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    Delta 9 - tetrahydrocannabinol THC , the main psychoactive constituent of cannabis, accumulates in adipose tissue where it is stored for long periods of time. Here we investigated whether conditions that promote lipolysis can liberate THC from adipocytes to yield increased blood levels of THC. In vitro studies involved freshly isolated rat adipocytes that were incubated with THC before exposure to the lipolytic agent adrenocorticotrophic hormone ACTH.

    Lipolysis promoted by ACTH or food deprivation was indexed by measurement of glycerol levels. The present study shows that lipolysis enhances the release of THC from fat stores back into blood.

    This suggests the likelihood of 'reintoxication' whereby food deprivation or stress may raise blood THC levels in animals chronically exposed to the drug. Further research will need to confirm whether this can lead to functional effects, such as impaired cognitive function or 'flashbacks'.

    Chronic - - delta 9 - tetrahydrocannabinol treatment induces sensitization to the psychomotor effects of amphetamine in rats. Clinical and basic research studies have linked cannabinoid consumption to the onset of psychosis, specially schizophrenia. In the present study we have evaluated the effects of the natural psychoactive constituent of Cannabis - - delta 9 - tetrahydrocannabinol on the acute actions of the psychostimulant, D-amphetamine, on behaviour displayed by male rats on a hole-board, a proposed animal model of amphetamine-induced psychosis.

    Cannabinoid-amphetamine interactions were studied 1 30 min after acute injection of - - delta 9 - tetrahydrocannabinol 0. Acute cannabinoid exposure antagonized the amphetamine-induced dose-dependent increase in locomotion, exploration and the decrease in inactivity. Chronic treatment with - - delta 9 - tetrahydrocannabinol resulted in tolerance to this antagonistic effect on locomotion and inactivity but not on exploration, and potentiated amphetamine-induced stereotypies.

    Lastly, 24 h of withdrawal after 14 days of cannabinoid treatment resulted in sensitization to the effects of D-amphetamine on locomotion, exploration and stereotypies.

    Since - - delta 9 - tetrahydrocannabinol is a cannabinoid CB1 receptor agonist, densely present in limbic and basal ganglia circuits, and since amphetamine enhances monoaminergic inputs i. These findings may be relevant for the understanding of both cannabinoid-monoamines interactions and Cannabis-associated psychosis.

    Chronic treatment with Delta 9 - tetrahydrocannabinol enhances the locomotor response to amphetamine and heroin. Implications for vulnerability to drug addiction. Cannabis sativa preparations are some of the most widely used illicit recreational drugs. In addition to their direct addictive potential, cannabinoids may influence the sensitivity to other drugs. The aim of the present study was to determine if a cross-sensitization between Delta 9 - tetrahydrocannabinol Delta 9 - THC and other drugs amphetamine and heroin could be demonstrated.

    We examined the effects of a chronic treatment with Delta 9 - THC 0. Chronic treatment with Delta 9 - THC resulted in tolerance to the initial hypothermic and anorexic effects. Pre-treatment with Delta 9 - THC increased the locomotor responses to amphetamine and heroin. This cross-sensitization was time-dependent as it was observed three days after the last injection of Delta 9 - THC for amphetamine, and a relatively long time after the end of chronic treatment 41 days for heroin.

    Moreover, the enhanced response to amphetamine or heroin was noted in some individuals only: These animals have previously been shown to be vulnerable to drug taking behaviors.

    It is hypothesised that repeated use of Cannabis derivates may facilitate progression to the consumption of other illicit drugs in vulnerable individuals. Cannabis contains over 70 unique compounds and its abuse is linked to an increased risk of developing schizophrenia.

    The behavioural profiles of the psychotropic cannabis constituent Delta 9 - tetrahydrocannabinol Delta9- THC and the non-psychotomimetic constituent cannabidiol CBD were investigated with a battery of behavioural tests relevant to anxiety and positive, negative and cognitive symptoms of schizophrenia. Delta9- THC produced the classic cannabinoid CB1 receptor-mediated tetrad of hypolocomotion, analgesia, catalepsy and hypothermia while CBD had modest hyperthermic effects.

    Prepulse inhibition was increased by acute treatment with Delta9- THC 0. Chronic Delta9- THC decreased locomotor activity before and after dexamphetamine administration suggesting functional antagonism of the locomotor stimulant effect. Delta - 9 - tetrahydrocannabinol THC in the treatment of end-stage open-angle glaucoma. Evidence exists that the administration of cannabinoid derivatives can lower intraocular pressure. Some patients with glaucoma believe they are being deprived of a potentially beneficial treatment.

    Therefore, the Research Advisory Panel of California instituted the Cannabis Therapeutic Research Program to permit compassionate access to cannabinoid derivatives.

    Data about the potential therapeutic usefulness and toxicity of these agents were collected. This study reviews the results of this program with the specific aim of providing further direction for these investigational efforts. A survey of local ophthalmologists indicated an impressive interest in participating in and contributing patients with glaucoma unresponsive to treatment to this study.

    Appropriate patients were treated with either orally administered delta - 9 - tetrahydrocannabinol capsules or inhaled marijuana in addition to their existing therapeutic regimen. Although 20 ophthalmologists were approved as investigators, only nine patients were enrolled in the study.

    An initial decrease in intraocular pressure was observed in all patients, and the investigator's therapeutic goal was met in four of the nine patients. However, the decreases in intraocular pressure were not sustained, and all patients elected to discontinue treatment within 1 to 9 months for various reasons. This uncontrolled, unmasked, nonrandomized study does not permit definitive conclusions about the efficacy or toxicity of cannabinoids in the treatment of glaucoma.

