THC Concentrations Research Articles

Chemical analysis and concentrations of cannabidiol substances used for refractory epilepsy in Chilean patients. An underestimated worldwide risk.

The purpose of this study is to analyze composition of HMS (homemade CBD), NLS (non-licensed commercial products), and bioequivalent CBD (BES) collected from Chilean patients that voluntary accepted to analyze the "CBD-substance." Samples were collected through an open invitation for different patients to anonymously and free of charge participate in the analysis of CBD oil. The analysis of the active principle was performed using High-Resolution Liquid Chromatography (HPLC). A total of 35 samples were collected between March 2020 and September 2021, including two BES, six NLS, and 27 HMS products. The BES had an average CBD concentration of 89.15 mg/mL and an average THC concentration of 0.015 mg/mL, which complied with the maximum THC levels required by regulatory authorities (<0.2% THC.). The NLS (six samples) exhibited significant variability in CBD concentrations, ranging from a maximum of 78.5 mg/mL to a minimum of 0.1 mg/mL, with an average of 25.41 mg/mL. The THC concentrations ranged from 0 mg/mL to 2.43 mg/mL with an average of 0.62 mg/mL. The HMS products exhibited even higher variations of CBD concentrations, ranging from 0 to a maximum of 6.6 mg/mL. THC concentrations were even more variable, ranging from 0 mg/mL to 388 mg/mL. The medical community and patients involved should be aware that Hemp products are not pure and/or innocuous. HMS are likely to have high levels of THC and very low CBD, far away from therapeutic doses of CBD. CBD used in epilepsy should be restricted to licensed products, especially in children where THC toxicity is much more harmful. The study analyzed three types of CBD (cannabidiol) oils: homemade, non-licensed, and bioequivalent. Homemade and non-licensed products showed nonacceptable variance of CBD and THC concentration (tetrahydrocannabinol), in some cases with 0 mgs of CBD and many beyond THC maximum accepted. The THC is another component found in cannabis and is responsible for the neurotoxic effects. Only bioequivalent products showed concentrations of CBD and THC acceptable for epilepsy treatment, therefore are the only products recommended for such purpose.

The annual trend of suicide rates from 2010 to 2021 in patients with cannabis use disorder – a national registry study

Abstract Purpose The temporal trend of suicide in patients with cannabis use disorder (CUD) is important to investigate, considering the recent increases in THC concentration in cannabis products. This study describes the annual suicide rates in patients with CUD from 2010 to 2021. To investigate if any change in suicide rate was specific to CUD, we compared these suicide rates with corresponding data for patients with alcohol use disorders (AUD) and other substance use disorders (SUDs). Method The study used a time series design. We used a national registry linkage between the Norwegian Cause of Death Registry and the Norwegian Patient Registry from 2010 to 2021, including patients with CUD (ICD-10 code F12), AUD (F10), or other SUDs (F11; F13-F16; F18-F19) who died by suicide, supplemented with the total number of patients treated with specific disorders to estimate the suicide rates. The trend was analyzed by comparing the annual suicide rate to 2010 and using Poisson regression, adjusting for gender, age, and mental disorders. Results We found increased annual incidence rate ratios for patients with CUD in 2018 (IRR = 2.14 (95% CI 1.14–3.99)) and onwards and an increasing time trend over the study period (IRR = 1.08 (1.05–1.12)). No increases in trends were found for AUD or other SUDs. The time trend for CUD was attenuated when adjusting for depressive or anxiety disorders (aIRR = 1.00 (0.92–1.08)) or other SUDs (aIRR = 0.96 (0.87–1.06)). Conclusions Increasing suicide rates were found in patients with CUD. Comorbid anxiety and depression or other SUDs, but not other mental disorders, could partly explain these results.

