Comparison of Physical Effect Between Two Training Methods for Individuals With Substance Use Disorder

yanguang yang Shanghai University of sport Jing-yi Chen Shanghai University of Sport Xiao-wu Pang Shanghai University of Sport Meng-lu Shen Shanghai University of Sport Su-yong Yang Shanghai University of Sport Ding Xu Shanghai Drug Administration Ke Xiao Shanghai Gaojing Drug Compulsory Detoxi cation and Rehabilitation Center Tian-yuan Wang Shanghai University of Sport Jia-bin Wang Shanghai University of Sport Dong Zhu (  zhudong@sus.edu.cn ) School of international education, Shanghai University of Sport, 200438 https://orcid.org/0000-0002-6611-3695


Background
Substance use disorder (SUD) is a highly destructive, chronic and relapsing disease that brings adverse consequences to society and the individuals with SUD's own psychology and physical, requiring more effective treatment methods (1). The social harm caused by the illicit drug problem is huge. At the same time, how to help individuals rehabilitate from drug abuse and return to normal life have become an important eld of rehabilitation. Due to long-term drug abuse, individuals with SUD suffer serious physical and psychological damage, leading to the occurrence of various chronic diseases and complications (2,3). The individuals with SUD had less protein, muscle mass and fat loss than the general, which resulted in hypertension re exes, dyskinesia, and gait instability (4). In addition, SUD may lead to physical tness decline, tachycardia, high blood pressure and chronic cardiovascular diseases (5). Physical and mental injuries affect the life self-con dence of patients with SUD, but also have a negative impact on detoxi cation. Effective physical health education and exercise guide are the best carrier to promote the integration of individual's body and mind, the effective form to realize "strengthening the body and civilized the spirit", and the best way to improve the recovery rate of drug withdrawal and reduce the relapse rate (6). A study showed that exercise may serve to complement other therapy and medication approaches for methamphetamine users, particularly if users are able to more readily utilize relapse prevention skills and incorporate positive behavioral changes consistent with treatment goals (7). Currently, exercise is considered as a potential new treatment for SUD and exercise intervention is also considered as an independent and important supplemental means for SUD (8). Exercise has become one of promising intervention methods for SUD because it is economic, long-term effect.
A growing body of research has demonstrated that aerobic exercise can be an effective and persistent treatment for those with substance use disorders (SUD), which can effectively increase the abstinence rate, ease withdrawal symptoms, and reduce anxiety and depression (9). Study indicates that moderate-intensity aerobic exercise has shown good rehabilitation bene ts in assisting detoxi cation, relieving withdrawal syndrome and inhibiting relapse impulse and relapse behavior, and is considered relatively safe and green (10). Furthermore, a large number of theoretical and empirical studies have found that short-term, medium intensity aerobic exercise, traditional Chinese sports and resistance exercise can signi cantly improve the brain cognition, psychological behavior and physical function of the new type drug-dependent, improve the quality of life, and reduce the symptom of drug craving (11,12). In terms of psychological rehabilitation, many studies have shown that exercise can produce positive emotions for drug users, including emotion regulation, experiencing pleasure, reducing depression symptoms and insomnia (13,14).
Although the mechanism of exercise detoxi cation is not clear, it does bring bene ts to individuals with SUD. Studies have shown that exercise can improve executive function and brain activity (15), which may be an important reason to curb addiction in individuals with SUD. To further enhance the training effect, it is an important direction to explore the most suitable exercise mode. To date, many articles on drug rehabilitation have talked about bene ts of moderate intensity continuous training (MICT). However, future research in the eld of exercise intervention should focus on using anaerobic exercise as an intervention to explore whether there is a dose-effect relationship to inhibit relapse (16). Many studies compared the effect of HIIT and MICT. For example, research indicates HIIT have better effect on cognitive ability and cardiopulmonary function than MICT (17,18). In fact, the results of sports studies show that MICT and HIIT are both bene cial but have different effects on the improvement of body function (19). Moreover, meeting the 2008 Physical Activity Guidelines for Americans minimum by either moderate-or vigorous-intensity activities was associated with nearly the maximum longevity bene t (20).
While people pay attention to MICT exercise rehabilitation, the emergence of HIIT has attracted much concern. The mental and cognitive health by HIIT, comparing to the traditional high-intensity sports, as an effective way to improve physical, has also attracted great interest in recent years.
There is increasingly evidence that despite a reduction in exercise duration and volume, HIIT resulted in similar or greater physical adaptations relative to MICT, including improvements in body composition, cardiovascular function, and metabolic health (21). Studies also show that compared with the traditional moderate-intensity continuous aerobic training, HIIT has better exercise enjoyment, and provides the same effect in the same effect in aerobic tness, quality of life, e ciency, safety, tolerance and shortterm exercise adherence (22).
HIIT not only brings more effective training to healthy people but also gradually becomes an important means for the rehabilitation of many chronic diseases. In recent years, HIIT has become a form of alternative or complementary aerobic endurance training. In long-term and short-term studies, it has the same value as, if not better than, MICT in terms of tness, cardiovascular function, quality of life, exercise e ciency, safety, the tolerance and exercise adherence in a short period of time (23). The meta-analysis of 10 studies on patients with Coronary Artery Disease showed that HIIT was more effective in improving patients' mean VO 2 peak than MICT (24). Studies had con rmed that HIIT can effectively prevent and treat type 2 diabetes and cardiovascular disease, and has great potential in the eld of public health (25). Previous study has also found HIIT can improved SUD patients VO 2 max, indicating that not only will they have a strongly decreased mortality rate, but also a considerable reduced risk of developing cardiovascular disease (26). Because of its time-saving and remarkable effect, HIIT has gradually become an alternative to the traditional training mode and achieved good results. An acute bout of HIIT can also be more enjoyable than an acute bout of MICT (27). Importantly, sedentary young adults report greater enjoyment from a single bout of HIIT and endorsed it as an exercise regime they would chose to continue on their own (27). Furthermore, a six week long-term HIIT and MICT trial for sedentary people also showed that during the six week period, the subjects' enjoyment of HIIT increased while the pleasure of MICT decreased slightly (22). This seems to show that HIIT has better exercise enjoyment than MICT.
To date, only few articles in the literature discussed the effect of HIIT on substance abuse, one showed that HIIT was feasible for SUD patients in treatment, also, it is reported that HIIT can improve depression and reduce the risk of cardiovascular disease (26). However, the theoretical basis for adopting HIIT has not been fully con rmed in the scienti c reports. The effects of MICT on the physical functioning of individuals with SUD have been demonstrated, but it is not clear whether different intensity or form of exercise produces the same or superior results. Considering the bene ts and theoretical results of HIIT in the study of many chronic diseases, it is feasible to apply it in SUD. Therefore, the study puts forward the question-which exercise is better for SUD? HIIT or MICT? The purpose of this study was to compare on the physical tness of HIIT or MICT intervention on the individual with SUD, the hypothesis was the HIIT has better physical tness recovery effect than MICT for SUD.