    There is an impression that this treatment can lower intraocular pressure, but the development of tolerance and significant systemic toxicity appears to limit the usefulness of this potential treatment.

    Both patients and ophthalmologists greatly appreciated the opportunity to participate in this study. Cognitive and subjective dose-response effects of acute oral Delta 9 - tetrahydrocannabinol THC in infrequent cannabis users. Although some aspects of memory functions are known to be acutely impaired by delta 9 - tetrahydrocannabinol delta 9 - THC ; the main active constituent of marijuana , effects on other aspects of memory are not known and the time course of functional impairments is unclear.

    The present study aimed to detail the acute and residual cognitive effects of delta 9 - THC in infrequent cannabis users. A balanced, double-blind cross-over design was used to compare the effects of 7. Participants were assessed pre and 1, 2, 4, 6, 8, 24 and 48 h post-drug. Delta 9 - THC 15 mg impaired performance on two explicit memory tasks at the time of peak plasma concentration 2 h post-drug. At the same time point, performance on an implicit memory task was preserved intact.

    The higher dose of delta 9 - THC resulted in no learning whatsoever occurring over a three-trial selective reminding task at 2 h. Working memory was generally unaffected by delta 9 - THC. In several tasks, delta 9 - THC increased both speed and error rates, reflecting "riskier" speed-accuracy trade-offs. Subjective effects were also most marked at 2 h but often persisted longer, with participants rating themselves as "stoned" for 8 h.

    Participants experienced a strong drug effect, liked this effect and, until 4 h, wanted more oral delta 9 - THC. No effects of delta 9 - THC were found 24 or 48 h following ingestion indicating that the residual effects of oral delta 9 - THC are minimal. These data demonstrate that oral delta 9 - THC impairs episodic memory and learning in a dose-dependent manner whilst sparing perceptual priming and working memory. Delta - 9 - tetrahydrocannabinol THC affects forelimb motor map expression but has little effect on skilled and unskilled behavior.

    It has previously been shown in rats that acute administration of delta - 9 - tetrahydrocannabinol THC exerts a dose-dependent effect on simple locomotor activity, with low doses of THC causing hyper-locomotion and high doses causing hypo-locomotion. However the effect of acute THC administration on cortical movement representations motor maps and skilled learned movements is completely unknown.

    It is important to determine the effects of THC on motor maps and skilled learned behaviors because behaviors like driving place people at a heightened risk.

    Three doses of THC were used in the current study: Rats that received 2. Rats may be employing compensatory strategies after receiving THC , which may account for the robust changes in motor map expression but moderate effects on behavior. Published by Elsevier Ltd. Cannabis use is linked to positive and negative outcomes.

    Identifying genetic targets of susceptibility to the negative effects of cannabinoid use is of growing importance. Selection for THC -locomotor sensitivity was moderately heritable, with the greatest estimates of heritability seen in females from the F2 to S3 generations. Selection for locomotor sensitivity also resulted in increased anxiety-like activity in the open field.

    These results are the first to indicate that adolescent THC -locomotor sensitivity can be influenced via selective breeding. Development of lines with a genetic predisposition for THC -sensitivity or resistance to locomotor effects allow for investigation of risk factors, differences in consequences of THC use, identification of correlated behavioral responses, and detection of genetic targets that may contribute to heightened cannabinoid sensitivity. Acute psychotropic effects of oral cannabis extract with a defined content of Delta 9 - tetrahydrocannabinol THC in healthy volunteers.

    The medical use of cannabinoids is limited mainly by their undesirable effects. Sixteen healthy females participated in this randomized, double-blind, active comparator-controlled, single-dose, balanced 2-way cross-over study.

    Cannabis extract with standardised Delta 9 - tetrahydrocannabinol THC content 20 mg or active placebo 5 mg diazepam was administered orally. VAS showed significantly elevated fatigue, drowsiness, dizziness, and "feeling high" after cannabis as compared to baseline and diazepam.

    BPRS scores were significantly higher after cannabis intake. Only in one psychomotor test a decrease of psychomotor activity after cannabis was evident. One subject in the cannabis condition experienced severe transient psychotic symptoms. Orally administered cannabis produced significant central depressant side-effects compared to diazepam, mostly subjective effects VAS but marginal effects in psychomotor performance in 15 healthy females.

    Regarding the medical use of cannabis, a rigorous benefit-risk analysis and an exact psychiatric assessment before and during treatment are necessary. Delta - 9 - tetrahydrocannabinol THC serum concentrations and pharmacological effects in males after smoking a combination of tobacco and cannabis containing up to 69 mg THC. Delta 9 - Tetrahydrocannabinol THC is the main active constituent of cannabis. To be able to perform suitable exposure risk analysis, it is important to know if there is a linear relation at higher doses.

    This double-blind, placebo-controlled, four-way, cross-over study included 24 male non-daily cannabis users two to nine joints per month. Participants were randomly assigned to smoke cannabis cigarettes containing Serial serum samples collected over a period of h were analysed by liquid chromatography electrospray tandem mass spectrometry.

    Effects on heart rate, blood pressure and 'high' feeling were also measured. Mean maximal concentrations Cmax were A large inter-individual variability in Cmax was observed. Heart rate and 'high' feeling significantly increased with increasing THC dose. Adolescent delta - 9 - tetrahydrocannabinol THC exposure fails to affect THC -induced place and taste conditioning in adult male rats.

    The current study examined the effects of adolescent THC exposure on THC -induced place preference rewarding effects and taste avoidance aversive effects conditioning in adulthood. Forty-six male Sprague-Dawley adolescent rats received eight injections of an intermediate dose of THC 3.

    Animals were given four trials of conditioning with intervening water-recovery days, a final CPP test and then a one-bottle taste avoidance test.

