Delta-8 Tetrahydrocannabinol in the Emergency Department: A Case Series.

INTRODUCTION: "Delta-8," or delta-8 tetrahydrocannabinol (delta-8 THC), is a cannabinoid product that is growing in popularity for recreational use across the nation. This report aims to characterize the clinical presentation of acute delta-8 ingestions presenting to the emergency department. CASE SERIES: This is a case series of 6 patients who presented to a regional network of small- and medium-volume emergency departments in northwest Wisconsin. Patient histories confirmed that all patients had delta-8 exposure. Patient ages ranged from 5 to 57 years old. Amounts ingested and routes of ingestions varied from patient to patient. The most common symptoms reported were respiratory depression, unresponsiveness, altered mental status, tachycardia, and chest pressure. CONCLUSIONS: This case series is a snapshot of the burden experienced by emergency departments because of delta-8 availability. Clinicians should maintain a high index of suspicion for delta-8 use, especially in patients with altered mental status, anxiety, or cardiac.

Hot Dab Associated Pneumonitis - a case report.

BACKGROUND: Dabbing is recently getting popular among young adults. It is a new method of using the most active form of marijuana where large amounts of concentrated tetrahydrocannabinol are inhaled. Tetrahydrocannabinol is associated with a feeling of 'High' which makes the user feel joyous and relaxed. With increasing use of such techniques, dabbing becomes an important differential for evaluation of acute respiratory failure with pneumonitis especially in the adult population. CASE PRESENTATION: A Fifty-one years old Caucasian man presented to the hospital with chest pressure and shortness of breath. The patient was noted to be hypoxic, desaturating down to 82-83% on nasal cannula oxygen. Imaging revealed bilateral lung infiltrates. Patient was started on high flow oxygen, broad spectrum antibiotics and intravenous corticosteroids. The patient gradually improved and was able to come off oxygen completely. He was discharged home on prednisone taper. CONCLUSIONS: Dabbing is a newer technique which has been gaining popularity for marijuana usage. With the legalization of marijuana, newer techniques are getting popular. Our case report emphasizes the importance of keeping dabbing as a differential when a patient presents with respiratory failure and has concerns for pneumonitis. Patients might not reveal until specifically asked about their practices.

Dose Estimation Utility in a Population Pharmacokinetic Analysis of Inhaled Δ9-Tetrahydrocannabinol Cannabis Market Products in Occasional and Daily Users.

BACKGROUND: Unusually high variability in blood Δ9-tetrahydrocannabinol (THC) concentrations have been observed in subjects inhaling similar cannabis products over similar time periods when consumption is ad libitum. This makes simple gravimetric dose estimation a poor predictor of THC exposure. Population pharmacokinetic analyses of blood THC concentration versus time data are routinely used to estimate pharmacokinetic parameters. The aim of this study was to estimate the inhaled dose of THC in occasional and daily users of high potency market cannabis. METHODS: Blood THC concentrations were measured for 135 minutes from 29 participants who either smoked high concentration flower or inhaled concentrates ad libitum during a 15-minute session. Frequent blood samples were obtained over the following 135 minutes. RESULTS: The estimated central and rapidly equilibrating volumes of distribution of a 3-compartment model were 19.9 ± 1.2 and 51.6 ± 4.7 L whereas the intercompartmental clearances were 1.65 ± 0.14 and 1.75 ± 0.10 L/min, respectively. Covariate-adjusted analysis revealed that the estimated inhaled THC dose was considerably less among occasional users compared with daily users. CONCLUSIONS: Three-compartment pharmacokinetics of THC did not differ among the 3 user groups, and the early phase (first 135 minutes postinception of inhalation) kinetics were similar to those previously described after smoking low potency cannabis products. Therefore, inhaled THC dose can be estimated from pharmacokinetic data and covariate-driven adjustments can be used to estimate THC doses, based on the participant cannabis usage pattern (occasional versus daily), improving the accuracy of THC exposure estimates compared with those derived from weighed THC content alone.

Multi-modal and bi-directional effects of a synthetic Δ9-Tetrahydrocannabinol (THC) analogue, Nabilone, on spatio-temporal binding windows: Evidence from the projected hand illusion.

