Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis.

OBJECTIVE: To determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Five electronic databases of published literature (Cochrane Central Register of Controlled Trials, Medline, Embase, Science Citation Index and Conference Proceedings Citation Index, and PsycInfo) and four databases of unpublished and international literature (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ProQuest Dissertations and Theses Global, and PsycEXTRA), and handsearching of reference lists, conference proceedings, and abstracts. DATA SYNTHESIS AND STUDY QUALITY: Information on potential treatment effect moderators was extracted, including depression type (primary or secondary), previous use of psychedelics, psilocybin dosage, type of outcome measure (clinician rated or self-reported), and personal characteristics (eg, age, sex). Data were synthesised using a random effects meta-analysis model, and observed heterogeneity and the effect of covariates were investigated with subgroup analyses and metaregression. Hedges' g was used as a measure of treatment effect size, to account for small sample effects and substantial differences between the included studies' sample sizes. Study quality was appraised using Cochrane's Risk of Bias 2 tool, and the quality of the aggregated evidence was evaluated using GRADE guidelines. ELIGIBILITY CRITERIA: Randomised trials in which psilocybin was administered as a standalone treatment for adults with clinically significant symptoms of depression and change in symptoms was measured using a validated clinician rated or self-report scale. Studies with directive psychotherapy were included if the psychotherapeutic component was present in both experimental and control conditions. Participants with depression regardless of comorbidities (eg, cancer) were eligible. RESULTS: Meta-analysis on 436 participants (228 female participants), average age 36-60 years, from seven of the nine included studies showed a significant benefit of psilocybin (Hedges' g=1.64, 95% confidence interval (CI) 0.55 to 2.73, P<0.001) on change in depression scores compared with comparator treatment. Subgroup analyses and metaregressions indicated that having secondary depression (Hedges' g=3.25, 95% CI 0.97 to 5.53), being assessed with self-report depression scales such as the Beck depression inventory (3.25, 0.97 to 5.53), and older age and previous use of psychedelics (metaregression coefficient 0.16, 95% CI 0.08 to 0.24 and 4.2, 1.5 to 6.9, respectively) were correlated with greater improvements in symptoms. All studies had a low risk of bias, but the change from baseline metric was associated with high heterogeneity and a statistically significant risk of small study bias, resulting in a low certainty of evidence rating. CONCLUSION: Treatment effects of psilocybin were significantly larger among patients with secondary depression, when self-report scales were used to measure symptoms of depression, and when participants had previously used psychedelics. Further research is thus required to delineate the influence of expectancy effects, moderating factors, and treatment delivery on the efficacy of psilocybin as an antidepressant. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023388065.

Effect of MDMA-assisted therapy on mood and anxiety symptoms in advanced-stage cancer (EMMAC): study protocol for a double-blind, randomised controlled trial.

BACKGROUND: Symptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several centres have reported that one dose of the serotonergic psychedelic psilocybin, combined with therapeutic support, improves these symptoms for up to 6 months in this patient group. Drawing upon related therapeutic mechanisms, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy may have the potential to achieve similar, positive mental health outcomes in this group. Preliminary evidence also supports the tolerability of MDMA-assisted therapy for anxiety and depression in advanced-stage cancer. METHODS: Up to 32 participants with advanced-stage cancer and associated depression and anxiety will be randomised in a 1:1 ratio into one of two blinded parallel treatment arms. The intervention group will receive 120 mg (+ 60 mg optional supplemental dose) MDMA-assisted therapy. The psychoactive control group will receive 20 mg oral (+ 10 mg optional supplemental dose) methylphenidate-assisted therapy. For each medication-assisted therapy session, participants will undergo two 90-min therapeutic support sessions in the week preceding, and one 90-min support session the day after the experimental session. A battery of measures (mood, anxiety, quality of life, mystical experience, spiritual wellbeing, attitudes towards death, personality traits, holistic health and wellbeing, connectedness, demoralisation, expectations, qualitative data and safety measures) will be assessed at baseline and through to the end of the protocol. Participants will be followed up until either 12 months post-randomisation or death, whichever occurs first. DISCUSSION: This study will examine the effect of MDMA-assisted therapy on symptoms of anxiety and depression in advanced-stage cancer. Potential therapeutic implications include establishing the safety and effectiveness of a novel treatment that may relieve mental suffering in patients with life-threatening illness. TRIAL REGISTRATION: Trial registered on Australian New Zealand Clinical Trials Registry. REGISTRATION NUMBER: ACTRN12619001334190p. Date registered: 30/09/2019. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378153&showOriginal=true&isReview=true.

