Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cannabinol”

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 37 records · Page 2Linked to original sources
PubMed1975

Clinical pharmacology of nabilone, a cannabinol derivative.

Nabilone is a modified cannabinol derivative with central nervous system activity. Administration of nabilone in single doses of 1 to 5 mg results in dose-related pharmacologic effects in man. One and 2.5 mg doses of nabilone induced relaxant and sedative effects in all subjects. No euphoria, dry mouth, tachycardia, or postural hypotension was seen after 1 mg, minimal effects were seen after 2.5 mg, and marked effects were seen after 5 mg. Effects were evident within 60 to 90 min and persisted for 8 to 12 hr. Nabilone produced no significant tachycardia. There were no changes in supine blood pressure; however, marked postural hypotension occurred after the 5-mg dose. The administration of nabilone at doses of 1 mg or 2 mg two times daily resulted in euphoria and dry mouth during the first two days of drug; thereafter tolerance developed to these effects but there was no apparent decrease in relaxation. Subjects challenged with a single 5-mg dose of nabilone showed a 66% reduction in symptoms and signs after the 7-day drug period compared to that of the same dose after 1 wk of placebo. Comparison of nabilone with other cannabinol derivatives suggests that some of the undesirable pharmacologic effects can be separated within the group.

Adult↗
PubMedDate not supplied

Cardiovascular effects of cannabinol during oral surgery.

Fifty-five clinical trials were conducted to determine the cardiovascular combined effects of stressful oral surgery and systemic cannabinols. In a first study, delta9-tetrahydrocannabinol (THC) was given IV as a premedicant and compared with diazepam and with a placebo. A classic dose-related tachycardia followed THC injection. The peak heart rate response of patients premedicated with 0.044 mg/kg THC was 24.1% higher (p less than 0.05) than the peak effect for a nonsurgerized control group, suggesting a synergistic effect between THC and surgical stress. A predisposition to syncopal hypotension followed THC premedication, and antiarrhythmic effects were observed after large doses. The injection of local anesthetic preparations containing epinephrine did not alter THC cardiovascular response. An apparent drug interaction was observed, however, in a second study, in patients given general anesthesia within 72 hours after smoking marijuana. These patients demonstrated sustained abnormal postoperative tachycardia when compared with control nonsmokers, an effect which may have resulted from an interaction between stored cannabinol metabolites and atropine administered as part of the anesthetic technic. It was concluded that THC had no particular advantage over diazepam or placebo as a premedicant. Further, THC altered the patients' adaptivity to stress and interacted undesirably with other anesthetic medications.

Adult↗
PubMed1975

Plasma cannabinoids measured by radioimmunoassay in rabbits after intravenous injection of tetrahydrocannibinol, 11-hydroxy-tetrahydrocannabinol, cannabinol and cannabidiol.

An antiserum raised in sheep against a conjugate of tetrahydrocannabinol with bovine serum albumin has been used as the basis of a radioimmunoassay for cannabinoids in the blood of rabbits given tetrahydrocannabinol, 11-hydroxy-tetrahydrocannabinol, cannabinol or cannabidiol by rapid intravenous injection. In the case of both 11-hydroxy-tetrahydrocannabinol and cannabinol plasma cannabinoid concentrations fell exponentially from an initial peak plasma level attained immediately after the completion of intravascular distribution of the injected bolus. In the case of tetrahydrocannabinol itself, however, there was a progressive rise in plasma cannabinoid concentration between five and fifteen minutes after the rapid intravenous injection. The reasons for this rise in plasma cannabinoid concentration are discussed.

Animals↗
PubMed1977

Synthesis and characterization of glucuronides of Cannabinol, cannabidiol, delta9-tetrahydrocannabinol and delta8-tetrahydrocannabinol.

Partially purified glucuronyltransferase immobilized on beaded sepharose has been used to synthesize the glucuronide conjugates of cannabinol, cannabidol, delta9-tetrahydrocannabinol and delta8-tetrahydrocannabinol. Trimethylsilylated methyl esters and per(trimethylsilyl) derivatives of these conjugates have been characterized by their gas chromatographic retention times and their electron impact and ammonia chemical ionization mass spectra.

