Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cannabinoids”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources
PubMed1998

Cannabinoid receptor-mediated inhibition of the rat tail-flick reflex after microinjection into the rostral ventromedial medulla.

Systemic administration of cannabinoids produce profound antinociception in rodents. The purpose of this study was to examine the contribution of the rostral ventromedial medulla (RVM) to cannabinoid-mediated inhibition of the tail-flick reflex. Rats received direct injections of two selective cannabinoid agonists, WIN55,212-2 and HU210, into the RVM. Both compounds significantly elevated tail-flick latencies by over 50%. WIN55,212-3, the inactive enantiomer, was without effect. Furthermore, co-administration of the selective cannabinoid receptor antagonist, SR141716A greatly attenuated the antinociception produced by HU210. Finally, injections of WIN55,212-2 outside the region of the RVM did not affect tail-flick latencies. These results demonstrate that the cannabinoid receptor system participates in the descending control of nociception and raise the possibility that actions of endogenous cannabinoids in the RVM may modulate nociceptive responsiveness.

Analgesics↗
PubMed2003

The rodent amygdala contributes to the production of cannabinoid-induced antinociception.

The amygdala is a temporal lobe region that is implicated in emotional information processing. The amygdala also is associated with the processing and modulation of pain sensation. Recently, we demonstrated that in nonhuman primates, the amygdala is necessary for the full expression of cannabinoid-induced antinociception [J Neurosci 21 (2001) 8238]. The antinociceptive effect of the cannabinoid receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo(1,2,3-de)-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone (WIN55,212-2) was significantly reduced in rhesus monkeys with large bilateral lesions of the amygdaloid complex. In the present study, we investigated the contribution of the amygdala to cannabinoid-induced antinociception in the rat. Using bilateral local microinjections of the GABA(A) receptor agonist muscimol, we inactivated neurons originating from the central nucleus of the amygdala (CeA) or basolateral nucleus of the amygdala (BLA). In rats injected with intra-CeA saline, the cannabinoid receptor agonist WIN55,212-2 produced dose-dependent antinociception on the noxious heat-evoked tail flick assay. In rats treated with intra-CeA muscimol, however, the antinociceptive effect of WIN55,212-2 was significantly reduced. Rats treated with intra-BLA muscimol showed no deficit in WIN55,212-2-induced antinociception. The effect of CeA inactivation on WIN55,212-2-induced suppression of prolonged pain in the formalin test also was tested. In rats treated with intra-CeA saline, WIN55,212-2 reduced the incidence of formalin-induced nociceptive behaviors and also reduced formalin-evoked c-fos expression in both superficial and deep laminae of the spinal cord dorsal horn. In rats treated with intra-CeA muscimol, however, these effects of WIN55,212-2 were significantly reduced. The results constitute the first causal data demonstrating the necessity of descending pain-modulatory circuitry (of which the CeA is a component) for the full expression of cannabinoid-induced antinociception in the rat. Furthermore, the results complement previous findings suggesting an overlap in neural circuitry activated by opioids and cannabinoids.

Amygdala↗
PubMed1999

Cannabinoid receptor binding and mRNA levels in several brain regions of adult male and female rats perinatally exposed to delta9-tetrahydrocannabinol.

The present study was designed to elucidate whether perinatal delta9-tetrahydrocannabinol (delta9-THC) exposure results in changes in cannabinoid receptor binding and mRNA levels in adulthood. Most of the brain areas studied, including the basal ganglia, the cerebellum, the limbic structures, and most of the hippocampal regions exhibited no changes in cannabinoid receptor binding and mRNA levels in adulthood as a consequence of the perinatal delta9-THC exposure. However, some subtle changes could be appreciated in specific regions, although their physiological relevance seems uncertain. For example, delta9-THC-exposed males exhibited a small decrease in binding in the superficial layer of the cerebral cortex, an effect that was not seen in delta9-THC-exposed females and in mRNA levels for both males and females. In the CA2 layer of the Ammon's horn, there was an increase in mRNA levels of delta9-THC-exposed animals, although this was statistically significant only in males. However, the more marked and probably relevant changes were seen in the arcuate nucleus, where delta9-THC-exposed males exhibited an increase in binding, whereas this tended to decrease in delta9-THC-exposed females. In an additional experiment, we analyzed the motor response of these animals to a challenge with SR141716, a specific antagonist for cannabinoid receptors. The delta9-THC-exposed animals tended to show a higher response to SR141716 challenge, with changes apparently more marked in delta9-THC-exposed females, although they did not reach statistical significance. In summary, perinatal cannabinoid exposure does not appear to significantly alter cannabinoid receptor binding and mRNA expression in the brain of adult rats, as well as the motor response caused by the blockade of these receptors with a specific antagonist. There were some changes in the status of cannabinoid receptors but they were very small and, hence, of debatable physiological relevance. The most significant of these effects was the increase in binding observed in the arcuate nucleus of delta9-THC-exposed males.

