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The influence of ceremonial settings on mystical and challenging experiences occasioned by ayahuasca A survey among ritualistic and religious ayahuasca users.

Recent studies have recognized the importance of non-pharmacological factors such as setting to induce or promote mystical experiences or challenging experiences among ayahuasca users. This study aimed to evaluate the association between the setting in which ayahuasca is consumed and the intensity of mystical and challenging experiences considering three ayahuasca using traditions (União do Vegetal, Santo Daime and neo-shamanic groups). A cross-sectional analysis was performed on survey data collected online from 2,751 participants. The Setting Questionnaire for the Ayahuasca Experience (SQAE) was used to evaluate six dimensions of the setting characteristics. The Mystical Experience Questionnaire (MEQ) and the Challenging Experience Questionnaire (CEQ) were used to quantify the psychedelic experience. Ratings on every SQAE setting dimension were negatively correlated with ratings of the CEQ (

Medicinal cannabis for the treatment of anxiety disorders.

Anxiety is second most common reason for medicinal cannabis prescription in Australia and is being treated with both Δ9-tetrahydrocannabinol (THC)-containing and cannabidiol (CBD)-dominant products. The aim of this article is to summarise recent advances in the understanding of medicinal cannabis in treating anxiety and recent trends in prescribing. Clinical trials and laboratory studies provide evidence of anxiolytic effects of CBD in healthy volunteers and clinical populations, although current evidence is insufficient to support CBD as a first-line treatment. The evidence regarding the use of THC-dominant products for anxiety is ambiguous, with exacerbation of anxiety in some individuals and relief in others. Caution is required as THC can impair driving and cognitive function. Despite the lack of robust supportive evidence, prescription of medicinal cannabis products for anxiety is increasing rapidly, while illicit cannabis is widely used in the community to self-medicate anxiety. Approximately 17% of current prescriptions for anxiety are for CBD- dominant liquid products (oils), wafers and capsules, while the remainder are for THC-containing liquid products (33%) and herbal cannabis for vaporisation (50%). Medical practitioners should carefully consider potential risks and benefits when prescribing medicinal cannabis for anxiety disorders and should start low and go slow.

Simultaneous quantification of urinary tobacco and marijuana metabolites using solid-supported liquid-liquid extraction coupled with liquid chromatography tandem mass spectrometry.

Co-exposure to tobacco and marijuana has become common in areas where recreational marijuana use is legal. To assist in the determination of the combined health risks of this co-exposure, an analytical method capable of simultaneously measuring tobacco and marijuana metabolites is needed to reduce laboratory costs and the required sample volume. So far, no such analytical method exists. Thus, we developed and validated a method to simultaneously quantify urinary levels of trans-3-hydroxycotinine (3OH-COT), cotinine (COT), and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (COOH-THC) to assess co-exposure to tobacco and marijuana. Urine (200 µL) was spiked with labelled internal standards and enzymatically hydrolyzed to liberate the conjugated analytes before extraction using solid-supported liquid-liquid extraction (SLE) with ethyl acetate serving as an eluent. The target analytes were separated on a C18 (4.6 × 100 mm, 5 μm) analytical column with a gradient mobile phase elution and analyzed using tandem mass spectrometry with multiple reaction monitoring of target ion transitions. Positive electrospray ionization (ESI) was used for 3OH-COT and COT, while negative ESI was used for COOH-THC. The total run time was 13 min. The extraction recoveries were 18.4-23.9 % (3OH-COT), 65.1-96.8 % (COT), and 80.6-95.4 % (COOH-THC). The method limits of quantification were 5.0 ngmL (3OH-COT) and 2.5 ngmL (COT and COOH-THC). The method showed good accuracy (82.5-98.5 %) and precision (1.22-6.21 % within-day precision and 1.42-6.26 % between-day precision). The target analytes were stable for at least 144 h inside the autosampler (10 °C). The analyses of reference materials and 146 urine samples demonstrated good method performance. The use of a 96-well plate for preparation makes the method useful for the analysis of large numbers of samples.

Medical cannabis use in Australia consumer experiences from the online cannabis as medicine survey 2020 (CAMS-20).

Australia has had a framework for legal medicinal cannabis since 2016, yet prior online surveys in 2016 and 2018 indicated that most consumers continued to use illicit medical cannabis products. Regulatory data indicate an increase in the prescription of medicinal cannabis since 2019, and this survey examines consumer experiences of prescribed and illicit medical cannabis (MC) use in Australia. A cross-sectional anonymous online survey was administered September 2020 to January 2021. Recruitment via social media, professional and consumer forums, and medical practices. Participant eligibility ≥ 18 years used a cannabis product for self-identified medical reason(s) in the past year, and resident in Australia. Outcome measures included consumer characteristics, conditions treated, source and patterns of MC use, and perspectives on accessing MC. Of the 1600 participants (mean age 46.4 ± 14.3 years, 53% male), 62.4% (n 999) reported using only illicit and 37.6% (n 601) used prescribed MC in the past year. MC was used on a median of 28 (IQR 12, 28) of the past 28 days and cost $AUD 74 ± 72 weekly (median $40, IQR $7, $100). Prescribed participants were more likely to treat pain conditions than those using illicit MC (52% v 40%, OR 1.7, 1.3-2.1) and less likely to treat sleep conditions (6% v 11%, OR 0.5, 0.3-0.8), with mental health conditions also a common indication in both groups (26%, 31%). Prescribed MC was consumed predominately by oral routes (72%), whereas illicit MC was most commonly smoked (41%). Prescribed MC was mainly THC (26%), equal THCCBD (40%), mainly CBD (31%) and uncertain (3%), while 34% of those using illicit MC were uncertain of the cannabinoid profile. Cost and difficulties finding medical practitioners to prescribe remain significant barriers to accessing prescribed MC, and few (10.8%) described the existing model for accessing prescribed MC as straightforward or easy. There has been a notable shift from illicit to prescribed MC by many consumers compared to prior surveys. Consumers using prescribed MC reported a range of advantages compared to illicit MC, including safer routes of administration, and greater certainty regarding access and composition of products.

Active mechanisms of ketamine-assisted psychotherapy A systematic review.

Few studies have evaluated the efficacy of ketamine-assisted psychotherapy (KAP) in the treatment of treatment-resistant depression (TRD) and substance use disorders (SUD). A systematic review of clinical trials reporting on the efficacy of KAP and discussing mechanisms of action, identified on PubMed and PsycInfo. Five randomized-controlled trials reported on the efficacy of KAP treatment and discussed active mechanisms. Four of the studies treated adults with SUD and a single study treated adults with TRD. Overall, KAP had a significant positive effect on primary outcome measures compared to controls, however, the data is mixed. The study examining KAP for TRD found no benefit. Lack of large, replicated clinical trials. No studies actively examining mechanisms of action. Evidence suggests that temporary neural changes caused by ketamine such as n-methyl-d-aspartate receptor (NMDAR) inhibition and increase of synaptic neuroplasticity affect treatment outcomes of KAP. Based on reports of preliminary findings, we speculate that adjunct psychotherapy, changes in perspective, and spirituality may also play a role.

A trauma model of substance use Elaboration and preliminary validation.

The current study expands on and integrates previous theoretical models concerning the pathways that link child maltreatment to substance use disorder. The proposed model, based on the self-medication hypothesis, suggests that experiences of neglect and abuse during childhood can lead to substance use and abuse both directly and indirectly, via dissociation resulting from failed attempts to integrate experiences of maltreatment in childhood. The model was tested on ten substances (painkillers, stimulants, sedatives, marijuana, cocaine, ecstasy, hallucinogens, heroin, inhalants, and methamphetamine) via structural equation modeling (SEM) in a sample comprising 1040 community-dwelling adults (67 % women) aged between 18 and 78 (M 29.55, SD 11.37). Fit indexes of the SEM were good, thus supporting the hypothesized model. Specific forms of child maltreatment were related to increased use of specific substances however, experience of childhood neglect (both physical and emotional) was found to have a central role in predicting use of most substances. Although no single pathway can fully explain the origins of substance abuse, the current study provides evidence of a critical developmental pathway to it, with implications for theory and clinical practice.

Alcohol, smoke, cannabis, new psychoactive substances, and non-prescribed drugs consumption among school student in an area of Nord-West of Italy.

Alcohol andor substance use disorders are known to be a significant phenomenon in the Western world. The aim of the present study was to evaluate the consumption of alcohol, cigarette smoking, cannabis, new psychoactive substances (NSP) non prescribed drug (NPD) in a student population in the north-west of Italy (metropolitan area of Genoa). Fourteen comprehensive schools in the metropolitan area of Genoa (Italy) have requested to participate in the education for correct lifestyles meetings (from December 16, 2021, to May 30, 2022). Before each meeting, a meeting was held with the reference teachers 3805 students aged 9 to 17 were involved. The group was divided by age group 9-11, 12-13, 14-15 and 16-17 years. Before the lesson, the students were given a questionnaire relating to various topics related to lifestyle or resulting from an incorrect lifestyle (alcohol consumption, cigarette smoking, cannabis, NPSNPD, psychological path). The questionnaire was anonymous and was approved by the teachers in the preparation phase of the meeting. Logistic regression analysis found that cannabis use in the age of 14-15 increases the risk of consuming NPDNPD by more than 26 times (odd ratio 26.3012 95% CI 15.9656 to 43.3275 P<0.0001). In the age of 16-17, this risk increases approximately 14 times (odd ratio 14.0625 95% CI 6.1729 to 32.0360 P<0.0001). In the age of 14-15 years, cannabis consumption, alcohol consumption >2 alcoholic units (AUs) on one occasion, NPD increases the probability of the need for a psychological path (cannabis odds ratio 14.0254, 95% CI 10.9-17.9, P<0.0001 alcohol odds ratio 3.68, 95% CI 3-4.4, P<0.0001 NPSNPD odds ratio 20.98, 16.4-38.4, P<0.0001). In the age of 14-15 and 16-17 years, respectively, 53% (95% CI 50-58%) and 68% (95% CI 66-71%) of students declared that they had neither the parents nor the psychologist of having used alcohol andor substances. These data should be useful to policy makers to implement prevention and health promotion policies through teaching (education for correct lifestyles) to be permanently included in school programs and to be recognized in the curricular path.

Association of cannabis potency with mental ill health and addiction a systematic review.

Cannabis potency, defined as the concentration of Δ

Tolerance and Cross-Tolerance among Psychedelic and Nonpsychedelic 5-HT

Classical psychedelics represent a subgroup of serotonergic psychoactive substances characterized by their distinct subjective effects on the human psyche. Another unique attribute of this drug class is that such effects become less apparent after repeated exposure within a short time span. The classification of psychedelics as a subgroup within the serotonergic drug family and the tolerance to their effects are replicated by the murine head twitch response (HTR) behavioral paradigm. Here, we aimed to assess tolerance and cross-tolerance to HTR elicited by psychedelic and nonpsychedelic serotonin 2A receptor (5-HT

From Mushrooms to Myolysis A Case of Rhabdo in Psilocybin-Induced Mood and Psychotic Disorder.

The involvement of certain recreational drugs, namely, hallucinogens, in the development of hyperactive syndromes is well known, but not well studied. In this report, we expand on this relationship by documenting the development of substance-induced psychosis in a young patient who used a large amount of psilocybin and developed symptoms of a first psychotic and manic episode, complicated by violent behavior and rhabdomyolysis. We further evaluate the association between psilocybin use and rhabdomyolysis and explore this understudied phenomenon and differentiate it from the diagnoses of other hyperactive syndromes seen in psychiatry. This case exemplifies the need for increased vigilance in psilocybin microdosing therapy and for physicians to be mindful of how each patient responds to its use to prevent life-threatening hyperactive syndromes in its wake.

Young Adult Cannabis Users Perceptions of Cannabis Risks and Benefits by Chronic Pain Status.

Impact of the COVID-19 pandemic on recreational drug intoxications.

To investigated the impact of the lockdown during the COVID-19 pandemic, since March 2020, on the occurrence and characteristics of recreational drug intoxications in the Emergency Department (ED), compared to previous years. Retrospective cohort study METHOD Patients ≥ 18 years old who presented to the ED of OLVG hospital in Amsterdam with recreational drug intoxication(s), with or without alcohol, were divided into the pre-COVID-19-period (January 2017 to February 2020), and the COVID-19-period (March to December 2020). An intoxication was registered by the treating physician, or retrospectively by researchers. Subgroup analysis was performed for foreign tourists, Dutch tourists and Amsterdam residents, as for the four most common drugs used. A total of 3,881 patients (73.6% male, aged 32 (±12) years) were included, of whom 49.0% were tourists. During the COVID-19-period, a 53% decrease of intoxications was observed (1090.1 vs. 514.8 patientsyear), with an 83% decrease of tourists (574 vs. 98.4 patientsyear), 20% decrease in Dutch residents (516 vs. 416 patientsyear) and 4,5% decrease in Amsterdam residents (354 vs.338 patientsyear). Among Dutch patients, a significant decrease in cocaine (85.6 vs. 75.6 patientsyears), MDMA (25.1 vs. 27.6 patientsyear), and THC (108.6 vs. 76.8 patientsyear) intoxications were observed. However, the amount of GHBGBL related intoxications was comparable between groups (100.7 vs. 105.6 patientsyear). During the COVID-19-period, drug-related intoxications decreased by 53%. Among Dutch residents this decrease was 20%, with a significant decrease in cocaine, MDMA and THC intoxications. However, the amount of GHBGBL related intoxications was comparable with the pre-COVID-19 period.

European Epidemiological Patterns of Cannabis- and Substance-Related Body Wall Congenital Anomalies Geospatiotemporal and Causal Inferential Study.

As body wall congenital anomalies (BWCAs) have a long history of being associated with prenatal or community cannabis exposure (CCE), it was of interest to investigate these epidemiological relationships in Europe given the recent increases in cannabis use prevalence, daily intensity, and Δ9-tetrahydrocannabinol (THC) potency. Methods This study makes use of BWCA data from Eurocat, drug exposure data from the European Monitoring Centre for Drugs and Drug Addiction, and income from the World Bank. Results The mapping analysis showed that BWCARs increased in France, Spain, and the Netherlands. The bivariate mapping analysis showed that the BWCA rates (BWCAR) and the cannabis resin THC concentration rose simultaneously in France, the Netherlands, Bulgaria, Sweden, and Norway. The bivariate ranking of the BWCARs by median minimum E-value (mEV) was omphalocele > diaphragmatic hernia > abdominal wall defects > gastroschisis. With inverse probability weighted multivariable panel regression, the series of BWCAs, including gastroschisis, omphalocele, and diaphragmatic hernia, was positively related to various metrics of cannabis use from p 2.45 × 10−14, 4.77 × 10−7 and <2.2 × 10−16. With geospatial regression, the same series of BWCAs was related to cannabis metrics from p 0.0016, 5.28 × 10−6 and 4.88 × 10−9. Seventeen out of twenty-eight (60.7%) of the E-value estimates were >9 (high range), as were 1428 (50.0%) of the mEVs. Conclusion The data confirm the close relationship of the BWCARs with the metrics of CCE, fulfill the quantitative criteria of causal inference, and underscore the salience of the public health impacts of cannabinoid teratogenicity. Of major concern is the rising CCE impacting exponential cannabinoid genotoxic dose-response relationships. CCE should be carefully restricted to protect the food chain, the genome, and the epigenome of coming generations.

A Dose of Creativity An Integrative Review of the Effects of Serotonergic Psychedelics on Creativity.

This integrative review was conducted to summarize the knowledge pertaining to the effects that serotonergic psychedelics can have on creativity, a multi-dimensional construct referring to the ability to produce original and valuable artifacts. Psychedelics, which have long been hailed as substances that can enhance the creative process in their users, have experienced a recent resurgence in research, allowing the opportunity to better understand this relationship. To this end, I reviewed literature which attempted to study the effects of serotonergic psychedelics on creativity through psychometric methods. A total of eleven studies were reviewed, with four psychedelic compounds represented. Every study assessed components and subcomponents of divergent and convergent thinking, with only one instance of product assessment. Results suggest that convergent thinking may increase during the post-acute phases of the drugs intake, fostering the capacity for development of previously generated ideas. However, this evidence may be circumstantial based on the low number of studies available, small sample sizes, overall lack of randomized controlled trials, and significant methodological limitations throughout most studies. Potential mechanisms underlying these effects are discussed, along with the current state of the research and implications for future studies.

5-HT

Serotonin (5-hydroxytryptamine 5-HT) 2A receptor (5-HT2AR) signaling is essential for the actions of classical psychedelic drugs. In this study, we examined whether sequence variations in the 5-HT2AR gene affect the signaling of four commonly used psychedelic drugs. We examined the

Prenatal Exposure to Delta-9-tetrahydrocannabinol (THC) Alters the Expression of miR-122-5p and Its Target

As cannabis use during pregnancy increases, it is important to understand its effects on the developing fetus. Particularly, the long-term effects of its psychoactive component, delta-9-tetrahydrocannabinol (THC), on the offsprings reproductive health are not fully understood. This study examined the impact of gestational THC exposure on the miRNA profile in adult rat ovaries and the possible consequences on ovarian health. Prenatal THC exposure resulted in the differential expression of 12 out of 420 evaluated miRNAs. From the differentially expressed miRNAs, miR-122-5p, which is highly conserved among species, was the only upregulated target and had the greatest fold change. The upregulation of miR-122-5p and the downregulation of its target insulin-like growth factor 1 receptor (

The Origin and Biomedical Relevance of Cannabigerol.

The constant search for new pharmacologically active compounds, especially those that do not exhibit toxic effects, intensifies the interest in plant-based ingredients and their potential use in pharmacotherapy. One of the plants that has great therapeutic potential is

Anti-Inflammatory and Analgesic Properties of the Cannabis Terpene Myrcene in Rat Adjuvant Monoarthritis.

Ketamine plus Alcohol What We Know and What We Can Expect about This.

Drug abuse has become a public health concern. The misuse of ketamine, a psychedelic substance, has increased worldwide. In addition, the co-abuse with alcohol is frequently identified among misusers. Considering that ketamine and alcohol share several pharmacological targets, we hypothesize that the consumption of both psychoactive substances may synergically intensify the toxicological consequences, both under the effect of drugs available in body systems and during withdrawal. The aim of this review is to examine the toxicological mechanisms related to ketamine plus ethanol co-abuse, as well the consequences on cardiorespiratory, digestive, urinary, and central nervous systems. Furthermore, we provide a comprehensive discussion about the probable sites of shared molecular mechanisms that may elicit additional hazardous effects. Finally, we highlight the gaps of knowledge in this area, which deserves further research.

MIL-100(Fe) Sub-Micrometric Capsules as a Dual Drug Delivery System.

Nanoparticles of metal-organic frameworks (MOF NPs) are crystalline hybrid micro- or mesoporous nanomaterials that show great promise in biomedicine due to their significant drug loading ability and controlled release. Herein, we develop porous capsules from aggregate of nanoparticles of the iron carboxylate MIL-100(Fe) through a low-temperature spray-drying route. This enables the concomitant one-pot encapsulation of high loading of an antitumor drug, methotrexate, within the pores of the MOF NPs, and the collagenase enzyme (COL), inside the inter-particular mesoporous cavities, upon the formation of the capsule, enhancing tumor treatment. This association provides better control of the release of the active moieties, MTX and collagenase, in simulated body fluid conditions in comparison with the bare MOF NPs. In addition, the loaded MIL-100 capsules present, against the A-375 cancer cell line, selective toxicity nine times higher than for the normal HaCaT cells, suggesting that MTXCOLMIL-100 capsules may have potential application in the selective treatment of cancer cells. We highlight that an appropriate level of collagenase activity remained after encapsulation using the spray dryer equipment. Therefore, this work describes a novel application of MOF-based capsules as a dual drug delivery system for cancer treatment.

The Reshaping of the E-Cigarette Retail Environment Its Evolution and Public Health Concerns.

E-cigarette use represents a public health controversy in the US and globally. Despite the potential of e-cigarettes to support cigarette cessation, their use increases health risks and risk for addiction, particularly in young people. Various federal, state, and local laws have impacted tobacco retail in general and e-cigarettes in particular. In the US, 2019-2020 federal laws increased in the minimum legal sales age for tobacco to 21 and banned flavored cartridge-based e-cigarettes. Many states and localities were early adopters of Tobacco 21 and implemented more comprehensive flavor restrictions than the federal ban. Meanwhile, cannabis retail is increasingly being legalized in the US-while cannabis-based product regulation has notable gaps at the federal, state, and local levels. These regulatory complexities have impacted specialized retailers selling e-cigarettes, including vape shops that exclusively sell e-cigarettes, smoke shops that sell e-cigarettes and other tobacco (and potentially CBDTHC and other un- or under-regulated products), and online retail. This commentary outlines public health concerns related to (1) youth access (2) consumer exposure to a broader range of tobacco products and marketing in retail settings where they may seek products to aid in cigarette cessation (i.e., such broad product exposure could hinder cessation attempts) (3) consumer exposure to un-under-regulated products (e.g., delta-8-THC, kratom) and (4) federal, state, and local regulations being undermined by consumer access to prohibited products online and via the mail. These concerns underscore the need for ongoing surveillance of how retailers and consumers respond to regulations.

Development of Nanomaterial-Modified Impedimetric Aptasensor-A Single-Step Strategy for 3,4-Methylenedioxymethylamphetamine Detection.

Developing rapid, sensitive detection methods for 3,4-Methylenedioxymethylamphetamine (MDMA) is crucial to reduce its current misuse in the world population. With that aim, we developed an aptamer-modified tin nanoparticle (SnNP)-based nanoarchitecture as an electrochemical sensor in this study. This platform exhibited a high electron transfer rate with enhanced conductivity arising from its large surface area in comparison to the bare electrode. This observation was explained by the 40-fold higher electroactive surface area of SnNPsAu, which provided a large space for 1.0 μM

Psilocybin reduces low frequency oscillatory power and neuronal phase-locking in the anterior cingulate cortex of awake rodents.

Psilocybin is a hallucinogenic compound that is showing promise in the ability to treat neurological conditions such as depression and post-traumatic stress disorder. There have been several investigations into the neural correlates of psilocybin administration using non-invasive methods, however, there has yet to be an invasive study of the mechanism of action in awake rodents. Using multi-unit extracellular recordings, we recorded local field potential and spiking activity from populations of neurons in the anterior cingulate cortex of awake mice during the administration of psilocybin (2 mgkg). The power of low frequency bands in the local field potential was found to significantly decrease in response to psilocybin administration, whilst gamma band activity trended towards an increase. The population firing rate was found to increase overall, with just under half of individual neurons showing a significant increase. Psilocybin significantly decreased the level of phase modulation of cells with each neural frequency band except high-gamma oscillations, consistent with a desynchronization of cortical populations. Furthermore, bursting behavior was altered in a subset of cells, with both positive and negative changes in the rate of bursting. Neurons that increased their burst firing following psilocybin administration were highly likely to transition from a phase-modulated to a phase unmodulated state. Taken together, psilocybin reduces low frequency oscillatory power, increases overall firing rates and desynchronizes local neural activity. These findings are consistent with dissolution of the default mode network under psilocybin, and may be indicative of disruption of top-down processing in the acute psychedelic state.

5-HT5A Receptor Antagonist ASP5736 Ameliorates Several Abnormal Behaviors in an Fmr1-Targeted Transgenic Male Rat Model of Fragile X Syndrome.

Fragile X syndrome (FXS) is a genetic condition that causes a range of developmental problems, including intellectual disability, aggressive behavior, anxiety, abnormal sensory processing, and cognitive impairment. Despite intensive preclinical research in Fmr1-targeted transgenic mice, an effective treatment for FXS has yet to be developed. We previously demonstrated that ASP5736, a 5-Hydroxytryptamine (serotonin) receptor 5A receptor antagonist, ameliorated scopolamine-induced working memory deficits in mice, reference memory impairment in aged rats, and methamphetamine-induced positive symptoms and phencyclidine-induced cognitive impairment in animal models of schizophrenia. We hypothesized that ASP5736 may be effective for ameliorating similar behavior deficits in male Fmr1-targeted transgenic rats as a preclinical model of FXS. We evaluated the effect of acute oral administration of ASP5736 on the abnormal behavior of hyperactivity (0.01, 0.1 mgkg), prepulse inhibition (0.01, 0.03, 0.1 mgkg), and the novel object recognition task (0.1 mgkg) in Frmr1-knockout (KO) rats. Fmr1-KO rats showed body weight gain, hyperactivity, abnormal sensory motor gating, and cognitive impairment. ASP5736 (0.1 mgkg) reversed the hyperactivity and ameliorated the sensory motor gating deficits (0.03-0.1 mgkg). ASP5736 (0.01 mgkg) also improved cognitive impairment. ASP5736 is a potential drug candidate for FXS. Further studies are needed to confirm its clinical efficacy.

Zelquistinel Is an Orally Bioavailable Novel NMDA Receptor Allosteric Modulator That Exhibits Rapid and Sustained Antidepressant-Like Effects.

The role of glutamatergic receptors in major depressive disorder continues to be of great interest for therapeutic development. Recent studies suggest that both negative and positive modulation of N-methyl-D-aspartate receptors (NMDAR) can produce rapid antidepressant effects. Here we report that zelquistinel, a novel NMDAR allosteric modulator, exhibits high oral bioavailability and dose-proportional exposures in plasma and the central nervous system and produces rapid and sustained antidepressant-like effects in rodents by enhancing activity-dependent, long-term synaptic plasticity. NMDAR-mediated functional activity was measured in cultured rat brain cortical neurons (calcium imaging), hNR2A or B subtype-expressing HEK cells, and synaptic plasticity in rat hippocampal and medial prefrontal cortex slices in vitro. Pharmacokinetics were evaluated in rats following oral administration. Antidepressant-like effects were assessed in the rat forced swim test and the chronic social deficit mouse model. Target engagement and the safetytolerability profile was assessed using phencyclidine-induced hyperlocomotion and rotarod rodent models. Following a single oral dose, zelquistinel (0.1-100 µgkg) produced rapid and sustained antidepressant-like effects in the rodent depression models. Brain cerebrospinal fluid concentrations associated with zelquistinel antidepressant-like activity also increased NMDAR function and rapidly and persistently enhanced activity-dependent synaptic plasticity (long-term potentiation), suggesting that zelquistinel produces antidepressant-like effects by enhancing NMDAR function and synaptic plasticity. Furthermore, Zelquistinel inhibited phencyclidine (an NMDAR antagonist)-induced hyperlocomotion and did not impact rotarod performance. Zelquistinel produces rapid and sustained antidepressant effects by positively modulating the NMDARs, thereby enhancing long-term potentiation of synaptic transmission.

Pharmacological, neural, and psychological mechanisms underlying psychedelics A critical review.

This paper provides a critical review of several possible mechanisms at different levels of analysis underlying the effects and therapeutic potential of psychedelics. At the (1) biochemical level, psychedelics primarily affect the 5-HT

Molecular mechanisms underlying the N-methyl-d-aspartate receptor antagonists Highlighting their potential for transdiagnostic therapeutics.

The so-called psychedelic renaissance has stimulated expanded interest in several classes of drugs that appear to possess transdiagnostic effects in the treatment of mental health disorders, specifically. N-methyl-d-aspartate receptor (NMDAR) antagonists are one such class with diverse therapeutic potential. NMDARs mediate excitatory postsynaptic signalling in the central nervous system (CNS) and are integral to normal neurobiological processes including neuronal development, synaptic transmission, and plasticity, and thus involved in learning and memory. However, NMDAR hyper-function is also implicated in acute CNS trauma, neuropsychiatric and neurodegenerative disorders, as well as chronic pain. The complex structure of NMDARs permits several locations for therapeutic inhibition, making these receptors a potential target for multiple drugs which modulate them in different ways. NMDAR antagonists, which may be competitive, non-competitive, or uncompetitive, either block glutamate from binding the receptor or modulate the response to glutamate binding. Despite longstanding concerns about side effects of NMDAR antagonists, recent research suggests that, when appropriately used, these agents have favourable safety profiles. Furthermore, their fast-acting mechanism of action, resulting in rapid effects compared to other therapeutic agents, makes them a promising class of drugs that may yield effective therapeutics for multiple CNS disorders.

Common opioids and stimulants in autopsy and DUID cases A comparison of measured concentrations.

Quantitative results from toxicological analyses of autopsy material are widely compared to ranges in reference works to determine if drug concentrations are in relevant levels for establishing intoxication. This study compares concentrations of commonly used opioids and stimulants from drug addict autopsies and driving under the influence of drugs (DUID) cases to supplement current knowledge of the possible span and overlaps of measured concentrations. The study included whole-blood results from forensic autopsies of drug addicts performed from 2015 to 2020 (n 220) and DUID cases from 2015 to 2019 (n 7088). The focus was on heroinmorphine, methadone, cocaine, amphetamine and MDMA concentrations because these drugs are commonly encountered in both fatal intoxications and DUID cases and the potential for abuse is well known. In the DUID group, the opioids heroinmorphine and methadone and the stimulants amphetamine and MDMA were often seen in concentrations above the reported lower comatose-fatal level whereas cocaine was almost always below. Thus, based on our data, the potential for false assessment of intoxication cases when comparing to reported comatose-fatal limits appears greatest on lower end concentrations of heroinmorphine, methadone, amphetamine and MDMA, whereas false assessment of cocaine appears less likely because most control cases are below reported comatose-fatal levels.

Magic Mushrooms - an exploratory look at how mental health professionals feel and think about Psilocybin.

Psilocybin recently received breakthrough status by the FDA for its use in treatment of depression. We therefore investigated mental health professionals (MHPs) opinions on Psilocybin (n 155). Overall, attitudes were neutral but self-rated knowledge of Psilocybin was low. The term used in the survey, Psilocybin or Magic Mushrooms, did not significantly affect their responses. Some variables (i.e., gender, attitudes towards medical cannabis, and personal history of psychedelic usage) were associated with ratings of Psilocybin. These results provide a baseline of MHPs thoughts on Psilocybin and what should be considered in the future if it is FDA-approved.

Single-Session Interventions Embedded Within Tumblr Acceptability, Feasibility, and Utility Study.

Existing mental health treatments are insufficient for addressing mental health needs at scale, particularly for teenagers, who now seek mental health information and support on the web. Single-session interventions (SSIs) may be particularly well suited for dissemination as embedded web-based support options that are easily accessible on popular social platforms. We aimed to evaluate the acceptability and effectiveness of three SSIs, each with a duration of 5 to 8 minutes (Project Action Brings Change, Project Stop Adolescent Violence Everywhere, and REFRAME)-embedded as Koko minicourses on Tumblr-to improve three key mental health outcomes hopelessness, self-hate, and the desire to stop self-harm behavior. We used quantitative data (ie, star ratings and SSI completion rates) to evaluate acceptability and short-term utility of all 3 SSIs. Paired 2-tailed t tests were used to assess changes in hopelessness, self-hate, and the desire to stop future self-harm from before to after the SSI. Where demographic information was available, the analyses were restricted to teenagers (13-19 years). Examples of positive and negative qualitative user feedback (ie, written text responses) were provided for each program. The SSIs were completed 6179 times between March 2021 and February 2022. All 3 SSIs generated high star ratings (>4 out of 5 stars), with high completion rates (approximately 25%-57%) relative to real-world completion rates among other digital self-help interventions. Paired 2-tailed t tests detected significant pre-post reductions in hopelessness for those who completed Project Action Brings Change (P<.001, Cohen d Very brief SSIs, when embedded within popular social platforms, are one promising and acceptable method for providing free, scalable, and potentially helpful mental health support on the web. Considering the unique barriers to mental health treatment access that many teenagers face, this approach may be especially useful for teenagers without access to other mental health supports.

The modern clinical use of hallucinogens. What can we learn from the natural product research

Can the emerging field of psychedelic research benefit from natural product research We believe it can. In this manuscript we delineate certain topics of research with hallucinogens that directly connect with research on natural products in general.

Synthesis, Structural Characterization, and Pharmacological Activity of Novel Quaternary Salts of 4-Substituted Tryptamines.

Aeruginascin (4-phosphoryloxy-

Decreases in State and Trait Anxiety Post-psilocybin A Naturalistic, Observational Study Among Retreat Attendees.

Anxiety disorders are the most common type of psychiatric disorders among Western countries. Evidence-based treatment modalities including pharmacological and cognitive-behavioral therapy result in deficient treatment responses. Historical and recent research suggests psychedelic drugs may be efficacious in alleviating anxiety-related symptoms among healthy and clinical populations. The main aim of the present study was investigation of the effects of psilocybin-containing truffles, when taken in a supportive group setting, on ratings of state and trait anxiety across self-reported healthy volunteers. Attendees of psilocybin ceremonies were asked to complete a test battery at three separate occasions before the ceremony (baseline), the morning after, and 1 week after the ceremony. The test battery included questionnaires assessing state and trait anxiety (State-Trait Anxiety Inventory), mindfulness capacities (Five Facet Mindfulness Questionnaire), and personality (Big Five Inventory). Additionally, the psychedelic experience was quantified with the Persisting Effects Questionnaire and the Ego Dissolution Inventory. The total amount of psilocybin-containing truffles consumed by each participant was recorded, and a sample of the truffles was analyzed to determine psilocin concentrations. Fifty-two attendees (males 25 females 25 others 2) completed parts of the baseline assessment, 46 (males 21 females 24 others 1) completed assessments the morning after the ceremony, and 23 (males 10 females 13) completed assessments at the 1-week follow-up. Average psilocin consumption across individuals was 27.1 mg. The morning after the ceremony, we observed medium reductions in anxiety measures (both state and trait) compared to baseline (

Are you tripping comfortably Investigating the relationship between harm reduction and the psychedelic experience.

Alongside a recent revival in the use of psychedelics in clinical settings, there have been increases in the prevalence of recreational use, with many using psychedelics to deal with difficult emotions or to improve well-being. While clinical research is conducted in carefully controlled settings, this is not necessarily the case for recreational use. In this mixed methods online survey study, we aimed to develop an understanding of frequently used psychedelic harm reduction practices in recreational settings and how their use relates to the psychedelic experience. We also aimed to characterise users first and most recent psychedelic trips to understand how harm reduction changes with experience. Participants (n 163) recounted their first and most recent psychedelic experience by providing details about the harm reduction practices they employed and completing the Challenging Experience Questionnaire (CEQ) and Emotional Breakthrough Inventory (EBI). We also asked open-ended questions for a more in-depth qualitative understanding of their views on psychedelic harm reduction. Using ANOVA, we observe greater use of harm reduction practices for participants most recent versus first psychedelic experience and that use of these practices is positively associated with EBI scores and negatively associated with CEQ scores (particularly for the first experience). Participants engaged in a wide range of harm reduction practices and we provide details of those which are most commonly used and those which are deemed most important by experienced users. Our qualitative analysis indicated that participants were largely positive about psychedelics and many recounted profound positive experiences. While specifics of the drug they were taking was important for aspects of harm reduction, participants largely focused on the importance of ensuring a good set and setting for enhancing positive effects. Our research helps us understand how engagement in harm reduction may increase with experience. Our mixed methods data shed light on the perceived importance of different harm reduction practices and examine their association with the psychedelic experience itself. Together, our research has important implications for the development of psychedelic harm reduction advice and provides opportunities for future research to explore the importance of these different practices in more detail.

Impact of cannabis legalization in the United States on trends in cannabis use and daily cannabis use among individuals who smoke cigarettes.

Cannabis legalization and increases in cannabis use are occurring rapidly in the United States (US). Cannabis and tobacco are often used together, but it is unclear whether cannabis legalization will differentially affect cannabis use among those using cigarettes. This study estimated changes from 2004 to 2017 in the prevalence of cannabis use and daily cannabis use by cigarette use status and examined whether state-level cannabis policy modified these trends. Public and restricted-use data from the 2004-2017 National Survey on Drug Use and Health were analyzed. Weighted logistic regressions were used to examine time trends in past-30-day cannabis use and daily caunabis use by cigarette use and cannabis law status from 2004 to 2017. Cannabis use and daily use increased significantly among those with and without cigarette smoking. Cannabis use and daily cannabis use were consistently 2-10x more common throughout this time among those with, versus without, cigarette smoking. In 2017, cannabis use and daily cannabis use were substantially more common among individuals who use cigarettes, and even greater among those who live in states where cannabis was legal for medical or recreational (i.e., non-medical) use. Cannabis use and daily cannabis use are increasing among US individuals who both smoke and do not smoke cigarettes. Cannabis and daily cannabis use are more common among those who smoke cigarettes and elevated even further among those residing in states that have legalized cannabis for recreational (i.e., non-medical) use. Tobacco control efforts should be adjusted to address increases in cannabis use among Americans who smoke cigarettes.

Understanding the effects of serotonin in the brain through its role in the gastrointestinal tract.

The neuromodulatory arousal system imbues the nervous system with the flexibility and robustness required to facilitate adaptive behaviour. While there are well understood mechanisms linking dopamine, noradrenaline and acetylcholine to distinct behavioural states, similar conclusions have not been as readily available for serotonin. Fascinatingly, despite clear links between serotonergic function and cognitive capacities as diverse as reward processing, exploration, and the psychedelic experience, over 95% of the serotonin in the body is released in the gastrointestinal tract, where it controls digestive muscle contractions (peristalsis). Here, we argue that framing neural serotonin as a rostral extension of the gastrointestinal serotonergic system dissolves much of the mystery associated with the central serotonergic system. Specifically, we outline that central serotonin activity mimics the effects of a digestionsatiety circuit mediated by hypothalamic control over descending serotonergic nuclei in the brainstem. We review commonalities and differences between these two circuits, with a focus on the heterogeneous expression of different classes of serotonin receptors in the brain. Much in the way that serotonin-induced peristalsis facilitates the work of digestion, serotonergic influences over cognition can be reframed as performing the work of cognition. Extending this analogy, we argue that the central serotonergic system allows the brain to arbitrate between different cognitive modes as a function of serotonergic tone low activity facilitates cognitive automaticity, whereas higher activity helps to identify flexible solutions to problems, particularly if and when the initial responses fail. This perspective sheds light on otherwise disparate capacities mediated by serotonin, and also helps to understand why there are such pervasive links between serotonergic pathology and the symptoms of psychiatric disorders.

Determination of Cross-Reactivity of Contemporary Cannabinoids with THC Direct Immunoassay (ELISA) in Whole Blood.

Immunoassay procedures, such as enzyme-linked immunosorbent assay (ELISA), are widely used for screening samples in both driving under the influence of drugs (DUID) and postmortem (PM) investigations. While these are sensitive and widely used techniques, they lack specificity compared to more novel instrumental screening platforms. In this study, the cross-reactivities of several cannabinoid isomers and related compounds were evaluated in whole blood using the Cannabinoids Direct ELISA kit from Immunalysis. The compounds of interest were supplemented individually at three different concentrations, ranging from 10 to 100 ngmL or 10 to 1,000 ngmL depending on analyte, to determine initial feasibility. Compounds exhibiting cross-reactivity were then tested to create dose-response curves to calculate the percent cross-reactivity. The cross-reactivity was determined to be 200% for delta-8-carboxy-tetrahydrocannabinol (THC) (delta-8-carboxy-THC), 25% for delta-9,11-THC, 13% for delta-10-THC, 7% for delta-6a(10a)-THC, 3% for THC-O-acetate and 0.5% for tetrahydrocannabiphorol. To determine potential impacts on forensic laboratory casework, a review of DUID and PM casework was also performed. From November 2020 to June 2021, a random sampling of DUID and PM cases was selected monthly and evaluated for the presence of cannabinoid isomer(s) in the absence of a reportable delta-9-carboxy-THC result. While validated techniques for the identification and confirmation of these isomer(s) did not exist at the time of routine testing, delta-8-carboxy-THC was believed to be the most common isomer finding based on current testing capability. This study demonstrated a noticeable increase in the presence of isomeric cannabinoid compounds in both forensic DUID and PM casework sampled during this period and suggests potential impacts for clinical casework as well.

Analytical method validation for assay determination of cannabidiol and tetrahydrocannabinol in hemp oil infused products by RP-HPLC.

A simple quantitative reverse phase high performance liquid chromatographic (RP-HPLC) method has been developed and validated for assay determination of cannabidiol and tetrahydrocannabinol in hemp oil infused products. The RP-HPLC method was developed and optimized for the mobile phase composition, flow rate, column selection and detector wavelength. An isocratic elution of samples were performed on SOLAS 100 Å C18 150 mm × 4.6 mm, 5 μm column with a mobile phase containing 7525 acetonitrilewater vv, with a flow rate of 1.5 mLmin by using an ultraviolet-visible (UVVis) detector operating at 214 nm. The RP-HPLC method was validated to meet regulatory requirements which covers specificity, accuracy, range, linearity, precision, system suitability and robustness. The validated assay test method was applied successfully to quantify cannabidiol and tetrahydrocannabinol in commercial hemp oil infused products such as tablets, soft gel capsules, plant extract oils, oral drops, tincture, and beverage enhancers. All the test results were found acceptable as per ICH guidelines, and this confirmed the feasibility of this method for its intended use in regular quality control and assay of cannabidiol and tetrahydrocannabinol in hemp oil infused products.

Cannabinoids to Improve Health-Related Quality of Life in Patients with Neurological or Oncological Disease A Meta-Analysis.

Evaluation of the Effects of Harmine on β-cell Function and Proliferation in Standardized Human Islets Using 3D High-Content Confocal Imaging and Automated Analysis.

Restoration of β-cell mass through the induction of proliferation represents an attractive therapeutic approach for the treatment of diabetes. However, intact and dispersed primary islets suffer from rapidly deteriorating viability and function

Ketamine for Bipolar Depression Biochemical, Psychotherapeutic, and Psychedelic Approaches.

Bipolar disorder (type 1) is a serious and chronic psychiatric illness that can be difficult to treat. Many bipolar patients have refractory depressive episodes. Racemic ketamine, a glutamate modulator with prominent dissociate and psychedelic properties, has been demonstrated to have rapid acting antidepressant and anti-obsessional effects which may be useful for treating the symptoms of bipolar depression. Most of the existing research literature on unipolar and bipolar depression has looked at racemic ketamine in the sub-psychedelic dose range given by infusion as a stand-alone treatment (without concurrent psychotherapy). This article expands on the existing research by articulating three different paradigms for ketamine treatment biochemical, psychotherapeutic, and psychedelic. The authors use composite clinical vignettes to illustrate different ways of working with ketamine to treat bipolar depression, and discuss a variety of clinical considerations for using ketamine with this population, including route, dose, frequency, chemical mitigators, and adverse events. Note that the conceptual paradigms could be applied to any ketamine treatment, with broad applicability beyond bipolar treatment.

Randomized controlled trials on the use of cannabis-based medicines in movement disorders a systematic review.

Anecdotal references, preclinical, and non-randomized studies support the therapeutic potential of cannabinoids for movement disorders (MD). To create an evidenced-based point of view for patients and physicians, we performed a systematic review of randomized controlled trials (RCT) on the use of cannabinoids in MD. The seven RCTs found on PD used different cannabis formulations. No improvement of motor symptoms was shown in any of the two RCTs with this as primary outcome (PO), but in the nabilone group, an improvement in quality of life was documented. Of the three RCTs having levodopa-induced dyskinesia as PO, only one using nabilone showed a reduction. Anxiety and anxiety-induced tremor could be reduced in the cannabidiol group as well as anxiety and sleeping problems in the nabilone group in another RCT. In two RCTs with Tourette syndrome, an improvement in tics was revealed. From three RCTs on Huntingtons disease only one found symptoms relief using nabilone. No reduction of dystonia could be shown in the two included RCTs. The limited number of available but small and inhomogeneous RCTs precludes reliable conclusions. Therefore, more and smartly designed RCTs are urgently needed.

Cannabinoid Content and Label Accuracy of Hemp-Derived Topical Products Available Online and at National Retail Stores.

Products containing cannabinoids such as cannabidiol (CBD) have proliferated since 2018, when the Agriculture Improvement Act removed hemp (ie, cannabis containing <0.3% Δ9-tetrahydrocannabinol THC) from the US controlled substances list. Topical cannabinoid products can be purchased nationwide at retail stores and over the internet, yet research on these products is scarce. To evaluate the cannabinoid content (ie, CBD and THC) and label accuracy of topical cannabinoid products and to quantify their therapeutic and nontherapeutic claims. Product inclusion criteria included designation as hemp products, intended for topical or transdermal application, and purported to contain cannabinoids (eg, CBD). All unique products available at each retail store were purchased. Online products were identified via Google using relevant keywords (eg, hemp or CBD topical). Various products (eg, lotions and patches) were purchased from retail stores (eg, pharmacies, grocery stores, and cosmetic or beauty stores) in Baltimore, Maryland, and online. Data analysis was performed from March to June 2022. Labeled and actual total amounts of CBD and THC, measured via gas chromatography-mass spectrometry. Therapeutic and nontherapeutic claims and references to the US Food and Drug Administration were quantified. A total of 105 products were purchased, 45 from retail locations and 60 online. Of the 89 products that listed a total amount of CBD on the label, 18% (16 products) were overlabeled (ie, contained >10% less CBD than advertised), 58% (52 products) were underlabeled (ie, contained >10% more CBD than advertised), and 24% (21 products) were accurately labeled. The median (range) percentage deviation between the actual total amount of CBD and the labeled amount was 21% (-75% to 93%) for in-store products and 10% (-96% to 121%) for online products, indicating that products contained more CBD than advertised overall. THC was detected in 37 of 105 products (35%), although all contained less than 0.3% THC. Among the 37 THC-containing products, 4 (11%) were labeled as THC free, 14 (38%) indicated they contained less than 0.3% THC, and 19 (51%) did not reference THC on the label. Overall, 28% of products (29 products) made therapeutic claims, 14% (15 products) made cosmetic claims, and only 47% (49 products) noted that they were not Food and Drug Administration approved. In a case series of topical cannabinoid products purchased online and at popular retail stores, products were often inaccurately labeled for CBD and many contained THC. These findings suggest that clinical studies are needed to determine whether topical cannabinoid products with THC can produce psychoactive effects or positive drug tests for cannabis.

Enhanced Glioblastoma Selectivity of Harmine via the Albumin Carrier.

Glioblastoma, the most common tumor in the brain, has witnessed very little clinical progress over the last decades. Exploring and discovering new therapeutic strategies for glioblastoma has become a critical problem. Harmine (HM), belonging to the beta-carboline alkaloid, is a natural product and isolated from the seeds of

A membrane solid-phase extraction method based on MIL-53-mixed-matrix membrane for the determination of estrogens and parabens Polyvinylidene difluoride membrane versus polystyrene-block-polybutadiene membrane.

In this work, MIL-53(Al), as an inorganic filler component, was embedded in polyvinylidene difluoride (PVDF) and polystyrene-block-polybutadiene (SBS) matrices to prepare two mixed-matrix membranes (MMMs), using a simpler method than that previously reported. The PVDF and SBS membranes retained much of the properties of PVDF, SBS, and native MIL-53(Al). The prepared MMMs were then placed in a vortex-stirred sample solution to develop a membrane solid-phase extraction method to extract estrogens and parabens, which were determined by high-performance liquid chromatography with fluorescence detection. The extraction efficiencies of the two membranes were compared, with the PVDF membrane exhibiting superior performance. In addition, the PVDF membrane was more freestanding and flexible, and its preparation method was also more facile and simple. The extraction conditions were optimized, and the analytical method showed low limits of detection (0.005-0.18 ngmL), good linearity, and high accuracy, with recoveries ranging from 90.7% to 102.5%. As a result, this membrane solid-phase extraction method indicated its potential for application in aqueous sample pretreatment. For metal-organic framework-based MMM used in this method, in addition to being durable, freestanding, mechanically stable, and possessing a large area, it should also exhibit high metal-organic framework incorporation, good flexibility, and appropriate thickness and weight.

Association of Cannabis Use With Nausea and Vomiting of Pregnancy.

Our objective was to evaluate whether cannabis use was associated with nausea and vomiting in early pregnancy. Participants from nuMoM2b (Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-Be) enrolled from October 2010 through September 2013 with a PUQE (Pregnancy-Unique Quantification of Emesis) questionnaire and an available stored urine sample from the first study visit (median gestational age 12 weeks) were included. Cannabis exposure was ascertained by urine immunoassay for 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH) positive results were confirmed with liquid chromatography tandem mass spectrometry. The primary outcome was moderate-to-severe nausea by the PUQE score. Overall, 9,250 participants were included, and 5.8% (95% CI 5.4-6.3%) had detectable urine THC-COOH. In adjusted analyses, higher THC-COOH levels were associated with greater odds of moderate-to-severe nausea (20.7% in the group with THC-COOH detected vs 15.5% in the group with THC-COOH not detected, adjusted odds ratio 1.6, 95% CI 1.1-2.2 for a 500 ngmg Cr THC-COOH increment).

Umbilical Cord Collection and Drug Testing to Estimate Prenatal Substance Exposure in Utah.

Our primary objective was to estimate statewide prenatal substance exposure based on umbilical cord sampling. Our secondary objectives were to compare prevalence of prenatal substance exposure across urban, rural, and frontier regions, and to compare contemporary findings to those previously reported. We performed a cross-sectional prevalence study of prenatal substance exposure, as determined by umbilical cord positivity for 49 drugs and drug metabolites, through the use of qualitative liquid chromatography-tandem mass spectrometry. All labor and delivery units in Utah (N45) were invited to participate. Based on a 2010 study using similar methodology, we calculated that a sample size of at least 1,600 cords would have 90% power to detect 33% higher rate of umbilical cords testing positive for any substance. Deidentified umbilical cords were collected from consecutive deliveries at participating hospitals. Prevalence of prenatal substance exposure was estimated statewide and by rurality using weighted analysis. From November 2020 to November 2021, 1,748 cords (urban n988, rural n384, frontier n376) were collected from 37 hospitals, representing 92% of hospitals that conduct 91% of births in the state. More than 99% of cords (n1,739) yielded results. Statewide, 9.9% (95% CI 8.1-11.7%) were positive for at least one substance, most commonly opioids (7.0%, 95% CI 5.5-8.5%), followed by cannabinoid (11-nor-9-carboxy-delta-9-tetrahydrocannabinol THC-COOH) (2.5%, 95% CI 1.6-3.4%), amphetamines (0.9%, 95% CI 0.4-1.5), benzodiazepines (0.5%, 95% CI 0.1-0.9%), alcohol (0.4%, 95% CI 0.1-0.7%), and cocaine (0.1%, 95% CI 0-0.3%). Cord positivity was similar by rurality (urban10.3%, 95% CI 8.3-12.3%, rural7.1%, 95% CI 3.5-10.7%, frontier9.2%, 95% CI 6.2-12.2%, P.31) and did not differ by substance type. Compared with a previous study, prenatal exposure to any substance (6.8 vs 9.9%, P.01), opioids (4.7 vs 7.0% vs 4.7%, P.03), amphetamines (0.1 vs 0.9%, P.01) and THC-COOH (0.5 vs 2.5%, P<.001) increased. Prenatal substance exposure was detected in nearly 1 in 10 births statewide.

Monitoring of changes in illicit drugs, alcohol, and nicotine consumption during Ramadan via wastewater analysis.

Illicit drug use is a global problem imposing social, economic, and health burdens on society. Wastewater-based epidemiology is an approach based on calculating the consumption of substances in the target population by analyzing the concentrations of human metabolic excretion products of licit and illicit substances in wastewater. This study estimated the changes in illicit drugs (cocaine, amphetamine, methamphetamine, ecstasy (3,4-Methylenedioxymethamphetamine), heroin, and marijuana (THC)), alcohol, and nicotine consumption in Adana Province during Ramadan compared to normal periods using wastewater-based epidemiology. An overall decrease was observed during the Ramadan Period, most strongly for ecstasy (29%) followed by heroin (19%). For cocaine, the variation was the slightest (8.6%). The differences were statistically significant for ecstasy, heroin, nicotine, and alcohol but not for cocaine, amphetamine, methamphetamine, and marijuana. This study is the first to show changes in the use of illicit drugs, alcohol, and nicotine under the influence of religious beliefs. In addition, there is limited data about illicit drugs, alcohol and nicotine abusersusers in Ramadan. This study provides information on the literature on this subject.

Polysubstance use in young people accessing residential and day-treatment services for substance use substance use profiles, psychiatric comorbidity and treatment completion.

People with substance use disorders (SUDs) frequently present to treatment with polysubstance use and mental health comorbidities. Different combinations of substance use and mental health problems require different treatment approaches. Our study aimed to (i) identify the shared substance use classes among young people at treatment admission, (ii) determine which mental health symptoms, quality of life (QoL) and service types were associated with the identified substance use classes, and (iii) prospectively determine which substance use classes and service types were more likely to complete treatment. Cross-sectional and prospective study using service and outcome data. Substance use treatment services in Queensland and New South Wales, Australia. De-identified service and outcome measure data were extracted from the files of 744 clients aged 18-35 years (48% male) admitted into seven residential and four day-treatment programmes. Substance use and severity among tobacco, alcohol, cannabis, cocaine, amphetamine-type stimulants, opioids, sedatives and inhalants. Other variables included depression, anxiety, post-traumatic stress and psychotic symptoms, as well as QoL. Latent class analysis identified three polysubstance use classes wide-ranging polysubstance users (WRPU 22.45%), primary amphetamine users (56.45%) and alcohol and cannabis users (21.10%). The WRPU class had higher odds of psychotic symptoms than the alcohol and cannabis use class odds ratio (OR) 1.30 95% confidence interval (CI) 1.11-1.11 and double the odds of residential programme enrolment than those in the amphetamine use class (OR 2.35 95% CI 1.50-3.68). No other class differences on mental health or QoL variables were found. Clients enrolled in day-programmes had higher odds of completing treatment. There appear to be high levels of polysubstance use among young people entering substance use treatment in Australia. Wide-ranging polysubstance users were more likely to report psychotic symptoms and be enrolled into a residential programme than primary amphetamine users and alcohol and cannabis users.

Therapeutic potential of PIMSR, a novel CB1 receptor neutral antagonist, for cocaine use disorder evidence from preclinical research.

Cannabinoid CB1 receptors (CB1Rs) have been major targets in medication development for the treatment of substance use disorders. However, clinical trials with rimonabant, a CB1R antagonistinverse agonist, failed due to severe side effects. Here, we evaluated the therapeutic potential of PIMSR, a neutral CB1R antagonist lacking an inverse agonist profile, against cocaines behavioral effects in experimental animals. We found that systemic administration of PIMSR dose-dependently inhibited cocaine self-administration under fixed-ratio (FR5), but not FR1, reinforcement, shifted the cocaine self-administration dose-response curve downward, decreased incentive motivation to seek cocaine under progressive-ratio reinforcement, and reduced cue-induced reinstatement of cocaine seeking. PIMSR also inhibited oral sucrose self-administration. Importantly, PIMSR alone is neither rewarding nor aversive as assessed by place conditioning. We then used intracranial self-stimulation (ICSS) to explore the possible involvement of the mesolimbic dopamine system in PIMSRs action. We found that PIMSR dose-dependently attenuated cocaine-enhanced ICSS maintained by electrical stimulation of the medial forebrain bundle in rats. PIMSR itself failed to alter electrical ICSS, but dose-dependently inhibited ICSS maintained by optical stimulation of midbrain dopamine neurons in transgenic DAT-Cre mice, suggesting the involvement of dopamine-dependent mechanisms. Lastly, we examined the CB1R mechanisms underlying PIMSRs action. We found that PIMSR pretreatment attenuated Δ

A Delightful Trip Along the Pathway of Cannabinoid and Endocannabinoid Chemistry and Pharmacology.

After a traumatic childhood in Europe during the Second World War, I found that scientific research in Israel was a pleasure beyond my expectations. Over the last 65 year, I have worked on the chemistry and pharmacology of natural products. During the last few decades, most of my research has been on plant cannabinoids, the endogenous cannabinoids arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol, and endogenous anandamide-like compounds, all of which are involved in a wide spectrum of physiological reactions. Two plant cannabinoids, Δ

Elucidation of partial activation of cannabinoid receptor type 2 and identification of potential partial agonists Molecular dynamics simulation and structure-based virtual screening.

Cannabinoid receptor type 2 (CB2R) is a member of the class A G protein-coupled receptor (GPCRs) family and a component of the endocannabinoid system that is modulated by the psychoactive chemical from Cannabis sativa, partial agonist Δ

Simulated microgravity contributed to modification of callogenesis performance and secondary metabolite production in CannabisIndica.

In vitro plant culture paves the way for meeting the industrial demand of pharmaceutically valuable secondary metabolites. This study intends to monitor how callus cells of Cannabis indica respond to the simulated microgravity (clinorotation a Man-made technology). Callus initiation resulted from the culture of the leaf explant in a medium supplemented with kinetin (0.5 mgL

Engineering silica encapsulated composite of acyltransferase from Mycobacterium smegmatis and MIL-88A A stability-and activity-improved biocatalyst for N-acylation reactions in water.

Here the metal-organic framework material MIL-88A is used to purify and immobilize an acyltransferase from Mycobacterium smegmatis (MsAcT) simultaneously from the broken bacterial liquid. Regarding the possibility that the MsAcTMIL-88A may display weak stability in its application, a silica layer is further introduced around it as a shield to protect the enzyme from degradation. The obtained MsAcTMIL-88Asilica can exhibit high activity recovery, excellent thermal, pH, and storage stabilities compared with those of MsAcTMIL-88A. The MsAcTMIL-88Asilica can also be effectively recycled, and its initial activity of 84.0 % ± 1.2 % can be retained after the 5th cycle for N-acylation reaction in water. More importantly, the MsAcTMIL-88Asilica can display much higher catalytic activity towards the reactions between ethyl or vinyl esters and aniline than those of free MsAcT and MsAcTMIL-88A in aqueous media. This study provides a simple and inexpensive strategy to prepare MsAcTMIL-88Asilica with high activity, stability, and excellent recyclability, and highlights its application potential as a biocatalyst.

Rapid In Situ Detection of THC and CBD in

The need to find a rapid and worthwhile technique for the in situ detection of the content of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in

Psychedelic drugs for psychiatric disorders.

Existing pharmacological treatments for psychiatric disorders have demonstrated limited efficacy, delayed onset of action, and significant burden of side effects. Recent findings from human studies with psychedelics have shown promise, demonstrating rapid and sustained clinical benefits of these compounds for a variety of psychiatric disorders. Classical psychedelics have a rich history and some of these compounds have been used in shamanic and spiritual ceremonies for millennia. The psychoactive effects of these drugs, particularly on human consciousness, have generated great scientific curiosity, and early research on psychedelics suggested their clinical benefits for psychiatric conditions, including alcohol use disorders and anxiety and depressive symptoms in terminal illness and life-threatening conditions. Since the 1990s, after a period of dormancy that followed the criminalization of psychedelic drugs since the Controlled Substance Act of 1970, the continued interest in their unique psychoactive effects along with the pursuit for novel and more effective treatments in psychiatry have led to a renewed interest in research on these compounds. While preliminary findings on psychedelics are encouraging, current evidence is still insufficient to support extensive use of these drugs routinely. Long-term safety and efficacy of these compounds remain unclear, and several clinical trials are underway and may add clarity to these questions. Therefore, this article intends to provide an overview of the evidence to date on psychedelic drugs - particularly psilocybin, MDMA, and LSD - for the treatment of psychiatric disorders.

MIL-125-based nanocarrier decorated with Palladium complex for targeted drug delivery.

The aim of this work was to provide a novel approach to designing and synthesizing a nanocomposite with significant biocompatibility, biodegradability, and stability in biological microenvironments. Hence, the porous ultra-low-density materials, metal-organic frameworks (MOFs), have been considered and the MIL-125(Ti) has been chosen due to its distinctive characteristics such as great biocompatibility and good biodegradability immobilized on the surface of the reduced graphene oxide (rGO). Based on the results, the presence of transition metal complexes next to the drug not only can reinforce the stability of the drug on the structure by preparing π-π interaction between ligands and the drug but also can enhance the efficiency of the drug by preventing the spontaneous release. The effect of utilizing transition metal complex beside drug (Doxorubicin (DOX)) on the drug loading, drug release, and antibacterial activity of prepared nanocomposites on the P. aeruginosa and S. aureus as a model bacterium has been investigated and the results revealed that this theory leads to increasing about 200% in antibacterial activity. In addition, uptake, the release of the drug, and relative cell viabilities (in vitro and in vivo) of prepared nanomaterials and biomaterials have been discussed. Based on collected data, the median size of prepared nanocomposites was 156.2 nm, and their biological stability in PBS and DMEM 10% FBS was screened and revealed that after 2.880 min, the nanocomposites size reached 242.3 and 516 nm respectively. The MTT results demonstrated that immobilizing PdL beside DOX leads to an increase of more than 15% in the cell viability. It is noticeable that the ASTALT result of prepared nanocomposite was under 1.5.

Evaluation of Cytotoxic, Necrotic, Apoptotic, and Autophagic Effects of Methamphetamine and 3,4-Methylenedioxymethamphetamine on U-87 MG (Glial) and B104-1-1 (Neuronal) Cell Lines.

Methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) are empathogen (entactogen) psychoactive designer drugs which are mainly used for recreational purposes. Both MA and MDMA are central nervous system stimulants which are classified as monoamine neurotransmitter reuptake inhibitors. They have strong cytotoxic effects on dopaminergic and serotonergic neurons. Neurotoxicities of MA and MDMA by glial activation have been shown. The present work has investigated and measured cytotoxic, necrotic and apoptotic, and autophagic effects of MA and MDMA on U-87 MG (glial) and B104-1-1 (neuronal) cell lines by janus green, ethidium bromideacridine orange, and monodansylcadaverinepropidium iodide staining to evaluate and compare their effects on glial and neuronal cells, respectively. The results of the present work showed that (1) MDMA induced more potent mitochondrial toxicity, stronger necrotic and autophagic effects than MA in both B104-1-1 (neuronal) and U-87 MG (glial) cell lines (2) although MDMA induced stronger apoptotic effect than MA on U-87 MG cell line, it had equal apoptotic effect on B104-1-1 cell line with MA and (3) MDMA induced more potent mitochondrial toxicity, stronger necrotic, apoptotic, and autophagic effects than MA in B104-1-1 cell line than U-87 MG cell line.

Occasions of Alcohol and Cannabis Use and Associated Risk for Sexual Assault Among College Women With Higher Sexual Risk Alcohol Expectancies.

College women report high rates of sexual assault. Research focused on womens risk factors for sexual assault remains necessary to assist women in reducing their risk. Previous work has shown alcohol use and cannabis use to be associated with sexual assault. The current study examined whether individual difference variables moderated womens risk for sexual assault during occasions of alcohol use and cannabis use using ecological momentary assessment (EMA). Participants were 18- to 24-year-old first-year undergraduate women ( Among women who experienced sexual assault during the EMA period ( Several modifiable risk factors for sexual assault and individual differences factors may exacerbate risk. Ecological momentary interventions may be useful to reduce sexual assault risk for women with high sexual risk expectancies who use alcohol or cannabis.

Cannabis Adaptation During and After Alcohol Ignition Interlock Device Installation A Longitudinal Study.

A common intervention to prevent alcohol-impaired driving are alcohol ignition interlock devices (IIDs), which prevent drivers with a blood alcohol concentration greater than .025% from starting the car. These devices force drivers to adapt their drinking to accommodate the device. Prior studies indicated a transfer of risk as some drivers with an IID may increase cannabis use as they decrease alcohol use. This study examines whether this increase in cannabis use persists after IID removal when alcohol use reverts to pre-IID levels. The data are from the Managing Heavy Drinking (MHD) study of drivers in New York State. The MHD is a comprehensive three-wave study of drivers convicted of driving under the influence from 2015 to 2020. Participants ( In aggregate, participants increased their cannabis use over the course of the study. Drivers who decreased their alcohol use while the IID was installed on their car significantly increased their cannabis use while the IID was in place and further increased cannabis use after the devices removal. IIDs are efficacious in preventing alcohol-impaired driving. However, in some cases, they may have the unintended effect of increasing other substance use. The current study outlines the need for supplemental treatment interventions while on IID to prevent a transfer of risk to other substances, or polysubstance use after the device is removed.

Three Naturally-Occurring Psychedelics and Their Significance in the Treatment of Mental Health Disorders.

Classical psychedelics represent a family of psychoactive substances with structural similarities to serotonin and affinity for serotonin receptors. A growing number of studies have found that psychedelics can be effective in treating various psychiatric conditions, including post-traumatic stress disorder, major depressive disorder, anxiety, and substance use disorders. Mental health disorders are extremely prevalent in the general population constituting a major problem for the public health. There are a wide variety of interventions for mental health disorders, including pharmacological therapies and psychotherapies, however, treatment resistance still remains a particular challenge in this field, and relapse rates are also quite high. In recent years, psychedelics have become one of the promising new tools for the treatment of mental health disorders. In this review, we will discuss the three classic serotonergic naturally occurring psychedelics, psilocybin, ibogaine, and N, N-dimethyltryptamine, focusing on their pharmacological properties and clinical potential. The purpose of this article is to provide a focused review of the most relevant research into the therapeutic potential of these substances and their possible integration as alternative or adjuvant options to existing pharmacological and psychological therapies.

The Impact of Cannabis Packaging Characteristics on Perceptions and Intentions.

As cannabis increasingly becomes a consumer product in the U.S., its product packaging has become critically important to regulators. This study examined the influence of recreational cannabis packaging characteristics. Five online between-subjects experiments were conducted in April 2021, and data were analyzed in May 2021-July 2021. Experiments randomized participants to view different (1) types of cannabis, (2) visual displays of tetrahydrocannabinol content, (3) cannabis packages designed around brand personality research, (4) health warnings, and (5) health claims. Outcomes included cognitive, affective, and behavioral responses. A total of 841 adults from the U.S. (49% male, 50% young adults, 44% White, 17% Hispanic) were included in the study. Edible gummies were perceived as healthier (β0.32, 95% CI0.03, 0.62), less grown up (β -0.58, 95% CI -0.86, -0.28), and more socially acceptable to consume (β0.30, 95% CI0.01, 0.59) than cannabis concentrate in a medical dropper. Participants also had more interest in trying edible gummies (β1.33, 95% CI1.04, 1.62) and trying a free sample (β1.30, 95% CI1.01, 1.60) than trying cannabis concentrate. Cannabis packages with a helps-you-relax health claim elicited more happy (β0.34, 95% CI0.04, 0.64) and good (β0.37, 95% CI0.07, 0.67) feelings than cannabis packages without this claim. Minimal effects were found for visual displays of tetrahydrocannabinol content and health warnings. Edibles are a unique type of cannabis that should be given special consideration under state laws, and lawmakers should consider limiting and governing the use of both implicit and explicit health claims on recreational cannabis packages when implementing laws.

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Psychedelic Therapies at the Crossroads of Trauma and Substance Use Historical Perspectives and Future Directions, Taking a Lead From New Mexico.

Post-traumatic stress disorder (PTSD), a common condition with potentially devastating individual, family, and societal consequences, is highly associated with substance use disorders (SUDs). The association between PTSD and SUD is complex and may involve adverse childhood experiences (ACEs), historical and multi-generational traumas, and social determinants of health as well as cultural and spiritual contexts. Current psychosocial and pharmacological treatments for PTSD are only modestly effective, and there is a need for more research on therapeutic interventions for co-occurring PTSD and SUD, including whether to provide integrated or sequential treatments. There is a current resurgence of interest in psychedelics as potential treatment augmentation for PTSD and SUDs with an appreciation of the risks in this target population. This paper reviews the historical perspective of psychedelic research and practices, as well as the intersection of historical trauma, ACEs, PTSD, and SUDs through the lens of New Mexico. New Mexico is a state with high populations of Indigenous and Hispanic peoples as well as high rates of trauma, PTSD, and SUDs. Researchers in New Mexico have been leaders in psychedelic research. Future directions for psychedelic researchers to consider are discussed, including the importance of community-based participatory approaches that are more inclusive and respectful of Indigenous and other minority communities.

The effects of ketamine and classic hallucinogens on neurotrophic and inflammatory markers in unipolar treatment-resistant depression a systematic review of clinical trials.

Although results are still preliminary, ketamine and classical hallucinogens have shown promise in recent years as novel, fast-acting antidepressants, especially for the treatment of unipolar treatment-resistant depression (TRD). Depression also seems to be related to abnormal levels of peripheral inflammatory and neurotrophic biomarkers, which may one day help to diagnose of this disorder. In this context, this systematic review of clinical trials evaluated the current evidence that relates the antidepressant effects of ketamine and classical hallucinogens on TRD with changes in inflammatory and neurotrophic biomarkers. Twelve studies were found (n 587), 2 with oral ayahuasca (1 mLkg) and 10 with ketamine (mostly intravenous 0.5 mgkg) administration. Results for all biomarkers assessed were contradictory and thus inconclusive. Randomized controlled trials with bigger samples and higher statistical power are warranted to clarify if peripheral biomarkers can confidently be used to indicate and measure ketamines and classical hallucinogens antidepressant effect. The PROSPERO ID for this study is CRD42021249089.

E-cigarette vaping associated acute lung injury (EVALI) state of science and future research needs.

E-Cigarette (e-cig) Vaping-Associated Acute Lung Injury (EVALI) has been linked to vitamin-E-acetate (VEA) and Δ-9-tetrahydrocannabinol (THC), due to their presence in patients e-cigs and biological samples. Lacking standardized methodologies for patients data collection and comprehensive physicochemicaltoxicological studies using real-world-vapor exposures, very little data are available, thus the underlying pathophysiological mechanism of EVALI is still unknown. This review aims to provide a comprehensive and critical appraisal of existing literature on clinicalepidemiological features and physicochemical-toxicological characterization of vaping emissions associated with EVALI. The literature review of 161 medical case reports revealed that the predominant demographic pattern was healthy white male, adolescent, or young adult, vaping illicitinformal THC-containing e-cigs. The main histopathologic pattern consisted of diffuse alveolar damage with bilateral ground-glass-opacities at chest radiographCT, and increased number of macrophages or neutrophils and foamy-macrophages in the bronchoalveolar lavage. The chemical analysis of THCVEA e-cig vapors showed a chemical difference between THCVEA and the single THC or VEA. The chemical characterization of vapors from counterfeit THC-based e-cigs or in-house-prepared e-liquids using either cannabidiol (CBD), VEA, or medium-chain triglycerides (MCT), identified many toxicants, such as carbonyls, volatile organic compounds, terpenes, silicon compounds, hydrocarbons, heavy metals, pesticides and various industrialmanufacturingautomotive-related chemicals. There is very scarce published toxicological data on emissions from THCVEA e-liquids. However, CBD, MCT, and VEA emissions exert varying degrees of cytotoxicity, inflammation, and lung damage, depending on puffing topography and cell line. Major knowledge gaps were identified, including the need for more systematic-standardized epidemiological surveys, comprehensive physicochemical characterization of real-world e-cig emissions, and mechanistic studies linking emission properties to specific toxicological outcomes.

Modalities of the psychedelic experience Microclimates of set and setting in hallucinogen research and culture.

Mid-20th-century American research on psychedelics evinced a stunning diversity of interpretations of hallucinogenic effects. While some researchers viewed psychedelics as invaluable tools for psychotherapy, others persisted in treating them as psychosis-inducing agents. As some groups considered psychedelics as catalysts for artistic creativity, others investigated their potential use as psychochemical weapons in the battlefield, or conversely as tools for spiritual ecstasy and revelation. This bewildering array of perceptions regarding the nature of hallucinogenic effects led to stark contrasts in the contexts (set and setting) of psychedelic research and experimentation, leading to wildly divergent outcomes and reports on the effects of the drugs, and strident disagreements between the actors in the field. Examining this remarkable historical moment of epistemological unclarity regarding psychedelics and their effects, this article describes how distinct scientific and cultural trends and moments of mid-20th-century America contributed to the creation of diverse microclimates of set and setting that reproduced investigator beliefs and attitudes and brought about a beguiling Pygmalion effect that left researchers befuddled and perplexed. I propose the concept of

An efficient and simple SERS approach for trace analysis of tetrahydrocannabinol and cannabinol and multi-cannabinoid detection.

Many countries have legalized cannabis and its derived products for multiple purposes. Consequently, it has become necessary to develop a rapid, effective, and reliable tool for detecting delta-9-tetrahydrocannabinol (THC) and cannabinol (CBN), which are important biologically active compounds in cannabis. Herein, we have fabricated SERS chips by using glancing angle deposition and tuned dimensions of silver nanorods (AgNRs) for detecting THC and CBN at low concentrations. Experimental and computational results showed that the AgNR substrate with film thickness (or nanorod length) of 150 nm, corresponding to nanorod diameter of 79 nm and gap between nanorods of 23 nm, can effectively sense trace THC and CBN with good reproducibility and sensitivity. Due to limited spectral studies of the cannabinoids in previous reports, this work also explored towards identifying characteristic Raman lines of THC and CBN. This information is critical to further reliable data analysis and interpretation. Moreover, multianalyte detection of THC and CBN in a mixture was successfully demonstrated by applying an open-source independent component analysis (ICA) model. The overall method is fast, sensitive, and reliable for sensing trace THC and CBN. The SERS chip-based method and spectral results here are useful for a variety of cannabis testing applications, such as product screening and forensic investigation.

At-home, sublingual ketamine telehealth is a safe and effective treatment for moderate to severe anxiety and depression Findings from a large, prospective, open-label effectiveness trial.

At-home Ketamine-assisted therapy (KAT) with psychosocial support and remote monitoring through telehealth platforms addresses access barriers, including the COVID-19 pandemic. Large-scale evaluation of this approach is needed for questions regarding safety and effectiveness for depression and anxiety. In this prospective study, a large outpatient sample received KAT over four weeks through a telehealth provider. Symptoms were assessed using the Patient Health Questionnaire (PHQ-9) for depression, and the Generalized Anxiety Disorder scale (GAD-7) for anxiety. Demographics, adverse events, and patient-reported dissociation were also analyzed. Symptom trajectories were identified using Growth Mixture Modeling, along with outcome predictors. A sample of 1247 completed treatment with sufficient data, 62.8 % reported a 50 % or greater improvement on the PHQ-9, d 1.61, and 62.9 % on the GAD-7, d 1.56. Remission rates were 32.6 % for PHQ-9 and 31.3 % for GAD-7, with 0.9 % deteriorating on the PHQ-9, and 0.6 % on the GAD-7. Four patients left treatment early due to side effects or clinician disqualification, and two more due to adverse events. Three patient subpopulations emerged, characterized by Improvement (79.3 %), Chronic (11.4 %), and Delayed Improvement (9.3 %) for PHQ-9 and GAD-7. Endorsing side effects at Session 2 was associated with delayed symptom improvement, and Chronic patients were more likely than the other two groups to report dissociation at Session 4. At-home KAT response and remission rates indicated rapid and significant antidepressant and anxiolytic effects. Rates were consistent with laboratory- and clinic-administered ketamine treatment. Patient screening and remote monitoring maintained low levels of adverse events. Future research should assess durability of effects.

Amitriptyline Accelerates SERT Binding Recovery in a Rat 3,4-Methylenedioxymethamphetamine (MDMA) Model In Vivo 4-

Numerous studies have confirmed that 3,4-Methylenedioxymethamphetamine (MDMA) produces long-lasting changes to the density of the serotonin reuptake transporter (SERT). Amitriptyline (AMI) has been shown to exert neuroprotective properties in neuropathologic injury. Here, we used a SERT-specific radionuclide, 4-

Classic Psychedelics and Human-Animal Relations.

Previous research has found associations between classic psychedelic use and nature-relatedness, but the link between classic psychedelic use and human−animal relations remains largely unexplored. Using data representative of the US adult population, with regard to age, sex and ethnicity (N 2822), this pre-registered study assessed lifetime classic psychedelic use, ego dissolution during respondents’ most intense experience using a classic psychedelic, and three measures related to human−animal relations speciesism, animal solidarity and desire to help animals. The results showed that lifetime classic psychedelic use was negatively associated with speciesism (β −0.07, p 0.002), and positively associated with animal solidarity (β 0.04, p 0.041), but no association was found with desire to help animals (β 0.01, p 0.542). Ego dissolution during the respondents’ most intense experience using a classic psychedelic was negatively associated with speciesism (β −0.17, p < 0.001), and positively associated with animal solidarity (β 0.18, p < 0.001) and desire to help animals (β 0.10, p 0.007). The findings indicate that classic psychedelics and ego dissolution may have an impact on human−animal relations. As these results cannot demonstrate causality, however, future studies should use longitudinal research designs to further explore the potential causal link between classic psychedelic use and human−animal relations.

Vaping Cannabinoid Acetates Leads to Ketene Formation.

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Technology and addiction What drugs can teach us about digital media.

Comparisons between digital media and narcotic drugs have become increasingly common in the vigorous discussion on

Tetrahydrocannabinol and cannabidiol medicines for chronic pain and mental health conditions.

Combination tetrahydrocannabinol (THC)cannabidiol (CBD) medicines or CBD-only medicines are prospective treatments for chronic pain, stress, anxiety, depression, and insomnia. THC and CBD increase signaling from cannabinoid receptors, which reduces synaptic transmission in parts of the central and peripheral nervous systems and reduces the secretion of inflammatory factors from immune and glial cells. The overall effect of adding CBD to THC medicines is to enhance the analgesic effect but counteract some of the adverse effects. There is substantial evidence for the effectiveness of THCCBD combination medicines for chronic pain, especially neuropathic and nociplastic pain or pain with an inflammatory component. For CBD-only medication, there is substantial evidence for stress, moderate evidence for anxiety and insomnia, and minimal evidence for depression and pain. THCCBD combination medicines have a good tolerability and safety profile relative to opioid analgesics and have negligible dependence and abuse potential however, should be avoided in patients predisposed to depression, psychosis and suicide as these conditions appear to be exacerbated. Non-serious adverse events are usually dose-proportional, subject to tachyphylaxis and are rarely dose limiting when patients are commenced on a low dose with gradual up-titration. THC and CBD inhibit several Phase I and II metabolism enzymes, which increases the exposure to a wide range of drugs and appropriate care needs to be taken. Low-dose CBD that appears effective for chronic pain and mental health has good tolerability and safety, with few adverse effects and is appropriate as an initial treatment.

Psilocybin induces spatially constrained alterations in thalamic functional organizaton and connectivity.

Classic psychedelics, such as psilocybin and LSD, and other serotonin 2A receptor (5-HT Baseline rsfMRI data (n38) from healthy individuals with a long-term meditation practice was utilized to generate a statistical template of thalamic functional subdivisions. This template was then applied in a novel ICA-based analysis of the acute effects of psilocybin on intra- and extra-thalamic functional organization and connectivity in follow-up scans from a subset of the same individuals (n18). We examined correlations with subjective reports of drug effect and compared with a previously reported analytic approach (treating the thalamus as a single functional unit). Several intrathalamic components showed significant psilocybin-induced alterations in spatial organization, with effects of psilocybin largely localized to the mediodorsal and pulvinar nuclei. The magnitude of changes in individual participants correlated with reported subjective effects. These components demonstrated predominant decreases in thalamocortical connectivity, largely with visual and default mode networks. Analysis in which the thalamus is treated as a singular unitary structure showed an overall numerical increase in thalamocortical connectivity, consistent with previous literature using this approach, but this increase did not reach statistical significance. We utilized a novel analytic approach to discover psilocybin-induced changes in intra- and extra-thalamic functional organization and connectivity of intrathalamic nuclei and cortical networks known to express the 5-HT

Psychedelics in the treatment of unipolar and bipolar depression.

This is a narrative review about the role of classic and two atypical psychedelics in the treatment of unipolar and bipolar depression. Since the 1990s, psychedelics experience a renaissance in biomedical research. The so-called classic psychedelics include lysergic acid diethylamide (LSD), psilocybin, mescaline and ayahuasca. Characteristic effects like alterations in sensory perception, as well as emotion- and self-processing are induced by stimulation of serotonin 2A receptors in cortical areas. The new paradigm of psychedelic-assisted psychotherapy suggests a therapeutic framework in which a safely conducted psychedelic experience is integrated into a continuous psychotherapeutic process. First randomized, controlled trials with psilocybin show promising efficacy, tolerability, and adherence in the treatment of unipolar depression. On the other hand, classic psychedelics seem to be associated with the induction of mania, which is an important issue to consider for the design of research and clinical protocols. So called atypical psychedelics are a heterogeneous group with overlapping subjective effects but different neurobiological mechanisms. Two examples of therapeutic value in psychiatry are 3,4-methyl​enedioxy​methamphetamine (MDMA) and ketamine. Since 2020 the ketamine enantiomer esketamine has been granted international approval for treatment-resistant unipolar depression, and also first evidence exists for the therapeutic efficacy of ketamine in bipolar depression. Whether psychedelics will fulfil current expectations and find their way into broader clinical use will depend on future rigorous clinical trials with larger sample sizes. A well-considered therapeutic and legal framework will be crucial for these substances to create new treatment settings and a potential paradigm shift.

Relative response factors and multiple regression models in liquid chromatography to quantify low-dosed components using alternative standards-proof of concept total Δ9-THC content in cannabis flowers using CBD as reference.

A classical quantitative analysis in liquid chromatography is performed using either a one-point calibration or a calibration line, prepared using a reference standard of the compound(s) of interest. However, in some cases, adequate reference standards may be very expensive, rare to obtain, or have limited shelf-life properties. Also, in herbal matrices, multiple compounds could be necessary to be quantified, needing a whole series of different (related) reference standards. In these cases, the use of relative response (sometimes called relative correction factors) factors (RRFs) towards reference standards, different of the compound to be quantified, gained attraction. This study performed a comparison of the use of RRFs and linear relative response factor models (LRRFM) for the quantification of targeted low-dosed compounds using an alternative standard, since it is known that classical RRFs often fail in lower concentration ranges. For this purpose, the determination of the total Δ9-tetrahydrocannabinol (Δ9-THC Δ9-THC-A) content in dried cannabis flowers, using UHPLC-DAD, was used as a case study. A chromatographic method was implemented and validated, and the use of classical calibration lines, classical RRF, and the LRRFM was applied and compared, with special focus on the concentration around 0.2% (ww) total Δ9-THC, the legal limit (in most European countries) in these products. Results showed that the newly presented and validated LRRFM approach outperformed the classical RRFs, especially in the low-concentration ranges and that concentrations obtained with the LRRFM were in accordance with the interpolation results obtained with a calibration line.

A Randomized, Triple-Blind, Comparator-Controlled Parallel Study Investigating the Pharmacokinetics of Cannabidiol and Tetrahydrocannabinol in a Novel Delivery System, Solutech, in Association with Cannabis Use History.

Association of Tetrahydrocannabinol Content and Price in Herbal Cannabis Products Offered by Dispensaries in California A Purview of ConsumersPatients.

The U.S. legal cannabis market is saturated with products containing high levels of tetrahydrocannabinol (THC), with no distinction between medical and recreational programs. This omnipresence of potent cannabis products seems to be driven by the recreational realm, where cannabis with the highest THC content is prized. This prevalence of highly potent cannabis is conveyed to medical programs, which places consumers (patients) at higher risk for over consumption and cannabis use disorder. Thus, understanding what factors influence the market that patients face in medical cannabis programs could shed light on the risks of legal cannabis. The supply and demand dynamic of the US for-profit cannabis market could explain the current market composition therefore, we postulate that a financial gain could influence the perpetuation of the prevalence of high THC products in legal cannabis dispensaries. We investigate whether THC content in popular cannabis products correlates with higher prices and assess whether some attributes (type of product, chemovars, or presence of cannabidiol (CBD) affect the association of THC with price. We focus on the worlds largest cannabis market, California. We randomly selected dispensaries across the state, screened for a web presence and product menu, determined the most prevalent product type, and collected THC and CBD concentration, price, and other product attributes. We observed that herbal products were more common, they had THC concentrations greater than 10%, and THC concentrations positively correlated with price. This correlation existed in flower and preroll presentations, all chemovar, and independently of the level of CBD. CBD did not correlate with price however, the presence of CBD diminished the THC and price correlation particularly in products with high THC (>15%). Overall, highly potent herbal cannabis products (>15% THC) are the majority of products offered and more expensive regardless of product type or chemovar in California dispensaries, suggesting that a financial gain contributes to the current market composition. Efforts to limit the availability of highly potent THC products and educate consumers about potential harms are needed.

From Underground to Mainstream Establishing a Medical Lexicon for Psychedelic Therapy.

We argue that non-stigmatizing and precise terminology grounded in the medical model will advance both the science and public acceptance of psychedelics. Researchers and clinicians should take care to distinguish between medical, recreational, and spiritual uses to set clear boundaries and expectations for patients. Ethically fraught or stigmatizing terms should be replaced with terminology that is medically and scientifically descriptive and accurate. A medicalized linguistic framework around psychedelics will potentially yield benefits and mitigate risks. Replacing colloquial names with scientific names for medicines and therapies may help correct misconceptions about psychedelics commonly held by both professionals and the public. A harmonized medical lexicon will also provide a common language for important instances of communication-such as the informed consent process-between professionals and participants. Our recommendations draw upon communications research in addiction medicine and aim to encourage the development, acceptance, and implementation of non-stigmatizing terminology in psychedelic research and treatment.

Recent advances in digital health interventions for substance use disorders.

The purpose of this review is to provide an update of the recently published randomized controlled trials in the field of digital health interventions for substance use disorders. Over the past 2 years, five cannabis-specific and seven polysubstance-focused randomized controlled trials were published. No studies were found that focused on opioid or psychostimulant use disorders. Most studies examined feasibility but were underpowered to assess effectiveness. Given the optimistic results of the studies in regards to feasibility more fully powered trials should be conducted. In addition, the literature is in need for an increased focus on comorbidity and outcome standardization. Although the number of studies targeting new target groups, technologies and new delivery settings has increased - future studies should consider the identified gaps and suggestions to further strengthen the evidence of digital interventions targeting substance use disorders.

Metastability, fractal scaling, and synergistic information processing What phase relationships reveal about intrinsic brain activity.

Dynamic functional connectivity (dFC) in resting-state fMRI holds promise to deliver candidate biomarkers for clinical applications. However, the reliability and interpretability of dFC metrics remain contested. Despite a myriad of methodologies and resulting measures, few studies have combined metrics derived from different conceptualizations of brain functioning within the same analysis - perhaps missing an opportunity for improved interpretability. Using a complexity-science approach, we assessed the reliability and interrelationships of a battery of phase-based dFC metrics including tools originating from dynamical systems, stochastic processes, and information dynamics approaches. Our analysis revealed novel relationships between these metrics, which allowed us to build a predictive model for integrated information using metrics from dynamical systems and information theory. Furthermore, global metastability - a metric reflecting simultaneous tendencies for coupling and decoupling - was found to be the most representative and stable metric in brain parcellations that included cerebellar regions. Additionally, spatiotemporal patterns of phase-locking were found to change in a slow, non-random, continuous manner over time. Taken together, our findings show that the majority of characteristics of resting-state fMRI dynamics reflect an interrelated dynamical and informational complexity profile, which is unique to each acquisition. This finding challenges the interpretation of results from cross-sectional designs for brain neuromarker discovery, suggesting that individual life-trajectories may be more informative than sample means.

Visible-light-assisted persulfate activation by SnS

Herein, a highly efficient Z-scheme SnS

Modulation of DNA methylation and protein expression in the prefrontal cortex by repeated administration of D-lysergic acid diethylamide (LSD) Impact on neurotropic, neurotrophic, and neuroplasticity signaling.

Psychedelic compounds elicit relief from mental disorders. However, the underpinnings of therapeutic improvement remain poorly understood. Here, we investigated the effects of repeated lysergic acid diethylamide (LSD) on whole-genome DNA methylation and protein expression in the mouse prefrontal cortex (PFC). Whole genome bisulphite sequencing (WGBS) and proteomics profiling of the mouse prefrontal cortex (PFC) were performed to assess DNA methylation and protein expression changes following 7 days of repeated LSD administration (30 μgkgday) a treatment we previously found to potentiate excitatory neurotransmission and to increase dendritic spine density in the PFC in mice. qRT-PCR was employed to validate candidate genes detected in both analyses. LSD significantly modulated DNA methylation in 635 CpG sites of the mouse PFC, and in an independent cohort the expression level of 178 proteins. Gene signaling pathways affected are involved in nervous system development, axon guidance, synaptic plasticity, quantity and cell viability of neurons and protein translation. Four genes and their protein product were detected as differentially methylated and expressed, and their transcription was increased. Specifically, Coronin 7 (Coro7), an axon guidance cue Penta-EF-Hand Domain Containing 1 (Pef1), an mTORC1 and cell cycle modulator Ribosomal Protein S24 (Rps24), required for pre-rRNA maturation and biogenesis of proteins involved with cell proliferation and migration, and Abhydrolase Domain Containing 6, Acylglycerol Lipase (Abhd6), a post-synaptic lipase. LSD affects DNA methylation, altering gene expression and protein expression related to neurotropic-, neurotrophic- and neuroplasticity signaling. This could represent a core mechanism mediating the effects of psychedelics.

Acute pancreatitis as a rare adverse event among cannabis users A systematic review.

Cannabis use has been steadily rising in the United States and can have multiple adverse effects, including cannabis-induced acute pancreatitis. This study aims to collate and highlight the significant demographics, clinical presentation, and outcomes in patients with cannabis-induced acute pancreatitis. A systematic literature search of electronic databases for peer-reviewed articles was conducted. After an initial search, we found 792 articles through different electronic databases. After manually removing duplicates and articles that did not meet the criteria, 25 articles were included in our review. A total of 45 patients were studied, 35 (78%) cases were male and 10 (22%) cases were female, showing male predominance. The mean age of all participants was 29.2 ± 10.3 years. The most common presenting symptoms were abdominal pain 21 of 21 (100%), nausea 17 of 21 (81%), and vomiting 12 of 20 (60%). Ultrasound was normal in the majority of patients, with findings of mild pancreatitis. Computerized tomography scans revealed pancreatic edema and inflammation in 7 of 20 (35%) patients, and findings of necrotizing pancreatitis and complex fluid collection were visualized in 3 of 20 (15%) patients. Dilatation of intrahepatic or extrahepatic biliary ducts was not seen in any patients. The overall prognosis was good, with reported full recovery. Cannabis should be included in the differential diagnosis for the etiology of acute pancreatitis, which would help in early intervention and treatment for the mitigation of the rapidly progressive disease.

Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls.

Psilocybin microdosing involves repeated self-administration of mushrooms containing psilocybin at doses small enough to not impact regular functioning. Microdose practices are diverse and include combining psilocybin with substances such as lions mane mushrooms (Hericium erinaceus HE) and niacin (vitamin-B3). Public uptake of microdosing has outpaced evidence, mandating further prospective research. Using a naturalistic, observational design, we followed psilocybin microdosers (n 953) and non-microdosing comparators (n 180) for approximately 30 days and identified small- to medium-sized improvements in mood and mental health that were generally consistent across gender, age and presence of mental health concerns, as we all as improvements in psychomotor performance that were specific to older adults. Supplementary analyses indicated that combining psilocybin with HE and B3 did not impact changes in mood and mental health. However, among older microdosers combining psilocybin, HE and B3 was associated with psychomotor improvements relative to psilocybin alone and psilocybin and HE. Our findings of mood and mental health improvements associated with psilocybin microdosing add to previous studies of psychedelic microdosing by using a comparator group and by examining the consistency of effects across age, gender, and mental health. Findings regarding the combination of psilocybin, HE and B3 are novel and highlight the need for further research to confirm and elucidate these apparent effects.

Psychedelic-assisted psychotherapy to treat psychiatric and existential distress in life-threatening medical illnesses and palliative care.

Psychiatric and existential distress commonly occur in advanced cancer and other serious, life-threatening or end-of-life medical illnesses and are associated with poor medical and psychiatric outcomes. Currently available treatment modalities in this patient population, including medication and psychotherapy, are limited in effectiveness, especially regarding existential distress. The lack of effective psycho-spiritual interventions is a critical shortcoming in palliative care and represents a high unmet need in medicine. In this commentary, we review the rationale of researching and developing psychedelic-assisted psychotherapy as a novel pharmacologic-psychotherapeutic intervention to treat psychiatric and existential distress in life-threatening medical conditions and palliative care. This paper reviews efficacy data from first and second waves of psychedelic research, and future directions for research and implementation science. More rigorous research, especially funded by governments, is needed to assess effectiveness and mechanisms of action of psychedelic therapies to treat psychiatric and existential distress in life-threatening medical illnesses and palliative care. If psychedelic-assisted treatments were made available as approved and prescribable medications in people with serious medical illnesses, it could be a significant development that opens up a pathway for clinical dissemination and public health impact internationally.

Urinary Excretion Profile of Cannabinoid Analytes Following Acute Administration of Oral and Vaporized Cannabis in Infrequent Cannabis Users.

Traditionally, smoking has been the predominant method for administering cannabis, but alternative routes of administration have become more prevalent. Additionally, research examining urinary cannabinoid excretion profiles has primarily focused on 11-nor-9-carboxy-∆9-tetrahydrocannabinol (∆9-THC-COOH), a metabolite of ∆9-tetrahydrocannabinol (∆9-THC), as the primary analyte. The aim of the current study was to characterize the urinary excretion profile of ∆9-THC-COOH, ∆9-THC, ∆8-tetrahydrocannabinol (∆8-THC), 11-hydroxy-∆9-tetrahydrocannabinol (11-OH-∆9-THC), ∆9-tetrahydrocannabivarin (THCV), 11-nor-∆9-tetrahydrocannabivarin-9-carboxlic acid (THCV-COOH), cannabidiol (CBD), cannabinol (CBN) and 8,11-dihydroxytetrahydrocannabinol (8,11-diOH-∆9-THC) following controlled administration of both oral and vaporized cannabis. Participants (n 21, 11 men10 women) who were infrequent cannabis users ingested cannabis-containing brownies (0, 10 and 25 mg ∆9-THC) and inhaled vaporized cannabis (0, 5 and 20 mg ∆9-THC) across six double-blind outpatient sessions. Urinary concentrations of ∆9-THC analytes were measured at baseline and for 8 h after cannabis administration. Sensitivity, specificity and agreement between the three immunoassays (IAs) for ∆9-THC-COOH (cutoffs of 20, 50 and 100 ngmL) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) analyses (confirmatory cutoff concentrations of 15 ngmL) were assessed. Urinary concentrations for ∆9-THC-COOH, ∆9-THC, 11-OH-∆9-THC, THCV, CBN and 8,11-diOH-∆9-THC all peaked at 5-6 h and 4 h following oral and vaporized cannabis administration, respectively. At each active dose, median maximum concentrations (Cmax) for detected analytes were quantitatively higher after oral cannabis administration compared to vaporized. Using current recommended federal workplace drug-testing criteria (screening via IA with a cutoff of ≥50 ngmL and confirmation via LC-MS-MS at a cutoff of ≥15 ngmL), urine specimens tested positive for ∆9-THC-COOH in 97.6% of oral sessions and 59.5% of vaporized sessions with active ∆9-THC doses. These data indicate that while ∆9-THC-COOH may serve as the most consistent confirmatory analyte under the current drug-testing guidelines, future work examining 11-OH-∆9-THC under similar parameters could yield an alternative analyte that may be helpful in distinguishing between licit and illicit cannabis products.

Unraveling the Mysteries of Mental Illness With Psilocybin.

Current medications have not been effective in reducing the prevalence of mental illness worldwide. The prevalence of illnesses such as treatment-resistant depression has increased despite the widespread use of a broad set of psychopharmaceuticals. Transcranial magnetic stimulation and ketamine therapy are making great strides in improving treatment-resistant depression outcomes but they have limitations. New psychotherapeutics are required that specifically target the underlying cellular pathologies leading to neuronal atrophy. This neuronal atrophy model is supplanting the long-held neurotransmitter deficit hypothesis to explain mental illness. Interest in psychedelics as therapeutic molecules to treat mental illness is experiencing a 21st-century reawakening that is on the cusp of a transformation. Psilocybin is a pro-drug, found in various naturally occurring mushrooms, that is dephosphorylated to produce psilocin, a classic tryptamine psychedelic functional as a 5-hydroxytryptamine 2A receptor agonist. We have focused this review to include studies in the last two years that suggest psilocybin promotes neuronal plasticity, which may lead to changes in brain network connectivity. Recent advancements in clinical trials using pure psilocybin in therapy suggest that it may effectively relieve the symptoms of depression in patients diagnosed with major depressive disorder and treatment-resistant depression. Sophisticated cellular and molecular experiments at the systems level have produced evidence that demonstrates psilocybin promotes neuritogenesis in the mouse brain - a mechanism that may address the root cause of depression at the cellular level. Finally, studies with psilocybin therapy for major depressive disorder suggest that this ancient molecule can promote functionally connected intrinsic networks in the human brain, resulting in durable improvements in the severity of depressive symptoms. Although further research is necessary, the prospect of using psilocybin for the treatment of mental illness is an enticing possibility.

Suitability of SoToxa® Oral Fluid Screening Over Time Re-Examination of Drugged Driving in Wisconsin.

Drug-impaired driver detection is a critical element of traffic safety. However, shifting drug use patterns over time and geography may limit the long-term reliability of assay-based screening tools. In this work, we compare qualitative results from the Abbott SoToxa® oral fluid (OF) screening device to Quantisal™ OF and whole blood. Our objective was to examine these three qualitative toxicological approaches, scope applicability of OF collection at the roadside, and compare them with a previous analysis of SoToxa® in Wisconsin. OF specimens were screened with the SoToxa® for six drugs or drug classes including amphetamine, benzodiazepines, cocaine, methamphetamine, opioids and tetrahydrocannabinol (THC). OF and blood specimens were collected from 106 participants. Quantisal™ OF and blood specimens were screened for drugs on ultra-performance liquid chromatography coupled to quadrupole time-of-flight high-resolution mass spectrometry (UPLC-QToF-HRMS) using a data-independent acquisition mode. UPLC-QToF-HRMS data were compared to comprehensive spectral libraries, and drugs were qualitatively identified. Drug Recognition Expert evaluations were performed, and face sheets submitted for 21 participants in this work. In general, the SoToxa® results were consistent with the combined qualitative results observed in Quantisal™ OF specimens and whole blood specimens. Limitations were uncovered for benzodiazepines, opioids and THC. The SoToxa® benzodiazepine assay has high cutoff concentrations for diazepam and clonazepam, limiting its sensitivity and positive predictive value when considering these drugs. SoToxa® opioid screening did not detect fentanyl, which is increasingly prevalent among drug users. Finally, ∆9-THC and its major metabolite 11-nor-9-carboxy-∆9-THC are lipophilic, limiting partitioning into OF. Despite these limitations, the SoToxa® instrument may be useful in assisting law enforcement with identifying individuals driving under the influence of drugs and establishing probable cause at roadside for making impaired driving arrests. Furthermore, Quantisal™ OF may be useful as screening specimens due to their ease of collection and results consistent with whole blood.

Highly efficient peroxidase-like activity of a metal-oxide-incorporated CeO

The illegal addition of melamine to dairy products and the contamination of water with mercury (Hg

May the 4Cs be with you an overview of complexity-inspired frameworks for analysing resting-state neuroimaging data.

Competing and complementary models of resting-state brain dynamics contribute to our phenomenological and mechanistic understanding of whole-brain coordination and communication, and provide potential evidence for differential brain functioning associated with normal and pathological behaviour. These neuroscientific theories stem from the perspectives of physics, engineering, mathematics and psychology and create a complicated landscape of domain-specific terminology and meaning, which, when used outside of that domain, may lead to incorrect assumptions and conclusions within the neuroscience community. Here, we review and clarify the key concepts of connectivity, computation, criticality and coherence-the 4Cs-and outline a potential role for metastability as a common denominator across these propositions. We analyse and synthesize whole-brain neuroimaging research, examined through functional magnetic imaging, to demonstrate that complexity science offers a principled and integrated approach to describe, and potentially understand, macroscale spontaneous brain functioning.

Ketamine history and role in anesthetic pharmacology.

Ketamine (Ket) was developed in 1962 as a less hallucinogenic and shorter acting agent than phencyclidine. It was given to humans for the first time in 1964. However, Ket produces several adverse reactions such as raised intracranial and blood pressures along with seizures, and patients still show low acceptance due to hallucinations. As new volatile and intravenous anesthetic agents with good emergence and favorable side effect profiles were developed, Ket use markedly decreased. In the 1990s, as the ultrashort-acting opioid remifentanil was developed, high dose opioid could be used to reduce surgical stress in highly invasive procedures. However, high dose opioids can produce hyperalgesia and acute tolerance. As Ket can exert anti-hyperalgesic actions, the clinical use of low dose Ket has been reconsidered. Other beneficial effects of Ket such as analgesia, anti-shock in hemorrhagic and septic insults, anti-inflammatory effects, anti-tumor effects, brain and spinal cord neuroprotection, and bronchodilation, have all been reported. Moreover, this anesthetic agent at low dose has been recently recognized to possess anti-depressive actions. This diverse profile extends Ket far beyond anesthesia practice and the operating room.

Cannabis - miracle medicine or psychosis-inducing drug

Throughout history, cannabis has been suggested as a treatment for numerous diseases. Despite being in use for over 5000 years, cannabis is still a hot topic of debate and the subject of discussion among politicians and the medical community.

Illicit drug consumption estimated using wastewater analysis and compared by settlement size in New Zealand.

Estimation of consumption of illicit drugs by wastewater-based epidemiology provides estimates of community drug-use patterns. This study describes monitoring data of three illicit drugs in New Zealand using wastewater-based epidemiology. Wastewater samples were collected at monthly intervals for larger (population 50,000) cities or in smaller towns where more data was required by authorities. In other smaller towns, samples were collected every 2 months. Samples were extracted and analysed for parent compounds and metabolites of methamphetamine, MDMA, cocaine, heroin and fentanyl consumption using solid-phase extraction followed by liquid chromatography coupled with tandem-mass spectrometry (LC-MSMS) detection. Back calculations were performed to estimate the consumption of each drug in each catchment area. Methamphetamine was the drug measured with the highest estimated mean consumption rates (724 mg1000 people per day) in New Zealand. North Island small urban settlements had the highest estimated mean methamphetamine consumption rates (1259 mg1000 peopleday). Cocaine had the lowest estimated consumption rates (9.4 mg1000 peopleday). The highest estimated mean cocaine consumption rate was in North Island major urban settlements (24.4 mg1000 peopleday). Major urban settlements had the highest estimated mean MDMA (420 mg1000 peopleday) and cocaine consumption rates (18.8 mg1000 peopleday). South Island medium urban settlements had unexpectedly high estimated mean consumption rates of MDMA (533 mg1000 peopleday) and cocaine (17.0 mg1000 peopleday). The higher-than-expected estimated cocaine consumption was from one medium urban settlement that is also a popular tourist destination in the South Island. Heroin biomarkers were not detected at any locations, and fentanyl was detected around or below the limit of reporting. This research provides information for appropriate responses for improved social and health investment to support social services associated with illicit drug consumption.

A randomized controlled trial of social media interventions for risky drinking among adolescents and emerging adults.

Alcohol use among adolescents and emerging adults is an important public health issue requiring prevention approaches. Herein, we describe outcomes from a randomized controlled trial testing the efficacy of group-based social media interventions targeting risky drinking among youth. Using social media advertisements to screen potential participants, we recruited 955 youth (ages 16-24) reporting recent risky drinking. After completing a baseline assessment, participants were randomized to 8-week secret Facebook group conditions Social Media Intervention Incentives for engagement, Social Media Intervention only, and attention-placebo control. Electronic coaches trained in motivational interviewing facilitated interaction in intervention groups. Primary outcomes include past 3-month alcohol use and consequences over 3-, 6-, and 12-month follow-ups. Secondary outcomes include other drug use, consequences, and impaired driving. We also measured intervention engagement and acceptability. The interventions were well-received, with significantly greater acceptability ratings and engagement in the SMII condition relative to other groups. In adjusted analyses, there were no significant differences between interventions and control on alcohol-related outcomes, with all groups showing reductions. Regarding secondary outcomes (70.4% used other drugs), compared to control, the incentivized group reduced other drug use, consequences, and cannabis-impaired driving the non-incentivized group did not significantly differ from the control condition. Among this predominantly poly-substance using sample, findings were mixed, with significant effects of the incentivized social media intervention on drug (but not alcohol) outcomes. Future studies are needed to further refine social media-delivered interventions to reduce alcohol and other drug use. ClinicalTrials.gov NCT02809586 University of Michigan HUM00102242.

Stairway to Heaven A First-Person Account of Noesis.

Mystical and spiritual experiences have been reported throughout human history. Causal explanations for these range from psychopathology of mental illness, drugs such as hallucinogens, neurological disorders including temporal lobe epilepsy, and genuine mystical or spiritual awakening. There is a common core of phenomena in such experiences, as described both in historical accounts and recent research, but also evidence of cultural specificity. This article is a personal account of such an experience, which occurred in a postanesthetic state. A striking feature of the experience was noesis a sense of revelation and complete understanding. I argue that while there must be a neural basis to these phenomena, it is difficult to reduce the subjective meaning of the experience purely to a brain dysfunction. Reconciling mechanism and meaning of such experiences remains a challenge for both neuroscience and philosophy.

Self-Reported Efficacy of Treatments in Cluster Headache a Systematic Review of Survey Studies.

The use and efficacy of various substances in the treatment of CH have been studied in several retrospective surveys. The aim of the study is to systematically review published survey studies to evaluate the reported efficacies of both established and unconventional substances in abortive and prophylactic treatment of both episodic and chronic CH, specifically assessing the consistency of the results. No systematic review have been conducted of these studies previously. A systematic literature search with a set of search terms was conducted on PubMed. Retrospective surveys that quantified the self-reported efficacy of two or more CH treatments, published in English during 2000-2020, were included. Several key characteristics and results of the studies were extracted. A total of 994 articles were identified of which 9 were found to be eligible based on the selection criteria. In total, 5419 respondents were included. Oxygen and subcutaneous triptan injections were most reported as effective abortive treatments, while psilocybin and lysergic acid diethylamide were most commonly reported as effective prophylactic treatments. The reported efficacy of most substances was consistent across different studies, and there were marked differences in the reported efficacies of different substances. The reported order of efficacy is generally in agreement with clinical studies. The findings suggest that retrospective surveys can be used to obtain supporting information on the effects of various substances used in the treatment of CH and to form hypotheses about novel treatment methods. The consistently reported efficacy of psilocybin and LSD in prophylactic treatment indicates need for clinical studies.

The Readiness of Psychiatrists to Implement Psychedelic-Assisted Psychotherapy.

Psychedelic-Assisted Psychotherapy-A Systematic Review of Associated Psychological Interventions.

Modern clinical research on psychedelics is generating interesting outcomes in a wide array of clinical conditions when psychedelic-assisted psychotherapy is delivered to appropriately screened participants and in controlled settings. Still, a number of patients relapse or are less responsive to such treatments. Individual and contextual factors (i.e., set and setting) seem to play a role in shaping the psychedelic experience and in determining clinical outcomes. These findings, coupled with data from literature on the effectiveness of psychotherapy, frame the therapeutic context as a potential moderator of clinical efficacy, highlighting the need to investigate how to functionally employ environmental and relational factors. In this review, we performed a structured search through two databases (i.e., PubMedMedline and Scopus) to identify records of clinical studies on psychedelics which used and described a structured associated psychotherapeutic intervention. The aim is to construct a picture of what models of psychedelic-assisted psychotherapy are currently adopted in clinical research and to report on their clinical outcomes.