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.

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.

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.

Emerging Issues in Cannabis Law: Big Business and Equity Challenges.

The cannabis industry continues to evolve at a dizzying pace. Across the United States, states and cities shape and reshape their cannabis policies and regulations, cannabis businesses jockey for position and profit, and consumers sift through a marketplace brimming with cannabis products. It is difficult for many stakeholders to make sense of these rapid changes, and by the time they do, the landscape will likely shift again. This article identifies and explores some emerging legal challenges facing the cannabis industry and its stakeholders. It begins with a breakdown of the state of legalization initiatives in the United States as well as the less than ironclad nature of federal prohibition. Next, the article explores the business of cannabis, considering the size of the industry, the interplay between regulated and unregulated markets, and the regulatory challenges facing cannabis businesses today. Finally, the article explores notions of justice and equity as they relate to the cannabis industry and the role governments can play to right the wrongs of the war on drugs while spreading the benefits of legalization equitably.

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.

Assessment of Medical Cannabis and Health-Related Quality of Life.

Importance: The use of cannabis as a medicine is becoming increasingly prevalent. Given the diverse range of conditions being treated with medical cannabis, as well as the vast array of products and dose forms available, clinical evidence incorporating patient-reported outcomes may help determine safety and efficacy. Objective: To assess whether patients using medical cannabis report improvements in health-related quality of life over time. Design, Setting, and Participants: This retrospective case series study was conducted at a network of specialist medical clinics (Emerald Clinics) located across Australia. Participants were patients who received treatment for any indication at any point between December 2018 and May 2022. Patients were followed up every mean (SD) 44.6 (30.1) days. Data for up to 15 follow-ups were reported. Statistical analysis was conducted from August to September 2022. Exposure: Medical cannabis. Product types and cannabinoid content varied over time in accordance with the treating physician's clinical judgement. Main Outcomes and Measures: The main outcome measure was health-related quality of life as assessed using the 36-Item Short Form Health Survey (SF-36) questionnaire. Results: In this case series of 3148 patients, 1688 (53.6%) were female; 820 (30.2%) were employed; and the mean (SD) age was 55.9 (18.7) years at baseline before treatment. Chronic noncancer pain was the most common indication for treatment (68.6% [2160 of 3148]), followed by cancer pain (6.0% [190 of 3148]), insomnia (4.8% [152 of 3148]), and anxiety (4.2% [132 of 3148]). After commencing treatment with medical cannabis, patients reported significant improvements relative to baseline on all 8 domains of the SF-36, and these improvements were mostly sustained over time. After controlling for potential confounders in a regression model, treatment with medical cannabis was associated with an improvement of 6.60 (95% CI, 4.57-8.63) points to 18.31 (95% CI, 15.86-20.77) points in SF-36 scores, depending on the domain (all P < .001). Effect sizes (Cohen d) ranged from 0.21 to 0.72. A total of 2919 adverse events were reported, including 2 that were considered serious. Conclusions and Relevance: In this case series study, patients using medical cannabis reported improvements in health-related quality of life, which were mostly sustained over time. Adverse events were rarely serious but common, highlighting the need for caution with prescribing medical cannabis.

Using in vitro receptor activity studies of synthetic cannabinoids to support the risk assessment of new psychoactive substances - A Swedish strategy to protect public health from harm.

In the past 15 years, close to 1000 of new psychoactive substances (NPS) have been reported in Europe and globally. At the time of identification, data on safety, toxicity and carcinogenic potential of many NPS are not available or very limited. To work more efficiently, a strategy and collaboration between the Public Health Agency of Sweden (PHAS) and the National Board of Forensic Medicine was established involving in vitro receptor activity assays to demonstrate neurological activity of NPS. This report summarizes the first results on the synthetic cannabinoid receptor agonists (SCRAs), and subsequent actions taken by PHAS. A total of 18 potential SCRAs were selected by PHAS for in vitro pharmacological characterization. 17 compounds could be acquired and investigated for their activity on the human cannabinoid-1 (CB1) receptors expressed together with the AequoScreen system in CHO-K1 cells. Dose-response curves were established using eight different concentrations in triplicates at three occasions with JWH-018 as reference. For the MDMB-4en-PINACA, MMB-022, ACHMINACA, ADB-BUTINACA, 5F-CUMYL-PeGACLONE, 5C-AKB48, NM-2201, 5F-CUMYL-PINACA, JWH-022, 5Cl-AB-PINACA, MPhP-2201, 5F-AKB57 the half maximal effective concentration values ranged from 2.2 nM (5F-CUMYL-PINACA) to 171 nM (MMB-022). EG-018 and 3,5-AB-CHMFUPPYCA were none-active. The results contributed to 14 of these compounds being scheduled as narcotics in Sweden. In conclusion, many of the emerging SCRAs are potent activators of the CB1 receptor in vitro, although some lack activity or are partial agonists. The new strategy proved useful when data on psychoactive effects of the SCRAs under investigation were not available or limited.