Concentrations of Delta 9-tetrahydrocannabinol (THC) in oral fluid at different time points after use: An individual participant meta-analysis

BackgroundDelta 9-tetrahydrocannabinol (THC) concentrations in oral fluid (OF) at different time points after cannabis administration and factors related to these concentrations have not been previously described in a meta-analysis. This information is critical for better understanding of these tests for detection of prior cannabis use and cannabis impairment. Objectives1: To describe the summary statistics of THC concentrations at different time points after cannabis administration. 2: To describe the relationship between the variables of dose of THC, frequency of using cannabis, route of administration (i.e., inhaled or ingested), OF collection device and sex, with THC concentrations in OF, based on bivariate analyses. 3: To describe the independent contribution of each of the variables in Objective 2, based on a multivariate analysis of THC concentrations. MethodsA meta-analysis of studies from two databases (PubMed and Scopus) was conducted. Our inclusion criteria included published empirical articles that administered natural cannabis to subjects in a controlled setting, with OF drug tests showing the exact THC concentrations in OF for each subject (i.e., raw data) for at least two time points after cannabis administration using confirmatory methods. Seven studies of tests with published raw data for OF THC after cannabis administration met these criteria (n observations=1157). ResultsSummary statistics showed OF THC concentrations by time after use were highly dispersed at every time point, positively skewed, and declined over time. Many positive OF THC concentrations were found after 24-hours in one study, but most studies did not conduct observations past 24 hours. In a multivariate analysis, we found that increased dose, increased frequency of cannabis use, and inhaled (versus ingested) cannabis were statistically related to higher OF THC concentrations. OF collection with the intercept DOA device was significantly higher than expectorant (i.e. saliva) and being male (versus female) were only significant in a bivariate analysis. Too little data existed to reliably analyze the possible influence of other variables of age, race and body mass index (BMI) on OF THC concentrations. DiscussionFalse negatives exist when the tests are used to detect prior use. OF test results are related to confounders of frequency of cannabis use and inhaled (versus ingested) cannabis. OF tests can produce positives at a cut-off 1.0 ng/mL well beyond 24 hours. The tests are not valid to detect cannabis impairment. More information is needed on the influence of potential confounders for OF concentrations. We do not have a good idea of the degree to which the subjects in these studies are representative of persons who use cannabis. Overall, more research is needed for these tests to be used in workplace settings.

Can the THC concentration predict the number of patients with cannabis-related diagnoses?

The use of high-potency cannabis products is associated with an increased risk of mental disorders. This study investigates whether the rising THC concentration in Germany is associated with an increase in cannabis-related diagnoses. The number of insured persons with at least one cannabis-related ICD-10 F12 diagnosis (e.g., harmful use, dependence) in outpatient care was provided by statutory health insurance funds between 2009 and 2021. The dependent variable is the ratio of (a) the number of insured persons with at least one F12 diagnosis to (b) all insured persons who have used cannabis in the last year. Information on THC concentration in cannabis flower was provided by law enforcement agencies. Using generalised mixed linear models, the dependent variable was predicted by the median THC concentration in cannabis flower. The regression results show that an increase in THC concentration by one percentage point is significantly associated with an increase in the proportion of diagnoses (women: +0.17; men: +0.42). THC concentration positively predicted the proportion of diagnoses in all 16 federal states for men and in 15 federal states for women. Compared to low-potency products, using high-potency products may pose additional health risks, which may be particularly pronounced in men. Acknowledging the limitations of the ecological study design and uncertainties inherent to the analysed data, further investigations on the sex-specific impact of THC exposure are required. Limiting the THC concentration in cannabis products and closely monitoring THC consumption in the population appears necessary.

Cannabinoids detected in exhaled breath condensate after cannabis use

Cannabinoids can be detected in breath after cannabis use, but different breath matrices need to be explored as studies to date with filter-based devices that collect breath aerosols have not demonstrated that breath-based measurements can reliably identify recent cannabis use. Exhaled breath condensate (EBC) is an unexplored aqueous breath matrix that contains condensed volatile compounds and water vapor in addition to aerosols. EBC was collected from participants both before and at two time points (0.7 ± 0.2 h and 1.7 ± 0.3 h) after observed cannabis use. Eleven different cannabinoids were monitored with liquid chromatography tandem mass spectrometry. Five different cannabinoids, including Δ9-tetrahydrocannabinol (THC), were detected in EBC collected from cannabis users. THC was detected in some EBC samples before cannabis use, despite the requested abstinence period. THC was detected in all EBC samples collected at 0.7 h post use and decreased for all participants at 1.7 h. Non-THC cannabinoids were only detected after cannabis use. THC concentrations in EBC samples collected at 0.7 h showed no trend with sample metrics like mass or number of breaths. EBC sampling devices deserve further investigation with respect to modes of cannabis use (e.g, edibles), post use time points, and optimization of cannabinoid recovery.

