Positive and negative affect following marijuana use in naturalistic settings: An ecological momentary assessment study

Accepted Manuscript Positive and negative affect following marijuana use in naturalistic settings: An ecological momentary assessment study

Craig S. Ross, Daniel R. Brooks, Ann Aschengrau, Michael B. Siegel, Janice Weinberg, Lydia A. Shrier PII: DOI: Reference:

S0306-4603(17)30271-X doi: 10.1016/j.addbeh.2017.07.020 AB 5234

To appear in:

Addictive Behaviors

Received date: Revised date: Accepted date:

26 April 2017 30 June 2017 13 July 2017

Please cite this article as: Craig S. Ross, Daniel R. Brooks, Ann Aschengrau, Michael B. Siegel, Janice Weinberg, Lydia A. Shrier , Positive and negative affect following marijuana use in naturalistic settings: An ecological momentary assessment study. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Ab(2017), doi: 10.1016/j.addbeh.2017.07.020

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ACCEPTED MANUSCRIPT Positive and Negative Affect Following Marijuana Use in Naturalistic Settings: An Ecological Momentary Assessment Study Craig S. Ross, PhD, MBA*,a, Daniel R. Brooks, DSca, Ann Aschengrau, ScDa, Michael B. Siegel, MD, MPHb, Janice Weinberg, ScDc, Lydia A. Shrier, MD, MPHd,e a

Epidemiology Department, Boston University School of Public Health, Boston MA USA Department of Community Health Sciences, Boston University School of Public Health, Boston MA USA c Department of Biostatistics, Boston University School of Public Health, Boston MA USA d Division of Adolescent/Young Adult Medicine, Boston Children’s Hospital, Boston, MA USA e Department of Pediatrics, Harvard Medical School, Boston, MA USA

Corresponding author at: Epidemiology Department, Boston University School of Public Health, 715 Albany Street, Boston , MA 02118 tel: 508-638-7775 E-mail Address: [email protected]

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Abbreviations: EMA Ecological Momentary Assessment NA Negative Affect PA Positive Affect PANAS Positive-Affect Negative-Affect Schedule

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1. Introduction 1.1 Marijuana Epidemiology Marijuana is the most commonly used illicit drug in the United States, with the lifetime

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prevalence of use among U.S. high school students increasing from 22.7% in 1991 to 30.0% in

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2015 (Miech, Johnston, O'Malley, Bachman, & Schulenberg, 2016). Marijuana use is associated with educational underachievement, cognitive impairment, diminished life satisfaction and

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achievement, chronic bronchitis, increased risk of psychosis disorder among those at risk, and addiction (Volkow, Compton, & Weiss, 2014). As commercial interests begin to promote and

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distribute marijuana, the public health experience with alcohol and tobacco has established the

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need to be proactive in identifying behavioral motivations for using marijuana, and monitoring

1.2 Affect and Marijuana Use

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health consequences associated with its use (Caulkins & Kilmer, 2016).

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Young people report a number of marijuana use motives, including social conformity,

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coping with negative affect, and sensory alteration (Aarons, Brown, Stice, & Coe, 2001; Simons, Correira, Carey, & Borsari, 1998). Affect-related motives for marijuana use seem to be

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particularly salient because tension reduction and relaxation motives have been associated with more frequent marijuana use (Buckner & Schmidt, 2008), and coping motives for marijuana use have been associated with psychopathology symptoms, and distress (Brodbeck, Matter, Page, & Moggi, 2007). The association between elevated negative affect, coping motives for using marijuana, and subsequent marijuana use is consistent with the self-medication hypothesis (Khantzian, 1997). Under the self-medication hypothesis, persons experiencing overwhelming affective

ACCEPTED MANUSCRIPT extremes use substances to regulate their affect. However, it is not clear that use of substances such as marijuana actually produce relief from dysregulated affect. At least one theory suggests that use of marijuana may lead to continued elevated anxiety, resulting in a vicious cycle of continued substance use (Stewart & Conrod, 2008).

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Further, there is potential for a cycle of positive reinforcement of marijuana use from

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increased positive affect following its use. Marijuana has been shown to produce feelings of

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euphoria, not blunted by frequent use (D'Souza et al., 2008). Drugs of addiction, including marijuana, have been shown to release dopamine into the striatum, a key process in the brain’s

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reward system (Bossong et al., 2009), producing a physiological trigger for continued use.

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Repeated use of substances under these circumstances may begin to modify brain reward and

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stress systems, with the potential to develop dependence (Edwards & Koob, 2010).

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1.3 Existing research on affect and marijuana use Affective states are difficult to study using recall survey methods. Ecological Momentary

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Assessment (EMA) studies use real-time data collection methods to capture time-specific

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information about psychological and environmental factors in naturalistic settings (Schwartz & Stone, 2007). For example, Shrier and colleagues (L. A. Shrier, Ross, & Blood, 2014) used EMA

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to examine affective states immediately preceding marijuana use, compared to times distant from marijuana use, for youth and young adult frequent marijuana users. They found negative affect was higher in time periods immediately antecedent to marijuana use compared to background time periods distant from marijuana use, thus providing some support for a self-medication model of marijuana use. Several other EMA and field studies have found anxiety and increased negative affect preceding marijuana use, perhaps acting as a trigger for use of the substance

ACCEPTED MANUSCRIPT under the self-medication hypothesis (Bhushan, Blood, & Shrier, 2012; Buckner, Crosby, Silgado, Wonderlich, & Schmidt, 2012; Johnson, Bonn-Miller, Leyro, & Zvolensky, 2009; L. A. Shrier, Walls, Kendall, & Blood, 2012; Wills, Sandy, Shinar, & Yaeger, 1999). Many of these studies have found complex interactions between individual trait

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characteristics, baseline psychopathology symptoms, and contextual factors that modify the

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association between affect and marijuana use (Buckner, Bonn-Miller, Zvolensky, & Schmidt,

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2007; Buckner, Crosby, Wonderlich, & Schmidt, 2012; Cheetham, Allen, Yücel, & Lubman, 2010; Hussong & Hicks, 2003; Shoal & Giancola, 2003). Of particular note, Buckner and

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colleagues (Buckner et al., 2007) found that social anxiety was associated with marijuana use,

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but only when motivated by coping or conforming expectations in contrast to other marijuana use motives. In addition, Cheetham and colleagues (Cheetham et al., 2010) found that the

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association between affective states and marijuana use was modified by the stage of engagement

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with marijuana: onset, risky use, and addiction. Given these previous findings of contextual (e.g. motivational) and physiological (e.g., addiction) interactions between affective states and

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marijuana use, it is important that studies of affect following marijuana use evaluate effect

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modification (i.e., changes in the association across strata), particularly with regard to marijuana use motives and stage of use.