Metabolism and cytotoxicity studies of the two hallucinogens 1cP-LSD and 4-AcO-DET in human liver and zebrafish larvae models using LC-HRMS/MS and a high-content screening assay.

The continuous emergence of new psychoactive substances (NPS) attracted a great deal of attention within recent years. Lately, the two hallucinogenic NPS 1cP-LSD and 4-AcO-DET have appeared on the global market. Knowledge about their metabolism to identify potential metabolic targets for analysis and their cytotoxic properties is lacking. The aim of this work was thus to study their in vitro and in vivo metabolism in pooled human liver S9 fraction (pHLS9) and in zebrafish larvae (ZL) by means of liquid chromatography-high-resolution tandem mass spectrometry. Monooxygenases involved in the initial metabolic steps were elucidated using recombinant human isozymes. Investigations on their cytotoxicity were performed on the human hepatoma cell line HepG2 using a multiparametric, fluorescence-based high-content screening assay. This included measurement of CYP-enzyme mediated effects by means of the unspecific CYP inhibitor 1-aminbenzotriazole (ABT). Several phase I metabolites of both compounds and two phase II metabolites of 4-AcO-DET were produced in vitro and in vivo. After microinjection of 1cP-LSD into the caudal vein of ZL, three out of seven metabolites formed in pHLS9 were also detected in ZL. Twelve 4-AcO-DET metabolites were identified in ZL after exposure via immersion bath and five of them were found in pHLS9 incubations. Notably, unique metabolites of 4-AcO-DET were only produced by ZL, whereas 1cP-LSD specific metabolites were found both in ZL and in pHLS9. No toxic effects were observed for 1cP-LSD and 4-AcO-DET in HepG2 cells, however, two parameters were altered in incubations containing 4-AcO-DET together with ABT compared with incubations without ABT but in concentrations far above expected in vivo concentration. Further investigations should be done with other hepatic cell lines expressing higher levels of CYP enzymes.

Cannabis use and dependence among festival attendees: results from the French OCTOPUS survey.

BACKGROUND: Chronic use of cannabis is associated with an increased risk of psychosocial, mental and physical health impairments. Sociohealth institutions reach a very limited proportion of cannabis users in need of treatment. Using data collected from festival attendees, this study aimed to estimate the prevalence of dependent cannabis users and to characterize cannabis dependence. METHODS: We used data from the cross-sectional OCTOPUS survey carried out at 13 music events in the French department of Loire-Atlantique between July 2017 and July 2018. 383 participants aged 18 or older underwent a face-to-face interview about their basic sociodemographics, tobacco use, alcohol use and past-year substance use. Using the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria, we estimated the prevalence of dependent cannabis users and characterized their dependence. RESULTS: More than two-thirds of participants reported that they had used cannabis in the past 12 months. Among 194 regular cannabis users (at least monthly), 63.4% were dependent. At least 40% of regular users reported health and/or social consequences of cannabis use. Compared to nondependent cannabis users, dependent cannabis users were more likely to be stimulant users and hallucinogen users. CONCLUSIONS: Dependent cannabis use is common among festival attendees, especially among stimulant or hallucinogen users. Festival settings may be important arenas for i) implementing efficient harm reduction measures to prevent dependence and ii) providing information on care structures and promoting the use of care to dependent users. In addition, healthcare professionals should be aware of trends in polysubstance use among dependent cannabis users.

Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis.

