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Plasma and urine profiles of Delta 9 - tetrahydrocannabinol and its metabolites hydroxy- Delta 9 - tetrahydrocannabinol and norcarboxy- Delta 9 - tetrahydrocannabinol after cannabis smoking by male volunteers to estimate recent consumption by athletes.
Since , cannabis has been prohibited by the World Anti-Doping Agency for all sports competitions. In the years since then, about half of all positive doping cases in Switzerland have been related to cannabis consumption. However, the wide urinary detection window of the long-term metabolite of Delta 9 - tetrahydrocannabinol THC does not allow a conclusion to be drawn regarding the time of consumption or the impact on the physical performance.
The purpose of the present study on light cannabis smokers was to evaluate target analytes with shorter urinary excretion times. Twelve male volunteers smoked a cannabis cigarette standardized to 70 mg THC per cigarette. Plasma and urine were collected up to 8 h and 11 days, respectively.
The limits of quantitation were 0. Eight puffs delivered a mean THC dose of 45 mg. Peak concentrations were observed at 5, , and min. Urine levels were measured in the ranges 0. The times of the last detectable levels were , , and h.
In the case of light cannabis use, this may allow the estimation of more recent consumption, probably influencing. Spray freeze drying to produce a stable Delta 9 - tetrahydrocannabinol containing inulin-based solid dispersion powder suitable for inhalation. The purpose of this study is to investigate whether spray freeze drying produces an inhalable solid dispersion powder in which Delta 9 - tetrahydrocannabinol THC is stabilised.
Delta - 9 - tetrahydrocannabinol THC , a cannabinoid agonist, is the active components of marijuana. In this study we examined the role of ultralow dose THC 0. This extremely low dose of THC was previously found by us to protect the mice brain and heart from a variety of insults. The PNL is composed of lipid and emulsifying excipients of GRAS status and are known to increase solubility and reduce Phase I metabolism of lipophilic active compounds.
These molecules are natural alkaloids and phenolic compounds which were reported to inhibit certain phase I and phase II metabolism processes. Here we use piperine, curcumin and resveratrol to formulate the Advanced-PNL formulations.
This co-localization provides an increase in CBD and THC bioavailability by its effect at the pre-enterocyte and the enterocyte levels of the absorption process. These novel results pave the way to utilize piperine-PNL delivery system for other poorly soluble, highly metabolized. Neuroprotection by delta 9 - tetrahydrocannabinol , the main active compound in marijuana, against ouabain-induced in vivo excitotoxicity. Excitotoxicity is a paradigm used to explain the biochemical events in both acute neuronal damage and in slowly progressive, neurodegenerative diseases.
Here, we show in a longitudinal magnetic resonance imaging study that delta 9 - tetrahydrocannabinol delta9- THC , the main active compound in. Cannabis affects cognitive performance through the activation of the endocannabinoid system, and the molecular mechanisms involved in this process are poorly understood. Using the novel object-recognition memory test in mice, we found that the main psychoactive component of cannabis, delta 9 - tetrahydrocannabinol THC , alters short-term object-recognition memory specifically involving protein kinase C PKC -dependent signaling.
Indeed, the systemic or intra-hippocampal pre-treatment with the PKC inhibitors prevented the short-term, but not the long-term, memory impairment induced by THC. In contrast, systemic pre-treatment with mammalian target of rapamycin complex 1 inhibitors, known to block the amnesic-like effects of THC on long-term memory, did not modify such a short-term cognitive deficit.
Thus, THC administration induced the phosphorylation of a specific Ser residue in the hydrophobic-motif at the C-terminal tail of several PKC isoforms. Moreover, THC transiently enhanced the phosphorylation of the postsynaptic calmodulin-binding protein neurogranin in a PKC dependent manner. Determination of delta - 9 - tetrahydrocannabinol content of cannabis seizures in Egypt. To determine the delta - 9 - tetrahydrocannabinol THC content of cannabis seizures in Egypt.
Unheated and heated extracts of cannabis seizures were prepared from the dried flowering tops and leaves marijuana or from the resin hashish and subjected to analysis using high performance liquid chromatography HPLC.
The heated resin extract had the peak of THC in a relative ratio of On the other hand, marijuana showed minimum percentage of THC at These results indicate the high potency of the abused cannabis plant in the illicit Egyptian market.
