Participants were patients with MAMP use disorder receiving outpatient treatment at a psychiatric hospital in Japan. Because MAMP use is illegal in Japan and many people who use it are concerned about the confidentiality of their information, recruiting participants from the general population was considered difficult. Therefore, we targeted individuals receiving outpatient treatment, for whom face-to-face recruitment was feasible. The inclusion criteria were (1) severity of MAMP use within the past year assessed as a score between 1 and 8 on the Drug Abuse Screening Test 10-item version (DAST-10) [28,29], (2) ownership of a smartphone (iOS 14 or later or Android 7.0 or later), (3) ability to wear a Fitbit continuously and to record daily entries using a self-monitoring app for 8 weeks, and (4) age 20 years or older. The exclusion criteria were (1) inability to speak or write in Japanese, (2) lack of internet access or inability to complete web-based surveys, (3) inability to participate for the entire 8-week study period, and (4) determination by the primary physician that study participation was inappropriate.

Psychiatrists specializing in SUDs screened potential participants based on the predefined inclusion and exclusion criteria. All participants were informed of the study aim and procedures and submitted written informed consent. A total of 13 participants were enrolled from September 2021 to April 2022. For this study, we used data from the 7 participants who used MAMP during the study period and with Fitbit data when they used MAMP. We excluded participants (n=6) who did not use MAMP at all during the study period or did not wear a Fitbit device when they used MAMP.

We previously reported the study protocol [30], providing an overview of the obtained data and preliminary analysis methods. In this study, we conducted a more detailed analysis, focusing specifically on individual differences in physiological responses before and after MAMP use events.

This study was approved by the Ethics Committee of the Faculty of Medicine and Graduate School of Medicine at Tokyo Medical and Dental University (M2020-189) and the participating hospital. Data collected from the self-monitoring app and the Fitbit server were automatically stored in a secure database without any personally identifiable information. These datasets were then matched using participant IDs. All participants provided written informed consent prior to participating in the study. The participants received a prepaid card worth JP¥ 3,000 (US $19.36) as a reward for participating in the study, and received a Fitbit used in the study as compensation after the study.

Table 1 presents the demographic characteristics and conditions related to MAMP use during the study period. The mean age of participants was 47.0 (SD 9.7) years, and the majority were male (6/7, 86%). The average Fitbit wearing rate throughout the study period was 70.1%. The severity of drug dependence assessed using DAST-10 was substantial, with a mean score of 6.0 (SD 1.3). The mean resting heart rate over the study period was 69.8 (SD 8.2) bpm. Emotional status was most frequently reported as “good” (121/308, 39.3%) or “not good” (129/308, 41.9%).

Detailed patterns of MAMP use are presented in Table 2 and Multimedia Appendix 1. The mean number of days of MAMP use during the study period was 13.4 (SD 13.9) days over the 56-day study period, ranging from 1 day to 41 days across participants. The number of consecutive days of MAMP use and days of weekend use varied among participants, with mean values of 2.3 (range 1.0-5.9) days and 4.3 (range 0-13) days, respectively. On MAMP use days, the average number of uses was <2 (mean 1.4, SD 0.8). The most frequently reported time of MAMP use depended on the participant; however, it was most commonly in the morning (6-12 AM) or at night (6‐12 PM), accounting for 48.8% (63/129) and 21.7% (28/129) of use events, respectively. Participants who used MAMP frequently (IDs B and C) showed relatively higher resting heart rates than those with less frequent MAMP use.

The completion rate of self-monitoring during the study period and psychological and physiological conditions on MAMP use days are shown in Table 3 and . Throughout the study period, the mean completion rates for self-monitoring of craving and emotional status were 64% (SD 28.4%) and 78.6% (SD 27.3%), respectively. On days when participants used MAMP, emotional status was most frequently reported as “not good” (mean 51%, SD 54.3%) or “sad” (mean 20%, SD 21.3%). The mean craving score was 5.8 (range 2.2-9.8), and resting heart rate averaged 71.3 (range 60.0 to 78.2) bpm; both were higher than the overall averages for the study period. The mean Fitbit wearing rate was 82.1% (range 0%-94.3%), indicating that participants wore the device relatively consistently even on days they used MAMP. However, econsiderable variation in emotional status and craving existed between participants. Sleep duration and frequency tended to be reduced or absent on MAMP-use days or the day afterand Figure S1 in Multimedia Appendix 2).

