Dependence potential and abuse liability of nicotine replacement therapies

doi:10.1016/0753-3322(89)90185-6

Biomedicine & Pharmacotherapy

Volume 43, Issue 1, 1989, Pages 11-17

https://doi.org/10.1016/0753-3322(89)90185-6 Get rights and content

Abstract

Some abstinent smokers develop withdrawal symptoms when they stop using nicotine gum or when placebo is substituted; thus, physical dependence on nicotine gum does occur. Some smokers also use nicotine gum beyond the recommended period; thus, behavioral dependence on the gum occurs. Many (7–41 %) smokers misuse nicotine gum by smoking cigarettes and chewing the gum concurrently. Among smokers who stop using the gum, many (35–90 %) do not stop gum use by the recommended 3 months, and a substantial percentage (13–38 %) persist in gum use for 1 year. Among quitters, long-term use of nicotine gum appears to be greater than that of placebo gum. If rapidity of onset and frequency of use are determinants of dependence potential, then nasal sprays and aerosols but not nicotine patches should have dependence potential. There are no reports of misuse of the gum by non-smokers; thus, the gum appears to have little if any abuse liability.

Résumé

Responsabilité de l'abus dans la dépendance aux produits nicotinés de substitution. Certains ex-fumeurs développent des symptômes de sevrage quand ils cessent d'utiliser un chewing-gum à la nicotine ou quand un placebo lui est substitué. Ainsi voit-on bien apparaître une dépendance physique au chewing-gum à la nicotine. Quelques fumeurs aussi se servent de cette gomme au-delà de la durée recommandée. On peut donc également observer une dépendance comportementale pour la gomme. Beaucoup de fumeurs (7–41 %) se servent de la gomme à la nicotine d'une manière inappropriée en consommant des cigarettes de façon concomitante. Parmi les fumeurs qui abandonnent la gomme, beaucoup (35–90 %) ne se conforment pas à la durée d'utilisation recommandée de 3 mois, et une proportion notable (13–38 %) continue jusqu'à 1 an. Parmi ceux qui arrêtent la gomme, l'utilisation au long cours apparaît plus fréquente pour celle qui contient de la nicotine que pour le placebo. Si la rapidité d'action et la fréquence d'utilisation sont des facteurs déterminants pour la dépendance, les sprays par voie nasale et les aérosols devraient comporter un risque de dépendance, mais non les patches de nicotine. Aucune observation d'usage inapproprié de gomme n'a été rapportée chez les non-fumeurs. Par conséquent, la gomme elle-même ne semble guère avoir de responsabilité, pour autant qu'elle en ait, dans l'abus du produit nicotine de substitution.

References (27)

J.L. Falk
Drug dependence: myth or motive ?
Pharmacol. Biochem. Behav.
(1983)
J.C. Killen et al.
Nicotine gum and self-regulation training in smoking relapse prevention
Behav. Ther.
(1984)
American Psychiatric Association
A. Axellson et al.
The anti-smoking effect of chewing gum with nicotine of high and low bioavailability
British Thoracic Society
Comparison of four methods of smoking withdrawal in patients with smoking related diseases
Br. Med. J.
(1983)
K.O. Fagerstrom et al.
Nicotine chewing gum in smoking cessation: efficiency, nicotine dependence, therapy duration, and clinical recommendations
S.W. Gust et al.
A randomized, placebo-controlled study of the effects of dose on nicotine gum self-administration
S.M. Hall et al.
Nicotine gum and behavioral treatment: a placebo controlled trial
J. Consult. Clin. Psychol.
(1988)
A.I. Hjalmarson
Effect of nicotine chewing gum in smoking cessation
J. Am. Med. Assoc.
(1984)
J.R. Hughes et al.
Efficacy of nicotine gum in general practice

J.R. Hughes et al.

Physical dependence on nicotine gum: a placebo-substitution trial

J. Am. Med. Assoc.

(1986)

J.R. Hughes et al.