T19 - Relationship Between Blood THC and Metabolite Concentrations and Rapidly Collected and Analyzed Breath Samples in Heathy Volunteers After Smoking Marihuana

T19 - Relationship Between Blood THC and Metabolite Concentrations and Rapidly Collected and Analyzed Breath Samples in Heathy Volunteers After Smoking Marihuana

Dose of Product or Product Concentration: A Comparison of Change in Heart Rate by THC Concentration for Participants Using Cannabis Daily and Occasionally.

Introduction: Studies show that acute cannabis use significantly increases heart rate (HR) and mildly raises blood pressure in the minutes following smoked or inhaled use of cannabis. However, less is known about how the THC concentration of the product or an individual's frequency of use (i.e., tolerance) may affect the magnitude of the change in HR. It is also relatively unexamined how the physical effects of increased HR after acute cannabis use relate to self-reported drug effects or blood THC levels. Aims: To describe the relationship between THC concentration of product used, self-reported subjective intoxication, THC blood levels, and frequency of cannabis use with the change in HR after acute cannabis use. Materials and Methods: Participants (n = 140) were given 15 min to smoke self-supplied cannabis ad libitum, HR was measured at baseline and an average of 2 min post-cannabis smoking. The ARCI-Marijuana scale and Visual Analog Scales (VAS) were administered, and blood samples were taken at both time points. Participants were asked about their frequency of use. Information about the product used was recorded from the package. Linear regression was used to analyze the relationship between changes in HR (post-pre cannabis use) and post-cannabis use HR, blood THC concentration, THC product concentration, frequency of use, and self-reported drug effect. Results: There was a significantly higher HR among those who smoked cannabis compared to the controls (p < 0.001), which did not significantly differ by frequency of use (p = 0.18). Higher concentration THC (extract) products did not produce a significantly different HR than lower concentration (flower) products (p = 0.096). VAS score was associated with an increase in HR (p < 0.05). Overall, blood THC levels were not significantly related to the change in HR (p = 0.69); however, when probed, there was a slight positive association among the occasional use group only. Discussion: Cardiovascular effects of cannabis consumption may not be as subject to tolerance with daily cannabis use and do not directly increase with THC concentration of the product. This is a departure from other effects (i.e., cognitive, subjective drug effects) where tolerance is well established. These findings also suggest that, at least among those with daily use, higher concentration THC products (>60%) do not necessarily produce cardiovascular physiological effects that are significantly more robust than lower concentration (<20%) products.

Simple method for detecting tetrahydrocannabinolic acid and tetrahydrocannabinol in cannabis tissues using urine-based drug diagnostic device

Tetrahydrocannabinolic acid (THCA, or THC in the decarboxylated form), synthesized by cannabis plant (Cannabis sativa L.), is a cannabinoid that can be used as a therapeutic drug but is a dangerous psychoactive compound. Cannabis grown for industrial fiber hemp must contain little THCA to prevent misuse. Many attempts to develop new cultivars with low THCA contents have therefore been made. It is time-consuming and expensive to determine THCA in cannabis plant tissues by high-performance liquid chromatography, so we attempted to develop a simple and quick method for selected cultivars with low THCA contents. The diagnostic device, which is an immunoassay based on the principle of competitive binding of drug metabolites, was initially developed for human drug testing in urine. We aim to determine whether the diagnostic device can be applied to natural cannabinoids from cannabis plant. The devices were not suitable for aqueous extracts with methanol contents >20 %. The test (T) line on each device was less intense for leaf and flower extracts than the negative control (water). The THCA contents of water extracted leaves determined by HPLC and calculated based on the cannabidiolic acid contents were 7.5 and 15 μg mL−1 for SuperwomanS1 and Spectrum303 cultivars, respectively. When THCA and THC standards were loaded onto Abon devices, the T line disappeared at the THCA concentration 20 μg mL−1 and the THC concentration 1 μg mL−1, respectively. Using extracts of 0.2 g fresh leaves, SuperwomanS1 and Spectrum303 will give faint and strong T lines, respectively, indicating that the devices could be used to test cannabis tissue THCA contents against the international regulatory limit (≤ 0.3 % w/w). The results indicated that the THCA contents of cannabis tissues at the flowering stage can readily be estimated using drug diagnostic devices, making it convenient for cannabis growers and breeders to semi-quantify THCA.

