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Also, the computational idea of catalysis by water to catalysis by an acid , put forward by Li and Brill, and Churchev and Belbruno was extended, and a new direct keto-enol route was found. Evidence for this was found by performing an extraction experiment with Cannabis Flos.
It revealed the presence of short chain carboxylic acids supporting this hypothesis. The effect of conditions influencing endogenous prostaglandins on the activity of delta'- tetrahydrocannabinol in mice. The neuroprotective actions of cannabidiol and other cannabinoids were examined in rat cortical neuron cultures exposed to toxic levels of the excitatory neurotransmitter glutamate.
Cannabinoids protected equally well against neurotoxicity mediated by N-methyl-d-aspartate receptors, 2-amino 4-butylhydroxyisoxazolyl propionic acid receptors, or kainate receptors.
The neuroprotection observed with cannabidiol and THC was unaffected by cannabinoid receptor antagonist, indicating it to be cannabinoid receptor independent.
Previous studies have shown that glutamate toxicity may be prevented by antioxidants. Cannabidiol, THC and several synthetic cannabinoids all were demonstrated to be antioxidants by cyclic voltametry. Cannabidiol and THC also were shown to prevent hydroperoxide-induced oxidative damage as well as or better than other antioxidants in a chemical Fenton reaction system and neuronal cultures.
These data also suggest that the naturally occurring, nonpsychotropic cannabinoid, cannabidiol, may be a potentially useful therapeutic agent for the treatment of oxidative neurological disorders such as cerebral ischemia.
Jerry; Beardsley, Patrick M. These receptors are normally activated by endogenous lipids, including anandamide and 2-arachidonoyl glycerol 2-AG. To this end, adult male mice and rats were trained to discriminate THC 5. Significant decreases in responding may have prevented assessment of adequate endocannabinoid doses. In rats, neither URB nor JZL engendered significant THC-appropriate responding, but co-administration of these two enzyme inhibitors approached full substitution.
The present results highlight the complex interplay between anandamide and 2-AG and suggest that endogenous increases of both endocannabinoids are most effective in elicitation of THC-like discriminative stimulus effects.
Methamphetamine METH is a potent psychostimulant with neurotoxic properties. Heavy use increases the activation of neuronal nitric oxide synthase nNOS , production of peroxynitrites, microglia stimulation, and induces hyperthermia and anorectic effects. Most METH recreational users also consume cannabis. This final rule adopts without changes an interim final rule with request for comments published in the Federal Register on March 23, On July 1, , the U.
Food and Drug Administration FDA approved a new drug application for Syndros, a drug product consisting of dronabinol [ - -deltatrans- tetrahydrocannabinol deltaTHC ] oral solution. Neither absolute THC content nor morphology allows the unequivocal discrimination of fiber cultivars and drug strains of Cannabis sativa L. Using PCR-based markers in two segregating populations, we proved that the THCA synthase gene represents the postulated B locus and that specific sequence polymorphisms are absolutely linked either to the THC-predominant or the THC-intermediate chemotype.
The absolute linkage provides an excellent reliability of the marker signal in forensic casework. For validation, the species-specific marker system was applied to a large number of casework samples and fiber hemp cultivars.
Cannabinoid ester constituents from high-potency Cannabis sativa. Eleven new cannabinoid esters, together with three known cannabinoid acids and Delta9- tetrahydrocannabinol Delta9-THC , were isolated from a high-potency variety of Cannabis sativa. The structures were determined by extensive spectroscopic analyses to be beta-fenchyl Delta9- tetrahydrocannabinolate 1 , epi-bornyl Delta9- tetrahydrocannabinolate 2 , alpha-terpenyl Delta9- tetrahydrocannabinolate 3 , 4-terpenyl Delta 9- tetrahydrocannabinolate 4 , alpha-cadinyl Delta9- tetrahydrocannabinolate 5 , gamma-eudesmyl Delta9- tetrahydrocannabinolate 6 , gamma-eudesmyl cannabigerolate 7 , 4-terpenyl cannabinolate 8 , bornyl Delta9- tetrahydrocannabinolate 9 , alpha-fenchyl Delta9- tetrahydrocannabinolate 10 , alpha-cadinyl cannabigerolate 11 , Delta9- tetrahydrocannabinol Delta9-THC , Delta9- tetrahydrocannabinolic acid A Delta9- THCA , cannabinolic acid A CBNA , and cannabigerolic acid CBGA.