Nicotine gum to help stop smoking

J. Am. Med. Assoc.

(1984)

K. Jamorzik et al.

Placebo controlled trial of nicotine gum in general practice

Br. Med. J.

(1984)

Cited by (45)

Abuse liability assessment of the JUUL system in four flavors relative to combustible cigarette, nicotine gum and a comparator electronic nicotine delivery system among adult smokers
2020, Drug and Alcohol Dependence
The abuse liability of the JUUL System (JS) in four flavors were evaluated compared to combustible cigarettes, nicotine gum, and a comparator electronic nicotine delivery system (ENDS) with pharmacokinetics (PK) and subjective effects.
Adult smokers (N = 66; 50.0 % female; mean age = 41.1; 63.6 % white) completed a 7-arm within-subjects cross-over product-use study while confined to a clinical laboratory. Participants used JS in four flavors (Virginia Tobacco, Mango, Mint, Creme, [5.0 % nicotine; 59 mg/mL]), their usual brand (UB) cigarette, a comparator ENDS (VUSE Solo; 4.8 % nicotine, tobacco-flavor), and mint nicotine gum (4 mg) under controlled use conditions. After each product use, nicotine PK and subjective effects were assessed.
Maximum plasma nicotine levels (C_max-BL), rate of plasma nicotine rise, overall nicotine exposure (AUC_0−60-BL), and subjective liking and satisfaction of JS were significantly lower than UB cigarettes. These parameters were generally greater for JS than nicotine gum; the comparator ENDS was somewhat lower but within the range of JS. Nicotine PK did not differ among the Mint, Mango, and Virginia Tobacco JS flavors. Mint and Mango were rated as more satisfying than Virginia Tobacco and Creme.
Controlled use of JS among adult smokers resulted in nicotine delivery, product liking, and satisfaction that were less than that of combustible cigarettes but generally greater than nicotine gum. These results support the conclusion that JS has lower abuse liability than combustible cigarettes, higher abuse liability than nicotine gum, and may provide sufficient nicotine delivery and satisfying effects to support substitution for combustible cigarettes among adult smokers.
Neurotensin in the nucleus accumbens reverses dopamine supersensitivity evoked by antipsychotic treatment
2017, Neuropharmacology
Citation Excerpt :
Indeed, CONT-HAL but not INT-HAL treatment produced an upward shift in the dose-response curve for amphetamine-induced locomotion. The kinetics of administration can transform the effects of many drugs [including levodopa (Juncos et al., 1989), cocaine (Reith et al., 1987), amphetamine (Lillrank et al., 1991) and nicotine (Hughes, 1989)], and perhaps most notably within the dopamine system (Allain et al., 2015; Post, 1980). By disrupting normal D2-mediated signalling unrelentingly, continuous antipsychotic exposure might promote compensatory changes that drive dopamine supersensitivity.
Long-term exposure to antipsychotics like haloperidol can increase sensitivity to dopamine agonist stimulation. This could contribute to treatment failure and increase relapse to psychosis. Chronic antipsychotic treatment elevates neurotensin levels in the nucleus accumbens (NAc), where the neuropeptide modulates dopamine function by signalling through NTS1 receptors. We hypothesized that increasing neurotensin activity in the NAc attenuates the expression of antipsychotic-induced dopamine supersensitivity, which is indicated by a potentiated psychomotor response to amphetamine. Rats received either continuous (CONT-HAL; achieved via subcutaneous osmotic minipump) or intermittent (INT-HAL; achieved via daily subcutaneous injection) haloperidol treatment for 16–17 days. Three to 5 days later, we injected neurotensin into the NAc and measured amphetamine-induced locomotion. Only CONT-HAL rats showed potentiated amphetamine-induced locomotion, indicating dopamine supersensitivity. Compared to intra-NAc saline, intra-NAc neurotensin suppressed amphetamine-induced locomotion in CONT-HAL rats, but not in INT-HAL or control rats. In a new cohort of CONT-HAL and INT-HAL rats, we measured striatal levels of proneurotensin mRNA and NTS1 receptors. The two treatments led to overlapping but also distinct neurochemical profiles. Neither treatment altered NTS1 receptor levels in the NAc, but both increased proneurotensin mRNA levels in the NAc core. In the caudate-putamen, only INT-HAL increased NTS1 receptor levels, while only CONT-HAL increased proneurotensin mRNA expression. Thus, antipsychotic-induced dopamine supersensitivity enhances the ability of neurotensin in the NAc to regulate dopamine-mediated behaviours, and this likely does not involve changes in local levels of NTS1 receptors or proneurotensin mRNA. We conclude that increasing neurotensin activity could be considered to attenuate antipsychotic-induced dopamine supersensitivity.
How fast and how often: The pharmacokinetics of drug use are decisive in addiction
2015, Neuroscience and Biobehavioral Reviews
Citation Excerpt :
Addiction is more likely and more severe in individuals who take drugs via rapid routes of drug delivery. For instance, addiction to cocaine, amphetamine, methamphetamine, nicotine or heroin is more probable in people who consume these drugs via smoking or i.v. injection than in individuals who use slower routes of drug administration (e.g., the intranasal or transdermal routes; Barrio et al., 2001; Budney et al., 1993; Carpenter et al., 1998; Ferri and Gossop, 1999; Gossop et al., 1992, 1994; Hatsukami and Fischman, 1996; Hughes, 1989; Rawson et al., 2007; Van Dyke and Byck, 1982; Volkow and Swanson, 2003; Winger et al., 1992). Compared to intranasal drug users, individuals who smoke or inject drugs i.v. also use drugs more frequently, for a longer time, spend more money on drugs, report a greater loss of control over drug taking and are more likely to overdose (Barrio et al., 2001; Carpenter et al., 1998; Ferri and Gossop, 1999; Gossop et al., 1992, 1994; Hatsukami and Fischman, 1996; Hughes, 1989; Rawson et al., 2007; Van Dyke and Byck, 1982; Volkow and Swanson, 2003; Winger et al., 1992).