    THC induced dose-dependent taste avoidance but did not produce place conditioning. None of these effects was impacted by adolescent THC exposure. The failure to see an effect of adolescent exposure was addressed in the context of other research that has assessed exposure of drugs of abuse during adolescence on drug reactivity in adulthood. Abstinence phenomena of chronic cannabis-addicts prospectively monitored during controlled inpatient detoxification Part II: Psychiatric complaints and their relation to delta - 9 - tetrahydrocannabinol and its metabolites in serum.

    To investigate the impact of inpatient detoxification treatment on psychiatric symptoms of chronic cannabis addicts and to analyze the influence of serum cannabinoid levels on the severity of these symptoms.

    All patients improved significantly within 16 days of the treatment. Effect sizes ranged from 0. Cohen's d for the respective scales. All other test results were not significantly related to the serum levels of the measured cannabinoids. Effects of the cannabis withdrawal syndrome and executive dysfunctions might explain the discrepancy between the observer ratings and self-reported psychiatric burden.

    Inpatient cannabis detoxification treatment significantly improved psychiatric symptoms. Serum THC -levels were not associated with affective symptoms and anxiety but predicted cognitive impairment and motor retardation. Published by Elsevier Ireland Ltd. Effect of the psychoactive metabolite of marijuana, delta 9 - tetrahydrocannabinol THC , on the synthesis of tumor necrosis factor by human large granular lymphocytes. Repression of this system is therefore likely to contribute to susceptibility to opportunistic infections.

    In this report, we examine the possibility that human large granular lymphocytes LGL can be immunosuppressed by exposure to THC at physiologically relevant concentrations and probed two functions associated with LGL, i. Maternal substance abuse is an ongoing concern and detecting drug use during pregnancy is an important component of neonatal care when drug abuse is suspected.

    Meconium is the preferred specimen for drug testing because it is easier to collect than neonatal urine and it provides a much broader time frame of drug exposure. The samples are then extracted with an organic solvent mixture as part of a sample "cleanup. Following extraction with a second organic mixture, the organic layer is removed and concentrated to dryness.

    Blunting of the HPA-axis underlies the lack of preventive efficacy of early post-stressor single-dose Delta - 9 - tetrahydrocannabinol THC. The outcome measures included behavior in an elevated plus-maze and acoustic startle response 1, 6 and 24 h or 7 days after exposure and freezing behavior upon exposure to a trauma cue on day 8.

    Pre-set cut-off behavioral criteria classified exposed animals as those with "extreme," "minimal" or "intermediate" partial response. The behavioral effects of a CB1 antagonist AM administered systemically 1h post exposure were evaluated. In the longer-term 7 days , it showed no effect in attenuating PTSD-like behavioral stress responses, or freezing response to trauma cue. The endocannabinoids exert complex effects on behavioral responses mediating glucocorticoid effects on memory of traumatic experiences.

    A radioimmunoassay for delta THC in plasma, whole blood, or hemolyzed blood specimens has been presented. Samples and standards were diluted with methanol and centrifuged. Solid phase goat anti-rabbit immunoglobulins were added to separate bound from free THC.

    After centrifugation the supernatant fluid was aspirated and the radioactivity of the precipitate was counted in a gamma counter. The concentration of THC was calculated from a standard curve using the logit-log transformation of the average counts of duplicate tubes. The assay had several advantages.

    The immunological separation of antibody-bound THC from free THC was better than separation techniques using ammonium sulfate and activated charcoal. THC was determined in 0. The acidic forms of cannabinoids, THC -A and CBD-A are naturally present in cannabis plants and preparations and are generally decarboxylated to the active compounds before the use e. Hence, the identification of the acidic compounds in urine could be an evidence of cannabis ingestion rather than a passive exposure to smoke.

    This case report described a month-old child that suffered an acute intoxication by accidental cannabis ingestion. It is important to assess the ingestion and to discriminate it from a passive exposure to better interpret the clinical findings and to establish the correct therapeutic procedure. A triple quad in MRM negative mode was used to monitor the three analytes.

    A LOD of 3. The analytical procedure was validated accordingly to international guidelines. The two urine samples collected from the month-old child at the hospitalization and after three days provided positive results for THCCOOH THC -A was found only in the urine sample collected at the hospitalization concentration: THC -A was detected and quantitated in a urine sample of a month-old child.

    Validation of a two-dimensional gas chromatography mass spectrometry method for the simultaneous quantification of cannabidiol, Delta 9 - tetrahydrocannabinol THC , hydroxy- THC , and norcarboxy- THC in plasma.

    The lower calibration curve was linear from 0. This procedure prevented laborious re-extraction by allowing the same specimen to be re-injected for quantification on the high calibration curve. Analytes were stable when stored at 22 degrees C for 16 h, 4 degrees C for 48 h, after three freeze-thaw cycles at degrees C and when stored on the autosampler for 48 h.

    This sensitive and specific 2D-GCMS assay provides a new means of simultaneously quantifying CBD, THC and metabolite biomarkers in clinical medicine, forensic toxicology, workplace drug testing, and driving under the influence of drugs programs. Brain imaging study of the acute effects of Delta 9 - tetrahydrocannabinol THC on attention and motor coordination in regular users of marijuana.

    In both sessions, a virtual reality maze task was performed during the FDG uptake period. When subject to the effects of 17 mg THC , regular marijuana smokers hit the walls more often on the virtual maze task than without THC. Compared to results without THC , 17 mg THC increased brain metabolism during task performance in areas that are associated with motor coordination and attention in the middle and medial frontal cortices and anterior cingulate, and reduced metabolism in areas that are related to visual integration of motion in the occipital lobes.