The isolated acids and the ester-containing fractions showed low affinity to the CB-1 receptor. Rapid identification of drug-type strains in Cannabis sativa using loop-mediated isothermal amplification assay. In Cannabis sativa L. Both strains are prohibited by law in many countries including Japan, whereas the drug-type strains are regulated in Canada and some European countries. As the two strains cannot be discriminated by morphological analysis, a simple method for identifying the drug-type strains is required for quality control in legal cultivation and forensic investigation.
We have developed a novel loop-mediated isothermal amplification LAMP assay for identifying the drug-type strains of C. The assay showed high specificity for the drug-type strains and its sensitivity was the same as or higher than that of conventional polymerase chain reaction. We also showed the effectiveness of melting curve analysis that was conducted after the LAMP assay. The melting temperature values of the drug-type strains corresponded to those of the cloned drug-type THCA synthase gene, and were clearly different from those of the cloned fiber-type THCA synthase gene.
Our rapid, sensitive, specific, and simple assay is expected to be applicable to laboratory and on-site detection. The parameters and variables affecting the extraction were investigated. Under optimum conditions 1 wt. The limit of detection was 0. Compared with conventional solid-liquid extraction, this new method avoids the use of volatile organic solvents, therefore is environmentally safer. 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.
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.
Stevens; Lichtman, Aron H. A growing body of evidence implicates endogenous cannabinoids as modulators of the mesolimbic dopamine system and motivated behavior. In this study, we investigated the impact of THC and inhibitors of the endocannabinoid hydrolytic enzymes fatty acid amide hydrolase FAAH and monoacylglycerol lipase MAGL on operant responding for electrical stimulation of the medial forebrain bundle [intracranial self-stimulation ICSS ], which is known to activate the mesolimbic dopamine system.
These drugs were also tested in assays of operant responding for food reinforcement and spontaneous locomotor activity. In contrast, the FAAH inhibitor PF Npyridinyl[[3-[[5- trifluoromethyl pyridinyl]oxy]phenyl]methyl]piperidinecarboxamide was largely without effect in these assays.
The cannabinoid receptor type 1 receptor antagonist rimonabant, but not the cannabinoid receptor type 2 receptor antagonist SR, blocked the attenuating effects of THC, JZL, and SA on. On the pharmacological properties of Delta9- tetrahydrocannabinol THC. Cannabis is one of the first plants used as medicine, and the notion that it has potentially valuable therapeutic properties is a matter of current debate.
The isolation of its main constituent, Delta9- tetrahydrocannabinol THC , and the discovery of the endocannabinoid system cannabinoid receptors CB1 and CB2 and their endogenous ligands made possible studies concerning the pharmacological activity of cannabinoids.
This paper reviews some of the most-important findings in the field of THC pharmacology. Clinical trials, anecdotal reports, and experiments employing animal models strongly support the idea that THC and its derivatives exhibit a wide variety of therapeutic applications. However, the psychotropic effects observed in laboratory animals and the adverse reactions reported during human trials, as well as the risk of tolerance development and potential dependence, limit the application of THC in therapy.
Nowadays, researchers focus on other therapeutic strategies by which the endocannabinoid system might be modulated to clinical advantage inhibitor or activator of endocannabinoid biosynthesis, cellular uptake, or metabolism. However, emerging evidence highlights the beneficial effects of the whole cannabis extract over those observed with single components, indicating cannabis-based medicines as new perspective to revisit the pharmacology of this plant.
Obesity is one of the highest preventable causes of morbidity and mortality in the developed world . It has been well known for a long time that exposure to cannabis produces an increase of appetite a phenomenon referred to as the 'munchies'. This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome.
This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile .
Despite being efficacious, Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market. We recently discovered that the prevalence of obesity is paradoxically much lower in cannabis users as compared to non-users and that this difference is not accounted for by tobacco smoking status and is still present after adjusting for variables such as sex and age.
Medicinal applications of delta 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 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. Effects of delta tetrahydrocannabinol on evaluation of emotional images. There is growing evidence that drugs of abuse alter processing of emotional information in ways that could be attractive to users. In this study, we examined the effects of acute THC on evaluation of emotional images. Healthy volunteers received two doses of THC 7.
THC significantly impaired recognition of facial fear and anger, but it only marginally impaired recognition of sadness and happiness. The drug did not consistently affect ratings of emotional scenes. THC' effects on emotional evaluation were not clearly related to its mood-altering effects.
These results support our previous work, and show that THC reduces perception of facial threat. The potential for false-positive oral fluid cannabinoid results from passive exposure to THC-laden cannabis smoke raises concerns for this promising new monitoring technology. THCCOOH concentrations are in the picogram per milliliter range in oral fluid and pose considerable analytical challenges.