Abnormally widened spatial and temporal binding windows (SBW/TBWs; length of space/time whereby stimuli are considered part of the same percept) are observed in schizophrenia. TBW alterations have been associated with altered sense of agency (hereafter referred to as agency), and an associative relationship between embodiment (body ownership) and agency has been proposed. SBWs/TBWs are investigated separately, but no evidence exists of these being separate in mechanism, system or function. The underlying neural substrate of schizophrenia remains unclear. The literature claims either pro-psychotic or anti-psychotic effects of Δ9-Tetrahydrocannabinol (THC) in patients and healthy individuals, but major support for cannabis in the aetiology of schizophrenia is associative, not causal. To clarify if THC is pro- or anti-psychotic, this single-blind, placebo-controlled within-subjects cross-over study tested several hypotheses. 1) Competing hypotheses that a synthetic THC analogue, Nabilone (NAB, 1-2 mg), would alter measures of agency and embodiment in healthy volunteers (n = 32) similarly, or opposite, to that of in patients with schizophrenia. 2) That there would be significant associations between any NAB-induced alterations in individual agency and embodiment measures in the Projected Hand Illusion (PHI). 3) That there is a unitary spatio-temporal binding window (STBW). A large proportion of individuals did not experience the PHI. Multimodal and bi-directional effects of NAB on the PHI were observed. Evidence of a unitary spatio-temporal binding window (STBW) was observed. NAB widened the STBW in some but narrowed it in others as a function of space and delay. No associations were found between agency and embodiment.

The relationship between clinical impairment and blood drug concentration: Comparison between the most prevalent traffic relevant drug groups.

AIM: The aim of the present study was to investigate the relationship between blood concentrations of four different drug classes; ethanol, benzodiazepines, amphetamines and tetrahydrocannabinol (THC) and driver impairment as assessed by a clinical test of impairment (CTI). METHODS: Data was retrieved from a national database on CTI assessments and accompanying blood drug concentrations from apprehended drivers. All drug concentrations in blood were quantified using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS), and compared to the results of the CTI which were categorized as either "not impaired", "mildly impaired", "moderately impaired", or "considerably impaired". RESULTS: A total number of 15 514 individual mono drug-cases collected over 9 years was included. 89 % were men and the median age was 34 years. In addition, 3 684 individual cases with similar age and gender distribution where no drugs were detected, were included as a reference group. For ethanol and benzodiazepines the percentage of clinically impaired cases increased markedly from lower to higher concentration windows, from 60 % to 97 % for ethanol and from 38 % to 76 % for benzodiazepines. The corresponding increase for amphetamines and THC was modest, from 43 % to 58 % for amphetamines and from 41 % to 55 % for THC. The correlation between drug concentration and degree of impairment was high for ethanol (Spearman´s rho=0.548, p<0.001) and relatively high for benzodiazepines (Spearman´s rho=0.377, p<0.001), but low for amphetamines (Spearman´s rho=0.078, p<0.001) and THC (Spearman´s rho=0.100, p<0.001). CONCLUSION: The percentage of impaired drivers increased with increasing blood drug concentration for all four drug classes, most pronounced for ethanol and benzodiazepines and much less for amphetamines and THC. The median blood drug concentration increased with increasing magnitude of impairment for ethanol and benzodiazepines, while this was much less pronounced for amphetamines and THC. The ranges of drug concentrations, however, were wide for all four drug classes in all impairment categories as assessed by individual clinical examination.

Rapid In Situ Near-Infrared Assessment of Tetrahydrocannabinolic Acid in Cannabis Inflorescences before Harvest Using Machine Learning.