Animals↗
PubMed2000

Synthesis and pharmacology of a hybrid cannabinoid.

A pentacyclic hybrid cannabinoid (4) has been synthesized, which combines structural elements of traditional cannabinoids and cannabmimetic indoles. Cannabinoid 4 contains a 1-pentylindole structure fused to the 2,3-positions of the partially reduced hydroxydibenzopyran system of THC. The successful approach to 4 employed 9-benzoyl-5,7-dimethoxy-1,2,3,4-tetrahydrocarbazole (17) as the starting material. Dehydrogenation to carbazole 18, followed by demethylation and condensation with trans-p-menthadienol gave N-benzoyl hybrid cannabinoid 22, N-alkylation of which afforded target cannabinoid 4. The hybrid cannabinoid had affinity for the CB1 receptor approximately equal to that of delta8-THC (Ki = 19.3+/-3 nM), and shows comparable potency in vivo.

Animals↗
PubMed1998

Determination of cannabinoids in water and human saliva by solid-phase microextraction and quadrupole ion trap gas chromatography/mass spectrometry.

Solid-phase microextraction (SPME) is applied to the determination of cannabidiol, delta 8-tetrahydrocannabinol (delta 8-THC), delta 9-tetrahydrocannabinol (delta 9-THC), and cannabinol in pure water and human saliva. The inherent extraction behavior of the cannabinoids in pure water is evaluated along with optimization of the method in human saliva. The commercially available poly(dimethylsiloxane) (PDMS) SPME fibers were found to be the best class for the cannabinoid analysis. Partition coefficients were found to be extremely large for all of the cannabinoids (log K > 4.0). Equilibrium times for the 7- and 30-micron PDMS fibers were 50 and 240 min, respectively. A shorter extraction time of 10 min with the 30-micron PDMS fiber may be used for multiple extractions from the same vial, thus conserving the sample necessary for analysis and speeding up the total analysis time. Recoveries for the cannabinoids in saliva, relative to pure water, were dramatically improved by a method developed in our laboratory involving addition of glacial acetic acid to the sample vial prior to performing SPME. Using this method, recoveries relative to SPME in pure water ranged from 21 to 47% depending on the cannabinoid. The linear range for spiked saliva samples was established at 5-500 ng/mL (r2 > 0.994) with precisions between 11 and 20% RSD. The ultimate level of detection by SPME for the cannabinoids in saliva was 1.0 ng/mL, with signal-to-noise values of > or = 12. A saliva sample collected 30 min after marijuana smoking was subject to SPME and traditional liquid-liquid extraction analysis. Internal standard quantitation results for delta 9-THC by both methods yielded comparable results, indicating that the SPME method of analysis is highly accurate and precise. The level of delta 9-THC by SPME was found to be 9.54 ng/mL for the saliva sample.

Cannabinoids↗
PubMed1989

The importance of the orientation of the C9 substituent to cannabinoid activity.