After solid phase extraction, chromatography was performed on a Kinetex C18 column with a gradient of 0. Mean extraction efficiencies and matrix effects evaluated at low and high quality control QC concentrations were Analytical recoveries bias and total imprecision at low, mid, and high QCs were Delta tetrahydrocannabinol THC is the main psychoactive ingredient of cannabis, a drug which is commonly smoked This paper focuses on the pharmacokinetics of THC.
In a cigarette containing 3. THC is quickly cleared from plasma in a multiphasic manner and is widely distributed to tissues, leading to its pharmacologic effects. Body fat is a long-term storage site. This particular pharmacokinetic behavior explains the lack of correlation between the THC blood level and clinical effects, contrary to ethanol. Cannabis is the main illicit drug found among vehicle drivers. Various traffic safety studies indicate that recent use of this drug at least doubles the risk of causing an accident, and that simultaneous alcohol consumption multiplies this risk by afactor of Since , synthetic cannabinoids have emerged on the illicit drug market.
Their pharmacokinetics differs from that of THC, as they are metabolized into multiple derivatives, most of which are more active than THC itself. Effects of tetrahydrocannabinol on glucose uptake in the rat brain. The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain. For data acquisition a Focus small animal PET scanner was used and Nine volumes of interest were defined, and the cerebral glucose uptake was calculated for each brain region.
The effective concentration in this region was estimated 2. This glucose PET study showed that stimulation of CB1 receptors by THC affects the glucose uptake in the rat brain, whereby the effect of THC is regionally different and dependent on dose - an effect that may be of relevance in behavioural studies. Tetrahydrocannabinol THC impairs encoding but not retrieval of verbal information. Cannabis and agonists of the brain cannabinoid receptor CB 1 R produce acute memory impairments in humans.
However, the extent to which cannabinoids impair the component processes of encoding and retrieval has not been established in humans. Healthy subjects were recruited from the community. Subjects received intravenous THC, in a placebo-controlled, double-blind, randomized manner at doses known to produce behavioral and subjective effects consistent with cannabis intoxication.
Total immediate recall, short delayed recall, and long delayed recall were reduced in a statistically significant manner only when the RAVLT was administered to subjects while they were under the influence of THC experiment 2 and not when the RAVLT was administered prior. THC acutely interferes with encoding of verbal memory without interfering with retrieval.
These data suggest that learning information prior to the use of cannabis or cannabinoids is not likely to disrupt recall of that information.
Future studies will be necessary to determine whether THC impairs encoding of non-verbal information, to what extent THC impairs memory consolidation, and the role of other cannabinoids in the memory-impairing effects of cannabis. Careful consideration of the extraction method is very important for the measurement of cannabinoids in hemp seeds. Yang, Yi; Lewis, Melissa M. It is recognized that the endocannabinoid system ECS plays a crucial role in the modulation of food intake and other aspects of energy metabolism.
THC treatment increased culture protein content and reduced methyl- 3 H-thymidine incorporation. The effects on methyl- 3 H-thymidine incorporation and lipolysis seem to be mediated through CB1- and CB2-dependent pathways. These results show that the ECS interferes with adipocyte biology and may contribute to adipose tissue AT remodeling.
Although these observations point toward increased AT deposition, the stimulation of adiponectin production and inhibition of lipolysis may be in favor of improved INS sensitivity under cannabinoid influence. Delta 9 - tetrahydrocannabinol and ethanol: Serum dopamine beta-hydroxylase activity, a useful biochemical index of peripheral sympathetic nervous activity, was measured in rats treated with Delta 9 - tetrahydrocannabinol or ethanol or both substances.
After 7 days of treatment with either substance, serum dopamine beta-hydroxylase activity decreased significantly. Combined treatment with both agents enhanced the effects of each given alone.
In rats subjected to immobilization stress, treatment with Delta 9 - tetrahydrocannabinol appeared to potentiate the stress-induced increase in serum enzyme activity.
Treatment with ethanol, with or without Delta 9 - tetrahydrocannabinol , effectively blocked this increase in enzyme activity. These results show that both substances have significant effects on the sympathetic nervous system which are critically influenced by environmental setting. Chronic - -delta9- 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 - -delta9- 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 - -delta9- tetrahydrocannabinol 0. Acute cannabinoid exposure antagonized the amphetamine-induced dose-dependent increase in locomotion, exploration and the decrease in inactivity. Chronic treatment with - -delta9- 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 - -delta9- 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. Human urinary excretion profile after smoking and oral administration of sup 14 C delta 1- tetrahydrocannabinol.