Acute Cannabis Administration Transiently Reduces Mitochondrial DNA in Young Adults: Findings from a Secondary Analysis of a Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

Background: Cannabis is one of the world's most commonly used substances; however, many questions remain unanswered as to how cannabis impacts the body. Recently, there has been a resurgence of research into the effects of plant-derived cannabinoids on mitochondrial health. In particular, a number of studies implicate mitochondrial-Δ9-tetrahydrocannabinol (Δ9-THC) interactions with altered memory, metabolism, and catalepsy in mice. Although the research in this field is expanding rapidly, there is little known about the effects of cannabis on mitochondria health in human subjects either in acute or chronic term use. Methods: Blood samples were obtained from a double-blind, placebo-controlled, parallel-group randomized clinical trial in which adults who regularly use cannabis (1-4 days/week) aged 19-25 years were randomized 2:1 to receive either an active (12.5% Δ9-THC) cigarette or placebo (<0.01% Δ9-THC) cigarette containing 750 mg of cannabis before driving simulator testing. DNA was extracted from whole blood using commercial spin columns, followed by measurement of mt-ND1, mt-ND4, and β2M using quantitative polymerase chain reaction. One-way repeated measures analysis of variance (ANOVA) followed by Dunnett's multiple comparisons test was used to observe changes in mitochondrial DNA (mtDNA) copy number over time. A two-tailed Pearsons R test was used to assess correlations between mtDNA copy number and cannabinoid levels (Δ9-THC and metabolites) in blood. Results: We found that exposure to active cannabis containing Δ9-THC, as opposed to placebo, was associated with an acute reduction in mitochondrial DNA copy number in whole blood at 15 min and 1 h after smoking. The observed decrease in mtDNA copy number negatively correlated with blood concentrations of 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH), the two primary metabolites of Δ9-THC, but not Δ9-THC itself. Further, the negative correlation between 11-OH THC and THC-COOH concentrations and mtDNA copy number was found in only a subgroup of participants who use cannabis infrequently, suggesting a tolerance effect. Conclusions: These results illuminate mitochondrial alterations attributed to Δ9-THC consumption, which may be mediated by metabolites. These results appear to suggest stronger effects in individuals who consume cannabis less frequently, suggesting some form of tolerance to the effects of Δ9-THC and its metabolites on mtDNA content in whole blood. Keywords: Mitochondria; mtDNA; cannabis; THC; THC metabolites; blood; THC-COOH; 11-OH-THC.

Applying machine learning to international drug monitoring: classifying cannabis resin collected in Europe using cannabinoid concentrations.

In Europe, concentrations of ∆9-tetrahydrocannabinol (THC) in cannabis resin (also known as hash) have risen markedly in the past decade, potentially increasing risks of mental health disorders. Current approaches to international drug monitoring cannot distinguish between different types of cannabis resin which may have contrasting health effects due to THC and cannabidiol (CBD) content. Here, we compared concentrations of THC and CBD in different types of cannabis resin collected in Europe (either Moroccan-type, or Dutch-type). We then tested the ability of machine learning algorithms to classify the type of cannabis resin (either Moroccan-type, or Dutch-type) using routinely collected monitoring data on THC and CBD. Finally, we applied the optimal algorithm to new samples collected in countries where the type of cannabis resin was unknown, the UK and Denmark. Results showed that overall, Dutch-type samples had higher THC (Hedges' g = 2.39) and lower CBD (Hedges' g = 0.81) than Moroccan-type samples. A Support Vector Machine algorithm achieved classification accuracy exceeding 95%, with little variation in this estimate, good interpretability, and plausibility. It made contrasting predictions about the type of cannabis resin collected in the UK (94% Moroccan-type; 6% Dutch-type) and Denmark (36% Moroccan-type; 64% Dutch-type). In conclusion, we provide proof-of-concept evidence for the potential of machine learning to inform international drug monitoring. Our findings should not be interpreted as objective confirmatory evidence but suggest that Dutch-type cannabis resin has higher THC concentrations than Moroccan-type cannabis resin, which may contribute to variation in drug markets and health outcomes for people who use cannabis in Europe.