Delta - 9 - tetrahydrocannabinol -induced dopamine release as a function of psychosis risk: Full Text Available Cannabis use is associated with psychosis, particularly in those with expression of, or vulnerability for, psychotic illness.
The biological underpinnings of these differential associations, however, remain largely unknown. PET data were analyzed applying the linear extension of the simplified reference region model LSRRM, which accounts for time-dependent changes in 18F-fallypride displacement.
This was most pronounced in caudate nucleus. Genetic dissection of behavioural and autonomic effects of Delta 9 - tetrahydrocannabinol in mice.
Full Text Available Marijuana and its main psychotropic ingredient Delta 9 - tetrahydrocannabinol THC exert a plethora of psychoactive effects through the activation of the neuronal cannabinoid receptor type 1 CB1, which is expressed by different neuronal subpopulations in the central nervous system. The exact neuroanatomical substrates underlying each effect of THC are, however, not known.
We tested locomotor, hypothermic, analgesic, and cataleptic effects of THC in conditional knockout mouse lines, which lack the expression of CB1 in different neuronal subpopulations, including principal brain neurons, GABAergic neurons those that release gamma aminobutyric acid, cortical glutamatergic neurons, and neurons expressing the dopamine receptor D1, respectively.
Surprisingly, mice lacking CB1 in GABAergic neurons responded to THC similarly as wild-type littermates did, whereas deletion of the receptor in all principal neurons abolished or strongly reduced the behavioural and autonomic responses to the drug. Moreover, locomotor and hypothermic effects of THC depend on cortical glutamatergic neurons, whereas the deletion of CB1 from the majority of striatal neurons and a subpopulation of cortical glutamatergic neurons blocked the cataleptic effect of the drug.
These data show that several important pharmacological actions of THC do not depend on functional expression of CB1 on GABAergic interneurons, but on other neuronal populations, and pave the way to a refined interpretation of the pharmacological effects of cannabinoids on neuronal functions.
Effect of Delta - 9 - tetrahydrocannabinol on mouse resistance to systemic Candida albicans infection. Mouse resistance to the infection was assessed by survival and tissue fungal load. Serum cytokine levels were determine to evaluate the immune responses. Passive inhalation of marijuana smoke: In two separate studies, 5 drug-free male volunteers with a history of marijuana use were passively exposed to the sidestream smoke of 4 and 16 marijuana cigarettes 2.
A third study was similarly performed with 2 marijuana-naive subjects passively exposed to the smoke of 16 marijuana cigarettes. Passive smoke exposure was conducted in a small, unventilated room. All urine specimens were collected and analyzed by EMIT d.
The studies show that significant amounts of THC were absorbed by all subjects at the higher level of passive smoke exposure eg. However, it seems improbable that subjects would unknowingly tolerate the noxious smoke conditions produced by this exposure. At the lower level of passive marijuana-smoke exposure, specimens tested positive only infrequently or were negative. Room air levels of THC during passive smoke exposure appeared to be the most critical factor in determining whether a subject produced cannabinoid-positive urine specimens.
Sixteen metabolites were characterized: The major biotransformation pathway was hydroxylation at C 11 to give the major metabolite, followed by oxidation of this compound to a carboxylic acid.
Hydroxylated analogues of these two compounds were substituted mainly in the side-chain. Although metabolism was very similar to that of the naturally occurring - -isomer as far as positions of substitution were concerned, some differences were observed.
These related mainly to the positions of hydroxylation on the side-chain, where 1'-hydroxylation was preferred to hydroxylation at the 2'-position. The major difference in metabolism between the two isomers was that much less oxidation of the hydroxy group to a carboxylic acid occurred and there was less hydroxylation at the 8-position.
Correlations and agreement between delta - 9 - tetrahydrocannabinol THC in blood plasma and Timeline Follow-Back TLFB -assisted self-reported use of cannabis of patients with cannabis use disorder and psychotic illness attending the CapOpus randomized clinical trial.
Self-report of cannabis-use last month by TLFB. Pearson's r, sensitivity and specificity calculated as measures of correlation or agreement.