Urine was collected for five days after each administration route and analyzed for total delta 1-THC metabolites by radioactivity determination, for delta 1-THCoic acid by high-performance liquid chromatography, and for cross-reacting cannabinoids by the EMIT d. However, in the chronic users the excretion profiles of delta 1-THCoic acid and EMIT readings did not resemble the radioactive excretion due to the heavy influence from previous Cannabis use.
The experiments, conducted with Science, , , Engineering yeasts as platform organisms for cannabinoid biosynthesis. The discovery of the human endocannabinoid system in the late s resulted in a growing number of known physiological functions of both synthetic and plant derived cannabinoids. Thus, manifold therapeutic indications of cannabinoids currently comprise a significant area of research.
Here we reconstituted the final biosynthetic cannabinoid pathway in yeasts. The use of the soluble prenyltransferase NphB from Streptomyces sp. In addition to the desired product cannabigerolic acid , NphB catalyzes an O-prenylation leading to 2-O-geranyl olivetolic acid.
We show for the first time that the bacterial prenyltransferase and the final enzyme of the cannabinoid pathway tetrahydrocannabinolic acid synthase can both be actively expressed in the yeasts Saccharomyces cerevisiae and Komagataella phaffii simultaneously.
While enzyme activities in S. This study is an important step toward total biosynthesis of valuable cannabinoids and derivatives and demonstrates the potential for developing a sustainable and secure yeast bio-manufacturing platform.
To ensure complete hydrolysis of conjugates and capture of total analyte content, urine samples were hydrolyzed by two methods in series.
Extracted analytes were derivatized with BSTFA and quantified by gas chromatography—mass spectrometry with electron impact ionization. Standard curves were linear from 2. Extraction efficiencies were Intra- and interassay precision across the linear range of the assay ranged from 0. This method was applied to the analysis of urine specimens collected from individuals participating in controlled administration cannabis studies, and it may be a useful analytical procedure for determining recency of cannabis use in forensic toxicology applications.
A comparison of the apoptotic effect of Delta 9 - tetrahydrocannabinol in the neonatal and adult rat cerebral cortex. The maternal use of cannabis during pregnancy results in a number of cognitive deficits in the offspring that persist into adulthood. The endocannabinoid system has a role to play in neurodevelopmental processes such as neurogenesis, migration and synaptogenesis. However, exposure to phytocannabinoids, such as Delta 9 - tetrahydrocannabinol , during gestation may interfere with these events to cause abnormal patterns of neuronal wiring and subsequent cognitive impairments.
Aberrant cell death evoked by Delta 9 - tetrahydrocannabinol may also contribute to cognitive deficits and in cultured neurones Delta 9 - tetrahydrocannabinol induces apoptosis via the CB 1 cannabinoid receptor. In this study we report that Delta 9 - tetrahydrocannabinol microM activates the stress-activated protein kinase, c-jun N-terminal kinase, and the pro-apoptotic protease, caspase-3, in in vitro cerebral cortical slices obtained from the neonatal rat brain.
The proclivity of Delta 9 - tetrahydrocannabinol to impact on these pro-apoptotic signalling molecules was not observed in in vitro cortical slices obtained from the adult rat brain. In contrast, in vivo administration of Delta 9 - tetrahydrocannabinol to adult rats was not associated with the apoptotic pathway in the cerebral cortex. The data provide evidence which supports the hypothesis that the neonatal rat brain is more vulnerable to the neurotoxic influence of Delta 9 - tetrahydrocannabinol , suggesting that the cognitive deficits that are observed in humans exposed to marijuana during gestation may be due, in part, to abnormal engagement of the apoptotic cascade during brain development.
Repeated exposure to delta 9- tetrahydrocannabinol reduces prefrontal cortical dopamine metabolism in the rat. Long-term abuse of marijuana by humans can induce profound behavioral deficits characterized by cognitive and memory impairments. In particular, deficits on tasks dependent on frontal lobe function have been reported in cannabis abusers.
In the current study, we examined whether long-term exposure to delta9- tetrahydrocannabinol , the active ingredient in marijuana, altered the neurochemistry of the frontal cortex in rats.
Two weeks administration of delta9- tetrahydrocannabinol reduced dopamine transmission in the medial prefrontal cortex, while dopamine metabolism in striatal regions was unaffected. These data are consistent with earlier findings of dopaminergic regulation of frontal cortical cognition. Thus, cognitive deficits in heavy abusers of cannabis may be subserved by drug-induced alterations in frontal cortical dopamine transmission. 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 Delta9- 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.