Roadside inspections, traffic events and traffic accidents from 2010–2022 in the experience of the Institute of Forensic Research as a consulting body in light of the proposed thresholds for the states of ‘after use’ and ‘under the influence’ for THC = Kontrole, zdarzenia i wypadki drogowe z lat 2010–2022 w praktyce opiniodawczej Instytutu Ekspertyz Sądowych w świetle propozycji progów „po

Road traffic safety depends largely on the psychophysical fitness of drivers. Apart from ethyl alcohol, this efficiency is influenced by many other factors, including: presence in the blood of the so-called substances that act similarly to alcohol, and cannabinols constitute one of the most popular groups of these substances. The paper presents statistics on delta-9-tetrahydrocannabinol (THC) – the main psychoactive ingredient of cannabis detected in the blood of drivers subjected to 7269 road inspections and involved in 4697 road events and accidents in the years 2010–2022 throughout Poland. Based on the results obtained, it was found that THC is present in the blood of 25–61% of roadside inspection cases, and in the case of road incidents and accidents, 5–15% of drivers have THC in a concentration equal to or higher than 1 ng/ml. The data in the charts are given in relation to two THC concentration ranges: 1.0–2.5 ng/ml and above 2.5 ng/ml (the value proposed as the limit of the state “after use” and “under the influence” of THC) and in relation to concentration ranges based on the THC elimination curve in human serum. The study did not distinguish between chronic or acute participants and occasional participants. It was based on THC and THCCOOH concentrations. The analyzes were performed using the enzyme-linked immunosorbent method (ELISA) and confirmatory methods such as liquid and gas chromatography coupled with mass spectrometry, in which the limit of quantification of 1 ng/ml was in accordance with the applicable requirement contained in the Regulation of the Minister of Health of July 16, 2014 on the list of similarly acting agents to alcohol and the conditions and method of conducting tests for their presence in the body.

Cannabinoid levels description in a cohort of patients with chronic and neuropathic pain treated with Cannabis decoction: A possible role of TDM

The phytocomplex of Cannabis is made up of approximately 500 substances: terpeno-phenols metabolites, including Δ-9-tetrahydrocannabinol and cannabidiol, exhibit pharmacological activity.Medical Cannabis has several pharmacological potential applications, in particular in the management of chronic and neuropathic pain. In the literature, a few data are available concerning cannabis pharmacokinetics, efficacy and safety.Thus, aim of the present study was the evaluation of cannabinoid pharmacokinetics in a cohort of patients, with chronic and neuropathic pain, treated with inhaled medical cannabis and decoction, as a galenic preparation.In this study, 67 patients were enrolled. Dried flower tops with different THC and CBD concentrations were used: Bedrocan® medical cannabis with THC level standardized at 19% and with a CBD level below 1%, Bediol® medical cannabis with THC and CBD level standardized at similar concentration of 6.5% and 8%, respectively.Cannabis was administered as a decoction in 47 patients and inhaled in 11 patients. The blood withdrawn was obtained before the new dose administration at the steady state and metabolites plasma concentrations were measured with an UHPLC-MS/MS method.Statistically significant differences were found in cannabinoids plasma exposure between inhaled and oral administration of medical cannabis, between male and female and cigarette smokers.For the first time, differences in cannabinoid metabolites exposures between different galenic formulations were suggested in patients. Therapeutic drug monitoring could be useful to allow for dose adjustment, but further studies in larger cohorts of patients are required in order to confirm these data.

Exploring the potentialities of industrial hemp for sustainable rural development

This literature review paper explores the potential sustainable applications of industrial hemp, contextualizing it within the UN Agenda 2030 Sustainable Development Goals (SDGs). Hemp is a dioecious, herbaceous, anemophilous (wind-pollinated) annual crop that grows from one to five meters in height. However, monoecious varieties have been developed through breeding and selection. Historically versatile, Cannabis sativa L. has faced stigmatization and unfounded prohibitions, having played crucial roles in different civilizations, including during World War I. A member of the Cannabaceae family, it is a versatile non-psychoactive crop, with low concentrations of THC. Recently, the global market for hemp has grown. It is an eco-friendly option in the food, textile, pharmaceutical, and energy sectors. This study is based on bibliographic research covering primary and secondary sources, including technical reports, academic journals, and scientific repositories. The origin, characteristics and cultivation methods of industrial hemp are discussed, besides its practical applications, including the production of fibers, health food grains, medicinal phytocannabinoids, biofuels, sustainable biomass energy, and carbon offsetting. Its potential to contribute to sustainable agriculture and achieve SDG targets stands out, considering environmental benefits, product diversification, resistance, and integration into agroforestry systems. Regenerative agriculture is explored as a promising approach, aligned with the principles of sustainable agriculture and the SDGs, aiming to restore agricultural ecosystems, promote soil health, and improve climate resilience. The research highlights the importance of reforming cannabis-related policies to achieve goals relating to health, justice, and global partnerships, emphasizing the need for sustainable approaches to exploiting this natural resource.

