Disposition of cannabinoids and their metabolites in serum, oral fluid, sweat patch and urine from healthy individuals treated with pharmaceutical preparations of medical cannabis

Author(s):  
Ana P. Pérez‐Acevedo ◽  
Roberta Pacifici ◽  
Giulio Mannocchi ◽  
Massimo Gottardi ◽  
Lourdes Poyatos ◽  
...  
2021 ◽  
Vol 14 (1) ◽  
pp. 59
Author(s):  
Francesco Paolo Busardò ◽  
Ana Pilar Pérez-Acevedo ◽  
Roberta Pacifici ◽  
Giulio Mannocchi ◽  
Massimo Gottardi ◽  
...  

Inhalation by vaporization is a useful application mode for medical cannabis. In this study, we present the disposition of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, and their metabolites in serum, oral fluid, and urine together with the acute pharmacological effects in 14 healthy individuals treated with vaporized medical cannabis. THC and CBD peaked firstly in serum and then in oral fluid, with higher concentrations in the first biological matrices and consequent higher area under the curve AUCs. Acidic precursors Δ-9-tetrahydrocannabinolic acid A (THCA) and cannabidiolic acid (CBDA) showed a similar time course profile but lower concentrations due to the fact that vaporization partly decarboxylated these compounds. All THC and CBD metabolites showed a later onset with respect to the parent compounds in the absorption phase and a slower decrease to baseline. In agreement with serum kinetics, THC-COOH-GLUC and 7-COOH-CBD were the significantly most excreted THC and CBD metabolites. The administration of vaporized medical cannabis induced prototypical effects associated with the administration of cannabis or THC in humans, with a kinetic trend overlapping that of parent compounds and metabolites in serum. The pharmacokinetics of cannabinoids, their precursors, and their metabolites in biological fluids of individuals treated with vaporized medical cannabis preparations showed a high interindividual variability as in the case of oral medical cannabis decoction and oil. Inhaled medical cannabis was absorbed into the organism earlier than decoction and oil. Cannabinoids reached higher systemic concentrations, also due to the fact that the acid precursors decarboxylated to parent cannabinoids at high temperatures, and consequently, the physiological and subjective effects occurred earlier and resulted with higher intensity. No serious adverse effects were observed.


2021 ◽  
Vol 74 (7) ◽  
pp. 1695-1698
Author(s):  
Oleg V. Rybalov ◽  
Pavel I. Yatsenko ◽  
Olga Yu. Andriyanova ◽  
Elena S. Ivanytska ◽  
Maria A. Korostashova

The aim: Is to assess the functional state of parotid glands and general secretion in patients with compression, dislocation dysfunction of TMJ, to correct the revealed disorders. Materials and methods: We examined 46 patients with dysfunction of TMJ. Examination included TMJ zonography and salivary glands sonography. We studied the general and parotid secretion, transparency, viscosity, pH of the oral fluid and the secretions of the parotid glands before and after treatment. The treatment of dysfunction and hyposialosis included the repositioning of the articular heads of the lower jaw in the correct anatomical position, the use of a repositioning plate on the posterior teeth at the compression side of the articular head, bougienage of the duct of the parotid gland, administration of 10% magnesium-mineral solution of bischofite into the gland. Results: In patients with TMJ dysfunction, a significant decrease in the oral fluid content was noted before treatment. The saliva transparency was reduced, the viscosity was increased, the pH was slightly acidic. A study, which was carried out a month after completion of the course of treatment showed that all the studied parameters corresponded to those in healthy individuals. Conclusions: The study confirmed that in compression and dislocation dysfunction of TMJ, there are disorders of the functional state of the salivary glands.


2019 ◽  
Vol 15 (3) ◽  
pp. 56-61 ◽  
Author(s):  
Артем Саркисов ◽  
Artem Sarkisov ◽  
Владимир Зеленский ◽  
Vladimir Zelenskiy ◽  
Екатерина Полунина ◽  
...  