How much, how often and how fast a drug reaches the brain determine the behavioural and neuroplastic changes associated with the addiction process. Despite the critical nature of these variables, the drug addiction field often ignores pharmacokinetic issues, which we argue can lead to false conclusions. First, we review the clinical data demonstrating the importance of the speed of drug onset and of intermittent patterns of drug intake in psychostimulant drug addiction. This is followed by a review of the preclinical literature demonstrating that pharmacokinetic variables play a decisive role in determining behavioural and neurobiological outcomes in animal models of addiction. This literature includes recent data highlighting the importance of intermittent, ‘spiking’ brain levels of drug in producing an increase in the motivation to take drug over time. Rapid drug onset and intermittent drug exposure both appear to push the addiction process forward most effectively. This has significant implications for refining animal models of addiction and for better understanding the neuroadaptations that are critical for the disorder.
Tobacco harm reduction in people with serious mental illnesses
2015, The Lancet Psychiatry
Dependence levels in users of electronic cigarettes, nicotine gums and tobacco cigarettes
2015, Drug and Alcohol Dependence
Citation Excerpt :
The speed of nicotine delivery to the blood may be slower for e-cigarettes than for tobacco cigarettes, but is certainly similar to or faster than for nicotine medications (Choi et al., 2003; Bullen et al., 2010; Dawkins and Corcoran, 2014; Nides et al., 2014; Spindle et al., 2014), including the nicotine gum (Henningfield, 1995). Because the addictiveness of a drug-delivery device is in part determined by the speed of drug delivery to the brain (Le Houezec, 2003), the differences across devices suggest the hypothesis that some e-cigarettes may be less addictive than tobacco cigarettes, but as or more addictive than nicotine medications, which themselves are not at all (patch), or not very addictive (gum, lozenge; Hughes, 1989; Shiffman et al., 2003). This hypothesis is partially supported by data showing that the abuse liability of e-cigarettes is less than that of tobacco cigarettes, at least for smokers trying an e-cigarette for the first time (Vansickel et al., 2012).
To assess dependence levels in users of e-cigarettes, and compare them with dependence levels in users of nicotine gums and tobacco cigarettes.
Self-reports from cross-sectional Internet and mail surveys. Comparisons of: (a) 766 daily users of nicotine-containing e-cigarettes with 30 daily users of nicotine-free e-cigarettes; (b) 911 former smokers who used the e-cigarette daily with 451 former smokers who used the nicotine gum daily (but no e-cigarette); (c) 125 daily e-cigarette users who smoked daily (dual users) with two samples of daily smokers who did not use e-cigarettes (2206 enrolled on the Internet and 292 enrolled by mail from the general population of Geneva). We used the Fagerström test for nicotine dependence, the nicotine dependence syndrome scale, the cigarette dependence scale and versions of these scales adapted for e-cigarettes and nicotine gums.
Dependence ratings were slightly higher in users of nicotine-containing e-cigarettes than in users of nicotine-free e-cigarettes. In former smokers, long-term (>3 months) users of e-cigarettes were less dependent on e-cigarettes than long-term users of the nicotine gum were dependent on the gum. There were few differences in dependence ratings between short-term (≤3 months) users of gums or e-cigarettes. Dependence on e-cigarettes was generally lower in dual users than dependence on tobacco cigarettes in the two other samples of daily smokers.
Some e-cigarette users were dependent on nicotine-containing e-cigarettes, but these products were less addictive than tobacco cigarettes. E-cigarettes may be as or less addictive than nicotine gums, which themselves are not very addictive.
EPA Guidance on tobacco dependence and strategies for smoking cessation in people with mental illness
2014, European Psychiatry
Tobacco dependence is the most common substance use disorder in adults with mental illness. The prevalence rates for tobacco dependence are two to four times higher in these patients than in the general population. Smoking has a strong, negative influence on the life expectancy and quality of life of mental health patients, and remains the leading preventable cause of death in this group. Despite these statistics, in some countries smokers with mental illness are disadvantaged in receiving intervention and support for their tobacco dependence, which is often overlooked or even tolerated. This statement from the European Psychiatric Association (EPA) systematically reviews the current evidence on tobacco dependence and withdrawal in patients with mental illness and their treatment. It provides seven recommendations for the core components of diagnostics and treatment in this patient group. These recommendations concern: (1) the recording process, (2) the timing of the intervention, (3) counselling specificities, (4) proposed treatments, (5) frequency of contact after stopping, (6) follow-up visits and (7) relapse prevention. They aim to help clinicians improve the care, health and well-being of patients suffering from mental illness.