Methods
Design This single-blind (assessors-blind), two-group randomized controlled trial was conducted from January 2019 to December 2019. The study protocol was approved by the Ethical Committees of the Shanghai University of Sport and the Shanghai Narcotics Control Commission. Written consent was obtained from each participant.

Participants
The participants were all male amphetamine-type stimulant (ATS) dependent individuals. At the time of recruitment, a total 1200 individuals with SUD were receiving treatment in a Shanghai Compulsory Rehabilitation Center (SCRC). There were 120 ATS dependent subjects voluntarily participated in this study. The inclusion criteria were 1) age 18-40; 2) subjects who met the diagnosis of MA dependence according to Diagnostic and Statistical Manual of Mental Disorders criteria (DSM-IV); 3) the treatment duration in SCRC should be more than 1 year;4) no serious medical or mental illness; 5) primary school or above of education. Exclusion criteria: 1) currently diagnosed diseases of the cardiovascular system, respiratory system, and nervous system; 2) anti-social personality disorder and borderline personality disorder; 3) subjects who were unwilling to accept the assigned intervention conditions were excluded.

Intervention
The participants were assigned randomly by computer-generated randomization to either the HIIT (n = 60) or MICT groups (n = 60).
They participated in exercise sessions three times a week for 12 consecutive months.