Background. The study of the features of the course and the general links of pathogenesis in patients with chronic generalized periodontitis (CGP) with comorbid pathology is one of the priorities of modern medicine. Objectives ― to assess and analyze the level of apoptosis marker annexin A5 and the value of dental indices in patients with CGP of varying severity without General somatic pathology and against the background of bronchiectatic disease Methods. The study involved 90 patients with present study included varying degrees (light, medium, heavy), which were divided into two groups: patients with no somatic pathology (n=40) and patients with comorbid pathology in the form of bronchoectatic disease (n=50). Somatically healthy individuals with intact periodontal disease (n=40) were examined as a control group. The values of dental indices – PMA, PI, Muhlemann and OHI-s. The level of annexin A5 was determined in the oral fluid by enzyme immunoassay. Results. In patients with CGP revealed a statistically significant higher value of the level of annexin A5 compared with somatically healthy individuals with intact periodontal and statistically significantly higher in patients with more severe periodontitis. At the same time, in patients with comorbid pathology, the level of annexin A5 in patients with CGP with bronchoectatic disease with mild, average and heavy degree of periodontitis is statistically significantly higher than in patients with CGP without somatic pathology. The revealed relationships between the value of dental indices and the level of annexin A5 indicate the influence of the studied marker of apoptosis on the state of periodontal tissues. Moreover, the patients with comorbidity the power value of the identified links more than the present study included patients with no somatic pathology. Conclusion. The obtained data show the influence on the currents present study included the presence of comorbid pathology in the form of bronchoectatic disease and presence of common mutually aggravating link of pathogenesis of apoptosis and the opportunity to use annexin A5 as predictive marker of progression, as the present study included patients with no somatic pathology and in the background bronchoectatic disease.


2013 ◽  
Vol 94 (5) ◽  
pp. 752-754
Author(s):  
N A Terekhina ◽  
S E Reuk ◽  
T I Atamanova

Aim. To compare the levels of ceruloplasmin in tears, saliva and blood serum of patients with herpetic stomatitis and eye herpes to evaluate the effectiveness of treatment. Methods. Ceruloplasmin levels were determined in tears, saliva and blood serum of 30 children, 22 adult patients with herpetic keratitis and 27 children with acute herpetic stomatitis. Biological fluids of 62 healthy individuals were used as the control group. Results. In patients with eye herpes infection, сeruloplasmin levels increased in oral fluid and blood serum and markedly decreased in tears of both affected and intact eye. Ceruloplasmin levels in biological fluids normalized only among children with light forms of eye herpes at discharge. In the case of acute herpetic stomatitis, ceruloplasmin levels increased in oral fluid and blood serum, depending on the severity of the disease. After the treatment, ceruloplasmin levels in tears, oral fluid and blood plasma normalized only in children with dendritic ulcer (herpes epithelial keratitis), while in adult patients with chronic relapsing eye herpes and in children with highly invasive eye herpes ceruloplasmin levels did not normalize. Conclusion. In the case of infection detected multidirectional ceruloplasmin levels in tears, oral fluids and blood serum changes were found in patients with herpes. Ceruloplasmin level decreased in tears, and increased in blood serum and oral fluid.


2020 ◽  
Vol 65 (2) ◽  
pp. 100-105
Author(s):  
I. A. Selezneva ◽  
F. N. Gilmiyarova ◽  
I. A. Borodina ◽  
A. A. Ereshchenko ◽  
E. M. Gilmiyarov ◽  
...  

In order to find a connection between the alteration of oral tissues and genetic predisposition to inflammatory and destructive processes in oral media, the cytokine profile of the oral fluid of clinically healthy individuals was determined for various blood group affiliations according to the AB0 system. The group-specific features of individuals with B(III) blood group were revealed: an increase of 32,5% in the content of interleukin-6 and 63,1% in the content of interleukin-8 compared with similar data for people with 0(I), A(II), AB(IV) blood groups, which can predispose to the greatest activity of the inflammatory process in the oral cavity in individuals with antigen B. Confirmation of this fact is an increase of IgA antibodies to gliadin in the blood among patients with chronic generalized periodontitis with B(III) blood group, up to 5,00 U/ml (p<0,01), which indicates the processes of acute inflammation, and along with an increase in blood IgG antibodies to transglutaminase in comparison with a group of clinically healthy individuals, it serves as an indicator of damage to the body’s connective tissue at the molecular level. When examining the dental status, pronounced clinical manifestations of chronic generalized periodontitis were found in patients with A(II) blood group, the molecular foundation of which is the highest content of IgA and IgG antibodies to transglutaminase in the oral fluid (0,35 U/ml and 0,45 U/ml), which contributes to the activation of periodontal-destroying inflammatory and inflammatory processes, obviously, with a tendency to the chronic course of the disease. The studies performed allowed us to analyze in clinically healthy individuals a predisposition to alternative processes in oral environments, using gradation by group blood affiliation.