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1.4 Objectives of this study

In this study, we sought to determine how positive and negative affect change following marijuana use among adolescents and young adults who are frequent users of marijuana. We examined changes in mean affect in time periods subsequent to marijuana use, compared to time periods immediately antecedent to marijuana use, as well as background time periods distant

ACCEPTED MANUSCRIPT from marijuana use. Finally, we explored whether these associations were modified by coping motives or marijuana dependence. 2. Materials and method 2.1 Participants

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Details of the study sample and procedures have been reported previously (L. A. Shrier et

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al., 2012). Briefly, forty-four primary care patients of two adolescent/young adult medical clinics who reported marijuana use at least twice a week were enrolled upon consent, of whom 41

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(93%) provided EMA data (two participants were lost to follow up; one did not follow the EMA protocol). Participants were not enrolled if under the influence of marijuana at the time of the

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interview. The institutional review board of the participating hospital approved the study

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protocol with a waiver of parental permission for participants under the age of 18.

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2.2 Procedures

Participants completed a baseline interview that assessed marijuana use history and

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psychopathology symptoms. Next, participants were trained to use a personal digital assistant

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(PDA; Palm Tungsten E2, Palm Inc., Sunnyvale, CA) that was programmed with the Configurable Electronic Real-Time Assessment System (CERTAS) program (PICS, Inc., Reston,

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VA); all other functions were locked out. The PDA was programmed to signal at random times within 3-hour intervals during each participant’s waking hours, approximately 4-6 signals/day. In addition to random prompts, participants were instructed to complete a report immediately prior to and following marijuana use. All reports contained measures of positive and negative affect. The participants used the devices for approximately 12-14 days of data collection. Participants were compensated up to $140 based on the proportion of study activities completed and

ACCEPTED MANUSCRIPT reimbursed for travel to and from study visits (participants were not compensated based on frequency of marijuana use). 2.3 Measures 2.3.1 Positive and Negative Affect

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Positive and negative affect (PA and NA) were measured using an abbreviated form of

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the Positive Affect- Negative Affect Schedule (PANAS) (L. A. Shrier et al., 2011; Watson, Clark, & Tellegen, 1988). Participants were asked to “indicate to what extent you currently feel

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each of the next 12 feelings” using a 5-point Likert-type scale (not at all, a little, moderately, quite a bit, extremely). PA was taken as the sum of responses for feelings interested, strong,

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proud, alert, inspired, and determined (Cronbach’s alpha = 0.84); NA was taken as the sum of

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responses for distressed, upset, guilty, scared, hostile, and irritable (Cronbach’s alpha = 0.86).

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We used the mean and standard deviation of positive and negative affect for each individual from their signal-prompted reports to calculate individual z-scores as the outcome measures.

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2.3.2 Covariates and Effect Modifiers

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Covariates and potential effect modifiers were identified from a review of previous research (Buckner, Crosby, Silgado, et al., 2012; Cornelissen et al., 2005; Miech et al., 2016;

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Watson et al., 1988). Personal attributes were measured at baseline and included age at the baseline interview - dichotomized at the median into 15 to 17 years (youth)(UNDESA, 2013) and 18 to 24 years (young adult) (The Society for Adolescent Health and Medicine, 2017) ; race/ethnicity recorded as White non-Hispanic, Black/African-American non-Hispanic, Hispanic, or other or mixed race/ethnicity, and dichotomized as white or non-white; sex; baseline depressive symptoms measured with Beck’s Depression Inventory-II (BDI-II; Cronbach alpha =

ACCEPTED MANUSCRIPT 0.91) (Beck, Steer, & Brown, 1996); baseline anxiety measured with the State-Trait Anxiety Inventory (STAI; Cronbach alpha = 0.74) (Spielberger, Gorsuch, & Lushene, 1970); cannabis dependence disorder with physiological dependence (“dependence”) was assessed according to DSM-IV criteria (American Psychiatric Association, 1994) using the Adolescent Diagnostic

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Interview (Winters & Henly, 1993) and dichotomized as present or absent.

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Attributes of the moment were captured from the EMA reports, including time of day

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dichotomized to morning (6 am to 11:59 am) versus other times; day of week was dichotomized into weekdays and weekend days. Companionship at the time of the EMA report was

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dichotomized as alone versus with companions (Buckner, Crosby, Wonderlich, et al., 2012;

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Buckner, Zvolensky, & Ecker, 2013; L. A. Shrier et al., 2012). Motives for marijuana use were measured by an abridged Marijuana Motives Measure (Zvolensky et al., 2007). Participants were

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asked “What is the MAIN reason that you are about to use marijuana?” with responses for social

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reasons, to cope, for pleasure, to conform, or to expand my mind. Participants were asked their motives for use both before and after marijuana use. We selected the motive before use since

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prior research has found that reported motives frequently change after marijuana use (Lydia A.

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Shrier & Scherer, 2014). We grouped motives into to cope or to conform versus for pleasure, to expand my mind, or for social reasons. Coping and conforming reasons were grouped since they

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represented similarly negative-valenced motivations; coping motives made up the majority of this category.

2.3.3 Creating Timelines We used the EMA reports to create a timeline for each participant and to classify time periods into those that were distant from marijuana use (background times), those immediately

ACCEPTED MANUSCRIPT preceding marijuana use (antecedent times), and those subsequent to marijua na use (subsequent times; Figure 1). Figure 1: Classification of Individual EMA Timeline into Background, Antecedent, and Figure 22: Classification of Individual Timeline into Background, Antecedent, and Subsequent Times Subsequent Times Antecedent Time

Timeline

Subsequent-to-Use Time

Background Time

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Background Time

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Marijuana Use

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Time periods outside of the sampling time windows were considered offline and not

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included in the analysis (e.g., sleep time). We varied the antecedent time periods from 12 down to 1 hour preceding marijuana use (measured at 12, 9, 6, 3, and 1 hours) to examine the impact of

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the duration of the time window on the change in negative and positive affect. In a similar

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manner, we varied the length of the subsequent period from 1 hour to 12 hours (at 1, 3, 6, 9, and 12 hours) to assess affective response to marijuana use. Background time periods were all times

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that fell outside of antecedent or subsequent time periods.

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2.4 Analysis

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2.4.1 Change in Mean Negative and Positive Affect Subsequent to Marijuana Use We assessed changes in mean PA and NA between subsequent times and antecedent

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times, and between subsequent times and background times. The outcome was reported as the difference in affect between time periods. We used a mixed effects model with a random subject intercept to estimate the mean level of PA and NA in each time period (Fitzmaurice, Laird, & Ware, 2004). We contrasted these means to calculate differences between subsequent and antecedent time periods, and between subsequent and background time periods. Covariates that modified the association between time periods and outcomes by 10% or more were kept in the final models as potential confounders (Mickey & Greenland, 1989) with final models adjusted

ACCEPTED MANUSCRIPT for time of day, time of week, age, race/ethnicity, and baseline depressive symptoms. We examined effect modification by reason for marijuana use (for coping or conforming versus all other motives) and by dependence status. Effect modification was assessed by calculating estimates and confidence intervals within strata of the effect modifiers, rather than testing the

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significance of an interaction term in the model (VanderWeele, 2009). Analyses were performed

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using SAS version 9.3 (SAS Institute, Cary, NC). 3. Results

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3.1 Participant Sample Characteristics

The 41 participants were age 18.6 ± 2.0 (mean ± sd), range 15 to 24 years (Table 1). Over

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half of the participants were female (56.1%) and non-Hispanic White (68.3%). Almost one-third

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(29.3%) met criteria for cannabis dependence. Participants recorded 3,570 momentary reports

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with complete affect information (92% of 3,868 total momentary reports) and 592 events of marijuana use, a signal response rate of 70%. In almost one-half of marijuana use events

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(49.2%), marijuana was used for pleasure, while in 10.4%, marijuana was used to cope or to

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conform.