HIIT group
The training contents in the HIIT group included non-confrontational basketball training, resistance training (weight training and strength machines), rope skipping and running. The exercise intensity was monitored by heart rate monitor (Polar TeamPro), and the heart rate was maintained at 80-85% of the subjects' maximum heart rate (80-85%HR max ). The duration of each training session was 60 minutes, 10 minutes for warm-up and 10 minutes for cool-down, 3 times a week. Trainings were arranged on Monday, Wednesday and Friday. The main content of each training session was divided into three parts: basketball (15 minutes), weight training (15 minutes) and running (10 minutes) from January to March; basketball (15 minutes), weight training (15 minutes) and rope skipping (10 minutes) from April to June; weight training (15 minutes), strength machines training (15 minutes) and running (10 minutes) from July to September; basketball (15 minutes), weight training (15 minutes) and running (10 minutes) from October to December. The training patterns were short interval training organized by the experienced instructors from Shanghai university of sport. An exercise training expertise team instructed and supervised the training plan of the HIIT group.

MICT group
The MICT group was trained with Tai Chi, mind-body exercise and recreation activity. The heart rate during the exercise was 55-65% of the maximum heart rate (55-65%HR max ). The duration of the MICT intervention was similar to that of the HIIT intervention and the training intervention of the two groups was conducted at the same time. The Tai Chi for the MICT group was a kind of modi ed Tai Chi . The recreation activity was adopted the ninth edition of "Guang Bo Ti Cao" designed by the China General Administration of Sports, while the mind-body exercise was adopted a kind of modi ed Qi Gong, Tai Chi and Yoga with moderate intensity. Each session in the MICT group included a 10 min recreation activity (Guang Bo Ti Cao), 10 min mind-body exercise and 20 min Tai Chi. The duration of Tai Chi in a training session was increased more than 20 minutes in the second half year, along with the reduction of the training duration of mind-body exercise and recreation activity. One experienced instructor from the Shanghai University of Sport instructed the MICT group.

Procedure
The participants were informed of the purpose of this study and signed a consent form during the admission process. The study was performed in accordance with the Declaration of Helsinki II. The HIIT and MICT interventions were performed on a basketball eld under fair weather or in an indoor tness gym. The intervention outcomes of physical tness were assessed at the baseline, 3 months, 6 months, 9 months and 12 months, the ATS craving level was assessed at the baseline, 6 months and 12 months. The experienced researchers conducted the assessment and were blinded to the two groups.

Outcome measures
The primary outcomes The physical tness tests were administrated by experienced investigators. Measurements were performed in the morning at the same time. Blood pressure was measured under standardized conditions prior to other tests: participants were asked to rest for 5 min and had not taken any caffeine or tobacco products within 30 minutes. Heart rate of individuals with SUD was monitored with Polar TeamPro.
The tness test followed the protocol of national physical tness test. Push-up, sit-and-reach, one-leg stand with eyes closed, vital capacity (VC), height and weight, choice reaction time, hand grip assessment were used the model of BW-FC-9201L (Fitness Assessment System) to test the physical tness outcomes. All tests were repeated twice and the best performance was recorded.
VC measurement requires that subject holds the test instrument and breathes out all the air with maximum force after the maximum inhalation. Muscle strength tests include hand grip and push-up. During the hand grip test, the subjects applied the dominant hand to grasp the grip strength device with the maximum strength. The push-up test was performed on the push-up testers, subjects' forefoot or toes on oor, hips and back keep straight, the push-up tester placed near subject's chest, the repetition numbers were counted automatically by push-up tester whenever the torso down-and-up front of the tester sensors. The test index of exibility is sit and reach. The subject sits in front of the device with slippers and knees straight. Stretch their hands and body forward as far as possible, measuring the maximum distance where subjects' ngertips can reach. In the choice reaction time test, the subjects used the middle and index ngers of the dominant hand to quickly press the random signal button. The balance function was measured by the duration of standing on one leg with eyes closed. During the test, the subjects stood on the test mat with the dominant leg, eyes closed, then recorded the time of standing on one leg.