Aims To assess correlations and agreement between timeline follow-back TLFB -assisted self-report and blood samples for cannabis use. Design Secondary analysis of a randomized trial. Participants One hundred and three patients from the CapOpus trial with cannabis use Conclusions Timeline follow-back TLFB -assisted self-report of cannabis use correlates highly with plasma- delta - 9 - tetrahydrocannabinol in patients with comorbid cannabis use disorder and psychosis.
Sensitivity and specificity of timeline follow-back appear to be optimized with 19 days as the cut-off point Proof of cannabis administration by sensitive detection of nor- Delta 9 - tetrahydrocannabinol carboxylic acid in hair using selective methylation and application of liquid chromatography- tandem and multistage mass spectrometry. However, its application to hair matrix is characterized by a lack of specificity which is due to the unspecific decarboxylation as most abundant fragmentation reaction.
The selective methylation of the 9-carboxyl-group proved to be the most efficient derivatization procedure. Cannabinoid concentrations in blood and urine after passive exposure to cannabis smoke under real-life conditions were investigated in this study. Eight healthy volunteers were exposed to cannabis smoke for 3 h in a well-attended coffee shop in Maastricht, Netherlands.
An initial blood and urine sample was taken from each volunteer before exposure. Blood samples were taken 1. It could be demonstrated that all volunteers absorbed THC. However, the detected concentrations were rather small. THC could be detected in trace amounts close to the detection limit of the used method in the first two blood samples after initial exposure 1.
In the 6 h blood samples, THC was not detectable anymore. Single-dose pharmacokinetics and tolerability of oral delta - 9 - tetrahydrocannabinol in patients with amyotrophic lateral sclerosis. Cannabinoids exert neuroprotective and symptomatic effects in amyotrophic lateral sclerosis ALS. Nine patients received THC single oral doses of 5mg and 10mg, separated by a wash-out period of two weeks.
Adverse events were assessed by visual analogue scales VAS. Plasma concentrations of the active metabolite THC -OH were submitted to sequential pharmacokinetic-pharmacodynamic population modeling on individual heart rate as a proxy for THC 's cardiovasculatory effects. Drowsiness, euphoria, orthostasis, sleepiness, vertigo and weakness were significantly more frequent in patients receiving 10mg compared to 5 mg THC.
PK data did not support any clinically relevant deviation from linear PK in the investigated range of concentrations.
Delta - 9 - tetrahydrocannabinol differentially suppresses cisplatin-induced emesis and indices of motor function via cannabinoid CB 1 receptors in the least shrew. We have recently shown that the cannabinoid CB 1 receptor antagonist, SR A, produces emesis in the least shrew Cryptotis parva in a dose- and route-dependent manner.
This effect was blocked by delta - 9 - tetrahydrocannabinol Delta 9 - THC. Intraperitoneal administration of Delta 9 - THC 1, 2. The lowest significantly effective antiemetic dose of Delta 9 - THC for the latter emesis parameters was 2. Subcutaneous injection of SR A 0. Relative to its motor suppressant effects, Delta 9 - THC is a more potent antiemetic agent.
Both effects are probably mediated via CB 1. Delta 9 - tetrahydrocannabinol inhibits 17beta-estradiol-induced proliferation and fails to activate androgen and estrogen receptors in MCF7 human breast cancer cells. Delta 9 - tetrahydrocannabinol THC exerts palliative effects in cancer patients, but produces adverse effects on the endocrine and reproductive systems. Experimental evidence concerning such effects is controversial.
Whether THC exhibits estrogenic or androgenic activity in vitro was investigated. Androgenic activity was investigated by the A-Screen assay that measures androgen-dependent inhibition of proliferation of the androgen receptor AR -positive human mammary carcinoma cell line, MCF7-AR1.
THC failed to act as an estrogen, but antagonized 17beta-estradiol-induced proliferation. This effect was independent of the AR expression level. Assessment of driving capability through the use of clinical and psychomotor tests in relation to blood cannabinoids levels following oral administration of 20 mg dronabinol or of a cannabis decoction made with 20 or 60 mg Delta9- THC.
Delta 9 - Tetrahydrocannabinol THC is frequently found in the blood of drivers suspected of driving under the influence of cannabis or involved in traffic crashes.
The present study used a double-blind crossover design to compare the effects of medium Forensic interpretation of cannabinoids blood concentrations were attempted using the models proposed by Daldrup cannabis influencing factor or CIF and Huestis and coworkers. Compared to smoking studies, relatively low concentrations were measured in blood.