Cannabidiol↗
PubMed1987

Single-dose kinetics of deuterium-labelled cannabinol in man after intravenous administration and smoking.

The single dose pharmacokinetics of deuterium-labelled cannabinol (2H2-CBN) were evaluated in six male cannabis users with different degree of abuse after smoking an average dose of 19 mg and after intravenous administration of 20 mg CBN. Plasma levels were measured for up to 72 h with selected ion monitoring by GC/MS using 2H7-CBN as internal standard. The systemic availability of smoked CBN was found to be 39 +/- 26% (min-max 6-65%). The mean plasma clearance was 19.1 +/- 2.6 ml min-1 kg-1 and the volume of distribution was determined to 50 +/- 23 l kg-1. The apparent terminal half lives for CBN were 32 +/- 17 h and 43 +/- 29 h after intravenous administration and smoking, respectively.

Adult↗
PubMed2000

AP-1 activity is negatively regulated by cannabinol through inhibition of its protein components, c-fos and c-jun.

Regulation of the activator protein-1 (AP-1) complex is very intricate because it involves phosphorylation state, protein-protein, and protein-DNA interactions. In these studies, the regulation of AP-1 activity, with emphasis on c-fos and c-jun regulation, was investigated using cannabinol (CBN) in primary mouse splenocytes in vitro. Cannabinoid compounds exhibit immunosuppressive actions that are putatively mediated through Gi-protein coupled receptors that negatively regulate adenylate cyclase. However, recent studies suggest that cannabinoids modulate other signaling cascades. Indeed, we demonstrate that CBN inhibited binding to AP-1-containing sites from the interleukin-2 promoter. This inhibition of binding was, in part, due to decreased nuclear expression of c-fos and c-jun. We further determined that the effects of CBN were due to posttranslational modifications of these phosphoproteins and showed that CBN inhibited the activation of ERK MAP kinases. Thus, cannabinoid-induced immunosuppression involves disruption of the ERK signaling cascade.

Animals↗
PubMed2005

Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol.

Increasing interest in the biology, chemistry, pharmacology, and toxicology of cannabinoids and in the development of cannabinoid medications necessitates an understanding of cannabinoid pharmacokinetics and disposition into biological fluids and tissues. A drug's pharmacokinetics determines the onset, magnitude, and duration of its pharmacodynamic effects. This review of cannabinoid pharmacokinetics encompasses absorption following diverse routes of administration and from different drug formulations, distribution of analytes throughout the body, metabolism by different tissues and organs, elimination from the body in the feces, urine, sweat, oral fluid, and hair, and how these processes change over time. Cannabinoid pharmacokinetic research has been especially challenging due to low analyte concentrations, rapid and extensive metabolism, and physicochemical characteristics that hinder the separation of drugs of interest from biological matrices--and from each other--and lower drug recovery due to adsorption of compounds of interest to multiple surfaces. delta9-Tetrahydrocannabinol, the primary psychoactive component of Cannabis sativa, and its metabolites 11-hydroxy-delta9-tetrahydrocannabinol and 11-nor-9-carboxy-tetrahydrocannabinol are the focus of this chapter, although cannabidiol and cannabinol, two other cannabinoids with an interesting array of activities, will also be reviewed. Additional material will be presented on the interpretation of cannabinoid concentrations in human biological tissues and fluids following controlled drug administration.

Absorption↗
PubMed2005

Simultaneous determination of cannabidiol, cannabinol, and delta9-tetrahydrocannabinol in human hair by gas chromatography-mass spectrometry.

An analytical method was developed for evaluating the cannabidiol (CBD), cannabinol (CBN), and delta9-tetrahydrocannabinol (delta9-THC) level in human hair using gas chromatography-mass spectrometry (GC-MS). Hair samples (50 mg) were washed with isopropyl alcohol and cut into small fragments (< 1 mm). After adding a deuterated internal standard, the hair samples were incubated in 1.0 M NaOH for 10 min at 95 degrees C. The analytes from the resulting hydrolyzed samples were extracted using a mixture of n-hexane-ethyl acetate (75:25, v/v). The extracts were then evaporated, derivatized, and injected into the GC-MS. The recovery ranges of CBD, CBN, and delta9-THC at three concentration levels were 37.9-94.5% with good correlation coefficients (r2 >0.9989). The intra-day precision and accuracy ranged from -9.4% to 17.7%, and the inter-day precision and accuracy ranged from -15.5% to 14.5%, respectively. The limits of detection (LOD) for CBD, CBN, and delta9-THC were 0.005, 0.002, and 0.006 ng/mg, respectively. The applicability of this method of analyzing the hair samples from cannabis abusers was demonstrated.