3.3 Affect Following Marijuana Use Relative to Antecedent Times

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We report results using antecedent and background time periods of equal length from 1 to 12 hours, assessed at 1, 3, 6, 9, and 12 hours. Results for all other time combinations may be found in the supplemental tables. 3.3.1 Negative Affect In the first hour following marijuana use, NA was elevated by 0.20 standard deviations (SD) (95% confidence interval [CI] -0.01-0.41) relative to the matched antecedent time period

ACCEPTED MANUSCRIPT (Figure 2A). Elevated NA was not observed for time periods of 3 hours or more. On occasions when marijuana was used for coping or conforming (Figure 2B), NA was elevated in the first hour by 0.34 SD (95% CI 0.14-0.54). However, on occasions when other motives were reported for marijuana use (Figure 2C), the difference was effectively zero. Participants who met the

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criteria for dependence did not exhibit a significant change in NA (Figure 2D). However,

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participants who did not meet the criteria for dependence showed an increase of 0.27 SD (95%

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CI 0.01-0.54) over the first hour following marijuana use and an increase of 0.22 SD (95% CI

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0.04-0.40) over the 9-hour period following marijuana use (Figure 2E).

ACCEPTED MANUSCRIPT Figures 2A-2E: Changes in individual-standardized negative affect between periods 1 to 12 hours subsequent to marijuana use and matching antecedent time periods preceding marijuana use 0.80

A. All

B. Coping+

C. Coping-

D. Dependence+

E. Dependence-

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CHANGE IN INDIVIDUAL STANDARDIZED NEGATIVE AFFECT (STANDARD DEVIATION UNITS)

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LENGTH OF ANTECEDENT AND SUBSEQUENT TIME PERIODS (HOURS)

Change estimates are in standard deviation units adjusted for time of day, time of week, age, race/ethnicity, and depressive symptoms All: All participants and all marijuana use events Coping+: Only marijuana events during which the participant reported using the drug to cope or to conform

ACCEPTED MANUSCRIPT Coping-: Only marijuana events during which the participant reported using the drug for reasons other than coping or conforming (e.g., for pleasure, to expand my mind, or for social reasons) Dependence+: Only participants meeting DSM-IV criteria for cannabis dependence disorder with physiological dependence Dependence-: Only participants not meeting DSM-IV criteria for cannabis dependence disorder with physiological dependence

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3.3.2 Positive Affect

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Overall, PA was unchanged following marijuana use compared to antecedent time

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periods (Figure 3A). Similarly, PA remained unchanged regardless of the motive for

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using marijuana (Figures 3B-C). However, PA following marijuana use was higher for participants who met dependence criteria. For time periods of 1, 3, and 6 hours, PA was

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0.22 SD (95% CI -0.13-0.56), 0.29 SD (95% CI 0.004-0.57), and 0.30 SD (95% CI 0.05-

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0.55) higher following marijuana use (Figure 3D). By contrast, participants without

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dependence had no significant change in PA (Figure 3E).

ACCEPTED MANUSCRIPT Figures 3A-3E: Changes in individual-standardized positive affect between periods 1 to 12 hours subsequent to marijuana use and matching antecedent time periods preceding marijuana use

HANGE IN INDIVIDUAL STANDARDIZED POSITIVE AFFECT (STANDARD DEVIATION UNITS)

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Dependence+

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Change estimates are in standard deviation units adjusted for time of day, time of week, age, race/ethnicity, and depressive symptoms All: All participants and all marijuana use events Coping+: Only marijuana events during which the participant reported using the drug to cope or to conform Coping-: Only marijuana events during which the participant reported using the drug for reasons other than coping or conforming (e.g., for pleasure, to expand my mind, or for social reasons) Dependence+: Only participants meeting DSM-IV criteria for cannabis dependence disorder with physiological dependence Dependence-: Only participants not meeting DSM-IV criteria for cannabis dependence disorder with physiological dependence

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3.4 Affect Following Marijuana Use Relative to Background Times

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3.4.1 Negative Affect

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NA was higher following marijuana use compared to background times (Figure

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4A). In the first hour following use, NA was 0.22 SD (95% CI 0.12-0.31) higher. NA following use remained from 0.10 to 0.16 SD higher for all time periods up to 12 hours.

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When marijuana was used to cope or conform, NA was 0.37 SD (95% CI 0.25-

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0.50) higher following use compared to background times, although this difference disappeared over a 6-hour time period or longer (Figure 4B). When marijuana use was

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motivated by other reasons (e.g., NA remained elevated for time periods up to 6 hours

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(Figure 4C).

For participants who met dependence criteria, NA was higher than background

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times for the first hour following marijuana use but appeared to be lower than

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background times for time periods of 6 hours or longer (Figure 4D). However, for participants who did not meet criteria for dependence, NA was higher than background

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times for all time periods (Figure 4E).

ACCEPTED MANUSCRIPT Figures 4A-4E: Changes in individual-standardized negative affect between periods 1 to 12 hours subsequent to marijuana use and background time periods distant from marijuana use, overall and by coping/conform status and dependence 0.60

CHANGE IN INDIVIDUAL STANDARDIZED NEGATIVE AFFECT (STANDARD DEVIATION UNITS)

A. All

B. Coping Conform+

C. Coping-

D. Dependence+

E. Dependence-

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0.40

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LENGTH OF ANTECEDENT AND SUBSEQUENT TIME PERIODS (HOURS)

Change estimates are in standard deviation units adjusted for time of day, time of week, age, race/ethnicity, and depressive symptoms All: All participants and all marijuana use events Coping+: Only marijuana events during which the participant reported using the drug to cope or to conform

ACCEPTED MANUSCRIPT Coping-: Only marijuana events during which the participant reported using the drug for reasons other than coping or conforming (e.g., for pleasure, to expand my mind, or for social reasons) Dependence+: Only participants meeting DSM-IV criteria for cannabis dependence disorder with physiological dependence Dependence-: Only participants not meeting DSM-IV criteria for cannabis dependence disorder with physiological dependence

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3.4.1 Positive Affect

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Across the entire sample, PA following marijuana use was similar to background

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times (Figure 5A). PA was 0.13 SD (95% CI 0.01-0.24) higher following marijuana use

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on occasions when marijuana was used to cope or conform (Figure 5B). PA declined over longer time periods, although the confidence intervals contained zero. A similar pattern

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was observed for occasions when marijuana use was motived by other reasons, for

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example for pleasure or social reasons (Figure 5C).

For persons who met the criteria for dependence, PA was higher following

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marijuana use compared to background times 0.47 SD (95% CI 0.30-0.64) and this

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difference was observed for time periods up to 6 hours (Figure 5D). PA was lower in the first hour following use for persons who did not meet the dependence criteria by -0.10 SD

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(Figure 5E).