The highest mean THC concentration 8. Individual blood levels showed considerable intersubject variability. The willingness to drive was influenced by the importance of the requested task. Under significant cannabinoids influence, the participants refused to drive when they were asked whether they would agree to accomplish several unimportant tasks, e. Most of the participants reported a significant feeling of intoxication and did not appreciate the effects, notably those felt after drinking the strongest decoction.
Road sign and tracking testing revealed obvious and statistically significant differences between placebo and treatments. A marked impairment was detected after ingestion of the strongest decoction. A CIF value, which relies on the. Quantitative analysis was corrected by an isotope internal standard method using delta THC -D3 as internal standard. Average recoveries for the target compounds varied from The limits of detection LOD of the method were from 0. Activation of cannabinoid CB1 receptors CB1R by delta 9 - tetrahydrocannabinol THC produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents.
For this reason, there is a tremendous medical interest in harnessing the beneficial effects of THC. We found that specific effects of THC such as memory deficits, anxiolytic-like effects, and social interaction are under the control of 5-HT2AR, but its acute hypolocomotor, hypothermic, anxiogenic, and antinociceptive effects are not. In biochemical studies, we show that CB1R and 5-HT2AR form heteromers that are expressed and functionally active in specific brain regions involved in memory impairment.
Remarkably, our functional data shows that costimulation of both receptors by agonists reduces cell signaling, antagonist binding to one receptor blocks signaling of the interacting receptor, and heteromer formation leads to a switch in G-protein coupling for 5-HT2AR from Gq to Gi proteins.
Synthetic peptides with the sequence of transmembrane helices 5 and 6 of CB1R, fused to a cell-penetrating peptide, were able to disrupt receptor heteromerization in vivo, leading to a selective abrogation of memory impairments caused by exposure to THC. Full Text Available Activation of cannabinoid CB1 receptors CB1R by delta 9 - tetrahydrocannabinol THC produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents.
Disposition of smoked cannabis with high [ Delta ] 9 - tetrahydrocannabinol content: Introduction No model exists to describe the disposition and kinetics of inhaled cannabis containing a high THC dose.
Psychoactive drugs and false memory: Rationale Several psychoactive drugs are known to influence episodic memory. Participants studied DRM word lists under the influence of the drugs, and their recognition memory for the studied words was tested 2 days later, under sober conditions.
Although neither drug significantly affected false memory relative to placebo, AMP increased false memory relative to THC. Conclusions Our results indicate that AMP and THC have opposing effects on true memory, and these effects appear to correspond to similar, albeit more subtle, effects on false memory. These findings are consistent with previous research using the DRM illusion and provide further evidence that psychoactive drugs can affect the encoding processes that ultimately result in the creation of false memories.
Determination of delta 9 - tetrahydrocannabinol in indoor air as an indicator of marijuana cigarette smoking using adsorbent sampling and in-injector thermal desorption gas chromatography-mass spectrometry. The marijuana leaves are usually mixed with tobaccos and smoked at amusement places in Taiwan. Recently, for investigation-legal purposes, the police asked if we can identify the marijuana smoke in a KTV stateroom a private room at the entertainment spot for singing, smoking, alcohol drinking, etc.
A personal air-sampler pump fitted with the GC liner-tube packed with Tenax-TA adsorbent was used for air sampling. The mean delta9- THC contained in the 15 marijuana plants seized from diverse locations was measured to be 0.
The delta9- THC in room air can be successfully identified from mock marijuana cigarettes, mixtures of marijuana and tobacco, and an actual case. The characteristic delta9- THC peak in chromatogram can serve as the indicator of marijuana. Positive result suggests marijuana smoking at the specific scene in the recent past, facilitating the formulation of further investigation. Research typically characterizes cannabis use by self-report of cannabis intake frequency.
Participants were 35 young adult male cannabis users who completed a calibrated TLFB measure of cannabis use over the past 30 days, including time of last use. The calibration required participants handling four plastic bags of a cannabis substitute 0. Participants provided blood and urine samples for analysis of THC and metabolites, at two independent laboratories.
Participants abstained from cannabis use on the day of sample collection. The calibration of cannabis intake in grams was associated with each biometric, although the simple TLFB measure of times of use produced the strongest relationships with all five biometrics.