2019 ◽  
Vol 21 (2) ◽  
pp. 313-322
Author(s):  
N. S. Aliakhnovich ◽  
D. K. Novicov

There are some data about various immunopathology effects of food dyes. Their use in food and medicines may induce hypersensitivity, which is regarded as a side effect of drugs or intolerance to food substances. Evaluation of the effect caused by food and drugs colorants on the immunity was conducted in 68 patients with chronic allergic diseases without the exacerbation and 23 healthy individuals. The provocative oral test was supplied with 2 mg of titanium dioxide (TiO2) in powder or 2 mg of tartrazine in wheat flour processed at a cooking temperature or in a gelatin capsule containing 0.2 mg of titanium dioxide. The oral fluid and/or venous blood were taken up on an empty stomach and 40 minutes after the test. The peroxidase activity of oral fluid and the expression of CD203c and IgE markers on blood basophils were studied. The blood of 20 patients with allergopathology was incubated for 3 and 24 hours with 0.001% and 0.01% mixture of tartrazine, carmoazine, ponso, sanset, TiO2solutions with the determination interleukin 17 (IL17) level in the supernatants. Peroxidase activity of oral fluid increased on 30% or more in 30% of cases after tartrazine and wheat flour provocation in patients with allergies (12.5% in healthy persons), 44% - after TiO2in patients with allergies (22% of cases in healthy individuals), 63% - after tartrazine and TiO2in the white gelatin capsule in patients with allergies (in healthy individuals, p = 0.047). The number of IgE+CD203c+basophils increased in 44% cases and decreased in 50% cases after provocation with TiO2in the group of allergic patients, compared with 22% increasing and 22% decreasing in healthy (p = 0.007). A lower concentration of the dye mixture (0.001%) induced IL17 secretion in the supernatant in all 20 patients with allergic diseases, the maximum permissible concentration (0.01%) of the dyes solution - less often in 40% of the examined (p = 0.0002). Secretion of IL17 under the influence of the both concentrations was higher than in the control samples (p <0.05). Thus, the dyes of food and drugs show immunomodulatory activity in patients with allergic diseases (more often) and in healthy individuals. The connection of a positive provocation test with food dyes tartrazine and titanium dioxide with oral fluid peroxidase activity increasing and the number of IgE+CD203c+basophils and IgEbrightbasophils increasing and IL17 secretion under the influence of these dyes was found.


2020 ◽  
Vol 13 (12) ◽  
pp. 459
Author(s):  
Ana Pilar Pérez-Acevedo ◽  
Francesco Paolo Busardò ◽  
Roberta Pacifici ◽  
Giulio Mannocchi ◽  
Massimo Gottardi ◽  
...  