We have found a correlation between cannabinoid psychopharmacological activity and the orientation of the C9 substituent in one class of cannabinoid derivatives. We report here a study of the active cannabinoids delta 9-tetra-hydrocannabinol (delta 9-THC), delta 8-tetrahydrocannabinol (delta 8-THC), and 11 beta-hexahydrocannabinol (11 beta-HHC); the minimally active cannabinoid 11 alpha-hexahydrocannabinol (11 alpha-HHC); and the inactive cannabinoids delta 7-tetrahydrocannabinol (delta 7-THC) and delta 9,11-tetrahydrocannabinol (delta 9,11-THC). Our working hypothesis is that there are two components of cannabinoid structure which confer upon these compounds reactivity characteristics crucial to activity: the directionality of the lone pairs of electrons of the phenyl group hydroxyl oxygen and the orientation of the carbocyclic ring relative to this oxygen. The structures of these six molecules were optimized by using the method of molecular mechanics as encoded in the MMP2(85) program. Other possible minimum-energy conformations of the carbocyclic ring were calculated by driving one torsion angle in this ring by use of the dihedral driver option in MMP2(85). The rotational energy behavior of the phenyl group hydroxyl in each molecule was studied also by using the dihedral driver option in MMP2(85). We found that the carbocyclic ring in 11 alpha-HHC can exist in either a chair or a twist conformation. The carbocyclic ring in delta 9-THC, in delta 8-THC, and in delta 7-THC was found to exist only in a half-chair conformation, while the carbocyclic ring in 11 beta-HHC and in delta 9,11-THC was found to exist only in a chair form. The results of the rotational energy profiles indicated that the minimum-energy positions of the phenyl group hydroxyls are nearly identical in all molecules. These molecules, then, were found to differ only in the conformation of the carbocyclic ring in each. This conformation, in turn, determines the orientation of this ring and its C9 substituent relative to the oxygen of the phenyl group hydroxyl. In order to assess the orientation of the carbocyclic ring with respect to the phenyl group hydroxyl oxygen in each optimized structure, the following nonbonded torsion angles were measured: C10-C10a-C1-O, C8-C7-C1-O, C11-C9-C1-O, and C9-Q-C1-O (where Q is a dummy atom placed midway between C8 and C10).(ABSTRACT TRUNCATED AT 400 WORDS)

Cannabinoids↗
PubMed1997

Effects of cannabinoid receptor ligands on electrophysiological properties of myenteric neurones of the guinea-pig ileum.

1. The effect of cannabinoid receptor agonists was studied in guinea-pig myenteric neurones in vitro by use of conventional intracellular recording techniques. 2. Exposure of myenteric neurones of the S-cell type to the cannabinoid receptor agonists WIN 55,212-2 (100 nM) and CP 55,940 (100 nM) reversibly and significantly depressed the amplitude of fast excitatory synaptic potentials (fast e.p.s.ps) by 46% and 37%, respectively. 3. The depressant effect of WIN 55,212-2 and CP 55,940 on fast e.p.s.p. amplitude (expressed as the area above the amplitude-time curve (mVs)) was significantly greater than that of the vehicle, Tween 80, which had no detectable effect. 4. The inhibitory effect of WIN 55,212-2 appeared to be concentration-dependent over the range 1-100 nM. WIN 55,212-3, its (-)-enantiomer (100 nM), was inactive. 5. The cannabinoid CB1 receptor antagonist, SR141716A (1 microM), reversed the inhibitory effects of WIN 55,212-2 on fast e.p.s.ps in 38% of neurones tested (3/8) and acetylcholine (ACh)-induced depolarizations in 42% of neurones tested (5/12). 6. When tested on its own, SR141716A (1 microM) caused a 40-50% reduction in the amplitude of fast e.p.s.ps (n = 9). 7. WIN 55,212-2 reversibly depressed the amplitude of the slow e.p.s.p. and, in 2 out of 7 neurones, this effect was reversed by SR141716A (1 microM). 8. It is concluded that cannabinoid-induced inhibition of fast cholinergic synaptic transmission occurred by reversible activation of both presynaptic and postsynaptic CB1 receptors and that slow excitatory synaptic transmission can also be reversibly depressed by cannabinoids. Furthermore, it would seem that subpopulations of myenteric S-neurones and their synapsing cholinergic and non-cholinergic, non-adrenergic terminals are not endowed with cannabinoid receptors.

Acetylcholine↗
PubMed1998

Comparison of cannabinoid binding sites in guinea-pig forebrain and small intestine.