These findings suggest that combined self-report and biometric data together convey the complexity of cannabis use, but allow that either the use of calibrated TLFB measures or biometrics may be sufficient for assessment of cannabis use in research. A study investigating the acute dose-response effects of 13 mg and 17 mg Delta 9 - tetrahydrocannabinol on cognitive-motor skills, subjective and autonomic measures in regular users of marijuana. Heavy use of marijuana is claimed to damage critical skills related to short-term memory, visual scanning and attention.
Motor skills and driving safety may be compromised by the acute effects of marijuana. The aim of this study was to investigate the acute effects of 13 mg and 17 mg Delta 9 - tetrahydrocannabinol THC on skills important for coordinated movement and driving and on subjective and autonomic measures in regular users of marijuana. Fourteen regular users of marijuana were enrolled. Each subject was tested on two separate days. On each test day, subjects smoked two low-nicotine cigarettes, one with and the other without THC.
Seventeen mg THC was included in the cigarette on one test day and 13 mg on the other day. The sequence of cigarette types was unknown to the subject. During smoking, heart rate and blood pressure were monitored, and the subjects performed a virtual reality maze task requiring attention and motor coordination, followed by 3 other cognitive tasks Wisconsin Card Sorting Test WCST , a "gambling" task and estimation of time and distance from an approaching car.
After smoking a cigarette with 17 mg THC , regular marijuana users hit the walls more often on the virtual maze task than after smoking cigarettes without THC ; this effect was not seen in patients after they smoked cigarettes with 13 mg THC. Smoking cigarettes with 13 and 17 mg THC increased subjective ratings of pleasure and satisfaction, drug "effect" and drug "high". These findings imply that smoking of 17 mg THC results in impairment of cognitive-motor skills that could be important for coordinated movement and driving, whereas the lower dose of 13 mg THC appears to cause less impairment of such skills in regular users of marijuana.
Effects of chronic delta THC treatment on cardiac beta-adrenoceptors in rats. This study was designed to determine if chronic treatment with delta - 9 - tetrahydrocannabinol THC alters cardiac beta-adrenoceptors in the rat. These results suggest that the tolerance to cardiovascular effects of THC which develops during chronic exposure in the rat is not associated with alterations in cardiac beta-adrenoceptors as monitored by radiolabeled antagonist binding.
Different doses of an adenosine A2A receptor antagonist MSX-3 [3,7-dihydro[ 1E 3-ethoxyphenyl ethenyl]-7 methyl[3- phosphooxy propyl 2 propynil -1H-purine-2,6-dione] were found previously to either decrease or increase self- administration of cannabinoids delta - 9 - tetrahydrocannabinol THC or anandamide in squirrel monkeys.
It was hypothesized that the decrease observed with a relatively low dose of MSX-3 was related to blockade of striatal presynaptic A2A receptors that modulate glutamatergic neurotransmission, whereas the increase observed with a higher dose was related to blockade of postsynaptic A2A receptors localized in striatopallidal neurons.
This hypothesis was confirmed in the present study by testing the effects of the preferential presynaptic and postsynaptic A2A receptor antagonists SCH [2- 2-furanyl [3- 4-methoxyphenyl propyl]-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidinamine] and KW [ E -1, 3-diethyl 3,4-dimethoxystyryl methyl-3,7-dihydro-1H-purine-2,6-dione], respectively, in squirrel monkeys trained to intravenously self-administer THC.
SCH produced a significant shift to the right of the THC self- administration dose-response curves, consistent with antagonism of the reinforcing effects of THC. Conversely, KW produced a significant shift to the left, consistent with potentiation of the reinforcing effects of THC. These results show that selectively blocking presynaptic A2A receptors could provide a new pharmacological approach to the treatment of marijuana dependence and underscore corticostriatal glutamatergic neurotransmission as a possible main mechanism involved in the rewarding effects of THC.
Delta - 9 - tetrahydrocannabinol accumulation, metabolism and cell-type-specific adverse effects in aggregating brain cell cultures.
Despite the widespread use of Cannabis as recreational drug or as medicine, little is known about its toxicity. The accumulation, metabolism and toxicity of THC were analyzed 10 days after a single treatment, and after repeated exposures during 10 days. Mixed-cell aggregate cultures of fetal rat telencephalon were used as in vitro model, as well as aggregates enriched either in neurons or in glial cells.