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(95% CI -0.19--0.01) and this pattern was observed for all time periods up to 12 hours

ACCEPTED MANUSCRIPT Figures 5A-5E: Changes in individual-standardized positive affect between periods 1 to 12 hours subsequent to marijuana use and background time periods distant from marijuana use, overall and by coping/conform status and dependence 0.80

CHANGE IN INDIVIDUAL STANDARDIZED POSITIVE AFFECT (STANDARD DEVIATION UNITS)

A. All

B. Coping+

C. Coping-

E. Dependence-

D. Dependence+

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LENGTH OF ANTECEDENT AND SUBSEQUENT TIME PERIODS (HOURS)

Change estimates are in standard deviation units adjusted for time of day, time of week, age, race/ethnicity, and depressive symptoms All: All participants and all marijuana use events Coping+: Only marijuana events during which the participant reported using the drug to cope or to conform Coping-: Only marijuana events during which the participant reported using the drug for reasons other than coping or conforming (e.g., for pleasure, to expand my mind, or for social reasons)

ACCEPTED MANUSCRIPT Dependence+: Only participants meeting DSM-IV criteria for cannabis dependence disorder with physiological dependence Dependence-: Only participants not meeting DSM-IV criteria for cannabis dependence disorder with physiological dependence

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4. Discussion

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4.1 Interpretation of Findings with Regard to Negative Affect

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Among a group of young, frequent marijuana users, we found that marijuana use

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was associated with higher NA, on average, in the first hour subsequent to marijuana use compared to the first hour immediately preceding marijuana use. For time periods longer

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than one hour, we found NA was effectively unchanged.

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When marijuana was used to cope or to conform, we found levels of NA were particularly high in the first hour following marijuana use compared to the matched

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antecedent time period, but this difference disappeared over time periods of 3 hours or

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longer. This finding, which was specific to occasions when marijuana was used for coping purposes, is consistent with a self-medication hypothesis in which people are

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attempting to use marijuana to reduce negative affective states (Buckner, Crosby,

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Silgado, et al., 2012; Buckner, Crosby, Wonderlich, et al., 2012; Buckner & Schmidt, 2009; Johnson et al., 2009).

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When comparing negative affect subsequent to marijuana use to background

times distant from marijuana use, participants who were not dependent experienced higher negative affect proximal to marijuana use, but those with dependence may have achieved some relief from negative affect. Thus self-medication may also be a factor among participants meeting criteria for dependence. Depending on time between marijuana use, withdrawal symptoms such as irritability and cravings for marijuana may

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be elevated during background time periods and, once marijuana has been consumed, these symptoms may diminish (Budney, Moore, Vandrey, & Hughes, 2003). It is possible that the increase in NA for those without dependence and for those

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using marijuana for pleasure, expansion, or social reasons may be due to responses to the drug which can cause unpleasant physical symptoms such as tachycardia or increased

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anxiety, as reported by less experienced marijuana users (D'Souza et al., 2008). We tested

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whether these differences between those with and without dependence could be related to the number of years the participant had used marijuana. When we added number of years

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of marijuana use as a variable to the model, we found no significant change in the results.

over a longer period of time.

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Therefore, it does not appear these results are a conditioned response to using marijuana

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4.2 Interpretation of Findings with Regard to Positive Affect

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PA under the influence of marijuana differed for participants by dependence criteria. Participants with dependence had an increase in PA following marijuana use

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relative to both antecedent and background times, peaking approximately 1 hour after

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use. This is consistent with the report of a euphoric state achieved in response to using marijuana. Participants without dependence had a decrease in PA following use relative to background times. In contrast to the results of our study, other studies have found that feelings of euphoria under the influence of marijuana were similar for both experienced and inexperienced marijuana users (D'Souza et al., 2008). If people who experience euphoria following use are more likely to use more frequently and develop dependence, then that would explain these differences. In addition, tests of expectancy theory and

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marijuana use have shown that positive expectancies may influence early initiation and faster use trajectories (Fulton, Krank, & Stewart, 2012; Skenderian, Siegel, Crano, Alvaro, & Lac, 2008). Our findings provide preliminary evidence of a feedback loop

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between expectancies, affect regulation, and dependence. However, a long-term longitudinal study is needed to determine the temporality of this association. Further,

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those who meet the criteria for dependence may have set expectancies with regard to

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affect following marijuana use and these findings provide further evidence to support this hypothesis, which could be tested in future research.

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4.5 Strengths and Limitations of the Current Study

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Our findings must be interpreted in light of several limitations. The study used an abbreviated form of PANAS (L. A. Shrier et al., 2011) to measure positive and negative

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affect that may not fully capture the arousal and euphoric states that may accompany

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marijuana use. Response rates to random signals for momentary assessments were 70%, in the range reported for other EMA studies (Hufford, Shields, Shiffman, Paty, &

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Balabanis, 2002; Shiffman, Stone, & Hufford, 2008). Selection bias may occur if non-

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response to random signals was associated with use of marijuana and associated with affect. Non-response is likely to be associated with extremes of negative or positive affect because participants may not respond to a signal if they are experiencing emotional distress, are too “high” to focus on the task, or do not wish to respond because reporting would detract from their high (Black, de Moor, Kendall, & Shrier, 2014). In these situations, any bias introduced by non-response to random signals would be toward the

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null, not toward higher levels of negative and positive affect following marijuana use, compared to background levels. This study was based on an urban, primary care population of adolescent and

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young adult frequent marijuana users and may not be representative of marijuana users in other settings or with lower levels of use. Our measure of the primary outcome was based

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on self-report, using an abbreviated form of the PANAS scale to minimize task fatigue.

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Finally, we did not assess potency of the marijuana being used by participants in the

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study. 5. Conclusion

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To summarize, we found that marijuana use is associated with subsequent

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increased negative affect, relative to background times. In addition, we found support for affect regulation based on certain participant and marijuana use event characteristics.

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Following marijuana use, participants using marijuana to cope or to conform had a

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reduction in negative affect and those meeting criteria for cannabis dependence disorder with physiological dependence had an increase in positive affect. This study provides

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strong evidence of an affective response to marijuana use that may reinforce use of the substance for regulating affective states. Future research following a cohort of marijuana users over time, sampling periodically with EMA methods, would reveal the temporal association between dependence and affective responses found in this study. The expanding commercial market for marijuana compels the public health community to make such research a high priority. With commercialization, the population at risk from

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marijuana exposure is likely to grow and clinicians need clear guidance on how

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marijuana may affect certain individuals when it is used for self-medication.

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Acknowledgements :

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The authors thank Elizabeth Henehan for her insightful reviews and editing of the

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manuscript. We also thank faculty of the Epidemiology Department at Boston University School of Public Health and trainees in the Boston University

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Reproductive Perinatal and Pediatric Epidemiology Training Grant who provided

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feedback on earlier versions of the manuscript. Finally, the authors are grateful to

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the volunteers who participated in the study. Role of funding sources: This work was funded by NIDA grant R21DA021713 to Dr.