We have investigated the nature of cannabinoid receptors in guinea-pig small intestine by establishing whether this tissue contains cannabinoid receptors with similar binding properties to those of brain CB1 receptors. The cannabinoids used were the CB1-selective antagonist SR141716A, the CB2-selective antagonist SR144528, the novel cannabinoid receptor ligand, 6'-azidohex-2'-yne-delta8-tetrahydrocannabinol (O-1184), and the agonists CP55940, which binds equally well to CB1 and CB2 receptors, and WIN55212-2, which shows marginal CB2 selectivity. [3H]-CP55940 (1 nM) underwent extensive specific binding both to forebrain membranes (76.3%) and to membranes obtained by sucrose density gradient fractionation of homogenates of myenteric plexus-longitudinal muscle of guinea-pig small intestine (65.2%). Its binding capacity (Bmax) was higher in forebrain (4281 fmol mg(-1)) than in intestinal membranes (2092 fmol mg(-1)). However, the corresponding KD values were not significantly different from each other (2.29 and 1.75 nM respectively). Nor did the Ki values for its displacement by CP55940, WIN55212-2, O-1184, SR141716A and SR144528 from forebrain membranes (0.87, 4.15, 2.85, 5.32 and 371.9 respectively) differ significantly from the corresponding Ki values determined in experiments with intestinal membranes (0.99, 5.03, 3.16, 4.95 and 361.5 nM respectively). The Bmax values of [3H]-CP55940 and [3H]-SR141716A in forebrain membranes did not differ significantly from each other (4281 and 5658 fmol mg(-1)) but were both greater than the Bmax of [3H]-WIN55212-2 (2032 fmol mg(-1)). O-1184 (10 or 100 nM) produced parallel dextral shifts in the log concentration-response curves of WIN55212-2 and CP55940 for inhibition of electrically-evoked contractions of the myenteric plexus-longitudinal muscle preparation, its KD values being 0.20 nM (against WIN55212-2) and 0.89 nM (against CP55940). We conclude that cannabinoid binding sites in guinea-pig small intestine closely resemble CB1 binding sites of guinea-pig brain and that 0-1184 behaves as a cannabinoid receptor antagonist in the guinea-pig myenteric plexus-longitudinal muscle preparation.

Analgesics↗
PubMed1999

Effects of the endogeneous cannabinoid, anandamide, on neuronal activity in rat hippocampal slices.

1. The arachidonic acid derivative arachidonylethanolamide (anandamide) is an endogeneous ligand of cannabinoid receptors that induces pharmacological actions similar to those of cannabinoids such as delta9-tetrahydrocannabinol (THC). We examined whether anandamide can influence excessive neuronal activity by investigating stimulation-induced population spikes and epileptiform activity in rat hippocampal slices. For this purpose, the effects of anandamide were compared with those of the synthetic cannabinoid agonist WIN 55,212-2 and its inactive S(-)-enantiomer WIN 55,212-3. 2. Both anandamide (1 and 10 microM) and WIN 55,212-2 (0.1 and 1 microM) decreased the amplitude of the postsynaptic population spike and the slope of the field excitatory postsynaptic potential (field e.p.s.p.) without affecting the presynaptic fibre spike of the afferents. At a concentration of 1 microM, WIN 55,212-2 completely suppressed the postsynaptic spike, whereas the S(-)-enantiomer WIN 55,212-3 produced only a slight depression. The CB1 receptor antagonist SR 141716 blocked the inhibition evoked by the cannabinoids. SR 141716 had a slight facilitatory effect on neuronal excitability by itself. 3. Anandamide shifted the input-output curve of the postsynaptic spike and the field e.p.s.p. to the right and increased the magnitude of paired-pulse facilitation indicating a presynaptic mechanism of action. 4. Anandamide and WIN 55,212-2, but not WIN 55,212-3, attenuated both stimulus-triggered epileptiform activity in CA1 elicited by omission of Mg2+ and spontaneously occurring epileptiform activity in CA3 elicited by omission of Mg2+ and elevation of K+ to 8 mM. The antiepileptiform effect of these cannabinoids was blocked by SR 141716. 5. In conclusion, cannabinoid receptors of the CB1 type as well as their endogeneous ligand, anandamide, are involved in the control of neuronal excitability, thus reducing excitatory neurotransmission at a presynaptic site, a mechanism which might be involved in the prevention of excessive excitability leading to epileptiform activity.