Cannabis is cultivated for therapeutic and recreational purposes where delta-9 tetrahydrocannabinol (THC) is a main target for its therapeutic effects. As the global cannabis industry and research into cannabinoids expands, more efficient and cost-effective analysis methods for determining cannabinoid concentrations will be beneficial to increase efficiencies and maximize productivity. The utilization of machine learning tools to develop near-infrared (NIR) spectroscopy-based prediction models, which have been validated from accurate and sensitive chemical analysis, such as gas chromatography (GC) or liquid chromatography mass spectroscopy (LCMS), is essential. Previous research on cannabinoid prediction models targeted decarboxylated cannabinoids, such as THC, rather than the naturally occurring precursor, tetrahydrocannabinolic acid (THCA), and utilize finely ground cannabis inflorescence. The current study focuses on building prediction models for THCA concentrations in whole cannabis inflorescences prior to harvest, by employing non-destructive screening techniques so cultivators may rapidly characterize high-performing cultivars for chemotype in real time, thus facilitating targeted optimization of crossbreeding efforts. Using NIR spectroscopy and LCMS to create prediction models we can differentiate between high-THCA and even ratio classes with 100% prediction accuracy. We have also developed prediction models for THCA concentration with a R2 = 0.78 with a prediction error average of 13%. This study demonstrates the viability of a portable handheld NIR device to predict THCA concentrations on whole cannabis samples before harvest, allowing the evaluation of cannabinoid profiles to be made earlier, therefore increasing high-throughput and rapid capabilities.

Bioelectronic sensing platform emulating the human endocannabinoid system for assessing and modulating of cannabinoid activity.

Cannabinoids are involved in physiological and neuromodulatory processes through their interactions with the human cannabinoid receptor-based endocannabinoid system. Their association with neurodegenerative diseases and brain reward pathways underscores the importance of evaluating and modulating cannabinoid activity for both understanding physiological mechanisms and developing therapeutic drugs. The use of agonists and antagonists could be strategic approaches for modulation. In this study, we introduce a bioelectronic sensor designed to monitor cannabinoid binding to receptors and assess their agonistic and antagonistic properties. We produced human cannabinoid receptor 1 (hCB1R) via an Escherichia coli expression system and incorporated it into nanodiscs (NDs). These hCB1R-NDs were then immobilized on a single-walled carbon nanotube field-effect transistor (swCNT-FET) to construct a bioelectronic sensing platform. This novel system can sensitively detect the cannabinoid ligand anandamide (AEA) at concentrations as low as 1 fM, demonstrating high selectivity and real-time response. It also successfully identified the hCB1R agonist Δ9-tetrahydrocannabinol and observed that the hCB1R antagonist rimonabant diminished the sensor signal upon AEA binding, indicating the antagonism-based modulation of ligand interaction. Consequently, our bioelectronic sensing platform holds potential for ligand detection and analysis of agonism and antagonism.

A randomized, double-blind, placebo-controlled trial to evaluate the effect of nabiximols oromucosal spray on clinical measures of spasticity in patients with multiple sclerosis.

BACKGROUND: Spasticity is a common and potentially debilitating symptom of multiple sclerosis (MS) with a highly variable presentation. Understanding, quantifying, and managing MS-associated spasticity (MSS) is a challenge for research and in clinical practice. The tetrahydrocannabinol:cannabidiol oromucosal spray nabiximols has demonstrated beneficial effects in the treatment of MSS in clinical studies as well as real-world observational studies, and is approved for the treatment of MSS in 29 countries globally. Most randomized studies evaluated the efficacy of nabiximols using the change in average daily spasticity scores reported by patients using the spasticity Numeric Rating Scale as a primary endpoint. This study, RELEASE MSS1 (NCT04657666), was conducted using a prespecified primary endpoint of change in spastic muscle tone (Modified Ashworth Scale Lower Limb Muscle Tone-6 [MAS LLMT-6]) to corroborate the efficacy of nabiximols as adjunctive therapy observed with the patient-measured spasticity Numeric Rating Scale primary endpoint in the previous pivotal studies. METHODS: This was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 2-treatment, 2-period, crossover trial. Because of the prevalence and functional impact of lower limb spasticity on the individual patient's overall experience of MS spasticity, the MAS LLMT-6 was derived from the clinician-rated MAS. The MAS LLMT-6 is the average transformed MAS score of 6 muscle groups (knee flexors, knee extensors, and ankle plantar flexors; all assessed bilaterally). Secondary measures included MAS LLMT-4 scores, defined as the average of the 4 individual MAS-transformed scores of knee flexors and knee extensors bilaterally. Patients had a diagnosis of MS and an untransformed MAS score of at least 2 in ≥2 of 6 LLMT-6 muscle groups despite current treatment with ≥1 of the following oral antispasticity agents: baclofen, tizanidine, or dantrolene. Eligible participants were randomly assigned to 1 of 2 treatment sequences. Each treatment sequence consisted of two treatment periods, each consisting of a 14-day dose titration phase followed by a 7-day dose maintenance phase. RESULTS: Of 68 patients enrolled, 33 were assigned to nabiximols followed by placebo and 35 were assigned to placebo followed by nabiximols. Least squares mean changes in MAS LLMT-6 scores from baseline to day 21 were -0.23 for nabiximols and -0.26 for placebo; the least squares mean treatment difference in MAS LLMT-6 scores for nabiximols versus placebo was 0.04, which was not statistically significant (P = 0.7152). Mean changes in MAS LLMT-4 scores from baseline to day 21 also were not significantly different between the nabiximols and placebo groups. Safety results in this study were consistent with the known safety profile of nabiximols in patients with MSS. CONCLUSION: Despite the established efficacy of nabiximols in MSS observed using patient-reported measures, the primary endpoint was not met in this study. The findings from this study reflect and emphasize some of the challenges in the evaluation and treatment of MS spasticity. CLINICAL TRIAL REGISTRATION NUMBER (CLINICALTRIALS.GOV): : NCT04657666.