View all citing articles on Scopus

^☆: In: Pomerleau O. et al., eds.: Nicotine Replacement in the Treatment of Smoking: A Critical Review. Alan R. Liss, New York (in press).

View full text

DossierDependence potential and abuse liability of nicotine replacement therapies☆

Abstract

Résumé

Pharmacol. Biochem. Behav.

Behav. Ther.

The anti-smoking effect of chewing gum with nicotine of high and low bioavailability

Comparison of four methods of smoking withdrawal in patients with smoking related diseases

Br. Med. J.

Nicotine chewing gum in smoking cessation: efficiency, nicotine dependence, therapy duration, and clinical recommendations

A randomized, placebo-controlled study of the effects of dose on nicotine gum self-administration

Nicotine gum and behavioral treatment: a placebo controlled trial

J. Consult. Clin. Psychol.

Effect of nicotine chewing gum in smoking cessation

J. Am. Med. Assoc.

Efficacy of nicotine gum in general practice

Physical dependence on nicotine gum: a placebo-substitution trial

J. Am. Med. Assoc.

Nicotine gum to help stop smoking

J. Am. Med. Assoc.

Placebo controlled trial of nicotine gum in general practice

Br. Med. J.

Dossier
Dependence potential and abuse liability of nicotine replacement therapies☆