63ODONTOLOGÍA VITAL ENERO-JUNIO 2020

Changes in salivary composition of

chemically dependent subjects

Changes in salivary composition of

chemically dependent subjects

Luciana Lyra, Universidade Federal do Paraná, Curitiba, Brazil, lulyra@hotmail.com

William Bellani, Universidade Federal do Paraná, Curitiba, Brazil, william.bellani@gmail.com

Carolina E. Mazur, Universidade Federal do Paraná, Curitiba, Brazil, carolmazur6@hotmail.com

João A. Brancher, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil, jabrancher@hotmail.com

Antonio Adilson S. de Lima, Universidade Federal do Paraná, Curitiba, Brazil, antollima@gmail.com

José Miguel Amenábar, Universidade Federal do Paraná, Curitiba, Brazil, jamenaba@gmail.com

ABSTRACT

Chemically dependent subjects may present relevant changes in the volume and composition of salivary ﬂuid

because the secretion of the salivary glands is controlled by the parasympathetic and sympathetic system. The

aim of this study was to compare the salivary concentration of total proteins, amylase, urea, calcium, phosphate

and ﬂow rate between chemically dependent and non-chemically dependent subjects. Saliva ﬂow rate, calcium,

phosphate, total protein, amylase and urea concentrations were measure in both groups: chemical dependent

group (n=27) and control group (n=27). Saliva samples, from the chemically dependents, were taken one day

before the beginning of the detoxiﬁcation treatment. Statistical analysis was undertaken using t-test. The

salivary ﬂow and the urea concentration did not present statistically signiﬁcant difference between the groups.

However, total proteins, amylase, calcium and phosphate concentrations were statistically higher on the chemical

dependents group. Saliva composition seems to be modiﬁed by the chronic use of alcohol and illicit drugs.

KEYWORDS

Saliva, alcohol, cannabis, cocaine, salivary composition, substance-related disorders, substance dependence,

drugs

RESUMEN

Los dependientes químicos pueden presentar cambios relevantes en el volumen y la composición de la saliva,

debido a que la secreción de las glándulas salivales es controlada por el sistema parasimpático y simpático.

El objetivo de este estudio fue comparar la concentración salival de proteínas totales, amilasa, urea, calcio,

fosfato y la velocidad de ﬂujo salival entre personas con dependencia química y no dependientes. Cada grupo

fue formado por 27 participantes. La velocidad del ﬂujo salival y las concentraciones de calcio, fosfato, proteína

total, amilasa y urea se midieron en ambos grupos. Las muestras de saliva de los dependientes químicos se

tomaron un día antes de comenzar el tratamiento de desintoxicación. El análisis estadístico se realizó por medio

del test t de student. El ﬂujo salival y la concentración de urea no presentaron diferencias estadísticamente

signiﬁcativas entre los grupos. Sin embargo, las concentraciones de proteínas totales, amilasa, calcio y fosfato

fueron estadísticamente mayores en el grupo de dependientes químicos. El uso crónico de alcohol y de drogas

ilícitas provocan modiﬁcaciones en la composición salival.

PALABRAS CLAVE

Saliva, alcohol, cannabis, cocaína, composición salival, desórdenes asociados a sustancias, dependencia a

sustancias, drogas

Recibido: 17 junio, 2019

Aceptado para publicar: 5 diciembre, 2019

Cambios en la composición salival de personas

químicamente dependientes

Cambios en la composición salival de personas

químicamente dependientes

Lyra, L., Bellani, W., Mazur, C. E., Brancher, J. A., Adilson, A. & Amenábar, J. M. (2020). Changes in salivary composition

of chemically dependent subjects. Odontología Vital, 1(32), 63-70 https://doi.org/10.59334/ROV.v1i32.381

ISSN 2215-5740

Odontología Vital Enero-Junio 2020. Volumen 1 No. 32 Año 18 https://doi.org/10.59334/ROV.v1i32.381

64 ODONTOLOGÍA VITAL ENERO-JUNIO 2020

INTRODUCTION

Chemical dependency, which in-

cludes both alcoholism and drug

addiction, is a primary illness char-

acterized by the dependence to a

mood-altering chemical (Kalivas &

Volkow, 2005). A chemically depen-

dent person is not able to stop drink-

ing or using a drug despite serious

social and health consequences.