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Shrier. Dr. Ross’s participation in the study was funded in part by NIH grant T32

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HD052458 (Boston University Reproductive, Perinatal, and Pediatric Epidemiology training program). No funders had any role in study design, collection, analysis, or

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interpretation of data, writing the manuscript, and the decision to submit the manuscript for publication.

Contributors: Dr. Ross developed the study analysis plan, conducted the analysis, and wrote the manuscript. Dr. Shrier designed the study and obtained funding, wrote the ecological momentary assessment protocol, and supervised data collection. All authors reviewed analysis results, contributed to and approved the final manuscript.

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Conflicts of Interest: All authors declare they have no conflicts of interest.

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Table 1 Participant characteristics and momentary attributes of the participants in the Feelings and Marijuana Ecological Momentary Assessment study Participant Characteristic

N = 41 18.6 ± 2.0 23 (56.1)

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Age in years (mean ± SD) Female Sex, N (%) Race/Ethnicity, N (%) Hispanic African-American/Black non-Hispanic White non-Hispanic Depressive Symptomsa (mean ± SD)

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12 (28.3) 1 (2.4) 28 (68.3)

15.0 ± 27.6

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Cannabis Dependence Disorder with Physiological Dependenceb , N (%)

Momentary Attributes Positive Affect (mean ± SD)

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Momentary Affectc, N

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Negative Affect (mean ±SD) Marijuana Use Events, N Reason for Marijuana Use, N (%) To cope or conform Other reasons Pleasure Expansion Social reasons Marijuana Use by Time of Day, N (%) 6:00am to 11:59am Other Times Marijuana Use by Day of Week, N (%) Weekday (M-Th) Weekend (F-Su) a

12 (29.3)

3,570 11.5 ± 6.1 2.6 ± 4.1 592 61 (10.3) 531 (89.7)

74 (12.5) 518 (87.5) 330 (55.7) 262 (44.3)

Depressive symptoms measured with Beck's Depression Index – II (possible score range 0-63). Assessed with Adolescent Diagnostic Interview using DSM-IV criteria. c Affect measured with abbreviated Positive Affect ─ Negative Affect Schedule. b

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Appendix A - Supplemental Tables - Complete Results for All Time Intervals Table 1a: Differencea in individual-standardized negative affect between times subsequent to marijuana use and background times

T P

I R

Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs) Antecedent Time (Hrs)

1

3

6

9

1

0.22 (0.12,0.31)

0.15 (0.05,0.24)

0.10 (0.01,0.20)

0.13 (0.04,0.23)

3

0.23 (0.13,0.33)

0.16 (0.07,0.26)

0.12 (0.02,0.22)

0.14 (0.04,0.23)

6

0.22 (0.12,0.32)

0.16 (0.06,0.26)

0.11 (0.01,0.21)

0.14 (0.04,0.23)

9

0.22 (0.11,0.32)

0.16 (0.06,0.26)

0.10 (0.002,0.21)

0.13 (0.03,0.23)

0.10 (0.003,0.21)

12

0.21 (0.11,0.31)

0.15 (0.05,0.26)

0.10 (-0.01,0.20)

0.13 (0.03,0.23)

0.10 (0.0004,0.20)

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A

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0.10 (0.00,0.20) 0.11 (0.00,0.21) 0.11 (0.01,0.21)

Table 1b: Differencea in individual-standardized negative affect between times subsequent to marijuana use and background times when using marijuana for coping or conforming reasonsb

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Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs) Antecedent Time (Hrs)

1

3

1

0.37 (0.25,0.50)

3

T P

6

9

12

0.11 (0.003,0.22)

0.05 (-0.05,0.15)

0.04 (-0.08,0.16)

0.39 (0.26,0.51)

0.12 (0.02,0.23)

0.02 (-0.08,0.12)

0.06 (-0.04,0.16)

0.05 (-0.07,0.17)

6

0.38 (0.25,0.50)

0.12 (0.01,0.23)

0.01 (-0.09,0.11)

0.06 (-0.05,0.16)

0.05 (-0.07,0.17)

9

0.38 (0.25,0.50)

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0.002 (-0.10,0.10)

0.12 (0.01,0.23)

0.00 (-0.10,0.11)

0.05 (-0.05,0.15)

0.05 (-0.07,0.16)

12

0.38 (0.25,0.50)

0.12 (0.01,0.23)

0.00 (-0.10,0.10)

0.05 (-0.05,0.15)

0.04 (-0.08,0.16)

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Table 1c: Differencea in individual-standardized negative affect between times subsequent to marijuana use and background times when using marijuana for reasons other than coping or conformingb Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs)

T P

Antecedent Time (Hrs)

1

3

6

9

12

1

0.14 (0.04,0.23)

0.10 (0.004,0.19)

0.07 (-0.02,0.17)

0.10 (0.01,0.20)

0.07 (-0.03,0.17)

3

0.15 (0.05,0.24)

0.11 (0.02,0.21)

0.09 (-0.01,0.19)

0.11 (0.01,0.21)

6

0.14 (0.04,0.24)

0.11 (0.01,0.21)

0.08 (-0.02,0.18)

0.11 (0.01,0.21)

9

0.14 (0.03,0.24)

0.11 (0.01,0.21)

0.08 (-0.03,0.18)

0.10 (0.01,0.20)

12

0.13 (0.03,0.23)

0.10 (0.001,0.20)

0.07 (-0.04,0.17)

0.10 (0.001,0.20)

I R

U N

C S

0.08 (-0.03,0.18) 0.08 (-0.02,0.18) 0.08 (-0.03,0.18) 0.07 (-0.03,0.18)

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Table 1d: Differencea in individual-standardized negative affect between times subsequent to marijuana use and background times for persons with dependencec

D E

M

Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs) Antecedent Time (Hrs)

T P

1

3

1

0.17 (0.01,0.34)

0.08 (-0.09,0.25)

3

0.18 (0.004,0.35)

6

0.18 (0.002,0.36)

9

0.20 (0.02,0.39)

12

0.19 (0.01,0.38)

9

12

-0.08 (-0.25,0.09)

-0.12 (-0.27,0.03)

-0.10 (-0.27,0.06)

0.08 (-0.10,0.26)

-0.10 (-0.28,0.07)

-0.15 (-0.30,0.01)

-0.11 (-0.28,0.05)

0.08 (-0.10,0.26)

-0.11 (-0.30,0.07)

-0.14 (-0.30,0.02)

-0.10 (-0.27,0.06)

0.10 (-0.09,0.29)

-0.12 (-0.31,0.07)

-0.14 (-0.31,0.02)

-0.11 (-0.28,0.06)

0.09 (-0.10,0.28)

-0.13 (-0.32,0.06)

-0.15 (-0.31,0.01)

-0.11 (-0.28,0.05)

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C A

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Table 1e: Differencea in individual-standardized negative affect between times subsequent to marijuana use and background times for persons without dependencec Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs) Antecedent Time (Hrs)

1

3

6

9

1

0.23 (0.11,0.35)

0.16 (0.04,0.27)

0.16 (0.04,0.28)

0.23 (0.11,0.36)

3

0.24 (0.12,0.36)

0.18 (0.06,0.30)

0.19 (0.07,0.31)