Table 4 shows the correlations between psychological and behavioral states and MAMP use. Negative emotions (such as feeling sad or angry) were associated with a higher number of MAMP uses per day. Craving (r=0.32, P<.001) and resting heart rate (r=0.16, P<.01) were positively correlated with the number of daily MAMP uses. However, these correlations varied across participants and were not observed in some cases. The Fitbit wearing rate was positively correlated with the number of MAMP uses per day (r=0.17, P<.001), suggesting that participants tended to wear the device even on days when they used MAMP.

Heart rate tended to increase following MAMP use (Figures 1 and 2, Figure S1 in Multimedia Appendix 2). Table 5 presents the results of a linear mixed effects model evaluating changes in heart rate before and after drug use. A total of 122 observations were included in the analysis, with 5 to 50 observations per participant. The model demonstrated a good fit (log-likelihood=−2626.359). The mean heart rate during the reference period (6‐9 h before drug use) was 89.89 (95% CI 76.88 to 102.89) bpm. At 0 hours to 3 hours postdrug use, mean heart rate increased significantly compared with the reference period (+5.44, 95% CI 3.26 to 7.62 bpm; P<.001), and this elevated level was maintained at 3 hours to 6 hours postuse (+5.51, 95% CI 3.04 to 7.98 bpm; P<.001). A significant increase was also observed at 6 hours to 9 hours postuse (+3.84, 95% CI 1.27 to 6.41 bpm; P=.003). Heart rate during the 0 hours to 3 hours before drug use did not differ significantly from the reference period. However, at 3 hours to 6 hours before drug use, heart rate was significantly lower than during the reference period (−2.71, 95% CI −5.25 to −0.17 bpm; P=.04).

Analysis of variance revealed substantial interindividual and intraindividual variability in heart rate responses. Variance was observed at multiple levels: between participants (SD 15.88 bpm), between events within participants (SD 6.76 bpm), and in the residual error (SD 9.80 bpm). The between-participant variance was 250.66, with an intraclass correlation coefficient of 0.64, indicating that approximately 64% of the total variability in heart rate measurements was attributable to differences between individuals. The variance between events within participants was 45.9, accounting for roughly 12% of the total variance. The residual variance was 96.0, suggesting that the same individual may exhibit different heart rate responses to MAMP use on different occasions.

This pilot study presented detailed patterns of MAMP use, along with interindividual and intraindividual variability in physiological and psychological data, using Fitbits and a mobile-based self-monitoring app with individuals with MAMP use disorder. Patterns of MAMP use varied across participants. Craving for MAMP and negative emotions tended to be associated with the number of MAMP uses per day. A persistent increase in heart rate was observed following MAMP use. However, these trends differed between individuals and across MAMP use events. Because the sample size was small and there was considerable variability in the number of MAMP use days across participants, a larger-scale study will be necessary to further examine these associations. In particular, additional analyses are needed to clarify the relationships among craving, emotional states, and MAMP use.

Among the participants, the frequency of MAMP use varied widely, with the total number of use days ranging from 1 day to 41 days, and consecutive days of use ranging from 1.0 day to 5.9 days. In contrast, the number of MAMP uses per day was relatively consistent among the participants, typically fewer than 2 times per MAMP use day. The participants tended to use MAMP in the mornings and at night on both weekdays and weekends. MAMP is often used to improve performance for daily activities or work, staying awake, helping manage stress, or increasing sexual performance and impulses [38,39]. The participants might also use MAMP when they need to motivate their behavior for specific purposes, whether on weekdays or weekends. This finding is consistent with previous wastewater-based epidemiology studies, which revealed no significant differences in MAMP use between weekdays and weekends [40-42].