It is possible that chemically depen-

dent subjects may present relevant

changes in the volume and compo-

sition of the salivary ﬂuid because

the secretion of the salivary glands

is controlled by the parasympa-

thetic and sympathetic systems,

simultaneously (Carpenter, 2013;

Proctor & Carpenter, 2007) which

can be affected by alcohol, drugs or

both (Aps & Martens, 2005; Enberg,

Alho, Loimaranta, & Lenander-Lu-

mikari, 2001; Newlin, 1995). Those

changes can be responsible for the

disturbances on the integrity of the

enamel, periodontal tissues and

oral mucosa (Antoniazzi et al., 2018;

Cho, Hirsch, & Johnstone, 2005;

da Fonseca, 2009; Rawal, Tatakis,

& Tipton, 2012; Reddy et al., 2012;

Sordi, Massochin, Camargo, Lemos,

& Munhoz, 2017).

Some studies have shown that sali-

vary constituents, such as proteins,

calcium, phosphate, potassium,

bicarbonate, IgA, lisozyme and

lactoferrin may undergo changes

in their concentrations due to the

abuse of alcohol (Enberg et al.,

2001; Waszkiewicz et al., 2017;

Waszkiewicz, Zalewska-Szajda,

Zalewska, Waszkiewicz, Szajda,

Repka, Szulc, Kpka, et al., 2012;

Waszkiewicz, Zalewska-Szajda, Za-

lewska, Waszkiewicz, Szajda, Rep-

ka, Szulc, Kepka, et al., 2012; Wasz-

kiewicz, Zalewska, Szajda, Szulc, et

al., 2012; Waszkiewicz, Zalewska,

Szajda, Waszkiewicz, et al., 2012).

Nevertheless, there are no studies

evaluating if the salivary composi-

tion of patients with an alcohol or

illicit drug dependency is altered.

The objective of this study was to

compare the salivary concentra-

tion of proteins, amylase, urea,

calcium, phosphate and ﬂow rate

between chemically dependent

and non-chemically dependent

subjects.

MATERIALS AND METHODS

Ethical approval

The study´s protocol was approved

by the Research Ethics Committee

of the Federal University of Paraná,

Brazil (Approval number: 84071).

All the participants received de-

tailed information concerning

the nature and the procedures in-

volved in the study and signed in-

formed consent forms.

Subject´s selection

Twenty-seven volunteers, males,

aged between 18 and 50 years old,

with alcohol dependence and drug

addiction, attending the Institute

for Research and Treatment of

Alcohol (Campo Largo, Paraná,

Brazil) were recruited. All the par-

ticipants were going to begin the

detoxiﬁcation program.

The control group consisted of 27

healthy males, 18-50 years of age,

recruited from the Police Academy

of Curitiba, Paraná, Brazil. These

participants did not have alcohol

dependence nor reported the use

of drugs. Only healthy volunteers

were accepted for this group, and

individuals with any regular medi-

cation, substance-related addic-

tion or illness were excluded from

the study.

Saliva Collection

Saliva samples, from the chemi-

cally dependent group, were taken

one day before the detoxiﬁcation

treatment started.

Stimulated saliva was collected be-

tween 09:00 A.M. and 11:00 A.M. in

a quiet room, free from external in-

terferences. The participants were

previously instructed to refrain from

eating, drinking, or cleaning their

teeth for 2 hours before the collec-

tion process. The saliva sample was

obtained with the use of parafﬁn ﬁlm

in order to perform a ﬁve-minute

stimulation. Then, they spitted their

saliva into a sterile container (Sterile

Universal Collector - J.PROLAB 80

ml). The sample volumes were mea-

sured gravimetrically according to

the method of Banderas-Tarabay et

al., (1997) using a precision balance

(MARTE AM200, Santa Rita do Sa-

pucaí/MG, Brazil) and the samples

were immediately frozen at -20 °C

until further analysis. All the samples

were processed within 7 to 10 days.

Biochemical Analysis

All the samples were centrifuged at

2,600g for 10 min at 4°C to remove

cellular and food debris and none

of them were contaminated with

blood. Calcium and phosphate

concentrations were determined

by colorimetric testing. (Calcio

Liquiform, Labtest diagnostica,

Lagoa Santa/MG, Brazil; Fósforo,

Labtest diagnostica, Lagoa Santa/

MG, Brazil). Determination of pro-

tein concentration was carried out

using Coomassie blue with bovine

serum albumin as the standard.