    These findings suggest that in regular marijuana users, the immediate effects of marijuana may impact on cognitive-motor skills and brain mechanisms that modulate coordinated movement and driving. An exploratory study of the combined effects of orally administered methylphenidate and delta - 9 - tetrahydrocannabinol THC on cardiovascular function, subjective effects, and performance in healthy adults.

    Illicit users often coadminister MPH with marijuana. Little is known about physiologic and subjective effects of these substances used in combination. In this double-blind, cross-over experiment, sixteen healthy adult subjects free from psychiatric illness including ADHD and reporting modest levels of marijuana use participated in 6 experimental sessions wherein all combinations of placebo or 10mg oral doses of deltatetrahydocannibinol THC ; and 0mg, 10mg and 40 mg of MPH were administered.

    Sessions were separated by at least 48 hours. Vital signs, subjective effects, and performance measure were collected. These results suggest that the combination of low to moderate doses of MPH and THC produces unique effects on cardiovascular function, subjective effects and performance measures. In this double-blind, cross-over experiment, sixteen healthy adult subjects free from psychiatric illness including ADHD and reporting modest levels of marijuana use participated in 6 experimental sessions wherein all combinations of placebo or 10 mg oral doses of deltatetrahydocannibinol THC ; and 0 mg, 10 mg and 40 mg of MPH were administered.

    Today, the main route of introduction of tetrahydrocannabinol THC , the main active substance of cannabis, into the human body is via the lungs, from smokes produced by combustion of a haschich-tobacco mixture. The use of a water pipe nargileh-like intensifies its fast supply to the body. THC reaches the brain easily where it stimulates CB1 receptors; their ubiquity underlies a wide variety of effects.

    THC disappears from extracellular spaces by dissolving in lipid rich membranes, and not by excretion from the body. This is followed by a slow release, leading to long lasting effects originating from brain areas containing a large proportion of spare receptors "reserve receptors". Far from mimicking the effects of endocannabinoids, THC caricatures and disturbs them.

    It induces both psychical and physical dependencies, but the perception of withdrawal is weak on account of its very slow elimination. Acutely, it develops anxiolytic- and antidepressant-like effects, which causes a lot of users to abuse THC , thus leading to a tolerance desensitization of CB1 receptors making anxiety and depression to reappear more intensely than originally.

    THC has close relationships with schizophrenia. It incites to tobacco, alcohol and heroine abuses. Topical delta 9 - tetrahydrocannabinol and aqueous dynamics in glaucoma. Systemic delta 9 - tetrahydrocannabinol THC , administered either by smoking marihuana or as synthetic THC in soft gelatin capsules, lowers ocular tension in various glaucomas, but at the expense of significant decreases in systolic blood pressure. Topical THC in light mineral oil vehicles, though effective in laboratory animals, was not shown effective in 0.

    Light mineral oil, which has an affinity for corneal epithelium, is an optimum vehicle for administering drugs whose mechanisms of action are systemic rather than local within the eye. Further glaucoma research should therefore proceed with marihuanas containing insignificant levels of THC less than 0. Inhibition of cortiocosteroidogenesis by delta - 9 - tetrahydrocannabinol. ACTH, cholera toxin, cyclic AMP but not pregnenolone-induced steroidogenesis in Y-1 functional mouse adrenal tumor cells was significantly inhibited by delta - 9 - tetrahydrocannabinol , cannabidiol, and cannabinol.

    The inhibition of steroidogenesis could not be correlated with a general depression in cell function or viability. The data suggest that cannabinoids inhibit corticosteroidogenesis at a site between the synthesis of cAMP and of pregnenolone.

    Sex differences in antinociceptive tolerance to delta - 9 - tetrahydrocannabinol in the rat. Background Sex differences in cannabinoid effects have been reported in rodents, with adult females typically being more sensitive than adult males.

    The present study compared the development of antinociceptive tolerance to delta - 9 - tetrahydrocannabinol THC in adult, gonadally intact female vs. Methods Cumulative dose-effect curves were obtained for THC 1. Results On the pre- chronic test day, THC was significantly more potent in females than males in producing antinociception on the tail withdrawal and paw pressure tests. After 9 days of twice-daily THC treatment 5.

    On the tail withdrawal test, chronic THC produced 4. On the paw pressure test, chronic THC produced 4. Chronic THC treatment did not significantly disrupt estrous cycling in females.

    Conclusions These results demonstrate that — even when sex differences in acute THC potency are controlled for — females develop more antinociceptive tolerance to THC than males.

    Given the importance of drug tolerance in the development of drug dependence, these results suggest that females may be more vulnerable than males to developing dependence after chronic cannabinoid exposure. Medicinal applications of delta - 9 - tetrahydrocannabinol and marijuana. The use of crude marijuana for herbal medicinal applications is now being widely discussed in both the medical and lay literature.

    Ballot initiatives in California and Arizona have recently made crude marijuana accessible to patients under certain circumstances. As medicinal applications of pure forms of delta - 9 - tetrahydrocannabinol THC and crude marijuana are being considered, the most promising uses of any form of THC are to counteract the nausea associated with cancer chemotherapy and to stimulate appetite.

    We evaluated the relevant research published between and on the medical applications, physical complications, and legal precedents for the use of pure THC or crude marijuana. Our review focused on the medical use of THC derivatives for nausea associated with cancer chemotherapy, glaucoma, stimulation of appetite, and spinal cord spasticity.

    Despite the toxicity of THC delivered in any form, evidence supports the selective use of pure THC preparations to treat nausea associated with cancer chemotherapy and to stimulate appetite.

    The evidence does not support the reclassification of crude marijuana as a prescribable medicine. 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.

    Randomized, double-blind, placebo-controlled study about the effects of cannabidiol CBD on the pharmacokinetics of Delta 9 - tetrahydrocannabinol THC after oral application of THC verses standardized cannabis extract.