Clearing cannabis criminal records: A survey of criminal record expungement availability and accessibility among US States and Washington DC that decriminalized or legalized cannabis.

BACKGROUND: In 2022, despite expanding state-level legalization, cannabis remained illegal at the federal level, driving drug offenses, and contact with the justice system. Cannabis criminalization disproportionately impacts minorities, and criminal records carry negative economic, health, and social consequences. Legalization prevents future criminalization but fails to assist existing record-holders. We surveyed 39 states and Washington DC where cannabis was decriminalized or legalized to determine record expungement availability and accessibility for cannabis offenders. METHODS: We performed a retrospective, qualitative survey of state expungement laws allowing record sealing or record destruction where cannabis use was decriminalized or legalized. Statutes were collected between February 25, 2021, and August 25, 2022, from state websites or NexisUni. We collected pardon information for two states from online state government resources. Materials were coded in Atlas.ti to determine if states had general, cannabis, and other drug conviction expungement regimes, petitions, or automated systems, waiting periods, and financial requirements. Codes were developed via inductive and iterative coding of materials. RESULTS: Among places surveyed, 36 provided any conviction expungement, 34 provided general relief, 21 offered cannabis-specific relief, and 11 offered general drug relief, nonexclusively. Most states used petitions. Thirty-three general and 7 cannabis-specific programs required waiting periods. Nineteen general and 4 cannabis programs imposed administrative fees, and 16 general and one cannabis-specific program required legal financial obligations to be paid. CONCLUSION: Among the 39 states and Washington DC that decriminalized or legalized cannabis and offered expungement, more states relied on general rather than cannabis-specific systems, and the majority of these required record holders to petition for relief and imposed waiting periods and financial requirements. Research is needed to determine if automating expungement, reducing or eliminating waiting periods, and eliminating financial requirements may expand record relief for former cannabis offenders.

Assessment of Orally Administered Δ9-Tetrahydrocannabinol When Coadministered With Cannabidiol on Δ9-Tetrahydrocannabinol Pharmacokinetics and Pharmacodynamics in Healthy Adults: A Randomized Clinical Trial.

Importance: Controlled clinical laboratory studies have shown that cannabidiol (CBD) can sometimes attenuate or exacerbate the effects of Δ9-tetrahydrocannabinol (Δ9-THC). No studies have evaluated differences in pharmacokinetics (PK) of Δ9-THC and pharmacodynamics (PD) between orally administered cannabis extracts that vary with respect to Δ9-THC and CBD concentrations. Objective: To compare the PK and PD of orally administered Δ9-THC-dominant and CBD-dominant cannabis extracts that contained the same Δ9-THC dose (20 mg). Design, Setting, and Participants: This randomized clinical trial was a within-participant, double-blind, crossover study conducted from January 2021 to March 2022 at the Johns Hopkins University Behavioral Pharmacology Research Unit, Baltimore, MD. Eighteen healthy adults completed 3 randomized outpatient experimental test sessions that were each separated by at least 1 week. Interventions: Brownies containing (1) no cannabis extract (ie, placebo); (2) Δ9-THC-dominant extract (20 mg Δ9-THC with no CBD); and (3) CBD-dominant extract (20 mg Δ9-THC + 640 mg CBD) were administered to participants 30 minutes prior to administering a cytochrome P450 (CYP) probe drug cocktail, which consisted of 100 mg caffeine, 20 mg omeprazole, 25 mg losartan, 30 mg dextromethorphan, and 2 mg midazolam. Main Outcomes and Measures: Change-from-baseline plasma concentrations for Δ9-THC or Δ9-THC metabolites and scores for subjective drug effects, cognitive and psychomotor performance, and vital signs. The area under the plasma vs concentration vs time curve (AUC) and maximum plasma concentration (Cmax) were determined. Results: The participant cohort of 18 adults included 11 males (61.1%) and 7 females (38.9%) with a mean (SD) age of 30 (7) years who had not used cannabis for at least 30 days prior to initiation of the study (mean [SD] day since last cannabis use, 86 [66] days). The CYP cocktail + placebo brownie and the CYP cocktail did not affect any PD assessments. Relative to CYP cocktail + Δ9-THC, CYP cocktail + Δ9-THC + CBD produced a higher Cmax and area under the plasma concentration vs time curve for Δ9-THC, 11-OH-Δ9-THC, and Δ9-THC-COOH. The CYP cocktail + Δ9-THC + CBD increased self-reported anxiety, sedation, and memory difficulty, increased heart rate, and produced a more pronounced impairment of cognitive and psychomotor performance compared with both CYP cocktail + Δ9-THC and CYP cocktail + placebo. Conclusions and Relevance: In this randomized clinical trial of oral Δ9-THC and CBD, stronger adverse effects were elicited from a CBD-dominant cannabis extract compared with a Δ9-THC-dominant cannabis extract at the same Δ9-THC dose, which contradicts common claims that CBD attenuates the adverse effects of Δ9-THC. CBD inhibition of Δ9-THC and 11-OH-Δ9-THC metabolism is the likely mechanism for the differences observed. An improved understanding of cannabinoid-cannabinoid and cannabinoid-drug interactions are needed to inform clinical and regulatory decision-making regarding the therapeutic and nontherapeutic use of cannabis products. Trial Registration: clinicaltrials.gov Identifier: NCT04201197.