Delta9- 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.
Delta9- Tetrahydrocannabinol mainly modulated activation in frontal and parietal areas. Delta9- 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. Plasma and urine profiles of Delta9- tetrahydrocannabinol and its metabolites hydroxy-Delta9- tetrahydrocannabinol and norcarboxy-Delta9- 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. The effects of pH and temperature on the in vitro bindings of delta tetrahydrocannabinol and other cannabinoids to bovine serum albumin.
Albumin is a major carrier of drugs and fatty acids in biological fluids. These protein-drug complexes serve to solubilize, transport these compounds to sites of action, and have been associated with increased half-life for these compounds. The authors are interested in the pH and temperature effects of the binding of delta tetrahydrocannabinol to albumin.
Ultrafiltration techniques were used in the separation of free to bound compounds. Cannabinoids bind to bovine serum albumin rapidly. The cannabinoid binding sites are more sensitive to temperature changes degrees C than changes in pH with 37 degrees C and pH 7. These conditions would result in the greatest viability in the cells, while allowing for the use of a variety of compounds in in vitro studies for the administration of compounds to isolated cells and cell lines.
The immunosuppression induced by both compounds could be blocked by SR, an antagonist specific for the CB2 receptor, but not by SR, a CB1 antagonist. These studies are novel in that they show that both anadamide and THC are active in the nanomolar to picomolar for anandamide range in these assays of immune function, and that both mediate their effects directly on cells of the immune system through the CB2 receptor.
Effects of delta9- 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 delta9- tetrahydrocannabinol delta9-THC as low as 0. Pentobarbital tended to increase the latency of the evoked wave, an effect not seen with delta9-THC. Inhibition of the cataleptic effect of tetrahydrocannabinol by other constituents of Cannabis sativa L. Tetrahydrocannabinol THC induced catalepsy in mice, whereas a cannabis oil 6.
Quality Control of Traditional Cannabis Tinctures: Pattern, Markers, and Stability. Traditional tinctures of Cannabis sativa L. Yet storage and use of non-stabilized tinctures remain critical without authorized specification and stability data because a consistent cannabinoid content is not guaranteed. The two-phase solvent system composed of chloroform-methanol-water-acetic acid 4: The revolution speed of the separation column, flow rate of the mobile phase and separation temperature were rpm, 1.
From mg of the crude extract, Nonpsychoactive phytocannabinoids pCBs from Cannabis sativa may represent novel therapeutic options for cachexia because of their pleiotropic pharmacological activities, including appetite stimulation.
We have recently shown that purified cannabigerol CBG is a novel appetite stimulant in rats. No significant effect was observed on ambulatory activity or rearing behaviour. Abstinence phenomena of chronic cannabis-addicts prospectively monitored during controlled inpatient detoxification Part II: Psychiatric complaints and their relation to delta 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.
Memory deficits produced by marijuana arise partly via interaction of the psychoactive component, [Deta][superscript 9]- tetrahydrocannabinol [Deta][superscript 9]-THC , with cannabinoid receptors in the hippocampus. Although cannabinoids acutely reduce glutamate release and block hippocampal long-term potentiation LTP , a potential substrate for…. Various factors considered and applied included drug-excipient compatibility, use of antioxidants, cross-linking in polymeric matrices, microenvironment pH, and moisture effect.
Instability of THC in polyethylene oxide PEO -vitamin E succinate VES patches was determined to be due to chemical interaction between the drug and the vitamin as well as with the atmospheric oxygen. Of the different classes and mechanisms of antioxidants studied, quenching of oxygen by reducing agents, namely, ascorbic acid was the most effective in stabilizing THC in PEO-VES matrices.
This coupled with the cross-linking extent and adjustment of the pH microenvironment, which seemed to have an impact on the THC degradation, might be effectively utilized towards stabilization of the drug in these polymeric matrices and other pharmaceutical dosage forms.
These studies are relevant to the development of a stable transmucosal matrix system for the therapeutic delivery of amorphous 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.
Determination of delta tetrahydrocannabinol content of cannabis seizures in Egypt. To determine the delta 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.
Sample preparation consisted of a protein precipitation with acetonitrile. 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. Cannabinoid receptor agonists produce reliable antinociception in most preclinical pain assays but have inconsistent analgesic efficacy in humans. This disparity suggests that conventional preclinical assays of nociception are not sufficient for the prediction of cannabinoid effects related to clinical analgesia.