    As a reason, pharmacodynamic as well as pharmacokinetic mechanisms were suggested. Blood samples were taken 30 minutes before and 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 9 hours and 24 hours after the intake.

    The concentration versus time curves maximum concentrations Cmax, corresponding time tmax and areas under the curves AUC were evaluated by statistical methods with respect to equivalence or differences between the CAN-set and the THC -set.

    The probability for this inhibition is particularly high for oral intake because THC and CBD attain relatively high concentrations in the liver and because of the high first-pass metabolism of THC. However, the effect of CBD is small in comparison to the variability caused by other factors.

    Therefore, a pharmacokinetic reason for the differences determined between pure THC and cannabis extract is improbable at. 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.

    Chronic or acute exposure to delta - 9 - tetrahydrocannabinol THC , the main psychoactive compound in cannabis, has been associated with numerous neuropsychiatric side-effects, including dysregulation of emotional processing and associative memory formation. Clinical and pre-clinical evidence suggests that the effects of THC are due to the ability to modulate mesolimbic dopamine DA activity states in the nucleus accumbens NAc and ventral tegmental area VTA.

    Nevertheless, the mechanisms by which THC modulates mesolimbic DA function and emotional processing are not well understood. Using an olfactory associative fear memory procedure combined with in vivo neuronal electrophysiology, we examined the effects of direct THC microinfusions targeting the shell region of the NAc NASh and examined how THC may modulate the processing of fear-related emotional memory and concomitant activity states of the mesolimbic DA system.

    We report that intra-NASh THC dose-dependently potentiates the emotional salience of normally sub-threshold fear-conditioning cues. These findings demonstrate that THC can act directly in the NASh to modulate mesolimbic activity states and induce disturbances in emotional salience and memory formation through modulation of VTA DAergic transmission.

    This article is protected by copyright. Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown.

    To investigate the effects of 2 main psychoactive constituents of Cannabis sativa Delta 9 - tetrahydrocannabinol [Delta9- THC ] and cannabidiol [CBD] on regional brain function during emotional processing. Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety.

    Each scanning session was preceded by the ingestion of either 10 mg of Delta9- THC , mg of CBD, or a placebo in a double-blind, randomized, placebo-controlled design. Fifteen healthy, English-native, right-handed men who had used cannabis 15 times or less in their life. Regional brain activation blood oxygenation level-dependent response , electrodermal activity skin conductance response [SCR] , and objective and subjective ratings of anxiety.

    Delta 9 - Tetrahydrocannabinol increased anxiety, as well as levels of intoxication, sedation, and psychotic symptoms, whereas there was a trend for a reduction in anxiety following administration of CBD.

    Cannabidiol attenuated the blood oxygenation level-dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdalar and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations.

    Delta 9 - Tetrahydrocannabinol mainly modulated activation in frontal and parietal areas. Delta 9 - Tetrahydrocannabinol and CBD had clearly distinct effects on the neural, electrodermal, and symptomatic response to fearful faces.

    The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to. Effects of delta 9 - tetrahydrocannabinol and pentobarbital on a cortical response evoked during conditioning. A surface-negative wave, evoked by tone cues, appeared in monkey post-arcuate cortex as the monkey learned that the cue signaled the availability of reward.

    This evoked activity was depressed, concomitantly with changes in the animal's behavioral responding, by doses of delta 9 - tetrahydrocannabinol delta9- THC as low as 0. Pentobarbital tended to increase the latency of the evoked wave, an effect not seen with delta9- THC.

    Suppression of human macrophage function in vitro by delta 9 - tetrahydrocannabinol. The ability of macrophages to function in the presence of delta 9 - tetrahydrocannabinol THC , the major psychoactive component in marijuana, was evaluated.

    THC added to macrophage cultures prepared from human peripheral blood inhibited macrophage spreading and phagocytosis of yeast. These results suggest that macrophages are more sensitive to THC than are lymphocytes because macrophage functions were inhibited by THC at concentrations that did not affect lymphocyte function. Thus, inhibition of lymphocyte function s by THC could be attributed to a direct effect of the drug on macrophages which indirectly results in lowered lymphoid cell activity.

    Suppressive effect of delta 9 - tetrahydrocannabinol in vitro on phagocytosis by murine macrophages. The THC in a dose-related manner suppressed the percentage of macrophages per culture which ingested yeast and the average number of yeast particles ingested by the phagocytizing macrophages. The vehicle used to suspend the THC in vitro, i. Suppression of phagocytosis with no effects on viability or cell number occurred with doses of 10 micrograms or less THC per milliliter culture medium.

    Measurable suppression also occurred after to hr treatment of the macrophages with the THC. This compound had little if any detectable effect on phagocytosis when added directly to the cultures shortly before testing for phagocytosis.

    Further studies concerning the effects of THC on macrophage function appear warranted. Gonadal hormones do not alter the development of antinociceptive tolerance to delta - 9 - tetrahydrocannabinol in adult rats. The purpose of this study was to determine whether sex differences in the development of antinociceptive tolerance to delta - 9 - tetrahydrocannabinol THC are due to activational effects of gonadal hormones.

    Two weeks later, antinociceptive potency of THC was determined pre- chronic test on the warm water tail withdrawal and paw pressure assays. Vehicle or a sex-specific THC dose females, 5. On the pre- chronic test both assays , THC was more potent in sham-GDX females than males, and gonadectomy did not alter this sex difference.

    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. 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.