Animals↗
PubMed2006

Cannabinoid agonists induce relaxation in the bovine ophthalmic artery: evidences for CB1 receptors, nitric oxide and potassium channels.

Glaucoma pathophysiology appears to involve vascular deficits, which may contribute to initiation and progression of the disease. Anandamide, the endogenous cannabinoid ligand, and WIN55212-2, a synthetic cannabinoid agonist, are able to evoke concentration-dependent relaxations in bovine ophthalmic artery rings, precontracted with 5-hydroxytryptamine (5-HT) (1 microM). Endothelium removal reduces cannabinoid agonist potency and efficacy. The selective cannabinoid 1 (CB1) receptor antagonists SR141716A (100 nM) and AM251 (100 nM) cause a shift to the right in the concentration-response curves to anandamide and WIN55212-2 in arterial rings both in the presence and in the absence of endothelium. In endothelium-intact arteries, the nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA, 300 microM), completely blocked the anandamide- and WIN55212-2-relaxant responses; by contrast, the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP, 100 microM) induced an increase in vasorelaxant responses to cannabinoid agonists. Relaxations to anandamide and WIN55212-2 were inhibited by iberiotoxin (IbTX, 200 nM), a blocker of large conductance, Ca2+-activated K+ channel (BK(Ca)), and by 4-aminopyridine (4-AP; 1 mM), a blocker of delayed rectifier K+ channel, whereas the blockade of K(ATP) channels by glibenclamide (5 microM) and of small conductance Ca2+-activated K+ channels (SK(Ca)) by apamin (100 nM) did not produce any effects. These data suggest that anandamide and WIN55212-2 relax the bovine ophthalmic artery by involving CB1 the cannabinoid receptor-sensitive pathway. In endothelium-intact arteries, relaxation occurs through activation of nitric oxide synthase cyclic GMP and Ca2+-activated K+ channels. They also cause endothelium-independent relaxation by involving potassium channel opening.

Animals↗
PubMed2006

mu opioid and CB1 cannabinoid receptor interactions: reciprocal inhibition of receptor signaling and neuritogenesis.

Several studies have described functional interactions between opioid and cannabinoid receptors; the underlying mechanism(s) have not been well explored. One possible mechanism is direct receptor-receptor interactions, as has been demonstrated for a number of G-protein-coupled receptors. In order to investigate interactions between opioid and cannabinoid receptors, we epitope tagged mu, delta and kappa opioid receptors with Renilla luciferase and CB1 cannabinoid or CCR5 chemokine receptors with yellow fluorescent protein and examined the extent of substrate hydrolysis induced bioluminescence resonance energy transfer (BRET) signal. We find that coexpression of opioid receptors with cannabinoid receptors, but not with chemokine receptors, leads to a significant increase in the level of BRET signal, suggesting that the opioid-cannabinoid interactions are receptor specific. In order to examine the implications of these interactions to signaling, we used GTPgammaS binding and mitogen-activated protein kinase (MAPK) phosphorylation assays and examined the effect of receptor activation on signaling. We find that the mu receptor-mediated signaling is attenuated by the CB1 receptor agonist; this effect is reciprocal and is seen in heterologous cells and endogenous tissue expressing both receptors. In order to explore the physiological consequences of this interaction, we examined the effect of receptor activation on the extent of Src and STAT3 phosphorylation and neuritogenesis in Neuro-2A cells. We find that the simultaneous activation of mu opioid and CB1 cannabinoid receptors leads to a significant attenuation of the response seen upon activation of individual receptors, implicating a role for receptor-receptor interactions in modulating neuritogenesis.

Cells, Cultured↗
PubMed1999

Pain modulation by release of the endogenous cannabinoid anandamide.

