Substance use disorders (SUD) have wide-reaching impacts on health and well-being and contribute substantially to the global disease burden [1]. They are associated with shorter life expectancy, and comorbid medical conditions are common [2]. The prevalence of co-occurring personality and other psychiatric disorders is high, with estimates ranging from 50% to 90% [3]. Mood and anxiety disorders are prevalent and affect both the severity and outcome of treatment [4]. Current treatment options for SUDs include cognitive behavioral therapy, motivational interviewing, and medication. Although documented as effective, these methods do not help all patients. Relapse rates range between 40% and 60% [5], and dropout rates from in-patient treatment is around 30% [6].

Despite their high prevalence, few people with SUDs ever receive treatment, and there is a need for more treatment options [7,8]. One potential explanation for poor help seeking is the perceived stigma associated with traditional treatments [9,10]. Lifestyle-focused interventions have potential to increase help seeking by reducing this stigma.

Physical activity has been suggested as an alternative or complementary treatment option for SUDs [11-13]. The rationale is that physical exercise might be effective due to its beneficial effects on factors related to relapse and the maintenance of the disorder, such as comorbid mental disorders, craving, and emotional dysregulation [14-17].

Regular physical activity increases fitness and lowers the probability of chronic diseases [18,19]. It has been proposed as a strategy for alleviating symptoms of psychiatric disorders in general [20,21], and its application in the mental health care system is increasing. Regular physical activity has been shown to be effective in the prevention and treatment of common mental health conditions [22]. Studies also indicate that physical activity alleviates symptoms in people suffering from severe mental disorders [23]. Acute bouts of exercise have cognitive and mood-enhancing benefits, including improved executive functioning and lower state anxiety and stress reactivity [24,25]. The mechanisms behind the psychological benefits of exercise in SUDs are not well established, but one tenable hypothesis is that they are partly mediated by changes in the stress hormone cortisol [24].

While the effects of exercise are well documented for common mental disorders, there has been less research focus on SUDs. Most studies have addressed the effect of chronic exercise interventions on smoking cessation or alcohol misuse. Long-term exercise programs might affect smoking behavior [26] and lower tobacco cravings [27]. A meta-analysis of 21 exercise studies for alcohol use disorder concluded that, while regular exercise did not seem to affect consumption, it had beneficial effects on depression and physical fitness [28]. In another meta-analysis, Wang et al [29] found that exercise was associated with greater abstinence rates among illicit drug users compared with those using alcohol and nicotine. The effect of exercise on withdrawal symptoms, anxiety, and depression was not moderated by the type of substance used. Colledge et al [30] reviewed the effects of anaerobic exercise on SUDs. The results were mixed, with some evidence of a positive effect on abstinence from nicotine. No conclusions could be drawn regarding the effects of exercise among illicit drug users.

One plausible explanation for the beneficial long-term effects of an exercise program is that many single sessions have a cumulative long-term benefit. Few studies have addressed the short-term effects of physical activity in SUDs. A study of 45 regular smokers found that bouts of moderate and vigorous exercise provided relief from withdrawal symptoms, while moderate exercise relieved distress and improved mood [31]. Studies addressing alcohol urges or cravings show promising results, with lower craving after low-to-moderate intensity exercise [13,32]. Wang et al [33] studied the development of craving for amphetamines and found a reduction in cravings during and immediately after stationary cycle exercise. Results suggest that the intensity of the exercise may affect craving, with the lowest craving following moderate-to-vigorous exercise [34].

The misuse of a single substance is exceptional in SUDs [35]. Whether acute exercise can benefit people with polysubstance dependencies is unclear. Most studies have assessed aerobic forms of exercise, often in laboratory conditions using stationary bicycles [12,28]; little is known about other forms of exercise in clinical settings. With some exceptions [25], psychological benefits across different forms of exercise have not been compared, and it is unclear how long the changes last following a single exercise session. Studies have mostly used pre- and postassessments only, which is a limitation.

