergency department and none were fatal. Overdose events were more common among hospital inpatients compared to community clients (6.6 vs 2.2 per 1000 visits respectively p value 0.046). This unique OPS is an example of a hospital-based harm reduction initiative. Use of the site increased over time among both groups with no fatal overdose events occurring.

Expectancy in placebo-controlled trials of psychedelics if so, so what

Modern psychedelic research remains in an early phase, and the eventual introduction of psychedelics into clinical practice remains in doubt. In this piece, we discuss the role of blinding and expectancy in psychedelic trials, and place this in a broader historical and contemporary context of blinding in trials across the rest of healthcare. We suggest that premature and uncritical promotion (hype) of psychedelics as medicines is not only misleading, but also directly influences participant expectancy in ongoing psychedelic trials. We argue that although psychedelic trials are likely to significantly overestimate treatment effects by design due to unblinding and expectancy effects, this is not a unique situation. Placebo-controlled RCTs are not a perfect fit for all therapeutics, and problems in blinding should not automatically disqualify medications from licencing decisions. We suggest that simple practical measures may be (and indeed already are) taken in psychedelic trials to partially mitigate the effects of expectancy and unblinding, such as independent raters and active placebos. We briefly suggest other alternative trial methodologies which could be used to bolster RCT results, such as naturalistic studies. We conclude that the results of contemporary placebo-controlled RCTs of psychedelics should neither be dismissed due to imperfections in design, nor should early data be taken as firm evidence of effectiveness.

Portable biosensors for rapid on-site determination of cannabinoids in cannabis, a review.

Recent studies highlight the therapeutic virtues of cannabidiol (CBD). Furthermore, due to their molecular enriched profiles, cannabis inflorescences are biologically superior to a single cannabinoid for the treatment of various health conditions. Thus, there is flourishing demand for Cannabis sativa varieties containing high levels of CBD. Additionally, legal regulations around the world restrict the cultivation and consumption of tetrahydrocannabinol (THC)-rich cannabis plants for their psychotropic effects. Therefore, the use of cannabis varieties that are high in CBD is permitted as long as their THC content does not exceed a low threshold of 0.3%-0.5%, depending on the jurisdiction. These chemovars are legally termed hemp. This controlled cannabinoid requirement highlights the need to detect low levels of THC, already in the field. In this review, cannabis profiling and the existing methods used for the detection of cannabinoids are firstly evaluated. Then, selected valuable biosensor technologies are discussed, which suggest portable, rapid, sensitive, reproducible, and reliable methods for on-site identification of cannabinoids levels, mainly THC. Recent cutting-edge techniques of promising potential usage for both cannabis and hemp analysis are identified, as part of the future cultivation and agricultural improvement of this crop.

Coping motives mediate the relationship between PTSD and MDMA use in adolescents with substance use disorders.

Post-traumatic stress disorder (PTSD) and substance use disorders (SUDs) often co-occur in adolescent patients. Previous research has shown that these patients differ from SUD patients without PTSD in terms of their substance use patterns. In this study, we aimed to test whether substance use in this population is related to an attempt to self-medicate PTSD-related symptoms. German adolescent patients (aged 13-18 years) at an outpatient clinic for SUD treatment, n 111 (43% female), completed a self-designed questionnaire on use motives, a measure of PTSD-related experiences, and underwent a standardized psychiatric interview including structured substance use questions. Participants were subsequently classified as no traumatic experiences (noTEs but SUD), traumatic experiences but no current PTSD diagnosis (TEs with SUD), and PTSD with SUD. After establishing a self-designed motive measurement through exploratory and confirmatory factor analyses, we calculated non-parametric group differences and a mediation analysis in a linear regression framework. The past-year frequency of MDMA use was highest in the PTSD group and lowest in the noTE group (H (2) 7.2, p .027, η In adolescent SUD patients, we found an association of current PTSD and lifetime traumatic experiences with higher MDMA use that could be partially explained by substance use being motivated by an attempt to cope with mental health symptoms. This indicates a coping process involved specifically in MDMA use compared to the use of other psychoactive substances, possibly due to unique psychoactive effects of MDMA.

Recreational drug toxicity with severe hyperthermia Rapid onsite treatment and clinical course.