Effects of recent cannabis consumption on eye-tracking and pupillometry.

Cannabis consumption is known to immediately affect ocular and oculomotor function, however, cannabis consumption is also known to affect it for a prolonged period of time. The purpose of this study is to identify an eye tracking or pupillometry metric which is affected after recent cannabis consumption but is not confounded by cannabis consumption history or demographic variables. Quasi-experimental design. Participants who would consume inhalable cannabis (n = 159, mean age 31.0 years, 54% male) performed baseline neurobehavioral testing and eye-function assessments when they were sober. Eye function assessments included eye-tracking [gaze (point of visual focus), saccades (smooth movement)] and pupillometry. Participants then inhaled cannabis until they self-reported to be high and performed the same assessment again. Controls who were cannabis naïve or infrequent users (n = 30, mean age 32.6 years, 57% male) performed the same assessments without consuming cannabis in between. Cannabis significantly affected several metrics of pupil dynamics and gaze. Pupil size variability was the most discriminant variable after cannabis consumption. This variable did not change in controls on repeat assessment (i.e., no learning effect), did not correlate with age, gender, race/ethnicity, or self-reported level of euphoria, but did correlate with THC concentration of cannabis inhaled. A novel eye-tracking metric was identified that is affected by recent cannabis consumption and is not different from non-users at baseline. A future study that assesses pupil size variability at multiple intervals over several hours and quantifies cannabis metabolites in biofluids should be performed to identify when this variable normalizes after consumption and if it correlates with blood THC levels.

THC and sperm: Impact on fertilization capability, pre-implantation in vitro development and epigenetic modifications.

Global cannabis use has risen 23% since 2010, with 209 million reported users, most of whom are males of reproductive age. Delta-9-tetrahydrocannabinol (THC), the main psychoactive phytocannabinoid in cannabis, disrupts pro-homeostatic functions of the endocannabinoid system (ECS) within the male reproductive system. The ECS is highly involved in regulating morpho-functional and intrinsic sperm features that are required for fertilization and pre-implantation embryo development. Previous work by our group demonstrated that THC altered sperm capacitation and the transcriptome, including several fertility-associated microRNAs (miRs). Despite the prevalent use of cannabis among males of reproductive age, clinical and pre-clinical research investigating the impact of paternal cannabis on sperm function and the outcomes of artificial reproductive technologies (ARTs) remains inconclusive. Therefore, the present study investigates the impact of in vitro THC exposure on morpho-functional and intrinsic sperm functions, including contributions to embryo development following IVF. Bovine sperm were used as a translational model for human and treated with concentrations of THC that reflect plasma levels after therapeutic (0.032μM), and low (0.32μM)-high (4.8μM) recreational cannabis use. After 6-hours of treatment, THC did not alter the acrosomal reaction, but 4.8μM significantly reduced mitochondrial membrane potential (MMP) (p<0.05), primarily through agonistic interactions with CB-receptors. Fertilization of bovine oocytes with THC-treated sperm did not alter developmental rates, but blastocysts generated from sperm treated with 0.32-4.8μM THC had fewer trophoblasts (p<0.05), while blastocysts generated from sperm exposed to any concentration of THC had fewer cells in the inner cell mass (ICM), particularly within the 0.032μM group (p<0.001). Fertility associated miRs, including miR-346, miR-324, miR-33b, and miR-34c were analyzed in THC-exposed sperm and associated blastocysts generated by IVF, with lower levels of miRs-346, -324, and -33b found in sperm treated with 0.32μM THC, while miR-34c levels were higher in sperm treated with 0.032μM THC (p<0.05). Levels of miR-346 were also lower in sperm treated with 0.032μM THC, but higher in blastocysts generated from sperm exposed to 0.32μM THC (p<0.05). Our findings suggest that THC may alter key morpho-functional and epigenetic sperm factors involved in fertilization and embryo development. This is the first study to demonstrate that sperm exposed to THC in vitro negatively affects embryo quality following IVF.