We aim to systematically review and meta-analyze the effectiveness and safety of psychedelics [psilocybin, ayahuasca (active component DMT), LSD and MDMA] in treating symptoms of various mental disorders. Web of Science, Embase, EBSCO, and PubMed were searched up to February 2024 and 126 articles were finally included. Results showed that psilocybin has the largest number of articles on treating mood disorders (N = 28), followed by ayahuasca (N = 7) and LSD (N = 6). Overall, psychedelics have therapeutic effects on mental disorders such as depression and anxiety. Specifically, psilocybin (Hedges' g = -1.49, 95% CI [-1.67, -1.30]) showed the strongest therapeutic effect among four psychedelics, followed by ayahuasca (Hedges' g = -1.34, 95% CI [-1.86, -0.82]), MDMA (Hedges' g = -0.83, 95% CI [-1.33, -0.32]), and LSD (Hedges' g = -0.65, 95% CI [-1.03, -0.27]). A small amount of evidence also supports psychedelics improving tobacco addiction, eating disorders, sleep disorders, borderline personality disorder, obsessive-compulsive disorder, and body dysmorphic disorder. The most common adverse event with psychedelics was headache. Nearly a third of the articles reported that no participants reported lasting adverse effects. Our analyses suggest that psychedelics reduce negative mood, and have potential efficacy in other mental disorders, such as substance-use disorders and PTSD.

Single administration of a psychedelic [(R)-DOI] influences coping strategies to an escapable social stress.

Psychedelic compounds have potentially rapid, long-lasting anxiolytic, antidepressive and anti-inflammatory effects. We investigated whether the psychedelic compound (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI], a selective 5-HT2A receptor partial agonist, decreases stress-related behavior in male mice exposed to repeated social aggression. Additionally, we explored the likelihood that these behavioral changes are related to anti-inflammatory properties of [(R)-DOI]. Animals were subjected to the Stress Alternatives Model (SAM), an escapable social stress paradigm in which animals develop reactive coping strategies - remaining in the SAM arena (Stay) with a social aggressor, or dynamically initiated stress coping strategies that involve utilizing the escape holes (Escape) to avoid aggression. Mice expressing these behavioral phenotypes display behaviors like those in other social aggression models that separate animals into stress-vulnerable (as for Stay) or stress-resilient (as for Escape) groups, which have been shown to have distinct inflammatory responses to social stress. These results show that Stay animals have heightened cytokine gene expression, and both Stay and Escape mice exhibit plasma and neural concentrations of the inflammatory cytokine tumor necrosis factor-α (TNFα) compared to unstressed control mice. Additionally, these results suggest that a single administration of (R)-DOI to Stay animals in low doses, can increase stress coping strategies such as increasing attention to the escape route, promoting escape behavior, and reducing freezing during socially aggressive interaction in the SAM. Lower single doses of (R)-DOI, in addition to shifting behavior to suggest anxiolytic effects, also concomitantly reduce plasma and limbic brain levels of the inflammatory cytokine TNFα.

Psychedelic Therapy: A Primer for Primary Care Clinicians-Ketamine.

BACKGROUND: Ketamine, an arylcyclohexylamine dissociative anesthetic agent, has evolved into a versatile therapeutic. It has a rapid-onset, well-understood cardiovascular effects and a favorable safety profile in clinical use. Its enantiomeric compound, esketamine, was approved by the Food and Drug Administration in 2019 for both treatment-resistant depression and major depressive disorder with suicidal ideation. AREAS OF UNCERTAINTY: Research indicates dose-dependent impacts on cognition, particularly affecting episodic and working memory following both acute administration and chronic use, albeit temporarily for the former and potentially persistent for the latter. Alongside acute risks to cardiovascular stability, ketamine use poses potential liver toxicity concerns, especially with prolonged or repeated exposure within short time frames. The drug's association with "ketamine cystitis," characterized by bladder inflammation, adds to its profile of physiological risks. THERAPEUTIC ADVANCES: Data demonstrate a single intravenous infusion of ketamine exhibits antidepressant effects within hours (weighted effect size averages of depression scores (N = 518) following a single 0.5 mg/kg infusion of ketamine is d = 0.96 at 24 hours). Ketamine is also effective at reducing posttraumatic stress disorder (PTSD) symptom severity following repeated infusions (Clinician-Administered PTSD Scale scores: -11.88 points compared with midazolam control). Ketamine also decreased suicidal ideation in emergency settings (Scale for Suicidal Ideation scores: -4.96 compared with midazolam control). Through its opioid-sparing effect, ketamine has revolutionized postoperative pain management by reducing analgesic consumption and enhancing recovery. LIMITATIONS: Many studies indicate that ketamine's therapeutic effects may subside within weeks. Repeated administrations, given multiple times per week, are often required to sustain decreases in suicidality and depressive symptoms. CONCLUSIONS: Ketamine's comprehensive clinical profile, combined with its robust effects on depression, suicidal ideation, PTSD, chronic pain, and other psychiatric conditions, positions it as a substantial contender for transformative therapeutic application.