Electronic dance music festivals have gained notoriety in the critical care and emergency medicine fields due to an alarming incidence of hospitalizations and deaths related to the high prevalence of recreational drug use. Recreational drug use toxicity, in part related to sympathomimetic toxidromes, may cause hyponatremia, seizures, rhabdomyolysis, hyperkalemia, acidosis, coagulopathy, circulatory shock, multi-organ failure, and even death. This wide-ranging syndrome has been referred to as psychostimulant drug-induced toxicity. Rapid onsite diagnosis and treatment, with attention to the A-B-Cs of clinical emergencies, is essential to preserve life. We describe a patient presenting with the highest recorded core temperature in a survivor of psychostimulant drug-induced toxicity, and emphasize management principles of this life-threatening and increasingly prevalent condition.

Psychological reactance and adolescent cannabis use The role of parental warmth and monitoring.

Psychological reactance (PR) is a psychological state or trait typified by resistant responses to threats to behavioral freedom. PR has been linked with negative health behaviors, including risky substance use however, factors that may foster approaches to mitigate the impact of PR on these behaviors, as well as rejection of other health promotion communications is less understood. The current studies examined relations between parental warmth and monitoring with trait PR and responses to preventive cannabis communications and usage intentions. Two in-school surveys were administered to two difference samples of middle school students (Study 1, N 1,416 Study 2, N 1,118). Path analytic models tested multivariable linkages among relevant parenting variables, PR, and outcomes associated with cannabis use. Follow-up regression analyses explored significant interaction effects. In Study 1 (p <0.001) and Study 2 (p <0.01), parental warmth moderated the relation between monitoring and trait PR High monitoring was a protective factor only when combined with high warmth. In turn, PR mediated the relationships between parenting practices and cannabis intentions in both studies (p <0.001). In Study 2, PR also was linked with resistance to persuasion via more unfavorable reactions to anti-cannabis appeals (p <0.001). Findings indicated that low parental warmth combined with high parental monitoring was associated with high trait reactance in adolescents, which predisposed them to stronger resistance to preventive communications. Interventions might focus on counseling parents about the likely outcomes of parenting style, and ways to implement beneficial approaches.

High-order functional redundancy in ageing explained via alterations in the connectome in a whole-brain model.

The human brain generates a rich repertoire of spatio-temporal activity patterns, which support a wide variety of motor and cognitive functions. These patterns of activity change with age in a multi-factorial manner. One of these factors is the variations in the brains connectomics that occurs along the lifespan. However, the precise relationship between high-order functional interactions and connnectomics, as well as their variations with age are largely unknown, in part due to the absence of mechanistic models that can efficiently map brain connnectomics to functional connectivity in aging. To investigate this issue, we have built a neurobiologically-realistic whole-brain computational model using both anatomical and functional MRI data from 161 participants ranging from 10 to 80 years old. We show that the differences in high-order functional interactions between age groups can be largely explained by variations in the connectome. Based on this finding, we propose a simple neurodegeneration model that is representative of normal physiological aging. As such, when applied to connectomes of young participant it reproduces the age-variations that occur in the high-order structure of the functional data. Overall, these results begin to disentangle the mechanisms by which structural changes in the connectome lead to functional differences in the ageing brain. Our model can also serve as a starting point for modeling more complex forms of pathological ageing or cognitive deficits.

Serotonin 5-HT

The psychedelic 5-HT

Analytical investigation of cannabis biomarkers in raw urban wastewater to refine consumption estimates.

Wastewater analysis of Δ

To treat or not to treat High-potency benzodiazepine use in a case of comorbid hallucinogen persisting perception disorder and alcohol use disorder.

Hallucinogen persisting perception disorder (HPPD) is characterized by visual disturbances that resemble psychedelic intoxication and linger after use has ceased. The most common substances precipitating HPPD, lysergic acid diethylamide (LSD) and psilocybin, are posited to do so via damage to serotonergic neurons involved in vision. Mr. N is a 37-year-old with a history of alcohol, cannabis, LSD, cocaine, and nicotine use disorders who described visual distortions that resolved when he drank heavily or received benzodiazepines for withdrawal. He did not appear psychotic. Over 20 years after his last LSD use, he continued to experience illusions of halos around objects, moving walls, and figures appearing cartoonish. He understood that his perceptual disturbances were not reality based. During hospitalization for suicidal ideation, laboratory tests, head computed tomography (CT), and electroencephalogram (EEG) studies offered no explanation for his visual disturbances other than HPPD. The visual distortions remitted with scheduled clonazepam treatment, although chemical dependency treatment programs were hesitant to accept him while on a benzodiazepine. This case emphasizes the importance of diagnostic clarification when patients present with perceptual disturbances that do not fit typical psychotic presentations. Our discussion will distinguish misperceptions from hallucinations and review the pathophysiology of HPPD. Last, we will discuss management strategies for patients with co-occurring HPPD and substance use disorders. It is necessary to discern the correct cause of visual disturbances in order to provide proper treatment. The risks and benefits of long-term benzodiazepine use must be weighed when deciding whether to prescribe them for patients with comorbid HPPD and alcohol use disorder. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Ketamine and Its Emergence in the Field of Neurology.