Delays in blood collection and drug toxicology results among crash-involved drivers arrested for impaired driving

Objective The concentration of drugs in a driver’s system can change between an impaired driving arrest or crash and the collection of a biological specimen for drug testing. Accordingly, delays in specimen collection can result in the loss of critical information that has the potential to affect impaired driving prosecution. The objectives of the study were: (1) to identify factors that influence the time between impaired-driving violations and specimen collections (time-to-collection) among crash-involved drivers, and (2) to consider how such delays affect measured concentrations of drugs, particularly with respect to common drug per se limits. Method Study data included blood toxicology results and crash-related information from 8,923 drivers who were involved in crashes and arrested for impaired driving in Wisconsin between 2019 and 2021. Analyses examined how crash timing and severity influenced time-to-collection and the effects of delays in specimen collection on blood alcohol concentrations (BACs) and blood delta-9-tetrahydrocannabinol (THC) concentrations. Results The mean time-to-collection for the entire sample was 1.80 h. Crash severity had a significant effect on time-to-collection with crashes involving a fatality having the longest duration ( M = 2.35 h) followed by injury crashes ( M = 2.06 h) and noninjury crashes ( M = 1.69 h). Time of day also affected time-to-collection; late night and early morning hours were associated with shorter durations. Both BAC (r = −0.11) and blood THC concentrations (r = −0.16) were significantly negatively correlated with time-to-collection. Conclusions Crash severity and the time of day at which a crash occurs can result in delays in the collection of blood specimens after impaired driving arrests. Because drugs often continue to be metabolized and eliminated between arrest and biological specimen collection, measured concentrations may not represent the concentrations of drugs that were present at the time of driving. This has the potential to affect drug-impaired driving prosecution, particularly in jurisdictions whose laws specify per se impairment thresholds.

Vaporized D-limonene selectively mitigates the acute anxiogenic effects of Δ9-tetrahydrocannabinol in healthy adults who intermittently use cannabis

BackgroundCannabis contains hundreds of chemical constituents beyond delta-9-tetrahydrocannabinol (THC), which is believed to drive most of its acute pharmacodynamic effects. The entourage effect theory asserts that non-THC constituents can impact acute cannabis effects, but few empirical studies have systematically evaluated this theory in humans. This study assessed whether the cannabis terpenoid d-limonene mitigates the acute anxiogenic effects of THC. MethodsTwenty healthy adults completed nine, double-blind outpatient sessions in which they inhaled vaporized THC alone (15mg or 30mg), d-limonene alone (1mg or 5mg), the same doses of THC and d-limonene together, or placebo; a subset of participants (n=12) completed a tenth session in which 30mg THC+15mg d-limonene was administered. Outcomes included subjective drug effects, cognitive/psychomotor performance, vital signs, and plasma THC and d-limonene concentrations. ResultsWhen d-limonene was administered alone, pharmacodynamic outcomes did not differ from placebo. Administration of 15mg and 30mg THC alone produced subjective, cognitive, and physiological effects typical of acute cannabis exposure. Ratings of anxiety-like subjective effects qualitatively decreased as d-limonene dose increased and concurrent administration of 30mg THC+15mg d-limonene significantly reduced ratings of “anxious/nervous” and “paranoid” compared with 30mg THC alone. Other pharmacodynamic effects were unchanged by d-limonene. D-limonene plasma concentrations were dose orderly, and concurrent administration of d-limonene did not alter THC pharmacokinetics. ConclusionsD-limonene selectively attenuated THC-induced anxiogenic effects, suggesting this terpenoid could increase the therapeutic index of THC. Future research should determine whether this effect extends to oral dose formulations and evaluate the interactions between other cannabis terpenoids or cannabinoids and THC.

Pharmacokinetic of two oral doses of a 1:20 THC:CBD cannabis herbal extract in cats.