    Production and hosting by Elsevier B. Cortical neuroinflammation contributes to long-term cognitive dysfunctions following adolescent delta - 9 - tetrahydrocannabinol treatment in female rats. Over million people consume cannabis globally. Cannabis use peaks during adolescence with a trend for continued consumption by adults. Notably, several studies have shown that long-term and heavy cannabis use during adolescence can impair brain maturation and predispose to neurodevelopmental disorders, although the neurobiological mechanisms underlying this association remain largely unknown.

    In this study, we evaluated whether, in female rats, chronic administration of increasing doses of the psychotropic plant-derived cannabis constituent, delta - 9 - tetrahydrocannabinol THC , during adolescence PND could affect microglia function in the long-term. Furthermore, we explored a possible contribution of microglia to the development of THC -induced alterations in mood and cognition in adult female rats.

    This neuroinflammatory phenotype is associated with down-regulation of CB1 receptor on neuronal cells and up-regulation of CB2 on microglia cells, conversely.

    In contrast, THC -induced depressive-like behaviors were unaffected by ibudilast treatment. Our findings demonstrate that adolescent THC administration is associated with persistent neuroinflammation within the PFC and provide evidence for a causal association between microglial activation and the development long-term cognitive deficits induced by adolescent THC treatment.

    Cannabidiol reverses the reduction in social interaction produced by low dose Delta 9 - tetrahydrocannabinol in rats. While Delta 9 - tetrahydrocannabinol THC is the main psychoactive constituent of the cannabis plant, a non-psychoactive constituent is cannabidiol CBD.

    CBD has been implicated as a potential treatment of a number of disorders including schizophrenia and epilepsy and has been included with THC in a 1: This study investigated the effect of THC and CBD, alone or in combination, on some objective behaviours of rats in the open field. Pairs of rats were injected with CBD or vehicle followed by THC or vehicle and behaviour in the open field was assessed for 10 min.

    However, the combination of high dose CBD and high dose THC significantly reduced social interaction between rat pairs, as well as producing a significant decrease in locomotor activity. Psychomotor performance in relation to acute oral administration of Delta 9 - tetrahydrocannabinol and standardized cannabis extract in healthy human subjects.

    Abnormalities in psychomotor performance are a consistent finding in schizophrenic patients as well as in chronic cannabis users. The high levels of central cannabinoid CB 1 receptors in the basal ganglia, the cerebral cortex and the cerebellum indicate their implication in the regulation of motor activity. Based on the close relationship between cannabis use, the endogenous cannabinoid system and motor disturbances found in schizophrenia, we expected that administration of cannabinoids may change pattern of psychomotor activity like in schizophrenic patients.

    This prospective, double-blind, placebo-controlled cross-over study investigated the acute effects of cannabinoids on psychomotor performance in 24 healthy right-handed volunteers age Psychomotor performance was assessed by using a finger tapping test series.

    Cannabis extract, but not Delta 9 - THC , revealed a significant reduction of right-hand tapping frequencies that was also found in schizophrenia. These effects are thought to be related to cannabinoid actions on CB 1 receptors in the basal ganglia, the cerebral cortex and the cerebellum.

    Our data further demonstrate that acute CB 1 receptor activation under the cannabis extract condition may also affect intermanual coordination IMC as an index of interhemispheric transfer.

    AIR-Scale scores as a measure of subjective perception of intoxication were dose-dependently related to IMC which was shown by an inverted U-curve. This result may be due to functional changes involving GABAergic and glutamatergic neurotransmission within the corpus callosum. Alteration in the level of endogenous hypothalamic prostaglandins induced by delta 9 - tetrahydrocannabinol in the rat.

    The behavioural changes consisted mainly of catatonia most apparent at 30 min after administration of delta 9- THC , followed by sedation most evident at 60 min. Hypothermia was marked from 30 min after administration of delta 9- THC.

    Abstract Cannabidiol CBD , a major cannabinoid of hemp, does not bind to CB1 receptors and is therefore devoid of psychotomimetic properties. It has been argued that this may occur also after oral administration in humans. However, the experimental conversion of CBD to THC and delta8- THC in simulated gastric fluid SGF is a highly artificial approach that deviates significantly from physiological conditions in the stomach; therefore, SGF does not allow an extrapolation to in vivo conditions.

    In addition, the typical spectrum of side effects of THC , or of the very similar synthetic cannabinoid nabilone, as listed in the official Summary of Product Characteristics e. Cannabidiol CBD , a major cannabinoid of hemp, does not bind to CB1 receptors and is therefore devoid of psychotomimetic properties. 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. 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. Delta - 9 - tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response. In the current study, we tested the central hypothesis that exposure to Delta - 9 - tetrahydrocannabinol Delta9- THC , the major psychoactive component in marijuana, can lead to enhanced growth of tumors that express low to undetectable levels of cannabinoid receptors by specifically suppressing the antitumor immune response.

    Furthermore, exposure of mice to Delta9- THC led to significantly elevated 4T1 tumor growth and metastasis due to inhibition of the specific antitumor immune response in vivo. The suppression of the antitumor immune response was mediated primarily through CB2 as opposed to CB1. This possibility was further supported by microarray data demonstrating the up-regulation of a number of Th2-related genes and the down-regulation of a number of Th1-related genes following exposure to Delta9- THC.

    Effects of perinatal exposure to delta 9 - tetrahydrocannabinol on operant morphine-reinforced behavior. The present study examined the effects of Delta 9 - tetrahydrocannabinol Delta 9 - THC when administered during the perinatal period on morphine self-administration in adulthood.

    To this end, pregnant Wistar rats were daily exposed to Delta 9 - THC from the fifth day of gestation up to pup weaning, when they were separated by gender and left to mature to be used for analyses of operant food- and morphine-reinforced behavior in a progressive ratio PR schedule.