Adult↗
PubMedDate not supplied

In vitro metabolism of cannabinol in rat, mouse, rabbit, guinea pig, hamster, gerbil and cat.

Metabolism of cannabinol (CBN) was studied in hepatic microsomal incubates from mouse, rat, rabbit, guinea pig, cat, hamster and gerbil. Metabolites were extracted with ethyl acetate, concentrated by chromatography on Sephadex LH-20 and identified by GC/MS as TMS derivatives. Six monohydroxy metabolites were identified. These had hydroxy groups at C-11 and at all positions of the pentyl side-chain. Metabolism varied considerably between the species. 11-Hydroxylation was the most prominent route in the majority of species, but in the hamster and cat the major metabolic pathway was 4'-hydroxylation. Metabolites hydroxylated in the pentyl chain were generally more abundant in guinea pig, hamster and cat.

Animals↗
PubMed1986

Cannabidiol attenuates delta 9-tetrahydrocannabinol-like discriminative stimulus effects of cannabinol.

Interaction effects of cannabidiol (CBD) and cannabinol (CBN) were examined using a drug discrimination procedure in which rats had been trained to discriminate between 3 mg/kg of delta 9-tetrahydrocannabinol (delta 9-THC) and vehicle (2 ml/kg). The generalization effects of CBN to delta 9-THC were attenuated when CBN was administered together with CBD. The results were time- and dose-dependent.

Animals↗
PubMed1979

Abomasal function following injections of elfazepam and 9-aza-cannabinol.

The feed intake stimulants elfazepam (E), a benzodiazepine, and 9-aza-cannabinol (9-AC) decrease rumen contractions and abomasal acid content in sheep and E increases rumen fluid volume, digestibility and overall nutrient availability. E has been hypothesized to decrease the propulsive activity of the entire GI tract. To further examine the effects of E and 9-AC on gastric function, 4 ewes were prepared with abomasal cannulas and 3 silver/silver chloride monopolar electrodes alternated with 2 strain gauges on the distal one-third of the abomasal serosa. Electromyographical (slow waves and action potentials) and contractile (rates and forces) activities and abomasal pH were measured. Treatment of 8 and 16 mg E had no effect on slow wave frequency, action potential rate, contraction rate, or contraction force. Abomasal content pH was decreased with 8 mg E. Treatments of 125 and 250 microgram 9-AC depressed action potential and contraction rates and contraction force but had no effect on slow wave frequency or pH.

Abomasum↗
PubMed1980

3H-delta 9-Tetrahydrocannabinol, 3H-cannabinol and 3H-cannabidiol: penetration and regional distribution in rat brain.

3H-delta 9-Tetrahydrocannabinol (3H-delta 9-THC), 3H-cannabidiol (3H-CBD) and 3H-cannabinol (3H-CBN) were administered (1 mg/kg) to male rats which were decapitated either 0.5, 1, 15, 30 or 90 min later. The plasma concentration was similar for all cannabinoids throughout the time course. After 5 min greater than 80% of the plasma radioactivity in each treatment was due to metabolites. Radioactivity rapidly entered brain after the administration of 3H-CBD, 3H-CBN, and 3H-delta 9-THC. The concentrations of unchanged 3H-CBD aand 3H-CBN in whole brain were higher than that of 3H-delta 9-THC 5 min after administration. Regional distribution of radioactivity in the brain after 5 min was similar for all three cannabinoids, the only significant difference being in hypothalamus. Coadministration of 3H-delta 9-THC with a five-fold excess of either CBD or delta 9-THC did not produce any significant alteration in the levels of radioactivity in brain or plasma 5 min after their injection. The difference in behavioral activity of delta 9-THC, CBD and CBN cannot be explained by penetrability or regional distribution in the brain.

Animals↗
PubMed1985

The quasi-morphine withdrawal syndrome: effect of cannabinol, cannabidiol and tetrahydrocannabinol.