0.25 (0.12,0.37)

6

0.23 (0.10,0.35)

0.17 (0.04,0.29)

0.18 (0.06,0.30)

0.24 (0.12,0.37)

9

0.21 (0.09,0.34)

0.16 (0.03,0.28)

0.17 (0.04,0.29)

0.24 (0.11,0.36)

T P

I R

12

C S

U N

0.20 (0.07,0.33) 0.21 (0.08,0.34) 0.21 (0.08,0.34) 0.21 (0.08,0.34)

12 0.21 (0.08,0.34) 0.15 (0.03,0.28) 0.16 (0.04,0.29) 0.24 (0.11,0.36) 0.21 (0.08,0.34) Difference estimates are in standard deviation units (95% confidence interval) adjusted for time of day, time of week, age, race/ethnicity, and depressive symptoms b Motives for use measured with modified form of Marijuana Motives Measure c Dependence is defined as meeting criteria for Cannabis Dependence Dis order with Physiological Dependence based on the Adolescent Diagnostic Interview

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a

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Table 2a: Differencea in individual-standardized negative affect between times subsequent to marijuana use and antecedent times

3

6

9

12

0.20 (-0.01,0.41)

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0.15 (-0.08,0.38)

0.09 (-0.16,0.34)

0.05 (-0.22,0.31)

0.01 (-0.31,0.33)

3

0.16 (0.01,0.31)

0.08 (-0.08,0.24)

0.02 (-0.16,0.19)

0.07 (-0.11,0.25)

-0.02 (-0.23,0.20)

6

0.21 (0.07,0.34)

0.12 (-0.02,0.26)

0.07 (-0.08,0.21)

0.09 (-0.06,0.24)

-0.01 (-0.19,0.17)

9

0.21 (0.09,0.34)

0.13 (-0.002,0.26)

0.10 (-0.04,0.23)

0.11 (-0.02,0.25)

0.04 (-0.13,0.21)

12

0.22 (0.10,0.34)

0.14 (0.01,0.27)

0.11 (-0.02,0.24)

0.13 (-0.01,0.26)

0.06 (-0.11,0.23)

Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs) Antecedent Time (Hrs)

1

1

C A

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Table 2b: Differencea in individual-standardized negative affect between times subsequent to marijuana use and antecedent times when using marijuana for coping or conforming reasonsb Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs)

T P

Antecedent Time (Hrs)

1

3

6

9

1

0.34 (0.14,0.54)

0.13 (-0.08,0.33)

-0.001 (-0.22,0.21)

-0.03 (-0.26,0.21)

3

0.31 (0.15,0.47)

0.05 (-0.11,0.20)

-0.08 (-0.23,0.08)

-0.01 (-0.17,0.16)

6

0.35 (0.21,0.50)

0.09 (-0.05,0.22)

-0.03 (-0.16,0.10)

0.01 (-0.13,0.16)

9

0.36 (0.21,0.50)

0.09 (-0.04,0.22)

-0.003 (-0.13,0.12)

0.04 (-0.10,0.17)

-0.02 (-0.20,0.16)

12

0.36 (0.22,0.50)

0.10 (-0.03,0.23)

0.01 (-0.11,0.13)

0.04 (-0.09,0.17)

0.0004 (-0.18,0.18)

C S

U N

A

D E

T P

C A

E C

I R

M

12

-0.05 (-0.36,0.26) -0.08 (-0.30,0.14) -0.07 (-0.25,0.12)

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Table 2c: Differencea in individual-standardized negative affect between times subsequent to marijuana use and antecedent times when using marijuana for reasons other than coping or conformingb Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs)

T P

Antecedent Time (Hrs)

1

3

6

9

1

0.11 (-0.10,0.32)

0.10 (-0.13,0.33)

0.06 (-0.19,0.31)

0.02 (-0.24,0.28)

3

0.07 (-0.08,0.22)

0.03 (-0.14,0.19)

-0.01 (-0.19,0.16)

0.04 (-0.14,0.22)

6

0.12 (-0.01,0.25)

0.07 (-0.07,0.21)

0.04 (-0.11,0.18)

0.06 (-0.08,0.21)

9

0.13 (0.003,0.25)

0.08 (-0.05,0.21)

0.06 (-0.07,0.20)

0.09 (-0.05,0.23)

0.01 (-0.16,0.18)

12

0.14 (0.02,0.26)

0.09 (-0.03,0.22)

0.08 (-0.05,0.21)

0.10 (-0.03,0.23)

0.03 (-0.14,0.20)

C S

I R

U N

12

-0.02 (-0.33,0.30) -0.05 (-0.26,0.17) -0.03 (-0.22,0.15)

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Table 2d: Differencea in individual-standardized negative affect between times subsequent to marijuana use and antecedent times for persons with dependencec

D E

M

Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs) Antecedent Time (Hrs)

1

3

1

0.07 (-0.27,0.41)

0.03 (-0.36,0.43)

3

0.11 (-0.15,0.36)

6

0.12 (-0.11,0.34)

9

0.09 (-0.12,0.30)

12

0.11 (-0.09,0.32)

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C A

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6

9

12

-0.15 (-0.57,0.27)

-0.29 (-0.67,0.09)

-0.17 (-0.63,0.30)

0.07 (-0.21,0.35)

-0.01 (-0.30,0.27)

-0.06 (-0.33,0.20)

-0.05 (-0.38,0.27)

0.07 (-0.17,0.30)

-0.02 (-0.26,0.22)

-0.11 (-0.34,0.11)

-0.11 (-0.39,0.17)

0.03 (-0.19,0.25)

-0.03 (-0.26,0.19)

-0.11 (-0.32,0.10)

-0.09 (-0.36,0.18)

0.05 (-0.16,0.27)

-0.02 (-0.24,0.20)

-0.09 (-0.30,0.11)

-0.06 (-0.32,0.20)

ACCEPTED MANUSCRIPT

Table 2e: Differencea in individual-standardized negative affect between times subsequent to marijuana use and antecedent times for persons without dependencec Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs) Antecedent Time (Hrs)

1

3

6

9

1

0.27 (0.01,0.54)

0.23 (-0.06,0.51)

0.23 (-0.08,0.54)

0.25 (-0.10,0.59)

3

0.19 (0.002,0.39)

0.08 (-0.12,0.28)

0.03 (-0.18,0.25)

0.14 (-0.09,0.37)

6

0.25 (0.09,0.42)

0.15 (-0.02,0.32)

0.11 (-0.07,0.29)

0.19 (0.001,0.39)

9

0.28 (0.12,0.43)

0.17 (0.01,0.33)

0.16 (-0.01,0.33)

0.22 (0.04,0.40)

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0.12 (-0.31,0.54) 0.01 (-0.28,0.29) 0.06 (-0.18,0.29) 0.12 (-0.10,0.34)

12 0.28 (0.13,0.43) 0.18 (0.02,0.33) 0.17 (0.01,0.33) 0.23 (0.06,0.40) 0.13 (-0.09,0.35) Difference estimates are in standard deviation units (95% confidence interval) adjusted for time of day, time of week, age, race/ethnicity, and depressive symptoms b Motives for use measured with modified form of Marijuana Motives Measure c Dependence is defined as meeting criteria for Cannabis Dependence Dis order with Physiological Dependence based on the Adolescent Diagnostic Interview a