Urea and amylase concentrations

were analyzed using enzymatic

colorimetric test kits (Urea UV

Liquiform, Labtest diagnostica, La-

goa Santa/MG, Brazil and Amilase,

Labtest diagnostica, Lagoa Santa/

MG, Brazil). All biochemical analy-

ses were done 3 times for each sali-

va sample using a spectrophotom-

eter (S-2000 UV - VIS, SP, Brazil).

Statistical analysis

The results were expressed as

mean ± standard deviation. Sta-

tistical analysis was undertaken

Odontología Vital Enero-Junio 2020. Volumen 1 No. 32 Año 18

65ODONTOLOGÍA VITAL ENERO-JUNIO 2020

Table 1. Age, alcohol and illicit drugs use

(quantity and duration) by groups

Age: mean years (SD) Chemically dependent (27) Control (27)

Alcoholic beverage

Use (n)

Quantity, ml/day (SD)

Duration, years (SD

37.56 (10.70)

1598.62 (660.72)

21.92 (12.05)

38.15 (11.12)

Cocaine

Use (n)

Quantity, mg/day (SD)

Duration, years (SD)

60.4 (30.7)

11.62 (8.82)

Smoke Cocaine

Use (n)

Quantity, mg/day (SD)

Duration, years (SD)

66.6 (22.5)

7.46 (4.20)

Cannabis

Use (n)

Quantity, g/week (SD)

Duration, years (SD

6.84 (2.72)

13.15 (8.45)

Table 2. Comparison of the salivary variables between the groups.

Chemically

dependent (27)

Control

(27)

value

Saliva ﬂow rate, ml/min (SD) 0.94 ± 0.80 0.84 ± 0.42 0.595

Total protein, mg/mL (SD) 0.45 ± 0.31 0.28 ± 0.22 0.022

Amylase, U/dL (SD) 766.7 ± 6.6 753.6 ± 28.3 0.035

Urea, mg/mL (SD) 3.04 ± 2.67 3.05 ± 2.26 0.988

Calcium, mg/mL (SD) 0.12 ± 0.06 0.050 ± 0.04 <

0.0005

Phosphate, mg/mL (SD 0.78 ± 0.22 0.55 ± 0.17 <

0.0005

Student’s t test for independent samples, p<0.05

using Student’s t test for indepen-

dent samples. A p-value <0.05 was

accepted to be statistically signiﬁ-

cant. Statistical analysis was per-

formed with Statistical Package for

the Social Sciences for Windows

(SPSS, version 20.0, SPSS Inc., Chi-

cago, IL, USA).

RESULTS

The mean age of the chemically

dependent group was 37.56 ± 10.70

years, while the control group

showed 38.15 ± 11.12 years. None

of the participants of the control

group reported the use of alcohol

or illicit drugs. On the other hand,

all subjects in the addiction group

conﬁrmed using alcohol and co-

caine. Also, 48% of these partici-

pants used to smoke cocaine or

cannabis. The quantity and dura-

tion of the consumption are pre-

sented in Table 1.

Salivary ﬂow and urea concen-

tration did not show statistically

signiﬁcant differences between

groups, however, total proteins,

amylase, calcium and phosphate

concentration were higher on the

chemically dependent group. Ta-

ble 2 shows the comparison of the

analyzed variables.

DISCUSSION

The results of the study show alter-

ations of the salivary composition

among the chemically dependent

subjects. Several studies have re-

ported the dangerous character of

alcohol and illicit drugs, as well as

their physiological consequences

in short and long terms (Cho et al.,

2005; Gossop, Manning, & Ridge,

2006; Pateria, de Boer, & MacQuil-

lan, 2013; Singh et al., 2017). On the

other hand, there are no studies

evaluating the salivary composi-

tion on chemically dependent sub-

jects, or they were not found dur-

ing the literature review made for

this research.

66 ODONTOLOGÍA VITAL ENERO-JUNIO 2020

Alcohol acts as a central nervous

system (CNS) depressant and it´s

effects are potentially deleterious

and irreversible to the CNS (Ron &

Barak, 2016). There is an increase

in the synthesis and release of

noradrenaline through the blood

vessels (Koob, 1992). The salivary

ﬂuid becomes thicker due to the

sympathetic adrenergic stimulus

by increasing the effects of sympa-

thetic nervous activity (Carpenter,

2013). Consequently, saliva may

present lower ﬂuidity and higher

secretion of proteins and calcium,

as observed in the study.

