THC and CBD: Villain versus Hero? Insights into Adolescent Exposure.
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ABSTRACT:
SUBMITTER: Pintori N
PROVIDER: S-EPMC10048857 | biostudies-literature | 2023 Mar
REPOSITORIES: biostudies-literature
Publications
THC and CBD: Villain versus Hero? Insights into Adolescent Exposure.
Pintori Nicholas N Caria Francesca F De Luca Maria Antonietta MA Miliano Cristina C
International journal of molecular sciences 20230309 6
Cannabis is the most used drug of abuse worldwide. It is well established that the most abundant phytocannabinoids in this plant are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). These two compounds have remarkably similar chemical structures yet vastly different effects in the brain. By binding to the same receptors, THC is psychoactive, while CBD has anxiolytic and antipsychotic properties. Lately, a variety of hemp-based products, including CBD and THC, have become widely available in ...[more]
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Project description:BackgroundCannabis availability with high concentrations of Δ-9-tetrahydrocannabinol (THC) and a range of THC to cannabidiol (CBD) ratios has increased in parallel with a rise in daily cannabis consumption by adolescents. Unanswered questions in adolescents include: 1) whether THC blood concentrations and THC metabolites remain stable or change with prolonged daily dosing, 2) whether CBD modulates THC pharmacokinetic properties and alters THC accumulation in brain, 3) whether blood THC levels reflect brain concentrations.MethodsIn adolescent squirrel monkeys (Saimiri boliviensis), we determined whether a four-month regimen of daily THC (1 mg/kg) or CBD (3 mg/kg) + THC (1 mg/kg) administration (IM) affects THC, THC metabolites, and CBD concentrations in blood or brain.ResultsBlood THC concentrations, THC metabolites and CBD remained stable during chronic treatment. 24 h after the final THC or CBD + THC injection, blood THC and CBD concentrations remained relatively high (THC: 6.0-11 ng/mL; CBD: 9.7-19 ng/mL). THC concentrations in cerebellum and occipital cortex were approximately twice those in blood 24 h after the last dose and did not significantly differ in subjects given THC or CBD + THC.ConclusionsIn adolescent monkeys, blood levels of THC, its metabolites or CBD remain stable after daily dosing for four months. Our model suggests that any pharmacological interactions between CBD and THC are unlikely to result from CBD modulation of THC pharmacokinetics. Finally, detection of relatively high brain THC concentrations 24 h after the final dose of THC suggests that the prolonged actions of THC may contribute to persistent cognitive and psychomotor disruption after THC- or cannabis-induced euphoria wane.
| S-EPMC7371526 | biostudies-literature
Project description:Background: The popularity of edible cannabis products continues to grow in states with legal cannabis access, but few studies have investigated the acute effects of these commercially available products. The present study sought to explore the effects of three commercially available edible products with different levels of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Methods: A sample of regular cannabis users (N=99) were evaluated. Fifty participants completed the study procedures in-person, whereas 49 participants completed the study procedures remotely via Zoom. Subjective effects and plasma cannabinoid levels (in-person participants only) were assessed before and 2 h after participants self-administered one of three products ad libitum: a THC-dominant edible product, a CBD-dominant edible product, or a THC+CBD edible product. Results: At the 2-h post-use assessment, among in-person participants, plasma THC and CBD levels were robustly correlated with self-reported milligrams of THC and CBD consumed, respectively. Across all three conditions, in-person and remote participants experienced (1) an increase in subjective intoxication and elation, (2) a decrease in tension, and (3) no change in paranoia from pre-use to post-use. At post-use, participants who used a CBD product reported less intoxication relative to participants who used a THC+CBD or THC-only product. Participants who used a THC+CBD product reported consuming less THC-and displayed lower plasma THC levels (in-person participants)-relative to participants who used a THC-only product, despite reporting similar levels of positive (intoxication, elation, liking) and psychotomimetic (paranoia, tension) effects. Psychotomimetic effects were very low among both in-person and remote participants across all three conditions, and there were no post-use differences across conditions. Conclusions: Findings suggest that experienced users who consumed a THC+CBD product reported similar levels of positive and psychotomimetic effects relative to those who consumed a THC-only product, despite consuming less THC and displaying lower plasma THC concentrations. Given the potential harms associated with acute cannabis reward and long-term THC exposure, further research is needed to establish whether edible cannabis products with CBD pose less risk to users. Future studies should examine whether these effects generalize to samples of infrequent users, who may have less experience with edible cannabis use. ClinicalTrials.gov ID: NCT03522103.