Synthetic cannabinoids produce behavioral analgesia and suppress pain neurotransmission, raising the possibility that endogenous cannabinoids serve naturally to modulate pain. Here, the development of a sensitive method for measuring cannabinoids by atmospheric pressure-chemical ionization mass spectrometry permitted measurement of the release of the endogenous cannabinoid anandamide in the periaqueductal gray (PAG) by in vivo microdialysis in the rat. Electrical stimulation of the dorsal and lateral PAG produced CB1 cannabinoid receptor-mediated analgesia accompanied by a marked increase in the release of anandamide in the PAG, suggesting that endogenous anandamide mediates the behavioral analgesia. Furthermore, pain triggered by subcutaneous injections of the chemical irritant formalin substantially increased the release of anandamide in the PAG. These findings indicate that the endogenous cannabinoid anandamide plays an important role in a cannabinergic pain-suppression system existing within the dorsal and lateral PAG. The existence of a cannabinergic pain-modulatory system may have relevance for the treatment of pain, particularly in instances where opiates are ineffective.

Analgesia↗
PubMed1995

Stimulation of cannabinoid receptor CB1 induces krox-24 expression in human astrocytoma cells.

The recent isolation and cloning of the G protein-coupled central cannabinoid receptor (CB1) from brain tissue has provided a molecular basis to elucidate how cannabinoid compounds may mediate their psychoactive effects. Here we report the high expression of cannabinoid receptors in human astrocytoma tumors of different grades, in the astrocytoma cell lines U373 MG and GL-15, as well as in normal astrocytes. From an analysis of the coupling mechanisms of functional CB1 receptors in U373 MG, we show that, in addition to the inhibition of adenylyl cyclase, activation by the cannabinoid agonist CP-55940 induces the expression of the immediate-early gene krox-24, also known as NGFI-A, zif/268, egr-1, and TIS8. The amount of Krox-24 protein and the level of Krox-24 DNA binding activity, as measured by Western blot and electrophoretic mobility shift assay, respectively, were also increased by the addition of CP-55940. These effects were blocked by incubation with pertussis toxin but not by treatment with hydrolysis-resistant cAMP analogues, suggesting that the transduction pathway between the cannabinoid receptor and krox-24 involves a pertussis toxin-sensitive GTP-binding protein and is independent of cAMP metabolism. The specific involvement of CB1 in Krox-24 induction was demonstrated in Chinese hamster ovary cells transfected with the human CB1 receptor and also in experiments using the CB1-selective cannabinoid antagonist SR 141716A.

Animals↗
PubMed1996

(-)-Delta9-tetrahydrocannabinol antagonizes the peripheral cannabinoid receptor-mediated inhibition of adenylyl cyclase.

(-)-Delta9-Tetrahydrocannabinol ((-)-Delta9-THC) is the major active psychotropic component of the marijuana plant, Cannabis sativa. The membrane proteins that have been found to bind this material or its derivatives have been called the cannabinoid receptors. Two GTP-binding protein-coupled cannabinoid receptors have been cloned. CB1 or the neuronal cannabinoid receptor is found mostly in neuronal cells and tissues while CB2 or the peripheral cannabinoid receptor has been detected in spleen and in several cells of the immune system. It has previously been shown that activation of CB1 or CB2 receptors by cannabinoid agonists inhibits adenylyl cyclase activity. Utilizing Chinese hamster ovary cells and COS cells transfected with the cannabinoid receptors we report that (-)-Delta9-THC binds to both receptors with similar affinity. However, in contrast to its capacity to serve as an agonist for the CB1 receptor, (-)-Delta9-THC was only able to induce a very slight inhibition of adenylyl cyclase at the CB2 receptor. Morever, (-)-Delta9-THC antagonizes the agonist-induced inhibition of adenylyl cyclase mediated by CB2. Therefore, we conclude that (-)-Delta9-THC constitutes a weak antagonist for the CB2 receptor.

Adenylyl Cyclase Inhibitors↗
PubMedDate not supplied

Chronic ethanol consumption regulates cannabinoid CB1 receptor gene expression in selected regions of rat brain.