Cannabis also affects the CNS in a

similar way to alcohol. It has depres-

sant and psychomimetic effects.

Muscarinic receptors, from acetyl-

choline, are coupled to G protein

and produce excitatory and stimu-

latory effects of salivary gland se-

cretion, known as parasympathetic

stimulation (Proctor & Carpenter,

2014). The abusive use of canna-

bis results in anticholinergic activ-

ity such as a blockage of the effects

of acetylcholine on muscarinic M3

receptors (Ralevic, 2003), that may

decrease salivary secretion. There-

fore, this constant sympathetic

stimulation leads to the production

of viscous saliva, low in quantity and

but rich in proteins and inorganic

electrolytes (Aps & Martens, 2005).

This may also explain the difference

found between groups, in the total

protein and calcium concentration.

On the other hand, cocaine (crack)

is a sympathomimetic drug of in-

direct action, since it blocks the

transport of noradrenaline, sero-

tonin and dopamine in the syn-

aptic cleft, occurring prolongation

of the user’s euphoric sensation

(Dackis & O’Brien, 2001). It inhib-

its the capture of catecholamines

by noradrenaline and dopamine

transporters to noradrenergic

nerve terminals, intensifying the

effects of sympathetic nervous ac-

tivity (Riezzo et al., 2012). These

may induce changes in the saliva

ﬂow rate. While some authors re-

ported that saliva ﬂow does not

change (Woyceichoski et al., 2013),

but others had found a signiﬁcant

association between the use of

crack and a reduced salivary ﬂow

(Antoniazzi et al., 2018). In the

present study we did not see any

difference on stimulated salivary

ﬂow between groups.

Stimulated saliva provides infor-

mation about the secretory capac-

ity of the salivary glands. The sali-

vary composition is inﬂuenced by

the taste and mechanical stimulus

(Carpenter, 2013). The acid stimu-

lus may interfere with the buffer

capacity and cause precipitation

of certain salivary proteins and

calcium (Dawes, 1984). In order

to avoid alterations in the salivary

composition in this study it was

used only a mechanical stimula-

tion with insipid wax.

The signiﬁcant increase of total

proteins, amylase, calcium and

phosphate found in the saliva of

the chemically dependent group

may be explained by the control of

the central and autonomic nervous

system in the salivary glands (Proc-

tor & Carpenter, 2014). Secretion of

the salivary glands is qualitatively

and quantitatively modiﬁed in the

presence of sympathetic and para-

sympathetic nervous stimulus (Aps

& Martens, 2005) and both, alcohol

and illicit drugs inﬂuence the re-

sponse of the sympathetic system

(Koob, 1992; Magura & Rosen-

blum, 2000; Olière, Joliette-Riopel,

Potvin, & Jutras-Aswad, 2013).

The salivary parameters that pre-

sented statistical differences (to-

tal proteins, amylase, calcium and

phosphate) are related to the au-

tonomic nervous mechanism in

the salivary secretion (Proctor &

Carpenter, 2014). The nerve ﬁbers

of the sympathetic system release

noradrenalin that binds α and β

adrenergic receptors. β -receptors,

whose second messenger is cyclic

AMP (cyclic adenosine monophos-

phate) stimulates the precipitation

of enzymes and proteins. There is

an increase in permeability of the

membranes of acinar cells, which

contain zymogen granules that

stores proteins that are liberated

in high amounts (Castle & Castle,

1998; Proctor, 2016; Turner & Sugi-

ya, 2002). That is why β-adrenergic

stimulus results in increased pro-

tein (Turner & Sugiya, 2002) and

salivary phosphate concentration

(Beal, 1991).

The α-adrenergic receptors activate

P substance, a peptidergic receptor

that acts as mediator of the nervous

stimulus, present in the acinar cell

membrane. This increases the lev-

els of calcium and the quantity of

salivary, by potentiating the effect of

acetylcholine (Aps & Martens, 2005;

Proctor, 2016), which can explain

why the salivary calcium concen-

tration in the chemical dependent

group was higher.

Urea is a normal component of

saliva and it is passively diffused

from blood (Macpherson & Dawes,

1991; Thorn, Prause, & Oxholm,

1989). The results of the biochemi-

cal analysis of urea showed no

signiﬁcant difference between the

two groups. The urea concentra-

tion is dependent on the salivary

ﬂow (Thorn et al., 1989) and since

there was no variation of the sali-

vary ﬂow between the groups, it

can be expected that urea concen-

tration remained the same.