The secondary outcome
The craving level was assessed using the visual analog scale (VAS), which is a response scale that measures subjective attitudes that could not be observed directly. Subjects were asked to indicate, on a scale from 0 (no craving for ATS drugs) to 10 (strong craving for ATS drugs), the extent of their craving for ATS drugs, a VAS is considered an appropriate means of assessing cueinduced ATS craving (28).

Statistical analyses
Statistical analyses were performed using SPSS 22.0 (Chicago, USA). Pearson chi-squared test was applied for categorical variables of demography, and independent sample t-test was applied for continuous variables at the baseline comparison. Pearson chi-squared test and independent sample t-test was used to compare the demographic characteristics differences at baseline.
A two-way repeated measures analysis of variance (ANOVA) was applied to test whether the treatments were different after 24 weeks. Time (baseline, 3 month, 6 month, 9 month, 12 month) was the within-group factor, groups (HIIT and MICT) were the between-group factors for the physical tness comparison. Time (baseline, 6 month, 12 month) was the with-group factor, groups (HIIT and MICT) were there between-group factors for the craving level of VAS comparison. A post hoc test with LSD correction was used to examine which group was different if the ANOVA showed a signi cant interaction. All data were presented as the mean ± standard deviation and a p-value <0.05 was considered statistically signi cant.

Results
A total of 120 male individuals with SUD participated in the study, in which, 86 completed the intervention, 34 subjects dropped out because of different reasons. The details were shown in gure 1.
The subjects in the HIIT group were: age, 33

Physical tness
After the 12 months exercise intervention, signi cant differences were found in the within-group factor in SBP (F (4,336) =12.799, P<0.001) and DBP (F (4,336) =9.495, P<0.001). No signi cant interactions of group × time were found in SBP and DBP.
Although the balance in both groups was improved from the beginning, the both groups was found that the improvement occurred in the rst half year, the balance test by one-leg stand with eyes closed was not improved in the second half year. The result indicated that the MICT group had better balance score comparing to the HIIT group ( Figure 2). Subjects both in HIIT and MICT improved the upper-limb strength gradually tested by push-up, although the mean differences of subjects in HIIT group was 4.4 more than subjects in MICT group, there was no signi cant difference with interaction of group × time found in this test (Figure 3).

The level of craving
The craving level of VAS after the 12 months exercise intervention was found signi cantly decrease (F (2,168) =11.25, P<0.001) in both groups, but no signi cant difference with interactions of group × time were found in VAS ( Figure 4).

Physical tness improved in both groups
In this study, a randomized controlled trial of HIIT and MICT was conducted to explore whether HIIT is more conducive to the rehabilitation of physical functions for individuals with SUD. During the 12 months exercise intervention, HIIT and MICT groups were found signi cantly improved in VC, grip strength, sit-and-reach, choice reaction time, one-leg stand with eyes closed, push-up. The blood pressure and the craving level in the two groups decreased signi cantly, but no signi cant differences were found between the HIIT group and MICT group.

Choice reaction time declined
Choice reaction time (CRT) is one of the most important indicators of physical tness. It re ects the function of the human nervous system to some extent. The smaller the reaction time, the faster the human body responses, the better the function of the nervous system is. Performance in a CRT task is applied as an indicator of cognitive capacity, including aspects of eye-hand reaction time, attentiveness, and processing speed (29). In this study, The CRT in the experimental group decreased by 0.03s, the CRT in the control group decreased by 0.04s. There was no signi cant difference between groups, whereas, both groups found a signi cant difference in CRT compared to the baseline. The results are consistent with that physical activity can improve CRT, which indicates that no matter what form of exercise, it is helpful to improve the reaction time. The improvement of reaction time may be explained by the fact that physical exercise can improve the function of central nervous system ( Figure 5).

Balance improved
The one-leg stand with eyes-closed test was performed to measure the balance control of the subjects. The increase in time spent standing on one foot with eyes closed in individuals with SUD indicated the improvement of their balance ability. Previous study showed an improvement in balance control after long term practice of Tai Chi (30). In this study, the MICT group was able to stand on one leg with eyes closed for 14s longer than baseline while the HIIT group was 11s longer than baseline. The evidence proved that both HIIT and MICT can improve balance ability. However, although there was no signi cant difference between groups, MICT group seems to have more potential to improve balance than HIIT group because of Tai Chi content arranged.