Insight into the mechanism of adsorption and release of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in sewage by modeling regional suspended particles for evaluation of the influence on monitoring of cannabis illicit abuse.

The adsorption of 11-nor-9-carboxy-∆9-tetrahydrocannabinol (THC-COOH) by the suspended particles in sewage makes it fail to accurately monitor cannabis abuse. In this work, the model sewage sample was prepared through equivalent mixing the sewage from 10 different sewage treatment plants in Guangdong province of China and used as a comprehensive representative for investigating the adsorption and release behavior of THC-COOH on the suspended particles under different temperature and pH. The solid-liquid distribution of THC-COOH in sewage depended strongly on the adsorption and release properties which were susceptible to the temperature and pH, specially adjusting pH to 11.0 could release more than 90 % of THC-COOH from the suspended particles. By means of the kinetics models, pseudo-second-order kinetic and Weber-Morris models revealed the mechanism of adsorption and release of THC-COOH in sewage that was a relatively reversible and controllable process with multiple interactions, and then it was further confirmed by the validation experiment in a variety of actual sewage samples. According to the suggested pH, the modification of the existing detection protocol prior to high performance liquid chromatography-tandem triple quadrupole mass spectrometry (HPLC-TQ-MS/MS), was successfully applied to determination of THC-COOH in the stimulated positive samples, and the recoveries and RSDs were respectively 95.48-99.79 % and 4.0-5.6 %. The finding could greatly help improving the accuracy of not only the detection of THC-COOH in sewage but also the estimation data of the consumption level of cannabis in the related regions.

Unlocking the Reverse Targeting Mechanisms of Cannabidiol: Unveiling New Therapeutic Avenues.

Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), the main components of Cannabis sativa plants, have attracted a significant amount of attention due to their biological activities. This study identified GPR18 as the target of partial agonist CBD activating the p42/p44 MAPK pathway leading to migration of endometrial epithelial cells. Induced fit docking (IFD) showed that the affinity of THC for GPR18 is higher than that of CBD, and molecular dynamics (MD) simulations showed that CBD-GPR18 complexes at 130/200 ns might have stable conformations, potentially activating GPR18 by changing the distances of key residues in its active pocket. In contrast, THC maintains "metastable" conformations, generating a "shrinking space" leading to full agonism of THC by adding mechanical constraints in GPR18's active pocket. Steered molecular dynamics (SMD) revealed GPR18's active pocket was influenced more by CBD's partial agonism compared with THC. This combined IFD-MD-SMD method may be used to explain the mechanism of activation of partial or full agonists of GPR18.

Unveiling the potential of the capillary-driven microfluidic paper-based device integrated with smartphone-based for simultaneously colorimetric salivary ethanol and △9-tetrahydrocannabinol analysis.