    In both reinforcement paradigms, food and morphine, females always reached higher patterns of self-administration than males, but this occurred for the two treatment groups, Delta 9 - THC or vehicle.

    All these changes, however, disappeared after 15 days of morphine self-administration and they did not reappear after 15 additional days of extinction of this response. Our data suggest that females are more vulnerable than males in a PR schedule for operant food and morphine self-administration; perinatal Delta 9 - THC exposure is not a factor influencing this vulnerability.

    The neurochemical analysis revealed that the activity of limbic dopaminergic neurons prior to morphine self-administration was higher in females than males, as well as that the perinatal Delta 9 - THC treatment reduced the activity of these neurons only in females, although this had no influence on morphine vulnerability in these animals. 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. Gene expression changes in human small airway epithelial cells exposed to Delta 9 - tetrahydrocannabinol. Marijuana smoking is associated with inflammation, cellular atypia, and molecular dysregulation of the tracheobronchial epithelium. While marijuana smoke shares many components in common with tobacco, it also contains a high concentration of Delta 9 - tetrahydrocannabinol THC.

    THC induced a time- and concentration-dependent decrease in cell viability, ATP level, and mitochondrial membrane potential. Treatment with selected prototypical toxicants, 2,3,7,8-tetrachlorodibenznzo-p-dioxin TCDD and carbonyl cyanide-p- trifluoramethoxy -phenyl hydrazone FCCP , produced partially overlapping gene expression profiles suggesting some similarity in mechanism of action with THC.

    THC , delivered as a component of marijuana smoke, may induce a profile of gene expression that contributes to the pulmonary pathology associated with marijuana use.

    Acute effects of Delta 9 - tetrahydrocannabinol and standardized cannabis extract on the auditory evoked mismatch negativity. Reduced amplitudes of auditory evoked mismatch negativity MMN have often been found in schizophrenic patients, indicating deficient auditory information processing and working memory.

    Cannabis-induced psychotic states may resemble schizophrenia. Currently, there are discussions focusing on the close relationship between cannabis, the endocannabinoid and dopaminergic system, and the onset of schizophrenic psychosis. The deviant stimuli differed in frequency Hz.

    There were no significant differences between MMN amplitudes at frontal electrodes. Since the main difference between Delta 9 - THC and standardized cannabis extract is CBD, which seems to have neuroprotective and anti-psychotic properties, it can be speculated whether the greater MMN amplitude that may imply higher cortical activation and cognitive performance is related to the positive effects of CBD.

    This effect may be relevant for auditory cortex activity in particular because only MMN amplitudes at the central, but not at the frontal electrodes were enhanced under cannabis. Effects of daily delta - 9 - tetrahydrocannabinol treatment on heroin self-administration in rhesus monkeys. Opioid abuse remains a significant public health problem; together with the greater availability of marijuana in some regions there is an increasing likelihood that opioids and marijuana will be used together.

    Poly-drug abuse is associated with increased toxicity and poorer treatment outcome; thus, a better understanding of the consequences of repeated co-administration of these drugs will facilitate the development of better prevention and treatment strategies. In addition, daily treatment did not significantly impact extinction of heroin self-administration or resumption of responding for heroin after extinction.

    These data suggest that repeated administration of a cannabinoid receptor agonist likely does not increase, and possibly decreases, the positive reinforcing effects of a mu opioid receptor agonist.

    Polydrug abuse is associated with increased toxicity and poorer treatment outcome; thus, a better understanding of the consequences of repeated coadministration of these drugs will facilitate the development of better prevention and treatment strategies. Cannabis use is frequent among adolescents. Its main component, delta - 9 - tetrahydrocannabinol THC , affects the immune system.

    We recently demonstrated that chronic exposure of adolescent mice to THC suppressed immunity immediately after treatment but that after a washout period THC induced a long-lasting opposite modulation towards a proinflammatory and T-helper-1 phenotype in adulthood.

    The main objective of this study was to investigate whether the same effect was also present in brain regions such as the hypothalamus and hippocampus. Thirty-three-day-old adolescent and day-old adult male mice were used. Acute THC administration induced a similar reduction of macrophage proinflammatory cytokines and an IL increase in adult and adolescent mice. Big engery super smooth smoke with a light after taste that will put you in a zen like meditative state towards the climax of the high.

    So easy to use! Really good weed nice and dense nugs taste awesome not to harsh. But the only reason i gave it a 4 and not a 5 was cause with all the others i get from here are always to that the pic looks like or even better.

    Maybe i just got a batch that was not as much Chrystal as above but was green rather none the less still some top notice grade buds and the fact the i got my oz in 2 tuna cans was even better. Great for the lazy baker! I warm the bottle up in a cup of hot water and mix it into a batch of chocolate chip cookies. It makes 48 cookies. I had to check for breathing after a 10 hour sleep. Now… she eats cookies every night. Ordered on the 6th tuesday and received in the mail on the 8th Friday.

    Really potent stuff, has very nice aroma and does indeed have a piney taste. Gotta love the Trainwreck. Ol lady n I ordered an Oz last Wednesday with 1 day shipping and always a great strain.

    This 1 was made for my brother. Ordered 2 bags 1 puff, 1 rosin!! Great taste and great buzz. Try again on Sunday. Has like a grapefruit taste, my second order and its amazing again, 4 days to show up and perfectly packed.

    The smell is strong and sweet and this is a delicious strain will definitely get again. Nice bud, Nice buzz. You wont be finding a strain close to this in your any shops around your town.

    Beautiful buds literally dripping in crystal, after the smoke it was hibernation mode for an evening…. I justs LOVE the smell of this stuff!! Gives off a nice earthy floral smell and taste, from the beginning of toke, to end.