It was found that THC accumulated preferentially in neurons, and that glia-neuron interactions decreased THC accumulation. Only the GABAergic marker was affected after the single treatment, whereas the GABAergic, cholinergic and astrocytic markers were decreased after the repeated treatments.
These results suggest that the adverse effects of THC were related either to THC accumulation or to cannabinoid receptor activation and associated with IL-6 upregulation. Suppression of polymorphonuclear PMN and monocyte-mediated inhibition of Candida albicans growth by delta - 9 - tetrahydrocannabinol.
This study was an in vitro attempt to identify the effector cells responsible for growth inhibition of the opportunistic fungus, candida albicans, and to determine if THC or another marijuana derivatives, hydroxy THC , would adversely affect their function.
Using a 24h radiolabel assay, the authors found that growth inhibition of C. Maximal suppression was obtained with 7. These drug concentrations did not affect lymphoid cell viability or candida growth in the absence of lymphoid effector cells. Marijuana derivatives, therefore, are doubly dangerous in that opportunistic fungi such as C. Full Text Available Rapid screening of seized drugs is a continuing problem for governmental laboratories and customs agents.
Recently new and cheaper methods based on electrochemical sensing have been developed for the detection of illicit drugs. Screen printed electrodes are particularly useful in this regard and can provide excellent sensitivity. In this study, a carbon screen printed electrode for the voltammetric analysis of D9- THC was developed.
The analysis was performed using cyclic voltammetry with 0. In the analysis, a D9- THC standard solution was added to the surface electrode by a drop coating method. A study of scan rate, time of pre-concentration, and concentration influence parameters showed versatility during the investigation. The high sensitivity, quantitative capability and low limit of detection 1. However, a relationship between impairment in cognitive functioning with THC administration and THC -induced change in hemodynamic response has not been demonstrated.
We explored the feasibility of using functional near-infrared spectroscopy fNIRS to examine the functional changes of the human PFC associated with cannabis intoxication and cognitive impairment.
Functional data were collected using a continuous-wave NIRS device, in which 8 Sources and 7 detectors were placed on the forehead, resulting in 20 channels covering PFC regions. Physiological changes and subjective intoxication measures were collected. We found a significant increase in the oxygenated hemoglobin HbO concentration after THC administration in several channels on the PFC during both the high working memory load 2-back and the low working memory load 0-back condition.
The increased HbO response was accompanied by a trend toward an increased number of omission errors after THC administration. The current study suggests that cannabis intoxication is associated with increases in hemodynamic blood flow to the PFC, and that this increase can be detected with fNIRS.
Unheated Cannabis sativa extracts and its major compound THC -acid have potential immuno-modulating properties not mediated by CB1 and CB2 receptor coupled pathways. There is a great interest in the pharmacological properties of cannabinoid like compounds that are not linked to the adverse effects of Delta 9 - tetrahydrocannabinol THC , e. The present paper describes the potential immuno-modulating activity of unheated Cannabis sativa. An indoor air quality-pharmacokinetic simulation of passive inhalation of marijuana smoke and the resultant buildup of nor- delta - 9 - tetrahydrocannabinol carboxylic acid in urine.
The defense will contend the defendant unwittingly breathed side-stream marijuana smoke, thus resulting in the presence of THCA in the defendant's urine. The purpose of this work was to link an indoor air quality model IAQ with a pharmacokinetic PK model to predict a passive marijuana smoker's resultant concentration of the major urinary metabolite THCA.
In vivo metabolism of the methyl homologues of deltatetrahydrocannabinol, delta - 9 - tetrahydrocannabinol and abn-deltatetrahydrocannabinol in the mouse.
In addition, metabolic fractions were reduced with lithium aluminium deuteride to convert carboxylic acids to alcohols for structural correlation. Metabolites from methyl-delta THC were similar with respect to the positions substituted to those produced by higher homologues; the major metabolite was methyl-delta THC oic acid.
The location of the aromatic methyl group at the position adjacent to ring fusion appeared to inhibit metabolism at C 11 to a considerable extent and also to reduce the amount of the resulting alcohol from being oxidized to a carboxylic acid. This caused other metabolic pathways to become dominant, with the result that a compound containing a hydroxy group at the gem-methyl position was the major metabolite. Hydroxylation at this position has not been confirmed with any other cannabinoid, although it is thought to result in trace concentrations of hydroxy metabolites from some compounds.