Intraperitoneal injection of dilute lactic acid 1. Repeated THC produced tolerance to sedative rate-decreasing effects of THC on control ICSS in the absence of the noxious stimulus but failed to unmask antinociception in the presence of the noxious stimulus. THC and CP also failed to block pain-related depression of feeding in rats, although THC did attenuate satiation-related depression of feeding.
The poor efficacy of THC and CP to block acute pain-related depression of behavior in rats agrees with the poor efficacy of cannabinoids to treat acute pain in humans. The tumour suppressor protein, p53, is involved in the activation of the apoptotic cascade by Delta9- tetrahydrocannabinol in cultured cortical neurons. Cannabis is the most commonly used illegal drug of abuse in Western society.
Delta 9 - tetrahydrocannabinol , the psychoactive ingredient of marijuana, regulates a variety of neuronal processes including neurotransmitter release and synaptic transmission. An increasing body of evidence suggests that cannabinoids play a key role in the regulation of neuronal viability.
In cortical neurons tetrahydrocannabinol has a neurodegenerative effect, the mechanisms of which are poorly understood, but involve the cannabinoid receptor subtype, CB 1.
In this study we report that tetrahydrocannabinol 5 muM evokes a rapid phosphorylation, and thus activation, of the tumour suppressor protein, p53, in a manner involving the cannabinoid CB 1 receptor, and the stress-activated protein kinase, c-jun N-terminal kinase, in cultured cortical neurons.
Tetrahydrocannabinol increased expression of the ptranscriptional target, Bax and promoted Bcl phosphorylation. These events were abolished by the p53 inhibitor, pifithrin-alpha nM. The tetrahydrocannabinol -induced activation of the pro-apoptotic cysteine protease, caspase-3, and DNA fragmentation was also blocked by pifithrin-alpha. A siRNA knockdown of p53 further verified the role of p53 in tetrahydrocannabinol -induced apoptosis. This study demonstrates a novel cannabinoid signalling pathway involving p53 that culminates in neuronal apoptosis.
These compounds were isolated by liquid-liquid extraction using cold acetonitrile. The following transition ions were monitored by multiple reaction monitoring MRM: Within-run and between-run precisions for all the analytes yielded coefficients of variation of The effects of Delta- tetrahydrocannabinol and cannabidiol alone and in combination on damage, inflammation and in vitro motility disturbances in rat colitis. Cannabis is taken as self-medication by patients with inflammatory bowel disease for symptomatic relief.
Cannabinoid receptor agonists decrease inflammation in animal models of colitis, but their effects on the disturbed motility is not known. The 2,4,6-trinitrobenzene sulphonic acid TNBS model of acute colitis in rats was used to assess damage, inflammation myeloperoxidase activity and in vitro colonic motility.
Sulphasalazine was used as an active control drug. Sulphasalazine, THC and CBD proved beneficial in this model of colitis with the dose-response relationship for the phytocannabinoids showing a bell-shaped pattern on the majority of parameters optimal THC and CBD dose, 10 mg. THC was the most effective drug. The effects of these phytocannabinoids were additive, and CBD increased some effects of an ineffective THC dose to the level of an effective one.
In this model of colitis, THC and CBD not only reduced inflammation but also lowered the occurrence of functional disturbances. The endocannabinoid EC system regulates bone mass. Because cannabis use during pregnancy results in stature shorter than normal, we examined the role of the EC system in skeletal elongation. We show that CB1 and CB2 cannabinoid receptors are expressed specifically in hypertrophic chondrocytes of the epiphyseal growth cartilage EGC , which drives vertebrate growth.
These cells also express diacylglycerol lipases, critical biosynthetic enzymes of the main EC, and 2-arachidonoylglycerol 2-AG , which is present at significant levels in the EGC. This in turn results in lower body weight, but unaltered fat content. The relevance of the present findings to humans remains to be studied.
Solubility, stability and in vitro transcorneal permeability of the relatively hydrophilic hemiglutarate ester derivative, THC-HG, was studied in the presence of surfactants. The solutions were characterized with respect to micelle size, zeta potential and solution viscosity. In vivo studies were carried out in New Zealand albino rabbits. Aqueous solubility and stability and in vitro transcorneal permeability of THC-HG was enhanced significantly in the presence of surfactants.
THC levels in the ocular tissues except cornea were found to be below detection limits from mineral oil, surfactant or emulsion based formulations containing THC. In this study, although delivery of THC to the anterior chamber ocular tissues could be significantly increased through the prodrug and formulation approaches tested, further studies are needed to increase penetration to the back-of-the eye.