Prices and Purchase Sources for Dried Cannabis Flower in the United States, 2019-2020.

Introduction: The price of cannabis has major implications for public health, public safety, social equity, and government revenues. This article examines prices and sources of purchased dried cannabis flower among consumers facing different state laws in the United States. Methods: Repeat cross-sectional survey data were collected from the International Cannabis Policy Study in 2019 and 2020. U.S. respondents were recruited through online commercial panels, ages 16-65, and purchased dried flower in the past year (n=9766). Weighted binary logistic regression models examined legal purchasing in states that had legalized recreational cannabis. Results: Compared with respondents in states with recreational stores, respondents living in "illegal," "medical," and "recreational" states without stores were associated with paying a higher unit price of dried flower (+20.5%, +23.6%, +27.4%, respectively; all p<0.05). The majority of respondents in states with recreational stores last purchased from stores/dispensaries (2019: 66.6%; 2020: 62.0%) and the odds of purchasing legally was greater with each additional year after stores opened (adjusted odds ratio=1.48, 95% confidence interval: 1.37, 1.60). Conclusions: Cannabis prices and purchase behaviors are strongly influenced by its legal status and presence of stores. After states legalize for recreational purposes, it takes multiple years for the legal market to become established as the number of retail stores increase and prices decrease. The findings demonstrate that consumers use sources that they are legally allowed to access, suggesting an increased number of physical retail stores and online delivery services could expand uptake of legal sources in states with recreational cannabis laws.

Clinician Attitudes, Training, and Beliefs About Cannabis: An Interprofessional Assessment.

Background: Medical use of cannabis is growing in popularity across the United States, but medical education and clinician comfort discussing cannabis use for medical purposes have not kept pace. Materials and Methods: A total of 344 clinicians in the state of Pennsylvania (response rate 14%) completed a brief online survey about their attitudes, training, and experiences regarding medical cannabis and certifying patients to use medical cannabis. Results: Only 51% of clinicians reported completing any formal training on medical cannabis. Compared with noncertifying clinicians (pharmacists, nurse practitioners, and physician assistants), physicians were significantly more comfortable with patient use of medical cannabis, saw fewer risks, more benefits, and felt better prepared to discuss its use with vulnerable populations. All clinicians noted significant limitations to their understanding of how medical cannabis can affect patients, and many indicated a desire for more research and training to fill in gaps in their knowledge. Conclusions: Insufficient medical curricula on the medical uses of cannabis are available to interprofessional clinicians across their disciplines, and clinicians report significant deficits in their knowledge base about its effects. Additionally, these data suggest an urgent need to expand training opportunities to the full spectrum of clinicians as all are involved in caring for patients who use medical cannabis.

Long-Term Outcomes of Adolescent THC Exposure on Translational Cognitive Measures in Adulthood in an Animal Model and Computational Assessment of Human Data.

