Addiction is a multidimensional psychiatric disorder that can involve various addictive
agents (drug, gambling, sex, shopping, games, etc.) (Lee et al., 2019). In recent
years, a subtype of non-substance behavioral addiction, gambling disorder (GD), has
been receiving increased attention. Reclassified from the category of impulse-control
disorders, GD is now a new category labeled “Substance-Related and Addictive Disorders”
and is the only behavioral addiction recognized in the fifth edition of the Diagnostic
and Statistical Manual [DSM-5, American Psychiatric Association (APA), 2013]. Notably,
It is estimated that ~14% of patients with substance use disorder (SUD) have GD as
well (Cowlishaw et al., 2014), since the two share many common factors, such as clinical
characteristics, social factors, personality traits (Petry et al., 2005), biochemistry
(Potenza, 2006), genetics (Leeman and Potenza, 2013), and neurocircuitry (van Holst
et al., 2010), leading to concurrent conditions in clinical population (Rush et al.,
2008; Lorains et al., 2011).
Few studies have examined the treatment options for comorbid GD/SUD. However, repetitive
transcranial magnetic stimulation (rTMS) is a promising tool in SUD that works by
modulating the impaired neural circuitry with prefrontal stimulation, to decrease
craving or drug intake (Gorelick et al., 2014; Rapinesi et al., 2016; Shen et al.,
2016; Terraneo et al., 2016; Liang et al., 2018; Lin et al., 2019; Liu et al., 2019).
Recently, a few pilot studies have shown that rTMS might be an effective treatment
for GD patients as well (Rosenberg et al., 2013; Zack, 2016; Gay et al., 2017).
In a recent study, Cardullo et al. (2019) investigated the effects of rTMS on cocaine-dependent
individuals with GD comorbidity for the first time, providing unprecedented insights
into the potential effect of rTMS as a therapeutic intervention for reducing both
gambling and cocaine use in these patients. In this study, seven male participants
who were diagnosed as having cocaine use disorder (CUD) and GD received the rTMS treatment
over 18 sessions, with 15 Hz rTMS (2,400 pulses/session, total 43,200 pulses) over
the left dorsal lateral prefrontal cortex (DLPFC). In addition, their level of gambling
severity and cocaine craving, as well as sleep quality and other negative symptoms,
was assessed using the Gambling-Symptom Assessment Scale (G-SAS), Cocaine Craving
Questionnaire (CCQ), Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory
(BDI), Self-rating Anxiety Scale (SAS), and Symptoms checklist-90 (SCL-90), respectively.
Assessments were made at baseline, immediately after completion of the first week
of treatment (twice/day), as well as at 30 and 60 days (one time/week) after the first
session. During the whole process, no aversive side effects were reported. Five days
after the first treatment, their level of both cocaine craving and gambling severity
dropped dramatically and stayed stable over time. Moreover, negative symptoms including
sleep disturbance, depression, and anxiety significantly decreased compared with the
baseline as reflected in their PSQI, BDI, and SAS scores. At the 60-days follow-up,
four out of seven patients had not relapsed, for either cocaine use or gambling.
The treatment effects observed for GD/CUD patients were in line with previous results
for patients with CUD or GD, separately. It is possible that these treatment effects
were due to increased dopaminergic system activity following brain stimulation, as
dopamine is implicated in both substance use and gambling. Substance-related disorder
is assumed to be associated with a dysregulation of dopamine transmission resulting
from learned drug-related reinforcers (Di Chiara and Imperato, 1988; Volkow et al.,
2007, 2017). Similarly, the uncertainty of rewards, a core characteristic of gambling,
may play the same role as drug-related reinforcers in dopamine pathways (Fiorillo
et al., 2003; Zald et al., 2004). Furthermore, some studies have indicated the reciprocal
priming effects of substance use and gambling. For instance, one study indicated an
acute effect of a psychostimulant in individuals with pathological gambling (PG, a
former name of GD), whose motivation for gambling was primed by amphetamine (Zack
and Poulos, 2004). Similarly, exposure to conditions of uncertain reward also promotes
the pursuit of amphetamine in rats (Mascia et al., 2019). It will be important to
investigate the modification of these reward-related behavioral changes in GD/CUD
patients after brain stimulation treatments.
Few studies have compared individuals who have substance dependence and pathological
gambling (SDPG) with individuals who only have substance dependents (SD), in personality
(Petry, 2001), cognitive function (Krmpotich et al., 2015), and brain alterations
(Yip et al., 2018). According to these studies, individuals with SDPG have elevated
impulsivity personality trait than those with SD when assessed by the Barratt Impulsiveness
Scale (BIS-11) (Krmpotich et al., 2015), Stanford Time Perception Inventory (STPI),
and Eysenck and Barratt scales (Petry, 2001). It would be interesting to know whether
rTMS treatment could restore the different behavioral aspects to similar extent in
SDPG and SD patients. This would provide additional support for rTMS to be used as
a treatment option for comorbidity patients. A recent study highlighted the potential
of prefrontal rTMS in reducing behavioral impulsivity of methamphetamine dependents
(Yuan et al., 2020), which would be an implication for treating GD/SUD patients, as
impulsivity is a shared feature.
This clinical research seems encouraging, as the first step toward investigating rTMS
intervention in patients with SDPG. The promising effects thus far suggest that rTMS
could be beneficial to comorbid cases, and may even pronounce greater efficiency than
when employed with addicts with a single diagnosis. Nevertheless, considering the
heterogeneity of addicts and types of addictions, patients with comorbid CUD and GD
present only one subtype of addiction. Therefore, it should be careful to generalize
such results of Cardullo's article to other types of addictions. In order to achieve
the maximal effectiveness of rTMS as a treatment for addiction and to better understand
the essence of addiction, further investigations are needed to explore other drug
abuses concurrent with GD, and compare the treatment effects of rTMS in patients with
SDPG and SD.
Author Contributions
HO, YZ, and WH conceived the idea and wrote the manuscript together. All authors contributed
to the article and approved the submitted version.
Conflict of Interest
The authors declare that the research was conducted in the absence of any commercial
or financial relationships that could be construed as a potential conflict of interest.