Additionally, abstinence following prolonged MAMP use can lead to withdrawal symptoms such as sleep disturbances, difficulty concentrating, fatigue, irritability, agitation, anxiety, sadness, depression, and an inability to engage in normal daily activities [43]. Some participants may struggle to manage these withdrawal symptoms and return to MAMP use. As a result, cycles of binge use and abstinence may occur among individuals with MAMP use disorder. To date, no medications have shown consistent effectiveness for treating MAMP withdrawal [44], and psychosocial treatments remain the primary approach. Cognitive-behavioral therapy (CBT) can be useful for managing withdrawal and craving, supporting sustained abstinence, and facilitating recovery following lapses or relapses [45,46]. Recently, online and computerized forms of CBT have become more widespread and have been shown to be safe, effective, and durable when compared with standard clinician-delivered therapy [47,48]. Incorporating online CBT modules into ecological momentary interventions may be a promising approach for supporting individuals with MAMP use disorder.

On MAMP use days, cravings and negative emotions (eg, feeling sad or unwell) were more frequently reported than in the overall study period. Significant correlations were observed between craving and the number of MAMP use episodes per day, consistent with findings from previous studies. MAMP craving has been shown to persist for at least 5 weeks into abstinence, with individuals being vulnerable to relapse during the first 7 days to 14 days [49] Craving is considered a significant predictor of subsequent MAMP use [50,51]. Negative emotions often intensify cravings, and individuals may be more likely to use MAMP if they do not effectively address these emotions [8,52]. Although the causal relationship between negative emotions and MAMP use was unclear in this study, some participants without adaptive coping strategies may use MAMP as a way to cope with negative emotions. When developing ecological momentary interventions for individuals with MAMP use disorder, incorporating modules for self-monitoring may be helpful to increase awareness of the relationships between emotions, craving, and MAMP use, even during abstinence periods. Additionally, modules for coping with negative emotions may be promising approaches to support MAMP use management.

Overall, tendencies for correlations between MAMP use and craving or negative emotions were observed; however, these relationships and trends varied across the participants. There were some participants without significant correlations between MAMP use and craving or negative emotions. MAMP is often used to reduce withdrawal symptoms from other substances or to cope with pain and discomfort [39]. Additionally, increased tolerance or experiencing a critical life event may lead to increased MAMP use [29]. A previous study suggested that individuals who initiate MAMP use at a later age may do so to “self-medicate” in response to stressful life events [19]. Long-term MAMP users may become less sensitive to cravings due to tolerance. Moreover, some individuals with chronic pain or persistent psychiatric symptoms (eg, depression, anxiety) may use MAMP regardless of craving and emotions. Promoting appropriate and fundamental treatments to address the underlying causes of MAMP use, such as chronic pain and mental health issues, is also essential.

After using MAMP, reduction or loss of sleep and a tendency for increased heart rate were observed. Participants with frequent MAMP use exhibited high resting heart rates. MAMP has a strong and relatively long-lasting stimulant effect on the central nervous and cardiovascular systems [20]. Findings from the linear mixed effects model suggest that the cardiovascular effects of MAMP persist for up to 9 hours after use, with an increase of 3 bpm to 5 bpm compared with baseline levels. In line with previous experimental studies [22], heart rate increased following MAMP use. Laboratory-based studies often evaluate short-term cardiovascular responses using standardized doses and predefined routes of administration. In contrast, this study suggests that, in real-world settings, heart rate elevation following MAMP use may persist for up to 9 hours. This study examined naturally occurring MAMP use events under free-living conditions, and despite variability in dosage, routes of administration, and contextual factors, sustained elevations in heart rate were observed. The average heart rates among the participants (approximately 60 bpm to 78 bpm) were within the normal range; however, chronically elevated heart rate can still lead to cardiovascular dysfunction [53-55]. Unexpected harms related to MAMP use, such as stroke, coronary artery disease, and sudden cardiac death, may occur in individuals who use MAMP frequently, even among young adults [19,55,56]. The implementation of an alert system within an ecological momentary intervention app designed to detect and notify individuals of sudden heart rate increases or arrhythmias may contribute to the prevention of cardiovascular events.