Blood pressure decreased
The subjects in HIIT and MICT group had the same effect on diastolic and systolic blood pressure, both types of training effectively reduced blood pressures for individuals of SUD. A reduction in blood pressure can have a positive effect on the health of individuals. At present, systemic blood pressure is controlled by total peripheral resistance, which is determined by the diameter of small arteries and arterioles (30). The decrease in blood pressure in individuals with SUD may be due to increased exibility in their blood vessels through training and reduced peripheral resistance. In this study, exercise intervention can signi cantly reduce blood pressure, which may be due to the Tai Chi and HIIT exercise which improve the cardiac function for subjects, as well as increase stroke output and blood circulation. The relaxation form of exercise may reduce the tension of vascular center and vascular smooth muscle, and accelerate blood ow leading to the reduction of blood pressure. The practice of regular physical exercise can reduce resting blood pressure chronically, as a result, it induce post-exercise hypotension, which is a reduction in blood pressure below resting values after exercise training (31). Therefore, HIIT and MICT have a similar effect to reduce blood pressure. Both HIIT and MICT can be applied as effective exercises for rehabilitation for individuals with SUD in term of reducing blood pressure.
Flexibility and vital capacity improved HIIT, MICT or Tai Chi exercise for different types of participants were all able to improve the exibility for subjects (32,33), which is the same as the results of this study. Result shows that the two kinds of exercises have similar promoting effects on muscle exibility.
In this study, vital capacity in HIIT group was increased by 496 ml, whereas, MICT group was increased by 514 ml. The results demonstrated improvements in vital capacity were similar. Some preliminary evidence suggests that Tai Chi exercise may increase lung function (34,35). One of the explanations is that Tai Chi combines breathing with movement closely to improve breathing e ciency. Furthermore, study shows HIIT and MICT are both effective for improving lung function (36). HIIT is at least as effective as MCT for improving functional capacity and quality of life measures in patients with pulmonary disease (36). Therefore, the experimental results are similar to those of some studies, which prove that both HIIT and MICT have similar effects on improving lung vital capacity.

HIIT is better in strength development
In this study, from the data, the grip strength of HIIT group was increased by 5.48kg, while subjects in MICT group was increased by 4.68kg; The number of push-up in HIIT group was increased by 7 repetitions, while subjects in MICT group was increased less than 5 repetitions. The results showed that the improvement of grip strength in the two groups was similar, but the improvement of push up in HIIT group was better than that in MICT group. This demonstrated both groups increased (P < 0.05) muscle strength; whereas, greater muscle strength gains in HIIT group. The possible explanation is the training content of HIIT group includes resistance training (37), which can effectively improve the muscle strength. This result has been supported in the previous study. A study reported HIIT is better at improving upper limb, waist and abdominal strength for individuals with SUD (33).
Interestingly, muscle strength increased was also observed in MICT group. Some preliminary evidence suggests that Tai Chi exercise may increase the body's muscle strength (38,39). However, study nds Tai Chi has no advantages in improving muscle strength (30). It is not sure whether Tai Chi intervention improved the strength in MICT group, because subjects in MICT group not only practiced Tai Chi, but also engaged in medium intensity broadcast exercise.
Does HIIT training has better effect than MICT?
After 12 months exercise training, the results showed HIIT and MICT training have the same effect on the physical tness for individuals with SUD. The results are not consistent with the previous hypothesis. Generally, the greater the intensity of exercise causing the more profound the stimulation to the human body, the more signi cant the training effect has. However, the differences of physical tness and craving level between the two groups were not signi cant. In terms of standing on one leg with eyes closed, the bene ts of the subjects in control group was even better than those of the experimental group. The advantage of HIIT over MICT is mainly in effect of cardiovascular function (40), but there is no evidence that HIIT training is superior to MICT.
Several studies have shown the same effect of HIIT and MICT. In the exercise intervention with HIIT for type 2 diabetes over 12week, it was found that there was no signi cant difference in the test indicators of positively altering body fat, increasing peak power output, glucose control, cardiovascular risk, and microvascular complication markers in the HIIT group and the MICT group (19). In an exercise intervention for obese men, HIIT was veri ed as an equally effective exercise mode for improving 24-h glycemic control in overweight and obese adults comparing to MICT (41). However, Haykowsky et al. (42) showed that HIIT was superior to MICT in terms of improving VO 2 peak for patients with congestive heart failure, with similar effects on left ventricular function and exercise compliance. Similarly, in patients with coronary heart disease, studies demonstrated HIIT has greater effect on ventilatory threshold and VO 2 peak compared to MICT, with similar effects on blood pressure (43,44).
As can be seen from this, the advantages and disadvantages of HIIT and MICT are still uncertain, many studies believe that these two training methods can produce equal bene ts. There may be several reasons for this phenomenon. First, patients with different symptoms are suitable for different training methods, and different training methods can produce different bene ts at different stages of the disease. For example, long term continuous aerobic exercise training plays an important role in maintaining the health and well-being of patients with cardiovascular disease, including the potential to maintain ability of self-care and clinical bene ts during aging (45)(46)(47). Short HIIT is useful in the initial and improved stages of cardiac rehabilitation, while MICT or HIIT regimens seem to be more appropriate for the improvement and maintenance stages, as they have higher physiological stimulation (24).
Secondly, the correlation between the physical bene ts and the amount of exercise generated by HIIT and MICT is greater than the intensity of exercise. Martin J. Gibala et al. (48) compared the 6-week HIIT based on Wingate with the traditional endurance training, it was found that although the weekly training amount (90% reduction in HIIT group) and time input (67% decreased in HIIT group), the training had similar improvement on various indexes of skeletal muscle and cardiovascular adaptation. Related studies focus more on the difference between these two training methods and less on the comparison of the total amount of exercise in the same or different situations. Thirdly, there is no exploration of the optimal intensity of HIIT training currently. Different intensity of HIIT training may have different effects on the various subjects.