The treatment of glioblastoma cells with both compounds led to significant modulations of the cell cycle and induction of reactive oxygen species ROS and apoptosis as well as specific modulations of extracellular signal-regulated kinase ERK and caspase activities. These specific changes were not observed with either compound individually, indicating that the signal transduction pathways affected by the combination treatment were unique.
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.
Cannabis users display a constellation of withdrawal symptoms upon drug discontinuation, including sleep disturbances, irritability, and possibly memory deficits. Here, we tested whether THC-dependent mice undergoing rimonabant-precipitated withdrawal display short-term spatial memory deficits, as assessed in the Morris water maze. We also evaluated whether rimonabant would precipitate adenylyl cyclase superactivation in hippocampal and cerebellar tissue from THC-dependent mice.
Rimonabant significantly impaired spatial memory of THC-dependent mice at lower doses than those necessary to precipitate somatic withdrawal behavior. In contrast, maze performance was near perfect in the cued task, suggesting sensorimotor function and motivational factors were unperturbed by the withdrawal state.
Finally, rimonabant increased adenylyl cyclase activity in cerebellar, but not in hippocampal, membranes. The memory disruptive effects of THC undergo tolerance following repeated dosing, while the withdrawal state leads to a rebound deficit in memory. These results establish spatial memory impairment as a particularly sensitive component of cannabinoid withdrawal, an effect that may be mediated through compensatory changes in the cerebellum.
ABCB1 CT polymorphism is associated with tetrahydrocannabinol blood levels in heavy cannabis users. ABCB1 polymorphisms are known to modify drug pharmacokinetics but have yet to be studied for their role in generating and maintaining cannabis dependence. In this population males: The exact mechanisms and roles that this may play in cannabis dependence genesis and evolution remain to be elucidated.
These results should be controlled in a replication study using a larger population. Tetrahydrocannabinol -induced suppression of macrophage spreading and phagocytic activity in vitro. The effects of tetrahydrocannabinol THC on several parameters of macrophage function in vitro were assessed. Delta 9 THC added to cultures of normal mouse peritoneal cells in vitro affected the ability of the cells to spread on glass surfaces and also had some effect on their ability to phagocytize yeast.
These effects were dose related. A concentration of 20 micrograms of THC almost completely inhibited macrophage spreading, but it also decreased viability and the total number of these cells. Doses of 10 or 5 micrograms of THC also inhibited spreading but had little effect on cell viability or number.
A dose of 1. Higher doses of THC were necessary to inhibit phagocytosis of yeast particles as determined by direct microscopic examination or use of radiolabeled yeast as the test particles. These results indicate that several readily measured functions of macrophages may be suppressed by THC.
The balance between detrimental, pro-aging, often stochastic processes and counteracting homeostatic mechanisms largely determines the progression of aging.
There is substantial evidence suggesting that the endocannabinoid system ECS is part of the latter system because it modulates the physiological processes underlying aging. The activity of the ECS declines during aging, as CB1 receptor expression and coupling to G proteins are reduced in the brain tissues of older animals and the levels of the major endocannabinoid 2-arachidonoylglycerol 2-AG are lower. However, a direct link between endocannabinoid tone and aging symptoms has not been demonstrated.
This behavioral effect was accompanied by enhanced expression of synaptic marker proteins and increased hippocampal spine density. THC treatment restored hippocampal gene transcription patterns such that the expression profiles of THC-treated mice aged 12 months closely resembled those of THC-free animals aged 2 months. The transcriptional effects of THC were critically dependent on glutamatergic CB1 receptors and histone acetylation, as their inhibition blocked the beneficial effects of THC.
Thus, restoration of CB1 signaling in old individuals could be an effective strategy to treat age-related cognitive impairments. Marijuana is a widely used illicit drug and its consumption during pregnancy has been associated with adverse reproductive outcomes.
The pathological characteristics and distribution of cannabinoid receptors in placenta were observed by immunohistochemical IHC staining. Cell migration in response to THC was measured by transwell assays. We found the placenta expressed two main cannabinoid receptors, suggesting that THC induced biological responses in placental cells.
Supporting this hypothesis, we observed dramatic alterations of placental morphology in marijuana users. Using THC and inhibitors of cannabinoid receptors, we demonstrated that THC impaired trophoblast cell migration and invasion partly via cannabinoid receptors.
Additionally, pregnant mice injected with THC showed adverse reproductive events including reduced number of fetuses, lower maternal and placental weights. Mechanistically, STAT3 signaling pathway was involved in the THC-induced suppression of trophoblast cell motility and pregnancy outcomes.
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.
Several psychoactive drugs are known to influence episodic memory. However, these drugs' effects on false memory, or the tendency to incorrectly remember nonstudied information, remain poorly understood.