Monitoring various biomarkers in saliva samples emerges as a dynamic and non-invasive method. However, the high viscosity of saliva presents a distinct challenge when integrating paper-based platforms for on-site analysis. In addressing this challenge, we introduced the capillary-driven microfluidic paper-based analytical devices (µCD-PAD) designed for user-friendly and simultaneous detection of ethanol and tetrahydrocannabinol (THC) in saliva without a sample preparation step. Employing a colorimetric approach, we quantified both analytes. Synthetic salivas of varying viscosity flowed seamlessly to the detection zone without needing a sample preparation step, and no impact on colorimetric detection due to viscosity was observed (RSD <5 %). Within 10 min after the solution reached the detection zone, the device produced a homogeneous color signal, easily analyzed by a smartphone camera. To extend the application for determination to cover a legal limit concentration of ethanol and concentration of salivary THC even 24 h after marijuana consumption, the detection time of 30 min was optimized. Moreover, a saliva sample containing both analytes was used to demonstrate the capability of the developed device to detect ethanol and THC simultaneously. No cross-talk between ethanol and THC occurred and showed recovery in the 98-102 % for ethanol and 95-105 % for THC with acceptable accuracy. This developed device exhibits excellent potential for forensic applications, providing a user-friendly, cost-effective, and real-time screening tool for detecting ethanol and THC in saliva.

An initial exploration of machine learning for establishing associations between genetic markers and THC levels in Cannabis sativa samples.

Cannabis sativa, a globally commercialized plant used for medicinal, food, fiber production, and recreation, necessitates effective identification to distinguish legal and illegal varieties in forensic contexts. This research utilizes multivariate statistical models and Machine Learning approaches to establish correlations between specific genotypes and tetrahydrocannabinol (Δ9-THC) content (%) in C. sativa samples. 132 cannabis leaves samples were obtained from legal growers in Piedmont, Italy, and illegal drug seizures in Turin. Samples were genetically profiled using a 13-loci STR multiplex and their Δ9-THC content was detected through quantitative GC-MS analysis. This study aims to assess the use of supervised classification modelling on genetic data to distinguish cannabis samples into legal and illegal categories, revealing distinct clusters characterized by unique allele profiles and THC content. t-distributed Stochastic Neighbor Embedding (t-SNE), Random Forest (RF) and Partial Least Squares Regression (PLS-R) were executed for the machine learning modelling. All the tested models resulted effective discriminating between legal samples and illegal. Although further validation is necessary, this study presents a novel forensic investigative approach, potentially aiding law enforcement in significant marijuana seizures or tracking illicit drug trafficking routes.

Effects of ∆-9 tetrahydrocannabinol on the small intestine altered by high fructose diet: A Histopathological study.

The consumption of fructose is increasing day by day. Understanding the impact of increasing fructose consumption on the small intestine is crucial since the small intestine processes fructose into glucose. ∆9-Tetrahydrocannabinol (THC), a key cannabinoid, interacts with CB1 and CB2 receptors in the gastrointestinal tract, potentially mitigating inflammation. Therefore, this study aimed to investigate the effects of the high-fructose diet (HFD) on the jejunum of rats and the role of THC consumption in reversing these effects. Experiments were conducted on Sprague-Dawley rats, with the experimental groups as follows: control (C), HFD, THC, and HFD + THC. The HFD group received a 10% fructose solution in drinking water for 12 weeks. THC groups were administered 1.5 mg/kg/day of THC intraperitoneally for the last four weeks. Following sacrification, the jejunum was evaluated for mucus secretion capacity. IL-6, JNK, CB2 and PCNA expressions were assessed through immunohistochemical analysis and the ultrastructural alterations via transmission electron microscopy. The results showed that fructose consumption did not cause weight gain but triggered inflammation in the jejunum, disrupted the cell proliferation balance, and increased mucus secretion in rats. Conversely, THC treatment displayed suppressed inflammation and improved cell proliferation balance caused by HFD. Ultrastructural examinations showed that the zonula occludens structures deteriorated in the HFD group, along with desmosome shrinkage. Mitochondria were found to be increased due to THC application following HFD. In conclusion, the findings of this research reveal the therapeutic potential of THC in reversing HFD-related alterations and provide valuable insights for clinical application.

Development of an accelerated ageing protocol for the study of phytocannabinoid stability in Cannabis sativa L.