Conclusion
The HIIT and MICT are both effective training methods to improve physical tness for individuals with SUD. HIIT training method doesn't show superior to MICT in terms of physical tness after 12 months intervention for subjects with SUD.

Limitations
The participants were selected from a Shanghai mandatory detoxi cation and rehabilitation center. As physical activity is bene t for drug dependents physically and mentally, exercise as a supplementary treatment is one of drug rehabilitation treatments listed in Shanghai detoxi cation and rehabilitation centers. All substance dependents need to participate in physical activity. Therefore, it is hardly to nd any participant does not engage in sports. This is a limitation that we can't con rm the level of bene ts brought by exercise training.
Generally, the exercise intensity of HIIT is 90%-95% HRmax (49,50), while the exercise intensity of the experimental group in this study was basically around 80%-85%HRmax. This is because most of the subjects belonged to the low-exercise group, their physical conditions were weak after taking illicit drugs. Considering the exercise risk of the subjects, the optimal exercise intensity could not be achieved. The actual exercise intensity in HIIT group may not be the optimal intensity to stimulate the physical function of individuals with SUD, which maybe one of the factors that caused no signi cant difference between the HIIT group and MICT group.
The long-term effect of HIIT training for individuals with SUD is still unclear, the mechanism of HIIT training needs further con rmation. In the future study of exercise intervention, the exercise intensity of the HIIT will be further enhanced to maintain at 90%HRmax or higher, and the interval time will be strictly controlled. The study was supported by staffs of Shanghai Gao Jing mandatory detoxi cation and rehabilitation center.

Authors contributions
Dong Zhu ,Yan-guang Yang and Jing-yi Chen contributed to design of the study, analysis and interpretation of the data and writing of the manuscript. Xiao-Wu Pang, Meng-lu Shen, Tian-yuan Wang and Jia-bin Wang designed the training plan , guided the participants in exercise and tested the participants. Su-yong Yang, Ding Xu and Ke Xiao collected data and approved nal version of manuscript. All authors read and approved the manuscript and have given consent for the submission of the nal article.
Ethics approval and consent to participate Ethics approval was obtained from the Ethical Committees of the Shanghai University of Sport and the Shanghai Narcotics Control Commission (SNCC). All subjects provided written informed consent to participate in the study and to have their results analyzed.

Not applicable
Availability of data and materials The datasets used and/or analysed during the current study are available from corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests.