Developing an Ethics and Policy Framework for Psychedelic Clinical Care: A Consensus Statement.

Importance: As government agencies around the globe contemplate approval of the first psychedelic medicines, many questions remain about their ethical integration into mainstream medical practice. Objective: To identify key ethics and policy issues related to the eventual integration of psychedelic therapies into clinical practice. Evidence Review: From June 9 to 12, 2023, 27 individuals representing the perspectives of clinicians, researchers, Indigenous groups, industry, philanthropy, veterans, retreat facilitators, training programs, and bioethicists convened at the Banbury Center at Cold Spring Harbor Laboratory. Prior to the meeting, attendees submitted key ethics and policy issues for psychedelic medicine. Responses were categorized into 6 broad topics: research ethics issues; managing expectations and informed consent; therapeutic ethics; training, education, and licensure of practitioners; equity and access; and appropriate role of gatekeeping. Attendees with relevant expertise presented on each topic, followed by group discussion. Meeting organizers (A.L.M., I.G.C., D.S.) drafted a summary of the discussion and recommendations, noting points of consensus and disagreement, which were discussed and revised as a group. Findings: This consensus statement reports 20 points of consensus across 5 ethical issues (reparations and reciprocity, equity, and respect; informed consent; professional boundaries and physical touch; personal experience; and gatekeeping), with corresponding relevant actors who will be responsible for implementation. Areas for further research and deliberation are also identified. Conclusions and Relevance: This consensus statement focuses on the future of government-approved medical use of psychedelic medicines in the US and abroad. This is an incredibly exciting and hopeful moment, but it is critical that policymakers take seriously the challenges ahead.

Safety and risk assessment of psychedelic psychotherapy: A meta-analysis and systematic review.

Psychotherapies assisted by psychedelic substances have shown promising results in the treatment of psychiatric disorders. The aim of this systematic review and meta-analysis was to evaluate safety data in human subjects. We carried out a search on MEDLINE, Embase and PsycINFO databases between 2000 and 2022. Standardized mean differences between different dose ranges and between acute and subacute phases were calculated for cardiovascular data after psychedelic administration. Risk differences were calculated for serious adverse events and common side effects. Thirty studies were included in this meta-analysis. There were only nine serious adverse events for over 1000 administrations of psychedelic substances (one during the acute phase and 8 during the post-acute phase). There were no suicide attempts during the acute phase and 3 participants engaged in self-harm during the post-acute phase. There was an increased risk for elevated heart rate, systolic and diastolic blood pressure for all dose range categories, as well as an increased risk of nausea during the acute phase. Other common side effects included headaches, anxiety, and decreased concentration or appetite. This meta-analysis demonstrates that psychedelics are well-tolerated, with a low risk of emerging serious adverse events in a controlled setting with appropriate inclusion criteria.

UK medical students' self-reported knowledge and harm assessment of psychedelics and their application in clinical research: a cross-sectional study.

OBJECTIVE: To capture UK medical students' self-reported knowledge and harm assessment of psychedelics and to explore the factors associated with support for changing the legal status of psychedelics to facilitate further clinical research. DESIGN: Cross-sectional, anonymous online survey of UK medical students using a non-random sampling method. SETTING: UK medical schools recognised by the General Medical Council. PARTICIPANTS: 132 medical students who had spent an average of 3.8 years (SD=1.4; range: 1-6) in medical school. RESULTS: Most students (83%) reported that they were aware of psychedelic research and only four participants (3%) said that they were not interested in learning more about this type of research. Although medical students' harm assessment of psychedelics closely aligned with that of experts, only 17% of students felt well-educated on psychedelic research. Teachings on psychedelics were only rarely encountered in their curriculum (psilocybin: 14.1 (SD=19.9), scale: 0 (never) to 100 (very often)). Time spent at medical schools was not associated with more knowledge about psychedelics (r=0.12, p=0.129). On average, this sample of medical students showed strong support for changing the legal status of psychedelics to facilitate further research into their potential clinical applications (psilocybin: 80.2 (SD=24.8), scale: 0 (strongly oppose) to 100 (strongly support)). Regression modelling indicated that greater knowledge of psychedelics (p<0.001), lower estimated harm scores (p<0.001), more time spent in medical school (p=0.024) and lower perceived effectiveness of non-pharmacological mental health treatments (p=0.044) were associated with greater support for legal status change. CONCLUSIONS: Our findings reveal a significant interest among UK medical students to learn more about psychedelic research and a strong support for further psychedelic research. Future studies are needed to examine how medical education could be refined to adequately prepare medical students for a changing healthcare landscape in which psychedelic-assisted therapy could soon be implemented in clinical practice.

Derived psychoactive cannabis products and 4/20 specials: An assessment of popular brands and retail price discounts in Fort Worth, Texas, 2023.

BACKGROUND: Retail sales of derived psychoactive cannabis products (DPCPs) have increased in the U.S. since passing the 2018 Farm Bill and is unregulated in most states. This study investigated the types and commonly sold brands of DPCPs as well as promotional pricing on April 20th, a day associated with cannabis use. METHODS: On April 19-20, 2023, investigators conducted telephone surveys with 98 retail stores that sold DPCPs in Fort Worth, Texas (where the market was largely unregulated). RESULTS: Delta-8, Delta-9, and Delta-10 THC products were widely available, with 97%, 72%, and 82% of stores selling each type, respectively. Fifteen additional DPCPs were identified, and selling blends containing multiple types of THC was common. Frequently sold brands included Cake, Medusa/Modus, Torch, Urb, Kik, Tyson, 3Chi, Casper, Hidden Hills, Esco Bars, Happi, Hometown Hero, STNR, Bomb Bars, Baked, Hi On Nature, Looper, and Space God. Overall, 45% reported having 4/20 specials discounting prices on DPCPs, smoking devices/accessories, or everything in the store. Several stores also sponsored 4/20 promotional events including free THC gummies and "live delta demos where people can test cartridges and try smoking flower in the store." CONCLUSIONS: Findings highlight the growing complexity of the DPCP market, including numerous different intoxicating compounds and blends. Policymakers, researchers, and public health professionals should consider these complexities, as well as the commonly sold brands, when developing strategies to regulate DPCPs and protect consumer safety. Pricing policies may be an especially important form of harm reduction during events associated with heavy cannabis use, including 4/20.

Public opinion on the expenditure of adult-use cannabis tax revenue: Evidence from New Jersey.

OBJECTIVES: To describe New Jersey residents' relative priorities for the allocation of tax revenue generated by recreational cannabis sales. We aim to assess preferences for public health initiatives, including drug treatment, compared to a range of alternatives, including traditional policing, especially within the social and demographic groupings of people generally most impacted by punitive drug enforcement policies. METHODS: We collected population-representative survey data four months post-implementation of recreational cannabis sales in New Jersey (N = 1,006). We gauge respondents' top preferences for the allocation of new revenue generated by the legal cannabis market. Using multinomial logistic regression, we assess how various demographic and political factors shape public support for devoting revenue toward public health initiatives. RESULTS: While priorities are mixed within the sample, we find more general support for funding community-based initiatives in public health, housing, and education than for funding police, courts, and prisons. Among Black residents, the largest proportion chose investments in affordable housing. Regression analysis reveals political orientation as having the most consistent association with expressed preferences, with Republicans favoring investments in traditional law enforcement priorities over other potential funding domains. CONCLUSIONS: Recreational cannabis legalization is occurring at a rapid pace, yet important context, including how the tax revenue could be invested in communities, remains unclear. Insight into current public opinion on funding priorities suggests a desire for investment in fundamental societal institutions, including education and public health, rather than the punitive enforcement mechanisms that have defined cannabis policy for many decades.

Immigration status-related exclusive e-cigarette use and cannabis use and their dual use disparities associated with mental health disorder symptoms.

INTRODUCTION: E-cigarette and cannabis use has been linked to various health risks, including respiratory and cardiovascular conditions. Yet, extant knowledge about the risk factors for exclusive and dual use of e-cigarettes and cannabis is limited, especially among immigrants. We examined exclusive e-cigarette and cannabis use and their dual use associated with mental health disorders among immigrants and U.S.-born. METHODS: We analyzed national cross-sectional data collected between May 13, 2021, and January 9, 2022, among adults aged >18 years (n= 4766) living in U.S. Multinomial logistic regression analyses were conducted to model the associations of exclusivity and dual-use (reference group= non-use) with anxiety/depression. RESULTS: The dual-use prevalence was higher than exclusive e-cigarette and cannabis use, especially among U.S.-born (dual use= 14.79% vs. cannabis use= 13.53% vs. e-cigarette use= 7.11%) compared to immigrants (dual use= 8.23% vs. cannabis use= 5.03% vs. e-cigarette use= 6.31%). Immigrants had lower risks of exclusive cannabis and dual use compared to U.S.-born. Anxiety/depression was associated with higher risks of exclusive cannabis use and dual use across immigration status, but was associated with exclusive e-cigarette use among only immigrants. While effect sizes of dual-use associated with anxiety/depression were higher among U.S.-born, the effect sizes of exclusive e-cigarette and cannabis use associated with anxiety/depression were higher among immigrants. CONCLUSIONS: The findings revealed significant mental health risks for e-cigarette, cannabis, and their dual use among immigrants and U.S.-born, especially among U.S.-born. These findings highlight the need for public health research and interventions to consider immigration status-related disparities in substance use.

The changing outlook of psychedelic drugs: The importance of risk assessment and occupational exposure limits.

Serotonergic psychedelics, such as lysergic acid diethylamide (LSD), psilocybin, dimethyltryptamine (DMT), and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), are currently being investigated for the treatment of psychiatric disorders such as depression and anxiety. Clinical trials with psilocybin and LSD have shown improvement in emotional and psychological scores. Although these drugs are reported to be safe in a controlled environment (such as clinical trials), exposure to low doses of these drugs can result in psychedelic effects, and therefore, occupational safety is an important consideration to prevent adverse effects in the workplace from low daily exposure. This article will discuss the factors involved in the derivation of occupational exposure limits (OELs) and risk assessment of these psychedelic drugs. To support the OEL derivations of psychedelic drugs, information regarding their mechanism of action, adverse effect profiles, pharmacokinetics, clinical effects, and nonclinical toxicity were considered. Additionally, psilocybin and LSD, which are the most extensively researched psychedelic substances, are employed as illustrative examples in case studies. The OELs derived for psilocybin and for LSD are 0.05 and 0.002 µg/m3 , respectively, which indicates that these are highly hazardous compounds, and it is important to take into account suitable safety measures and risk-management strategies in order to minimize workplace exposure.

Assessment of the acute subjective psychedelic experience: A review of patient-reported outcome measures in clinical research on classical psychedelics.

BACKGROUND: The classical psychedelics psilocybin, peyote, ayahuasca/ N, N-dimethyltryptamine, and lysergic acid diethylamide can temporarily produce altered states of consciousness, characterized by changes in sensory perception, thought, mood, and the sense of self-reality and meaning. It is important to have reliable instruments for quantifying these altered states in trials, due to a plausible link between the acute subjective experience and treatment outcome. METHODS: We conducted a review of outcome measures applied in research on classical psychedelics to assess one or more dimensions of the acute subjective psychedelic experience. Three relevant databases were searched electronically. Two reviewers independently conducted article selection and data extraction regarding the instruments, dimensions, geography, population, and psychedelic substance investigated in the included studies. We identified the five most utilized instruments for the most recent 6 years, as well as the five most utilized instruments for each psychedelic. RESULTS: We included 93 papers, which reported on 93 unique trials and utilized 17 different rating scales. Of these, the most utilized were the Five-Dimensional Altered States of Consciousness Questionnaire, visual analog or Likert scales specially developed for the trials, the Hallucinogen Rating Scale, the States of Consciousness Questionnaire, and the Abnormer Psychischer Zustand. DISCUSSION: Considerable variability was found in the instruments utilized in clinical trials on classical psychedelics. We advise and encourage the development of a core outcome set for psychedelic research to enable altered state comparisons across compounds, participants, and settings. We further advise that instruments be designed to assess the "setting" of a psychedelic experience.

Cannabis use and neurocognitive performance at 13-14 Years-Old: Optimizing assessment with hair toxicology in the Adolescent brain cognitive development (ABCD) study.

OBJECTIVE: Cannabis is widely used, including in early adolescence, with prevalence rates varying by measurement method (e.g., toxicology vs. self-report). Critical neurocognitive development occurs throughout adolescence. Given conflicting prior brain-behavior results in cannabis research, improved measurement of cannabis use in younger adolescents is needed. METHODS: Data from the Adolescent Brain Cognitive Development (ABCD) Study Year 4 follow-up (participant age: 13-14 years-old) included hair samples assessed by LC-MS/MS and GC-MS/MS, quantifying THCCOOH (THC metabolite), THC, and cannabidiol concentrations, and the NIH Toolbox Cognitive Battery. Youth whose hair was positive for cannabinoids or reported past-year cannabis use were included in a Cannabis Use (CU) group (n = 123) and matched with non-using Controls on sociodemographics (n = 123). Standard and nested ANCOVAs assessed group status predicting cognitive performance, controlling for family relationships. Follow-up correlations assessed cannabinoid hair concentration, self-reported cannabis use, and neurocognition. RESULTS: CU scored lower on Picture Memory (p = .03) than Controls. Within the CU group, THCCOOH negatively correlated with Picture Vocabulary (r = -0.20, p = .03) and Flanker Inhibitory Control and Attention (r = -0.19, p = .04), and past-year cannabis use was negatively associated with List Sorting Working Memory (r = -0.33, p = .0002) and Picture Sequence Memory (r = -0.19, p = .04) performances. CONCLUSIONS: Youth who had used cannabis showed lower scores on an episodic memory task, and more cannabis use was linked to poorer performances on verbal, inhibitory, working memory, and episodic memory tasks. Combining hair toxicology with self-report revealed more brain-behavior relationships than self-report data alone. These youth will be followed to determine long-term substance use and neurocognition trajectories.

Enhanced cannabis timeline followback (EC-TLFB): Comprehensive assessment of cannabis use including standard THC units and validation through biological measures.

AIMS: The aims of this study were to present an enhanced cannabis timeline followback (EC-TLFB) enabling comprehensive assessment of cannabis use measures, including standard tetrahydrocannabinol (THC) units, and to validate these against objectively indexed urinary 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH) concentrations. DESIGN: We used cross-sectional baseline data from the 'CannTeen' observational longitudinal study. SETTING: The study was conducted in London, UK. PARTICIPANTS: A total of 147 participants who used cannabis regularly took part in the study (n = 71 female, n = 76 male; mean age = 21.90, standard deviation = 5.32). MEASUREMENTS: The EC-TLFB was used to calculate frequency of cannabis use, method of administration, including co-administration with tobacco, amount of cannabis used (measured with unaided self-report and also using pictorial aided self-report) and type of cannabis product (flower, hash) which was used to estimate THC concentration (both from published data on THC concentration of products and analysis of cannabis samples donated by participants in this study). We calculated total weekly standard THC units (i.e. 5 mg THC for all cannabis products and methods of administration) using the EC-TLFB. The outcome variable for validation of past week EC-TLFB assessments was creatinine-normalized carboxy-tetrahydrocannabinol (THC-COOH) in urine. FINDINGS: All measures of cannabis exposure included in this analysis were positively correlated with levels of THC-COOH in urine (r = 0.41-0.52). Standard THC units, calculated with average concentrations of THC in cannabis in the UK and unaided self-report measures of amount of cannabis used in grams showed the strongest correlation with THC-COOH in urine (r = 0.52, 95% bias-corrected and accelerated = 0.26-0.70). CONCLUSIONS: The enhanced cannabis timeline followback (EC-TLFB) can provide a valid assessment of a comprehensive set of cannabis use measures including standard tetrahydrocannabinol units as well as and traditional TLFB assessments (e.g. frequency of use and grams of cannabis use).

"It's a big added stress on top of being so ill": The challenges facing people prescribed cannabis in the UK.

BACKGROUND: This paper reports on the first qualitative study to interview people prescribed cannabis in the UK. Cannabis is a class B controlled substance under the 1971 Misuse of Drugs (MoD) Act, but a 2018 change to UK regulations provided for the prescription of cannabis for medical purposes. Relatively few people have been able to access a prescription, despite this policy change. This paper examines their experiences. METHODS: Qualitative, semi-structured interviews were conducted with 24 people with a prescription for cannabis, or their carers. Data was analysed using a reflextive thematic analysis approach. The findings are discussed using a zemiology (social harms) perspective which provides a language for critical reflection on the current cannabis policy context. RESULTS: All participants reported that cannabis had significantly improved their mental and/or physical health, across a broad range of conditions. Many had been able to reduce their use of conventional medicines and reported that cannabis had relatively few side effects. Despite the potentially life-enhancing benefits of cannabis medicine, patients in the UK face multiple barriers to access. These include a lack of funding streams, bureaucratic supply problems, and a lack of training for doctors and police. Even for the few people able to obtain a prescription, the ongoing criminalisation of cannabis in the UK contributed to their experiences of stigmatisation. This often made it difficult and anxiety-inducing to take their medicine in public spaces. CONCLUSION: The UK government's lack of implementation of medical cannabis legalisation, combined with their ongoing prohibition position, is producing multiple harms to people who need cannabis medicine. The policy context is perpetuating stigmatising attitudes to cannabis which, as we demonstrate, contribute to social harms. We make recommendations on equality of patient access, and highlight the importance of education and policy change as means of combatting stigma.

The development of a Cannabis Knowledge Assessment Tool (CKAT).

BACKGROUND: Misconceptions about the health risks of cannabis remain prevalent, indicating the need to improve public health messaging and determine the effectiveness of educational programming. Our objective was to develop a standardized questionnaire to measure knowledge about cannabis in the context of cannabis legalization. METHODS: A Cannabis Knowledge Assessment Tool (CKAT) was created using the Delphi method. A purposive sample of healthcare professionals, policymakers, academics, patients, and students served as the content and development experts. Principal component analysis from the codes identified from open-ended feedback guided the item development. Upon completion, the CKAT was administered as a pre- and post-test in four schools (7th and 9th Grade) in Canada. The data were analysed to determine whether knowledge scores changed after participating in a cannabis education program. RESULTS: Twenty-four experts initially participated in the Delphi process and 18 (75% retention) continued throughout. Principal component analysis identified 3 domains: 1) effects of cannabis on the individual, 2) general information about cannabis, and 3) cannabis harm reduction. The final questionnaire consisted of 16 multiple-true-false questions (64 items) and received a Flesch-Kincaid Grade Level of 6.3, and a SMOG index score of 7.6. The CKAT was completed by 132 students; seventy-three 7th grade and fifty-nine 9th grade students. The baseline mean CKAT score was 46.2 (SD:5.5), which increased to 50.7 (SD:4.6) after the cannabis educational program (p<0.05). CONCLUSIONS: A novel tool to measure knowledge of cannabis was developed and piloted in 7th grade and 9th grade students. Future studies are required to test usability and validity of the CKAT in other contexts.

Longitudinal and transcultural assessment of the relationship between hallucinogens, well-being, and post-traumatic growth during the COVID-19 pandemic.

The COVID-19 pandemic has had a devastating impact on the health and wellbeing of the global population. This paper presents the results of a longitudinal transcultural study that was begun at the peak of the pandemic (in April, 2020). An online survey was used to collect data from English-, Spanish-, and Portuguese-speaking participants. The survey collected information about sociodemographics, lifestyle activities, COVID-19-related circumstances, and drug use (with an emphasis on hallucinogenic drugs), as well as involving psychometric questionnaires. Users of hallucinogenic drugs had higher psychological well-being and lower scores on psychopathology scales, both at baseline and during follow-ups. This difference was larger when users were distinguished by frequency of use, as regular users scored higher on psychological well-being and lower on psychopathology scales. Subjects with more psychological distress had lower scores for all scales of post-traumatic growth, but if they were regular hallucinogens users, they had higher scores for post-traumatic growth. When comparing the results between cultural contexts, heterogeneous results were obtained. There were more English-speaking regular users of hallucinogenic drugs. Further research should analyse the potential role of hallucinogens in large-scale catastrophes, with a special focus on post-traumatic growth.

Molecular Docking Assessment of Cathinones as 5-HT2AR Ligands: Developing of Predictive Structure-Based Bioactive Conformations and Three-Dimensional Structure-Activity Relationships Models for Future Recognition of Abuse Drugs.

Commercially available cathinones are drugs of long-term abuse drugs whose pharmacology is fairly well understood. While their psychedelic effects are associated with 5-HT2AR, the enclosed study summarizes efforts to shed light on the pharmacodynamic profiles, not yet known at the receptor level, using molecular docking and three-dimensional quantitative structure-activity relationship (3-D QSAR) studies. The bioactive conformations of cathinones were modeled by AutoDock Vina and were used to build structure-based (SB) 3-D QSAR models using the Open3DQSAR engine. Graphical inspection of the results led to the depiction of a 3-D structure analysis-activity relationship (SAR) scheme that could be used as a guideline for molecular determinants by which any untested cathinone molecule can be predicted as a potential 5-HT2AR binder prior to experimental evaluation. The obtained models, which showed a good agreement with the chemical properties of co-crystallized 5-HT2AR ligands, proved to be valuable for future virtual screening campaigns to recognize unused cathinones and similar compounds, such as 5-HT2AR ligands, minimizing both time and financial resources for the characterization of their psychedelic effects.

Marijuana and Cannabidiol Use Prevalence and Symptom Management Among Patients with Cancer.

Symptoms such as pain, nausea, and anxiety are common in individuals with cancer. Treatment of these issues is often challenging. Cannabis products may be helpful in reducing the severity of these symptoms. While some studies include data on the prevalence of cannabis use among patients with cancer, detailed data remain limited, and none have reported the prevalence of cannabidiol (CBD) use in this population. Adult patients with cancer attending eight clinics at a large, NCI-designated Comprehensive Cancer Center completed a detailed, cannabis-focused questionnaire between 2021 and 2022. Eligible participants were diagnosed with invasive cancer and treated in the past 12 months. Summary statistics were calculated to describe the sample regarding cannabis use. Approximately 15% (n = 142) of consented patients (n = 934) reported current cannabis use (defined as use within the past 12 months). Among which, 75% reported cannabis use in the past week. Among current cannabis users, 39% (n = 56; 6% overall) used CBD products. Current users reported using cannabis a median of 4.5 (interquartile range: 0.6­7.0) days/week, 2.0 (1.0­3.0) times per use/day, and for 3 years (0.8­30.0). Use patterns varied by route of administration. Patients reported moderate to high relief of symptoms with cannabis use. This study is the most detailed to date in terms of cannabis measurement and provides information about the current state of cannabis use in active cancer. Future studies should include complete assessments of cannabis product use, multiple recruitment sites, and diverse patient populations. SIGNIFICANCE: Clinicians should be aware that patients are using cannabis products and perceive symptom relief with its use.

Medical cannabis laws lower individual market health insurance premiums.

BACKGROUND: To evaluate the impact of medical cannabis laws (MCLs) on health insurance premiums. We study whether cannabis legalization significantly impacts aggregate health insurer premiums in the individual market. Increases in utilization could have spillover effects to patients in the form of higher health insurance premiums. METHODS: We use 2010-2021 state-level U.S. private health insurer financial data from the National Association of Insurance Commissioners. We examined changes to individual market health insurance premiums after the implementation of medical cannabis laws. We employed a robust difference-in-differences estimator that accounted for variation in policy timing to exploit temporal and geographic variation in state-level medical cannabis legalization. RESULTS: Seven years after the implementation of Medical Cannabis laws, we observe lower health insurer premiums in the individual market. Starting seven years post-MCL implementation, we find a reduction of $-1662.7 (95% confidence interval [CI -2650.1, -605.7]) for states which implemented MCLs compared to the control group, a reduction of -$1541.8 (95% confidence interval [CI 2602.1, -481.4]) in year 8, and a reduction of $-1625.8, (95% confidence interval [CI -2694.2, -557.5]) in year 9. Due to the nature of insurance pooling and community rating, these savings are appreciated by cannabis users and non-users alike in states that have implemented MCLs. CONCLUSIONS: The implementation of MCLs lowers individual-market health insurance premiums. Health insurance spending, including premiums, comprises between 16% and 34% of household budgets in the United States. As healthcare costs continue to rise, our findings suggest that households that obtain their health insurance on the individual (i.e., not employer sponsored) market in states with MCLs appreciate significantly lower premiums.

An assessment of qualitative and quantitative cannabinoids analysis in selected commercially available cannabis oils in Argentina.

In recent years, the therapeutic use of cannabis products, especially cannabis oils, has increased significantly, due to the pharmacological potential of their cannabinoids, for the treatment of conditions, such as pain management, cancer, and epilepsy. In Argentina, patients with medical prescriptions can access to cannabis oil, through self-cultivation, a third-person (grower or importer), or a civil organization authorized for that purpose. However, these products remain largely unregulated in Argentina, and information available regarding labeling accuracy, especially cannabidiol (CBD)/ Δ9-tetrahydrocannabinol (Δ9-THC) concentrations are inconsistent or nonexistent, nor long-term product stability, and lot to lot variability. Understanding these properties is fundamental if these products are to be used in patients with a determinate pathology. Therefore, we analyzed commercially available cannabis oils (n: 500) in Argentina for qualitative and quantitative cannabinoids content. In order to provide a detailed overview of their cannabinoids profiles, and determine Δ9-THC, CBD, and cannabinol (CBN) concentrations, samples were diluted and analyzed by gas chromatography- mass spectrometry (GC/MS). Most of the samples tested positive for cannabinoids (n: 469) with Δ9-THC and CBD as the predominant cannabinoids. Among products tested, only 29.8% (n: 149) gave specific CBD label claims, and testing indicated a CBD tested positive of 70.5% (n: 105). For products (n: 17) with a THC-free label claim, testing indicated 76.5% (n: 13) of Δ9-THC positive, and cannabinoids were not detected in four products. Δ9-THC concentrations ranged from 0.1 to 143.0 mg/mL, CBD concentrations from 0.1 to 125.3 mg/mL, and CBN concentrations from 0.04 to 60.10 mg/mL; CBN/ Δ9-THC ratios ranged from 0.0012 to 2.31, and CBD/ Δ9-THC ratios from 0.0008 to 178.87. Furthermore, the (Δ9-THC + CBN)/CBD ratio of most samples was greater than one. In summary, our results indicate that cannabis oil products show wide variability in cannabinoids content, purity, and labeling.

Structure-Activity Assessment and In-Depth Analysis of Biased Agonism in a Set of Phenylalkylamine 5-HT2A Receptor Agonists.

Serotonergic psychedelics are described to have activation of the serotonin 2A receptor (5-HT2A) as their main pharmacological action. Despite their relevance, the molecular mechanisms underlying the psychedelic effects induced by certain 5-HT2A agonists remain elusive. One of the proposed hypotheses is the occurrence of biased agonism, defined as the preferential activation of certain signaling pathways over others. This study comparatively monitored the efficiency of a diverse panel of 4-position-substituted (and N-benzyl-derived) phenylalkylamines to induce recruitment of ß-arrestin2 (ßarr2) or miniGαq to the 5-HT2A, allowing us to assess structure-activity relationships and biased agonism. All test compounds exhibited agonist properties with a relatively large range of both EC50 and Emax values. Interestingly, the lipophilicity of the 2C-X phenethylamines was correlated with their efficacy in both assays but yielded a stronger correlation in the miniGαq- than in the ßarr2-assay. Molecular docking suggested that accommodation of the 4-substituent of the 2C-X analogues in a hydrophobic pocket between transmembrane helices 4 and 5 of 5-HT2A may contribute to this differential effect. Aside from previously used standard conditions (lysergic acid diethylamide (LSD) as a reference agonist and a 2 h activation profile to assess a compound's activity), serotonin was included as a second reference agonist, and the compounds' activities were also assessed using the first 30 min of the activation profile. Under all assessed circumstances, the qualitative structure-activity relationships remained unchanged. Furthermore, the use of two reference agonists allowed for the estimation of both "benchmark bias" (relative to LSD) and "physiology bias" (relative to serotonin).

Assessment of the Acute Effects of 2C-B vs. Psilocybin on Subjective Experience, Mood, and Cognition.

2,5-dimethoxy-4-bromophenethylamine (2C-B) is a hallucinogenic phenethylamine derived from mescaline. Observational and preclinical data have suggested it to be capable of producing both subjective and emotional effects on par with other classical psychedelics and entactogens. Whereas it is the most prevalently used novel serotonergic hallucinogen to date, it's acute effects and distinctions from classical progenitors have yet to be characterized in a controlled study. We assessed for the first time the immediate acute subjective, cognitive, and cardiovascular effects of 2C-B (20 mg) in comparison to psilocybin (15 mg) and placebo in a within-subjects, double-blind, placebo-controlled study of 22 healthy psychedelic-experienced participants. 2C-B elicited alterations of waking consciousness of a psychedelic nature, with dysphoria, subjective impairment, auditory alterations, and affective elements of ego dissolution largest under psilocybin. Participants demonstrated equivalent psychomotor slowing and spatial memory impairments under either compound compared with placebo, as indexed by the Digit Symbol Substitution Test, Tower of London, and Spatial Memory Task. Neither compound produced empathogenic effects on the Multifaceted Empathy Test. 2C-B induced transient pressor effects to a similar degree as psilocybin. The duration of self-reported effects of 2C-B was shorter than that of psilocybin, largely resolving within 6 hours. Present findings support the categorization of 2C-B as a psychedelic of moderate experiential depth at doses given. Tailored dose-effect studies are needed to discern the pharmacokinetic dependency of 2C-B's experiential overlaps.