| S-EPMC10874820 | biostudies-literature
Project description:The use of cannabidiol (CBD) in electronic cigarettes is widespread. Previously, it was reported that CBD is partly transformed to THC in case smoking as a cigarette, however, the pyrolysis of this compound has not been assessed extensively. The aim of our study was to investigate the effect of temperature on the composition of pyrolysis products of CBD. The experiments were performed in the typical operating temperature range of e-cigarettes (250-400 °C) and at 500 °C under both inert and oxidative conditions, and the pyrolysis products were identified and quantified by GC-MS. Depending on the temperature and atmosphere, 25-52% of CBD was transformed into other chemical substances: Δ9-THC, Δ8-THC, cannabinol and cannabichromene were the predominant pyrolysates in both conditions, all formed by cyclization reaction. THC was the main pyrolysis product at all temperatures under both oxidative and inert conditions. Our results point out that CBD in e-cigarettes can be considered as a precursor of THC, thus it bears all the dangers related to this psychoactive compound. Our findings are fundamental contributions to the safety profile of CBD-based e-cigarettes.
| S-EPMC8076212 | biostudies-literature
Project description:Nesidiocoris tenuis (Reuter) (Heteroptera: Miridae) is a tropical mirid bug used as a biocontrol agent in protected crops, including tomatoes. Although N. tenuis predates important insect pests, especially whitefly, it also causes damage by feeding on tomato plants when prey populations decline, resulting in significant economic losses for growers. The pest is now established in some all-year-round tomato crops in Europe and control measures involve the application of pesticides which are incompatible with current IPM programs. As part of future IPM strategies, the pheromone of N. tenuis was investigated. Volatile collections were made from groups and individuals of mated and unmated, females and males. In analyses of these collections by gas chromatography coupled with electroantennographic (EAG) recording from antennae of male bugs, two EAG-active components were detected and identified as 1-octanol and octyl hexanoate. Unlike other mirids, both male and female N. tenuis produced the two compounds, before and after mating, and both sexes gave EAG responses to both compounds. Furthermore, only octyl hexanoate was detected in whole body solvent washes from both sexes. These compounds are not related to the derivatives of 3-hydroxybutyrate esters found as pheromone components in other members of the Bryocrinae sub-family, and the latter could not be detected in volatiles from N. tenuis and did not elicit EAG responses. Nevertheless, experiments carried out in commercial glasshouses showed that traps baited with a blend of the synthetic pheromone components caught essentially only male N. tenuis, and significantly more than traps baited with octyl hexanoate alone. The latter caught significantly more N. tenuis than unbaited traps which generally caught very few bugs. Traps at plant height caught more N. tenuis males than traps 1 m above or at the base of the plants. The trap catches provided an indication of population levels of N. tenuis and were greatly reduced following an application of insecticide.
| S-EPMC8116296 | biostudies-literature
Project description:BackgroundSignificant interest has emerged in the therapeutic and interactive effects of different cannabinoids. Cannabidiol (CBD) has been shown to have anxiolytic and antipsychotic effects with high doses administered orally. We report a series of studies conducted to determine the vaporisation efficiency of high doses of CBD, alone and in combination with ∆9-tetrahydrocannabinol (THC), to achieve faster onset effects in experimental and clinical trials and emulate smoked cannabis.MethodsPurified THC and CBD (40 mg/ml and 100 mg/ml respectively) were loaded onto a liquid absorbing pad in a Volcano vaporiser, vaporised and the vapours quantitatively analysed. Preliminary studies determined 200 mg CBD to be the highest dose effectively vaporised at 230 ° C, yielding an availability of approximately 40% in the vapour phase. Six confirmatory studies examined the quantity of each compound delivered when 200 mg or 4 mg CBD was loaded together with 8 mg of THC.ResultsTHC showed 55% availability when vaporised alone or with low dose CBD, while large variation in the availability of high dose CBD impacted upon the availability of THC when co-administered, with each compound affecting the vaporisation efficiency of the other in a dynamic and dose-dependent manner. We describe optimised protocols that enable delivery of 160 mg CBD through vaporisation.ConclusionsWhile THC administration by vaporisation is increasingly adopted in experimental studies, often with oral predosing with CBD to examine interactive effects, no studies to date have reported the administration of CBD by vaporisation. We report the detailed methodology aimed at optimising the efficiency of delivery of therapeutic doses of CBD, alone and in combination with THC, by vaporisation. These protocols provide a technical advance that may inform methodology for clinical trials in humans, especially for examining interactions between THC and CBD and for therapeutic applications of CBD.Trial registrationCurrent Controlled Trials ISRCTN24109245.
| S-EPMC4274767 | biostudies-literature
Project description:This study aims to identify the proteomic targets of THC in the early postnatal hippocampus of developing mice. Therefore, early postnatal C57Bl/6 mice (P5) were exposed daily and for 30 days to plant extracted THC (either 1 mg/kg or 5 mg/kg) or vehicle solution (saline with 3% Tween® 80) for the control group. All animals stayed with their mothers until P25 and after the initial drug exposure time (until P35) animals were given a drug-free resting period. The animals were sacrificed, and their hippocampus was dissected and prepared for the following proteomic analysis at either P48 or after an extended resting period at P120. We found 31 proteins to be changed after THC exposure compared to vehicle at P48 and 186 proteins showing modifications at P120. Gene ontology classification of protein targets revealed a substantial amount of proteins involved in metabolic processes of neurons after THC exposure. The results highlight the vulnerability of the developing hippocampus towards THC exposure and identify the mitochondrial as well as other cell metabolic processes as potential drug targets.
2020-11-09 | PXD010802 | Pride
Project description:The market for products containing cannabidiol (CBD) is booming globally. However, the pharmacokinetics of CBD in different oral formulations and the impact of CBD use on urine drug testing outcomes for cannabis (e.g., 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (Δ9-THCCOOH)) are understudied. This study characterized the urinary pharmacokinetics of CBD (100 mg) following vaporization or oral administration (including three formulations: gelcap, pharmacy-grade syrup and or Epidiolex) as well as vaporized CBD-dominant cannabis (containing 100 mg CBD and 3.7 mg Δ9-THC) in healthy adults (n = 18). A subset of participants (n = 6) orally administered CBD syrup following overnight fasting (versus low-fat breakfast). Urine specimens were collected before and for 58 h after dosing on a residential research unit. Immunoassay (IA) screening (cutoffs: 20, 50 and 100 ng/mL) for Δ9-THCCOOH was performed, and quantitation of cannabinoids was completed via LC-MS-MS. Urinary CBD concentrations (ng/mL) were higher after oral (mean Cmax: 734; mean Tmax: 4.7 h, n = 18) versus vaporized CBD (mean Cmax: 240; mean Tmax: 1.3 h, n = 18), and oral dose formulation significantly impacted mean Cmax (Epidiolex = 1,274 ng/mL, capsule = 776 ng/mL, syrup = 151 ng/mL, n = 6/group) with little difference in Tmax. Overnight fasting had limited impact on CBD excretion in urine, and there was no evidence of CBD conversion to Δ8- or Δ9-THC in any route or formulation in which pure CBD was administered. Following acute administration of vaporized CBD-dominant cannabis, 3 of 18 participants provided a total of six urine samples in which Δ9-THCCOOH concentrations ≥15 ng/mL. All six specimens screened positive at a 20 ng/mL IA cutoff, and two of six screened positive at a 50 ng/mL cutoff. These data show that absorption/elimination of CBD is impacted by drug formulation, route of administration and gastric contents. Although pure CBD is unlikely to impact drug testing, it is possible that hemp products containing low amounts of Δ9-THC may produce a cannabis-positive urine drug test.
| S-EPMC9122505 | biostudies-literature
Project description:Background: The regular use of cannabis by young men has been associated with an increased incidence of testicular germ cell tumors (TGCT). TGCT, the most common cancer in young adults, is believed to arise from an alteration of testicular fetal germ cells differentiation during development, with a possible subsequent environmental trigger (eg drugs or other chemicals) during puberty or adulthood leading to cancer. Cannabis consumption by pregnant women is currently increasing worldwide, and legalization for its recreational and therapeutic purposes is debated in numerous countries. In this context, we aimed to determine whether cannabis exposure can affect development of the fetal testis. Methods: Since phytocannabinoids act on an endogenous system called the endocannabinoid system (ECS), we first investigated these signaling pathways in the human fetal testis, from 6 to 17 developmental weeks. We next investigated the effects of the two main components of cannabis, (−)-Δ9-trans-tetrahydrocannabinol (THC) and cannabidiol (CBD), on the human fetal testis ex vivo. Results: We show the presence of two key endocannabinoids, 2-arachidonylglycerol (2-AG) and anandamide (AEA), albeit with lower levels. The human fetal testis also expressed several enzymes and receptors of this signaling pathway. Human fetal testicular explants collected from first trimester were exposed to CBD, THC or CBD/THC [ratio 1:1] at concentrations ranging from 10-7 to 10-5M during 72h to 14 days. Phytocannabinoids treatments affected fetal testicular cell proliferation and viability, as well as testosterone secretion by Leydig cells and AMH secretion by Sertoli cells. Transcriptomic analysis performed by BRB-seq on exposed versus unexposed fetal testis explants showed 187 differentially expressed genes (DEGs), some of which involved in toxic substances response and steroid synthesis. Conclusions: Our study provides the first evidence of the presence of ECS in human fetal testis and support a potential adverse effect of cannabis consumption in pregnant women on the male reproductive function development.
2023-06-15 | GSE223827 | GEO
Project description:Cannabidiol (CBD)-containing products are widely marketed as over the counter products, mostly as food supplements, to avoid the strict rules of medicinal products. Side-effects reported in anecdotal consumer reports or during clinical studies were first assumed to be due to hydrolytic conversion of CBD to psychotropic ? 9-tetrahydrocannabinol (? 9-THC) in the stomach after oral consumption. However, research of pure CBD solutions stored in simulated gastric juice or subjected to various storage conditions such as heat and light with specific liquid chromatographic/tandem mass spectrometric (LC/MS/MS) and ultra-high pressure liquid chromatographic/quadrupole time-of-flight mass spectrometric (UPLC-QTOF) analyses was unable to confirm THC formation. Another hypothesis for the side-effects of CBD products may be residual ? 9-THC concentrations in the products as contamination, because most of them are based on crude hemp extracts containing the full spectrum of cannabinoids besides CBD. Analyses of 67 food products of the German market (mostly CBD oils) confirmed this hypothesis: 17 products (25%) contained ? 9-THC above the lowest observed adverse effects level (2.5 mg/day). Inversely, CBD was present in the products below the no observed adverse effect level. Hence, it may be assumed that the adverse effects of some commercial CBD products are based on a low-dose effect of ? 9-THC and not due to effects of CBD itself. The safety, efficacy and purity of commercial CBD products is highly questionable, and all of the products in our sample collection showed various non-conformities to European food law such as unsafe ? 9-THC levels, full-spectrum hemp extracts as non-approved novel food ingredients, non-approved health claims, and deficits in mandatory food labelling requirements. In view of the growing market for such lifestyle products, the effectiveness of the instrument of food business operators' own responsibility for product safety must obviously be challenged.
| S-EPMC7029751 | biostudies-literature
Project description:RationaleDelta-9-tetrahydrocannabinol (THC), an active component of cannabis, can cause anxiety in some users during intoxication. Cannabidiol (CBD), another constituent of cannabis, has anxiolytic properties suggesting that cannabis products containing CBD in addition to THC may produce less anxiety than THC-only products. Findings to date around this issue have been inconclusive and could conceivably depend on moderating factors such as baseline anxiety levels in users.ObjectiveThe present study examined whether anxiety following single doses of vaporised THC, CBD and THC/CBD might be explained by state and trait anxiety levels at baseline.MethodsA placebo-controlled, randomised, within-subjects study including 26 healthy recreational cannabis users tested the effects of vaporised THC-dominant cannabis (13.75 mg THC), CBD-dominant cannabis (13.75 mg CBD), THC/CBD-equivalent cannabis (13.75 mg THC/13.75 mg CBD) and placebo cannabis on anxiety. Self-rated trait anxiety was assessed with the State-Trait Anxiety Inventory (STAI). State levels of anxiety were objectively assessed with a computer-based emotional Stroop task (EST) and subjectively rated with the STAI-state questionnaire and a visual analogue scale.ResultsBoth THC and THC/CBD significantly increased self-rated state anxiety compared to placebo. State anxiety after THC/CBD was significantly lower than after THC alone. THC-induced anxiety was independent of anxiety at baseline. When baseline anxiety was low, CBD completely counteracted THC-induced anxiety; however, when baseline anxiety was high, CBD did not counteract THC-induced anxiety. There were no effects of any treatment condition on the EST.ConclusionOverall, the study demonstrated that the THC/CBD-equivalent cannabis induces less state anxiety than THC-dominant cannabis.
| S-EPMC9584997 | biostudies-literature