Findings from the analysis of varianceA indicated that increases in heart rate were attributable to both individual differences and MAMP use events. Approximately 64% of the variance in heart rate was due to differences between participants, suggesting significant heterogeneity in individual responses to MAMP use. Previous studies have suggested that gender differences and genetic variations may help explain individual differences in responses to MAMP use [57,58]. Identifying individuals who exhibit substantial increases in heart rate following MAMP use and providing real-time notifications of elevated heart rate may be a useful strategy for risk management. In contrast, variance between events within individuals accounted for approximately 12% of the total variance, indicating that even the same individual may experience different cardiovascular responses to MAMP on different occasions. These findings have important clinical implications, emphasizing that drug effects are not consistent, even within individuals. These differences may be influenced by the duration of MAMP effects and bioavailability, which are affected by various factors such as the route of administration (eg, injection, smoking) and the amount of MAMP used [20,43]. Even among individuals with relatively mild cardiovascular responses, any changes in the administration or dosage of use should be approached with caution. To comprehensively understand variability in heart rate response to MAMP use, it is essential to consider both interindividual and intraindividual variability.

As a pilot study, these findings provide important insights for the design of future EMA-based research on MAMP use. Specifically, the results can inform the optimization of EMA protocols, including the timing and frequency of pre- and post-MAMP use. In this study, we were unable to determine causal relationships between psychological states and MAMP use, as craving and emotional status were assessed only once per day. More frequent self-monitoring may enable more precise assessment of craving and emotional states and help elucidate their temporal associations with MAMP use. Such refinements may enhance the ability to capture within-person dynamics and identify high-risk periods that could be targeted in future intervention studies. Furthermore, the study findings may inform the development of personalized interventions that account for both between-person and within-person variability in associations with MAMP use and physiological responses or psychological states.

This pilot study has several limitations. First, self-monitoring was conducted only once per day, which limited our ability to evaluate causal relationships between craving, emotions, and MAMP use. In our ongoing study, self-monitoring is conducted 3 times per day using an EMA approach to address this limitation. Second, we did not assess nor adjust for potential confounding factors such as smoking habits, night shift work, or the use of alcohol and other substances, which may influence heart rate and sleep patterns. Although other drug use, such as opioids, was rare among participants in this study, these variables are assessed in our ongoing research. Third, the sample size was small, and the participants were only individuals who received outpatient treatment. This may have biased the results. Further research with a larger sample and individuals with more active MAMP use is needed, along with strategies to improve adherence to wearable devices and response rates to self-monitoring prompts. Last, we did not collect data on the route of administration or the quantity of MAMP. To more precisely evaluate heart rate responses, information on how MAMP is used and in what amounts may be important.

This pilot study captured psychological status and physiological responses related to MAMP use, using an EMA framework. Patterns of MAMP use varied among individuals with MAMP use disorder. Overall, craving and negative emotions were correlated with the frequency of MAMP use per day; however, this relationship differed across participants. Similar physiological responses were commonly observed following MAMP use, including persistent increases in heart rate and sleep disturbances, which can lead to cardiovascular dysfunction. Heart rate increased significantly by approximately 3 bpm to 5 bpm compared with the period before MAMP use and remained elevated for up to 9 hours. However, increases in heart rate were explained not only by MAMP use events but also by individual differences. To better understand the individualized predictors for use and physiological responses to use, it is essential to assess both interindividual and intraindividual variability. The findings should be interpreted as exploratory and reflective of within-person patterns rather than representative of group-level trends. Further studies with larger and more diverse samples are needed to assess generalizability.