A phase III multisite randomised controlled trial to compare the efficacy of cannabidiol to placebo in the treatment of cannabis use disorder: the CBD-CUD study protocol.

BACKGROUND: Cannabis use disorder (CUD) is increasingly common and contributes to a range of health and social problems. Cannabidiol (CBD) is a non-intoxicating cannabinoid recognised for its anticonvulsant, anxiolytic and antipsychotic effects with no habit-forming qualities. Results from a Phase IIa randomised clinical trial suggest that treatment with CBD for four weeks reduced non-prescribed cannabis use in people with CUD. This study examines the efficacy, safety and quality of life of longer-term CBD treatment for patients with moderate-to-severe CUD. METHODS/DESIGN: A phase III multi-site, randomised, double-blinded, placebo controlled parallel design of a 12-week course of CBD to placebo, with follow-up at 24 weeks after enrolment. Two hundred and fifty adults with moderate-to-severe CUD (target 20% Aboriginal), with no significant medical, psychiatric or other substance use disorders from seven drug and alcohol clinics across NSW and VIC, Australia will be enrolled. Participants will be administered a daily dose of either 4 mL (100 mg/mL) of CBD or a placebo dispensed every 3-weeks. All participants will receive four-sessions of Cognitive Behavioural Therapy (CBT) based counselling. Primary endpoints are self-reported cannabis use days and analysis of cannabis metabolites in urine. Secondary endpoints include severity of CUD, withdrawal severity, cravings, quantity of use, motivation to stop and abstinence, medication safety, quality of life, physical/mental health, cognitive functioning, and patient treatment satisfaction. Qualitative research interviews will be conducted with Aboriginal participants to explore their perspectives on treatment. DISCUSSION: Current psychosocial and behavioural treatments for CUD indicate that over 80% of patients relapse within 1-6 months of treatment. Pharmacological treatments are highly effective with other substance use disorders but there are no approved pharmacological treatments for CUD. CBD is a promising candidate for CUD treatment due to its potential efficacy for this indication and excellent safety profile. The anxiolytic, antipsychotic and neuroprotective effects of CBD may have added benefits by reducing many of the mental health and cognitive impairments reported in people with regular cannabis use. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry: ACTRN12623000526673 (Registered 19 May 2023).

Adolescent Δ8-THC and Marijuana Use in the US.