To determine the pharmacokinetics (PK) of two oral doses of a Cannabis herbal extract (CHE) containing 1:20 THC:CBD in 12 healthy Domestic Shorthair cats. Single-dose PK were assessed after oral administration of CHE at low or high dose (2 mg CBD + 0.1 mg THC, or 5 mg CBD + 0.25 mg THC per kg bw, respectively; n = 6 per group) in fasting cats. Blood samples were drawn up to 48 h following CHE administration. Plasma samples were analyzed for CBD, THC, and metabolites 6-OH-CBD, 7-OH-CBD, 11-OH-THC, and THC-COOH using a previously validated LC-MS/MS method. CBD and THC were quickly absorbed (mean Tmax of 2.4-2.9 h). Maximum plasma concentrations (Cmax) ranged from 36-511 ng/mL and 6.8-61 ng/mL for CBD and THC, respectively. Elimination was initially rapid for both CBD and THC, though a prolonged elimination phase was noted for CBD in some cats (T1/2 λ up to 26 h). Dose-adjusted Cmax and AUC0-last values were not statistically significantly different (p > 0.05) between dose groups indicating CBD and THC concentrations increased in a manner proportional (linear) to the dose. Dose-adjusted THC Cmax and AUC0-last were significantly higher than the corresponding dose-adjusted CBD parameters (p < 0.01). Low concentrations of the metabolite 6-OH-CBD were quantified but metabolites 7-OH-CBD, 11-OH-THC, and THC-COOH were not detected in any plasma samples. Inter-individual variance was notable. Salivation shortly after dosing was observed in two cats in the high dose group; these animals had substantially lower cannabinoid concentrations than other cats in this group. No adverse clinical signs (including vomiting, change in mentation or other neurological signs) were noted. Although cats did not display adverse effects after administration of a single oral dose of 1:20 THC:CBD CHE formulation at 2 or 5 mg CBD/kg bw, observed plasma concentrations were highly variable but generally lower than in dogs receiving the same dose and formulation. Administration of CHE in the fasting state may not optimize CBD absorption, and oral dosing may be challenging when administering an oil-based CHE in some cats.

Tolerability of High-Dose Oral Δ9-THC: Implications for Human Laboratory Study Design.

Background: Δ9-tetrahydrocannabinol (THC), the primary intoxicating compound in cannabis, has been tested extensively in controlled administration human studies. Some studies require a high THC dose that may induce adverse events (AEs), such as those testing novel treatments for cannabinoid overdose. Although there are ethical concerns related to administering high THC doses, there is no systematic analysis on studies utilizing these doses. In this review, we examine studies that administered oral THC doses ≥30 mg ("high-dose THC"), focusing on reported tolerability, subjective effects, and pharmacokinetics (PK), with the objective to inform the design of future studies. Methods: A comprehensive PubMed search was performed to identify studies meeting pre-specified criteria. Results: Our search identified 27 publications from 17 high-dose oral THC laboratory studies, with single doses up to 90 mg and multiple doses up to 210 mg per day. The maximum plasma THC concentration (Cmax) appeared to increase in a dose-proportional manner over this dose range. All high-dose THC studies enrolled participants with previous cannabis experience, although current use ranged from nonusers to regular cannabis users. High-dose THC was generally well tolerated with transient mild to moderate AE, including nausea and vomiting, anxiety, paranoia, and sedation. There were occasional participant withdrawals due to AEs, but there were no serious AE. Participants with frequent cannabis use tolerated high-dose THC best. Conclusion: Although based on limited data, THC was generally adequately tolerated with single oral doses of at least 50 mg in a controlled laboratory setting in healthy participants with past cannabis experience.

Oil droplet fouling on lesser sandeel (Ammodytes marinus) eggshells does not enhance the crude oil induced developmental toxicity

The oil industry's expansion and increased operational activity at older installations, along with their demolition, contribute to rising cumulative pollution and a heightened risk of accidental oil spills. The lesser sandeel (Ammodytes marinus) is a keystone prey species in the North Sea and coastal systems. Their eggs adhere to the seabed substrate making them particularly vulnerable to oil exposure during embryonic development. We evaluated the sensitivity of sandeel embryos to crude oil in a laboratory by exposing them to dispersed oil at concentrations of 0, 15, 50, and 150 µg/L oil between 2 and 16 days post-fertilization. We assessed water and tissue concentrations of THC and tPAH, cyp1a expression, lipid distribution in the eyes, head and trunk, and morphological and functional deformities. Oil droplets accumulated on the eggshell in all oil treatment groups, to which the embryo responded by a dose-dependent rise in cyp1a expression. The oil exposure led to only minor sublethal deformities in the upper jaw and otic vesicle. The findings suggest that lesser sandeel embryos are resilient to crude oil exposure. The lowest observed effect level documented in this study was 36 µg THC/L and 3 µg tPAH/L. The inclusion of these species-specific data in risk assessment models will enhance the precision of risk evaluations for the North Atlantic ecosystems.