Importance: Although perceived as relatively harmless and nonaddictive, adolescent cannabis use significantly increases the likelihood of developing cannabis use disorder in adulthood, especially for high-potency cannabis. Risky decision-making is associated with chronic cannabis use, but given confounds of human studies, it remains unclear whether adolescent cannabis exposure and Δ9-tetrahydrocannabinol (THC) potency specifically predicts risky decision-making or influences cognitive response to the drug later in life. Objective: To leverage a human data set of cannabis users and a rat model to evaluate the long-term outcomes of adolescent THC exposure on adult decision-making and impulse control. Design, Setting, and Participants: This translational rat study tested the link between adolescent THC exposure and adulthood decision-making. A reanalysis of a previously published dataset of human chronic cannabis users was conducted to evaluate decision-making phenotypes. Computational modeling assessed the human and animal results in a single framework. Data were collected from 2017 to 2020 and analyzed from 2020 to 2022. Main Outcomes and Measures: Decision-making was measured by the Iowa Gambling Task (IGT) and Rat Gambling Task (rGT). Impulse control was assessed in the rat model. Computational modeling was used to determine reward and punishment learning rates and learning strategy used by cannabis users and THC-exposed rats. Cell-specific molecular measures were conducted in the prefrontal cortex and amygdala. Results: Of 37 participants, 24 (65%) were male, and the mean (SD) age was 33.0 (8.3) years. Chronic cannabis users (n = 22; mean [SE] IGT score, -5.182 [1.262]) showed disadvantageous decision-making compared with controls (n = 15; mean [SE] IGT score, 7.133 [2.687]; Cohen d = 1.436). Risky choice was associated with increased reward learning (mean [SE] IGT score: cannabis user, 0.170 [0.018]; control, 0.046 [0.008]; Cohen d = 1.895) and a strategy favoring exploration vs long-term gains (mean [SE] IGT score: cannabis user, 0.088 [0.012]; control, 0.020 [0.002]; Cohen d = 2.218). Rats exposed to high-dose THC but not low-dose THC during adolescence also showed increased risky decision-making (mean [SE] rGT score: vehicle, 46.17 [7.02]; low-dose THC, 69.45 [6.01]; high-dose THC, 21.97 [11.98]; Cohen d = 0.433) and elevated reward learning rates (mean [SE] rGT score: vehicle, 0.17 [0.01]; low-dose THC, 0.10 [0.01]; high-dose THC, 0.24 [0.06]; Cohen d = 1.541) during task acquisition. These animals were also uniquely susceptible to increased cognitive impairments after reexposure to THC in adulthood, which was correlated with even greater reward learning (r = -0.525; P < .001) and a shift in strategy (r = 0.502; P < .001), similar to results seen in human cannabis users. Molecular studies revealed that adolescent THC dose differentially affected cannabinoid-1 receptor messenger RNA expression in the prelimbic cortex and basolateral amygdala in a layer- and cell-specific manner. Further, astrocyte glial fibrillary acidic protein messenger RNA expression associated with cognitive deficits apparent with adult THC reexposure. Conclusions and Relevance: In this translational study, high-dose adolescent THC exposure was associated with cognitive vulnerability in adulthood, especially with THC re-exposure. These data also suggest a link between astrocytes and cognition that altogether provides important insights regarding the neurobiological genesis of risky cannabis use that may help promote prevention and treatment efforts.

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

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

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

As the pharmacological properties and therapeutic applications of Cannabis sativa L. pace with the upsurge of interest of the scientific community in harnessing its constituent phytocannabinoids, illicit use may raise serious health issues. Tetrahydrocannabinol (THC) is one of the most well-known phytoactive constituents of cannabis and continues to garner scientific and public attention not only because of its pharmacological value but also because over-the-counter products of THC and prescription medications are becoming increasingly available from pharmacies, dispensaries, Internet, local retail stores, or by illicit means. Hence, a multidimensional approach was employed to examine the impact of THC on zebrafish larvae. The acute toxicity, expressed as LC50, was 1.54 mg/L. Adverse effects were observed on the phenotype, such as tail bending, pericardial edema, etc., even at concentrations lower than LC50, and fundamental functions of larvae (e.g., heart rate and cardiac contractility, and rhythm) were significantly affected. Behavioral changes were noticed, which were reflected in locomotor activity and sensitivity to light/dark changes. Finally, an untargeted metabolomic study was carried out to shed light on the metabolic alterations that occurred, providing substantiating evidence of the observed phenotype alterations. Overall, the potentially detrimental effects of THC on a vertebrate model are depicted.

Does cannabis testing in the military drive synthetic cannabinoid use? Self-reported use motivations among justice-involved veterans.