Importance: Gummies, flavored vaping devices, and other cannabis products containing psychoactive hemp-derived Δ8-tetrahydrocannabinol (THC) are increasingly marketed in the US with claims of being federally legal and comparable to marijuana. National data on prevalence and correlates of Δ8-THC use and comparisons to marijuana use among adolescents in the US are lacking. Objective: To estimate the self-reported prevalence of and sociodemographic and policy factors associated with Δ8-THC and marijuana use among US adolescents in the past 12 months. Design, Setting, and Participants: This nationally representative cross-sectional analysis included a randomly selected subset of 12th-grade students in 27 US states who participated in the Monitoring the Future Study in-school survey during February to June 2023. Exposures: Self-reported sex, race, ethnicity, and parental education; census region; state-level adult-use (ie, recreational) marijuana legalization (yes vs no); and state-level Δ8-THC policies (regulated vs not regulated). Main Outcomes and Measures: The primary outcome was self-reported Δ8-THC and marijuana use in the past 12 months (any vs no use and number of occasions used). Results: In the sample of 2186 12th-grade students (mean age, 17.7 years; 1054 [48.9% weighted] were female; 232 [11.1%] were Black, 411 [23.5%] were Hispanic, 1113 [46.1%] were White, and 328 [14.2%] were multiracial), prevalence of self-reported use in the past 12 months was 11.4% (95% CI, 8.6%-14.2%) for Δ8-THC and 30.4% (95% CI, 26.5%-34.4%) for marijuana. Of those 295 participants reporting Δ8-THC use, 35.4% used it at least 10 times in the past 12 months. Prevalence of Δ8-THC use was lower in Western vs Southern census regions (5.0% vs 14.3%; risk difference [RD], -9.4% [95% CI, -15.2% to -3.5%]; adjusted risk ratio [aRR], 0.35 [95% CI, 0.16-0.77]), states in which Δ8-THC was regulated vs not regulated (5.7% vs 14.4%; RD, -8.6% [95% CI, -12.9% to -4.4%]; aRR, 0.42 [95% CI, 0.23-0.74]), and states with vs without legal adult-use marijuana (8.0% vs 14.0%; RD, -6.0% [95% CI, -10.8% to -1.2%]; aRR, 0.56 [95% CI, 0.35-0.91]). Use in the past 12 months was lower among Hispanic than White participants for Δ8-THC (7.3% vs 14.4%; RD, -7.2% [95% CI, -12.2% to -2.1%]; aRR, 0.54 [95% CI, 0.34-0.87]) and marijuana (24.5% vs 33.0%; RD, -8.5% [95% CI, -14.9% to -2.1%]; aRR, 0.74 [95% CI, 0.59-0.94]). Δ8-THC and marijuana use prevalence did not differ by sex or parental education. Conclusions and Relevance: Δ8-THC use prevalence is appreciable among US adolescents and is higher in states without marijuana legalization or existing Δ8-THC regulations. Prioritizing surveillance, policy, and public health efforts addressing adolescent Δ8-THC use may be warranted.

Burden of alcohol and other substance use and correlates among undergraduate students at Busitema University in rural Eastern Uganda after COVID-19 lockdown.

Use of alcohol and other substances remains a major health concern among higher learning institutions. This study aimed at assessing the prevalence of alcohol and other substance use among students at Busitema University in Eastern Uganda. A cross sectional survey was conducted among 658 undergraduate students using a questionnaire consisting of Alcohol, Smoking and Substance Involvement Screening Tool and participant sociodemographic and clinical factors. Logistic regression was used to explore the associations. Two hundred sixty-five (40.3%) students reported ever using alcohol and 158 (24.0%) had used in last 3 months. Seventy-four (11.2%) students reported ever use of other substances including tobacco, cannabis, cocaine, stimulants sedatives and hallucinogens and 36 (5.5%) had used within the recent 3 months. After controlling for potential confounders, recent alcohol use was associated with engaging in romantic relationship (odd ratio (OR) = 1.9, P value (P) = 0.045) while having chronic medical conditions was protective (OR = 0.3, P = 0.031). On the other hand, recent use of other substances was 7 times higher among males (OR = 7.0, P = 0.008) compared to females while fourth year of study was protective (OR = 0.05, P = 0.011). Although alcohol use is a worsening challenge among university students, use of other substances is also highly prevalent after COVID-19 lockdown. There is need for universities to identify students with above factors and design interventions to address them in order to prevent the likely undesirable outcomes of alcohol and substance use.

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.

Accuracy and replicability of identifying eyelid tremor as an indicator of recent cannabis smoking.