Delta-9-tetrahydrocannabinol (THC), the main psychoactive principle of cannabis, has been shown to attenuate the exhibition of signs of the quasi-morphine withdrawal syndrome in rats. Cannabinol (CBN) showed the same activity but required a dosage of approximately eight times that of THC to produce an equivalent effect. Cannabidiol was without effect at the dosage levels used. The efficacy of these cannabinoids and the potency differences recorded in this study are in accord with their effects on other behaviours, both in experimental animals and in man. The activity of THC and CBN was not affected by the narcotic antagonist, naloxone.

Animals↗
PubMed1988

Cannabinol and cannabidiol in combination: temperature, open-field activity, and vocalization.

Rectal temperature as well as unconditioned activity in an open-field (O-F) arena, and palpation-induced vocalization were examined in rats treated intraperitoneally with cannabinol (CBN, 17.5 or 56 mg/kg) and cannabidiol (CBD, 10 or 30 mg/kg), either singly or in combination. CBN singly resulted in hypothermia which was not attenuated by the addition of CBD. CBN reduced ambulation and rearing activities as compared to vehicle-treated rats. CBD in combination with CBN did not attenuate these effects; the CBD doses in themselves appeared inactive. Vocalization occurred to a significantly greater extent in the CBN singly-treated rats as compared to the controls and the CBD singly-treated rats. Thus, CBD did not counteract the temperature and open-field effects induced by CBN. This is discussed in relation to previous results from drug discrimination experiments.

Animals↗
PubMed2006

Simple and sensitive determination of Delta(9)-tetrahydrocannabinol, cannabidiol and cannabinol in hair by combined silylation, headspace solid phase microextraction and gas chromatography-mass spectrometry.

A new method for determination of Delta(9)-tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) in hair based on alkaline hair hydrolysis, extraction by iso-octane, combined derivatization with N,O-bis-(trimethylsilyl)-trifluoroacetamide and headspace solid phase microextraction of the extract residue, and gas chromatography-mass spectrometry was developed and evaluated. The limits of detection of the three compounds were 0.01-0.02 ng/mg. The method was routinely applied to more than 250 hair samples. In 77 positive samples, the concentrations ranged from LOD to 4.2 ng/mg for THC (mean 0.49 ng/mg), to 12.1 ng/mg for CBD (mean 0.37 ng/mg) and to 0.85 ng/mg for CBN (mean 0.12 ng/mg) using a sample amount of 30 mg. The frequently observed increase of the segmental drug concentrations from proximal to distal is explained by progressive accumulation in the hair shaft from sebum or side stream smoke.

Calibration↗
PubMed1998

Inhibition of the cyclic AMP signaling cascade and nuclear factor binding to CRE and kappaB elements by cannabinol, a minimally CNS-active cannabinoid.

Immune suppression by cannabinoids has been widely demonstrated in a variety of experimental models. The identification of two major types of G-protein-coupled cannabinoid receptors expressed on leukocytes, CB1 and CB2, has provided a putative mechanism of action for immune modulation by cannabinoid compounds. Ligand binding to both receptors negatively regulates adenylate cyclase, thereby lowering intracellular cyclic AMP (cAMP) levels. In the present studies, we demonstrated that cannabinol (CBN), a ligand that exhibits higher binding affinity for CB2, modulates immune responses and cAMP-mediated signal transduction in mouse lymphoid cells. Direct addition of CBN to naive cultured splenocytes produced a concentration-dependent inhibition of lymphoproliferative responses to anti-CD3, lipopolysaccharide, and phorbol-12-myristate-13-acetate/ionomycin stimulation. Similarly, a concentration-related inhibition of the in vitro anti-sheep red blood cell IgM antibody forming cell response was also observed by CBN. Evaluation of cAMP signaling in the presence of CBN showed a rapid and concentration-related inhibition of adenylate cyclase activity in both splenocytes and thymocytes. This decrease in intracellular cAMP levels produced by CBN resulted in a reduction of protein kinase A activity, consequently leading to an inhibition of transcription factor binding to the cAMP response element and kappaB motifs in both cell preparations. Collectively, these results demonstrate that CBN, a cannabinoid with minimal CNS activity, inhibited both cAMP signal transduction and immune function, further supporting the involvement of CB2 receptors in immune modulation by cannabimimetic agents.