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Table 3a: Differencea in individual-standardized positive affect between times subsequent to marijuana use and background times

T P

Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs) Antecedent Time (Hrs)

1

1

0.06 (-0.02,0.15)

3

0.06 (-0.02,0.15)

6

0.05 (-0.04,0.14)

9 12

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6

9

12

0.004 (-0.08,0.09)

-0.02 (-0.10,0.07)

-0.04 (-0.13,0.04)

-0.05 (-0.15,0.05)

0.0002 (-0.09,0.09)

-0.02 (-0.11,0.07)

-0.05 (-0.14,0.04)

-0.05 (-0.16,0.05)

-0.01 (-0.10,0.08)

-0.04 (-0.13,0.05)

-0.06 (-0.15,0.03)

-0.06 (-0.16,0.04)

0.05 (-0.04,0.14)

-0.01 (-0.10,0.08)

-0.04 (-0.13,0.05)

-0.06 (-0.15,0.03)

-0.07 (-0.17,0.04)

0.05 (-0.04,0.14)

-0.01 (-0.10,0.08)

-0.04 (-0.13,0.06)

-0.06 (-0.15,0.03)

-0.07 (-0.17,0.03)

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ACCEPTED MANUSCRIPT

Table 3b: Differencea in individual-standardized positive affect between times subsequent to marijuana use and background times when using marijuana for coping or conforming reasonsb Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs)

T P

Antecedent Time (Hrs)

1

3

6

9

1

0.13 (0.01,0.24)

0.02 (-0.09,0.12)

-0.01 (-0.11,0.09)

-0.04 (-0.13,0.06)

3

0.13 (0.01,0.24)

0.01 (-0.09,0.12)

-0.01 (-0.11,0.08)

-0.04 (-0.14,0.06)

6

0.12 (-0.001,0.23)

0.01 (-0.10,0.11)

-0.03 (-0.12,0.07)

-0.05 (-0.15,0.05)

9

0.12 (0.001,0.23)

0.01 (-0.10,0.11)

-0.02 (-0.12,0.08)

-0.05 (-0.15,0.05)

-0.07 (-0.19,0.04)

12

0.12 (0.001,0.24)

0.01 (-0.09,0.12)

-0.02 (-0.12,0.08)

-0.05 (-0.15,0.05)

-0.08 (-0.19,0.04)

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12

-0.06 (-0.18,0.05) -0.06 (-0.18,0.05) -0.07 (-0.19,0.05)

ACCEPTED MANUSCRIPT

Table 3c: Differencea in individual-standardized positive affect between times subsequent to marijuana use and background times when using marijuana for reasons other than coping or conformingb Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs)

T P

Antecedent Time (Hrs)

1

3

6

9

1

0.07 (-0.01,0.16)

0.01 (-0.08,0.09)

-0.01 (-0.10,0.07)

-0.04 (-0.13,0.04)

3

0.07 (-0.02,0.16)

-0.008 (-0.09,0.09)

-0.02 (-0.11,0.07)

-0.05 (-0.14,0.04)

-0.05 (-0.15,0.05)

6

0.06 (-0.03,0.15)

-0.01 (-0.10,0.08)

-0.04 (-0.13,0.06)

-0.06 (-0.15,0.03)

-0.06 (-0.16,0.05)

9

0.06 (-0.04,0.15)

-0.01 (-0.10,0.09)

-0.04 (-0.13,0.06)

-0.06 (-0.15,0.03)

-0.06 (-0.16,0.04)

12

0.06 (-0.04,0.15)

-0.01 (-0.10,0.09)

-0.03 (-0.13,0.06)

-0.06 (-0.15,0.03)

-0.06 (-0.17,0.04)

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C S

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12

-0.05 (-0.15,0.05)

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Table 3d: Differencea in individual-standardized positive affect between times subsequent to marijuana use and background times for persons with dependencec

D E

M

Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs) Antecedent Time (Hrs)

1

3

1

0.47 (0.30,0.64)

0.35 (0.17,0.52)

3

0.49 (0.31,0.67)

6

0.48 (0.30,0.67)

9

0.48 (0.29,0.67)

12

0.47 (0.27,0.66)

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9

12

0.29 (0.11,0.47)

0.17 (-0.001,0.34)

0.05 (-0.14,0.25)

0.35 (0.17,0.54)

0.30 (0.11,0.49)

0.18 (0.01,0.35)

0.06 (-0.13,0.26)

0.34 (0.15,0.53)

0.28 (0.08,0.48)

0.17 (-0.01,0.35)

0.06 (-0.14,0.25)

0.35 (0.15,0.54)

0.30 (0.10,0.50)

0.17 (-0.02,0.35)

0.04 (-0.16,0.23)

0.33 (0.13,0.52)

0.30 (0.09,0.50)

0.16 (-0.02,0.34)

0.03 (-0.17,0.22)

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C A

6

ACCEPTED MANUSCRIPT

Table 3e: Differencea in individual-standardized positive affect between times subsequent to marijuana use and background times for persons without dependencec Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs)

T P

Antecedent Time (Hrs)

1

3

6

9

1

-0.10 (-0.19,-0.01)

-0.14 (-0.23,-0.04)

-0.15 (-0.25,-0.05)

-0.14 (-0.24,-0.04)

3

-0.11 (-0.20,-0.01)

-0.15 (-0.25,-0.05)

-0.16 (-0.26,-0.06)

-0.15 (-0.25,-0.05)

-0.13 (-0.25,-0.01)

6

-0.12 (-0.22,-0.03)

-0.16 (-0.26,-0.06)

-0.17 (-0.27,-0.07)

-0.17 (-0.27,-0.06)

-0.14 (-0.26,-0.02)

9

-0.12 (-0.22,-0.02)

-0.15 (-0.26,-0.05)

-0.18 (-0.28,-0.07)

-0.17 (-0.27,-0.06)

-0.14 (-0.26,-0.02)

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C S

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12

-0.13 (-0.25,-0.01)

12 -0.11 (-0.21,-0.01) -0.15 (-0.25,-0.04) -0.17 (-0.28,-0.07) -0.16 (-0.27,-0.06) -0.14 (-0.26,-0.02) Difference estimates are in standard deviation units (95% confidence interval) adjusted for time of day, time of week, age, race/ethnicity, and depressive symptoms b Motives for use measured with modified form of Marijuana Motives Measure c Dependence is defined as meeting criteria for Cannabis Dependence Disorder with Physiological Dependence based on the Adolesc ent Diagnostic Interview a

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Table 4a: Differencea in individual-standardized positive affect between times subsequent to marijuana use and antecedent times

T P

Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs) Antecedent Time (Hrs)

1

E C

C A

3

6

9

12

1

0.04 (-0.13,0.22)

0.02 (-0.18,0.22)

0.07 (-0.14,0.29)

0.03 (-0.20,0.27)

0.06 (-0.25,0.37)

3

0.06 (-0.07,0.19)

0.03 (-0.11,0.17)

0.05 (-0.10,0.20)