In this study, all the participants of

the chemically dependent group

reported that they used cocaine as

well as alcohol and sometimes can-

nabis. This is an important limita-

tion of the study, because it makes

very difﬁcult to draw speciﬁc con-

clusions for each substance and

it is impossible to discern if the

modiﬁcations in saliva composi-

Odontología Vital Enero-Junio 2020. Volumen 1 No. 32 Año 18

67ODONTOLOGÍA VITAL ENERO-JUNIO 2020

tion are due to the use of alcohol, a

speciﬁc drug or the combination of

all of them. On the other hand, it is

extremely difﬁcult to select chemi-

cally dependent users who con-

sume only one kind of drug.

CONCLUSION

Saliva composition can have an

impact in oral health, and it seems

to be altered on the chemically de-

pendent subjects. Future studies

with larger samples and analysis of

other salivary constituents should

be performed, as well as longitudi-

nal follow-up to verify if the chang-

es continue in the long term.

Acknowledgments: We thank the

Coordination for the Improvement

of Higher Level Education Person-

nel (CAPES) for the postgraduate

scholarship for LL, WB and CEM.

Autors

Luciana Lyraa, William Bellania, Carolina

E. Mazura, João A. Brancherb, Antonio

Adilson S. de Limaa, José Miguel Amená-

bara

a) Stomatology Department, Universida-

de Federal do Paraná, Curitiba, Paraná,

Brazil.

b) Department of Biological Sciences,

Pontifícia Universidade Católica do Para-

ná, Curitiba, Paraná, Brazil

Luciana Lyra:

lulyra@hotmail.com

William Bellani:

lulyra@hotmail.com

Carolina E. Mazur:

carolmazur6@hotmail.com

João A. Brancher:

jabrancher@hotmail.com

Antonio Adilson S. de Lima:

antollima@gmail.com

José Miguel Amenábar:

jamenaba@gmail.com

Corresponding Author:

José Miguel Amenábar

Posgraduate Program in Dentistry, Uni-

versidade Federal do Paraná, Curitiba,

Paraná, Brazil Av. Pref. Lothário Meissner,

632 – Jardim Botânico 80210-170 Curitiba,

PR. Tel: +55(41) 3360-4024 / Fax: +55(41)

3360-4134. jamenaba@gmail.com

BRASIL

68 ODONTOLOGÍA VITAL ENERO-JUNIO 2020

BIBLIOGRAFÍA

Antoniazzi, R. P., Lago, F. B., Jardim, L. C., Sagrillo, M. R., Ferrazzo, K. L., & Feldens, C. A. (2018). Impact of crack co-

caine use on the occurrence of oral lesions and micronuclei. Int J Oral Maxillofac Surg, 47(7), 888-895.

https://doi.org/10.1016/j.ijom.2017.12.005

Aps, J. K., & Martens, L. C. (2005). Review: The physiology of saliva and transfer of drugs into saliva. Forensic Sci

Int, 150(2-3), 119-131. https://doi.org/10.1016/j.forsciint.2004.10.026

Banderas-Tarabay, J. A., González-Begné, M., Sánchez-Garduño, M., Millán-Cortéz, E., López-Rodríguez, A., &

Vilchis-Velázquez, A. (1997). [The ﬂow and concentration of proteins in human whole saliva]. Salud Publica Mex,

39(5), 433-441. https://doi.org/10.1590/S0036-36341997000500006

Beal, A. M. (1991). Effect of phosphate-regulating hormones on plasma composition, cardiovascular function,

and parotid salivary phosphate secretion in red kangaroos (Macropus rufus). Gen Comp Endocrinol, 81(1), 64-71.

https://doi.org/10.1016/0016-6480(91)90125-P

Carpenter, G. H. (2013). The secretion, components, and properties of saliva. Annu Rev Food Sci Technol, 4, 267-

276. https://doi.org/10.1146/annurev-food-030212-182700

Castle, A. M., & Castle, J. D. (1998). Enhanced glycosylation and sulfation of secretory proteoglycans is coupled to

the expression of a basic secretory protein. Mol Biol Cell, 9(3), 575-583. https://doi.org/10.1091/mbc.9.3.575

Cho, C. M., Hirsch, R., & Johnstone, S. (2005). General and oral health implications of cannabis use. Aust Dent J,

50(2), 70-74. https://doi.org/10.1111/j.1834-7819.2005.tb00343.x

da Fonseca, M. A. (2009). Substance use disorder in adolescence: a review for the pediatric dentist. J Dent Child

(Chic), 76(3), 209-216.