To address these questions, we conducted a feasibility study to compare the short-term effects of 3 different exercises (soccer, circuit training, and walking) conducted in nonlaboratory settings [36]. Findings suggested that moderately intense exercise activities performed in natural settings may increase mood, help attenuate drug cravings, increase positive affect, decrease negative affect, and improve self-esteem. The results were promising but need to be replicated with a larger sample and a randomized design.

In this study, we are conducting a multicenter randomized controlled trial to compare the short-term effects of 2 forms of exercise (soccer and circuit training) with a control condition (a lecture on the health benefits of physical activity) in polydrug-dependent inpatients. We chose to compare the effects of exercise to a nonexercising control group (lecture) instead of a walking-based intervention, as previous studies have shown that even light physical activity can have mood-enhancing effects [37]. We are also performing biomarker analyses of cortisol to better understand the underlying mechanisms.

Key research questions that will be addressed include (1) What are the short-term effects of soccer and circuit training on mood (primary outcome), drug craving, positive and negative affect, state anxiety, and self-esteem in adults with SUD? (2) How long do the effects last after the exercise sessions end? (3) Are there differences between the two forms of exercise? (4) Do the effects differ with the intensity of the exercise? and (5) Are the study outcomes associated with changes in the stress hormone cortisol?

Based on previous studies [33,38], we hypothesize that there will be positive psychological effects on the study outcomes after exercise, with a reduction in craving and an improvement in mood and affects. We expect to find larger improvements in the intervention groups than in the control group.

We adhered to the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines in the preparation of this protocol. The study will be reported according to CONSORT (Consolidated Standards of Reporting Trials) ethical guideline recommendations.

Data collection was completed in August 2019. In total, 39 patients admitted at 3 treatment centers participated in the study. Data will be analyzed during 2020.

Many SUD clinics have begun to implement physical activity as part of routine inpatient treatment due to its reported benefits. This study on acute exercise will add clinically relevant information about the short-term effects of soccer and circuit training on mood, craving, state anxiety, and self-esteem in this population. Most previous studies have performed pre-exercise and postexercise assessments only. The current study will add information on how the effects develop beyond the immediate cessation of exercise. The activities in the study are readily available, inexpensive, and popular in the general population. If the interventions are effective, they can easily be integrated into different clinical settings, for both inpatients and outpatients, and adapted to the participant’s fitness level.

The study is designed to reflect the clinical realities of inpatient treatment for SUDs. Typically, patients use multiple substances [3,35]. The inclusion of patients with comorbid SUD and mental disorders will give the study a high ecological validity but might also make the results difficult to interpret. Different drugs and various mental disorders might be affected in different ways by the interventions. Gathering information on the participants’ co-occurring disorders will potentially enable subgroup analyses to differentiate exercise effects in those with different combinations of substance and mental health problems.

Craving is highly relevant in clinical settings, even though the nature of it and the items included in instruments that assess craving have been debated [15,46,47]. By using a single-item scale, it will not be possible to capture changes in different aspects of craving. The participants might have different perceptions of craving, varying from a subjective desire to consume a substance to various bodily sensations. This is a potential limitation. However, previous studies assessing acute craving have used single-item VAS scales [48,49]. As the aim of the present study is to assess changes in participants’ overall subjective experience of craving and whether exercise can help attenuate it, we believe that a single-item scale can adequately capture this.

Using saliva samples is a noninvasive method for assessing cortisol levels. There is no need for medical staff, and saliva can be stored at room temperature for several hours before freezing. The drawback of saliva cortisol (versus serum cortisol) is that the use of tobacco and the presence of blood in the samples may lead to falsely elevated cortisol levels [50]. To control for this, the laboratory will not analyze samples with traces of blood. Samples with cortisol levels above reference levels will be excluded from analysis.

Dropout rates from treatment studies of SUDs are often high [6,28]. To minimize the risk of dropout, a member of the research group visited the treatment center 1 week before the study to answer questions. The recruitment took place a maximum of two weeks ahead of the trial. We tried to minimize dropout by keeping the overall intervention period short and integrating the interventions into the usual treatment routines at the treatment centers. This also minimized interference in the patients’ usual treatment.