Activating Transcription Factor 2↗
PubMed2001

Modulation of CREB and NF-kappaB signal transduction by cannabinol in activated thymocytes.

Cannabinoid compounds inhibit the cAMP signalling cascade in leukocytes. One of these compounds, cannabinol (CBN) has been shown to inhibit interleukin-2 (IL-2) expression and the activation of cAMP response element binding protein (CREB) and nuclear factor for immunoglobulin kappa chain in B cells (NF-kappaB) following phorbol-12-myristate-13 acetate (PMA) plus ionomycin (Io) treatment of thymocytes. Therefore, the objective of the present studies was to determine the role of cAMP and protein kinase A (PKA) in the CBN-mediated inhibition of IL-2, CREB, and NF-kappaB in PMA/Io-activated thymocytes. The inhibition of CREB/ATF-1 phosphorylation, or cAMP response element (CRE) or kappaB DNA binding activity produced by CBN in PMA/Io-activated thymocytes, could not be reversed by DBcAMP costimulation. Furthermore, DBcAMP failed to reverse the concentration-dependent inhibition of IL-2 protein secretion by CBN. Pretreatment of thymocytes with H89 produced a modest inhibition of PMA/Io-induced CREB/ATF-1 phosphorylation and CRE DNA binding activity but H89 had no effect on protein binding to a kappaB motif. Additionally, H89 modestly inhibited PMA/Io-induced IL-2 secretion. In light of the modest involvement of the cAMP pathway in CBN-mediated inhibition of CREB and IL-2 in PMA/Io-activated thymocytes, PD098059 (PD), the MEK inhibitor, was utilized to determine the role of ERK MAP kinases in thymocytes. ERKs play a critical role in IL-2 production but not for CREB phsophorylation. Collectively, these findings suggest that CBN may modulate several signalling pathways in activated T cells.

Animals↗
PubMed2000

Novel cannabinol probes for CB1 and CB2 cannabinoid receptors.

The observation that the phenolic hydroxyl of THCs was important for binding to the CB1 receptor but not as critical for binding to the CB2 receptor prompted us to extend this finding to the cannabinol (CBN) series. To study the SAR of CBN analogues, CBN derivatives with substitution at the C-1, C-3, and C-9 positions were chosen since these positions have played a key role in the SAR of THCs. CBN-3-(1',1'-dimethylheptyl) analogues were prepared by sulfur dehydrogenation of Delta(8)-THC-3-(1',1'-dimethylheptyl) analogues. 9-Substituted CBN analogues were prepared by the standard sulfur dehydrogenation of 9-substituted Delta(8)-THC analogues (Scheme 1), which in turn were prepared following our previous procedure using selenium dioxide oxidation of the corresponding Delta(8)-THCs followed by sodium chlorite oxidation to give the 9-carboxy-Delta(8)-THC derivatives. 11-Hydroxy-CBN analogues were prepared from the corresponding 9-carbomethoxy-CBN analogues by reduction with LiAlH(4). Deoxy-CBN analogue 14 was prepared from the corresponding Delta(8)-THC analogue 11 by conversion of the phenolic hydroxyl to the phosphate derivative 12, followed by lithium ammonia reduction to provide the deoxy-Delta(8)-THC analogue 13, which in turn was dehydrogenated with sulfur to provide the deoxy-CBN analogue 14 (Scheme 2). The various analogues were assayed for binding both to the brain and the peripheral cannabinoid receptors (CB1 and CB2). We have found that the binding profile differs widely between the CBN and the THC series. Specifically, in the CBN series the removal of the phenolic hydroxyl decreases binding affinity to both the CB1 and CB2 receptors, whereas in the THC series, CB1 affinity is selectively reduced. Thus, in the CBN series, the selectivity of binding observed with the removal of the hydroxy group is decreased severalfold as compared to what occurs in the THC series. Generally, high affinity for the CB2 receptor was found in analogues when the phenolic hydroxyl was present. The 3-(1', 1'-dimethylheptyl) derivatives were found to have much higher affinities than the CBN analogues, which is in complete agreement with previously reported work by Rhee et al.

Animals↗