BACKGROUND: Though synthetic cannabinoid receptor agonists (SCRAs) were controlled after being introduced as a 'legal high,' SCRAs likely remain appealing to individuals subject to routine drug screens as not all testing programs consistently include SCRAs. Military populations have been linked to SCRAs due to the unconfirmed supposition that testing protocols led many to substitute SCRAs for cannabis. This study aimed to explore SCRA use prevalence, correlates, and use motivations among veterans, with a particular focus on whether United States military personnel substituted SCRAs for cannabis to subvert testing protocols. METHODS: All veterans appearing in one of eight civilian criminal courts in three U.S. states were invited to answer questionnaire items related to military service, court functionality, and substance use. Of the 579 veterans eligible, 54.9% chose to participate, yielding a cross-sectional sample of 318 veterans charged with a criminal offense by civilian authorities. RESULTS: Sixty-five (21.3%) justice-involved veterans reported lifetime SCRA use. Use while within the military was reported by 15.0% of veterans enlisting after 2008. Only eight (12.3%) reported SCRAs were used as a substitute for cannabis. Boredom (36.9%), experimentation (27.7%), and social aspects of SCRA use (32.3%) were more commonly reported motives. Logistic regression models indicated that use of cannabis (aPR=2.06, p<.05), hallucinogens (aPR=2.50, p<.01), and SCRAs (aPR=2.49, p<.05) while in the military were risk factors for SCRA use after leaving the military, whereas older age at time of military exist was a protective factor (aPR=.87, p<.01) CONCLUSIONS: Drug testing programs within the military do not appear to have the unintended consequence of routing individuals to more risky drugs; however, SCRAs appear to have been an underappreciated problem within the military. Further, use extends beyond the military with many only initiating use after discharge, suggesting SCRA use may jeopardize the health of veterans post-service.

Rating the comparative efficacy of state-level cannabis policies on recreational cannabis markets in the United States.

BACKGROUND: Cannabis policy is developing faster than empirical evidence about policy effects. With a panel of experts in substance use policy development and research, we identified key cannabis policies and their provisions enacted by U.S. states; rated their theoretical efficacy in a restrictive form for reducing problematic use and impaired driving in the context of a recreational cannabis market as judged by experts; and rated the strength of evidence for each policy. METHODS: Using a modified Delphi approach, 9 panelists rated the comparative efficacy of 18 state cannabis policies for reducing youth use of cannabis, excessive cannabis use among the general population, and cannabis-impaired driving. Each outcome was rated separately using a Likert scale, and panelists also rated the strength of evidence supporting each efficacy rating. Investigators provided descriptions of each policy so that the nine panelists had similar conceptions of each policy. RESULTS: State monopoly (state owns all production, manufacturing, wholesale, and retail operations) was rated as the most effective policy for all three outcome areas. Restrictions on retail physical availability, taxes, retail price restrictions, and retail operations restrictions were also highly rated for all three outcomes. Policies regulating cannabis businesses and products were judged more effective than policies targeting consumer use and behavior. Panelists reported there was little or no direct evidence from the cannabis policy literature for most of the included policies. CONCLUSION: These ratings can facilitate research as well as policy-making decisions. A relatively small number of policies were judged to be highly effective across all three domains, indicating that for the most part adult excessive use, youth use, and impaired driving can all be reduced with the same set of policies; these policies tended to target the behaviors of businesses rather than consumers. The low levels of direct evidence available to inform policy ratings, as reported by the policy panelists, makes clear the need for ongoing and sustained cannabis policy research.

Using ecological momentary assessment and a portable device to quantify standard tetrahydrocannabinol units for cannabis flower smoking.

AIMS: To evaluate the feasibility and validity of a new method of quantifying cannabis flower use, integrating the amount of cannabis flower smoked, and the potency of the cannabis flower. DESIGN: Ecological momentary assessment (EMA) for 14 days. SETTING: Participants' daily lives in Columbia, Missouri, USA. PARTICIPANTS: A total of 50 community participants, who were regular cannabis flower smokers (48% female). MEASUREMENTS: Momentary subjective intoxication ratings following cannabis flower smoking; momentary quantity of cannabis flower smoked; potency of cannabis flower smoked in terms of percentage of tetrahydrocannabinol (THC) concentration assessed with a portable device, the Purpl Pro; and time since finished smoking. FINDINGS: Participants completed our field testing of their cannabis flower (96.2%) and were compliant with our 2-week EMA protocol (73% for random prompts and 91% for morning reports). Momentary subjective intoxication ratings trended down as a function of time since smoking (r = -0.10, P = 0.004, 95% CI, [-0.17, -0.03]). Multi-level model (MLM) results indicated the momentary standard THC units (mg THC) were positively associated with momentary subjective intoxication ratings (b = 0.01, P = 0.03, 95% CI, [0.01, 0.012]). CONCLUSIONS: There is evidence to support the feasibility and initial validity of a new method of quantifying cannabis flower use into standard tetrahydrocannabinol units. Researchers investigating the effects of cannabis flower use on a range of outcomes (e.g. neurobehavioral effects, emotional sequelae, and driving impairment) as well as in clinical treatment trials might adopt this method to provide estimates of cannabis flower use.