Across participants, both drugs' effects on true memory were positively correlated with their effects on false memory. 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. Hourly intake and meal pattern data were recorded and analyzed using one-way analyses of variance followed by Bonferroni post-hoc tests.
The cannabis extract significantly increased food intake during the first hour of testing at 4. Meal size and duration were unaffected. 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. Delta 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 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. A reasonable option for some patients with multiple sclerosis. Conventional drugs have only a limited impact on spasticity associated with multiple sclerosis and are rarely satisfactory.
A solution for oral transmucosal delivery spray containing a mixture of cannabis extracts 2. Bhang Fresh leaves and stalk Mixed with food items and consumed orally 3.
Open in a separate window. Chemical Components of Cannabis The cannabis plant contains more than chemicals of which 61 are cannabinoids 9 , 10 Figure 1.
Table 2 Cannabinoids and their Properties Behavioral and Physiological Effects of Cannabis Cannabis is known to have behavioral and physiological effects 27 — Cannabis Dependence and Tolerance Cannabinoids appear to affect the same reward systems as alcohol, cocaine and opioids Psychiatric Conditions Associated with Cannabis Abuse In addition to producing dependence, cannabis use is associated with a wide range of psychiatric disorders Detection and Analysis of Cannabinoids by Different Analytical Techniques Measurement of cannabinoids is necessary for pharmacokinetic studies, drug treatment, workplace drug testing and drug impaired driving investigations Interactions of Cannabis with other Drugs of Abuse Interaction of chronic marijuana with other drugs of abuse has not been studied in detail.
Effects of Indirect Cannabis Exposure There can be indirect exposure to cannabis through passive smoking. Conclusions The recreational use of cannabis among youth has increased worldwide over the past few decades. Conflict of interest All the authors declare that they have no conflicts of interest.
Contributors PS conducted the literature searches and wrote the first draft of the manuscript. First identification of drugs in Egyptian mummies. The toxicology of cannabis and cannabis prohibition. Raharjo TJ, Verpoorte R. Methods for the analysis of cannabinoids in biological materials: Hazekamp A, Grotenhermen F.
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Cambridge university press; Chiarotti M, Costamagna L. Detection time of drugs of abuse in urine. Forensic aspects of the metabolism and excretion of cannabinoids following oral ingestion of cannabis resin. Binding of deltatetrahydrocannabinol to human plasma proteins. Do plasma concentrations of delta 9-tetrahydrocannabinol reflect the degree of intoxication? Metabolism and disposition of deltatetrahydrocannabinol in man.
Implications of plasma Delta9-tetrahydrocannabinol, hydroxy-THC, and norcarboxy-THC concentrations in chronic cannabis smokers. Kogan NM, Mechoulam R. Cannabinoids in health and disease. The pharmacological activity of the fatty acid conjugate palmitoyloxy-delta 9-tetrahydrocannabinol.
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Case study of 52 patients in a "low-step" detoxification ward. Extended urinary Delta9-tetrahydrocannabinol excretion in chronic cannabis users precludes use as a biomarker of new drug exposure.
Deltatetrahydrocannabinol pharmacokinetics] Ann Pharm Fr. Further urinary metabolites of delta 1-tetrahydrocannabinol in man. Urinary excretion half-life of norcarboxy-delta9-tetrahydrocannabinol in humans.
Kelly P, Jones RT. Metabolism of tetrahydrocannabinol in frequent and infrequent marijuana users. Urinary elimination half-life of deltatetrahydrocannabinoloic acid in heavy marijuana users after smoking. Temporal indication of marijuana use can be estimated from plasma and urine concentrations of delta9-tetrahydrocannabinol, hydroxy-delta9-tetrahydrocannabinol, and nor-delta9-tetrahydrocannabinolcarboxylic acid.
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Two studies of extreme cannabis smoke exposure in a motor vehicle. Presence of delta9-tetrahydrocannabinol in human milk. N Engl J Med. Cannabinoids and gene expression during brain development.
Breastfeeding and the use of recreational drugs--alcohol, caffeine, nicotine and marijuana. Support Center Support Center.
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Aug 20, Tetrahydrocannabinolic acid (THCA) is a non-psychoactive cannabinoid and a primary constituent of cured and live cannabis. THCA is the. +. Add To Bag. Compare. SKU: N/A Category: Tincture. Description; Additional information; Reviews (0). THCA Delayed-Release Capsules CBD/THCA. Have you tried THCA Delayed Release Capsules from Abatin Wellness Center? Submit a review and share your experience.