Cannabis sativa L. is a plant belonging to the Cannabaceae family known primarily for its recreational use due to the psychoactive properties of Δ9-tetrahydrocannabinol (THC). Despite this, several compounds belonging to the category of phytocannabinoids have shown in recent years a number of potentially promising therapeutic effects that have increased the interest in the pharmaceutical field towards this plant. However, the content of these compounds is very variable and influenced by different factors, such as growing conditions and time of the year. An indication of the status and age of Cannabis samples is provided by the content of CBN, a minor phytocannabinoid and degradation product of other phytocannabinoids, including THC. In this research work an innovative, solid state analytical approach has been developed to observe and evaluate the variations in the content of two phytocannabinoids (CBN and CBD) in Cannabis-derived products over time. In order to simulate the ageing of the Cannabis samples, an artificially accelerated ageing procedure has been developed and optimised by using high temperatures. The analyses were carried out using an innovative ATR-FTIR method for solid state analysis, enabling direct analysis of a solid sample without any pretreatment phase. This study has allowed the development of an innovative analytical approach for the evaluation of the age and state of conservation of Cannabis samples and may be a useful tool both in the industrial, pharmaceutical and forensic fields.

[Cannabis use and cannabis use disorders]. / Cannabiskonsum und Cannabiskonsumstörungen.

Cannabis use and cannabis use disorders have taken on a new social significance as a result of partial legalization. In 2021 a total of 4.5 million adults (8.8%) in Germany used the drug. The number of users as well as problematic use have risen in the last decade. Cannabis products with a high delta-9-tetrahydrocannabinol (THC) content and their regular use lead to changes in cannabinoid receptor distribution in the brain and to modifications in the structure and functionality of relevant neuronal networks. The consequences of cannabinoid use are particularly in the psychological functioning and can include intoxication, harmful use, dependence with withdrawal symptoms and cannabis-induced mental disorders. Changes in the diagnostics between ICD-10 and ICD-11 are presented. Interdisciplinary S3 guidelines on cannabis-related disorders are currently being developed and will be finalized shortly.

Dose-dependent effects of oral cannabidiol and delta-9-tetrahydrocannabinol on serum anandamide and related N-acylethanolamines in healthy volunteers.

BACKGROUND: The mental health benefits of cannabidiol (CBD) are promising but can be inconsistent, in part due to challenges in defining an individual's effective dosage. In schizophrenia, alterations in anandamide (AEA) concentrations, an endocannabinoid (eCB) agonist of the eCB system, reflect positively on treatment with CBD. Here, we expanded this assessment to include eCBs alongside AEA congeners, comparing phytocannabinoids and dosage in a clinical setting. METHODS: Liquid chromatography-tandem mass spectrometry quantified changes in serum levels of AEA, 2-arachidonoylglycerol (2-AG), alongside AEA-related compounds oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), which were attained from two independent, parallel-designed, clinical trials investigating single, oral CBD (600 or 800 mg), delta-9-tetrahydrocannabinol (Δ9-THC, 10 or 20 mg) and combination administration (CBD|800 mg+Δ9-THC|20 mg) in healthy volunteers (HVs, n=75). Concentrations were measured at baseline (t=0), 65 and 160 min post administration. RESULTS: CBD-led increases in AEA (1.6-fold), OEA and PEA (1.4-fold) were observed following a single 800 mg (pcorr<0.05) but not 600 mg dosage. Declining AEA was observed with Δ9-THC at 10 mg (-1.3-fold) and 20 mg (-1.4-fold) but restored to baseline levels by 160 min. CBD+Δ9-THC yielded the highest increases in AEA (2.1-fold), OEA (1.9-fold) and PEA (1.8-fold) without reaching a maximal response. CONCLUSION: CBD-administered effects towards AEA, OEA and PEA are consistent with phase II trials reporting clinical improvement for acute schizophrenia (CBD≥800 mg). Including Δ9-THC appears to enhance the CBD-induced response towards AEA and its congeners. Our results warrant further investigations into the potential of these lipid-derived mediators as metabolic measures for CBD dose prescription and co-cannabinoid administration.

A Case of Acute Intoxication from Sublingually Administering a Liquid Inhalation Product Containing a Marijuana Analogue.