The quest for a safe and effective anesthetic medication in the mid-20th century led to the discovery of CI-581, which was later named ketamine. Ketamine was labeled a dissociative anesthetic due to the state of sensory deprivation that it induces in the subjects receiving it. Although it enjoyed widespread use at the beginning of the Vietnam war, its use rapidly waned due to its psychedelic effect and it became more popular as a recreational drug, and in the field of veterinary medicine. However, as we gained more knowledge about its multiple sites of action, it has reemerged as a useful anestheticanalgesic agent. In the last decade, the field of neurology has witnessed the growing use of ketamine for the treatment of several neurological conditions including migraine, status epilepticus, stroke, and traumatic brain injury (TBI). Ketamine acts primarily as a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. The binding of ketamine to NMDA receptors leads to decreased frequency and duration of Ca

Impact of Cannabis Use, Substance Use Disorders, and Psychiatric Diagnoses on COVID-19 Outcomes A Retrospective Cohort Study.

Preparing for the Bursting of the Psychedelic Hype Bubble.

This Viewpoint presents impediments to the clinical application of psychedelics created by extreme shifts in public perception while advocating further study and encouraging the dispute of claims not supported by available evidence.

Using the BMD Approach to Derive Acceptable Daily Intakes of Cannabidiol (CBD) and Tetrahydrocannabinol (THC) Relevant to Electronic Cigarette Liquids.

In the past 60 years, Before an analysis to estimate a reference dose (RfD) for both cannabinoids, a systematic review of dose-response data was conducted. The data obtained were analyzed using the BMD approach to derive a benchmark dose lower confidence limit (BMDL). The BMDL was used as a point of departure to estimate the RfD. No adequate human data suitable for dose-response modeling were identified. Based on animal data, the RfD values for the most sensitive endpoints were selected. For CBD, an RfD for acute exposure of 1 mgkg body weight (bw) was estimated. For Δ Because of the limited availability and quality of dose-response data, it cannot be excluded that the estimated RfD values might be afflicted with considerable uncertainties. Therefore, it is recommended to conduct further research on dose-response data, preferably from human studies.

Separation of soy isoflavones from soy sauce residue by MIL-100(Fe).

Soy sauce residue (SSR) is a valuable biological resource, which contains soy isoflavones (SIs) with antioxidant activity and can be used to scavenge radicals. Herein, MIL-100(Fe) was synthesized for the extraction of SIs from SSR. Under the optimal adsorption conditions, the adsorption capacity of MIL-100(Fe) for SIs was 51.81 mgg, which could achieve a purity of 56.17% and a recovery of 93.8%. These results demonstrated MIL-100(Fe) possessed effective properties of adsorption and purification for SIs. The content of SIs in the purified product was 167 times than that of SSR. The purified total SIs had a good antioxidant activity. The established method had a good scavenging ability toward 2, 2-diphenyl-1-picrylhydrazyl, superoxide and hydroxyl radicals, with IC

The use of psilocybin for treatment-resistant depression.

The hallucinogen psilocybin is a potential novel treatment for treatment-resistant depression (TRD). Our goal is to review current knowledge on psilocybin and its efficacy in TRD. Literature searches were done on PubMed, Web of Science and Google Scholar, references reviewed in identified articles and other articles found on the website of COMPASS Pathways. Psilocybin treatment consists usually of a single oral administration of 25 mg of psilocybin along with psychological support for 5-8 hours during the ensuing hallucinogenic trip. Common side-effects include headache, nausea, fatigue and insomnia. A systematic review has demonstrated significant antidepressant efficacy in certain groups and a double-blind randomized study found antidepressant efficacy of psilocybin comparable to the SSRI escitalopram. In the phase 2 study of COMPASS Pathways, the psilocybin-COMP360 treatment led to a rapid response and remission as early as three weeks following the treatment for around one third of participants. Recent studies have shown that psilocybin significantly decreases the severity of depressive symptoms and is generally well tolerated. Further research will reveal whether it will be granted a license to treat treatment-resistant depression in the near future. There remains an urgent need for novel treatments for those who do not respond to current antidepressant therapies.