Dackis, C. A., & O’Brien, C. P. (2001). Cocaine dependence: a disease of the brain’s reward centers. J Subst Abuse

Treat, 21(3), 111-117. https://doi.org/10.1016/S0740-5472(01)00192-1

Dawes, C. (1984). Stimulus effects on protein and electrolyte concentrations in parotid saliva. J Physiol, 346, 579-

588. https://doi.org/10.1113/jphysiol.1984.sp015042

Enberg, N., Alho, H., Loimaranta, V., & Lenander-Lumikari, M. (2001). Saliva ﬂow rate, amylase activity, and pro-

tein and electrolyte concentrations in saliva after acute alcohol consumption. Oral Surg Oral Med Oral Pathol

Oral Radiol Endod, 92(3), 292-298. https://doi.org/10.1067/moe.2001.116814

Gossop, M., Manning, V., & Ridge, G. (2006). Concurrent use and order of use of cocaine and alcohol: behavioural

differences between users of crack cocaine and cocaine powder. Addiction, 101(9), 1292-1298.

https://doi.org/10.1111/j.1360-0443.2006.01497.x

Kalivas, P. W., & Volkow, N. D. (2005). The neural basis of addiction: a pathology of motivation and choice. Am J

Psychiatry, 162(8), 1403-1413. https://doi.org/10.1176/appi.ajp.162.8.1403

Koob, G. F. (1992). Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol

Sci, 13(5), 177-184. https://doi.org/10.1016/0165-6147(92)90060-J

Macpherson, L. M., & Dawes, C. (1991). Urea concentration in minor mucous gland secretions and the effect of

salivary ﬁlm velocity on urea metabolism by Streptococcus vestibularis in an artiﬁcial plaque. J Periodontal Res,

26(5), 395-401. https://doi.org/10.1111/j.1600-0765.1991.tb01728.x

Odontología Vital Enero-Junio 2020. Volumen 1 No. 32 Año 18

69ODONTOLOGÍA VITAL ENERO-JUNIO 2020

Magura, S., & Rosenblum, A. (2000). Modulating effect of alcohol use on cocaine use. Addict Behav, 25(1), 117-122.

Newlin, D. B. (1995). Effect of cocaine on vagal tone: a common factors approach. Drug Alcohol Depend, 37(3),

211-216. https://doi.org/10.1016/S0306-4603(98)00128-2

Olière, S., Joliette-Riopel, A., Potvin, S., & Jutras-Aswad, D. (2013). Modulation of the endocannabinoid system:

vulnerability factor and new treatment target for stimulant addiction. Front Psychiatry, 4, 109.

https://doi.org/10.3389/fpsyt.2013.00109

Pateria, P., de Boer, B., & MacQuillan, G. (2013). Liver abnormalities in drug and substance abusers. Best Pract Res

Clin Gastroenterol, 27(4), 577-596. https://doi.org/10.1016/j.bpg.2013.08.001

Proctor, G. B. (2016). The physiology of salivary secretion. Periodontol 2000, 70(1), 11-25.

https://doi.org/10.1111/prd.12116

Proctor, G. B., & Carpenter, G. H. (2007). Regulation of salivary gland function by autonomic nerves. Auton Neu-

rosci, 133(1), 3-18. https://doi.org/10.1016/j.autneu.2006.10.006

Proctor, G. B., & Carpenter, G. H. (2014). Salivary secretion: mechanism and neural regulation. Monogr Oral Sci,

24, 14-29. https://doi.org/10.1159/000358781

Ralevic, V. (2003). Cannabinoid modulation of peripheral autonomic and sensory neurotransmission. Eur J Phar-

macol, 472(1-2), 1-21. https://doi.org/10.1016/S0014-2999(03)01813-2

Rawal, S. Y., Tatakis, D. N., & Tipton, D. A. (2012). Periodontal and oral manifestations of marijuana use. J Tenn

Dent Assoc, 92(2), 26-31; quiz 31-22.