AIMS: The aim of this study was to examine the effects of chronic ethanol consumption in cannabinoid CB(1) receptor gene expression in Wistar rats. METHODS: Rats were exposed to a bottle containing a solution of ethanol (10% v/v) and saccharin (0.25% w/v) for 52 days. At the end of this period, rats were killed by decapitation and cannabinoid CB(1) receptor gene expression was measured by in situ hybridization histochemistry. RESULTS: Our results indicated that chronic ethanol consumption reduced cannabinoid CB(1) receptor gene expression in caudate-putamen (CPu) (24%), ventromedial nucleus of the hypothalamus (VMN) (43%), CA1 (27%) and CA2 (22%) fields of hippocampus and increased dentate gyrus (DG) (30%). CONCLUSIONS: These results reveal for the first time that prolonged exposure to ethanol produces marked alterations in cannabinoid CB(1) receptor gene expression in selected regions of the rat brain, supporting an interaction between ethanol consumption and the endogenous cannabinoid receptor. Furthermore, these findings suggest that cannabinoid CB(1) receptor may be considered as a new pharmacological target for treating ethanol dependence.

Alcohol Drinking↗
PubMedDate not supplied

Evaluation of the CEDIA DAU assays and the AxSym system for the analysis of cannabinoids in whole blood.

The Microgenics CEDIA DAU (EIA) and the Abbott AxSym system (FPIA) cannabinoids assays were evaluated for their combined effectiveness in the analysis of cannabinoids in whole blood. Blood samples were treated with acetone, evaporated, and reconstituted, and the supernatant was analyzed by the EIA cannabinoids assay. Blood samples determined positive by EIA were then treated with acetonitrile and sodium sulfate, and the resultant protein-free supernatant was analyzed using the FPIA cannabinoids assay. A total of 98 blood samples determined to be presumptively positive by both EIA and FPIA were further analyzed for the presence of 11-nor-carboxy-delta9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH). All 98 blood samples could be confirmed for the presence of THCCOOH by gas chromatography-mass spectrometry (GC-MS) at concentrations greater than the 10 ng/mL cutoff. The GC-MS results were found to correlate significantly better with those of the FPIA cannabinoids assay (r = 0.75) than with EIA (r = 0.22). Procedures for the rapid analysis of whole blood for cannabinoids using CEDIA DAU reagents and the AxSym system are presented.

Acetone↗
PubMedDate not supplied

Determination of the distribution of cannabinoids in cannabis resin using high performance liquid chromatography.

A high performance liquid chromatographic system is described for the separation of cannabinoids, which were detected by ultra-violet absorption at 220 nm. The identity of the cannabinoids was established by comparison of retention times with reference compounds, by simple chemical conversions to other known cannabinoids, and by mass spectrometry after isolation by preparative chromatography. Cannabis resin from Pakistan and Lebanon was examined for the presence of these cannabinoids. A study of the uniformity of distribution of cannabinoids in individual resin slabs was made by taking a total of 68 samples from 4 different slabs. The variations in cannabinoid content between slabs was measured by 85 different slabs. The validity of these measurements, to determine a common origin of resin for forensic purposes, was tested using resin obtained from 94 different law enforcement seizures.

Cannabinoids↗
PubMed1999

Elevated endogenous cannabinoids in schizophrenia.

Evidence suggests that cannabinoid receptors, the pharmacologcial target of cannabis-derived drugs, and their accompanying system of endogenous activators may be dysfunctional in schizophrenia. To test this hypothesis, we examined whether endogenous cannabinoid concentrations in cerebrospinal fluid of schizophrenic patients are altered compared to nonschizophrenic controls. Endogenous cannabinoids were purified from cerebrospinal fluid of 10 patients with schizophrenia and 11 non-schizophrenic controls by high-performance liquid chromatography, and quantified by isotope dilution gas-chromatography/mass-spectrometry. Cerebrospinal concentrations of two endogenous cannabinoids (anandamide and palmitylethanolamide) were significantly higher in schizophrenic patients than non-schizophrenic controls (p < 0.05). By contrast, levels of 2-arachidonylglycerol, another endogenous cannabinoid lipid, were below detection in both groups. The findings did not seem attributable to gender, age or medication. Elevated anandamide and palmitylethanolamide levels in cerebrospinal fluid of schizophrenic patients may reflect an imbalance in endogenous cannabinoid signaling, which may contribute to the pathogenesis of schizophrenia.

Adult↗