INTRODUCTION: Cannabis intoxication may increase the risk of motor vehicle crashes. However, reliable methods of assessing cannabis intoxication are limited. The presence of eyelid tremors is among the signs of cannabis use identified under the Drug Evaluation and Classification Program of the International Association of Chiefs of Police. Our objectives were to assess the accuracy and replicability of identifying eyelid tremor as an indicator of recent cannabis smoking using a blinded, controlled study design. METHODS: Adult subjects (N = 103) were recruited into three groups based on their cannabis use history: daily, occasional, and no current cannabis use. Participants' closed eyelids were video recorded for 30 seconds by infrared videography goggles before and at a mean ± standard deviation time of 71.4 ± 4.6 minutes after the onset of a 15-minute interval of ad libitum cannabis flower smoking or vaping. Three observers with expertise in neuro-ophthalmology and medical toxicology were trained on exemplar videos of eyelids to reach a consensus on how to grade eyelid tremor. Without knowledge of subjects' cannabis use history or time point (pre- or post-smoking), observers reviewed each video for eyelid tremor graded as absent, slight, moderate, or severe. During subsequent data analysis, this score was further dichotomized as a consensus score of absent (absent/slight) or present (moderate/severe). RESULTS: Kappa and intraclass correlation coefficient statistics demonstrated moderate agreement among the coders, which ranged from 0.44-0.45 and 0.58-0.61, respectively. There was no significant association between recent cannabis use and the observers' consensus assessment that eyelid tremor was present, and cannabis users were less likely to have tremors (odds ratio: 0.75; 95 percent confidence interval: 0.25, 2.40). The assessment of eyelid tremor as an indicator of recent cannabis smoking had a sensitivity of 0.86, specificity of 0.18, and accuracy of 0.64. DISCUSSION: Eyelid tremor has fair sensitivity but poor specificity and accuracy for identification of recent cannabis use. Inter-rater reliability for assessment of eyelid tremor was moderate for the presence and degree of tremor. The weak association between recent cannabis use and eyelid tremor does not support its utility in identifying recent cannabis use. LIMITATIONS: Videos were recorded at only one time point after cannabis use. Adherence to abstinence could not be strictly supervised. Due to regulatory restrictions, we were unable to control the cannabis product used or administer a fixed Δ9-tetrahydrocannabinol dose. Participants were predominately non-Hispanic and White. CONCLUSIONS: In a cohort of participants with a range of cannabis use histories, acute cannabis smoking was not associated with the presence of eyelid tremor, regardless of cannabis use history, at 70 minutes post-smoking. Additional research is needed to identify the presence of eyelid tremor accurately, determine the relationship between cannabis dose and timeline in relation to last cannabis use to eyelid tremor, and determine how it should be, if at all, utilized for cannabis Drug Recognition Evaluator examinations.

Perceptions of the Seriousness of Different Addictive Behaviors in the United Kingdom.

Background: Societal beliefs about the seriousness of different addictions were assessed in the United Kingdom (UK). Methods: An online panel, conducted in 2021 and sampled to be representative of the UK general population 18 years and over (N = 1499), was conducted and asked participants their views regarding the seriousness of different societal problems, including various addictive behaviors. Results: Cannabis was ranked as the least serious of the addictive behaviors. Other illicit drug use (cocaine, amphetamine, heroin) was rated as the most serious of addictive behaviors. None of the addictive behaviors were rated as being as serious a problem to society as environmental damage, violent crime, poverty, and the COVID-19 pandemic. Conclusions: Ratings of cannabis use were not as expected and stand in contrast to the current UK policy on cannabis use. In addition, the UK policy on alcohol consumption contrasts with societal concerns about alcohol use.

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.

Association of Cannabis Use Disorder with Major Adverse Cardiac and Cerebrovascular Events in Older Non-Tobacco Users: A Population-Based Analysis.

BACKGROUND: Tobacco use disorder (TUD) adversely impacts older patients with established cardiovascular disease (CVD) risk. However, CVD risk in chronic habitual cannabis users without the confounding impact of TUD hasn't been explored. We aimed to determine the risk of major adverse cardiac and cerebrovascular events (MACCE) in older non-tobacco smokers with established CVD risk with vs. without cannabis use disorder (CUD). METHODS: We queried the 2019 National Inpatient Sample for hospitalized non-tobacco smokers with established traditional CVD risk factors aged ≥65 years. Relevant ICD-10 codes were used to identify patients with vs. without CUD. Using multivariable logistic regression, we evaluated the odds of MACCE in CUD cohorts compared to non-CUD cohorts. RESULTS: Prevalence of CUD in the sample was 0.3% (28,535/10,708,815, median age 69), predominantly male, black, and non-electively admitted from urban teaching hospitals. Of the older patients with CVD risk with CUD, 13.9% reported MACCE. The CUD cohort reported higher odds of MACCE (OR 1.20, 95% CI 1.11-1.29, p < 0.001) compared to the non-CUD cohort. Comorbidities such as hypertension (OR 1.9) and hyperlipidemia (OR 1.3) predicted a higher risk of MACCE in the CUD cohort. The CUD cohort also had higher unadjusted rates of acute myocardial infarction (7.6% vs. 6%) and stroke (5.2% vs. 4.8%). CONCLUSIONS: Among older non tobacco smokers with known CVD risk, chronic cannabis use had a 20% higher likelihood of MACCE compared to those who did not use cannabis.