Reddy, S., Kaul, S., Agrawal, C., Prasad, M. G., Agnihotri, J., Bhowmik, N., . . . Kambali, S. (2012). Periodontal Status

amongst Substance Abusers in Indian Population. ISRN Dent, 2012, 460856. https://doi.org/10.5402/2012/460856

Riezzo, I., Fiore, C., De Carlo, D., Pascale, N., Neri, M., Turillazzi, E., & Fineschi, V. (2012). Side effects of cocaine

abuse: multiorgan toxicity and pathological consequences. Curr Med Chem, 19(33), 5624-5646.

https://doi.org/10.2174/092986712803988893

Ron, D., & Barak, S. (2016). Molecular mechanisms underlying alcohol-drinking behaviours. Nat Rev Neurosci,

17(9), 576-591. https://doi.org/10.1038/nrn.2016.85

Singh, A., Saluja, S., Kumar, A., Agrawal, S., Thind, M., Nanda, S., & Shirani, J. (2017). Cardiovascular Complica-

tions of Marijuana and Related Substances: A Review. Cardiol Ther. https://doi.org/10.1007/s40119-017-0102-x

Sordi, M. B., Massochin, R. C., Camargo, A. R., Lemos, T., & Munhoz, E. A. (2017). Oral health assessment for users

of marijuana and cocaine/crack substances. Braz Oral Res, 31, e102.

https://doi.org/10.1590/1807-3107bor-2017.vol31.0102

Thorn, J. J., Prause, J. U., & Oxholm, P. (1989). Sialochemistry in Sjögren’s syndrome: a review. J Oral Pathol Med,

18(8), 457-468. https://doi.org/10.1111/j.1600-0714.1989.tb01343.x

Turner, R. J., & Sugiya, H. (2002). Understanding salivary ﬂuid and protein secretion. Oral Dis, 8(1), 3-11.

https://doi.org/10.1034/j.1601-0825.2002.10815.x

Waszkiewicz, N., Galinska-Skok, B., Zalewska, A., Szajda, S. D., Zwierz, K., Wiedłocha, M., & Szulc, A. (2017). Sali-

vary immune proteins monitoring can help detection of binge and chronic alcohol drinkers: Preliminary ﬁndings.

Drug Alcohol Depend, 183, 13-18. https://doi.org/10.1016/j.drugalcdep.2017.10.016

Waszkiewicz, N., Zalewska-Szajda, B., Zalewska, A., Waszkiewicz, M., Szajda, S. D., Repka, B., . . . Zwierz, K. (2012).

Decrease in salivary lactoferrin output in chronically intoxicated alcohol-dependent patients. Folia Histochem

Cytobiol, 50(2), 248-254. https://doi.org/10.5603/FHC.2012.0024

70 ODONTOLOGÍA VITAL ENERO-JUNIO 2020

Waszkiewicz, N., Zalewska-Szajda, B., Zalewska, A., Waszkiewicz, M., Szajda, S. D., Repka, B., . . . Zwierz, K.

(2012). Salivary lysozyme in smoking alcohol dependent persons. Folia Histochem Cytobiol, 50(4), 609-612.

https://doi.org/10.5603/17840

Waszkiewicz, N., Zalewska, A., Szajda, S. D., Szulc, A., Kepka, A., Minarowska, A., . . . Zwierz, K. (2012). The effect

of chronic alcohol intoxication and smoking on the activity of oral peroxidase. Folia Histochem Cytobiol, 50(3),

450-455. https://doi.org/10.5603/19756

Waszkiewicz, N., Zalewska, A., Szajda, S. D., Waszkiewicz, M., Szulc, A., Kepka, A., . . . Zwierz, K. (2012). The effect of

chronic alcohol intoxication and smoking on the output of salivary immunoglobulin A. Folia Histochem Cytobiol,

50(4), 605-608. https://doi.org/10.5603/19709

Woyceichoski, I. E., Costa, C. H., de Araújo, C. M., Brancher, J. A., Resende, L. G., Vieira, I., & de Lima, A. A. (2013).

Salivary buffer capacity, pH, and stimulated ﬂow rate of crack cocaine users. J Investig Clin Dent, 4(3), 160-163.

https://doi.org/10.1111/j.2041-1626.2012.00126.x

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Brancher, Antonio Adilson S. de Lima y José Miguel Amenábar. Esta obra se encuentra protegida por una

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