Metabolism of methyl-delta THC was also similar to that of the higher homologues, with the exception that less metabolism occurred at C 8 and a higher percentage of the total metabolic fraction was accounted for by the oic acid metabolite. Minor metabolites were mainly dihydroxy compounds and hydroxylated derivatives of delta THC oic acid. THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the subchronic PCP model of schizophrenia.
Cannabis use has been associated with an increased risk to develop schizophrenia as well as symptom exacerbation in patients. In contrast, clinical studies have revealed an inverse relationship between the cerebrospinal fluid levels of the endocannabinoid anandamide and symptom severity, suggesting a therapeutic potential for endocannabinoid-enhancing drugs. Indeed, preclinical studies have shown that these drugs can reverse distinct behavioral deficits in a rodent model of schizophrenia. The mechanisms underlying the differences between exogenous and endogenous cannabinoid administration are currently unknown.
Using the phencyclidine PCP rat model of schizophrenia, we compared the effects on neuronal activity of systematic administration of delta - 9 - tetrahydrocannabinol THC with the fatty acid amide hydrolase inhibitor URB Specifically, we found that the inhibitory response in the prefrontal cortex to THC administration was absent in PCP-treated rats. In contrast, an augmented response to endocannabinoid upregulation was observed in the prefrontal cortex of PCP-treated rats.
Interestingly, differential effects were also observed at the neuronal population level, as endocannabinoid upregulation induced opposite effects on coordinated activity when compared with THC. Such information is important for understanding why marijuana and synthetic cannabinoid use may be contraindicated in schizophrenia patients while endocannabinoid enhancement may provide a novel therapeutic approach.
Chronic THC during adolescence increases the vulnerability to stress-induced relapse to heroin seeking in adult rats. Cannabis derivatives are among the most widely used illicit substances among young people.
The addictive potential of delta - 9 - tetrahydrocannabinol THC , the major active ingredient of cannabis is well documented in scientific literature. However, the consequence of THC exposure during adolescence on occurrence of addiction for other drugs of abuse later in life is still controversial.
One week after intoxication, the rats were tested for anxiety-like behavior in the elevated plus maze EPM test. One month later starting from PND 75 , rats were trained to operantly self-administer heroin intravenously. Finally, following extinction phase, reinstatement of lever pressing elicited by the pharmacological stressor, yohimbine 1. Data revealed that in comparison to controls, animals treated with chronic THC during adolescence showed a higher level of anxiety-like behavior.
Noteworthy, following the extinction phase, administration of yohimbine elicited a significantly higher level of heroin seeking in rats previously exposed to THC.
Altogether these findings demonstrate that chronic exposure to THC during adolescence is responsible for heightened anxiety and increased vulnerability to drug relapse in adulthood. Ecstasy is a drug that is usually consumed by young people at the weekends and frequently, in combination with cannabis.
In the present study we have investigated the long-term effects of administering increasing doses of delta - 9 - tetrahydrocannabinol [ THC ; 2. When tested one day after the end of the pharmacological treatment pnd 46 , MDMA administration induced a reduction in directed exploration in the holeboard test and an increase in open-arm exploration in an elevated plus maze.
In the long-term, cognitive functions in the novel object test were seen to be disrupted by THC administration to female but not male rats. In the prepulse inhibition test, MDMA-treated animals showed a decrease in prepulse inhibition at the most intense prepulse studied 80 dB , whereas in combination with THC it induced a similar decrease at 75 dB.
THC decreased hippocampal Arc expression in both sexes, while in the frontal cortex this reduction was only evident in females. Full Text Available Ecstasy is a drug that is usually consumed by young people at the weekends and frequently, in combination with cannabis.
When tested one day after the end of the pharmacological treatment pnd 46, MDMA administration induced a reduction in directed exploration in the holeboard test and an increase in open-arm exploration in an elevated plus maze. In the prepulse inhibition test, MDMA-treated animals showed a decrease in prepulse inhibition at the most intense prepulse studied 80 dB, whereas in combination with THC it induced a similar decrease at 75 dB. Impaired functional connectivity of brain reward circuitry in patients with schizophrenia and cannabis use disorder: It in fact was a amusement account it.
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