0.01 (-0.15,0.17)

0.02 (-0.19,0.23)

6

0.09 (-0.02,0.21)

0.05 (-0.07,0.17)

0.07 (-0.06,0.20)

0.04 (-0.09,0.17)

0.05 (-0.13,0.22)

9

0.09 (-0.02,0.19)

0.04 (-0.08,0.15)

0.05 (-0.06,0.17)

0.03 (-0.10,0.15)

0.07 (-0.09,0.24)

12

0.08 (-0.02,0.19)

0.03 (-0.08,0.14)

0.04 (-0.07,0.16)

0.01 (-0.11,0.13)

0.10 (-0.07,0.26)

ACCEPTED MANUSCRIPT Table 4b: Differencea in individual-standardized positive affect between times subsequent to marijuana use and antecedent times when using marijuana for coping or conforming reasonsb Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs) Antecedent Time (Hrs)

1

3

6

9

1

0.11 (-0.07,0.30)

0.03 (-0.16,0.23)

0.08 (-0.13,0.29)

0.03 (-0.20,0.26)

3

0.11 (-0.03,0.26)

0.03 (-0.11,0.18)

0.05 (-0.10,0.20)

0.01 (-0.15,0.17)

0.00003 (-0.22,0.22)

6

0.15 (0.01,0.28)

0.05 (-0.08,0.18)

0.06 (-0.07,0.19)

0.04 (-0.10,0.17)

0.02 (-0.16,0.21)

9

0.14 (0.01,0.27)

0.03 (-0.09,0.16)

0.04 (-0.08,0.16)

0.02 (-0.11,0.15)

0.05 (-0.13,0.22)

12

0.13 (0.01,0.26)

0.03 (-0.09,0.15)

0.03 (-0.09,0.15)

0.004 (-0.12,0.13)

0.07 (-0.10,0.24)

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D E

T P

C A

E C

M

C S

I R

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12 0.03 (-0.28,0.34)

ACCEPTED MANUSCRIPT Table 4c: Differencea in individual-standardized positive affect between times subsequent to marijuana use and antecedent times when using marijuana for reasons other than coping or conformingb Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs) Antecedent Time (Hrs)

1

3

6

9

1

0.04 (-0.14,0.22)

0.01 (-0.19,0.21)

0.07 (-0.14,0.29)

0.03 (-0.20,0.27)

3

0.06 (-0.07,0.19)

0.03 (-0.12,0.17)

0.05 (-0.10,0.20)

0.01 (-0.15,0.17)

6

0.10 (-0.02,0.21)

0.04 (-0.08,0.17)

0.07 (-0.05,0.20)

0.04 (-0.10,0.17)

9

0.09 (-0.02,0.20)

0.04 (-0.08,0.15)

0.06 (-0.06,0.17)

0.02 (-0.10,0.15)

12

0.09 (-0.02,0.19)

0.03 (-0.08,0.14)

0.04 (-0.07,0.16)

0.01 (-0.11,0.13)

12

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0.06 (-0.25,0.37)

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0.03 (-0.18,0.24) 0.05 (-0.13,0.23) 0.08 (-0.09,0.25) 0.10 (-0.06,0.26)

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Table 4d: Differencea in individual-standardized positive affect between times subsequent to marijuana use and antecedent times for persons with dependencec

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Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs) Antecedent Time (Hrs)

1

1

0.22 (-0.13,0.56)

0.28 (-0.11,0.68)

3

0.28 (0.02,0.54)

0.29 (0.004,0.57)

6

0.36 (0.13,0.59)

9 12

D E

3

M 6

9

0.26 (-0.17,0.68)

0.17 (-0.25,0.60)

0.09 (-0.45,0.64)

0.24 (-0.06,0.54)

0.11 (-0.19,0.41)

-0.01 (-0.39,0.38)

0.33 (0.09,0.57)

0.30 (0.05,0.55)

0.17 (-0.08,0.42)

0.04 (-0.29,0.37)

0.38 (0.17,0.59)

0.33 (0.11,0.56)

0.26 (0.03,0.50)

0.17 (-0.06,0.41)

0.15 (-0.17,0.46)

0.41 (0.20,0.62)

0.36 (0.14,0.58)

0.27 (0.05,0.50)

0.19 (-0.04,0.42)

0.19 (-0.12,0.50)

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E C

T P

12

ACCEPTED MANUSCRIPT Table 4e: Differencea in individual-standardized positive affect between times subsequent to marijuana use and antecedent times for persons without dependencec Difference in SD Units Assessed at Time Subsequent to Marijuana Use (Hrs) Antecedent Time (Hrs)

1

3

6

9

1

-0.04 (-0.25,0.16)

-0.11 (-0.34,0.11)

-0.03 (-0.27,0.22)

-0.04 (-0.32,0.24)

3

-0.05 (-0.19,0.10)

-0.09 (-0.25,0.07)

-0.04 (-0.21,0.13)

-0.03 (-0.22,0.15)

0.03 (-0.22,0.28)

6

-0.03 (-0.16,0.10)

-0.09 (-0.22,0.05)

-0.04 (-0.19,0.10)

-0.03 (-0.18,0.13)

0.03 (-0.18,0.24)

9

-0.05 (-0.17,0.07)

-0.10 (-0.23,0.03)

-0.05 (-0.19,0.08)

-0.05 (-0.19,0.10)

0.02 (-0.18,0.21)

C S

I R

T P

12 0.03 (-0.35,0.41)

12 -0.07 (-0.18,0.05) -0.12 (-0.24,0.01) -0.07 (-0.20,0.06) -0.07 (-0.21,0.07) 0.03 (-0.17,0.22) Difference estimates are in standard deviation units (95% confidence interval) adjusted for time of day, time of week, age, race/ethnicity, and depressive symptoms b Motives for use measured with modified form of Marijuana Motives Measure c Dependence is defined as meeting criteria for Cannabis Dependence Disorder with Physiological Dependence based on the Adolescent Diagnostic Interview a

A

U N

D E

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C A

E C

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ACCEPTED MANUSCRIPT

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ACCEPTED MANUSCRIPT Role of funding sources: This work was funded by NIDA grant R21DA021713 to Dr. Shrier. Dr. Ross’s participation in the study was funded in part by NIH grant T32 HD052458 (Boston University Reproductive, Perinatal, and Pediatric Epidemiology training program). No funders had any role in study design, collection, analysis, or interpretation of data, writing

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the manuscript, and the decision to submit the manuscript for publication.

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Contributors: Dr. Ross developed the study analysis plan, conducted the analysis, and wrote the manuscript. Dr.

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Shrier designed the study and obtained funding, wrote the ecological momentary assessment protocol, and supervised data

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collection. All authors reviewed analysis results, contributed to and approved the final manuscript.

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Conflicts of Interest: All authors declare they have no conflicts of interest.

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ACCEPTED MANUSCRIPT Highlights 

We used momentary assessment to assess change in affect following marijuana use



Overall, negative affect (NA) was higher and positive affect unchanged after marijuana use



After marijuana use to cope/conform, NA was highest and declined abruptly



Participants with dependence had increased positive affect after marijuana use

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