A semi-naturalistic open-label study examining the effect of prescribed medical cannabis use on simulated driving performance.

BACKGROUND: Despite increasing medical cannabis use, research has yet to establish whether and to what extent products containing delta-9-tetrahydrocannabinol (THC) impact driving performance among patients. Stable doses of prescribed cannabinoid products during long-term treatment may alleviate clinical symptoms affecting cognitive and psychomotor performance. AIM: To examine the effects of open-label prescribed medical cannabis use on simulated driving performance among patients. METHODS: In a semi-naturalistic laboratory study, 40 adults (55% male) aged between 23 and 80 years, consumed their own prescribed medical cannabis product. Driving performance outcomes including standard deviation of lateral position (SDLP), the standard deviation of speed (SDS), mean speed and steering variability were evaluated using the Forum8 driving simulator at baseline (pre-dosing), 2.5 h and 5 -h (post-dosing). Perceived driving effort (PDE) was self-reported after each drive. Oral fluid and whole blood samples were collected at multiple timepoints and analysed for THC via liquid chromatography-mass spectrometry. RESULTS: A significant main effect of time was observed for mean speed (p = 0.014) and PDE (p = 0.020), with patients displaying modest stabilisation of vehicle control, increased adherence to speed limits and reductions in PDE post-dosing, relative to baseline. SDLP (p = 0.015) and PDE (p = 0.043) were elevated for those who consumed oil relative to flower-based products. Detectable THC concentrations were observed in oral fluid at 6-h post-dosing (range = 0-24 ng/mL). CONCLUSIONS: This semi-naturalistic study suggests that the consumption of medical cannabis containing THC (1.13-39.18 mg/dose) has a negligible impact on driving performance when used as prescribed.

Efficient Capture of Cannabis Terpenes in Olive Oil during Microwave-Assisted Cannabinoid Decarboxylation.

The development of selective extraction protocols for Cannabis-inflorescence constituents is still a significant challenge. The characteristic Cannabis fragrance can be mainly ascribed to monoterpenes, sesquiterpenes and oxygenated terpenoids. This work investigates the entrapment of Cannabis terpenes in olive oil from inflorescences via stripping under mild vacuum during the rapid microwave-assisted decarboxylation of cannabinoids (MW, 120 °C, 30 min) and after subsequent extraction of cannabinoids (60 and 100 °C). The profiles of the volatiles collected in the oil samples before and after the extraction step were evaluated using static headspace solid-phase microextraction (HS-SPME), followed by gas chromatography coupled to mass spectrometry (GC-MS). Between the three fractions obtained, the first shows the highest volatile content (~37,400 mg/kg oil), with α-pinene, ß-pinene, ß-myrcene, limonene and trans-ß-caryophyllene as the main components. The MW-assisted extraction at 60 and 100 °C of inflorescences using the collected oil fractions allowed an increase of 70% and 86% of total terpene content, respectively. Considering the initial terpene amount of 91,324.7 ± 2774.4 mg/kg dry inflorescences, the percentage of recovery after decarboxylation was close to 58% (mainly monoterpenes), while it reached nearly 100% (including sesquiterpenes) after extraction. The selective and efficient extraction of volatile compounds, while avoiding direct contact between the matrix and extraction solvents, paves the way for specific applications in various aromatic plants. In this context, aromatized extracts can be employed to create innovative Cannabis-based products within the hemp processing industry, as well as in perfumery, cosmetics, dietary supplements, food, and the pharmaceutical industry.