A 20-year-old man was brought to the emergency room with chief complaints of dysarthria and vomiting after placing several drops of an inhalation liquid containing hexahydrocannabiphorol (HHCP) under his tongue. During ambulance transport, the patient had a post-vomiting convulsion that lasted approximately 1 minute. Upon arrival at the hospital, he was agitated, had dysarthria to the extent that he was in danger of falling from the stretcher, and was having visual hallucinations. Blood tests showed acidosis and a high lactic acid concentration. The patient was urgently admitted to the hospital with a diagnosis of acute poisoning and was started on supplemental intravenous fluids. The patient was able to communicate from the second day, started eating on the third day, finished receiving supplemental fluids on the fourth day, and was discharged from the hospital on the fifth day. HHCP was not illegal in Japan at the time and was distributed mainly through mail order. Clinical information on HHCP is lacking, but this case shows that the drug causes health problems. Although HHCP has been regulated by law in Japan since January 2024, clinicians and the general public should be aware that similar cases may occur in the future.

A preliminary investigation of the acute effects of delta-9-tetrahydrocannabinol on pain and opioid attentional bias among persons with opioid use disorder.

INTRODUCTION: Attentional bias (AB) is believed to be an important factor in the development and maintenance of both opioid use disorder (OUD) and chronic pain. Cannabis and its main psychoactive constituent, delta-9-tetrahydrocannabinol (THC), produce analgesic effects via processes that are potentially relevant to AB and is commonly used by persons with OUD. This exploratory study investigated if THC influences AB towards pain and opioid cues individuals with OUD. METHODS: Using a within-subject, crossover design, 27 adults receiving methadone were randomly assigned to receive single doses of oral THC (10 mg, 20 mg administered as dronabinol) or placebo across three, 5-h sessions. During each session, a visual probe task was used to measure AB to pain and opioid cues at baseline and 120 min post-THC administration. RESULTS: Mixed-effects models examined main effects of THC dose, time, and their interaction across all participants; findings were then stratified by methadone dose (low dose <90 mg/day and high dose ≥90 mg/day). Among individuals receiving high doses of methadone, a significant interaction was observed such that AB towards opioids increased following 10 mg THC administration and decreased following 20 mg THC administration. Additionally, participants receiving low doses of methadone showed significant increases in the variability of opioid-related AB post THC administration. CONCLUSION: We provide preliminary evidence showing that THC may cause dose-dependent effects on selective attention for opioid cues among methadone patients. These results underscore the need for further clinical investigation into the effects of cannabinoids and other substances with potential analgesic and addictive properties among persons with OUD.

Effects of in utero exposure to Δ-9-tetrahydrocannabinol on cardiac extracellular matrix expression and vascular transcriptome in rhesus macaques.

Delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabis, remains a schedule I substance, thus safety data regarding the effects on the cardiovascular and prenatal health are limited. Importantly, there is evidence showing prenatal cannabis exposure can negatively impact fetal organ development, including the cardiovascular system. THC can cross the placenta and bind to cannabinoid receptors expressed in the developing fetus, including on endothelial cells. To understand the impact of prenatal THC exposure on the fetal cardiovascular system, we used our rhesus macaque model of prenatal daily edible THC consumption. Before conception, animals were acclimated to THC (2.5 mg/7 kg/day, equivalent to a heavy medical cannabis dose) and maintained on this dose daily throughout pregnancy. Fetal tissue samples were collected at gestational day 155 (full term is 168 days). Our model showed that in utero THC exposure was associated with a decreased heart weight-to-body weight ratio in offspring, warranting further mechanistic investigation. Histological examination of the fetal cardiac and vascular tissues did not reveal any significant effect of THC exposure on the maturity of collagen within the fetal heart or the aorta. Total collagen III expression and elastin production and organization were unchanged. However, bulk RNA-sequencing of vascular cells in the umbilical vein, umbilical artery, and fetal aorta demonstrated that THC alters the fetal vascular transcriptome and is associated with upregulated expression of genes involved in carbohydrate metabolism and inflammation. The long-term consequences of these findings are unknown but suggest that prenatal THC exposure may affect cardiovascular development in offspring.NEW & NOTEWORTHY Prenatal cannabis use is increasing and despite the public health relevance, there is limited safety data regarding its impact on offspring cardiovascular health outcomes. We used a translational, nonhuman primate model of daily edible Δ-9-tetrahydrocannabinol (THC) consumption during pregnancy to assess its effects on the fetal cardiovascular system. THC-exposed fetal vascular tissues displayed upregulation of genes involved in cellular metabolism and inflammation, suggesting that prenatal THC exposure may impact fetal vascular tissues.