The use of cannabis flowering tops with standardized amounts of active phytocannabinoids was recently authorized in several countries to treat several painful pathological conditions. The acute pharmacological effects and disposition of Δ-9-tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors and THC metabolites after oil and decoction administration have been already described. In this study, the disposition of CBD metabolites: 7-carboxy-cannabidiol (7-COOH-CBD), 7-hydroxycannabidiol (7-OH-CBD), 6-α-hydroxycannabidiol (6-α-OH-CBD), and 6-β-hydroxycannabidiol (6-β-OH-CBD) in the serum and urine of healthy volunteers was presented. Thirteen healthy volunteers were administered 100 mL of cannabis decoction in the first experimental session and, after 15 days of washout, 0.45 mL of oil. Serum and urine samples were collected at different time points, and the CBD metabolites were quantified by ultra-high-performance liquid chromatography–tandem mass spectrometry. The most abundant serum metabolite was 7-COOH-CBD, followed by 7-OH-CBD, 6-β-OH-CBD, and6-α-OH-CBD, after decoction and oil. Both 7-OH-CBD and the 6-α-OH-CBD showed similar pharmacokinetic properties following administration of both cannabis preparations, whereas 7-COOH and 6-α-OH-CBD displayed a significant higher bioavailability after decoction consumption. All CBD metabolites were similarly excreted after oil and decoction intake apart from 6-α-OH-CBD, which had a significantly lower excretion after oil administration. The pharmacokinetic characterization of CBD metabolites is crucial for clinical practice since the cannabis herbal preparations are increasingly used for several pathological conditions.


2015 ◽  
Vol 142 (1) ◽  
pp. 101-110 ◽  
Author(s):  
Ayelet Zlotogorski-Hurvitz ◽  
Dan Dayan ◽  
Gavriel Chaushu ◽  
Tuula Salo ◽  
Marilena Vered

2020 ◽  
pp. 85-91
Author(s):  
K. V. Kovalyshyn ◽  
M. M. Rozhko

The aim of our research was to study the indicators changes in antioxidant protection and malonic dialdehyde (MDA) levels in the oral fluid in patients with  GP and rheumatoid arthritis (RA) who live in environmentally unfavorable areas and  assessment of the dynamics of changes in the studied indicators in the oral fluid under the influence of comprehensive treatment. Materials and methods. 105 patients with GP were examined and treated, of which 70 patients were with RA. Depending on the ecological living conditions of patients with RA was divided into two groups: group I (n = 35) - live in environmentally unfavorable areas; group II (n = 35) - live in environmentally favorable areas. Group III (n = 35) was formed by patients with GP without concomitant pathology. Each of the groups, depending on the severity of GP was divided into subgroups: A - GP of the I degree; B - GP of the II degree of severity. The control group consisted of 18 virtually healthy individuals with intact periodontium and preserved dentition. The state of the prooxidant system of the oral cavity was determined by the level of MDA. To study the state of the antioxidant defense system (AOS), the activity of superoxide dismutase (SOD) and catalase was determined. Research results.  Determining the level of MDA in oral fluid in all subgroups of patients with GP and RA and without concomitant pathology revealed an increase in this indicator before treatment. It increased most significantly in the IB subgroup to 1.19 ± 0.02 nmol/l and in the IA subgroup to 1.16 ±0.01 nmol/l, compared with 0.34 ± 0.17 nmol / l in healthy individuals. (* pIB-3 <0.001, * pIA-3 <0.001), which exceeded it by 3.5 and 3.4 times, respectively, which may be due to the negative impact of the environment. During all follow-up periods after conducted treatment, the level of MDA decreased and most closely approached the rate of healthy individuals after 6 months. However, before treatment, depletion of the antioxidant system was detected in all subgroups, as evidenced by the weakening of the AOS. In particular, in the IB subgroup there is the greatest decrease in the activity of SOD to 35.6 ± 0.56%, compared with the group of healthy individuals 49.06 ± 0.03% (p <0.001) and catalase to 4.42 ± 0.03 с.u along with healthy - 6.64 ± 0.01 c.u (p <0.001). The activity of certain antioxidant protection enzymes tends to increase after a comprehensive treatment in all subgroups after 6 months. And in the IB subgroup the activity of SOD after 6 months was 44.77 ± 0.35%, catalase 6.29 ± 0.03c.u. Conclusions. The results of the conducted biochemical researches of oral fluid in patients with GP and  RA, who live in environmentally unfavorable areas, showed a decrease in the activity of SOD enzymes, catalase and increased levels of MDA in these patients. After the conducted complex treatment there is a normalization of the AOS system, which is manifested in increased activity in the oral fluid SOD and catalase, as well as a decrease in MDA, which indicates a decrease in inflammation process and the effectiveness of our treatment and prevention complex on the antioxidant system, which provided remission GP in these patients.


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