    Product is as advertised. Very happy with my order and with QG. A bit dry but effects are there and lingers for a few hours. I would live to but this kit if it would just stay in stock ling enough maybe I will get a chance real soon. Amazing quality, got this on sale and i easily would of paid full price.

    Came in exactly 2 days, extremely happy will be ordering again. Got mine in the mail today and it works great. Easy to refill and recharge. The distillate in the pen was smooth and hits hard. Really like this stuff, great value all in all. My second order and my first comment. Good smooth inhale and exhale. A bit on the dry side but easy to take apart for quick draws. The E transfer takes a bit of play on your mind , yet when you get your order a week later for both occasions the anxiety of rolling one up made up for the wait.

    Hopefully this helped both of you buyer and seller. Hopefully will get a better count for this free promo. Some pretty quality bud here , for an amazing price! Got this in place of my other order because they had sold out, definitely not disappointed. Holy crap its purple! It smells so beautifully sweet and earthy i love it. For someone with insomnia i slept amazing last night will definitely be ordering here from now on. Dank weed soo frosty and purple dark purple beautiful bud would recommend to everyone smells good too just waiting for another oz they forgot to ship out.

    Omg this Kush is the Padre of kush! Je me roule une 0. I just received 7g off Skywalker OG This was my first order from quickgreens. I was a little disappointed, product was a little dry and I had about 1g of shake. But the buds were nice, a little small but very crystallized The smell is nice, and product look a lot like the pictures.

    I smoke a fat one, and the buzz is really nice, taste is good, very cerebral for a almost pure Indica, not too much couch lock puts you in a good mood. I was expecting better. Will be ordering again soon. Usually am a indica smoker, but decided to give this a try also got some godfather og kush. Such a beautiful taste and will be buying again!! Absolutely loved it as the same the other! Definitely will be buying from here again! Just received my order of this wonderful strain, and also got some hempstar.

    I highly recommend this strain for a relaxing night!! Nice nugs of a beautiful purple colour, everyone who has tried it here was not disappointed. Fast delivery also which was a plus! Was my first time ordering off here and definitely will be again. I got this not expecting much but wow was I suprised. It is quite above average and for half the price. Tastes good, does its job well. It tastes of peanut butter and has a delicious inhale and exhale.

    Top notch, great stuff. I love using an Indica to help sooth the aches and pain away at night and this one is amazing.

    I just got oz. Nice buds , cured properly! Looks and smells exactly as advertised. Great value for the price. I ordered an oz, it was my first order placed with QG and must say very impressed. Thank you so much!! This was my first distillate ever, Soni had no idea what to expect. I opened the pen and had no idea how to turn it on because there was no button. I took a puff and got a huge, lovely tasting, coughless cloud.

    So smooth and delicious. I will definitely be ordering again. Just got this strain and all I can say is wow huge dried perfect nugs very purple and smells super yummy all buds over a gram in fact got 4 nice tops weighing grams.

    Got this twice now in luck I watched everyday for it to come back in stock really good for smoking just pick the little bit of stick. Nice crystal covered nugs. Light and giggly for a couple hours before falling and staying asleep. It was my first time ordering from this site and I must say it was great! This strain lives up to its name! Burns beautifully and tastes great! I received exactly what was ordered and it looked exactly like the pictures that represent it which is very important to me.

    Overall I was happy because the quality was there but I removed a star because I found the weed to be a little too fresh for me. I know some would argue that there is an optimal humidity level but in my 25 years of smoking quality buds it was always better when it was very close to being dried out, nobody wants to buy weed and then have to dry it out afterwards. It is of my honest opinion that is more of a money grab.

    I rolled a joint immediately when I received but knew I would need to set some aside to dry as it felt too fresh, or at least more than what I am used to getting. So be prepared to lose some weight off your order for that reason. I initially had some miscommunication issues but they seemed interested in resolving them with me which they did. Jadore surtout pour loz. Nobody was disappointed who tried!

    Curing was just about perfect. Anyone who I let try was not disappointed. Nice dense nugs, heavy smoke , has a nice kick, makes you a little confused at first ,interesting ride. I was dead wrong. This stuff is fire.

    The effects hit you between the eyes and shows no mercy. I was a fair bit sceptical about receiving the product in the picture and boy I was wrong in such a wonderful way.

    What you see is what you get. It smells like piney orange vitamin c chewables and sweet sugar. The high is all in your head. Just a nice thought provoking feeling and it feels really clean and good. Yes, perfect and sooo pleasant to look at. It seriously looks like a cartoon and smells like one too.

    Just like how cereal may smell like a cartoon? On a more serious note. One complaint, which is beyond minor, was the packaging that all the products I got came in. It was really smell proof which was great, but each pack was compressed tight and had to be carefully taken apart. No damage after a minute or two of effort and off to the Boveda jar she goes.

    Anytime I had an issue in the whole process and I reached out to support, I got a response within the hour to give assurances. I also got the Violator Kush but will review separately.

    Really enjoyed these little treats in our order!!!! Best quality gummies I have tried and I have tried several other known brands. We took 2 of these candies before bed and slept so soundly. WoW im very happy!! Looks even better than the pictures. Dense deep purple buds. Smell is danky just like parent OG Kush. Really strong evening or night strain.

    Such a great escape from reality and an awesome stress relief. This kit is a good value, pen works good , weed was great , not a big fan of the oil but still say a good value. Got a bag of these today with purchase of an oz. Was walking around at work with my cane last night. Joint only has to be lit once and gets you fried. Best rso I had in a long time. Price is unbelievable for the amount and quality. A few lil drops and anfll pain just seized to exist. Love the taste, and the smell is great.

    Smokes very nice too, perfectly cured! Five thumbs up definitely!!!!! Lindsay OG was by far some dank stuff.

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